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Bond County, IllinoisEdit This Page
From FamilySearch Wiki
Revision as of 17:10, 8 August 2011 by HendricksonP (Talk | contribs)
Coordinates: 38.88°0′N 89.44°0′W / 38.88°N 89.44°W / 38.88; -89.44
Bond County, Illinois
Map
Location in the state of Illinois
Location of Illinois in the U.S.
Facts
Founded: January 4, 1817
County Seat Greenville
Courthouse
Photo courtesy Illinois Regional Archives Depository, Illinois State Archives
Address Bond County Courthouse
200 W. College Avenue
Greenville, Illinois 62246
(618) 664-3208
Bond County Website
United States Illinois Bond County
Contents
County Organization
Bond County is divided into 9 townships: Shoal Creek, LaGrange, Mulberry Grove, Old Ripley, Central, Pleasant Mound, Burgess, Mills, and Tamalco. It's civil records start the following years:
Birth Marriage Death Census Land Probate
1877 1817 1877 1820 1817 1821
County Courthouse
County records are most often kept at the County Courthouse or another local repository. For further information about where the records for Bond County are kept, see the Bond County Courthouse page.
Historical Facts
Bond County is named for Shadrach Bond, the first Governor of the State of Illinois.
Parent County
4 January 1817: -- Bond County was created from Madison County. [1]
Boundary Changes
See an interactive map of Bond County boundary changes.
Record Loss
Records and Resources
Bibles
Family Bibles of the Herndon and Howell families of Bond County are included in an Ancestry database ($). The database also includes Howell tombstone inscriptions and a will.[2]
Biography
Cemeteries
• Find A Grave can be searched by the name of a person or family to find where a person is buried. Usually gives birth and death dates often with a picture of the tombstone. May give obituaries, names of family members and links to their information in Find A Grave.
Census
Historical populations
Census Pop.
190016,078
191017,0756.2%
192016,045−6.0%
193014,406−10.2%
194014,5400.9%
195014,157−2.6%
196014,060−0.7%
197014,012−0.3%
198016,22415.8%
199014,991−7.6%
200017,63317.6%
Est. 200618,0552.4%
IL Counties 1900-1990
For tips on accessing census records online, see Illinois Census.
1840 Pensioners
• A Census of Pensioners for Revolutionary or Military Services: With their Names, Ages, and Places of Residence, as Returned by the Marshalls of the Several Judicial Districts, Under the Act for Taking the Sixth Census. Washington, D.C., 1841. FHL 973 X2pc 1840; FHL 2321; digital version at Google Books. [See Illinois, Bond County on page 186.]
Church History and Records
Court Records
IRAD Holdings
• Justice of the Peace Dockets 1858 to 1961
Family History Library holdings
• FHL film 1316516 (first of 22) This record includes court records, guardianships, loose papers, and various probate related records. Many records in in these series were eith missing or not filmed.
Ethnic Research
African American
The following have information concerning African American research.
Genealogy
Mailing Lists
Message Boards
History
Land and Property
BLM GLO Records. Search original land patents for Bond County from the Govenment Land Office (GLO) or Eastern States Office. Some searches include images of the original warrants. All search results include the patant details needed for requesting copies of the land entry files at the National Archives. The GLO is the custodian of millions of land title documents. The General Land Office Automated Records Project is responsible for making these important documents available to the public.
Land records that include Bond County at Ancestry.com $:
• "Illinois Public Land Purchase Records" This record extract includes over 538,000 land sales from the 19th Century. Each entry includes the purchaser's name, purchase date, number of acres, price per acre, and in some cases the purchaser's sex and residence.
• "U.S. General Land Office Records, 1796 to 1907:" Records of Illinois are among the 13 states included in this set. It includes images of the land patents which contain the information necessary for ordering the complete case files from the National Archives. This appears to be the same information that is online at the Federal Land Office site http://www.glorecords.blm.gov/.
• Sheldon, Theodore. Land registration in Illinois. Chicago: Callaghan & Co., 1901. Digital book. Expains the laws regarding land and the land systems used in Illinois. Includes court cases involving land issues. In addition to being on Ancestry, this book is available online at no cost at Internet Archives and Google Books.
FHL land records
• Bond County (Illinois). Recorder. Deed records, 1817-1921. FHL film 1315963 (first of 28)
• Family maps of Bond County, Illinois : with homesteads, roads, waterways, towns, cemeteries, railroads, and more, by Gregory A. Boyd. (Norman, Oklahoma : Arphax Pub. Co., c2007)FHL book 977.3873 E7bg This book identifies the early land owners of Bond County, placing them on township maps with other geographic and manmade landmarks.
Maps
Military
• Civil War
Civil War service men from Bond County served in various regiments. Men often joined a company (within a regiment) that originated in their county. Listed below are companies or regiments that were formed from men of Bond County.
- 35th Regiment, Illinois Infantry, Company H.
Military History and Records
Naturalization and Citizenship
Newspapers and Obituaries
Probate Records
Online abstracts from of Record Books A to 1, 1821 to 1838. Includes appraisals, administrations, wills, guardianships, land sales, and other records associated with probate matters. Transcribed by Donna Walton in 2007.
IRAD Holdings
• Probate Minutes 1877 to 1855
• Probate Records 1837 to 1849
Family History Library holdings
• Bond County (Illinois) County Court. Probate records 1817 to 1940 FHL film 1316516 (first of 22) This record includes court records, guardianships, administrators' bonds, loose papers, and various probate-related records. Many records in these series were either missing or not filmed. Not all types of records cover all years. Many volumes include an index.
Guardianships
The Family History Library has films of some guardianshipp records among the the probate records listed above with the probate records.
Some guardianships are listed in the Online Abstracts described under probate records.
Repositories
County Courthouse
County records are most often kept at the County Courthouse or another local repository. For further information about where the records for Adams County are kept, see the Bond County Courthouse page.
Family History Library
Illinois Regional Archives Depository (IRAD)
IRAD Depository
LIB 144
University of Illinois at Springfield
One University Plaza, MS BRK 140
Springfield IL 62703-5407
Telephone: (217) 206-6520
Public Libraries
Social Groups Online
Societies
Taxation
Vital Records
Bond County (Illinois) County Court. Births, marriages, and deaths 1817-1927. FHL film 1317522 (first of 8)
Newspapers
Births
IRAD Holdings
• Birth Records 1877 to 1915
• Birth Records Index 1863 to 1915
• Delayed Birth Records Index 1863 to 1915
Marriages
Illinois Statewide Marriage Index, 1763–1900 - An online searchable index, is an ongoing project of the Illinois State Archives and the Illinois State Genealogical Society The Bond County index includes 1817-1915.
IRAD Holdings
• Marriage License Application 1891 to1916
• Marriage Licenses 1817 to 1915
• Mariage Records 1817 to 1915
• Marriage Record Index 1817-1915
Available through Ancestry.com:
• Bond county marriages in "Illinois Marriages 1790 to 1860"
• Bond County marriages in "Illinois Marriages to 1850"
• Bond County marriages in "Illinois Marriages 1851 to 1900"
FamilySearch. Extracts of Bond County marriages without images are available on FamilySearch among the "Illinois County Marriages, 1810 to1934"
FHL records
• Bond County (Illinois) County Clerk. Marriage licenses 1817-1872 FHL film 688499 (first of 5)
• Bond County (Illinois) County lCerk. Bond County marriage licenses (adult and minor) & related material, 1873-1875, 1877-1886, 1890-1915. FHL film 1688489 (first of 9)
• Bond County, Illinois marriage records, 1817-1850, compiled by Robert E. and Phyllis J. Shelby. Kokamo, (Indiana: Shelby Pub., 1982). FHL book 977.3873 V2s
• Bond County, Illinois marriage records, 1851-1877, compiled by Evelyne McCracken. (Greenville, Illinois : Bond County Genealogical Society, c1984 ). FHL book 977.3873 V2m
• Bond County, Illinois marriage records, 1878-1899, compiled by Evelyne McCracken. (Greenville, Illinois : Bond County Genealogical Society, c1985 ). FHL book 977.3873 V2mb with supp.
• Bond County, Illinois marriage records, 1894-1915, compiled by Evelyne McCracken. (Greenville, Illinois : Bond County Genealogical Society, c1985 ).FHL book 977.3873 V2mba
Deaths
Index of Illinois Death Certificates, 1916–1950 listings the death certificates filed with the Illinois Department of Public Health
IRAD Holdings
• Death Records 1878 to 1915
• Death Records Index 1878 to 1915
Websites
References
1. WorldCat 50140092, FHL Handybook for Genealogists: United States of America, 10th ed.] (Draper, Utah: Everton Pub., 2002)
2. Illinois Miscellaneous Genealogical Records: From Counties, Bond, Boone, Calhoun, Cook, Crawford, Du Page, Johnson, Knox, Lake, Will, Pope: Kentucky county, Mercer: Missouri county, Ralls. Evanston, Ill.: Illinois Society, D.A.R., 1946. Digital version at Ancestry ($).
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Italy, Catania, Caltagirone Civil Registration (FamilySearch Historical Records)Edit This Page
From FamilySearch Wiki
Revision as of 16:26, 28 November 2012 by Barbarajens (Talk | contribs)
This article describes a collection of historical records available at FamilySearch.org.
Contents
Title in the Language of the Records
Stato Civile di Catania, Italia
Record Description
This Collection will include records from 1861 to 1941.
The collection consists of civil registration (stato civile) of births, marriages, and deaths within the custody of the Caltagirone Courthouse (Tribunale di Caltagirone). Includes annotations (annotazioni); supplemental records (allegati); and marriage banns (pubblicazioni). Availability of records is largely dependent on time period and locality.
For a list of records by localities and dates currently published in this collection, select the Browse.
Citation for This Collection
The following citation refers to the original source of the information published in FamilySearch.org Historical Records collections. Sources include the author, custodian, publisher, and archive for the original records.
Caltagirone Tribunale. Italy, Catania, Caltagirone, Civil Registration (Tribunale). Caltagirone Courthouse, Catania, Italy.
Suggested citation format for a record in this collection.
Record Content
For details about the contents of these records, their history, and help using them see the wiki article: Italy, Civil Registration (FamilySearch Historical Records)
How to Use the Record
To search the collection, select "Browse through images" on the initial collection page
⇒ Select the “Comune o frazione”
⇒ Select the “ Registro e L'Anno” which takes you to the images.
Look at the images one by one comparing the information with what you already know about your ancestors to determine which one is your ancestor. You may need to compare the information about more than one person to make this determination.
Known Issues with This Collection
Problems with this collection?
See a list of known issues, workarounds, tips, restrictions, future fixes, news and other helpful information.
For a full list of all known issues associated with this collection see the attached Wiki article. If you encounter additional problems, please email them to support@familysearch.org. Please include the full path to the link and a description of the problem in your e-mail. Your assistance will help ensure that future reworks will be considered.
Related Websites
Archivi di Stato: Elenco
Related Wiki Articles
Contributions to This Article
We welcome user additions to FamilySearch Historical Records wiki articles. Guidelines are available to help you make changes. Thank you for any contributions you may provide. If you would like to get more involved join the WikiProject FamilySearch Records.
Citing FamilySearch Historical Collections
When you copy information from a record, you should list where you found the information. This will help you or others to find the record again. It is also good to keep track of records where you did not find information, including the names of the people you looked for in the records.
A suggested format for keeping track of records that you have searched is found in the wiki article Help:How to Cite FamilySearch Collections.
Citation Example for a Record Found in This Collection
"Italy, Civil Registration, 1805-1940," digital images, FamilySearch (https://familysearch.org: accessed 22 April 2011), entry for Pietro Antonio De Lutis, died 8 May 1933; citing Civil Registrations, digital folder 4,404,467 image 00,103; Tribunale di Rovigo, Italy. Registri dello stato civile di Rovigo.
Need additional research help? Contact our research help specialists.
Need wiki, indexing, or website help? Contact our product teams.
Did you find this article helpful?
You're invited to explain your rating on the discussion page (you must be signed in).
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VESSEL
Unique ID: NARC-2E1915
Object type certainty: Certain
Workflow status: Awaiting validation
A rim sherd of Roman greyware. The rim is collared and the body shouldered. Greyware was common table and storage ware in the Roman period, typically dating from the 2nd to 4th centuries AD.
Subsequent actions
Subsequent action after recording: Returned to finder
Chronology
Broad period: ROMAN
Period from: ROMAN [scope notes | view all attributed records]
Period to: ROMAN [scope notes | view all attributed records]
Date from: Circa AD 100
Date to: Circa AD 350
Dimensions and weight
Length: 48 mm
Width: 38 mm
Thickness: 5 mm
Weight: 16.49 g
Quantity: 1
Personal details
Found by: This information is restricted for your login.
Recorded by: Ms Julie Cassidy - [ view all attributed records]
Identified by: Ms Julie Cassidy - [view all attributed records]
Other reference numbers
Materials and construction
Primary material: Ceramic [scope notes | view all attributed records]
Manufacture method: Wheel made [scope notes | view all attributed records]
Completeness: Fragment [scope notes | view all attributed records]
QR barcode
The barcode on the right is a unique identifier for this record. If your phone has scanning software installed, then this can be used for sharing or you can print it off and attach it to the object.
Spatial metadata
Region: East Midlands
County: Northamptonshire
District: South Northamptonshire
Parish: Rothersthorpe
Spatial coordinates
4 Figure: SP7156
Four figure Latitude: 52.197671 Four figure longitude: -0.962629
1:25K map: SP7156
1:10K map: SP75NW
WOEID: 33593
Grid reference source: GPS (from the finder)
Unmasked grid reference accurate to a 1 metre square.
Discovery metadata
Method of discovery: Metal detector [scope notes]
General landuse: Cultivated land[scope notes]
Specific landuse: Operations to a depth less than 0.25 m[scope notes]
Adjacent Domesday Book places
Domesday data within 2 km of discovery point is surfaced via the excellent Open Domesday website.
References cited
No references cited so far.
Similar objects
Find number: NARC-DDBCE5
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Broadperiod: ROMAN
A rim fragment of Roman grey ware storage jar. Wheel made. A collared rim 170mm in diameter. Typical of 2nd century AD greyware, notably Alic…
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Workflow: Awaiting validation
Spotted a mistake? Tell us. Be the first to comment
Comment on this artefact's record
Data entered via this form is checked against the akismet service to recognise spam.
Audit data
Created: Saturday 21st April 2012
Updated: Monday 23rd April 2012
This page is available in: qrcode json xml geojson representations.
Social Bookmarking:
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This article is part of the supplement: Quantitative inference of gene function from diverse large-scale datasets
Research
Predicting gene function in a hierarchical context with an ensemble of classifiers
Yuanfang Guan1,2, Chad L Myers2,3, David C Hess2, Zafer Barutcuoglu3, Amy A Caudy2 and Olga G Troyanskaya2,3*
Author Affiliations
1 Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
2 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
3 Department of Computer Science, Princeton University, Princeton, NJ 08544, USA
For all author emails, please log on.
Genome Biology 2008, 9(Suppl 1):S3 doi:10.1186/gb-2008-9-s1-s3
The electronic version of this article is the complete one and can be found online at: http://genomebiology.com/2008/9/S1/S3
Published:27 June 2008
© 2008 Guan et al; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background:
The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied to unicellular organisms with some success, but few have been extensively tested on higher level, multicellular organisms. A recent mouse function prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array of methodologies to mount the first large-scale effort to predict gene function in the laboratory mouse.
Results:
In this paper, we describe our contribution to this project, an ensemble framework based on the support vector machine that integrates diverse datasets in the context of the Gene Ontology hierarchy. We carry out a detailed analysis of the performance of our ensemble and provide insights into which methods work best under a variety of prediction scenarios. In addition, we applied our method to Saccharomyces cerevisiae and have experimentally confirmed functions for a novel mitochondrial protein.
Conclusion:
Our method consistently performs among the top methods in the MouseFunc evaluation. Furthermore, it exhibits good classification performance across a variety of cellular processes and functions in both a multicellular organism and a unicellular organism, indicating its ability to discover novel biology in diverse settings.
Background
An important challenge in the post-sequence era of modern biology is determining the functional role of all proteins in the cell. With the recent invention of several large-scale experimental methods, we have begun to accumulate a wealth of functional genomic data to help address this challenge, including expression and protein-protein interaction data, and phenotype and phylogenetic profiles. These large datasets have fuelled an interest in computational approaches to gene function prediction, which promise to harness the information present in these large collections of data to automatically derive accurate gene annotations [1-7].
Although a variety of computational approaches have been proposed for predicting gene function, most of them have been developed and applied in unicellular organisms such as Saccharomyces cerevisiae. Applying these methods to higher, multicellular organisms is non-trivial because of their intrinsic complexity, including different development stages, tissue types and physiological functions. However, we perhaps have the most to gain from computational annotation efforts based on diverse data, as our knowledge about the role of individual proteins in these systems is largely incomplete. In fact, although organisms such as the laboratory mouse tend to be of great scientific importance, the majority of their proteins are annotated electronically based on only a single data source (the IEA [inferred from electronic annotation] evidence code) [8]. Many sources of genome-scale data are available for most genes and, thus, functional prediction from multiple data sources for multicellular organisms is an important open problem whose solution is critical to functional genomics.
To explore the development of gene function prediction methods for multicellular organisms, several groups recently participated in an organized function prediction project for the laboratory mouse, MouseFunc [9]. Several state-of-the-art machine learning methods were applied, including support vector machines (SVMs), Bayesian networks, decision trees and random forests. Here, we describe our contribution to this effort, an ensemble classifier approach that is based on the SVM and integrates information in the context of the Gene Ontology (GO) hierarchy.
Our approach is motivated by three key aspects of the gene function prediction problem. First, we hope to accurately annotate function for a broad range of biological processes, molecular functions and cellular components. Given this diversity, it is unlikely that one learning model will perform the best in all possible contexts, thus motivating our choice of an ensemble of complementary approaches. Second, established knowledge of gene function (that is, the gold standard for learning) is organized in the hierarchical structure of the GO, which can be leveraged to improve overall prediction accuracy. Finally, the available genomic data (for example, gene expression and protein-protein interaction data) are heterogeneous both in terms of the functional information they capture and in their inherent structure; a model for learning must be flexible enough to accommodate these differences and leverage functional diversity within the data.
Our ensemble classifier is based on the SVM and leverages these characteristics unique to the gene function prediction setting (Figure 1). We illustrate that a combination of complementary strategies often outperforms a single SVM classifier and, furthermore, demonstrates consistently strong performance relative to competing groups in the MouseFunc submissions [9]. In the sections that follow, we provide an analysis of prediction performance and insights into when and why our ensemble framework performs well. Finally, we also demonstrate that our method can confidently predict novel biology with experimental confirmation of predictions in S. cerevisiae.
Figure 1. An ensemble framework based on the SVM that integrates diverse datasets in the context of GO hierarchy. After pre-processing the data, we developed an approach that consists of an ensemble of three different classifiers: 1, a single SVM classifier for each GO term was trained on combined data; 2, single SVM classifiers were combined through Bayesian networks to correct their predictions based on the hierarchical relationship between GO terms in the GO directed acyclic graph; and 3, a naïve Bayes classifier was built for each GO term to directly integrate the results of single-dataset SVM classifiers. The bootstrap held-out values on the training set were used to characterize each classifier's performance, and the ensemble prediction was formed by selecting the best performing classifier on each GO term. GO, Gene Ontology; SVM, support vector machine.
Results
Our approach consists of an ensemble of three different classifiers, all based on the SVM: a single SVM, single kernel classifier; a hierarchically corrected combination of SVM classifiers; and a naïve Bayes combination of single dataset SVM classifiers (Figure 1). The basic process we applied was to train all three classifiers for each GO term, use out-of-bag bootstrap values to assess their performance, and finally assemble combined predictions based on classifier performance. We describe each of these approaches and their combination into the ensemble framework in detail in Materials and methods.
We applied this method in the MouseFunc GO prediction project [9]. This project involved prediction of a total of 1,726 biological process terms, 326 cellular component terms and 763 molecular function terms for laboratory mouse. As described in [9], methods were evaluated according to two different benchmarks. The first set included 1,718 genes whose annotations were held-out in advance, and the second set consisted of novel annotations, including 1,954 genes, added by Mouse Genome Informatics (MGI) in the approximately 8 months between dataset assembly and the prediction submission deadline. Here we focus our analysis on the latter set, which could be considered the ideal test case to determine how well our approach can predict completely new biology. Furthermore, to simplify the discussion, we have also restricted most of our analysis to the biological process GO terms. The trends discussed here are similar for the other types of terms (cellular component and molecular function) and the prediction of biological process terms is generally more difficult as shown by lower average areas under receiver operating characteristic (ROC) curves (AUCs; see Figure 2 in [9]).
Figure 2. GO term size influences the performance of individual methods. GO term size appears to be a significant factor that influences the relative performance among groups (the performance of each group is shown by the average AUC values). Although there is no general trend common to all groups, individual groups demonstrate consistent trends regardless of what GO branch was tested. For example, groups B and D perform better on big GO terms. Group C performs better on small terms, and groups E to H perform well on intermediate-sized GO terms. Asterisks indicate second round submissions. AUC, area under receiver operating characteristic curve; BP, biological process; CC, cellular components; GO, Gene Ontology; MF, molecular functions.
The ensemble method performs among the top prediction methods
Our ensemble approach performs well across a broad range of processes (GO terms), including both large and small terms from all GO branches. We measure an overall average AUC of 0.72, with an average precision of 0.13 at 20% recall. Of the 2,172 total terms across all three ontologies, there are 188 with better than 90% precision at 20% recall. Furthermore, our method always performs in the top three of the nine MouseFunc submissions in terms of the average AUC across all categories of terms. These categories were defined by the project organizers for each GO branch (biological process, cellular component, and molecular function) based on the number of annotations to each term [9]. Our method achieves the best average AUC for 3 of these 12 categories, the second best AUC for 6 of the 12, and the third best AUC for 3 of the 12 (Table 1 and Figure 2).
Table 1. Ranking of the performance of our group based on the mean AUCs
Our method performs the best relative to the other submissions on large terms, that is, terms with many annotations. In fact, two of our three first-place finishes are for the largest terms (biological process terms with 101 to 300 annotations and cellular component terms with 101 to 300 annotations). Conversely, two of our three third-place finishes are for the smallest terms (biological process terms with three to ten annotations and cellular component terms with three to ten annotations). Thus, our method consistently performs among the top methods used in this project across a range of functional categories, although it does appear that our best performance occurs on large and medium-sized terms. We will explore this trend in greater detail below in this section.
Analysis of ensemble classifier performance
We further analyzed the individual components of our ensemble approach to gain knowledge about which methods perform the best under which circumstances.
Bagged SVM classifier performance is robust across a wide range of GO terms
Since the SVM on a combined input dataset served as the basis for our approach, we first compared its performance alone on the evaluation set to submissions from other teams. The mean AUCs for biological process GO terms for the bagged SVM range from 0.63 (terms with 3 to 10 annotations) to 0.69 (terms with 31 to 100 annotations). With this performance, the linear-kernel SVM ranks consistently among the top three or four methods for all size categories of GO terms (Figure 3). In fact, on average, only three methods (groups C, D [our group] and G) performed better than the single SVM classifier across the entire set of biological process terms. Furthermore, only the ensemble approach described here consistently outperformed the single SVM predictions regardless of the GO term size, while group C performed significantly well on small terms. We were surprised at the relative success of this approach since our implementation was straightforward with little 'fine-tuning' with the exception of some input data processing and bootstrap aggregation (described in Materials and methods). However, this result confirms our original choice of the SVM as a robust baseline method for the more sophisticated classifiers in our ensemble.
Figure 3. Comparison of the performance of a single SVM with other methods in predicting BP annotations of the novel set. This figure shows the AUC achieved by different submissions to the mouse function prediction project compared to a single SVM approach for GO BP terms of different sizes: (a) 3 to 10; (b) 11 to 30; (c) 31 to 100; and (d) 101 to 300. We found that a single SVM, after careful adjustment of parameters, performed relatively well across different sizes of GO terms, indicating the robustness of the SVM as a baseline prediction method. Only groups C, D and G performed better, on average, than the single SVM results. The dashed red lines represent the performance of single SVM in terms of AUC. Asterisks indicate second round submissions. AUC, area under receiver operating characteristic curve; BP, biological process; GO, Gene Ontology; SVM, support vector machine.
Hierarchical correction of SVM classifiers improves performance
We further applied our hierarchical correction based on GO hierarchies and measured its improvement over single SVMs (see Materials and methods for details). For all GO terms with five or more annotations in the training set, we applied both approaches to subgraph generation, including the Markov blanket graphs (HIER-MB), and the breadth-first search graphs (HIER-BFS; Figures 4 and 5). We examined how often the hierarchical correction from either of these yielded better prediction accuracy than the bagged SVM predictions.
Figure 4. Hierarchical correction using Markov blanket structure. (a) Schematic of the local Markov blanket surrounding a GO term (Y1 is the node of interest in this example). Each GO term is represented by a blank node while the SVM classifier output for that GO node is represented by a shaded node. To address the hierarchical relationships between GO terms, for each GO term (Y1), we included all neighboring nodes in its Markov blanket to construct a Bayesian network. The distribution of SVM outputs (observed nodes) for positive and negative examples was encoded in the conditional probability tables of the Bayesian network. We then infer the probability of a particular gene's involvement in each GO term (a hidden node) based on its values in these observed nodes. (b) Improvement of the AUC for the novel set using the HIER-MB classifiers compared to single SVM predictions for selected terms for biological process terms of size 101 to 300 (number of genes annotated to this GO term in the training set). For each GO term, the best-performing sub-hierarchy was selected, and the ones that performed better than single SVM (characterized by held-out values in the training set) are plotted in this figure. (c) Median improvement of predictions for selected GO terms over different biological process GO term sizes. Hierarchical correction using Markov blanket structure performs better (when selected) for smaller terms. AUC, area under receiver operating characteristic curve; GO, Gene Ontology; HIER-MB, Markov blanket hierarchical correction; SVM, support vector machine.
Figure 5. Hierarchical correction using BFS sub-networks. (a) Schematic of BFS sub-networks. Each GO term is represented by a blank node while the SVM classifier output for that GO node is represented by a shaded node. Starting from each GO term (Y1), we did a BFS to construct the local hierarchy, until a maximum of 30 terms were included. In this process, we considered only GO terms with five or more annotations in the training set. (b) Improvement of AUC for the novel set using the HIER-BFS classifier compared to single SVM predictions for selected terms for biological process terms of size 101 to 300 (genes annotated to this GO term in the training set). For each GO term, the best-performing sub-hierarchy was selected, and the ones that performed better than single SVM (characterized by held-out values in the training set) are plotted in this figure. (c) Median improvement of predictions for selected GO terms over different biological process GO term sizes. Again, hierarchical correction using BFS structure performs better for smaller terms when they were selected. AUC, area under receiver operating characteristic curve; BFS, breadth-first search; GO, Gene Ontology; HIER-BFS, breadth-first search hierarchical correction; SVM, support vector machine.
Predictions for a majority of GO terms are improved significantly by the hierarchical correction after selection of the subgraphs based on held-out values. The HIER-BFS classifier improved the single SVM predictions for 1,012 of 1,726 (59%) biological process GO terms by an average AUC of 0.049 (26% increase of random performance; Figure 5b). Similarly, the HIER-MB classifiers improved predictions for 996 of 1,726 (58%) terms by an average AUC of 0.044 (23% increase; Figure 4b). Through a combination of both strategies, the improvement is sustained across the whole range of GO term sizes, but both tend to improve prediction performance (AUC) more for smaller terms (Figures 4c and 5c). For instance, HIER-BFS improves predictions for terms with more than 200 annotations by an average of 0.018 (10% increase) but improves predictions for terms with between 3 and 10 annotations by an average of 0.095 (58% increase). We observed a similar trend for the HIER-MB classifier: 0.03 (17% increase) compared to 0.071 (43% increase) for smaller terms. Unsurprisingly, the two approaches improve predictions for largely the same set of GO terms. Of the 1,012 and 996 terms for which predictions were improved using the HIER-BFS and HIER-MB approaches, respectively, the combination of the two improved predictions for a total of 1,046 terms (61%) by an average of 0.048 (25%). Thus, including GO hierarchical information in function prediction can yield consistent improvements across a variety of terms, even in a challenging scenario such as mouse function prediction.
Naïve Bayes combination of SVMs on diverse data improves performance for large GO terms
We also measured the improvement offered by the third classifier in our ensemble, the naïve Bayes combination of per-dataset SVMs. The motivation behind this approach is that genomic data are heterogeneous in the specific functions they capture and very different in their accuracy in predicting different functions, which may not be harnessed effectively by a single-kernel SVM classifier. For this approach, we trained an SVM on each individual dataset for each GO term, using bootstrapping to characterize the output distribution of positive and negative examples. Generally, the distribution of SVM outputs for held-out positive examples was shifted higher with respect to that of negative examples (for example, see Figure 6a). A naïve Bayes classifier on discretized SVM outputs was then used to assign a probability of functional assignment to a GO term of interest given such distributions from each dataset (Figure 6b).
Figure 6. Bayesian combination of diverse datasets. (a) A typical example of distribution of SVM outputs of a single dataset. This distribution of SVM output (from the Su et al. expression dataset [34]) for positive examples is shifted slightly higher relative to the distribution of the negative examples. (b) Schematic of Bayesian combination of diverse datasets. For each GO term, we constructed a naïve Bayes classifier where the output of single-dataset SVMs was used as a single input node (observed node). (c) Improvement of AUC over single SVM predictions for selected terms for biological process terms with size 101 to 300 genes. The Bayesian combination of datasets was selected where the held-out results on the training set showed superior performance over the single SVM. (d) Median improvement of predictions for selected GO terms over different biological process GO term sizes. The Bayesian combination of diverse datasets performs well only for large GO terms. AUC, area under receiver operating characteristic curve; GO, Gene Ontology; SVM, support vector machine.
A naïve Bayes combination of per-dataset SVMs results in a significant improvement over the single SVM classifier for several GO terms (Figure 6c). In all, it resulted in a significantly higher classification performance for 403 of 1,726 (23%) biological process GO terms. Interestingly, this set includes 87% of the terms with more than 20 annotations, suggesting this strategy is very effective for larger terms. Further analysis confirms this trend: the naïve Bayes classifier averages a 0.03 AUC improvement (17% increase) for terms greater than 200 annotations yet results in a loss of performance of 0.06 (36% decrease) on smaller terms. We suspect that this behavior is due to a lack of positive examples to characterize the per-dataset SVM output distribution, and in light of this observation, we restricted this method to terms with more than 20 annotations. This result demonstrates why an ensemble of different learning models is critical in predicting diverse gene functions: the naïve Bayes combination of single dataset classifiers works well for large terms but must be complemented with other approaches when few positive examples are available.
Analysis of the source of ensemble predictions
Our ensemble method integrates output from the three base classifiers: the bagged single SVM, hierarchical Bayesian combination of SVM classifiers and the naïve Bayes combination of per-dataset SVMs. We evaluated how often each of these three approaches was selected for the final prediction set. As suggested by our earlier analysis, the majority of predictions are selected from the more sophisticated approaches, either the hierarchical classifier or the naïve Bayes combination (Figure 7). Specifically, the naïve Bayes combination was more likely to be selected for larger GO terms, while the hierarchical correction yields consistent improvements in all size categories, as suggested by our previous analysis. In all, for terms with more than 100 annotations, predictions for 99% were improved by one of these alternatives and predictions for 99%, 89%, and 37% were improved for GO terms with 31 to 100, 11 to 30, and 3 to 10 genes, respectively. Thus, the SVM provides a robust baseline classifier for gene function prediction, demonstrated by the performance on GO terms with fewer than five annotated genes, where only a single SVM was used. Nevertheless, SVM can often be significantly improved by leveraging unique properties of genomic data and the GO context, particularly when a reasonable number of positive examples are available.
Figure 7. Composition of selected approaches for different GO term sizes. In our ensemble method, three different approaches based on SVM were applied, including bagged single SVMs, SVMs with hierarchical correction, and Bayesian integration of single-dataset SVMs. Each of them exhibits good performance in a different domain, which is indicated in this figure by the percentage of terms where each of the different methods exhibited the best performance for four different size categories. For smaller GO terms, the single SVM and hierarchical correction often achieve superior performance. For larger GO terms, Bayesian integration of diverse datasets performed better than the other two methods. GO, Gene Ontology; SVM, support vector machine.
Discussion of evaluation results
We have demonstrated that our ensemble classifier achieves good performance across a variety of terms and performs consistently well relative to other methods contributed to the mouse function prediction project. As discussed earlier, one of the most important factors determining the relative performance of different methods was the size of the GO term (number of annotations or positive examples). The organizers grouped the set of predicted GO terms into 4 different size groups, based on the number of annotations in the training set: 3 to 10, 11 to 30, 31 to 100, and 101 to 300. These sets formed the basis of our earlier analysis. As one might suspect from the trends apparent in our method's performance, the participating groups' relative performance varied drastically across GO term size (Figure 2). For example, group B and group D (our group) were relatively better at predicting larger GO terms than smaller ones, while group C performed especially well on very small GO terms. We also observed that many groups, including groups E to H, performed well on intermediate-sized GO terms. These trends are usually consistent regardless of the GO term branch, indicating intrinsic properties of the specific methodologies used by each group.
The reasons for our improved performance at predicting larger terms are relatively clear based on our earlier analysis. First, the basis of our approach, the single SVM, shows significantly better performance than other approaches for larger GO terms. Second, as discussed above, the naïve Bayes combination is particularly effective on larger terms, which accounts for much of our superior performance in those cases. In general, because we used a supervised method for forming ensemble predictions (that is, through evaluation on the bootstrap held-out values), we require a reasonable number of examples to properly estimate relative performance of different classifiers. Thus, the ensemble yields improvement only where there are sufficient positive examples to support this estimation.
The variation among groups suggests an important lesson about gene function prediction. Namely, there is rarely one method that performs the best in all prediction scenarios. We anticipated this in designing our approach, which motivated our choice of an ensemble of classifiers, although all of our methods tended towards better performance on medium to large GO terms. Fortunately, there were other methods applied in this annotation prediction effort that show the opposite trend (for example, group C), suggesting that only a handful of methods may be able to provide superior results for most situations. In fact, a combination of our ensemble method's results for large terms and group C's results for small terms would nearly dominate all categories.
Another major source of variation in the relative performance of the different methods was the choice of the evaluation set. As mentioned earlier, two sets of annotations were used by the organizers to evaluate the submissions. The first evaluation was completed on a set of annotations simply held-out at the time of dataset distribution (the held-out set). Additionally, we were also able to evaluate our results on the new biological knowledge curated during the approximately eight month period after data assembly (the novel set). Our discussion here has been limited to evaluation of our method on the novel set, mainly because we think this set best models the real prediction scenario. Interestingly, we found that the relative performance of the different groups significantly differs between the held-out set and the novel set, although there is a slight correlation (Figure 8). Furthermore, the average AUC across all categories and groups drops significantly between the held-out set and the novel set. One characteristic that would potentially explain these differences is that the novel annotation set is dominated by ISS (inferred from sequence or structural similarity) annotations, while the test set has a significant fraction of RCA (inferred from reviewed computational analysis) annotations (Figure S3 in [9]). The similarity of the distributions of evidence codes between the test set and the training set makes the test set an easier prediction problem, which is confirmed by overall higher performance on that set. Despite these differences between the two evaluation sets, we were encouraged that our method performed among the top submissions using either benchmark (Table 1). In general, however, this alerts one to the fact that we should be very critical when evaluating our computational results using cross-validation analysis alone.
Figure 8. Relative performance of different methods with regard to the test set and novel set on GO biological process terms (size 101 to 300). The relative performance of individual groups differs between the test set and novel set. In addition, the performance on the novel set was generally worse than on the test set. This indicates that cross-validation should be used carefully in assessing the relative performance of different algorithms and that evaluation on novel biology is necessary. Asterisks indicate second round submissions. GO, Gene Ontology.
Literature follow-up on novel mouse gene function predictions
Encouraged by the good performance of our method across a variety of biological processes, we investigated a number of specific predictions for previously uncharacterized mouse genes. For example, in predicting the genes involved in chromatin modification (GO:0016568), we achieved an AUC of 0.8396 in the novel set, and 80% precision at 20% recall. One gene of high confidence (0.99) but not annotated to this term was PRDM14 (MGI:3588194). This gene has no biological process annotations yet, and based on previous computational analysis, this gene is suggested to localize to the nucleus [10]. Our prediction of its involvement in the chromatin modification process correlates with the findings of a recent publication that showed that stable expression of PRDM14 up-regulated expression of a variety of genes involved in breast cancer [11]. In particular, PRDM14 contains a PR domain, possibly a derivative of SET, which is known to affect chromatin structure [12]. Oncogenic properties have been shown in other chromatin modifiers as well, including EZH2 and SMYD3 [13,14]. Given this evidence, it is likely that PRDM14 regulates specific gene expression levels through the modification of chromatin structure. This literature study suggests that using our approach can enhance the efficiency of novel gene function discovery, including the identification of genes involved in a core process such as chromatin modification, which is potentially relevant to our understanding of human biology.
Experimental validation of gene function predictions in S. cerevisiae
The evaluations described above were based on cross-validation analysis and literature follow-up of specific predictions. We wanted to further verify that we are able to predict novel biology using our approach and, furthermore, that our method could be successfully extended to other species. Thus, we also applied our ensemble method (including single SVM, hierarchical correction and naïve Bayes integration of diverse datasets) to S. cerevisiae, and validated the top predictions of mitochondria-related function (GO:0007005, mitochondria organization and biogenesis). For this term, the naïve Bayes combination of diverse SVMs was selected as the best-performing method. The top uncharacterized gene predicted by our methods was ICY1. Though the function of this gene remains unknown, it was identified as a high-copy suppressor of the TIM22 mitochondrial protein import complex [15]. Furthermore, when ICY1 is deleted, these cells require mitochondrial DNA for survival (Saccharomyces normally can survive without mitochondrial DNA) [15]. Though the specific function of ICY1 remains unclear, these genetic phenotypes strongly suggest a role in mitochondrial membrane maintenance.
The second top uncharacterized gene was YDR316W (OMS1). Similar to ICY1, OMS1 was identified as a high copy suppressor of a mitochondrial protein (Oxa1). Though localization studies [16,17] have identified Oms1 as a mitochondrial protein, its function remains a mystery. Using a classic assay to measure perturbations in normal mitochondrial function [18], we experimentally verified that Oms1 is required to maintain functioning mitochondria. Briefly, wild-type and oms1Δ strains were grown in glycerol, which selects for cells that have functional mitochondria. These cultures are then plated for single colonies on rich media, which allows growth of cells without functional mitochondria. Resultant colonies are grown on rich media to measure the proportion of cells in the parent colony that lost mitochondrial function. This is done by plating single cells from the colony on rich media and overlaying the resulting colonies with tetrazolium, which stains colonies that have functioning mitochondria red while colonies lacking functioning mitochondria stay white (Figure 9). Eight independent frequencies were measured for both oms1Δ cells and wild type. The oms1Δ cells had 67% more colonies without functional mitochondria compared to wild type (P < 0.003, Mann Whitney U-test). This assay clearly demonstrates that Oms1 is required for the normal production of functional mitochondria and provides a strong validation of our prediction methodology.
Figure 9. Petite assay on the oms1Δgutant. To further evaluate the performance of our ensemble algorithm, we applied our methodology to S. cerevisiae. We tested the second most significant uncharacterized gene with predicted involvement in mitochondria organization and biogenesis (GO:0007005). For this GO term, the Bayesian integration of single-dataset SVM was selected as the best performer in the ensemble. Using an assay for measuring the frequency of petite colonies for deletion mutants, we found that compared to (a) the wild type, (b) the oms1Δ mutant showed 67% more cells without functional mitochondria. GO, Gene Ontology; SVM, support vector machine.
Conclusion
We have described an ensemble approach to gene function prediction based on three configurations of SVM classifiers. Specifically, we have demonstrated how the hierarchical context of the GO can be used to refine independent GO term predictions and how a naïve Bayes combination of single dataset classifiers can harness diverse functional information in heterogeneous data. We have shown that an ensemble of these approaches can significantly improve GO term predictions across a range of processes and performs very well relative to a number of other state-of-the-art machine learning approaches. Finally, we have demonstrated through prediction of novel annotations for mouse and experimental validation of our predictions in yeast that this method can be used to precisely discover new biology.
Materials and methods
Bagged SVM classifier for each GO term
The basis of our approach is a SVM classifier, which is a state-of-the-art machine learning method that has been used successfully for supervised learning on high-dimensional data in a number of different application domains [19]. Our application here is straightforward: we combine the raw input data into a single dataset, train a linear-kernel SVM on each GO term of interest using annotated genes as positive examples, and use bootstrap aggregation (bagging) to derive predictions. We evaluated several variations on data pre-processing and bootstrapping, and highlight some of the critical factors here.
One of the most critical choices in applying the single SVM was the way in which features from diverse input data types were combined. We found that direct concatenation of all datasets led to over-weighting of datasets with more features (for example, protein-protein interaction data), which is consistent with previous reports of feature scaling for improved performance (for example, [20]). Thus, to normalize each dataset's contribution to the Gram matrix, we separated all feature vectors for each gene into dataset-specific subsets of components, that is:
where is the feature vector for gene i from dataset k. Each of these dataset-specific gene vectors were then normalized separately as follows:
All normalized features for each gene were then concatenated in a single input matrix, D:
This matrix, D, defined the set of features for each gene that were input into each SVM. This simple procedure dramatically and consistently improves classifier performance. Before this normalization, all input genomic datasets were pre-processed as described in the 'Implementation details' section below.
A second critical aspect of our application of single SVMs was our use of bootstrapping. We applied bootstrap aggregation (bagging) for each GO term, where examples (genes) were randomly sampled with replacement (0.632 bootstrap, that is, the expected fraction of selected data points is 0.632) [21]. For each bootstrap sample, a model was learned based on the selected examples, and the resulting classifier was used to give an output for both non-selected (out-of-bag) examples and the unknown examples. The final classifier outputs were taken as the median of out-of-bag values across bootstraps for the training set, and as the median of all values across bootstraps for the unknown examples. We found that performance rises sharply with the number of bootstrapping rounds and levels off after approximately 25 rounds for all GO terms.
Bayesian hierarchical combination of SVM classifiers
The second component of our approach is a method for refining independent GO term classifiers by integrating them in the context of the GO hierarchy. The method we propose here is an extension of a simpler approach we developed and successfully applied to the problem of yeast gene function prediction in earlier work [22].
To briefly summarize, the basis of the approach is a Bayesian network that enforces hierarchical consistency across GO terms (for example, if a child node is predicted positive, then the parent node must also be a positive prediction). Each hidden node in the Bayesian network corresponds to a GO term and is associated with an observed node, which is the output of the single SVM for that GO term (Figures 4a and 5a). The Bayesian framework encodes both the hierarchical rules and the classification performance of the single node classifiers [22]. In our formulation here, the SVM classifiers at each node are first trained on the GO terms independently and performance characteristics are derived from bootstrapped outputs on held-out genes.
We apply this approach as described in [22], but extend it to work for the entire GO hierarchy (the initial method was developed for a small set of GO terms). To make inference on our Bayesian networks feasible, we split each GO branch (biological process, molecular function and cellular component) into several smaller subgraphs, each preserving the local neighborhood around each term. We used two different approaches for defining these subgraphs.
First, for each GO node on which we made predictions, we constructed Bayesian networks based on subgraphs including only other GO terms in its Markov blanket (Figure 4a). The nodes in a Markov blanket for Y are typically a subset of its parents, its children and its children's parents. The values of the variables corresponding to the nodes in the Markov blanket for Y contain all the necessary data to make a prediction for Y [23]. We refer to this approach as HIER-MB. Our second approach for defining subgraphs was to apply a breadth-first search (BFS) from each GO term to recover all descendants up to a maximum of 30 total GO terms, restricting our set to only terms with ≥ 5 annotations in the training set (Figure 5a). GO term predictions were made for all nodes present in these subgraphs. We refer to this method as HIER-BFS. Using these two approaches, each GO term occurred in several Bayesian networks, reflecting slightly different local GO term contexts. Finally, hierarchically corrected predictions for each GO term were chosen on the basis of the performance of the median of bootstrap outputs for bootstrap held-out genes.
Naïve Bayes combination of SVM classifiers on diverse data
The final component of our ensemble is a naïve Bayes combination of per-dataset SVM classifiers. The motivation behind this approach is the understanding that a single-kernel SVM on a concatenation of several diverse datasets may be less than optimal for the heterogeneity of the input genomic data. Thus, we applied an approach that learns at a dataset-specific level, but that also robustly integrates across several datasets. A naïve Bayes combination of per-dataset SVMs is ideal for this setting; naïve Bayes classifiers have been widely applied in a variety of domains and are known for their robust performance on diverse biological settings [5] and SVMs are able to provide good classification performance, particularly on high-dimensional datasets. This combination enabled us to capture the heterogeneity across datasets while still harnessing the accuracy of the SVM. SVMs were trained independently on each of the input datasets, and these outputs were combined with a naïve Bayes classifier on the basis of the held-out set performance. We used linear kernel SVMs for all datasets except the protein-protein interaction data, where we used a diffusion kernel [24] because it showed superior performance. Previous work on integration of diverse data with SVMs has focused on kernel-level integration (for example, [25-27]). We suggest this as an alternative, with the possible advantage that our framework allows for non-linear combinations of the input data, which is not always the case for kernel-level integration methods. Although direct comparison of these two approaches is beyond the scope of this work, we find that the one presented here can significantly improve a single SVM classifier's predictions in many cases (see Results). For all dataset classifiers, we used bootstrap aggregation (bagging) over 25 bootstrap samples, reporting the median output of all held-out SVM instances for each gene. These held-out values were used to characterize the distribution of positive and negative examples for each dataset and GO term (Figure 6a). We then applied a naïve Bayes classifier to estimate the probability of annotation to a certain GO term, given SVM outputs of all datasets for a gene:
where GOY stands for a positive GO term annotation (Yes), Ei represents the value of the SVM output for dataset i, and Z is a scaling factor depending only on E1, E2,.... En.
Forming an ensemble prediction
We measured the performance of each classifier (single SVM, hierarchical correction of SVMs, and a naïve Bayes combination of SVMs on diverse datasets) on each term using the AUC for the performance of the median of out-of-bag bootstrap outputs and selected the best-performing approach for each GO term.
One could imagine a more sophisticated scheme for combining these approaches and, in fact, we experimented with several. For instance, we evaluated using the naïve Bayes combined predictions as input to the hierarchical correction network. However, this and several other more complex methods resulted in poor classification performance, often characterized by overfitting. As we illustrate in the Results section, each of our individual methods shows improvement in relatively distinct areas of the GO, which may explain why simple combination schemes are effective.
Implementation details
Pre-processing of functional genomic data and gold standard
The MouseFunc benchmark datasets used in this study were provided by the organizers [9] and consisted of both binary and continuous features. The binary datasets, often very sparse, included the InterPro domain data [28], MGI phenotype data [29], Online Mendelian Inheritance in Man (OMIM) disease data [30] mapped to laboratory mouse [31], PfamA domain data [32] and protein-protein interaction data [33]. Because only non-zero entries were used as SVM input, feature columns that contained less than three non-zero entries were removed from the data matrix. All missing data were treated as zero entries.
Continuous-valued features included the Su et al. expression data [34], Zhang et al. expression data [35], expression data from Serial Analysis of Gene Expression (SAGE), and phylogenetic profiles from InParanoid [31]. All entries in these data matrices are usually non-zero. However, the values vary in scale across data matrices, making direct application of the SVM classifier impractical. As a result, for each continuous dataset, we z-score normalized the data by feature to zero-mean and unit-variance before normalizing each dataset's contribution to the Gram matrix (see the 'Bagged SVM classifier for each GO term' section).
All methods used here for gene function prediction are supervised, and thus require a gold standard set of positive and negative examples for each GO term. The positive examples for each term were taken as genes annotated directly or to a descendent term. Negative examples were assumed to be all other genes in the training set.
SVM implementation and parameter selection
In this study, we used the SVMlight software [36] as a basis to implement all SVM classifiers. We experimented with several parameters, including C (trade-off between training errors and margin), w (epsilon width), and j (cost-factor) over a wide range. We found that only the cost-factor had a significant impact on the classifier performance on our data, and we set its value to the ratio of negative examples to positive examples in the training set. With the exception of a diffusion kernel on the protein-protein interaction data, all other SVMs used a linear kernel. We also experimented with a radial basis function kernel but found that it resulted in poorer performance for many GO terms. For Bayesian network inference, we used the University of Pittsburgh Decision System Laboratory's SMILE library and GENIE modeling environment [37].
Computational cost of the algorithm
The most computationally intensive part of our method is training the SVMs, which in the worst case, is linear in the number of training examples (n) and the number of non-zero features (s) (O(sn)) [38]. SVMs are trained for each GO term, each dataset (approximately 10), and each bootstrap fold (25 total). The structure of the Bayesian networks for hierarchical correction are fixed based on the structure of the GO and the size of each subgraph is limited such that the time complexity of inference on each network is minimal (fewer than 30 total nodes). Parameter estimation for both the hierarchical and naïve Bayes classifiers is based on out-of-bag bootstrap values from the SVM classifiers and is also minimal compared to the SVM training phase.
Experimental protocol for yeast mitochondria assay
Yeast is able to grow and proliferate even without functional mitochondria on fermentable carbon sources. As such, yeast cells occasionally fail to pass respiratory competent mitochondria on to daughter cells, but these cells can continue to proliferate. Cells lacking functional mitochondria are called petite cells. In this assay we assessed the rate at which single gene knockout strains produced petite offspring as adapted from [18].
The oms1Δ:kanMX strain was obtained by fresh sporulation of the heterozygous deletion strain from the international consortium collection [39]; six independent spores were isolated by single colony purification on selective media for the kanMX cassette.
For each mutant strain tested, we grew several replicates of the strain for 48 hours in liquid YP Gycerol at 30°C [40]. Strains able to grow on glycerol were diluted and plated for single colonies on YPD plates, which releases the requirement for functional mitochondria. Thus, as colonies formed, cells without functional mitochondria were generated. When the colony is fully formed it comprises a mixture of cells with functional mitochondria and cells without functional mitochondria. We measured this ratio by re-suspending a colony and plating a dilution of this re-suspension such that 100 to 300 colonies were formed on a YPD plate. By overlaying with soft agar containing tetrazolium, cells with functional mitochondria were stained red, while cells without functional mitochondria remained white. The final mixture for agar overlay contained 0.2% 2,3,5-triphenyltetrazolium chloride (Sigma, St Louis, MO, USA), 0.067 M phosphate buffer pH 7.0 and 1.5% bacto agar. The ratio of white cells to total cells gives the petite frequency. Eight independent petite frequencies (biological replicates) were measured for each strain tested. The distribution of these frequencies was compared to the frequency of petite generation in wild-type yeast.
Abbreviations
AUC, area under ROC curve; BFS, breadth-first search; GO, Gene Ontology; HIER-BFS, breadth-first search hierarchical correction; HIER-MB, Markov blanket hierarchical correction; MGI, Mouse Genome Informatics; ROC, receiver operating characteristic; SVM, support vector machine.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
YG was responsible for developing, implementing and applying the approach and drafted the manuscript. CLM assisted in developing and applying the method, helped in interpreting the results, and helped draft the manuscript. DH and AC performed experimental confirmation on the yeast deletion mutant, and DH helped draft the manuscript. ZB originally conceived the idea of hierarchical correction and provided guidance in applying it to mouse data. OGT supervised the effort and provided feedback throughout the process. All authors read and approved the final version of the manuscript.
Acknowledgements
This research is partially supported by NSF CAREER award DBI-0546275 to OGT, NIH grant R01 GM071966, NIH grant T32 HG003284, and NIGMS Center of Excellence grant P50 GM071508. OGT is an Alfred P Sloan Research Fellow. We thank Rob Kuper, John Wiggins and Mark Schroeder for excellent technical support.
This article has been published as part of Genome Biology Volume 9 Supplement 1, 2008: Quantitative inference of gene function from diverse large-scale datasets. The full contents of the supplement are available online at http://genomebiology.com/supplements/9/S1
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Genomics 2001, 74:121-128. PubMed Abstract | Publisher Full Text
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Genetics 2003, 165:35-45. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
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J Biol Chem 2004, 279:47464-47472. PubMed Abstract | Publisher Full Text
17. Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK: Global analysis of protein localization in budding yeast.
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20. Pavlidis P, Weston J, Cai J, Noble WS: Learning gene functional classifications from multiple data types.
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22. Barutcuoglu Z, Schapire RE, Troyanskaya OG: Hierarchical multi-label prediction of gene function.
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24. Kondor R, Lafferty J: Diffusion kernels on graphs and other discrete input spaces. In Proceedings of the Nineteenth International Conference on Machine Learning: 8 to 12 July 2002; Sydney. Edited by Sammut C, Hoffmann AG. San Francisco, CA: Morgan Kaufmann; 2002:315-322.
25. Yamanishi Y, Vert JP, Kanehisa M: Protein network inference from multiple genomic data: a supervised approach.
Bioinformatics 2004, 20(Suppl 1):i363-370. PubMed Abstract | Publisher Full Text
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Bioinformatics 2005, 21:2488-2495. PubMed Abstract | Publisher Full Text
27. Ben-Hur A, Noble WS: Kernel methods for predicting protein-protein interactions.
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28. Mulder NJ, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bradley P, Bork P, Bucher P, Cerutti L, Copley R, Courcelle E, Das U, Durbin R, Fleischmann W, Gough J, Haft D, Harte N, Hulo N, Kahn D, Kanapin A, Krestyaninova M, Lonsdale D, Lopez R, Letunic I, Madera M, Maslen J, McDowall J, Mitchell A, Nikolskaya AN, et al.: InterPro, progress and status in 2005.
Nucleic Acids Res 2005, 33:D201-205. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
29. Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE: The mouse genome database (MGD): new features facilitating a model system.
Nucleic Acids Res 2007, 35:D630-D637. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
30. Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA: Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.
Nucleic Acids Res 2005, 33:D514-517. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
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32. Finn RD, Mistry J, Schuster-Böckler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, Eddy SR, Sonnhammer EL, Bateman A: Pfam: clans, web tools and services.
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1993-04 Bush assassination plot
From Issuepedia
Jump to: navigation, search
Contents
[edit] Overview
Allegedly, Iraqi then-president Saddam Hussein had planned to have then-former United States president George H.W. Bush assassinated when Bush was visiting Kuwait in April of 1993, in retaliation for Bush's involvement in the Gulf War. The plot was used by US then-president Bill Clinton as justification for launching a missile attack on Baghdad in June.
The existence of the plot has since been called into question.
[edit] Links
[edit] Filed Links
[edit] version 2
[refresh] The plot was real. Admiral Daniel J. Murphy (USN-ret.) former deputy director CIA and former chief of staff to VP Bush, and I help orchestrate the President Bush celebratory visit to Kuwait. We were briefed while in Kuwait. The threat was real and present.
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Mobil Kampung Pasir is on Kampung Pasir, J; is on E10 Npe (kuchai); is on E10 Npe (subang); is on Klang Lama (n), J; is near Klang Lama (s), J; is near Tmn Seri Sentosa, J; is near 18/14, J; is near 5/65, J; Mobil Kampung Pasir is geographically located at latitude(3.0839 degrees) 3° 5' 2" North of the Equator and longitude (101.6623 degrees) 101° 39' 44" East of the Prime Meridian on the Map of Kuala Lumpur.
The locations related to Mobil Kampung Pasir are represented by the shortest distances between two points on Earth and may not be nearest by road. For example, Mobil Kampung Pasir is located 46 metres from BHP Kampung Pasir. Mobil Kampung Pasir is located 130 metres from Sjk(t) Saraswathy. Mobil Kampung Pasir is located 134 metres from Esso Jalan Klang Lama (e). Mobil Kampung Pasir is located 179 metres from BHP Jalan Klang Lama (w). Mobil Kampung Pasir is located 266 metres from Indian Temple Kampung Pasir.
Featured Places Of Interest Located Nearby
Bkt Gasing Viewpoint is located 0.9 Kilometres away from Mobil Kampung Pasir. Bkt Gasing Viewpoint - 1 Photo(s) Featured.
Hindu Temple Bukit Gasing is located 1 Kilometres away from Mobil Kampung Pasir. Hindu Temple Bukit Gasing - 1 Photo(s) Featured.
Pearl Point is located 1.2 Kilometres away from Mobil Kampung Pasir. Pearl Point - 1 Photo(s) Featured.
Pearl Intl Hotel 1.2km, Shah Village Motel 2.7km, Hotel Singgahsana 3km, are places to stay (hotel, service apartment, inn) located near Mobil Kampung Pasir.
Tnb Shop 1km, Plaza Oug 1km, Central Hypermarket 1.1km, are places to shop (shopping mall, shop houses) located near Mobil Kampung Pasir.
Desa Water Park 3.9km, Muzium TUDM Sungai Besi 5.8km, Sunway Lagoon Park 6.3km, are places of interest (attraction) located near Mobil Kampung Pasir.
Sjk(t) Saraswathy 0.1km, Sr Agama Kampung Pasir Baru 0.6km, SMK (p) Sri Petaling 0.7km, are places of learning (school, college, university) located near Mobil Kampung Pasir.
Park Sec 5 Jalan 5 46 0.3km, Park Sec 5 Jalan 5 54 0.5km, Field Kampung Pasir 1.1km, are parks, playgrounds, open fields or commons located near Mobil Kampung Pasir.
Mobil Kampung Pasir
BHP Kampung Pasir
Sjk(t) Saraswathy
Esso Jalan Klang Lama (e)
BHP Jalan Klang Lama (w)
Indian Temple Kampung Pasir
Fire Dept Sri Sentosa
Park Sec 5 Jalan 5 46
Sec 5 Multipurpose Hall
KTM Petaling
Petronas Jalan 5 46a
Police Station Petaling
Park Sec 5 Jalan 5 54
Cameron Towers Condo
Sr Agama Kampung Pasir Baru
Avenue Court
Avant Court
SMK (p) Sri Petaling
Fraser Towers Condo
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Location Information
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Mobil Kampung Pasir
Shell Jalan Templer is about 0.9 km away.
Sentosa Court is about 0.9 km away.
Bkt Gasing Viewpoint is about 0.9 km away.
BHP Jalan Templer is about 0.9 km away.
Inai Court Apartment is about 0.9 km away.
Gasing Hill Reservoir is about 0.9 km away.
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You are here
Patent Trolls in the 21st Century
Moore's Law has been a powerful enabler of innovation because every 36-48 months you get twice the CPU cycles at half the price. In 8-12 years, Moore's law delivers 10x the performance at 1/10th the price, making the seemingly impossible relative cheap, if not free. Consequently, venture capitalists-even after the Internet bubble and the financial meltdown-largely prefer to invest in technology-driven companies in preference to almost anything else. Moore's Law simply opens up so many new business frontiers.
Except for one small problem...Patent Trolls, aka non-practicing entities.
The business model of a troll is not to open up a new field of business, but to merely place a fence across the frontier. In the good old days of America's western expansion, such a fencing strategy would be laughable, because the fence cost more than the land it was protecting, and because the land was so vast that it was virtually impossible to adequately build a fence that could contain any concerted effort. But patents, which can be written so broadly as to cover "Controlled Flight" can create a virtually infinite fence. And the cost of tying up an entire industry is a few tens of thousands of dollars for those who know what they are doing. This is the very opposite effect of what the US Patent system was originally designed to effect.
But it gets worse. It's bad enough that individuals might be placing these legal tripwires in front of all sorts of new potential fields, but now monopolies have recognized that they can use these non-practicing entities strategically, as shown in the above cartoon. What better way to kill innovation than to give ownership control to entities whose effect on the system is counter-innovation? Moreover, as the cartoon illustrates, it provides the desired anti-competitive effect without the monopoly itself acting as the direct anti-competitive agent.
I have long believed that software patents are like landmines, devices that have unpredictable destructive power, and a threat to innovators who often cannot know of their existence until the damage has been done. This latest chapter in the story tells me that they are more dangerous than ever, and that it is more urgent than ever to mount a serious campaign to disarm them all, before it is too late. If we can elect a government that believes that "open source is the best form of civic participation", then we can surely find the political will to make open source (and free software) innovation 100% legal. There are many places to make your voices heard. In the USA, you can start with End Software Patents. In Europe, No Software Patents!. And there are many others. It may seem like a bother, but sometimes political action is needed to enjoy necessary freedoms.
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20.109(F08)
From OpenWetWare
Revision as of 22:15, 26 July 2008 by Nkuldell (Talk | contribs)
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20.109(F08): Laboratory Fundamentals of Biological Engineering
Home People Schedule Fall 2008 Assignments Lab Basics OWW Basics
DNA Engineering Protein Engineering Biomaterials Engineering
Fall 2008
Instructors: Angela Belcher, Bevin Engelward, Natalie Kuldell and Agi Stachowiak
Writing Instructor: Neal Lerner, Mya Poe
Oral Presentation Instructor: Atissa Banuazizi
Graduate TAs: Luis Alvarez, Brian Belmont, Michelle Sukup,
Lecture: T/R 11-12 (66-168)
Lab: T/R 1-5 or W/F 1-5 (56-322)
Welcome to 20.109! For many of you this will be the first time in a research lab and for others it will not, but it is our goal to make this class a useful and fun introduction to experiments and techniques in biological engineering. There is not time enough to show you everything you’ll need to know if you go on to do research, but after taking this class you should feel confident and familiar with some fundamental experimental approaches and lab protocols. You will develop good habits at the bench, ones that will increase the likelihood of success in your work and ensure the health and safety of you and those around you. By the end of the semester, you should also be aware of good scientific practice, having had some experience with report writing, notebook keeping and publicly presenting your data. All of us involved in teaching 20.109 hope you will find it a satisfying challenge and an exciting experience that has lasting value.
Announcements
• You can find old announcements here
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20.109(F07): Genome engineering assessment
From OpenWetWare
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20.109(F07): Laboratory Fundamentals of Biological Engineering
Home People Schedule Fall 2007 Assignments Lab Basics OWW Basics
Genome Engineering Expression Engineering Biomaterials Engineering
Contents
General notes:
1. email these as .doc
2. email them to nkuldell, endy, nlerner and astachow AT MIT DOT EDU
3. use the following format to name your files: yourfirstname_yourlastname_Mod1_Pt1.doc, so you'll send four files: Bill_Gates_Mod1_Pt1.doc, Bill_Gates_Mod1_Pt2.doc, etc....
4. we will return Parts 1 and 4 with comments and you will have one week to re-submit these portions of your portfolio for up to 1 letter grade improvement in your score on these sections.
Portfolio components
Part 1: Rebuttal to editorial
This will be written as a homework assignment, exchanged with your lab partner for peer review, then submitted to the teaching faculty as part of your portfolio. This portion of the assignment accounts for up to 15% of your grade.
Part 2: M13.1 redesign description and parts
Submit your annotated sequence as well as a human-readable text to describe your refactoring. What do you need to do exactly? First, choose a section of the M13.1 scaffold in which you will do your refactoring work (you should choose what you want to refactor based on what seems interesting or important to you). Do not try to refactor all of M13. Only one section between two unique restriction endonuclease sites. Second, design the sequence of DNA for your refactored section of the M13 genome (NOTE: your DNA sequence must start and end with two of the available unique restriction endonuclease sites across the M13 genome). Third, provide the annotated sequence for your refactored section (follow the color scheme suggested, or a better, clearly defined scheme of your own). Don't do anything fancy. A rich text file, word document, or powerpoint file should be good enough. Fourth, provide a one paragraph description of what the purpose or goal of your refactored section is (e.g., what will it test? or, what new function will it provide?). Also, include a cost estimate for your refactored section ($1.35 per bp) and tell us whether or not you think we should have the section synthesized (GO or NO GO). We will quickly check your designs (regardless of GO/NOGO), follow-up w/ any questions, and then order them for DNA synthesis (if you or we say GO). Because we are trying to do this v. quickly this term, it is very important that your clearly annotate your designed sequence (so that we can check it), and provide a good written paragraph describing what your design goals are (so that we can more readily understand what you are hoping to do).This portion of the assignment accounts for up to 40% of your grade.
Redesign Ideas from 20.109(S07)
Gene Ideas
II
• make p2 sensitive to and perhaps degraded by any one of various stimuli (e.g. heat, light, pH, chemical input) so replication can be regulated.
• encode so that p2 can be switched on and off based on the environment which it's in, for example: stops replication of phage genome when in a certain concentration of Ca2+ enters the cell
• make p2 require a cofactor that must be added before replication of the phage begins
• make p2 count the number of times it nicks DNA
• modify p2 in a way that helps p5 sequester the + strands more effectively, perhaps making p5 work more efficiently by reducing competition.
• modify such that it not only nicks the double stranded form of the genome to initiate replication of the + strand, but also nicks the - strand to impede the formation of dsDNA (this would also help p5).
• separate g2 and g10 by inserting entire sequence of g10 after transcription end of g2/g10 (essentially repeating g10 twice in succession), so that the two genes are independent
• alter the gene to make it more active and thus replicate DNA more frequently- see how increased DNA production affects phage growth
• modify so it can nick foreign DNA (e.g. the E. coli's) and the phage can replicate and package a portion of the host DNA
• remove p2 and p5 to see if the bacteria still make the phage gene products without replicating the phage DNA
X
• make p10 sensitive to a different stimulus than p2 to again regulate replication.
• perhaps a dual control mechanism for p2 and p10 expression
• increase the number of p10 so that the phage can produce more double strands.
• modify such that the + strands of DNA are not soley dependent on the presence of p10. This modification works together with our modification of p2.
• put a tag on p10 to see what it binds at various parts of replication. This will help elucidate how it controls the amount of double stranded M13 genomes.
• modify to add another level of regulation for phage propagation. This, coupled with control of II, could allow complex control of the life cycle behavior of the virus.
• make pX more active so that more + strands will accumulate, allowing the host cell to produce even more phages.
• extract from gene II.
V
• add a tag different from p8 (e.g. RFP) to determine what stage of the phage life cycle it is in or to monitor levels of p5-ssDNA complex.
• alter interaction with p9/p7 so that a limited number of ssDNA may be surrounded by p8 at a time.
• make it sensitive to mechanism that allows for assay of DNA amount and location, change its assembly mechanism to influence phage size
• modify protein so that similar proteins, other than p8 can bind to the surface.
• remove overlap of p5 gene with start codon of gene for p7. An activation site could be added in prior to start codon in gene for p7 that could be used to allow only limited amounts of pV ( and pVII) to be expressed. This could give control over the the quantity of fully assembled phage to be produced by the host.
• modify such that p5 can sequester the + stranded DNA more effectively so that there is less competition with the formation of double stranded
• vary the activity of the protein and thus the competition between dsDNA formation and the sequestering of ssDNA- compare the results to find the optimum level of phage production possible
• modify expression so that we can control the amount of time the virus DNA spends inside the host (as opposed to actively being packaged and spreading to other bacteria).
• allow it to sequester double stranded DNA also, then it can be used as a vector for infecting cells with desired DNA fragments.
• add more DNA binding sites to see if more DNA can be packaged into phage.
• add some base pairs between V and VII to allow for a restriction site.
VII
• alter gene so protein adopts different/more flexible conformation. A change in conformation might expand the different residues that can be attatched to its N-terminal portion.
• change the way p7 interacts with p9
• modify to increase rate host will shed phage, i.e. decrease the phage-host interaction time.
• modify the last few codons to remove overlap with the gene encoding p9.
• add sequence to the 5' end of gene so protein could build nanowires or long filaments or other useful materials.
• delete to learn more about its function.
• increase it's expression to learn more about its function.
• tag protein to monitor interaction with p5/DNA complex.
IX
• modify p9 to bind to p3 to create long filaments of phage lined up end to end.
• modify to express different reactive chains on the phage surface.
• change the function so that p9 will now lyse the bacteria.
• modify to make the phage secretion occur at a faster rate so that interaction time with the host is reduced.
• modify beginning and end sequences so that g9 does not overlap with g7 and g8.
• modify the p9 so that it can bind to bacterial surface proteins (the way p3 does)- see if this allows the phage to interact with other bacteria (now that both ends of the phage can bind and perhaps bridge the two bacterial cells)
VIII
• add epitope or other tags, e.g. x-ray sensitive, UV sensitive, flourescent.
• alter gene so p8 has an affinity for certain residues or salts. This can vastly increase the function of m13 as a whole. It can be used to transport different things into bacteria.
• change p8 interactions with p5 to regulate size of phage or influence shape of phage by changing how it assembles into a coat.
• alter gene so fewer copies of p8 fit on phage coat allowing a more flexible packing structure.
• insert sequence between genes for p5 and p8 to isolate production of these proteins and control their expression levels via activation or repression sites.
• change amino acid sequence to allow p8 (and thus the entire virus) to bind to certain materials, like metals
• add a small protein to the gene for p8 to amplify because p8 is synthesized so many times
• uncoupled gene for p8 from the gene for p9.
III
• add epitope or other tags, e.g. x-ray sensitive, UV sensitive, flourescent.
• modify portion of p3 that normally interacts with TolA on bacterial pilus to vary phage selectivity to different or only certain bacteria.
• make p3 bigger so that the phage can bind to objects easier and so that they might bind to bigger objects.
• selective degredation of p3 to control the maximum amount of DNA allowable on the phage sequence.
• modify to monitor the timing of the phage escape from host.
• add sequence to make the tail protein longer.
• make series of changes to explore the mechanism by which p3 enters and exits the cell. For example: exchange charged amino acids for neutral, acidic for neutral or basic, etc.
• delay the time at which the p3/p6 cap is added by making p3 expression a function of environmental cues such as ionic strength or pH. Could also study the effect this would have on the infection process since p3 is also the protein which binds to the TolA protein on the bacterial pilus.
• change the GTG to ATG start.
Part 3: Data summary for p3-modifications you performed in lab
You'll find guidelines for writing here. Additionally, many of the "for next time" assignments can get you started on this part of the portfolio. Including but not limited to:
• Table: Oligonucleotide design, sequence consequences for phage when inserted and sequence data
• Table: Ligation results
• Figure: Agarose gel examining candidate clones
• Figure: Western results
• Table: Plaque assay
• Short paragraph for each table and figure describing and interpreting what's shown
• One or two sentence summary of your experimental results
• One or two sentence proposal for what you'd do next if we had one more month to spend on this project
This portion of the assignment accounts for up to 20% of your grade.
Part 4: Mini-business plan for the Registry of Standard Biological Parts
Put yourself 5 years in the future and imagine that the Registry is floundering. Though the number of useful parts has grown through the hard work and dedication of its volunteer workforce in the iGEM program, there is a notable lack of standards:
• around the parts themselves (some work always, some in rare conditions, some not at all)
• around the assembly process (alternative biobricks and registries have gained popularity)
• and around documentation for the parts (some have great spec sheets and some have nothing).
Decide that you will direct the Registry into a manufacturing, service, high tech, or retail business and then devise a plan to grow and stabilize that business. This portion of the assignment accounts for up to 25% of your grade.
In no more than three pages provide a business plan that includes:
1. An Executive Summary In 250 words or fewer, explain:
• what is your product
• who are your customers
• what the future holds for the registry in particular and synthetic biololgy more generally.
• what you see as the key to success
• This summary should sound enthusiastic, professional and be more readable than most "mission statements."
• consider writing this section after you've written the rest of the plan.
2. Summary of the current Registry
• describe what the Registry is, including products, services, customers, ownership, history, location, facilities.
• include strengths and core competencies of the Registry.
• segue into the next section by mentioning the significant challenges faced in the near and long term.
• this section should be no longer than 2 paragraphs.
3. Market analysis Dedicate one paragraph to a description of the market. You might consider including information like:
• who makes up your market?
• what is it's size now? how fast is it growing? how do you know?
• what percentage of the market do you expect the Registry to have now and 5 years from now?
• how could changes in technology, government, and the economy affect your business?
4. Business plan Specify your strategy for continued growth of the Registry. The emphasis of this section will differ depending on the kind of business model you have chosen (retail, manufacturing, service or high tech).
Here are some questions you might consider as you formulate your business plan:
• how will you promote the use of the Registry?
• how will you advertise?
• how will you price your product/services.
• where will you locate the Registry (or BioBrick franchises) and how you will distribute parts/services?
• how you will keep the Registry competitive?
• how/if you will protect intellectual property while also promoting sharing and community?
• does your plan emphasize increased production, diversification, or eventual sale of franchises?
• how long will your strategy take to be partially or fully realized?
• are there start-up costs associated with your business model? how much and where will the capital come from?
• will your registry require insurance coverage or litigation insurance?
• are there trademarks, copyrights, or patents (pending, existing, or purchased) considerations?
• how many and what kind (skilled, unskilled, and professional) of employees to you anticipate?
• where will you recruit employees?
• will top notch employees advance? to what?
• how will you training employees?
• what kind of inventory will you keep: raw materials, supplies, finished goods?
• will there be seasonal fluctuations to demand for parts?
• will you need lead-time for ordering?
• do you expect shortages or delivery problems?
• are supply costs steady? reliable?
• will you sell parts on credit?
• how will you set prices?
• what kind of guarantees and privacy protects will you offer?
This section has no defined length or format but should end on an enthusiastic note that might lead some venture capital firm or a funding agency to stay interested. A helpful link on persuasive writing techniques is here.
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He who wonders discovers that this in itself is wonder. Escher, M. C.
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The author is me, I've been writing for myself and for others over a period of twenty five years.. Succint phrases such as those found in the "Quotations Book" have been my morning resonance... Thank you, Don H Blum
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Life is a series of natural and spontaneous changes. Don't resist them -- that only creates sorrow. Let reality be reality. Let things flow naturally forward in whatever way they like. Lao-Tzu
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Hinotori Houou Hen: Gaou no Bouken
From StrategyWiki, the video game walkthrough and strategy guide wiki
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Hinotori Houou Hen: Gaou no Bouken
Developer(s) Konami
Publisher(s) Konami
Japanese title 火の鳥 鳳凰編 我王の冒険
Release date(s)
Genre(s) Platform
System(s) Famicom
Players 1
Title screen
Hinotori Houou Hen: Gaou no Bouken is a side scrolling platformer developed for the Famicom and published by Konami at the start of 1987. The title is roughly translates as "Phoenix - Firebird volume: Gaou's Adventure." The game is based on the manga series by Osamu Tezuka, creator of other famous anime icons such as Astroboy. Tezuka considered Phoenix his "life's work"; it consists of 12 books, each of which tells a separate, self-contained story and takes place in a different era.
The Famicom game is based primarily upon the fifth volume of the Saga (entitled Resurrection when published in English by Viz Media,) and focuses on the character Gaou, a man who lost an arm and an eye as a baby and was treated harshly by peers and adults alike while growing up. Angry and resentful, Gaou learns that no humans will give him a chance for a happy life, so he does whatever is necessary to survive, including murder if necessary. However, he reveres nature and will go out of his way to save the smallest insect's life. Along his travels, he meets a monk who changes his perspective on life and teaches him to tap into his innate talent to carve and sculpt. His creations are unrivaled in terms of the raw emotion that they communicate. Throughout his life he crosses paths with another sculptor whose arm Gaou once slashed. They each have they own encounters with the Phoenix, whose blood grants immortality to any human that drinks it.
In the game, Gaou must travel through 16 different stages collecting an artwork card from each stage which, when fully assembled, display the picture of the Phoenix. Many stages reference scenarios from other volumes of the Phoenix saga, and take place in the future as well as in the past. Some stages are linearly connected, while other stages from other time periods can only be accessed by finding the hidden warp that leads from one stage to another. At Gaou's disposal are his chisel (which he originally used to sculpt gargoyle head statues), and the gargoyle heads which he can deposit to form makeshift platforms. The game ends when all 16 cards are collected, and the Phoenix is revealed
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Perth
From Wikitravel
Oceania : Australia : Western Australia : Perth
Revision as of 06:40, 11 February 2013 by 58.7.145.132 (Talk)
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For other places with the same name, see Perth (disambiguation).
Perth is a huge city with several district articles containing sightseeing, restaurant, nightlife and accommodation listings — consider printing them all.
Perth is the capital city of Western Australia and is the most isolated capital city of over 1,000,000 people in the world.
Perth sprawls along a flat coastal plain, centred along the Swan River and bounded by the Darling Scarp to the east and the Indian Ocean coastline in the west. Perth has a population of around 1.6 million (2009), making it the fourth largest city in Australia. The many uncrowded beaches along the Perth coastline define the lifestyle: Perth is laid-back, quiet and safe.
Districts
Perth Metropolitan Area
While the CBD straddles the Swan River, most of Perth's residents live in suburbs along the coast.
Perth Districts Map
City
Where commerce and culture intermingle
Fremantle
A boatload of history and food and entertainment
Northbridge
Restaurants, bars, clubs, cafes and Art
The Coast
The place for a swim or watching the sun sink into the Indian Ocean
Northern Suburbs
Many, many houses and an aquarium
Southern Suburbs
Many, many more houses and the Zoo
The Hills
Wine, trees, a few hills, a couple rivers and a Weir
Outside the city
1-2 hr outside the city are many small townships and a big island
Perth surrounds
Outer Perth
Small townships out of the city
Rottnest Island
Where locals like to relax with the Quokka
Understand
History
The Perth region has been home to the indigenous Nyoongar people for at least the past 40,000 years.
British settlers established a free settler colony in 1829 as part of the Swan River Colony. The settlement was given the name "Perth" after the city of Perth, Scotland, the hometown of Sir George Murray, the British Colonial Secretary at that time. From 1850, an influx of convicts boosted the size of the colony and their labour helped shape the early architecture of the city. The discovery of gold in the 1890s triggered a boom which, with subsequent mineral discoveries, has been key to the city's economy. As capital of the state Western Australia, Perth joined the Commonwealth of Australia in 1901.
Once a small, isolated city, the mining boom in Western Australia following the end of World War 2 has led to a high rate of migration to Perth, which allowed its population to overtake that of Adelaide in the 1980's. While the actual mining takes places in distant, more remote parts of the state, much of the mining-related services sector is based in Perth. Today, Perth remains Australia's fastest growing city, and in recent years has transformed from a relatively laid back city to a fairly vibrant one. Due to the fact that Perth's population growth was relatively recent, it lacks the dense Victorian core of the eastern cities, but makes up for it with its own charm, particularly seen in the numerous parks and other green spaces within close proximity of the CBD.
People
Despite its isolation and relatively small population, Perth is a surprisingly culturally diverse city. Due to the high rate of migration to Perth, slightly less than half of Perth's residents were born outside Australia. Its proximity to Southeast Asia and Africa has led to an influx of migrants from countries such as Malaysia, South Africa and Thailand, and this is reflected in the diversity of cuisine available in Perth. If you wish to expereince a cosmopolitan culture without the hustle and bustle of larger cities, perhaps Perth would be your cup of tea.
Climate
The City has a temperate Mediterranean type climate. Summers are hot and dry whilst winters are generally wet and mild. Summer temperatures average 30°C/86°F between November and April. Maximum temperatures during the height of summer can reach and sometimes exceed the 40°C/104°F mark. Very hot days tend to have very low humidity making conditions more bearable.
In the Perth metropolitan area the summertime temperature rises rapidly during the morning, relived in the afternoon when the "Fremantle Doctor" blows inland from the ocean to cool the city by up to 15°C. The doctor runs out of puff before reaching the areas further inland, leaving the hills and beyond to swelter till after sunset.
Winter (Jun-Aug) temperatures are usually around 15°C. Minimum temperatures sometimes drop below 0°C on clear nights. Though Perth goes through lengthy dry spells, when it does rain, it pours. Storms with strong winds occasionally hammer a winter night, but they generally cause no more destruction than a toppled tree or flattened fence.
When to visit
Spring (Sep-Nov) and Autumn (Mar-May) are ideal times in which to visit Perth. Spring (particularly October / November periods) is perhaps the very best to see the sights as after a decent winter's rainfall, the famous wildflowers around Kings Park and the Avon Valley bloom splendidly. The metropolitan areas as well as the bushlands have many flowering species which often flower en-masse, so it is wise to purchase over-the-counter hayfever or antihistamines from a local chemist before making a trip to see them with minimal discomfort. Beach-goers from colder climes might find the summer months too harsh, usually reaching about 35°C and sometimes up to 45°C during the midday, so it is perhaps best to visit during March-April or October-November as well as taking a hat, sun-screen lotion and sunglasses.
The local inhabitants tend to holiday during the height of summer or winter, either to escape the climate, or to celebrate it. In winter Perth inhabitants often travel north to Broome or Bali for the warmth, or oppositely staying in small chalets in the southern country during the winter to enjoy the cool wet climate and seasonal foods.
Although Western Australia has many public holidays they are unlikely to cause much inconvenience to your travels. Shops are still open, public transport still runs and the sky is still blue. The exception may be New Years' Day (Jan 1), Australia Day (26 Jan), Good Friday (2 Apr), Easter Monday (5 Apr), Labour Day (first Monday of March), Queen's Birthday (27 Sep) and Foundation Day (first Monday in June) and Christmas Day (25 Dec). Most larger shops and shopping centers, pubs and restaurants are closed on these days but smaller convenience stores and some fast food chains keep their doors open. That said however, more and more stores are beginning to open on public holidays. Sunday trading came into fruition in late 2012 and most shops have quickly adapted to opening on Sundays.
Get in
By plane
All scheduled international and domestic flights arrive and depart from Perth Airport (IATA: PER). Though both international and domestic services operate under the same Perth Airport banner, the international terminal (Terminal 1) is in a completely separate area, about 10 km from the domestic terminals (Terminals 2 and 3).
The domestic terminals are both connected as part of the same building, and it is just a short walk between them.
Airlines & destinations
Major airlines operating from each terminal:
• Terminal 1 - Perth International Airport: AirAsia, Qantas, Malaysia Airlines, Singapore Airlines, Thai Air, Tiger Airways Singapore, Virgin Australia and a few others.
• Terminal 2 - Qantas Perth Domestic Airport: Qantas domestic flights QF400 and above, QantasLink (which services numerous regional centres in WA), Airnorth and Jetstar.
• Terminal 3 - Skywest, Tiger Airways Australia and Virgin Australia Domestic terminal. Other airlines flying from here include Alliance and other regional airlines.
Major domestic airlines servicing Perth Airport are Qantas (full-service), Virgin Australia (full-service), Jetstar (low-cost, owned by Qantas and from Perth, only flies to a few cities), Tiger Airways (low-cost, only flies to a few cities), QantasLink (a regional subsidiary of Qantas) and Skywest (regional full-service, although does fly to Melbourne via Kalgoorlie).
International connections are mainly to Asian cities such as Singapore, Bangkok, Kuala Lumpur, Dubai, Hong Kong and Guangzhou. From Africa, South African Airways operates a flight from Johannesburg.
International Terminal 1
The city and major hotels can be easily accessed by taxi or commercial shuttle buses from all terminals. Courtesy phones are located inside the terminals (for the domestic terminal, the courtesy phone is surrounded by a large board advertising accommodation past the baggage conveyor belt as you leave the arrivals area).
For more than two people it is often cheaper and faster to take a taxi into the city (waiting time and drop off other passengers can make a shuttle bus service to the city very long). A taxi by meter to the city will cost approximately $40 from the international airport; the shuttle costs about $16 per person.
There is no public transport to the international terminal.
Domestic Terminals 2 & 3
Transperth buses serve the domestic terminals. Useful services are:
• Bus 37 runs from Kings Park via Perth city and connects with the Victoria Park Transfer Station and Belmont Forum Shopping Centre for connections with other Transperth bus/rail services. (every 30mins, 6:19AM-11:56PM, $3.60)
There are a couple of coffee shops and food outlets both before and after security, as well as basic shopping, books and souvenirs. If you have some time to kill in transfers, there are some cafes open during business hours in the surrounding industrial park. Walk straight across the carpark, or turn right and walk past the long term car park to the Flight Path Cafe in the Civil Aviation Authority building.
Terminal transfers
A free transfer bus operates between T1 and T2/T3. The service runs every 50 minutes and the journey takes 10 minutes. During the night the service is still free but requires pre-booking by phone ☎ +61 410 636 418). [1]
A taxi between the terminals will still cost at least $20.
By boat
Once the only way to way to get into Perth, a limited number of passenger ships now dock at Fremantle. A number of round the world cruise ships including the Queen Mary 2 and Queen Victoria call into the Fremantle Passenger Terminal [2] on their own schedule. While sailing into Perth from over the Indian Ocean might sound romantic, its hardly the cheapest way in.
By train
The Indian Pacific [3] trans-continental railway runs from Perth to Sydney via Kalgoorlie, Adelaide and Broken Hill. It is generally not cheap, but this journey, which takes four days and three nights, is one of the world's great train journeys. The train traverses the longest stretch of straight track of any railway in the world (478km) as it journeys across The Nullarbor.
The Indian Pacific leaves from and arrives at the East Perth terminal, which connects with Perth's suburban rail network as well as the regional bus depot. The city centre is just a 5 min train ride away from the terminal. If you are carrying baggage, it is probably best to jump into a taxi as many of the city's hotels and hostels are located up to a few kilometres away from either of the stations.
International visitors intent on train travel might want to consider purchasing a rail pass for unlimited travel on any of Great Southern Railways' services including the Indian Pacific (Sydney to Perth), The Ghan (Adelaide to Darwin via Alice Springs) and The Overland (Adelaide-Melbourne). The rail pass entitles you to just a sitting seat on any train for 6 months for $700 ($100 less for students/backpackers). Taking your car with you is also possible between the capital cities and Alice Springs, for an additional fee.
Regular train services (one or two per day, depending upon whether you are travelling during the week or on Saturday/Sunday) are available to and from the regional cites of Kalgoorlie (departing from East Perth) and Bunbury (departing from the central station). The Get out section features more information regarding these regional services...
By road
There is currently no regular scheduled coach service across the Nullarbor Plain between Perth and Adelaide. People wishing to travel by road may wish to consider one of the adventure oriented tours that include camping and sightseeing. The only one currently operating on a regular schedule is Nullabor Traveller [4] Adelaide to Perth and Perth to Adelaide
Greyhound Australia [5] offers a daily coach service the length of the state from Darwin via Broome. At over 2 1/2 days this is not a trip to be taken lightly.
Driving a car from Perth and Adelaide is also an option and the road and accommodation infrastructure makes it achievable without too much stress. However, be warned that it is still a 2,700 km drive and is considered a 'once in a lifetime' activity for locals.
The main operator of regional bus services in south west Western Australia is the government run Transwa [6]. The Australind [7] train departs Perth Train Station at 9:30AM and 5:55PM daily for Bunbury in the south west with various coach connections, and The Prospector [8] departs from the Public Transport Centre (East Perth) at various time to the inland city of Kalgoorlie. Coaches also depart from the Public Transport centre to various locations around the state.
Coach services are available from Transwa or South West Coach Lines (enquire at their office in Esplanade Busport).
Get around
By public transport
The Perth metropolitan area has a fairly reliable and inexpensive public transport system operated by Transperth [9]. Information about timetables, disruptions or service alterations can be found on their website, by calling 13 62 13 or at 'Transperth Infocentres' located in at the central train station and a couple of branches in the City
Bus
A reasonably reliable network of public bus services run around the suburbs between bus and train stations.
Transperth also operates a free CAT bus service in Perth CBD, Northbridge, Fremantle and Joondalup. The large air-conditioned buses of different colours with the distinctive cat logo run about every 10 min on various routes around major facilities and attractions. They are a great way of getting from one place to another.
The buses are free leaving and entering the city within the Free Transit Zone- it runs from Newcastle Street down and from the end of Kings Park when going towards Subiaco. This does not require a Smartrider, just get on.
Train
The Swan City's suburban railway network is great for quickly getting to outlying suburban areas. All services stop at the central Perth station in the City on their way to or from the outlying terminating stations. The Mandurah line travels through the Esplanade station adjacent to the busport and the south of the city.
Train services run frequently during peak hours and every 15 min during weekday daylight hours and 30 min after 7PM and weekends. Services commence around 5:30AM cease at around midnight. During peak hours Perth Station can get quite busy.
Fares
The Transperth system is divided into 9 concentric zones, as well as the Free Transit Zone (city centre and surrounds). The Free Transit Zone on the trains is only available to SmartRider (transport card) holders, passengers without a card have to buy a ticket. Tickets and passes are valid on all buses and trains within a zone. Tickets are valid for two hours and can be used on your return trip.
Zone 2 extends as far as Fremantle and for most visitors a two zone ticket will suffice. Single trip, cash tickets can be purchased from bus drivers or coin-operated ticket machines located at train stations. The more convenient SmartRider cards automatically calculate your fare and deduct it from your card when you tag on and off upon boarding and alighting bus and train services. SmartRiders can be bought or recharged at Transperth Information Centres, major train and bus stations and/or from most Newsagents. Bus drivers can also charge your SmartCard for you, however they will not provide change. SmartRider cards carry a 15% discount over cash fares.
There are $9.30 Single Rider passes available after 9am most days. Family Rider passes also cost $9.30 and allow two standard fare passengers plus up to (five?) concession passengers unlimited travel- these are only available after 6pm Monday to Thursday, after 3pm on Fridays, and all day on weekends and school or public holidays. This is an excellent value for couples and couples with children, as a standard one-way fare alone runs from $2.60 for one zone, $3.80 for two zones, and $4.70 for three zones.
With the advent of the new SmartRider system those passengers not holding SmartRider cards will need to present their paper ticket to the transit guard upon entering and leaving Perth Station and selected suburban stations.
Taxi
Taxi experiences in Perth can range from hassle-free to problematic. Extended waits during peak periods (5AM-9AM Weekdays and Weekend Evenings) are common, but outside these times, taxis are plentiful. Booking a taxi is possible but only recommended if your journey is likely to be upwards of $25 or you are travelling to the airport. This is due to the convoluted way in which the dispatch services handle timed bookings. If your journey is likely to be short, it is better to simply call for a taxi once you are ready to leave, or hail a taxi if you are in a busy area.
Two major taxi companies are Swan Taxis (13 13 30), who dispatch Swan, TriColor, 13CABS, Yellow and Coastal taxis, and Black and White Taxis (131 008). There are numerous smaller companies that operate mainly out of the Central Business District. Fares are regulated by the state government and all dispatch companies charge the same rate. Flagfall is $3.90 during weekdays, increasing to $5.70 on weeknights and weekends. The kilometre rate is $1.59/km charged in $0.10 increments. Surcharges apply on designated holiday periods (New Years Eve and Christmas Day) and on weekend nights between midnight and 5AM. Tipping taxi drivers in Perth is not customary, but adding a small gratuity ($1 or $2) on top of the fare is common for exceptional service.
Catching a taxi from an entertainment precinct late on a Friday or Saturday night sees clubbers waiting at taxi stands up to 2 hours for a ride home. Drivers are known to avoid picking up drunken patrons from outside of pubs, clubs or from the entrance to Perth central station. There have been a recent spate of sexual assaults on female passengers so it is advisable to travel in groups. There are specially designated 'secure ranks' operating at these times where patrons can queue in (relative) safety. Another option is the late night Transperth trains and buses run specially for revellers after their night out.
Services at Perth Airport are reliable and taxis arrive continually 24hrs a day. A typical taxi ride from the Domestic Airport to the City is around $30 ($35 from the International). There is a $2 airport tax payable on top of the fare.
By bicycle or on foot
Perth and Fremantle can be comfortably explored on foot or by bicycle as Perth has some of the best cycling and pedestrian infrastructure in Australia. The Perth bicycle network features an ever growing, metro-wide system of bicycle/pedestrian paths. The system features;
• Principal Shared Paths (high standard shared paths that run adjacent to each railway lines and along major motorways).
• Local Bicycle Routes (a series of on-road routes as well as some suburban off-road sections that run through parks - these paths provide a connection to such destinations such as schools, shopping centres and other recreational facilities.
• Generic minor works (projects include general improvements to the cycling environment in local areas, such as on-road bike lanes and sealed shoulders).
• End of trip facilities (including; U-Rails, Cora bike racks and bike lockers and change-rooms).
Cycle maps are available from most bike shops, and at Planners Map [10]. The Department for Planning and Infrastructure provides a range of guides, maps and brochures for bike riders. If you have a scenic route in mind, these brochures can take you to the coast, Kings Park, Armadale and the Hills or around the Swan River.
A favourite amongst seasoned local cyclists is the ride along the North side of the Swan River between the City and Nedlands. Allow 60 min for a round trip along this route, as you might encounter a strong headwind.
Bicycles are allowed on board Transperth trains but not during peak hour, unless they are the type of bicycle that can be folded up.
Cycling at full pelt in the fully pedestrianised Hay and Murray St malls in the city centre is generally tolerated by the police. Doing this, however, is an easy way to cheese off local pedestrians if you are going too fast.
By car
Renting a car is the ideal means of transportation for traveling to outlying attractions. Perth's major freeways and highways are free from any tolls, as is not the case in Sydney and Melbourne and from either of these major arterial roads, it is possible to be surrounded by beautiful countryside within minutes.
Rent-a-car providers are located adjacent to the airport and there are quite a few scattered around the city and the suburbs.
The general speed limit within built-up areas is 50 km/h unless otherwise stated.
Note that traffic in Perth (as elsewhere in Australia) travels in the left-hand lane. It is advisable to travel on the left hand lane even in dual carriageways for tourist drivers. This might take a bit of getting used to if you drive on the right-hand side back home. Even for right-hand drivers some things are different here like the ability to overtake on the inside of a vehicle on a freeway.
Note that Police are rarely seen out on the roads but manned mobile speed cameras operated by public servants are very prevalent. Driving even 5km/hr above the placarded speed can incur a fine . Driving 40km/hr above the placarded speed means the car is impounded for 28 days even if it not your car (hire cars excepted).
See
There is plenty to see in the city centre within wandering distance or on a free CAT bus. Hidden among the sprawl of the surrounding and metropolitan area are a few worthwhile attractions usually less than an hour away by car, or a bit longer on public transport.
Outside of the metropolitan area are some unspoilt national parks, unpopulated coastline and other interesting locations.
Kangaroos
There is a designated area in the zoo for kangaroos where they can wander on visitors' paths and the animals are used to people so you can see them very close.
To see semi-wild kangaroos visit the Pinnaroo Valley Memorial Park (a cemetery, but not European style) [11] - it's a walking distance from Whitfords Transperth Train/Metro Station - just cross the highway, the highway exit and look for the entrance on the left. As there is plenty of space for them you may see them not only eating but also hopping.
Spectator sports
• Australian Rules Football. Perth, like Melbourne, is mad for its footy. Every weekend between (roughly) March and August, Subiaco fills to near-capacity with either West Coast Eagles or Fremantle Dockers supporters. Why not choose whose colours you like best and join in the fun? As the Eagles are the more popular and successful side in the Australian Football League, many of their games are already sold to capacity, so it is best to buy your tickets a couple of weeks before the scheduled fixture (Ticketek offer a pick-up service at the venue). Aussie rules football might be hard to understand at first, but it is quite exciting.
• Other sports Other professional sports have a presence in Perth:
• Perth Glory – If you prefer association football (generally known by Australians as "soccer") and find Australian Rules football too confusing, Perth Glory Football Club compete in the A-League, Australia's top level of football. The season runs over summer from October to March, with the possibility of qualification to the finals series (playoffs) running into April. They have a sister club, Perth Glory W-League, that competes in the women's W-League. Both teams play at Perth Oval, also known as NIB Stadium due to a sponsorship deal. The stadium is a 10 min walk from Northbridge, or a 3 min walk from Claisebrook Train Station.
• Western Warriors – Play cricket in all three of Australia's main domestic competitions—the Sheffield Shield ("first-class"; matches run for four days), the Ford Ranger Cup (one-day cricket; matches last about 8 hours), and the KFC Twenty20 Big Bash (matches last about 3 hours). Home ground is the WACA. The WACA also hosts one of the summer Test matches against England in January.
• Western Force – Rugby union team in the Super 15, involving teams from Australia, New Zealand, and South Africa. Season runs from February to late May. Western Force play at NIB Stadium.
• Perth Wildcats – Play in the National Basketball League.
• Perth Lynx – Play in the Women's National Basketball League.
• Perth Heat - Play in the Australian Baseball League
Do
A beach on Rottnest Island, off the coast of Perth
• Swim. Perth boasts some of the country's best beaches, which are ideal for swimming during the warmer months. Sunscreen is essential and insect repellent may come in handy during the evening. As the beaches are on the open ocean it is strongly advised that you only 'swim between the flags' at patrolled beaches. Probably the easiest beach to get to by public transport is Scarborough beach, which can be accessed by catching the Clarkson line from platform 1 at either Perth Underground or Esplanade stations, getting off at Glendalough station before catching the 400 bus. Alternatively, you can catch the 400 from the Wellington St bus station which is located down the far end of the central station - from any of its platforms, head west to the concourse, turn left and then head down the ramp. Cottesloe Beach, one of Perth's most famous, and a favourite among locals and tourists alike, it even easier to access by public transport. Take the Fremantle line to Cottesloe Station, exit the platform at the Perth end, and head west down Forrest Street for about 10 min. Or you can take bus 102 from Williams street or Esplanade station and it has a stop right by the Cottesloe beach. There is a shady grassed area as well as sand, and the beach is patrolled.
• Swim Naked. There is only one beach in Perth that permits nude bathing: Swanbourne. Males sunbathing topless at other beaches is the norm, however females will not usually get a police fine but will get stared at. The atmosphere at Swanbourne Clothing Optional Beach (about 500 m north of Swanbourne Beach) is friendly and relaxing. It is more of a sunbathing beach than a swimming beach, with a steep sandy descent into water which gets deep quickly. There are no lifeguards or red-and-yellow flags at this beach and so it is essential to keep a close eye on children near the water. The nude beach is frequented by a variety of sun-seekers of all ages; couples, families, groups. The easiest way to get there is by car, however there is a train station about 1km away. Alternatively, you can catch the bus 102, which is heading to Cottesloe. The bus will go through some residential area before reaching Cottesloe coast. As soon as you can see the ocean, get off the bus and Swanbourne beach is right cross the road. Heading north down the beach, you can reach the nude beach.
• Cycle. Perth has excellent bike paths and fantastic weather almost all year round which makes it perfect for cycling. The paths that follow the Swan River are very scenic and mostly flat. You can take your own bike, hire a bicycle from one of the bike hire providers located near the Swan River or take a tour with Bluetongue Bike Tours [12] or Pedal OZ [13].
• Parks. Perth has a number of fantastic parks, ranging from inner-city parks such as Kings Park, Bold Park, and Lake Monga, to outer city parks such as John Forrest and Whiteman Park
• Catch a flick. At one of the many independent or European cinemas, including Paradiso in Northbridge and The Luna cinemas in either Leederville or Fremantle. These cinemas showcase a range of local, Bollywood, French and Italian productions as well as International film festivals and documentaries throughout the year. Also check out the open air cinemas in summer, located in Kings Park, Movies by Burswood, Luna Leederville, and Mundaring.
• Get out. For a day in Fremantle; great for a walk around without a specific goal in mind or for some light shopping or why not enjoy a meal or coffee and cake whilst soaking in the atmosphere? Don't miss Fremantle Markets. Fremantle Prison, the Maritime Museum, the Round House and the Statue of AC/DC's Bon Scott are popular attractions.
• Take a Day Trip. As with any travelling in a country with as low a density as Perth, you will become accustomed to spending a lot of time travelling between the sights. One of the best day trips in Perth is to visit the nature reserve off the coast of Fremantle, Rottnest Island. You can access Rottnest Island by a ferry, 30 min from Fremantle or a longer from Barrack Street Jetty in Perth. The trip can be expensive, but Rottnest Express has a “Telethon Tuesday” deal with half price tickets ($35 instead of $70) every week for most of the year. Rottnest is a car free island, but plenty of bikes available for hire from the island or directly from the ferry company. There is a huge variety of wildlife to see (including the famous Quokka) and opportunities to see whales, dolphins and fur seals off the coast, but this will always depend on the season. Another (closer, cheaper but smaller) option is to visit Penguin Island, home of the "Little Penguins" or "Fairy Penguins", located 5 min off the coast of Rockingham, a 45 min drive south of Perth.
Perth boasts some of the country's best beaches, which are ideal for swimming during the warmer months. Sunscreen is essential and insect repellent may come in handy during the evening. As the beaches are on the open ocean it is strongly advised that you only 'swim between the flags' at patrolled beaches. Probably the easiest beach to get to by public transport is Scarborough beach, which can be accessed by catching the Clarkson line from platform 1 at either Perth Underground or Esplanade stations, getting off at Glendalough station before catching the 400 Bus. Alternatively, you can catch the 400 from the Wellington St bus station which is located down the far end of the central station - from any of its platforms, head West to the concourse, turn left and then head down the ramp.
• Go Wine Tasting. Well renowned amongst locals and tourists alike, the Swan Valley in the hills boasts some of the country's best wineries and micro-breweries. Although the wine is perhaps not as highly regarded by seasoned wine buffs as that produced in regions such as Margaret River, the Swan Valley features the advantage of being close to the city.
There are a lot of options if you have access to a car - from the city just head to the coast, then head north or south for some exploring.
Live music
Perth is well known for its indie music scene at established venues such as Amplifier Bar, Rosemount, Fly By Night, The Rocket Room and Mojos. The Big Day Out festival is held in early February every year. Visit YourGigs [14] for upcoming gigs or Perth Indie Bands [15] for a selection of good Perth bands.
• Raves and Festivals. If dance music is your thing, many top DJ and electronic music artists will make the trip out to Perth between October and March. Visit [16] for upcoming dates.
Buy
Kakulas Brothers shop on Williams Street
Previously known to be lacklusture, shopping options in Perth have improved dramatically in recent years, with major international luxury brands such as Burberry, Gucci and Louis Vuitton now having branches in Perth, along with many local Western Australian boutiques. As a general rule, the luxury brands are located around the junction King's Street and Hay Street in the city centre, while mid-range options are generally to be found at the pedestrian-only Hay Street and Murray Street malls.
The largest concentration of boutique shops is in the City centre while adjacent Northbridge is the place for niche independent stores. Trendier suburbs such as Mount Lawley, Leederville and Subiaco have a number of offbeat designer fashion stores.
Large shopping complexes located in the outer suburbs, such as in Morley, Carousel, Cannington, Midland, Joondalup, Booragoon (Garden City), Innaloo and Karrinyup have the usual department and chain stores.
Fremantle Markets offers an experience on its own with its over 150 independent stalls.
Hours
Shopping hours in Perth are mostly regulated by the government. Between January and November they are:
• 9-9 M-F (Mostly used by the large chain supermarket stores)
• 9-5 Sa
• Extended trading to 8 or 9PM on Thursday in suburbs or Friday night in the City Centre
• 11-5 Sun
In mid-December Christmas trading hours kick in and usually run until the end of December (individual shopping centres set their own times). Trading is extended to 9PM on weekdays and on Sundays most shops open 10AM-5PM.
A 10% Goods and Services Tax is included in listed prices. Harbour Town (Yellow CAT from any stop) is where manufacturers have their factory outlets; some good deals are to be had there.
After Christmas (and around July as well for many stores) is the best time to come to Perth for bargain shopping. Perth City as well as some regional (i.e. Bunbury, etc.) stores are open Boxing Day and suburban stores open on the 27th. Customers have been known to form a line across the street to even enter stores such as 'Guess' and Myer store entry and escalator movement is monitored by security guards to prevent floor crowding.
Eat
One of Perth's drawbacks is that its people have not embraced late night dining. Very few places will serve food after 10PM, even on Friday or Saturday nights. Most restaurants in Perth do not cater for vegetarians or vegans, and if they do - the range is extremely limited. If you are looking for a place that embraces vegetarian food, Fremantle is great.
Restaurants
There is an extensive array of restaurants in Northbridge. You will find a great selection of Southern European and Asian restaurants. Northbridge gets very busy on Friday and Saturday nights as Perth goes into party mode. Neighbouring Mount Lawley and Highgate also has some good options. Victoria Park has a stretch of restaurants along Albany Hwy which is a fairly steady location with the locals and has a few high quality restaurants, although is lower key and more casual.
Fremantle is a good eating option. Famous for its cappuccino strip lined with cafes next door to one another popular with the yuppie crowd. On weekends, a local tradition is to visit the Fisherman's Wharf on warm, sunny weekend evenings for fish and chips. There are a couple of options to choose from close to the beach. Just follow your nose or the seagulls. Further exploring in Fremantle, or "Freo" as it is locally known, can reveal lots of trendy, alternative restaurants that cater for the "careful" eaters. If you care about knowing what it is you are eating, (vegan, preservative free, fair trade, organic), try exploring the Freo markets area, or just ask around, they are often not in the "touristy areas". Little Creatures is a decent brewery, but is also a yuppie pub. If you are looking for a decent fish and chip or seafood dinner, it is typically far more expensive by the coast (where the tourists are), excellent seafood at a better price can be sourced in the central and eastern suburbs.
Subiaco is located just a couple of kilometres from the city center. It is a trendy but fun suburb which features some great food and entertainment, although it can be quite expensive.
Claremont is a suburb on the Fremantle railway line where you will find some good restaurants as well (including authentic Italian), although, again, it can quite expensive and there is a limited range.
The Swan Valley, especially along West Swan Road contains various wineries, food producers and restaurants with stunning views over the vineyards. Particularly good are The Black Swan Cafe, Duckstein Brewery, Elmar's and The Mallard Duck Cafe.
Kalamunda and other Eastern hills suburbs offer hidden gems of cafes, small shops and food producers in beautiful countryside with stunning city views. Traditionally Perth locals used to go for picnics and produce festivals in these areas back in the 19th and early 20th century, however as the practice waned with fashions leading towards the coast, it is an excellent place to visit away from the touristy areas for a relaxing or peaceful trip to the bush with fine views and decent food not too far from the city. People often do DIY food tours to local orchards, vineyards, cheesemakers, bakeries and other cottage industries, arts and cafes as its not really organised. Its usually best to visit during Spring or soon after the rains when the forest is at its best.
Guildford has many antique stores (although like all Australian antique markets are visited by many hundreds of tourists as well as locals, so real bargains can be rare), but you can get decent cafe morning teas and lunches in some fine old architecture. This area has some of Perths oldest residential houses and grand building museums & cafes. The old theatre now houses a large Asian textile and artworks store worth a visit and a quirky taxidermy museum a few doors down. Alfreds Kitchen is a tiny but legendary burger bar to the locals, who amass in large crowds that opens at night.
Local specialties
A large Western Rock Lobster (known locally by its former name of crayfish) industry. Most of the crayfish is exported to Asia and USA for vast sums of money. However, crayfish prices in Perth can be relatively cheap, especially during summer in a good season. A chance to give it a try without breaking the bank.
Chilli Mussels are a popular local speciality, consisting of mussels cooked in tomato and chilli jus, available in various restaurants.
Truffles are grown around Mundaring and Manjimup.
The ubiquitous fast food chains serve the usual oily stuff.
If you're interested in a gourmet road trip, nearby Margaret River (about a two hours drive away) is extremely popular for wine tasting, delicious chocolate and fresh, locally made food and produce. The Spring in the Valley Food & Wine Festival in the Swan Valley is increasingly popular, but at the cost of getting a place cheaply and it being overcrowded. Its best to visit the Swan Valley outside of the festival to get the best value, or during the festival if you like the crowds. Most of these places have websites that you can confirm times and dates and are open throughout the year.
Drink
Coffee
Perth has an abundance of Gloria Jeans, Miss Mauds and Dome stores mainly in the city centre and suburban shopping areas. Clusters of independent European style cafes line the trendy streets of suburbs around the city centre. The most well known place for a decent espresso is the Cafe Strip in Fremantle closely followed by the districts of Subiaco, Leederville and South Perth. Although Perth culture has a high quality taste for coffee and demands very high standards in product, in recent times Perth has the dubious honour of having some of the dearest average coffee prices in the country with a normal sized coffee coming close to $4, combined with the strong currency this must make Perth or WA one of the dearest drinking spots in the World.
Pubs and bars
Perth has bars scattered throughout the city but most bars are in the CBD, Northbridge, Subiaco, Leederville, Victoria Park, Mount Lawley & Fremantle areas. Bars usually become busy after 5pm with the afterwork crowd, but most locals tend to go to bars on Friday & Saturday nights. The CBD bars in particular get very busy on Friday nights with many of the popular bars forming long entry lines. Most bars open from around 11AM and close midnight (10PM on Sundays), a few bars do have special extended liquor trading hours to either 1, 2 or 3AM. There has been an increase in small bars and bistro dining in niche areas of the CBD, however these are typically expensive even though good quality, so shop around for a good value evening.
Clubs
Perth has a small but strong dance music scene which revolves heavily around drum & bass. Club nights and international gigs are held at a variety of venues across the city centre, Northbridge and outer suburbs (check out local street press magazines such as Xpress for gig guides and further info) for a comprehensive gig guide).
Almost all clubs in Western Australia have very strict ID policies and it is highly unlikely that you will get in if you do not have your passport or an ID issued in Australia by a government agency (either an Australian driver's license or proof of age card) with you, even if you definitely look over the legal age. Also most dance music bars/clubs close at 2AM following Friday and Saturday nights and are subjected to Police enforced lockdowns and lockouts (as is the case in Brisbane), so you will find yourself stuck in one place after 3AM, and be stranded should you be short on money for a cab.
Alternatives
• Drive Through Liquor Stores. These are usually open until quite late. It is considered polite to park your car outside and walk through if you are intending to browse and take your time. Many Australians enjoy to drink in the comfort of their own home or backyard as much as they enjoy drinking in their favourite pub.
Sleep
An unfortunate effect of the current mining boom is that the price of accommodation in Perth has skyrocketed in recent years, with average room rates currently higher than those in Sydney, Melbourne or even Rome. Figure on paying over $100 per night for even the most basic room, and over $200 for a 4-star hotel. In general, room rates tend to be most expensive in mid-week, when many business travellers visit, while (relative) bargains can often be found on the weekends.
Hotels and Motels
Most of Perth's hotels are concentrated in the city centre, the neighbouring suburb of East Perth, as well as the seaside suburb of Fremantle. Though slightly further, the coastal town of Mandurah, which is easily accessible by Perth's suburban railway system, is a popular weekend getaway for Perth's residents, and has several hotels and beach resorts to cater to that crowd.
Hostels and backpackers
Perth is very popular with backpackers and there are a large number of backpackers' hostels located in the city, particularly in the Northbridge area. Be warned there are a few hostels in Perth that are in terrible condition make sure to see your room or check the ratings online.
Caravan parks
Caravan parks are a cost effective and often good value family way to stay in Perth. Caravan parks are usually some distance from the city, but some have bus stops right out the front door. Caravan parks are generally clean and offer a variety of accommodation types.
Stay safe
The main dangers that an overseas visitor to Perth faces are sunburn and dehydration. Make sure you cover yourself with SPF 30+ sunscreen and a hat, and preferably a shirt and keep a bottle of water with you, especially in the warmer months. Also be wary of dehydration in the hot weather. An insect repellent such as 'Aeroguard' will be useful on summer evenings if you are outdoors.
Otherwise, Perth is relatively safe, though its best not to walk alone at night. Some areas such as Northbridge are also known to be 'trouble spots' on weekend nights and tourist should be careful. Perth citizens (as with most Australians) almost never carry firearms or other weaponry, therefore it is logical to avoid people and places whenever such things are observed and advise the local police service when safe to do so. Overall Perth is becoming safer, due to small alleyways and other niche problem zones being refurbished and unsuitable for loiterers.
Police are generally friendly and approachable. To contact the police, ambulance or fire brigade emergency service is "000" on the phone for emergencies. "131 444" is the recommended number for 24/7 Police assistance and general enquiries.
Trains are generally safe with transit guards travelling in pairs, patrolling most scheduled trains after peak hour. All train stations have a time to next train as well as an emergency button which can be used to call transit guards should the need arise. All stations have live monitored cameras and these can be activated by the simple push of the emergency button. In the train, there are "talk to driver" buttons in every carriage, but some older trains do not have them on every door. From 2011 the Armadale Train line especially in the areas of Burswood and Carlisle has had some high profile assaults from gangs travelling on the train system . The gangs usually comprise of disaffected Indigenous youth and although weapons are not usually involved attacks have become more vicious in their nature.
The bus network while generally safe, but after hours can be a little more dangerous than the train network, with extremely limited security patrols, and buses coming under increasing attacks by people throwing rocks and other anti social behaviour. Some bus stations (like Mirrabooka bus station and the associated buses) should be avoided where possible due to ethnic based gangs of youths and other anti-social behaviour. If you have to travel by bus at night, sit as close to the driver as possible and if a problem develops, tell the driver. Often incidents on buses continue for much longer than they should because no one asks the bus driver for assistance.
Exercise caution when crossing the road at zebra crossings, walking along the footpath at the entry/exit point of parking lots or when crossing the street at a T-intersection. Though pedestrians have the legal right of way, some motorists choose to ignore this rule. In the case of a zebra crossing, cars should slow down for you though caution is advisable. If you do not notice a car slowing down, do not begin to cross. It is usually best to follow the lead of the locals and to move as a group.
Driving in Perth can be straightforward as its highways tend to connect at various nodes making navigation easy. However, avoid travelling during business rush hour (between 7-9AM and 4-6PM), particularly in summer or hot days. Many of Perth's major roads were not designed for the volume of traffic currently experienced with recent high population growth. Perth drivers are increasingly known for being inconsiderate to other drivers on the roads during these times, which also has caused increased delays due to accidents.
The wiser solution is to take public transport such as the train or bus system. If you are driving or a passenger in a taxi or a local residents car, it is recommended to relax and not allow it to affect you or your holiday. Most Perth citizens work long hours and wish to get home quickly away from the heat and traffic so therefore their behaviour is not personal and while is often aggressive, is seldom reckless. Travelling outside of these hours and on weekends is typically low hassles. It is likely these problems will increase over the next few years from 2012, as major roads are being upgraded and/or expanded to cope with increased volumes with new infrastructure projects, especially around the airport domestic and international.
There are a few rules to take care of while during driving in WA. When stopped at a train crossing, do not proceed until the flashing lights have stopped even if the boom gate has fully lifted as fines are issued. There is a lower tolerance towards speeding so even a small excess over the road limit may warrant in an infringement and or fine. It is not mandatory or always observed, however it is polite to keep a gap at an unmarked road crossing when stuck in traffic to allow access for turning vehicles. If you have noticed the lane next to you leave a gap in these places, it is polite do the same. It is always wise to take great care during merging traffic lanes, especially during rush hour (as per above paragraph). Buses do have right of way when entering traffic and occasionally often pull out with little warning. Australians are allowed to overtake on the inside lane, so drivers should be aware of this to avoid any potential alarm.
Be wary of using ATMs, fraudulent devices have been added to some across Perth, but the prevalence is no higher than in any major city. ATMs are available outside nearly every bank branch.
Cope
Consulates
• United States, 16 St. Georges Ter, +61 8 9202-1224 (fax: +61 8 9231-9444), [19].
Get out
• Margaret River – has some of the world's best wines. Good food and pristine beaches make the South West region a favourite destination. It's about three hours south, making it an ideal weekend get away.
• Hyden – east of Perth is the closest town to Wave Rock. A granite rock formation that looks like a large breaking wave.
• Cervantes – north of Perth in the Wheatbelt, features thousands of limestone pillars rising out of the yellow the sand in the Pinnacles Desert. A nearby lake has stromatalites closely related to those found in rocks billions of years old.
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Research article
Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals
Barbara Buddeberg-Fischer1*, Richard Klaghofer1, Thomas Abel2 and Claus Buddeberg1
Author Affiliations
1 Department of Psychosocial Medicine, Zurich University Hospital, Haldenbachstrasse 18, CH-8091 Zurich, Switzerland
2 Department of Health Research, University of Bern, Niesenweg 6, CH-8013 Bern, Switzerland
For all author emails, please log on.
BMC Health Services Research 2006, 6:137 doi:10.1186/1472-6963-6-137
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1472-6963/6/137
Received:6 July 2006
Accepted:23 October 2006
Published:23 October 2006
© 2006 Buddeberg-Fischer et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
The medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality.
Methods
As part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance.
Results
In their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals.
Conclusion
Gender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored.
Background
The medical specialties chosen by doctors for their careers play an important role in the development of health-care services. There are some recent studies of how different medical specialities are perceived or how choices are made [1-3]. Several determinants have been identified: the feminisation of medicine, lifestyle, specialist status and the prospect of future income, as well as the structural conditions of the various residency programmes. Most studies addressed medical students, not residents. As far as we know there appear to be only a few studies on personality traits, career motivation and personal life goals as influencing factors on speciality choice [4].
Feminisation
Since the 1990s, more than half of the medical school graduates in Western countries have been women [5-8]. Although female physicians tend to specialise almost to the same degree, they enter other specialties than their male colleagues [9-12]. Especially in surgical specialities, female physicians are under-represented [13]. Gender differences in speciality choice can partly be explained as a function of socialisation [14-16], but also by structural operating barriers or closure mechanisms within specific fields [17-19].
Lifestyle
Several studies have reported that a so-called controllable lifestyle has become a determinant in physicians' speciality selection criteria [3,20-22]. The following characteristics of a controllable lifestyle have been defined: personal time free of practice requirements for leisure, family, and non-vocational pursuits and control of total weekly hours spent on professional responsibilities. For female physicians the prospect of combining their professional career with family responsibilities is a key issue in the process of speciality choice or changing the speciality to which they initially aspired to [16].
Status and income
Prestige within the medical profession, social status and income also play their role in the decision in favour of a medical speciality [23,24]. In some studies, students reported their student debt as one of the factors influencing their career choices [25,26]. Students with large debts tended to choose surgical specialities more often and were less likely to choose primary care.
Residency programmes
The application and selection procedures for residency programmes, the length, quality and structure of the programme, work schedules, mentorship, annual vacations are also factors which are considered when choosing a speciality [18,19,24,27,28].
Most studies investigated only one or two of the factors identified as influencing speciality choice. One has to consider, however, that Swiss studies addressing issues of speciality choice are lacking to date.
The aims of this study were to investigate (1) the development of the residents' speciality choices since graduating from medical school, and the differences compared to the speciality distribution of working doctors, and (2) what factors influence the young doctors' speciality choices. As shown in Figure 1, we hypothesised that gender and personality traits have an impact on speciality choice, and that career motivation as well as life goals have an influence, too. The present paper aimed to examine these hypotheses.
Figure 1. Conceptual framework of the study.
Methods
Study design, sample development, and study sample
The present study is part of an ongoing prospective survey of a cohort of graduates of the three medical schools in German speaking Switzerland, beginning in 2001 (T1). Of the 1004 registered final-year students, 715 (71%) participated in the first assessment (T1, in 2001) [15]. Subjects were re-evaluated after two years in 2003 (T2) [18,19]. The present paper refers to results of the third assessment (T3), conducted in the fourth year of residency (in 2005). Table 1 shows the sample development from T0 (questionnaires sent to all registered graduates at the medical schools of Basel, Bern, and Zurich) to T1, T2, and T3 for participants, non-participants and dropouts. There are no significant differences between the 193 dropouts (T1 – T3) and the 522 subjects participating at the third measurement with regard to socio-demographic data, personality traits, and career-related variables at T1.
Table 1. Development of the study sample
Of these 522 residents there were 281 females (53.8%) and 241 males (46.2%). The mean age was 31.3 years (SD 2.4 y, range 27 – 46 y). Of the residents 428 (82.0%) had a stable partnership, of whom 125 were married (65 females and 60 males). Only 26 (9.3%) of the females, but 36 (14.9%) of the males had own children (p = 0.03). 94.7% worked full-time, 5.3% part-time. The mean working hours per week were 55.4 hrs (SD 8.2 hrs, range 30 – 80 hrs).
Speciality training and residencies in Switzerland
There are 43 registered speciality qualifications in Switzerland. Most of the specialities require at least a six-year residency, and a final speciality qualification exam. One major problem with most of the speciality training courses is the lack of structured and time-limited residency programmes. Young doctors usually only get contracts for a year, i.e. they have to arrange and organize their residency posts every one to two years.
Instruments
The main characteristics of the applied instruments are given in Table 2. All instruments are self-assessment scales. In the following, it is described what constructs are measured by the instruments:
Table 2. Characteristics of the applied instruments
Questions concerning socio-demographic data and choice of medical speciality
Sense of Coherence Scale, SOC-13 [29], is a measure of a person's resistance to stress and his/her ability to manage stress (measure of traits, stability in this study T1 – T3: 0.56).
Rosenberg-Self-Esteem-Scale, RSE [30], assesses general self-esteem and includes items that express a general favourable or unfavourable attitude towards oneself (measure of traits).
Personal Attributes Questionnaire, GE-PAQ, German Extended Personal Attributes Questionnaire [31], is a self-rating instrument for the assessment of gender-role orientation (measure of traits). The Instrumentality (PAQ-I) scale contains instrumental traits (e.g. 'independent', 'decisive') that are considered to be socially desirable to some degree in both sexes but stereotypically more characteristic of males. The Expressiveness (PAQ-E) scale contains so-called 'feminine' items that describe socially desirable expressive, communal traits (e.g. 'helpful') that are stereotypically more characteristic of females.
Career Motivation Questionnaire, CMQ [32], consists of 3 scales (measure of traits): Intrinsic Career Motivation CMQ-I (i.e. enjoyment of and interest in professional activities) (stability in this study T1 – T3: 0.57), Extrinsic Career Motivation CMQ-E (i.e. striving for promotion, income, prestige) (stability 0.58) and Extraprofessional Concerns CMQ-EC (i.e. prioritising family, convenient working hours, job security) (stability 0.60).
Life Goals Questionnaire, GOALS [33], assesses 24 general, long-term life goals pertaining to six major life domains (measure of traits): intimacy (close relationships based on mutual trust and affection), affiliation (spending time with other people, common activities), altruism (acting for the welfare of others), power (asserting oneself, seeking social status), achievement (improving on oneself, meeting standards), and variation (seeking new experiences and excitement). Each goal is rated in regard to the importance (How important is it for you to reach this goal in your lifetime?). Importance ratings indicate which goals are desirable and valuable for the person and indicate the strength of his/her commitment to a goal.
Statistical analyses
All analyses were carried out with SPSS for windows, release 12.0. Descriptive statistics were given in terms of counts and percentages, means and standard deviations respectively. Gender-different speciality choice was tested by Chi2-test. Study hypotheses were tested by univariate analyses of variance, followed by Scheffé-tests, and multivariate analyses of variance and covariance.
Results
Residents' speciality choices at T3: Of the 522 physicians participating at the third assessment, 83 (15.9%) had not yet decided in which speciality they wanted to qualify. The remaining 439 residents had decided to qualify in the following specialities: 45 (8.6%) in primary care, 126 (24.1%) in internal medicine (including all sub-specialities of internal medicine), 68 (13.0%) in surgical disciplines, 31 (5.9%) in gynaecology & obstetrics, 40 (7.7%) in anaesthesiology and intensive care, 44 (8.4%) in paediatrics, 25 (4.8%) in psychiatry, and 60 (11.5%) in other specialities (such as dermatology, ENT, neurology, ophthalmology, radiology). The participants had a list of all 43 officially acknowledged medical specialities in Switzerland, marked with a code number, which they could fill in answering the question concerning the speciality choice.
The development of residents' speciality choices is shown in Figure 2. At the end of medical school 60% of the female and 51% of the male graduates had made their speciality choice. In their second year of residency, 71% of the female and 64% of the male residents had decided, and in the fourth year of residency, 83% of the female and 84% of the male participants named their speciality aspired to. The distribution of the different specialities within the gender group did not change much between the three measurements. However, the distribution of the specialities aspired to by the study participants is different from the speciality distribution represented by the working doctors who hold a speciality qualification. Compared to all working female specialists, there are significantly fewer female residents aspiring to become primary care physicians and psychiatrists; also the group of other specialities is smaller. It might be that some of the still undecided residents will choose one of those specialities later on. Looking at the male participants, fewer residents want to become primary care physicians, internists or psychiatrists but significantly more want to go into surgical disciplines compared to working male doctors.
Figure 2. Study residents' speciality choices over time (T1 – T3) and speciality distribution of working doctors (2005).
The speciality choice depending on gender in the study sample at T3 is listed in Table 3. Male residents more often chose surgical specialities, whereas females decided on paediatrics, gynaecology & obstetrics (G&O), and anaesthesiology. In the group of other specialities there was no relevant gender-different distribution.
Table 3. Frequency distribution of speciality aspired to shown by gender at T3 (n = 522)
Residents' characteristics depending on speciality aspired to are shown in Table 4. Participants choosing surgical specialities or anaesthesiology comparably show the highest scores for sense of coherence, self-esteem and instrumentality; psychiatry residents give low scores on these three personality scales. With regard to the scores for expressiveness there are no significant differences between the groups. Physicians aspiring to surgical specialities have comparatively high values for intrinsic and extrinsic career motivation, but low values for extraprofessional concerns. Primary care physicians and psychiatrists rate extraprofessional concerns comparatively high. The life goal 'intimacy' is especially important for G&Os. Physicians in the surgical specialities as well as in G&O attach particular importance to 'power'. Future primary care physicians assess the life goal 'achievement' lowest. Subjects pursuing internal medicine show medium level values on all scales.
Table 4. Means and standard deviations of personality traits, career motivation and importance of life goals according to speciality fields (n = 522)
The multivariate analyses of the influence of gender, personality traits, career motivation and importance of life goals is shown in Table 5. The effect of gender remained significant after controlling for personality traits, career motivation and life goals as covariates. The same does not apply to the influence of personality traits on the speciality choice after controlling for career motivation and life goals. In other words, there are no direct significant influences of personality traits on the speciality choice. This means that career motivation and life goals can be considered as mediator variables.
Table 5. Influence of gender, personality traits, career motivation and importance of life goals on speciality choice at T3 (n = 522), multivariate analyses
Discussion
The present study is part of an ongoing prospective survey of a cohort of Swiss medical school graduates. Subjects included in the study are fourth-year residents in different medical speciality fields. The aims of the study are to examine (1) the development of the residents' speciality choices since graduating from medical school and (2) what factors influenced their choices.
Development of the residents' speciality choices: at the end of medical school a considerable number of students have not yet developed precise ideas as to which speciality they want to work in. The main reason is lack of clinical experience. During the first and second years of post-graduate training they gain insight into various specialities, which makes it easier for them to make their decision. Some residents change the speciality they primarily aspired to, but not so many do. Nor is a marked shift away from one speciality towards another evident. Compared to the working doctors, significantly fewer young doctors aspire to become primary care physicians (PCPs) or psychiatrists. In the competition-based health care systems of Switzerland and the other German-speaking countries the professional prestige, social status, and income of other specialists is much higher than those of PCPs and psychiatrists. As long as the current health policy does not create better professional conditions, the shift away from PC and psychiatry will continue. If this trend prevails for some time, there will be a shortage of doctors providing basic somatic and mental health care, especially in rural areas.
Factors influencing speciality choice: As hypothesized, we found gender different speciality choices, female doctors being over-represented in specialities like gynaecology & obstetrics (G&O), paediatrics, and anaesthesiology and male doctors in surgical specialities. Similar results are reported in other studies [11-13,17,34]. Although G&O entails long hours and a heavy surgical workload, a growing number of women choose this speciality. Women are interested in surgical specialities, but often experience gender-relevant exclusion mechanisms in other surgical fields [17,35]. The marked gender shift in G&O is due to the growing attitude, starting in the late 1980s, that women should be treated by female physicians [36]. Paediatrics, the other speciality mainly chosen by women, is also a speciality in which gender schemas play a certain role [14]. This gender-distinct speciality choice was already found when the participants were in the last year of medical school [15]. The reasons for an increasing number of female doctors choosing anaesthesiology might be manifold: anaesthesiology is a professionally prestigious speciality like surgery but not as competitive, it covers a broad medical spectrum and offers good options for part-time work and good promotion prospects, all factors appreciated by females. Whether the decisive role of gender is based on internalised gender roles or whether there are open or masked deterrents cannot be distinguished by this study.
Personality, career motivation, life goals and speciality choice: According to our assumption, we found that gender, personality, career motivation and life goals have an impact on speciality choice. Petrides and McManus [1] described a mapping of medical careers based on the typology found by Holland in careers in general. Holland's theory [37] suggests that careers can be organised into six broad types, which can be represented around a hexagon, known by the acronym RIASEC, standing for 'Realistic', 'Investigative', 'Artistic', 'Social', 'Enterprising' and 'Conventional'. They also referred to the 'Things↔People' and 'Ideas↔Data' dimensions proposed by Prediger [38] which can be underpinned to Holland's typology. Both models use the attribution of the medical specialities based on the characteristics of their professional activities. We suppose that residents choose a medical speciality in which they can conduct their professional activities corresponding to their special personality traits, career motivation, and life goals aspired to. The residents in surgical specialities in our study were characterised by high values for instrumentality, intrinsic and extrinsic career motivation, 'power' and 'achievement' as life goals. These attributes and attitudes are mainly 'Things/technique-oriented' according to Prediger and can be assigned to Holland's realistic career type. Participants choosing anaesthesiology and intensive care assessed themselves almost as highly instrumental as doctors in surgery. They can also be mapped to the realistic type. Contrary to the study by Petrides & McManus [1], the G&O residents in our sample revealed characteristics of 'People Orientation', matching the social type, a fact which might be influenced by the high number of females in this group. They stated high expressiveness and life goals aiming at satisfying social relationships. Paediatricians in our study, mainly females, showed similar characteristics as the G&Os. Psychiatrists differed from all the other specialities by rating the extraprofessional concerns highest, while expressiveness and altruism were not values very high. They could not easily be assigned to one of the RIASEC types. The same applies for primary care physicians. They showed characteristics of 'People Orientation' (high extraprofessional concerns and altruism), and rated in the medium range in most of the other aspects. The internists were allocated to the investigative type by Petrides & McManus [1], a type in which patient-relationships and diagnostic investigations play their part. This might also apply to the internists in our study; they described themselves as empathetic (adequate expressiveness), but also instrumentally-oriented. The RIASEC mapping of medical specialities did not consider career motivation and life goals but focused only on personality traits. Our results indicate that career motivation and life goals are even more important for the speciality choice than personality traits.
In summary, the results of our study indicate that gender plays a decisive role in speciality choice, while the influence of personality declines after controlling for career motivation and life goals. The feminisation of medicine and especially of some specialities can be expected to lead to fundamental changes in the medical system. One can assume that the style of leadership in hospitals will change: As long as men are department heads, a "command and control style of managing others" will predominate, while women tend towards "interactive leadership" [39]. Other aspects concern employment: more part-time jobs have to be provided for women doctors with family obligations. However, the feminisation also carries the risk of the danger of vertical and horizontal gender segregation [40]: female physicians often spend more time with patients while male doctors look at what is more advantageous for their career, such as laboratory work, developing research projects and writing papers. These differences in working attitudes result in gender-different career opportunities: males taking over leadership positions and females looking after their patients' needs.
Conclusion
The speciality choice of the new generation of doctors is a matter of concern for the health care system in Switzerland. Ideally, as many doctors should practise in a speciality as are needed to cover the population's health care. As the statistics of the Swiss Medical Association and our study data show, a lack of primary care physicians as well as of psychiatrists will occur in the next decade. The question arises whether incentives, mainly financial, will encourage more young doctors to choose to become primary care physicians or psychiatrists, or whether access to the speciality qualification programmes and to the allocation of private practice licenses should be regulated by health policy.
There should be an acknowledgment of the distinctive features of female physicians' careers. Workplace conditions should allow women doctors, if they want, to combine pursuing a prestigious career in medicine with having a family. There is a need to promote and encourage their instrumental traits and extrinsic career motivation. Motivational guidance by senior physicians throughout medical training should not only focus on the professional career but should also consider the personal life goals of those being mentored.
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
All authors designed the study. BBF was responsible for data acquisition, RK conducted the statistical analyses. BBF, RK, TA and CB contributed to the interpretation of data, BBF drafted the manuscript versions, RK, TA and CB revised the drafts critically for important intellectual content. All authors gave final approval to the version to be published.
Acknowledgements
The study was supported by grants from the Swiss National Science Foundation (NF Nos. 3200-061906.00 and 3200 BO-102130).
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19. Buddeberg-Fischer B, Klaghofer R, Abel T, Buddeberg C: Junior physicians' workplace experiences in clinical fields in German-speaking Switzerland.
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20. Dorsey ER, Jarjoura D, Rutecki GW: Influence of controllable lifestyle on recent trends in specialty choice by US medical students.
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21. Lambert EM, Holmboe ES: The relationship between specialty choice and gender of U.S. medical students, 1990-2003.
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Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1472-6963/6/137/prepub
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Computerized Summative Assessment of Multiple-choice Questions: Exploring Possibilities with the Zimbabwe School Examination Council Grade 7 Assessments
Benjamin Tatira, Lillias Hamufari Natsai Mutambara, Conilius J. Chagwiza, Lovemore J. Nyaumwe
Abstract
The purpose of this study was to develop educational software for online assessment of multiple choice responses (MCQs). An automated assessment software program, duly developed in this study can display assessment items, record candidates' answers, and mark and provide instant reporting of candidates' performance scores. Field tests of the software were conducted on four primary schools located in Bindura town using a previous year summative Grade 7 assessment set by the Zimbabwe School Examination Council (ZIMSEC). Results were that computerized assessment in mathematics has the potential to enhance the quality of assessment standards and can drastically reduce material costs to the examination board. The paper exposes test mode benefits inherent in computer-based assessments, such as one-item display and ease of candidates selecting/changing optional answers. It also informs the ongoing debate on possible enhancement of candidates' performance on a computer-based assessment relative to the traditional pen-and-paper assessment format. The need for the development of diagnostic instructional software to compliment computerized assessments is one of the recommendations of the study.
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Ontologies Acquisition from Relational Databases
Shufeng Zhou, Guangwu Meng, Haiyun Ling
Abstract
Ontologies play an important role in solving the problem of semantic heterogeneity of heterogeneous data sources. The ontology acquisition from the relational database is one of the fundamental technologies on the information integration field. Ontology acquisition from relational database (OARDB) and transformation rules used are presented and discussed. The key technologies and model are given.
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Computer and Information Science ISSN 1913-8989 (Print) ISSN 1913-8997 (Online)
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You are here: Home / Data and maps / Maps and graphs / Conservation status of species of European Union interest in marine ecosystems
Conservation status of species of European Union interest in marine ecosystems
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• Some 74 % of the assessments of marine species linked to marine ecosystems are unknown.
• Twenty-four per cent of the assessments are unfavourable.
• Only 2 % of the assessments are favourable and are represented only in the Atlantic, Boreal and Marine Atlantic regions.
• The Atlantic, Continental and Marine Baltic regions have more than 80 % of unfavourable assessments.
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Campylobacteriosis
Campylobacteriosis
This article has been reviewed by the following Topic Editor: Sidney Draggan Ph.D.
Introduction
U.S. Department of Agriculture
The U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS) defines Campylobacter as a bacterium that is commonly found in the intestinal tracts of cats, dogs, poultry, cattle, swine, rodents, monkeys, wild birds, and some humans. The bacteria pass through feces to cycle through the environment and are also in untreated water. Campylobacter jejuni (C. jejuni), the strain associated with most reported human infections, may be present in the body without causing illness.
Campylobacteriosis is a diarrheal disease often caused by the bacterium known as Campylobacter jejuni (C. jejuni) associated with poultry, raw milk, and water. There are an estimated 2.5 million cases annually in the United States with 200 to 730 deaths. Campylobacteriosis has been linked to Guillain-Barre syndrome (a disease which paralyzes limbs and breathing muscles) as well as Epstein-Barr, Cytomegalovirus, and other viruses. USDA has estimated that this disease costs the United States between $1.2 to $1.4 billion annually in medical costs, productivity losses, and residential care.
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) has provided the following answers to questions about the organism:
What is campylobacteriosis?
Campylobacter jejuni. (Source: Centers for Disease Control and Prevention)
Campylobacteriosis is an infectious disease caused by bacteria of the genus Campylobacter. Most people who become ill with campylobacteriosis get diarrhea, cramping, abdominal pain, and fever within 2 to 5 days after exposure to the organism. The diarrhea may be bloody and can be accompanied by nausea and vomiting. The illness typically lasts 1 week. Some persons who are infected with Campylobacter don't have any symptoms at all. In persons with compromised immune systems, Campylobacter occasionally spreads to the bloodstream and causes a serious life-threatening infection.
How common is Campylobacter?
Campylobacter is one of the most common bacterial causes of diarrheal illness in the United States. Virtually all cases occur as isolated, sporadic events, not as a part of large outbreaks. Active surveillance through FoodNet indicates about 15 cases are diagnosed each year for each 100,000 persons in the population. Many more cases go undiagnosed or unreported, and campylobacteriosis is estimated to affect over 1 million persons every year, or 0.5% of the general population. Campylobacteriosis occurs much more frequently in the summer months than in the winter. The organism is isolated from infants and young adults more frequently than from other age groups and from males more frequently than females. Although Campylobacter doesn't commonly cause death, it has been estimated that approximately 100 persons with Campylobacter infections may die each year.
What sort of germ is Campylobacter?
The Campylobacter organism is actually a group of spiral-shaped bacteria that can cause disease in humans and animals. Most human illness is caused by one species, called Campylobacter jejuni, but 1% of human Campylobacter cases are caused by other species. Campylobacter jejuni grows best at the body temperature of a bird, and seems to be well adapted to birds, who carry it without becoming ill. The bacterium is fragile. It cannot tolerate drying and can be killed by oxygen. It grows only if there is less than the atmospheric amount of oxygen present. Freezing reduces the number of Campylobacter bacteria present on raw meat.
How is the infection diagnosed?
Many different kinds of infections can cause diarrhea and bloody diarrhea. Doctors can look for bacterial causes of diarrhea by asking a laboratory to culture a sample of stool from an ill person. Diagnosis of Campylobacter requires special laboratory culture procedures, which doctors may need to specifically request.
How can campylobacteriosis be treated?
Virtually all persons infected with Campylobacter will recover without any specific treatment. Patients should drink plenty of fluids as long as the diarrhea lasts. In more severe cases, antibiotics such as erythromycin or a fluoroquinolone can be used, and can shorten the duration of symptoms if they are given early in the illness. Your doctor will make the decision about whether antibiotics are necessary.
Are there long-term consequences?
Most people who get campylobacteriosis recover completely within 2 to 5 days, although sometimes recovery can take up to 10 days. Rarely, some long-term consequences can result from a Campylobacter infection. Some people may have arthritis following campylobacteriosis; others may develop a rare disease that affects the nerves of the body beginning several weeks after the diarrheal illness. This disease, called Guillain-Barré syndrome, occurs when a person's immune system is "triggered" to attack the body's own nerves, and can lead to paralysis that lasts several weeks and usually requires intensive care. It is estimated that approximately one in every 1000 reported campylobacteriosis cases leads to Guillain-Barré syndrome. As many as 40% of Guillain-Barré syndrome cases in this country may be triggered by campylobacteriosis.
How do people get infected with this germ?
Campylobacteriosis usually occurs in single, sporadic cases, but it can also occur in outbreaks, when a number of people become ill at one time. Most cases of campylobacteriosis are associated with handling raw poultry or eating raw or undercooked poultry meat. A very small number of Campylobacter organisms (fewer than 500) can cause illness in humans. Even one drop of juice from raw chicken meat can infect a person. One way to become infected is to cut poultry meat on a cutting board, and then use the unwashed cutting board or utensil to prepare vegetables or other raw or lightly cooked foods. The Campylobacter organisms from the raw meat can then spread to the other foods. The organism is not usually spread from person to person, but this can happen if the infected person is a small child or is producing a large volume of diarrhea. Larger outbreaks due to Campylobacter are not usually associated with raw poultry but are usually related to drinking unpasteurized milk or contaminated water. Animals can also be infected, and some people have acquired their infection from contact with the infected stool of an ill dog or cat.
How does food or water get contaminated with Campylobacter?
Many chicken flocks are silently infected with Campylobacter; that is, the chickens are infected with the organism but show no signs of illness. Campylobacter can be easily spread from bird to bird through a common water source or through contact with infected feces. When an infected bird is slaughtered, Campylobacter can be transferred from the intestines to the meat. More than half of the raw chicken in the United States market has Campylobacter on it. Campylobacter is also present in the giblets, especially the liver.
Unpasteurized milk can become contaminated if the cow has an infection with Campylobacter in her udder or the milk is contaminated with manure. Surface water and mountain streams can become contaminated from infected feces from cows or wild birds. This infection is common in the developing world, and travelers to foreign countries are also at risk for becoming infected with Campylobacter.
What can be done to prevent the infection?
There are some simple food handling practices for preventing Campylobacter infections. Physicians who diagnose campylobacteriosis and clinical laboratories that identify this organism should report their findings to the local health department. If many cases occur at the same time, it may mean that many people were exposed to a common contaminated food item or water source which might still be available to infect more people. When outbreaks occur, community education efforts can be directed at proper food handling techniques, especially thorough cooking of all poultry and other foods of animal origin, and common sense kitchen hygiene practices. Some data suggest that Campylobacter can spread through a chicken flock in their drinking water. Providing clean, chlorinated water sources for the chickens might prevent Campylobacter infections in poultry flocks and thereby decrease the amount of contaminated meat reaching the market place.
Some Tips for Preventing Campylobacteriosis
• Cook all poultry products thoroughly. Make sure that the meat is cooked throughout (no longer pink), any juices run clear, and the inside is cooked to 170°F (77°C) for breast meat, and 180°F (82°C) for thigh meat.
• If you are served undercooked poultry in a restaurant, send it back for further cooking.
• Wash hands with soap before handling raw foods of animal origin. Wash hands with soap after handling raw foods of animal origin and before touching anything else.
• Prevent cross-contamination in the kitchen:
• Use separate cutting boards for foods of animal origin and other foods.
• Carefully clean all cutting boards, countertops and utensils with soap and hot water after preparing raw food of animal origin.
• Avoid consuming unpasteurized milk and untreated surface water.
• Make sure that persons with diarrhea, especially children, wash their hands carefully and frequently with soap to reduce the risk of spreading the infection.
• Wash hands with soap after having contact with pet feces.
What are public health agencies doing to prevent or control campylobacteriosis?
To learn more about how Campylobacter causes disease and is spread, CDC began a national surveillance program in 1982. A more detailed active surveillance system was instituted in 1996; this will provide more information on how often this disease occurs and what the risk factors are for getting it. CDC is also making an effort to inform the public about campylobacteriosis and ways to avoid getting this disease. The U.S. Department of Agriculture conducts research on how to prevent the infection in chickens. The Food and Drug Administration has produced the Model Food Code, which could decrease the risk of contaminated chicken being served in commercial food establishments.
Date: October 6, 2005
Further Reading
Citation
USDA::CDC (Content Source);Sidney Draggan Ph.D. (Topic Editor) "Campylobacteriosis". In: Encyclopedia of Earth. Eds. Cutler J. Cleveland (Washington, D.C.: Environmental Information Coalition, National Council for Science and the Environment). [First published in the Encyclopedia of Earth August 23, 2008; Last revised Date August 23, 2008; Retrieved May 18, 2013 <http://www.eoearth.org/article/Campylobacteriosis>
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Germany, Bavaria, Freising Miscellaneous City Records (FamilySearch Historical Records)Edit This Page
From FamilySearch Wiki
This article describes a collection of historical records scheduled to become available at FamilySearch.org.
Contents
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Deutschland, Bavaria, Freising Archivgut
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This is a collection of mixed records from the city archives in the city of Freising, covering the years 1593-1949. Most of the records are handwritten in narrative style and, in later years, in formatted forms. The record text is written in German.
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Germany. Various local entities. Miscellaneous records, 1593-1949. Freising City Archive (Stadtarchiv), Bavaria, Germany.
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It is often helpful to extract the information on all children with the same parents. If the surname is unusual, you may want to compile baptism entries for every person of the same surname and sort them into families based on the names of the parents. Continue to search the baptism records to identify siblings, parents, and other relatives in the same or other generations who were born, married, and died in or near to the same place.
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• “El Salvador Civil Registration,” index and images, FamilySearch (https://www.familysearch.org: accessed 21 March 2011), entry for Jose Maria Antonio del Carmen, born 9 April 1880; citing La Libertad, San Juan Opico, Nacimientos 1879-1893, image 50; Ministerio Archivo Civil de la Alcaldia Municipal de San Salvador.
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Heyooo
Newbie Member
1May2007,01:16 #1
I'd just thought I'd stop in and introduce myself! My name is Mike. I've just started my web project for myself and not a client at tutorialstuff.com .
I have been browsing this forum for a few days and finally bit the bullet and joined.
So hi to everyone and if you would like to give any advice on my site at tutorialstuff.com , I'd be more than happy to hear it.
Thanks! - Mike
Go4Expert Founder
1May2007,09:08 #2
Very nicely designed site. I would suggest having more of the site navigation on the home page rather than have so much of ads. Ads will fetch you bucks but then its for the user the site is not for the bucks.
Newbie Member
1May2007,18:50 #3
I do plan on integrating the ads a little better. I don't want them to seem so obtrusive. Any suggestions on this?
Thanks - Mike
Go4Expert Founder
1May2007,20:30 #4
Keep them to a minimal and try having ads on pages that can provide you maximum output instead of having ads every where. Thats my idea and its working here as well. Do you think you are annoyed with the ads here?
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fjphowe7ls4xoos22wesksazd4i5sauu
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Help with 8085 entering in a number > 9
Newbie Member
29Sep2008,00:55 #1
Im trying to enter in a digit between 0 and 255 and store it in a register. I understand how to use BDOS to put a keyboard value into the A register but i cant figure out how to get the right value for a 2 or 3 digit number...
Mentor
22Oct2008,22:02 #2
Initialise some other register X to zero
1: Read the keyboard into A
Calculate the value represented (subtract the ASCII value of 0, probably, and range check it)
Error handling
X=X*10+A
Repeat from 1 until the input suggests the user has finished inputting data.
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23m3wnibblbk6aoltthaz7nrwupuxnu5
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RECURSION in c
Go4Expert Member
13Sep2006,10:31 #1
Can any help me to get th code to find al possible cominations of a string using recursion
Go4Expert Founder
13Sep2006,10:42 #2
You have posted in the Article and source code category and I have moved it to Queries and discussion category.
Refer All possible combinations of a string
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About this Journal Submit a Manuscript Table of Contents
Journal of Oncology
Volume 2012 (2012), Article ID 204946, 23 pages
doi:10.1155/2012/204946
Review Article
Tumor Lymphangiogenesis as a Potential Therapeutic Target
Institute for Molecular Bioscience, The University of QLD, Brisbane, QLD 4072, Australia
Received 1 August 2011; Revised 10 October 2011; Accepted 31 October 2011
Academic Editor: Debabrata Mukhopadhyay
Copyright © 2012 Tam Duong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.
1. Introduction
The spread of cancer to secondary sites (metastasis) is the main cause of morbidity for patients with solid tumors. Understanding of the molecular and cellular mechanisms that underpin tumor metastasis is therefore an important goal in cancer biology. Over a century ago, Stephen Paget proposed a “seed and soil” theory in which tumor cells have their propensity to seed certain particularly favourable organs [1]. For instance, prostate cancer often metastasizes to bones, colon cancer to the liver, and melanoma to the brain. This theory reflects the need of cancer cells to find a suitable milieu with appropriate molecular and cellular characteristics to be able to survive. In 1928, James Ewing suggested an alternative metastatic theory, proposing that cancer cell metastasis depends solely on available anatomical and mechanical routes [2]. Although tumorigenic cells certainly need to access the lymphatic or blood vascular system to spread, in accordance with Ewing’s theory, they also have different propensity to seed some organs in favour of the others. It is clear that both anatomical/mechanical and “seed and soil” theories partly explain the metastatic pattern.
Recent studies have revealed that the lymphatic vasculature is one of the major routes for tumor metastasis, raising the possibility that blocking tumor lymphangiogenesis might prevent the very initial stage of tumor spreading from the primary site. This review focuses on tumor lymphangiogenesis, its effect on cancer metastasis, and how targeting tumor lymphangiogenesis may provide a potential therapeutic strategy to treat cancer metastasis.
2. Lymphatic Vascular System and Its Function
The structural and functional features of the lymphatic vascular system make it particularly suited to a role as a major route of metastasis. The lymphatic system plays a vital role in maintaining tissue fluid homeostasis by draining protein-rich fluid from the interstitial space back to the general blood circulation. The lymphatic system is divided into the conducting vessel network and lymphoid tissue. The lymphatic vessel network consists of lymphatic capillaries, precollecting vessels, collecting vessels, and the thoracic duct. The initial lymphatic capillaries have a thin wall, built from a single layer of endothelial cells, and play a role in taking up the interstitial tissue fluid. Because cell-to-cell contact in these vessels is loose and specialized for fluid uptake, they are also well suited to invasion by cancer cells. Furthermore, the lymphatic capillaries are distributed throughout the body except for some avascular tissues such as the epidermis, cartilage, cornea, hair, nails, and some vascularized organs such as the brain and the retina (reviewed by [3]). Their broad distribution in the whole body therefore also provides ready routes for cancer cell metastasis. The larger lymphatic vessels have a smooth muscle cell layer and basement membrane surrounding the inner lining of endothelial cells (reviewed by [4]). In addition, they also contain intraluminal valves, which allow unidirectional flow to the thoracic duct in order to reach the general blood circulation (reviewed by [3]).
Lymphoid tissue includes structurally well-organized lymph nodes and loosely organized lymphoid follicles. The lymph nodes are located at intervals along the lymphatic vascular tree and filter the lymph. The lymph node therefore represents a preferred site for lodgement of metastasizing cancer cells during tumorigenesis [5].
Another important function of the lymphatic system is immune trafficking and surveillance. Through the lymphatic network, immune cells from the peripheral tissues navigate to regional lymph nodes in order to stimulate the immune response [6]. This navigation is also critical in modulating inflammatory lymphangiogenesis. Interestingly, this mechanism can also be utilised by cancer cells to escape from the primary tumor site and metastasize to the regional lymph nodes (discussed later in part 4.2.3).
3. Embryonic Lymphatic Vessel Development
Since the lymphatic developmental program can be re-activated during tumor lymphangiogenesis, it is important to understand early lymphatic vessel development in the embryo and the key factors involved in this process. It has been suggested that lymphatic vessels in mammals arise in the embryo from the preexisting blood vasculature and more particularly from the cardinal vein (CV) [7, 8]. Lymphatic endothelial cell (LEC) precursors from the CV migrate outwards and form the lymph sac (LS), from which lymphatic vessels start to develop throughout the body, connecting to form either deep or superficial lymphatic vessels (Figure 1(a)). Recent molecular studies based on lymphatic phenotypes of mutant mice have revealed several factors that regulate these steps in the embryo (Table 1). In this section, we will discuss the factors involved in establishing the lymphatic vasculature in the embryo, as a prelude to discussion of factors that are also involved in adult pathological conditions, especially tumor lymphangiogenesis.
Table 1: Lymphangiogenic factors in the early steps of embryonic development and in adult.
Figure 1: Embryonic lymphangiogenesis versus tumor lymphangiogenesis. (a) During early lymphatic vessel development, lymphatic endothelial precursor cells (SOX18+/COUP-TFII+/PROX-1+) from the CV migrate outwards and form lymph sacs (LS), from which lymphatic vessels start to extend throughout the body. (b) In a tumor microenvironment, various lymphatic growth factors are secreted from tumor cells, inflammatory cells (e.g., TAMs), and stroma cells. These factors stimulate the formation of tumor neolymphatics, either in the peritumoral or intratumoral area, which facilitate the intravasation of cancer cells into lymphatic vessels. Interestingly, several key early factors in embryonic lymphangiogenesis also play critical roles during tumor lymphangiogenesis. In particular, SOX18 is not required for maintenance of adult lymphatics but appears to be reactivated and regulate the formation of tumor neolymphatics. CV, cardinal vein; LS, lymph sac; dpc, days coitum; GF, growth factor; LN, lymph node; DLN, draining lymph node; TAMs, tumor-associated macrophages.
3.1. Lymphatic Endothelial Cell Specification and Expansion of the Lymphatic Network
3.1.1. Lymphatic Endothelial Cell Specification
During early lymphatic vascular development, lymphatic endothelial hyaluronan receptor-1 (LYVE-1) and vascular endothelial growth factor receptor-3 (VEGFR-3) are first expressed at sites where lymphangiogenesis will occur in the cardinal vein around 8.5 dpc [43]. Later, polarized expression of SOX18 is found in the dorsal-lateral side of the cardinal vein at 9.0 dpc [10]. SOX18 directly activates the transcription of Prox1 gene, which encodes the homeodomain transcription factor PROX1 (prospero-related homeobox-1) [10]. In addition, another transcription factor, COUP-TFII, has been identified as being essential for modulation of PROX1 expression in the cardinal vein [44]. These SOX18+/COUP-TFII+/PROX1+ lymphatic endothelial precursor cells then delaminate from the CV to form lymph sacs, the primary plexus of the lymphatic vasculature, around 11.5 dpc in mouse embryo [43, 45] (Figure 1(a)).
3.1.2. Expansion of the Lymphatic Vascular Network
A dorso-lateral gradient of VEGF-C guides the developing lymphatic endothelial cells during this early phase [46]. Disruption of Vegfc in mice, Xenopus tadpoles, and zebrafish leads to a defect in migration of early lymphatic endothelial cells from the cardinal veins to form a lymphatic plexus [1820]. VEGFR-3 is a specific receptor tyrosine kinase that binds to VEGF-C and VEGF-D and is highly expressed by blood endothelial cells (BECs) before the differentiation of lymphatic vasculature. However, its expression becomes restricted to lymphatic endothelial cells after 11.5 dpc [47]. VEGF-C/VEGFR-3 signalling induces proliferation, migration, and survival of endothelial cells [48], and transgenic overexpression of VEGF-C in the skin promotes lymphangiogenesis [49]. Maintenance of VEGF-C/VEGFR-3 signalling therefore is important in regulation of lymphatic vascular expansion.
A coreceptor for VEGF-C, neuropilin receptor-2 (Nrp-2), is also expressed only within the veins and lymphatics [29]. Both VEGF-C and VEGF-D bind to Nrp-2, and this ligand stimulation leads to internalization of Nrp-2 together with VEGFR-3 [50]. This finding suggests that both Nrp-2 and VEGFR-3 together increase the affinity of LECs toward VEGF-C gradients during lymphatic development.
After LEC specification and establishment of the lymphatic plexus, separation of the lymphatic vasculature from the blood vasculature is one of the most critical stages required to ensure proper function of the two vessel networks. Several key factors and different cell types that are involved in this process have been recently reviewed elsewhere, including tyrosine kinase SYK and its adaptor protein SLP-76, expressed by circulating endothelial progenitor cells, and podoplanin and C-type lectin receptor 2 (CLEC-2), expressed in platelets (see [51] for review) (Table 1).
3.2. Lymphatic Vessel Remodelling and Maturation
The next stages involved in the remodelling and maturation of the lymphatic network include the formation of lymphatic capillary network from the primary lymphatic plexus, and the assembly of collecting lymphatic vessels with recruitment of smooth muscle cells (SMCs) and formation of lymphatic valves [27, 52]. Angiopoietin-2 (Ang2), a growth factor binding to its receptor tyrosine kinase Tie2, has been found to be involved in lymphatic maturation. Ang2 mutant mice display an abnormal lymphatic network due to defective recruitment of smooth muscle cells to the lymphatic collecting vasculature [23]. Further, overexpression of Ang1, Ang2, and Ang3/Ang4 in adult tissues promotes lymphatic sprouting in vivo [5355].
The role of transmembrane growth factor ephrin-B2 in postnatal remodeling of lymphatic vasculature has also been explored using mice that express a mutated form of ephrin-B2 lacking the carboxy-terminal site for binding PDZ-domain-containing proteins. These mutant mice displayed major lymphatic defects, including disturbed postnatal remodeling of their primary lymphatic capillary plexus, hyperplasia, and lack of luminal valve formation, whereas the blood vasculature phenotype remained normal [30, 56, 57].
Taken together, it is clear that many factors are known to be involved in controlling the finely tuned stages of lymphatic vessel development in the embryo (summarized in Table 1). Understanding the early embryonic steps of lymphatic vessel formation will increase our knowledge of how a developmental program is reactivated in the adult under pathological condition, and the consequences of its dysregulation. In the following section, we will discuss the process of adult neo-lymphangiogenesis during pathological conditions, particularly in tumor metastasis.
4. Lymphangiogenesis and Tumor Metastasis
4.1. Tumor Microenvironment: Stroma versus Tumor Vasculature in Metastasis
Metastasis is a complex multistep process identified as the invasion-metastasis cascade, beginning with local invasion then intravasation of cancer cells into blood and lymphatic vessels, transit of cancer cells through these vascular trees, extravasation to the lymph node or distant organs, micrometastasis with small cancer nodules, and finally an invasion step in which micrometastasis becomes macrometastasis [58]. The ability of cancer cells to metastasize depends on many triggers such as the intrinsic properties of the tumor itself and the tumor microenvironment [59].
The tumor microenvironment consists of cancer cells, noncancer cells (e.g., endothelial cells (ECs), cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated macrophages (TAMs)), and noncellular components (extracellular matrix—ECM) [60]. Interaction between cancer cells and their adjacent microenvironment leads to a significant impact on the tumor progression and metastasis (see for review [60]). For instance, tumor chemoattractants including colony-stimulating factors (CSF-1) [61, 62], CC chemokines [63], and VEGF [64] stimulate the recruitment of the infiltrating cells (e.g., monocytes/macrophages) in the lymphatic and blood vessels towards the tumor. Further, several factors secreted by tumors, including interleukin-10, -4 (IL-10, -4), transforming growth factor-β (TGF-β), and CSF-1, can switch these TAMs into polarized type II or M2 macrophages [65]. Importantly, M2 macrophages have reduced T-cell activity, poor antigen-presenting capacity and concomitantly release several protumorigenic factors (TGF-β, IL-10), proangiogenic factors (VEGF, IL-1β), prolymphangiogenic factors (VEGF-C, VEGF-D), and extracellular matrix proteases (matrix metalloproteinases—MMPs) [65, 66]. During tumorigenesis, connective tissue growth factor (CTGF) is also highly expressed [67], which may lead to continued activation of the TGF-β signalling pathway [68]. Further, TGF-β secreted by tumor cells or host inflammatory cells might induce fibroblasts in the tumor microenvironment to become activated fibroblasts (myofibroblasts), which express high levels of α-smooth muscle actin [69, 70]. These activated fibroblasts in turn produce MMPs, which cleave E-cadherin and therefore further induce epithelial to mesenchymal transition (EMT) [71]. Cancer cells undergoing EMT have increased invasive ability because of their loose cell-to-cell contact and acquired mesenchymal properties [72]. In addition, TGF-β secreted by tumors also can induce activin receptor-like kinase 1 (ALK1 receptor) expressed by ECs, leading to endothelial cell proliferation, migration, remodelling [73], and eventually triggering tumor angiogenesis or lymphangiogenesis.
All of the events and complex interactions in the tumor microenvironment alter the nature of tumor stroma cells, which in turn significantly affects tumor progression and metastasis. However, since cell migration through connective tissue is relatively difficult and slow, cancer cells are able to spread more quickly and efficiently via blood or lymphatic vessels [60].
Here, we will focus on one aspect of the tumor microenvironment by examining tumor lymphangiogenesis and its impact on tumor metastasis. Lymphatic vessels, which have high permeability and a lack of tight junction structure compared to blood vessels, are particularly accessible for tumor cell invasion. Clinical studies on breast, cervical, head and neck, and ovarian cancer have revealed that, in most patients, an early sign of cancer spread is metastatic cells located in the regional draining lymph node [74] (reviewed by [5]). Clinical studies have also shown that the process of metastasis occurs in an orderly pattern, starting from the primary site, spreading through the lymphatic channel, and then to regional sentinel lymph nodes before disseminating systemically to distant organs (Figure 1(b)). Studies of micrometastasis in the sentinel lymph node have shown that 80% of metastasis follows this pattern, whereas 20% showed systemic metastasis bypassing the lymphatic system [75]. The lymphatic vasculature is thus one of the major routes for tumor metastasis and therefore is considered a potential target for blocking the spread of cancer.
4.2. Tumor Lymphangiogenesis: Cellular and Molecular Mechanisms
4.2.1. Growth Factors Involved in Tumor Lymphangiogenesis
During the 1990s, the first lymphangiogenic factor, VEGF-C, was identified [76]. Overexpression of VEGF-C by tumor cells can induce lymphangiogenesis and increase metastasis to the regional lymph node in a mouse model of breast and pancreatic cancer [7780]. As mentioned above, TAM has also been identified as a stroma cell critically responsible for production of lymphatic growth factors, VEGF-C, and -D [66, 81] (Figure 1(b)). In addition, VEGF-C overexpression induced enlargement of tumor-associated lymphatic vessels that can increase lymph flow and facilitate intravasation of cancer cells into the lymphatics [77] (Figure 2(b)). VEGF-C has been further shown to induce intercellular gaps that facilitate entry of tumor cells into the lumen of the vessels [82]. More than 65 studies have shown that VEGF-C expression correlates with lymph node metastasis and poor prognosis in a range of human tumors [14, 8389]. In patients with melanoma, mRNA levels of VEGF-C also correlate with stage of tumor progression [90].
Figure 2: Biology of tumor lymphangiogenesis and metastasis. (A), (B) Stimulation of tumor neo-lymphangiogenesis and enlargement of tumor lymphatics can facilitate intravasation of cancer cells into the lymphatics. (C) The interaction between tumor cells and LECs via tumor cell receptors (e.g., Integrin α4β1) and endothelial cell adhesion molecules (e.g., VCAM-1) or via chemokine receptor ligand interaction (e.g., CCR7/CCL21) can facilitate the invasion of cancer cells into lymphatic vessels (intralymphatic cancer cells). (E) Notably, lymphangiogenesis also occurs at the tumor draining lymph node (DLN) before metastasis of cancer cells to this site, probably to generate a favourable environment for in-coming metastatic cancer cells at this site. (F) Intralymphatic cancer cells then metastasize to the tumor DLN. (D), (sG) Additionally, tumor angiogenesis also contributes to distant organ metastasis. The tumor microenvironment has a critical impact on tumor progression and metastasis. LECs, lymphatic endothelial cells; DLN, draining lymph node.
Another structurally related lymphatic growth factor is VEGF-D, which also can bind to VEGFR-3 and activate lymphangiogenesis [91]. VEGF-C and -D share a central VEGF homology domain (VHD), containing receptor-binding sites, flanked by N- and C-terminal propeptides, which can be proteolytically cleaved to produce mature forms with higher affinity to receptors [92, 93]. These mature forms of VEGF-C and -D also can bind to VEGFR-2 and therefore can also promote angiogenesis [9496]. Vegf-d-deficient mice display a lack of lymphatic vascular phenotype, suggesting that VEGF-D might not play a major role in embryonic lymphatic vessel development [22, 97]. However, VEGF-D has been shown to play a role in stimulation of tumor neo-lymphangiogenesis, as the expression of VEGF-D in tumor cells induced tumor lymphangiogenesis and lymph node metastasis in several tumor mouse models [98, 99]. In addition, vegf-d-null mice displayed a reduction in peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumor model [100]. Analysis of VEGF-C and -D expression level in excised patient tumor tissues revealed that levels of these growth factors are associated with poor outcome and lymph node metastasis [101103].
Another VEGF family member, VEGF-A, initially identified as a key positive regulator of angiogenesis, primarily binds to VEGFR-1 and VEGFR-2 [104]. VEGF-A has no known function during embryonic lymphangiogenesis. However, VEGF-A has been shown to induce tumor lymphangiogenesis and tumor metastasis to regional and distant lymph nodes [105], and VEGF-A overexpressing tumors have high numbers of macrophages [106]. Further, Cursiefen et al. (2004) have shown an indirect lymphangiogenic role for VEGF-A via recruitment of bone marrow-derived macrophages (BDMs) by using a mouse model of inflammatory-induced corneal neovascularization. These BDMs in turn secrete angiogenic and lymphangiogenic factors that can stimulate both blood and lymphatic out-growth [107].
Several other factors have been recently identified as inducers of lymphangiogenesis, including hepatocyte growth factor, Angiopoietins 1 and 2 (Ang-1, -2), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor-BB (PDGF-BB), growth hormone (GH), adrenomedullin (AM), insulin-like growth factors 1 and 2, and endothelin-1 (ET-1) (the involvement of these factors in tumor lymphangiogenesis is summarized in Table 2). Some of these factors have already been identified from embryonic lymphatic vessel development studies, whereas others were discovered in tumor lymphangiogenesis studies. Further studies aimed at indentifying lymphangiogenic growth factors will help to provide more potential molecule targets in inhibiting tumor neo-lymphangiogenesis and metastasis.
Table 2: Tumor lymphangiogenic growth factors and their receptors.
4.2.2. Peritumoral and Intratumoral Lymphatics
The relative distance of the tumor to the lymphatic bed can also affect the ability of cancer cells to metastasize. It is well established that peritumoral lymphatics are predominantly responsible for the uptake of cancer cells during metastasis [128]. In fact, lymph node metastasis associated with melanoma can be predicted more accurately by quantitation of peritumoral lymphatic vessels than by quantitation of intratumoral vessels [129]. Also in a clinical study on a cohort of 123 patients with gastric cancer, peritumoral lymphatics were shown to exhibit higher density when compared to intratumoral lymphatics, and importantly these peritumoral lymphatics also play a role in gastric cancer progression [130].
In contrast, the role of intratumoral lymphatic vessels has remained unclear and controversial. Intratumoral lymphatics have been thought to be nonfunctional and are typically collapsed due to the high pressure found in intratumoural environment [128]. Nevertheless, in a mouse model of tumor overexpression of VEGF-C/VEGF-D, proliferation of intratumoral lymphatics was shown to correlate with lymph node metastasis [79, 98, 99, 131]. However, it still remains to be clarified whether function of intratumoral lymphatics is critical for tumor invasion and distant organ metastasis.
4.2.3. Interaction between Tumor Cells and Lymphatic Vasculature
Interactions between tumor cell surface receptors and endothelial cell adhesion molecules are thought to contribute to tumor cell arrest and extravasation during blood vessel-mediated metastasis. It has been shown that the interaction of melanoma cell integrin α4β1 (very late antigen-4, VLA-4) with VCAM-1 is critical for tumor cell arrest [132, 133]. Therefore, the expression of VCAM-1 on tumor lymphatics could lead to increased interaction with cancer cells and further facilitate metastasis. In addition, organ-specific increases in VCAM-1 expression correspond with reported clinical patterns of melanoma metastasis [134, 135].
During inflammatory response, lymphatic vessels play a critical role in the migration of dendritic cells to the draining lymph node to initiate the adaptive immune response [6]. The inflammatory cells interact with the lymphatic endothelium to find their way to the next lymphatic vessels and transmigrate into the vascular lumen [6]. Recent studies have revealed that this interaction occurs through the specific expression of ligands and their receptors. Lymphatic endothelium actively secretes the chemokine (C-C motif) ligand 21 (CCL21), which binds to the C-C chemokine receptor type 7 (CCR7) expressed on dendritic cells, thus creating a chemoattracting gradient for dendritic cells that migrate toward the lymphatic vasculature [136, 137]. Interestingly, tumor cells also can use this physiological chemokine receptor/ligand interaction to metastasize to the regional lymph node [138, 139]. In fact, CCR7 is expressed in some malignant melanoma cell lines [140], and it has been shown in melanoma mouse model that lymphatics can attract cancer cells through secretion of endogenous chemokine [141, 142]. Human breast cancer cells express the chemokine receptors CXCR4 and CCR7 [140]. Further, their respective ligands CXCL12 and CCL21 are highly expressed in the target organs of breast cancer metastasis that can partly explain the metastatic pattern in breast cancer patients [140]. In addition, fibroblasts, which constitute the majority of stromal cells in the tumor microenvironment of breast carcinoma, play an important role in establishment of the CXCL12-CXCR4 axis. In fact, CAFs elevate CXCL12 secretion, which in turn can stimulate proliferation and migration of CXCR4-expressing cancer cells in the tumor microenvironment [143, 144].
Understanding the interaction between tumor cells and LECs can help to identify an alternative way to block the intravasation of cancer cells into lymphatics. Inhibiting key factors involved in this process would provide novel potential therapeutic solution.
4.2.4. Intralymphatic Cancer Cells
Lymphatic invasion at either the primary tumor site or distant metastatic organs is characterised by the existence of cancer cells inside the lumen of the lymphatic vasculature (intralymphatic cancer cells or tumor emboli). The frequency of lymphatic invasion has been investigated in melanoma and gastric and breast cancer [145147]. Importantly, it has been shown that lymphatic invasion occurs more frequently than blood vessel invasion (16% versus 3% in melanoma) [145147]. 75% of melanoma patients that present intratumoral or peritumoral lymphatic invasion also exhibit sentinel lymph node metastasis [145]. Lymphatic invasion is therefore one of the most important adverse prognostic indicators for cancer recurrence rate and sentinel lymph node metastasis [145, 146, 148, 149].
Intralymphatic cancer cells have been also detected in distant organs. In a study using a mouse model of lymphangitic carcinomatosis, an extremely aggressive form of lung metastasis, cells expressing VEGF-C were specifically identified inside the peribronchial lymphatic vessels [150]. This observation suggests that conditioning of the intra-lymphatic vessel milieu with particular factors may have growth-promoting activity, which in turn facilitates tumor survival and promotes metastasis [150]. Since cancer cells remain essentially intra-lymphatic and do not invade the alveolar region, lungs still remain functional until a very advanced stage of the disease. This model of lung cancer metastasis recapitulates the human cancer situation in which patients with pulmonary lymphangitic carcinomatosis typically do not experience symptoms until a very late stage of disease when cancer cells start to extravasate from the lymphatics to invade the alveolar region of the lung [150].
4.2.5. Neo-Lymphangiogenesis in the Tumor Draining Lymph Node
It has been shown that the primary tumor has the ability to induce neo-lymphangiogenesis in the lymph node itself, so as to establish a “platform” from which cancer cells can disseminate [105, 129, 151, 152] (Figure 2(e)). VEGF-A-overexpressing primary tumors induce lymphangiogenesis at the sentinel lymph node even before cancer cells metastasize to this site [105]. Further, in mouse models of skin carcinogenesis in which VEGF-C was overexpressed in skin, lymphangiogenesis occurred at both the primary tumor site and the tumor draining lymph nodes [151]. VEGF-A and VEGF-C secreted from the primary tumor site can be drained to the regional lymph node where lymphangiogenesis is stimulated prior to the invasion of metastatic cancer cells. Once cancer cells metastasize to the regional lymph node, lymphangiogenesis is further enhanced [105, 151]. This observation indicates that lymphangiogenesis in the premetastatic lymph node creates a favourable environment, a premetastatic niche that might support the survival of in-coming metastatic cancer cells [83]. Tumor-induced neo-lymphangiogenesis in the regional lymph node triggers an increase of lymph flow. This upregulation in flow is a permissive factor that can actively enhance metastatic rate via the lymphatics [153]. Importantly, lymph node lymphangiogenesis is also detected in cancer patients suffering from melanoma and breast cancer [154, 155], two cancer types known for their high rate of metastasis.
Additionally, neo-lymphangiogenesis in a distant organ has also been investigated in a mouse model of breast cancer cells that overexpress VEGF-C [150]. The induction of lymphangiogenesis by VEGF-C at a secondary tumor site in the lung was shown to facilitate the expansion of already disseminated cancer cells throughout the lung tissue [150].
4.3. Cellular Origin of Tumor Lymphatic Endothelial Cells
4.3.1. Neolymphatic Vessels Arise Mainly from the Preexisting Vasculature
Identifying the cellular origin of tumor LECs can help to identify targets for anti-lymphangiogenic drugs in tumors. Growth of lymphatic vessels from preexisting vessels (neo-lymphangiogenesis) is regionally induced during tumorigenesis (Figure 3(a)). There is a strong body of evidence in the literature suggesting that neolymphatics mainly arise from preexisting lymphatic vessels, whereas bone marrow-derived endothelial progenitor cells did not significantly contribute to the formation of tumor lymphatic vessels in mouse models of melanoma and lung cancer [3, 156, 157]. This tumor-induced lymphangiogenesis is controlled by the stimulation of various lymphatic growth factors secreted by tumor cells, stroma cells, and inflammatory cells in the tumor microenvironment.
Figure 3: Potential cellular origins of tumor lymphatic endothelial cells. (A) Neolymphatics mainly arise from preexisting vasculature by proliferation and migration of LECs. (B) Bone marrow-derived endothelial progenitor cells (e.g., tumor-associated macrophages—TAMs) can also transdifferentiate into LECs, which further incorporate into the pre-existing lymphatic vasculature. (C) BECs can transdifferentiate into LECs under stimulation of reexpressed lymphatic transcription factors and lymphatic growth factor receptors. This mechanism has not been shown in in vivo (dashed line arrow).
4.3.2. Transdifferentiation from Nonendothelial Cell Types
Several independent studies have demonstrated significant contribution of bone marrow-derived cells (BMDCs) to the formation of new blood vessels during tumor angiogenesis [158, 159]. BMDCs, including endothelial progenitor cells, are recruited to angiogenic sites to support the formation of new vessels [158160]. Endothelial progenitor cells have been shown to play a critical role in regulating the angiogenic switch that eventually affects metastatic progression from micrometastasis to macrometastasis in mouse models of pulmonary metastasis [161].
Since there is a biological association between angiogenesis and lymphangiogenesis, it is important to identify whether BMDCs also play critical role during pathological lymphangiogenesis. It has not yet been established whether expansion of lymphatic vasculature during pathological conditions is critically driven by incorporation of endothelial progenitor cells. Endothelial progenitor cells are present in the newly formed lymphatic vessels in a corneal lymphangiogenesis mouse model and also in peritumoral lymphatic vessels of a fibrosarcoma [162]. Remarkably, depletion of bone marrow cells suppressed lymphangiogenesis in inflamed corneas that were implanted with fibroblast growth factor-2 (FGF-2) [162]. In another model of mouse inflammation after corneal transplant, Maruyama et al. (2005) showed that CD11b+ macrophages infiltrate the corneal stroma and transdifferentiate into lymphatic endothelial cells that integrate into existing lymphatic vessels [163]. Study of de novo lymphangiogenesis in human kidney transplants provided further evidence for the participation of recipient-derived lymphatic progenitor cells [164]. Specifically, myeloid cells present in murine inflamed corneas were found to express specific lymphatic marker VEGFR-3, and these specific cells also integrate into lymphatic vasculature during inflammation [165].
In a further study using bone marrow transplantation and genetic lineage-tracing, Zumsteg et al. (2009) demonstrated that cells derived from the myeloid lineage can contribute to tumor lymphangiogenesis by transdifferentiating to LECs and incorporating into tumor-associated lymphatics in a transgenic mouse model of pancreatic β-cell carcinogenesis and mouse model of transplanted prostate cancer [166] (Figure 3(b)).
Plasticity of macrophages has been demonstrated by the finding that these cells can transform from naïve monocytes into VEGF-C-producing cells. Additionally, TAMs have been shown to also express the lymphatic marker VEGFR-3 [66]. However, the contribution of BMDCs to tumor lymphangiogenesis is rather still controversial. In a study using Lewis lung carcinoma and B16-F1 melanoma cells in syngenic mice, no integration of BMDCs into newly formed lymphatic vessels was detected [156]. Therefore, more studies need to be performed to validate the transdifferentiation pathway of TAMs into LECs during tumorigenesis.
Recently, it has been reported that bone marrow-derived mesenchymal stem cells (MSCs) may also be able to differentiate into endothelial cells (ECs) under certain conditions [167, 168]. MSCs can form networks in a tube formation assay in vitro and also highly express endosialin, a tumor endothelial marker present in the microvascular and stroma of human tumors [167]. Under hypoxic culture conditions, human MSCs can differentiate into endothelial cells and show a significant increase in endothelial specific markers such as CD34, VWF, FLK1, FLT1, TIE2 [168]. Importantly, MSCs infiltrate tumors in high number and have been shown to enhance breast cancer cell metastasis [169]. These studies implicate important roles of MSCs during tumorigenesis, one of which is that MSCs may differentiate into ECs and therefore contribute to tumor angiogenesis and lymphangiogenesis. Conversely, ECs treated with bone morphogenetic protein (BMP4) or TGF-β2 can be reverted to a multipotent cell with MSCs phenotype [170]. This indicates that ECs and MSCs are able to interchange their phenotype. This transdifferentiation may be conditioned by the tumor microenvironment and further contributes to tumor progression.
4.3.3. Transdifferentiation from Blood Endothelial Cells-Endothelial Cell Plasticity
During embryonic lymphangiogenesis, lymphatic endothelial precursor cells arise from venous endothelial cells in cardinal vein. Notably, this specific population of venous endothelial cells expresses several key transcription factors, including SOX18, COUP-TFII, and PROX-1 that regulate the differentiation of venous endothelial cells into LECs [10, 12, 44]. Therefore, under pathological conditions in the adult, reactivation of a specific combination of transcription factors may modulate the plasticity of endothelial cells by turning on the molecular program required for transition from a BEC phenotype to a LEC fate (Figure 3(c)).
In support of this concept, the transcription factor COUP-TFII that is essential for inducing PROX1 expression in venous endothelial cells and triggering the lymphatic differentiation program [44] has been also shown to be required for adult lymphangiogenesis in an animal model of cancer [11] (Table 3). Similarly, although transcription factor SOX18 is not required for the maintenance of the LEC phenotype in adult during physiological condition, it is reexpressed on tumor blood vessels [172] and neolymphatics (unpublished data) suggesting a potential role in tumor-induced lymphangiogenesis. Potentially, the re-expression of SOX18 in BECs may trigger PROX-1 transactivation and induce the acquisition of a LEC phenotype. Moreover, blood vessels have been reported to express lymphatic marker VEGFR-3 in some tumors and chronic wounds [173175]. The expression of VEGFR-3 on BECs not only can contribute to angiogenenic activation via the VEGF pathway but also can induce the LEC phenotype, suggesting that its expression may be indicative of phenotypic transition between blood and lymphatic vessels.
Table 3: Tumor lymphangiogenic transcription factors.
Although there is no direct evidence so far supporting the concept of transdifferentiation from BECs, it is plausible to consider that embryonic lymphatic vascular development is recapitulated in a tumor setting. Further, experimental depletion of the venous endothelium or the macrophage population in a tumor model will yield a definitive answer to the question of key cellular differentiation mechanisms. Indentifying these differentiation programs can lead to more therapeutic options in targeting critical differentiation pathways that trigger lymphangiogenic switch during tumorigenesis.
5. Lymphatic Vasculature as a Potential Therapeutic Target
5.1. Limitations of Antiangiogenic Therapy
Although it has been well established in preclinical and clinical studies that antiangiogenic therapies have antitumoral effects and survival benefits, it also has emerged that tumor cells can eventually elicit multiple mechanisms of resistance that allow them to adapt to a new milieu. Angiogenic inhibitors (such as VEGFR2-specific antibody and sunitinib—an oral, small-molecule, multitargeted receptor tyrosine kinase inhibitor) targeting the VEGF pathway have been shown to display anti-tumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly induced tumor progression to greater malignancy with adaptive “evasive resistance” [183]. This mechanism is followed by increased invasion and distant metastasis. Notably, while both angiogenic inhibitors induced liver metastasis, sunitinib did not enhance lymph node metastasis [183]. The preferred explanation for this effect is that sunitinib potently blocks not only VEGFR-2 and platelet-derived growth factor receptors (PDGFRs) but also specific lymphatic receptor VEGFR-3 [184, 185]. The inhibition of VEGFR-3 in this context can block tumor lymphangiogenesis and lymph node metastasis. This raises the prospect that a potential therapeutic strategy could address both blood and lymphatic vessels to maximize antitumor and antimetastasis effects. Further, glioblastoma patients involved in antiangiogenic therapies, including VEGF ligand-trapping antibody and bevacizumab (a humanized monoclonal antibody that binds to VEGF-A), showed a proinvasive adaptive response where multifocal recurrence of tumors developed during the course of the therapy [186188].
The critical challenge is to manage metastatic disease after the primary tumor has been surgically removed or has been inhibited by antiangiogenic agents. This raises the question of how anti-lymphangiogenic therapeutics might help in blocking both lymph node and distant organ metastasis. Hence, the use of antiangiogenic agents could be considered alongside anti-lymphangiogenic therapeutic approaches with the aim of improving current therapy.
5.2. Targeting the VEGF Family
A number of independent studies have now shown that inhibiting tumor-induced neo-lymphangiogenesis can dramatically reduce the metastatic spread of cancer in mouse models [83, 189, 190] (see [191] for review). Recently, several therapeutic strategies that target outgrowth of lymphatics via the VEGFR-3/VEGF-C/VEGF-D axis have been developed, based on preclinical animal models (Table 4) or on clinical trials using VEGFR tyrosine kinase inhibitors (Table 5). It is important to note that VEGF-C/VEGFR-3 signalling is not required for the maintenance of lymphatic vasculature in the adult, as prolonged inhibition of the VEGFR-3 pathway using soluble VEGFR-3 decoy receptor does not affect preexisting lymphatic vessels in the adult [192].
Table 4: Preclinical studies of anti-lymphangiogenic effect on tumor metastasis.
Table 5: Clinical trials of tyrosine kinase inhibitors on the VEGF pathway.
In preclinical studies, the therapeutic effects of targeting VEGF pathways have been evaluated using antibodies to neutralize lymphatic growth factors/receptor, or a soluble form of VEGFR-3 to trap VEGF-C/D. Neutralization of VEGF-D with a specific antibody or genetic ablation of VEGF-D appears to suppress tumor metastasis in mice [100, 204, 205]. Further, anti-VEGF-R3-blocking antibody or VEGF-C/-D trap strategy (a soluble VEGF-R3 immunoglobulin G Fc-domain fusion protein) has been shown to reduce the rate of lymph node metastasis in mouse models by 60–70% [3, 129, 157, 192, 197, 206, 207] (see [51] for review).
Further, VEGF-C has been known to also bind to Nrp-2 coreceptor and play a role in regulation of small lymphatic vessel and capillary remodelling [29, 208]. An antibody against the Nrp-2 coreceptor that blocks VEGF-C binding has been shown to reduce tumor lymphangiogenesis and metastasis to regional lymph nodes and distant organs [189]. Targeting Nrp-2 therefore has been considered as a potential way to block tumor spread via inhibition of neo-lymphangiogenesis.
Another indirect approach is to target the pathway controlling VEGF-C/-D proteolysis. Proteolysis improves the affinity of VEGF-C and -D for both VEGFR-2 and VEGFR-3, which can further increase the induction of these growth factors during tumor angiogenesis and lymphangiogenesis [94, 108]. Recently, a novel enediynyl peptide inhibitor has been developed to block the furin-mediated processing of pro-VEGF-C to mature VEGF-C [209]; further studies using animal models need to be performed to clarify the in vivo effect and mechanism of this inhibition.
To date, several VEGF-receptor tyrosine-kinase inhibitors have entered phase I, II, or III clinical trials for cancer treatment, including BAY 43-9006, CEP-7055, PTK787/ZK 222584, JNJ-26483327, and SU-014813 (Table 5). These VEGF-receptor tyrosine-kinase inhibitors are well tolerated, display low toxicity and positive results such as an increase in response rate, progression-free survival, and overall survival, and have been observed in advanced colorectal, renal cell, breast, and non-small-cell lung cancer. This response is observed when treatment of VEGF-receptor tyrosine-kinase inhibitors is used alone or in combination with chemotherapy [216]. Although these multiple VEGF-receptor tyrosine-kinase inhibitors also affect tumor lymphangiogenesis via the VEGFR-3 pathway, most clinical investigations have focused on antiangiogenic and antitumor growth effects, and only a handful of reports describe antilymphangiogenic effect or anti-metastatic outcomes. More clinical evaluations on these tumor lymphatic aspects are required to develop a more efficient therapeutic approach against tumor growth and metastasis.
5.3. New Targets for Anti-Lymphangiogenesis
Over the past two decades, many key factors have been identified as important regulators for tumor lymphangiogenesis (Tables 2 and 3), but the major focus in anti-lymphangiogenic therapy has been targeting through VEGF-C and -D, and their membrane receptor VEGF-R3 and coreceptor (Nrp-2) [157, 206, 217]. Blocking only a single pathway related to the VEGF/VEGFR axis may not always be effective to prevent cancer metastasis. For instance, the lack of effect of PTK/ZK (a broad spectrum inhibitor of VEGF signalling) on tumor lymphangiogenesis and lymphatic metastasis in a mouse model of pancreatic β-cell carcinomas overexpressing VEGF-C or VEGF-D reveals the involvement of other pathways [218]. Adenoviral delivery of soluble VEGFR-3 also did not inhibit tumor lymphangiogenesis in these mice. This result suggests that the level of VEGF-C/D expression might be critical for drug effects and that there might be other important pathways involved in tumor lymphangiogenesis.
Various endogenous inhibitors of angiogenesis have been identified so far including matrix-derived group (e.g., collagen fragments, endostatin, tumstatin, …), and non-matrix-derived group (e.g., interferons, angiostatin, …) [219]; however, little is known about endogenous inhibitors of lymphangiogenesis. Using a mouse cornea model in which lymphangiogenesis is induced by factors including VEGF-A, FGF-2, and PDGF-BB, Vasohibin1 has been shown to have broad-spectrum anti-lymphangiogenic activity [220]. Vasohibin1 also appears to inhibit tumor lymphangiogenesis and regional lymph node metastasis in a mouse model of human lung cancer [220]. There is a need to identify novel endogenous lymphangiogenic inhibitors to broaden the therapeutic options in anticancer metastatic treatment.
Conspicuously, the current knowledge of the transcriptional control of pathological lymphangiogenesis has been disregarded, limiting the range of potential novel therapeutic targets. Recent studies have revealed the role of transcription factors in controlling neolymphatic formation during tumorigenesis. For instance, COUP-TFII has been shown to play a critical role in tumor lymphangiogenesis in a mouse model [11]. In addition, SOX18, a transcription factor regulating early vasculogenesis [221, 222] and lymphangiogenesis in the embryo [10], has been also identified to play a critical role in the initial steps of tumor angiogenesis and subsequent induction of the tumor growth. Sox18-mutant mice show greatly reduced tumor diameter compared to wild type [172]. The reexpression of SOX18 on tumor neo-lymphatics (unpublished data) suggests there might be an additional role of SOX18 in controlling tumor lymphangiogenesis. Considering that FOXC2 also plays a critical role during embryonic blood and lymphatic vessel development [17, 223], there is also evidence for the involvement of this transcription factor during tumor growth and angiogenesis. For instance, in aggressive basal-like breast cancers, FOXC2 is also highly expressed and contributes to cancer invasion and metastasis [224]. The tumoral endothelium in human and mouse express FOXC2, and Foxc2 +/− heterozygous mutant mice display reduced tumor growth due to a decrease in neoangiogenic activity [225]. The growing body of evidence supporting a critical of role of transcription factors as modulators of tumor-induced lymphangiogenesis provides new potential avenues in the design of novel therapeutic strategies. Engineering new ways to target transcription factors pharmacologically therefore represents an essential step towards further complementing therapeutic inhibition of the VEGF-VEGF-R axis.
Recent studies have broadened our knowledge about the molecular pathways that regulate tumor lymphatic formation and lymphatic spread. These include not only the group of lymphatic growth factors (Table 2) but also several transcriptional regulators (Table 3). In considering therapeutic application, targeting transcriptional factors may encounter the difficulty in delivery, as drugs need to be delivered to nucleus to be able to block the transcriptional factor targets. Nevertheless, further preclinical studies targeting both growth factors and transcription factors with an efficient delivery system may potentially inhibit tumor lymphangiogenesis and therefore metastasis. Additionally, further studies on the role of other groups of transcription factors that control tumor angiogenesis and tumor lymphangiogenesis will generate new therapeutic options for inhibiting the metastasis of solid tumors.
6. Summary and Conclusions
In preclinical studies using animal models, a variety of approaches have been investigated mainly targeting pro-lymphangiogenic signalling related to the VEGF axis, including neutralization using monoclonal antibodies, soluble receptors, chemical inhibitors, and shRNA. The next challenge is to establish translational studies to address metastasis via a more integrative approach that inhibit multiple pathways (related to both lymphatic growth factors and transcription factors) modulating tumor lymphangiogenesis. An anti-lymphangiogenic approach could be used together with antiangiogenic therapy and conventional chemotherapy, leading to a more efficient way to prevent cancer recurrence [171]. Recently, in a mouse model of gastric cancer, the combination of treatment with antiangiogenic agent (bevacizumab) and genetic blockade of IGF-1 (IGF-1R dominant negative) efficiently reduced tumor growth and importantly resulted in the complete regression of 43% of tumors by inhibiting both angiogenesis and lymphangiogenesis [114]. In humans, the benefit of treatments that combine sunitinib (an anti-angiogenic agent) with docetaxel (an anti-mitotic chemotherapeutic) has been evaluated in phase 1/2 clinical trials of prostate cancer patients. This combination was moderately well tolerated and showed a promising increase of progression-free survival [226].
Based on the most recent preclinical research, photodynamic ablation of in-transit metastatic cancer cells could also be applied to efficiently prevent the recurrence of cancer metastasis (Figure 4). This method relies on liposomes, which ensure lymphatic specific delivery of verteporfin, a drug that can be activated by a 689 nm laser light. The cytotoxic activity of light-activated verteporfin is thus restricted to lymphatic vessels and cancer cells within the vessel. This preclinical study on a mouse model has shown that the recurrent metastasis was reduced to 37.5% compared to untreated animals after laser treatment [227].
Figure 4: Schematic for potential clinical strategies in treatment of metastatic disease. (A) Tumor progression can be evaluated based on several prognostic indicators including tumor lymphangiogenesis and sentinal LNs status. These steps will guide the therapeutic decision to adopt anti-lymphangiogenic strategies if the tumor appears to be lymphangiogenesis-dependent and/or to have lymph node metastasis. (B) Antiangiogenesis, anti-lymphangiogenesis, and chemotherapy can be applied to reduce tumor growth and restrict metastasis before surgery. For advanced disease or nonresectable tumors, there will be no surgery [171]. (C) Photodynamic therapy (PDT) also can be performed before removal of the primary tumor, to eradicate in-transit tumor cells and prevent tumor relapse. Anti-lymphangiogenic, antiangiogenic, and chemotherapy can also be applied later, to prevent tumor regrowth and metastasis. (D) Cancer recurrence can be monitored by checking sentinel LN status, lymphangiogenic and angiogenic growth factor levels. PDT, photodynamic therapy; LN, lymph node; LVD, lymphatic vessel density; GF, growth factor (adapted from [171]).
To advance the prospect of anti-lymphangiogenic therapy, the next step would be to initiate trials on cancer types in which lymphangiogenesis has been clearly identified as a risk factor. Moreover, there are still several issues that need to be clarified which relate to the efficiency of anti-lymphangiogenic therapy in blocking metastasis. Firstly, inhibition of lymphangiogenesis does not seem to affect preexisting vessels [196], which are still potential routes for cancer cell dissemination. Secondly, there are some possible side effects of targeting tumor-associated lymphatic vessels [228]. Inhibition of lymphangiogenesis might interfere with physiological process such as wound healing and tissue regeneration [173]. Finally, lymphedema is a complication in 20%–30% of breast cancer patients after surgery to remove the tumor-metastasized lymph node [229, 230]. Therefore, preclinical studies using animal models have been performed in an attempt to restore lymphatic vessel function in secondary lymphedema, including VEGF-C, VEGF-D gene transfer using adenovirus or naked plasmids and recombinant VEGF-C protein [3, 231].
In conclusion, the study of embryonic lymphatic vessel development has revealed key factors that play a central role in controlling tumor-induced lymphangiogenesis. However only the VEGF/VEGF-R axis has been thoroughly investigated and exploited with a view to restricting tumor growth and metastasis, and so far the outcomes in terms of patient survival have been limited. Therefore, it is important to continue efforts to indentify factors and molecular mechanisms in order to fully comprehend how tumor neo-lymphangiogenesis is regulated and participates in tumor metastasis. These discoveries will lead to identification of potential new molecular targets and design of novel therapeutic avenues of metastatic disease. In addition, further preclinical studies focusing on delivery systems, side effects, drug resistance, and combination of anti-angiogenic and anti-lymphangiogenic therapies may eventually improve the efficacy of current treatments.
Abbreviations
Ang:Angiopoietin
BEC:Blood endothelial cell
BMDCs: Bone marrow-derived cells
CAFs: Cancer-associated fibroblasts
CV: Cardinal vein
dpc:days post coitum
ECs:Endothelial cells
LEC:Lymphatic endothelial cell
LN:Lymph node
LS:Lymph sac
MSCs:Mesenchymal stem cells
TAMs:Tumor-associated macrophages
VEGF:Vascular endothelial cell growth factor
VEGFR:Vascular endothelial cell growth factor receptor.
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Bibliography: 4X4
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Review of: 4X4
Book Authors: Michael T. Huyck, Jr. and Brian Keene and Geoff Cooper and Michael Oliveri
Reviewer: Paul Di Filippo
Year: 2002
Type: REVIEW
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Copyright (c) 1995-2011 Al von Ruff.
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OpenWetWare:Respond to NSF
From OpenWetWare
Revision as of 20:53, 18 January 2007 by Reshma P. Shetty (Talk | contribs)
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Contents
High Level Comments from NSF
1. Wants to see a 3-year plan (willing to hear case for 5 years, w/ evaluation point at EOY3)
2. Wants to see money spent on actual stuff (e.g., code) not project management
• Jasonk 19:16, 16 January 2007 (EST):What are the chances we can convince them a community developer (the position we outlined for the NIH $) is doing 'stuff'? This is not project management (e.g. not dealing with funding, strategic decisions, etc), but rather a person supporting the growth of various communities on OWW - communities that in the end will do more "stuff" then a couple paid programmers could ever do. Also, those communities will be persistent when the grant money ends in 3 years, while the programmers won't. Plus we'd really like to get a volunteer software developer community off the ground, since new code will need support when the 3 years is over as well.
• Vincent 13:01, 17 January 2007 (EST): Is there any possibilities to spend money on bringing face to face this virtual community in order to stimulate interactions/collaborations:
• OWW annual conference
• OWW workshops on hot OWW topics (characterization of parts, optimization of protocols, ethical issues ...)
• OWW twinning (money available for some OWW user to visit some other(s) on a specific OWW project )
What user types should OWW target for focused development support? What are the needs of these communities?
1. Individual researcher
2. Research lab
3. Research community
4. Educator
5. Journal
6. Organization
7. Other?
• Sri Kosuri (talk): The focus here should not be on user types, but on any of the above categories that are willing to share information openly on biology research.
How should OWW best leverage existing software development efforts?
1. MediaWiki
2. Jot/Google
3. Apple OS Next (e.g., an OS with a built-in wiki)
4. Other?
• Sri Kosuri (talk): It's somewhat silly to consider this question now. Currently, Jot/Apple is not available to us; and Mediawiki seems to be the best software for what we are doing. As opportunities arrive for better software in the future, the Steering Committee (w/ support by technical people hired by the grant) have already shown they are well positioned to make such decisions (i.e., private wikis, moving servers, user management system).
What should be the relationship between OWW and publishers?
1. None
2. Sell-out
3. Destroy
4. Creative partnership
5. Other?
• What does OWW get from working with publishers?
1. Increased legitimacy
2. Opportunity to subvert existing merit structure in science
3. Push forward more rapid publication options / technologies
4. others?
• Why publishers anyway? What should OWW's relationship be with facebook/myspace? or with slashdot/reddit/digg, or Google? There are other groups that could be considered for partnerships as well.
Framework for thinking about OpenWetWare's mission
in progress, please contribute
OpenWetWare's stated mission is to promote the open sharing of information in biological science and engineering research. There are three primary approaches to achieving this goal.
Developing tools and technologies
Example tools and technologies that reduce the barriers to sharing information include
1. Publish to OWW button for private wiki pages
2. Publish to DSpace button for public wiki pages
3. Mediawiki extension that allows auto import of information from existing scientific databases (analogous to the Biblio extension.
1. Genbank
2. PDB
3. Genome databases
4. Tools for visualization of scientific information on the wiki (note these would likely rely permitting users to use existing viewer inside OpenWetWare)
1. Sequence viewer
2. Structure viewer
3. Genome browser
5. Image editor for generating graphics in OWW
6. Tagging of wiki pages
7. Wiki forum
8. Dynamic ranking of pages (like Reddit or Digg but using your OWW account)
9. Introduction of WYSIWYG wiki interface and/or switchover to alternate wiki implementation
10. Semantic web tools for annotating data enhancing machine readability
11. Tools for conversion of word documents to wiki format
Fostering a community that values sharing
Efforts that may help promote community growth and involvement include
1. Developing tutorials for
1. Starting a userpage
2. Starting a class
3. Starting a lab
4. Starting a research community
2. Developing and piloting norms for categorization of pages
3. Establishing good examples of consensus protocols as a model for others to follow
4. Creating videos of protocols on OWW
5. Pushing through articles on OpenWetWare
Incentivizing sharing via the scientific reward structure
Ways for OWW to push back on the existing system
1. Getting journals to permit citations of OWW pages in papers
2. Promote publishing of supplementary information to papers on OWW (not large datasets but rather protocols and details of experimental setup)
3. Getting an "impact factor" for OWW (inclusion in the Thomson Scientific index)
Personal tools
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User:HyoEun Bhang
From OpenWetWare
Revision as of 23:44, 22 March 2007 by Hbhang (Talk | contribs)
Jump to: navigation, search
Go to JHIBRG
Contents
HyoEun Bhang
PhD candidate (Advisor: Martin G. Pomper, M.D., Ph.D.)
Department of Pharmacology and Molecular Sciences
Johns Hopkins University School of Medicine
E-Mail :hbhang1@jhmi.edu
Research
• in vivo molecular-genetic imaging of cancer by monitoring transcription factor activities
• Imaging cell trafficking in vivo
• Development of small animal models of cancer
Education and Professional Training
• Johns Hopkins University School of Medicine, Baltimore, Maryland (2004-Present)
Department of Pharmacology and Molecular Sciences
PhD candidate in Pharmacology
• University of California, San Diego, La Jolla, California (2001-2002)
Education Abroad Reciprocal Exchange Program
• Yonsei University College of Engineering, Seoul, Republic of Korea (1999-2003)
Department of Biotechnology
Bachelor of Science in Biotechnology
• Ewha Girls' Foreign Language High School (1996-1999)
French major
Honors and Awards
• The Scheinberg Travel Award (2006)
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine
• SMI Student Travel Stipend Award (2006)
- The Fifth Annual Meeting of the Society for Molecular Imaging (SMI)
• Korea Science and Engineering Foundation (KOSEF) Fellowship (2004-2006)
- The Graduate Studies Abroad Program
Publications
Personal tools
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[9]
Eratosthenes gives the distances as follows: From Mt. Caspius to the Cyrus River, about one thousand eight hundred stadia; thence to the Caspian Gates, five thousand six hundred; then to Alexandreia in the country of the Arians, six thousand four hundred; then to the city Bactra, also called Zariaspa, three thousand eight hundred and seventy; then to the Iaxartes River, to which Alexander came, about five thousand; a distance all told of twenty-two thousand six hundred and seventy stadia. He gives also the distance from the Caspian Gates to India as follows: To Hecatompylus, one thousand nine hundred and sixty stadia; to Alexandreia in the country of the Arians, four thousand five hundred and thirty; then to Prophthasia in Drangge, one thousand six hundred (others say one thousand five hundred); then to the city Arachoti, four thousand one hundred and twenty; then to Ortospana, to the junction of the three roads leading from Bactra, two thousand; then to the borders of India, one thousand; a distance all told of fifteen thousand three hundred stadia.1 We must conceive of the length of India, reckoned from the Indus River to the eastern sea, as continuous with this distance in a straight line. So much for the Sacae.
1 The sum total of the distances here given is 15,210 stadia, not 15,300 (15,500 MSS.). The total of 15,300 is again found in 15. 2. 8.
This work is licensed under a Creative Commons Attribution-ShareAlike 3.0 United States License.
An XML version of this text is available for download, with the additional restriction that you offer Perseus any modifications you make. Perseus provides credit for all accepted changes, storing new additions in a versioning system.
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Citation URN: urn:cts:greekLit:tlg0099.tlg001.perseus-eng1:11.8.9
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Google Sitemap - Is there a real benefit?
Jun 14, 2005 • 11:00 am | (7) by | Filed Under Google Search Engine
When we-won't-do-SEO's-any-favors Google launched its new Site Map application, it was like dangling a carrot in the air and seeing who would bite. Is it worth going through the hassle of learning this thing just to get more web pages indexed?
Curious Cre8asite members wanna know, in Effect of new Google Site Map on SEO?
Question being:
"If your site is already indexed and ranking well, is there any benefit to submitting the Google Site Map from an SEO viewpoint?"
Not everyone is drinking Google's Koolaid. Michael, (aka "Projectphp") quips:
"For a static site with little changes, SiteMaps is a useful as tits on a Bull"
Previous story: Whats Does A Search Engine Spider Look Like?
blog comments powered by Disqus
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User talk:Linny4tea
Watchers
Welcome
Welcome to WeRelate, your virtual genealogical community. We're glad you have joined us. At WeRelate you can easily create ancestor web pages, connect with cousins and other genealogists, and find new information. To get started:
1. Take the WeRelate tour to see what you can do.
2. Watch the "Getting Started" tutorial video to learn how to make ancestor web pages.
3. Explore the Step by step Tutorials, if needed.
If you need any help, I will be glad to answer your questions. Just click on my signature link below and then click on the “Leave a message” link under my name in the upper left corner of my profile page. Thanks for participating and see you around! --DFree 13:46, 30 April 2009 (EDT)
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ACC AHA guidelines classification scheme
Jump to: navigation, search
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The Class designation is used to indicate whether a therapy is recommended or not and the certainty surrounding that recommendation.
Classification of Recommendations
Class I: Benefit >>> Risk
Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective.
Class II:
Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.
Class IIa: Benefit >> Risk
Weight of evidence/opinion is in favor of usefulness/efficacy.
Class IIb: Benefit ≥ Risk
Usefulness/efficacy is less well established by evidence/opinion.
Class III: Risk ≥ Benefit
Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful.
Class III: No Benefit
Is not recommended, not indicated, should not be performed/ administered/ other. Is not useful/beneficial/effective.
Class III: Harm
Potentially harmful, causes harm, associated with excess morbidity/mortality. Should not be performed/administered/other.
Use the Level of Evidence designation to indicate the strength of the data associated with that recommendation.
Level of Evidence
Level of Evidence A:
Data derived from multiple randomized clinical trials or meta-analyses.
Level of Evidence B:
Data derived from a single randomized trial, or nonrandomized studies.
Level of Evidence C:
Only consensus opinion of experts,case studies, or standard-of-care.
Applying Classification of Recommendations and Level of Evidence
Navigation WikiDoc | WikiPatient | Popular pages | Recently Edited Pages | Recently Added Pictures
Table of Contents In Alphabetical Order | By Individual Diseases | Signs and Symptoms | Physical Examination | Lab Tests | Drugs
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Template:Osteochondrodysplasia
Jump to: navigation, search
Navigation WikiDoc | WikiPatient | Popular pages | Recently Edited Pages | Recently Added Pictures
Table of Contents In Alphabetical Order | By Individual Diseases | Signs and Symptoms | Physical Examination | Lab Tests | Drugs
Editor Tools Become an Editor | Editors Help Menu | Create a Page | Edit a Page | Upload a Picture or File | Printable version | Permanent link | Maintain Pages | What Pages Link Here
There is no pharmaceutical or device industry support for this site and we need your viewer supported Donations | Editorial Board | Governance | Licensing | Disclaimers | Avoid Plagiarism | Policies
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ARTICLE
Who’s the Man (Japanese Short Film)//
posted Sunday, June 5th, 2011
by | Comments (0)
Original Title: 男の証明
Release date: 2009
Director: Koji Kawano
Screenplay by: Mina Yoshikawa
Cast: Hairi Katagiri, Eiji Sugawara, Ryosei Konishi, Seiji Nozoe, Toru Shinagawa, Tetsuhiro Ikeda
Who’s the Man is also a comedy part of the Hijoshi Zukan short film collection — which also includes B.
The story begins with the casting call for a movie they’re making called Who’s the Man, where the producer and director are looking for the perfect actor to play The Man in a mafia film, which seems a tough task when the producer announces that the director is particularly picky. The director is sitting on his reviewing table waiting for the next batch of actors that are auditioning for the role, but he seems bored out of his mind.
His new batch of actors doesn’t look promising: an obvious Yakuza called Tsuyoshi, who’s auditioning because his older brother was set to audition. Pretty boy Morita with his cool and delicate mannerism, as well as otaku Adachi — the producer seems hopeless.
Finally actress Jun Karasawa (Hairi Katagiri) introduces herself, and despite the producer being taken aback by Karasawa’s participation for the male lead role, the director loves her as she answers questions like “what makes a man.
Actress Hairi Katagiri is pitch-perfect in her role as the inspirited actress. Her stern look and features enhance her performance here and lets us realize that she’s got great comedic timing — which she showcased on Kamome Diner.
Though the film isn’t really about a woman with Gender Identity Disorder — the producer clearly addresses this by asking Karasawa if she has a male heart in a female body, to which she just responds that it isn’t the case, Who’s the Man does make you wonder about the characteristics that make a man… whether it is biological or whether it goes beyond that. The producer continues being perplexed, considering the director doesn’t really care… at all.
In the end, after all the trials — which include a lot of funny moments… who’s the man? Jun Karasawa is.
You can actually stream this on IMDb apparently.
Rating:
Part of the 2011 LGBT Blogathon
UPCOMING EVENTS//
EVENTS//
ADS//
POLLS//
Who is your reigning Queen or Princess of Pop? [choose up to 5]
Total Voters: 252
Loading ...
TWEETS//
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
4441.0.55.002 - A Comparison of Volunteering Rates from the 2006 Census of Population and Housing and the 2006 General Social Survey, Jun 2012
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 08/06/2012 First Issue
Page tools: Print Page Print All RSS Search this Product
2. LITERATURE ON VOLUNTEERING
There are numerous theories to explain who engages in voluntary work. The Dominant Status model originally developed by Lemon et al. (1972) is frequently cited. According to this model, participation in voluntary activity is associated with a ‘dominant status’ position in society. That is, people who are highly educated and who have a high status job are likely to have a higher propensity of volunteering than people who do not (Lemon et al., 1972). Bales (1996) also comments that volunteering is associated with higher levels of education, income, and belonging to the dominant ethnic group. In Australia, level of educational attainment has also been found to be positively associated with the propensity to volunteer (Evans and Kelly, 2000). This association has been found in a number of studies (for example, Goss, 1999; Zwart and Perez, 1999; Davis Smith, 1998). However, while education level is associated with the propensity to volunteer, it may not be a determinant among people who commit a large amount of time to volunteering. Lyons and Hocking (2000) reported that among highly committed volunteers (those volunteering more than 300 hours a year) there was no difference in education level.
Other research has shown that people volunteer for activities that benefit their children, in areas such as sports teams or scouting (Smith, 1994). Furthermore, some researchers argue that motivational aspects (Clary and Snyder, 1991) and church attendance (Evans and Kelley 2000) have strong associations with volunteering, however this theory could not be tested in this analysis because similar information about religion and church participation were not available from both the GSS and the Census.
Analysis already published by the ABS is consistent with the themes of this research. People who volunteer generally have higher levels of education and higher incomes than those who do not volunteer. There are high rates of volunteering among people who are employed and parents with school-aged children. People in rural areas volunteer at slightly higher rates than people in major urban areas. The organisations that attract the highest number of volunteers include sports clubs, educational institutions and community/welfare organisations. While the rate of volunteering had risen over the ten or so years to 2006, the average number of hours people volunteered had fallen in 2006 (ABS 2006a; 2008).
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
1370.0 - Measures of Australia's Progress, 2010
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 15/09/2010
Page tools: Print Page RSS
Competitiveness and openness, while not given headline status, has nevertheless been included as a supplementary dimension because of its relevance to whether life in Australia is getting better.
Over the previous decade there has been a moderate decrease in real unit labour costs and this is likely to have had a positive effect on Australia's international competitiveness.
During the same period, the trade weighted index (the value of the Australian dollar relative to the currencies of our major trading partners) decreased between 1999 and 2001, increased until 2008 and then decreased.
Real unit labour costs
Trade weighted index
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Research article
Inhibition of hyaluronan export reduces collagen degradation in interleukin-1 treated cartilage
Barthold Deiters and Peter Prehm*
Author affiliations
Muenster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstr. 15, D-48129 Münster, Germany
For all author emails, please log on.
Citation and License
Arthritis Research & Therapy 2008, 10:R8 doi:10.1186/ar2357
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/10/1/R8
Received:31 July 2007
Revisions received:25 October 2007
Accepted:18 January 2008
Published:18 January 2008
© 2008 Deiters and Prehm; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Osteoarthrosis is characterized by cartilage erosion, proteolysis of aggrecan and collagen, and disturbed rates of synthesis of aggrecan and hyaluronan by chondrocytes, with hyaluronan over-production being an early reaction. We considered that inhibition of hyaluronan export might prevent subsequent proteoglycan loss and collagen degradation.
Methods
To test this hypothesis, we studied a tissue culture model using bovine cartilages explants activated with IL-1α to induce osteoarthritic reactions using the phosphodiesterase-5 inhibitors tadalafil, zaprinast and vardenafil.
Results
These drugs inhibited hyaluronan export, but they did not inhibit hyaluronan synthase activity. Simultaneously, they inhibited proteoglycan loss and collagen degradation, but not their synthesis. They also reduced the release of gelatinases into the culture media and diffusion of the indicator protein horseradish peroxidase through the cartilage explants. The mechanism of action of these compounds may be through inhibition of hyaluronan exporter multidrug resistance-associated protein 5 (MRP5), because the effective drug concentrations were much higher than required for phosphodiesterase-5 inhibition and intracellular cGMP accumulation.
Conclusion
Inhibition of hyaluronan over-production may be an appropriate target to attenuate IL-1-induced reactions in osteoarthritic cartilage.
Introduction
Destruction of joint cartilage is the major outcome of arthritic diseases such as osteoarthrosis and rheumatoid arthritis. Although chondrocytes represent only 5% of the tissue, these cells are responsible for cartilage matrix synthesis, which consists of two main components: the network of type II collagen, which provides the tensile strength and stiffness; and the large aggregating proteoglycan aggrecan, which is responsible for the osmotic swelling capability and elasticity. Aggrecan decorates a backbone of hyaluronan that is partially anchored in the plasma membrane of chondrocytes at the hyaluronan synthase site and is further bound by the cell surface receptor CD44. Aggregate formation is important from a physiological point of view because it ensures the retention of aggrecan within the collagen network.
The biosyntheses of hyaluronan and proteoglycans take place via different mechanisms and occur in different compartments [1]. Proteoglycans are synthesized in the Golgi and exocytosed by vesicles. Hyaluronan is polymerized at the inner side of plasma membranes [1-4] and was originally thought to be exported by the synthase itself [5,6], but recently the ATP-binding cassette transporter multidrug resistance protein (MRP)5 was identified as a hyaluronan exporter [7,8]. Both components aggregate in the extracellular matrix [9], with up to 200 aggrecan molecules decorating one hyaluronan chain [10]. In healthy cartilage, the hyaluronan and aggrecan are synthesized and degraded at similar rates [11], whereas the turnover of collagens is much slower [12]. The proteoglycan monomer is liberated from the hyaluronan binding region by aggrecanases, matrix metalloproteases and cathepsins [13-17]. In healthy cartilage, most of hyaluronan is removed by endocytosis through the CD44 receptor [18], whereas in osteoarthritic cartilage about 90% is liberated into the environment [19]. Aggrecan leaves cartilage either as intact molecule or after proteolysis, depending on the stimulus [20].
Key events in osteoarthritic cartilage are increased hyaluronan, decreased aggrecan synthesis [19,21], and proteolytic cleavage of collagen type II and aggrecan core protein [22,23]. For a long time it was believed that proteolytic degradation of collagen and aggrecan was the primary event in cartilage breakdown. Much effort to develop protease inhibitors led to compounds that were chondroprotective in vitro or in animal models [24-27], but the findings of clinical trials were equivocal [28,29].
Recently, we discovered that a variety of multidrug resistance inhibitors interfered with hyaluronan export by the the multidrug resistance-associated protein MRP5 [7,8]. Some of the hyaluronan export inhibitors have already been applied to prevent hyaluronan over-production and proteoglycan loss in IL-1α activated chondrocyte cell cultures, in cartilage organ cultures and in an animal model of osteoarthrosis [30]. Because hyaluronan export by MRP5 is regulated by intracellular cGMP [8] (also an MRP5 substrate [31]), we evaluated the effects of the drugs zaprinast, vardenafil and tadalafil. These agents are structural analogues of cGMP that inhibit the cGMP-specific phosphodiesterase (PDE5) at nanomolar concentrations [32] and so they increase intracellular cGMP levels. In addition, zaprinast is also known as a MRP5 inhibitor [33]. We analyzed their effects on hyaluronan export, proteoglycan loss and collagen degradation in IL-1α activated bovine articular cartilage explants.
Materials and methods
Materials
Articular cartilage was obtained from the knees of 2-year-old steer provided by a local slaughterhouse. Vardenafil was from Bayer AG (Leverkusen, Germany), tadalafil was from Elli Lilly (Indianapolis, IA, USA), hyaluronan binding protein (HABP) was from Calbiochem (Schwalbach, Germany), and hyaluronan (Healon®) was a gift from Genzyme (Cambridge, MA, USA). Polyclonal antibodies to matrix metalloprotease (MMP)9 were from Biomol (Hamburg, Germany). Additional chemicals were from Sigma-Aldrich Chemical Corporation (Taufkirchen, Germany).
General methods
The hyaluronan synthase activity was determined by incorporation of radioactive [14C]glucuronic acid from UDP- [14C]GlcA and UDP-GlcNac [7]. The cytotoxicity of the drugs was measured as described previously [34]. For all experiments, the weight of the explants was determined immediately after cutting to minimize evaporation and the data were related to wet weight.
Determination of hyaluronan
Cartilage explants were incubated in the absence or presence of IL-1 (2 ng/ml) and the inhibitors at various concentrations in serum-free Dulbecco's medium for 3 days. The amount of hyaluronan released into the culture medium was determined using biotinylated HABP, as described previously [30].
Determination of proteoglycans
Cartilage explants were weighed (average wet weight 20 mg) and incubated in the absence and presence of IL-1 (2 ng/ml) and the inhibitors at various concentrations for 5 days. The tissues were extracted with 1.5 ml of a solution of 4 mol/l guanidinium hydrochloride, 0.1 mol/l ε-aminohexanoid acid, 5 mmol/l benzamidine, 10 mmol/l N-ethylmaleinimide and 0.5 mmol/l phenalmethylsulfonyl fluoride for 3 days at 4°C. The solution was centrifuged for 5 minutes at 10.000 g and the proteoglycans were determined in the supernatant using the alcian blue method, as described previously [35].
Determination of the proteoglycan synthesis
Chondrocytes were cultured in alginate beads, as described above, and supplemented with 25 μl [35S]sulphate (0.5 mCi/ml) for 24 hours. The beads were washed three times with 102 mmol/l CaCl2 to remove un-incorporated radioactivity and dissolved in 55 mmol/l sodium citrate. Proteoglycans were isolated by the alcian blue precipitation method [36] and aliquots were used in the determination of radioactivity.
Measurement of degraded collagen
The procedure for measurement of degraded collagen is described in detail in the report by Kosaki and coworkers [37]. Cartilage explants were cultured in Dulbecco's medium for 28 days in the presence or absence of IL-1 (2 ng/ml), IL-17 (25 ng/ml), 2 μmol retinoic acid and hyaluronan export inhibitors, and media were changed every 2 days. The cartilage was weighed and extracted with 4 mol/l guanidinium hydrochloride in 0.1 mol/l Tris HCl (pH 7.3), 1 mmol/l Iodoacetamide, 1 mmol/l EDTA, and 10 μg/ml pepstatin A for 72 hours. The extracted explants were washed with 1 mmol/l iodoacetamide and 1 mmol/l EDTA, and 10 μg/ml pepstatin in 0.1 mol/l Tris-HCl (pH 7.3) three times for 2 hours. The denatured collagen was digested overnight at 37°C with a solution of 0.5 ml of α-chymotrypsin (0.5 mg/ml) in 1 mmol/l iodoacetamide and 1 mmol/l EDTA, and 10 μg/ml pepstatin in 0.1 mol/l Tris-HCl (pH 7.3). The mixture was centrifuged for 8 minutes at 10,000 g, and the supernatant containing the digested collagen was separated from the remaining insoluble matrix containing the intact collagen. The insoluble material was hydrolyzed with 500 μl of 6 mol/l HCl at 110°C for 20 hours. The hydrolysate was neutralized with 500 μl of 6 mol/l NaOH and undissolved material was removed by centrifugation. The amount of the collagen-specific amino acid hydroxyproline was determined. An aliquot (25 μl) was mixed with 975 μl citrate buffer (57 g sodium acetate, 37.5 g sodium citrate, 5.5 g citric acid and 385 ml 2-propanol in 1 l water). An aliquot (200 μl) of this mixture was added to 100 μl of a solution of 100 mg chloramine T in 1 ml water, 2 ml 2-propanol and 3 ml citrate buffer. After 20 minutes at room temperature, 100 μl of 6.2 mol/l perchloric acid was added and reacted for 12 minutes at room temperature. A solution of 100 μl Ehrlichs reagent (500 mg in 1.25 ml ethanol and 1.25 ml diethyleneglycol-monoethylether) was added and incubated at 60°C for 20 minutes. The adsorption was read at 565 nm and the content of hydroxyproline was calculated using 1 to 30 μg/ml calibration samples.
Determination of collagen synthesis
Chondrocytes were cultured in alginate beads for 1 week with 10% foetal calf serum in Dulbecco's medium. The medium was changed and supplemented with 1 mmol/l cysteine, 1 mmol/l pyruvate, 60 μg/ml β-aminopropionitril and 25 μg/ml ascorbic acid, and the beads were incubated for an additional 24 hours. The medium was replaced with serum-free medium containing the above supplements, IL-1, the inhibitors and [14C]proline (2 μCi/ml), and the cells were incubated for 24 hours. The beads were washed three times with 0.9% NaCl and CaCl2 (116 mg/l) for 30 minutes to remove unincorporated radioactivity, dissolved in 500 μl of 55 mmol/l sodium citrate, and the radioactivity was determined.
Zymography of matrix proteases
Bovine cartilage explants were cultured in serum-free Dulbecco's medium for 5 days in the presence or absence of IL-1α (2 ng/ml) and 10 or 30 μmol/l zaprinast, vardenafil, or tadalafil. The protein concentrations of the culture media were determined and equal amounts of proteins were directly applied to a 7.5% SDS-polyacrylamide gel that contained 0.1% gelatin. After electrophoresis, the gel was washed twice with 2.5% Triton X-100 for 30 minutes, three times with water for 10 minutes, and incubated in a solution of 50 mmol/l Tris-HCl, 5 mmol/l CaCl, 1 μmol/l ZnSO4 (pH 8.0) for 5 days at 37°C. The gel was stained with Coomassie blue.
Determination of protein infiltration into the cartilage matrix
Bovine cartilage explants were cultured in Dulbecco's medium and 10% foetal calf serum in the presence or absence of IL-1α (2 ng/ml) and the drugs zaprinast, tadalafil and vardenafil for 14 days. Pieces of 2 mm diameter and a volume of 3.15 mm3 were punched out. They were incubated in a solution of 10 units/ml of horseradish peroxidase (HRPO) in phosphate-buffered saline for 1 hour at 37°C. The pieces were rinsed with water and shaken in 250 μl phosphate-buffered saline overnight at 4°C to release the infiltrated enzyme. The concentrations of HRPO were determined in 50 μl of the supernatants. A solution (150 μl) of ABTS (2,2'-azino-bis [3-ethylbenzthiazoline-6-sulfonic acid]; 1 mg/ml) and 0.03% H2O2 was added, and after incubation for 30 minutes at 37°C the adsorbance at 405 nm was read.
Statistical analyses
Data are presented in the figures as mean ± standard deviation. The t-test was used, and a P value below 0.05 was considered statistically significant.
Results
Inhibition of hyaluronan export
The drugs tadalafil, zaprinast and vardenafil were analyzed for their effects on hyaluronan export from bovine cartilage explants in tissue culture. Cartilage explants were incubated for 3 days in the presence and absence of IL-1α and increasing concentrations of the drugs. Figure 1a shows that IL-1α stimulated an increase in hyaluronan export by about sixfold, and the inhibitors partially reversed it. In control experiments, the inhibitors were analyzed for their effect on the hyaluronan synthase activity of chondrocytes cultured in alginate beads. Activity was reduced by less than 20% up to concentrations of 400 μmol/l (Figure 1b). The toxicity of the drugs was less than 10% at a concentration of 100 μmol/l for the three inhibitors.
Figure 1. Inhibition of hyaluronan export in bovine chondrocytes. (a) Cartilage explants were incubated in the absence and presence of IL-1α and the drugs tadalafil (○), zaprinast (□), or vardenafil (△). The concentration of hyaluronan was determined in the supernatant after 3 days. The error bars indicate the standard deviation of three determinations. (b) Effect of inhibitors on hyaluronan synthase activity. A particulate fraction of chondrocytes was prepared and incubated with the substrates UDP-GlcNac and UDP-[14C]GlcA and increasing concentrations of tadalafil (○), zaprinast (□), or vardenafil (△), and the incorporation into [14C]hyaluronan was determined.
Inhibition of proteoglycan loss
The drugs tadalafil, zaprinast and vardenafil were analyzed for their effects on proteoglycan loss from IL-1α activated bovine cartilage explants. Proteoglycans were extracted from the tissues with guanidinium hydrochloride and determined colourimetrically. Figure 2a shows that IL-1α reduced the proteoglycan content in cartilage to less than 40% of that in the untreated control. The inhibitors protected the cartilage from proteoglycan loss. In a control experiment, the effect of the inhibitors on the proteoglycan synthesis rate was determined. Bovine chondrocytes were cultured in alginate beads and incubated with [35S]sulphate in the presence of drugs, and inhibition of proteoglycan synthesis was found to be reduced by less than 25% (Figure 2b). These findings confirm earlier observations obtained with other drugs [30] and suggest that zaprinast, vardenafil and tadalafil prevented proteoglycan loss from osteoarthritic cartilage primarily by inhibition of hyaluronan over-production.
Figure 2. Inhibition of proteoglycan loss in bovine chondrocytes. (a) Cartilage explants were incubated in the absence and presence of IL-1α and the drugs tadalafil, zaprinast, or vardenafil at concentrations of 50 μmol/l. The tissues were weighed, extracted with guanidinium hydrochloride, and the amount of proteoglycans was determined after 5 days. The data were related to controls without IL-1α as 100%. The error bars represent the standard deviation of three determinations; *P < 0.05. (b) Effect of inhibitor tadalafil (○), zaprinast (□), or vardenafil (△) on proteoglycan synthesis. Bovine chondrocytes were cultured in alginate beads and incubated with increasing concentrations of the inhibitors in the presence of [35S]sulphate. After 24 hours the radioactivity incorporated into [35S]proteoglycans was determined.
Inhibition of collagen degradation
The drugs were analyzed for their effects on collagen degradation in IL-1α activated cartilage explants. Preliminary experiments revealed that induction of osteoarthritic reactions by IL-1α was not sufficient to detect measurable amounts of collagen degradation products. Degradation can be enhanced substantially by addition of IL-17 and retinoic acid. Therefore, these activators were added. Activated cartilage explants were incubated with tadalafil, zaprinast, or vardenafil for 28 days, extracted with guanidinium hydrochloride, and digested with chymotrypsin. Degraded collagen was measured as the amount of hydroxyproline that was susceptible to chymotrypsin. Figure 3a shows that cartilage activation reduced the amount of chymotrypsin-resistant collagen to 65%. Inhibition of hyaluronan export restored the content of intact collagen. In a control experiment, the effect of zaprinast on collagen synthesis was measured (Figure 3b). Bovine chondrocytes were cultured in alginate beads and incubated in culture medium containing [14C]proline in the absence and presence of zaprinast and incorporation of radioactivity into pepsin-resistant collagen was determined. The total amount of collagen was not altered significantly at concentrations up to 100 μmol/l zaprinast. These findings suggest that the drugs did not affect collagen synthesis and that the protection from collagen degradation could involve other mechanisms.
Figure 3. Quantitative analysis of collagen degradation and its inhibition. (a) Cartilage explants were incubated with IL-1α, IL-17 and retinoic acid in the absence or presence of zaprinast, tadalafil, or vardenafil at concentrations of 50 μmol/l for 4 weeks at 37°C. The amount of chymotrypsin-resistant collagen was determined as hydroxyproline. The values were related to the control that contained 23 μg hydroxyproline/mg cartilage as 100%. The bars indicate the standard deviation of four determinations; *P < 0.05. (b) Bovine chondrocytes were grown in alginate beads and and collagen was labeled by incorporation of [14C]proline in the absence or presence of 30 μmol/l and 100 μmol/l zaprinast. The amount of [14C]collagen within the alginate beads was determined after 24 hours. The bars indicate the standard deviation of four determinations.
Inhibition of the action of gelatinases
A possible explanation for the protective effect of hyaluronan export inhibition on collagen degradation could be that the altered composition and permeability of osteoarthritic cartilage allowed the diffusion of metalloproteases. It is known that chondrocytes produce gelatinases, particularly if they are activated by IL-1 [38]. We tested this possibility by measuring the release of gelatinases from IL-1α activated cartilage. Cartilage explants were incubated in the absence and presence of IL-1α and vardenafil, and enzymes released from the cartilage explants were analyzed by gel zymography. We also included dibutyryl-cGMP in the analysis, because cGMP has been shown to mediate IL-1 signalling in chondrocytes [39]. Figure 4a shows three bands with molecular weights of 86 kDa, 66 kDa and 62 kDa. The upper band was probably pro-MMP9, because it reacted with monoclonal antibodies in Western blots (data not shown). The lower two bands comigrated with an authentic sample of pro-MMP2 and MMP2 gelatinases (from Dr R Dreier; data not shown). IL-1α enhanced the release of the gelatinases, and this release was not significantly altered by addition of dibutyryl-cGMP. Vardenafil reduced the gelatinase release in a concentration-dependent manner. Similar results were obtained with zaprinast and tadalafil (data not shown).
Figure 4. Effect on gelatinases. (a) Inhibition of gelatinase liberation from bovine cartilage explants. Cartilage explants were incubated in the absence or presence of IL-1α and 25 μmol/l dibutyryl-cGMP or 10 μmol/l or 30 μmol/l vardenafil for 4 days at 37°C. The lanes marked with (-) indicate two independent control experiments with IL-1 only. The activity of gelatin-degrading enzymes released into the culture supernatant was determined by zymography. (b) Unaffected gelatinase synthesis. Unstimulated explants were incubated for 10 days in the absence and presence of 100 μmol/l zaprinast, vardenafil and tadalafil, and the gelatinase activities were again analyzed by gel zymography. MMP, matrix metalloprotease.
In a control experiment, we analyzed whether inhibition of hyaluronan export altered the syntheses of gelatinases by chondrocytes in unstimulated cartilage explants. The explants were incubated in the absence and presence of 100 μmol/l zaprinast, vardenafil and tadalafil, respectively, and the gelatinase activities were again analyzed by gel zymography. Figure 4b shows no differences in enzyme activities between the samples. These results showed that inhibition of hyaluronan export in IL-1 activated cartilage explants inhibited the release of gelatinases into the culture medium.
Inhibition of protein diffusion through cartilage explants
If the altered composition of arthritic cartilage with increased hyaluronan and decreased proteoglycan content was responsible for facilitated diffusion of degrading enzyme through the matrix, exogenous enzymes should infiltrate better. This hypothesis was tested using HRPO as an indicator protein. Cartilage explants were incubated in the absence or presence of IL-1α and zaprinast, vardenafil, or tadalafil in increasing concentrations. The explants were incubated with the indicator protein HRPO to allow diffusion into the cartilage. After extensive washing, the explants were further incubated in phosphate-buffered saline to liberate the infiltrated enzyme. The amount of liberated enzyme was determined by a colour reaction. Control experiments indicated that the drugs did not have any direct effect on the peroxidase activity at micromolar concentrations. Figure 5 shows that IL-1α treatment led to an increase of enzyme infiltration of about 350% over the unstimulated control (100%). Inhibition of hyaluronan export reduced the IL-1α induced enzyme infiltration almost to control values.
Figure 5. Inhibition of protein infiltration into bovine cartilage explants. Cartilage explants were incubated in the absence or presence of IL-1α and (a) tadalafil, (b) zaprinast, or (c) vardenafil for 14 days at 37°C. The explants were then incubated with horseradish peroxidase as indicator protein for 1 hour. After washing, the amount of enzyme that had infiltrated the explants was determined by a colour reaction. The error bars represent the standard deviation of eight determinations.
Mechanism of inhibitor action
There are two possible mechanisms for the inhibitory action of the drugs zaprinast, vardenafil and tadalafil. Because of their PDE5 inhibitory activity, with Ki values of 300 nmol/l for zaprinast, 1.5 nmol/l for vardenafil and 2.9 nmol/l for tadalafil [40,41], they will certainly raise the concentration of intracellular cGMP that could inhibit hyaluronan export by MRP5 [8]. It is also possible that they additionally act as MRP5 inhibitors, because they are structural analogues of cGMP; also, it is known that zaprinast inhibits transport at concentrations between 20 nmol/l and 250 μmol/l, depending on the transported substrate [33,42,43]. If the drugs acted only through inhibition of PDE5, then also other unrelated PDE5 inhibitors or addition of other cGMP analogs should have similar effects. We therefore analyzed hyaluronan export, proteoglycan loss and collagen degradation of IL-1 activated cartilage explants in the presence of dibutyryl-cGMP and ODQ (1H-[1,2,4]-oxadiazolo [4,3a]quinoxaline-1-one), which is a selective inhibitor of the soluble nitric oxide inducible guanylate cyclase. Figure 6 shows that none of the parameters was significantly altered by these treatments. Similar results were obtained with bromo-cGMP (data not shown). These findings suggest that alterations of the intracellular cGMP concentration did not account for the inhibitory effects of the drugs zaprinast, vardenafil and tadalafil.
Figure 6. Influence of cGMP modulators. Shown is the influence of cGMP modulators on the hyaluronan (open bars), proteoglycan (solid bars), and collagen (cross-hatched bars) production of bovine cartilage. Cartilage explants were cultured in the presence of 2 ng/ml IL-1 and the guanylate cyclase inhibitor ODQ (1H-[1,2,4]-oxadiazolo [4,3a]quinoxaline-1-one; 25 μmol/l) or dibutyryl-cGMP (25 μmol/l). The incubation periods were for 3 days for hyaluronan, 5 days for proteoglycans and 28 days for collagens. For stimulation of collagen degradation, the cartilage explants were supplemented with 25 ng/ml IL-17, and 2 μmol/l retinoic acid. The concentrations of hyaluronan in the supernatant, proteoglycans and collagen (as hydroxyproline) were determined as described under Materials and methods. The error bars represent the standard deviation of three determinations.
Discussion
One of the earliest events in the pathogenesis of osteoarthritis is hyaluronan over-production of chondrocytes that precedes the stimulation of protease synthesis, collagen degradation and cartilage destruction [44-46]. It can be induced by IL-1 treatment in cell and organ culture and in animal models of osteoarthritis. IL-1 alters the cartilage composition by influencing the transcription rate of enzymes and matrix components [47].
In a previous report we showed that hyaluronan over-production led to loss of proteoglycans from osteoarthritic cartilage [30]. Inhibition of hyaluronan over-production normalized the proteoglycan content on alginate cultures of bovine chondrocytes, in cartilage explants and in an animal model of osteoarthrosis. We showed that enhanced intracellular cGMP levels reduce hyaluronan export from fibroblasts [8]. In the present study we extended the effect of hyaluronan export inhibitors to collagen degradation. We used the drugs zaprinast, vardenafil and tadalafil that were originally developed as PDE5 inhibitors [32].
We showed here that the drugs inhibited hyaluronan export, and protected cartilage from proteoglycan loss, release of metalloproteases into the medium and collagen degradation. The drugs did not influence substantially the rates of synthesis of hyaluronan, proteoglycans, metalloproteases and collagens. Our experiments also suggest a mechanism for how the inhibitors of hyaluronan export were able to prevent collagen degradation. Hyaluronan over-production increased the infiltration of the indicator protein HRPO into IL-1α treated cartilage, and this infiltration was reduced by inhibition of hyaluronan export. It is likely that this inhibition also applies to reduced diffusion of proteoglycans and gelatinases MMP2 and MMP9 or other degrading enzymes out of the cartilage or from their origin to the targets within the cartilage.
The reason for the enhanced diffusion of proteins through osteoarthritic cartilage can be found in the altered cartilage composition. Proteoglycans at high concentrations in cartilage play a critical role in the flow and diffusion of macromolecules. Because of the high density of fixed charges, they vigorously restrict diffusion [48,49]. If the dense packing of proteoglycans is lost and replaced by voluminous hyaluronan, degrading enzymes can freely reach their targets. It has indeed been demonstrated that aggrecan protects cartilage collagen from proteolytic degradation [50]. As a consequence of this scenario, collagen is protected from degradation by inhibition of hyaluronan export.
We also analyzed the mechanism of hyaluronan export inhibition. At nanomolar concentrations, the PDE5 inhibitors substantially elevate the intracellular cGMP levels [32]. Zaprinast acts also as a MRP5 inhibitor in micromolar concentrations [33]. Because the effects that we observed on hyaluronan export, proteoglycan loss and collagen degradation were all found in the micromolar range, it is likely that the drugs primarily exerted their effects on export by MRP5 rather than through an increase in intracellular cGMP levels. Although based on a limited dataset, the rank order of potency for PDE5 inhibition of zaprinast (Ki = 300 nmol/l), tadalafil (Ki = 2.9 nmol/l) and vardenafil (Ki = 1.5 nmol/l) does not correlate with the apparent potency of these compounds in inhibiting hyaluronan export induced by IL-1 (Figure 1). This notion was supported by our experiments that altered the intracellular cGMP by the specific guanylate cyclase inhibitor ODQ and the analogues dibutyryl-cGMP and bromo-cGMP. These compounds did not have any significant effect on hyaluronan export, proteoglycan loss and collagen degradation. The lack of an effect by cGMP analogues on chondrocytes is surprising and clearly different from the effects on fibroblasts [8]. Such cell-dependent discrepancies of MRP5 inhibition were previously observed in other cell lines and are probably due to different MRP5 copy numbers per cell [43].
The drugs zaprinast, tadalafil and vardenafil have been developed for other disturbances and are certainly not ideal for treatment of osteoarthrosis. It may be worthwhile to develop specific hyaluronan export inhibitors, because they could not only prevent proteoglycan loss and collagen degradation, but also inhibit subsequent reactions that lead to apoptosis of chondrocytes.
Conclusion
Inhibition of hyaluronan export from chondrocytes attenuated proteoglycan loss, collagen degradation, protein diffusion and metalloprotease activity in IL-1 activated cartilage and could be effective in osteoarthrosis.
Abbreviations
HABP = hyaluronan binding protein; HRPO = horseradish peroxidase; IL = interleukin; MMP = matrix metalloprotease; MRP = multidrug resistance-associated protein; ODQ = 1H-(1,2,4)-oxadiazolo (4,3a)quinoxaline-1-one.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
BD performed the experiments, evaluated the data and designed the experiments. PP evaluated the data, designed experiments and wrote the manuscript.
Acknowledgements
The authors thank Professors P Bruckner and JE Scott for their critical review of the manuscript, and U Rasmussen and R Schulz for technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 492).
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Ann N Y Acad Sci 1999, 878:413-419. PubMed Abstract | Publisher Full Text
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Drugs Aging 2001, 18:87-99. PubMed Abstract | Publisher Full Text
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J Rheumatol 2005, 32:690-696. PubMed Abstract | Publisher Full Text
31. Andric SA, Kostic TS, Stojilkovic SS: Contribution of multidrug resistance protein MRP5 in control of cGMP intracellular signaling in anterior pituitary cells.
Endocrinology 2006, 147:3435-3445. PubMed Abstract | Publisher Full Text
32. Kulkarni SK, Patil CS: Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects.
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33. Pratt S, Shepard RL, Kandasamy RA, Johnston PA, Perry W III, Dantzig AH: The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites.
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38. Sasaki K, Hattori T, Fujisawa T, Takahashi K, Inoue H, Takigawa M: Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes.
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40. Turko IV, Francis SH, Corbin JD: Potential roles of conserved amino acids in the catalytic domain of the cGMP-binding cGMP-specific phosphodiesterase.
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41. Blount MA, Zoraghi R, Ke H, Bessay EP, Corbin JD, Francis SH: A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization.
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42. Sundkvist E, Jaeger R, Sager G: Pharmacological characterization of the ATP-dependent low K(m) guanosine 3',5'-cyclic monophosphate (cGMP) transporter in human erythrocytes.
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44. Kozaci LD, Buttle DJ, Hollander AP: Degradation of type II collagen, but not proteoglycan, correlates with matrix metalloproteinase activity in cartilage explant cultures.
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49. Maroudas A, Scheiderman R, Popper O: The role of water, proteoglycan, and collagen in solute transport in cartilage. In Articular Cartilage and Osteoarthritis. Edited by Kuettner K, Schleyerbach R, Peyron JG, Hascall VC. New York, NY: Raven Press; 1992:355-371.
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Comedian Louis CK, on bypassing ticket retailers to sell seats directly to fans through his website:
Well, it’s all so interesting. It’s all so interesting. It really is. I love knowing why I was able to sell out in one town, and why I wasn’t in another town. I love knowing what goes into everything—the economics, the technical aspect, and how to create the ideas in the show. It’s great. If you can have access to all of that, why would you not want to know? I just love learning. I think learning is how you live. The verb of my life is learning.
There are people who find failure interesting. Those people's failures are often more interesting than their peers' successes. Their lives also tend towards success even though the prospect of a successful life motivates them less than the prospect of an interesting one.
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sfsmisc (1.0-23)
1 user
Utilities from Seminar fuer Statistik ETH Zurich.
http://cran.r-project.org/web/packages/sfsmisc
Useful utilities ['goodies'] from Seminar fuer Statistik ETH Zurich, quite a few related to graphics; many ported from S-plus times.
Maintainer: Martin Maechler
Author(s): Martin Maechler et al.
License: GPL (>= 2)
Uses: Matrix, cluster, lokern, nlme, MASS
Enhances: mgcv, nor1mix, rpart, sm, polycor
Reverse depends: ascrda, catIrt, catR, ChemometricsWithR, distr, FrF2, lokern, lordif, modiscloud, pcalg, plfm, polycor, random.polychor.pa, RTDAmeritrade
Reverse suggests: ChemometricsWithR, copula, expm, lme4, longmemo, nacopula, Rmpfr, robustbase, stabledist
Reverse enhances: Matrix
Released 7 months ago.
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Rewrite.NET -- A URL Rewriting Engine for .NET
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Rewrite.NET -- A URL Rewriting Engine for .NET (Unpublished)
This article examines how to take advantage of HttpModules to create a URL rewriting engine in .NET. This tool has been described as the Swiss Army Knife of URL manipulation. If you don't have a fundamental understanding of what HttpModules are and how to create and use them
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Why SOLID? GIMME AN O!
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Why SOLID? GIMME AN O! (Unpublished)
The next leg of our quest to uncover the deeper driving forces behind SOLID principles brings us to the Open/Closed Principal (OCP). To refresh, I think it's important that if we're going to say (read the next part in a mouth-breathing, war-hammer-playing, mega-nerd voice) "your design violates TLA," we had better back it up with some solid reasoning.
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Metatrichoniscoides celticus
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Scientific nameMetatrichoniscoides celticus Taxonomic rankQuestionnable
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INVESTIGATION ON IMPROVEMENT OF YANGTZE ESTUARY
Yen Kai, Yan Yixin
Abstract
The improvement of the Yangtze Estuary has attracted much attention in China. The fluvial processes of the estuary are rather complicated. The frequent move of sandbanks in the estuarine channels and the bar forming at the mouth give much trouble to navigation. Investigation on the guiding principles and schemes for the improvement of the Estuary has been carried out since 1958.Comprehensive field survey, laboratory experiments and numerical modeling as well as planning work have been done in the past 30 years with some preliminary achievement. A scale model study with horizontal scale 1:1600 and vertical scale 1:120 was conducted by the Nanjing Hydraulic Research Institute.
Keywords
estuary; Yangtze estuary; estuary improvement
Full Text: PDF
This work is licensed under a Creative Commons Attribution 3.0 License.
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Quotation added by staff
Why not add this quote to your bookmarks?
In a sense, each of us is an island. In another sense, however, we are all one. For though islands appear separate, and may even be situated at great distances from one another, they are only extrusions of the same planet, Earth. Walters, J. Donald
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It's easy! Just pick the product you like and click-through to buy it from trusted partners of Quotations Book. We hope you like these personalized gifts as much as we do.
Make and then buy your OWN fantastic personalized gift from this quote
Poetry should only occupy the idle. Byron, Lord
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212 - The Extra Degree
The one extra degree makes the difference. This simple analogy reflects the ultimate definition of excellence. Because it's the one extra degree of effort, in business and life, that can separate the good from the great. This powerful book by S.L. Parker and Mac Anderson gives great examples, great quotes and great stories to illustrate the 212° concept. A warning - once you read it, it will be hard to forget. Your company will have a target for everything you do ... 212°
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Blaming the victim
From RationalWiki
Jump to: navigation, search
Blaming the victim describes the attempt to escape responsibility by placing the blame for the crime at the hands of the victim. Classically this is the rapist claiming his victim was "asking for it" by, for example, wearing a short skirt.
Denying the victim is similar, but has a slight difference in that the perpetrator attempts to assert that he or she is the real victim. Denying the victim is generally less of a one-on-one scenario, and more topical. "The real victims of the supposed 'mistreatment of women' are the children who have to grow up on homes where their mother wants to work instead of care for them". Denying the victims, in this sense, is often an attempt at historical revisionism, to make those charged with the crimes, look more or even totally innocent in the light of modern society. Denial of the victim can also take the form of minimizing the number of victims or the severity of the offense. For example, the Roman Catholic Church played this game, when trying to claim the systematic child abuse by some priests were simply isolated events both individually and by priests at large. They also pushed the issue that the boys should not be described as children, but young men to minimize the sense of how horrific these rapes were.
Both blaming the victim and denying the victim are specific instances of neutralization.
Contents
[edit] Examples
• Representatives of the Papacy have lashed out at The New York Times for its investigative journalism of the cover-up of pedophile priests. Rev. Raniero Cantalamessa even compared the anger directed at the Vatican in the pedophilia scandal to "the most shameful aspects of anti-Semitism." News Report
• Blaming bullying and violence toward homosexuals on the homosexuals themselves. For instance, several anti-gay activists (including Bryan Fischer) has claimed that the murder of 15 year-old openly gay eighth grader Lawrence King[1] must be blamed on King himself. In a column called “Who will protect straights from homosexual bullies” Fischer alleged that King's killer was a victim of King's relentless sexual harassment,[2] and as a solution of anti-gay hate crimes Fischer suggested “placing reasonable curbs on the public expression of homosexual behavior."
[edit] See also
[edit] References
• Stanley Cohen. 2001. States of Denial: Knowing About Atrocities and Suffering. Cambridge: Polity Press. Pp. 96-97.
[edit] Footnotes
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Keepon finally for sale
Posted 8 Feb 2011 at 19:58 UTC by mwaibel
The funny yellow dancing robot KeepOn of youTube fame (see above) will finally be available in a toy version. The toy version will look the same as the current research version, which is used as a telepresence tool for autism research and therapy. However, unlike the research version which is priced at 30'000 dollars (!) a piece, the toy version will retail for a mere 40 dollars. For now it's not completely clear what the toy robot will be able to do, but according to the BeatBot's press release it will maintain the reactivity to touch and its ability to listen to music, detect the beat, and dance in a perfect rhythm.
See more of the latest robot news!
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Skip to content
Personalized Medicine: Real Clinical Examples!
There are more than 60 articles in the personalized medicine category on my blog and I have a page dedicated to this emerging field of medicine. I also wrote a summary about it. But now it is time to show you some real examples; some cases and ideas that could play a major role in the future of healthcare. Genetic tests and pharmacogenetic variants which are used in clinical practice or will be used soon. I would like to consider this post as a continuously developing collection or database of examples and ideas. Please let me know if you know other examples of personalized medicine that were published in a peer-reviewed journal.
• Azathioprine (AZA) and 6-mercaptopurine (6- MP) in inflammatory bowel disease¹:
Thiopurine S-methyltransferase (TPMT) is a key metabolic enzyme for azathioprine (AZA) and 6-mercaptopurine (6- MP), 2 widely used medications in the treatment of IBD. AZA is metabolized to 6-MP and subsequently 6-thioguanine (6-TG), the active metabolite. 6-MP can be inactivated by either TPMT or xanthine oxidase to nontoxic products. SNPs in the TPMT gene reduce TPMT activity, shunting metabolism to 6-TG and increasing toxicity, particularly neutropenia; TPMT deficiency can serve to lower the starting dose or to alternative therapies. TPMT enzyme (phenotype) activity in red blood cells and genotype testing to detect the major mutations that lower TPMT activity are both available and used by most physicians in the United Kingdom, including 75% of gastroenterologists. Approved by the US Food and Drug Administration (FDA), TPMT testing has led to relabeling for AZA and 6-MP to provide genomic information to providers.
• Methotrexate in Crohn’s disease¹:
This pharmacogenetic test is used in IBD treatment. The SNPs of methylenetetrahydrofolate reductase (MTHFR) are associated with increased toxicity of methotrexate used to treat Crohn’s disease.
• Her2/neu positivity in breast cancer²:
HER2/neu is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor.
Human epidermal growth factor receptor 2-overexpressing breast cancer is known to be associated with particularly aggressive disease and poor prognosis. On the other hand, human epidermal growth factor receptor 2/neu overexpression may predict response to endocrine therapy or chemotherapy. Nevertheless, trastuzumab increases the clinical benefit of first-line chemotherapy in patients with metastatic breast cancers that overexpress human epidermal growth factor receptor 2. In the pretrastuzumab era, retrospective analyses have shown that human epidermal growth factor receptor 2 overexpression is an adverse prognostic factor associated with an increased risk of disease recurrence and death. In the trastuzumab era, this drug has changed the natural history of human epidermal growth factor receptor 2-positive breast cancer, either in the metastatic or, according to the most recent evidences, in the adjuvant setting.
• VKORC1 and CYP2C9 polymorphisms in warfarin metabolism³:
Warfarin is the most widely prescribed oral anticoagulant, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. Pharmacogenetic analysis of two genes, the warfarin metabolic enzyme CYP2C9 and warfarin target enzyme, vitamin K epoxide reductase complex 1 VKORC1, confirmed their influence on warfarin maintenance dose. Possession of CYP2C9*2 or CYP2C9*3 variant alleles, which result in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose. Several single nucleotide polymorphisms (SNPs) in VKORC1 are associated with warfarin dose across the normal dose range. Haplotypes based on these SNPs explain a large fraction of the interindividual variation in warfarin dose, and VKORC1 has an approximately three-fold greater effect than CYP2C9. Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic, and clinical factors to estimate the warfarin dosage, could potentially minimize the risk of over dose during warfarin induction.
FDA approved it last year.
• CYP2C19 polymorphism in Helicobacter pylori–related disorders¹:
The treatment of H pylori infection requires a multidrug regimen that contains multiple antibiotics plus proton pump inhibitors (PPIs) or histamine-2 receptor blockers for eradication. Pharmacogenetic studies have revealed potentially important host genetic variability to PPI response; CYP2C19 SNPs define patients as rapid (RM), intermediate (IM), or poor metabolizers (PM). Asian populations demonstrate a higher frequency of PMs, higher PPI efficacy, and may have better H pylori eradication at standard doses. With omeprazole the most sensitive to CYP2C19 variation, H pylori eradication rates may vary with specific PPIs and are generally lower; higher PPI doses may be needed in RMs. Pretreatment PPI genotyping improves H pylori eradication rates but cost effectiveness has not yet been studied.
• UGT1A1 polymorphism in irinotecan treatment of colon cancer¹:
Irinotecan, a topoisomerase I inhibitor, is a first-line treatment for colon cancer, alone or in combination. Delivered as a prodrug, irinotecan must be metabolized to SN-38, an active compound that is then inactivated by UDP glucuronosyltransferases (UGTs). Variability in one of these enzymes, UGT1A1, leads to accumulation of SN-38 and increased toxicity, most notably neutropenia and diarrhea. Specific UGT1A1*28 and UGT1A1*6 (in Asians) SNPs markedly increase irinotecan toxicity risk. Further, Gilbert’s syndrome, a benign disorder of indirect hyperbilirubinemia, is caused by the same mutations and predicts irinotecan toxicity. The FDAhas relabeled irinotecan and approved tests for UGT1A1*28 SNPs; UGT1A1*6 analysis will be additionally needed for Asian patients. UGT1A1 testing may prevent severe irinotecan toxicity through dose reduction or switching to an alternative oxaloplatin-based regimens. For oxaloplatin, genetic testing for SNPs in the DNA repair genes XRCC1, ERCC1, and ERCC2 and glutathione-S-transferase (GST), predict better response, although diagnostic tests for these mutations are not yet routinely available.
• Polymorphism of 5-fluorouracil in the treatment of gastric cancer¹:
Even with the arrival of new biologic agents against colon cancer, 5-fluorouracil (5-FU) remains a mainstay of treatment but carries a high risk of adverse effects. Multiple SNPs in DPYD decrease DPY enzyme activity, which would normally inactivate 5-FU and its orally administered prodrug capecitabine; heterozygotes for these genetic variants reach a prevalence of 3%–5%. Cost effectiveness will determine the usefulness of DPD enzyme assays or genotype testing for DPYD variants prior to using 5-FU or capecitabine. In addition, genetic variants in the thymidylate synthase promoter lead to decreased tumor response to 5-FU–based regimens. Pharmacogenetic lessons learned in colon cancer treatment seem to apply to gastric cancer.
References:
1. Patel KK, Babyatsky MW. Medical Education: A Key Partner in Realizing Personalized Medicine in
Gastroenterology
. Gastroenterology. 2008 Mar;134(3):656-61.
2. Ferretti G, Felici A, Papaldo P, Fabi A, Cognetti F. HER2/neu role in breast cancer: from a prognostic foe to a predictive friend. Curr Opin Obstet Gynecol. 2007 Feb;19(1):56-62.
3. Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 – rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11.
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Document Type
Working Paper
Date
2000
Embargo Period
6-28-2012
Keywords
time-series models, dynamic quantile regressions, panel data, panel unit root tests, panel cointegration tests, estimation of panel cointegration models
Language
English
Disciplines
Mathematics
Description/Abstract
This paper provides an overview of topics in nonstationary panels: panel unit root tests, panel cointegration tests, and estimation of panel cointegration models. In addition it surveys recent developments in dynamic panel data models.
Source
Metadata from RePEc
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This work is licensed under a Creative Commons Attribution 3.0 License.
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Thread Tools Search this Thread
Posts: 25 | Thanked: 6 times | Joined on Dec 2007 @ US
#11
this is great, worked perfectly.
Super Moderator | Posts: 5,335 | Thanked: 8,167 times | Joined on Mar 2007 @ Pennsylvania, USA
#12
Originally Posted by jalladin
...naming the new folder stuff...
Just to be sure, did you name the folder "stuff" or "Stuff"? The system is case sensitive, so if it's "Stuff", you'll need to use:
Code:
cd /media/mmc2/Stuff
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#13
Originally Posted by jalladin
i dnt know why my Xterm isnt working, i saved the files to a new folder under the "internal memory" naming the new folder stuff... when i open up Xterm any type in ( cd /media/mmc2/stuff ) it say not found.
I am supose to save and not open each file right?
sorry for being such a bother...
Not a bother - I'm a complete Linux-nub myself
I'd say do this:
1) Open up File Manager
Click on the Internal memory card link in the left window.
Does Stuff show up in the list of content on the right hand side?
If it does - continue to step 3)
2) If Stuff is not listed in the right window it is most likely that you accidentally created the Stuff directory somewhere else - maybe under a different directory, etc.
You can spend some time digging around for this missing directory - or just create a new one. And since you are already in the file manager you can do that right in there by clicking >File>New Folder and create a folder on the internal memory card
3) So, we know that there is a folder on the internal memory card, at the top-level, named "Stuff" (or whatever).
4) Now launch X Terminal again
5) If you got rootsh installed run the command root
6) Your prompt should have changed to Nokia-N810-something
7) Now type in cd /media/mmc2
(note that you have to use forward-slashes (/) for it to work
ALSO note that you HAVE to put a space between the cd and the folder name
8) You should now be in the root folder of the internal memory card
9) issue the command ls -l
10) Scroll up, if needed, to ensure that you see your Stuff folder there
11) now do cd /Stuff
(and yes, it's case-sensitive so beware of that)
12) You SHOULD now be in the directory where you put the files you downloaded - so now execute the command(s) listed in the earlier posts - and do let us know how it went
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My Twenty Favorite OS2008 Applications:
AutoScan, Diablo5 Theme, Dialcentral, DragLock, EmelFM2, FlipClock, gPodder, Headphoned, Knots 2, Maemo Mapper, mPlayer, openNTPD, OpenSSH, Panucci, Personal Launcher, QuickNote, Seqretary, SlideLock, Telescope, YellowNotes
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#14
This is a must have.
Thanks Querty12 for the patched files and Silvermountain for your How To.
Posts: 283 | Thanked: 31 times | Joined on Jun 2009 @ US Air Force
#15
Thanks So Much guy's,
IT WORKED!!!
Thanks to you both,
@sjgadsby, it was the case sensitivity. turns out I over looked the fact that when i created a new folder it automatically starts off the name in caps, but when your in Xterm it doesnt. Thanks to you too @silvermountain, i really apriciate you helping make sure i figured this out. It was also me not fully knowing what you meant by running "root" ( type root ) and making sure every word is as is typed in as posted. You would think after wining a Superior Performer award in the Air Force Honor Guard I would have a bit more attention to Detail, lol, Thanks so much guys.
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Last edited by jalladin; 08-01-2009 at 02:48 AM.
Posts: 384 | Thanked: 90 times | Joined on Mar 2008
#16
What's the story behind the maemo folks not including this option in OS2008? They'd only have to use the device themselves for 24 hours before realizing locking down the applets is a must have feature. Just one of many things about maemo that scream "the developers do not use this device/OS outside of their office."
The Following User Says Thank You to st5150 For This Useful Post:
Posts: 441 | Thanked: 86 times | Joined on Jan 2009 @ Virginia, USA
#17
I finally got this to work. The problem is that the patched versions have exactly the same version numbers as the originals. Shouldn't the versions be updated or at least the release numbers? I can understand not wanting to update the version numbers, but you should be able to call them, for instance,
hildon-desktop_2.0.18-1fix1.1_armel.deb
libhildondesktop0_2.0.18-1fix1.1_armel.deb
libhildonwm0_2.0.18-1fix1.1_armel.deb
or something to differentiate them from the original debs.
But a very useful patch nonetheless. My only wish is that it would be persistent across reboots.
--vr
Posts: 1,665 | Thanked: 1,642 times | Joined on Jun 2008 @ Praha, Czech Republic
#18
Originally Posted by VulcanRidr
The problem is that the patched versions have exactly the same version numbers as the originals. Shouldn't the versions be updated or at least the release numbers?
Thought about other apps/libraries that have a = dependency on this package, instead of a >= dependency? :-)
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#19
Originally Posted by VulcanRidr
But a very useful patch nonetheless. My only wish is that it would be persistent across reboots.
http://talk.maemo.org/showpost.php?p...postcount=1046 =)
I keep the version numbers the same because you would have to install the osso-rx(34/44)-software-version-unlocked package to be able to install the debs otherwise. I also do not change the section to make it possible to install in Blue Pill mode as it would show up as an update in Blue Pill mode every time which'd be an annoyance.
Last edited by qwerty12; 08-04-2009 at 04:39 AM.
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#20
Worked great!
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User:Maj/Sandbox/Turkey
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Contents
[edit] Regiões
Geographically, Turkey can be divided in 7 regions:
• Akdeniz - region of the Mediterranean
• Anat�lia
• Ic Anadolu - Central Anat�lia
• Dogu Anadolu - Eastern Anat�lia
• Guney Dogu Anadolu - Southeastern Anat�lia
• Ege - region of the Aegean one
• Karadeniz - region of the Black Sea
• M�rmara
Administratively, Turkey is divided in 81 provinces (il) whose names follow of its capitals.
[edit] Cidades
Mapa of Turkey] * Ancara - the capital of Turkey has a museum of prehistoric civilizations and the mausoleum of Atat�rk, the politician who remodelled the country in the beginning of s�c. XX * Bodrum - a popular health-resort in the coast of the Aegean sea * Edirne - next historical City to the border with Bulgaria and Greece, was capital of the Ottoman Empire * Istambul - the biggest Turkish city is a vibrant metropolis with a foot in the Europe and another one in Asia * Konya - Old capital of the Selj�cida empire and cradle of the seita of the rodopiantes dervis
[edit] Outros destinos
* [[Capad�cia]] - a region of lunar landscapes, rocks and caves that had served of shelter the old Christians
[edit] Entenda
Old headquarters of the Bizantino Empire, Turkey were created from the dismemberment of the Ottoman Empire. Its geographic localization (4% of the territory are situated in the European continent) reflects the fact well of that the country is the bridge between two civilizations. With a predominantly Muslim population, Turkey is a democratic country and with a secular government. The country is part of NATO and claims the adhesion to the Europ�ia Union. [Greece makes border with [
and Bulgaria the west, with Armenian, [[Azerbaij�o ]] and [[Ge�rgia]] the northeast and with Syria, Iraq and [[Ir� ]] the Southeast.
[edit] História
História
Turkey is inhabited since very old times. For return of 7500 a.C. already had cities in the Anat�lia, also [[�atal H�y�k ]], next to current Konya, that it disputes the heading of older city of the world. Some objects of this time can be found in the Museum of the Civilizations in Ancara.
Some event-key in the history of Turkey:
• About 2500 a.C. - Sprouting of the Hitita empire, that took advantage until s�c. XI a.C.
• From 1200 a.C. - domain of the Fr�gios, Lydians and others
• 547 a.C. - Fond of the Persians. Bloom of the culture Greek in the j�nicas cities ([[�feso]], Mileto, Izmir etc.)
• 334 a.C. - Alexander, the Great one, crosses the strait of Dardanelos. After its death, in the following decade, some kingdoms if form, amongst which if] detaches of [[P�rgamo]
• About 190 a.C. - Conquest romana. In 129 a.C., is established the province of Asia, with capital in �feso
• S�c. III - With the decline of the Roman Empire of ocidente, deep Constantino a great city (Istambul) in the place of the Biz�ncio Greek.
File:HagiaSofia edit.jpg
Bas�lica Istanbul of Sofia Saint, Istambul
• S�c. VI - the Bizantino Empire blossoms under the command of Justiniano, that establishes the basilica of Sofia Saint, that if became the most splendid Christian time during 1000 years
• S�c. VII - Sprouting of the Isl� in Arabia and its fast expansion
• S�c. XI - Come of the P�rsia, the Selj�cidas Turks had formed an empire based in the city of Iznik and later in Konya. Established the order of the rodopiantes Dervis.
• Crusadas
• S�c. XIII - Foundation of the Ottoman Empire. Taking of Constantinopla (1453)
• 1922 - Foundation of the Turkish Republic. Beginning of the reforms of Atat�rk
• 2005 - Official beginning of the negotiation for the acession of Turkey to the Europ�ia Union
[edit] Fuso horário
All Turkey is in spindle UTC +2, that is, two hours to the front of Portugal and 5 hours to the front of Brazil (4 hours during the schedule of Brazilian summer). The country adopts the summer schedule, normally of the end of March to the October end, when the official schedule becomes UTC +3, that is, 6 hours to the front of Brazil.
[edit] Feriados
The religious holidays are mobile, therefore they follow the lunar calendar. Most important they are:
• Seker Bayrami - equivalent to the Eid al Arab Fitr, signals the end of the Ramazan, month of jejum. 23 the 25/10/2006, of 12 the 14/10/2007 and 30/09 the 2/10/2008.
• Kurban Bayrami - al Arab Adha, the party of the sacrifice is equivalent to the Eid. Of 31/12/2006 the 3/1/2007, 20 the 23/12/2007 and 8 the 11/12/2008.
The fixed holidays are:
• 1 of January: New year
• 23 of April: Independence and Day of the Children
• 19 of May: Day of Atat�rk and Festa of Youth
• 30 of August: Party of the Victory - the victory commemorates on the invading forces in 1922
• 29 of October: Day of the Republic
Although it is not a Turkish holiday, in the 25 of April [[Austr�lia|australianos]] and [[New Zel�ndia|neozelandeses]] relembram the Anzac Day. In this same date, in the year of 1915, troops of those countries had disembarked in [[Gal�poli]] with the objective to conquer Constantinopla (Istambul) and had been defeated. Every year, thousands of people travel for Turkey to participate of the religious cult in homage to deceased in that war. As consequ�ncia of the increase of the tourist flow, it is recommendable to reserve lodging and strolls with antecedence.
[edit] Chegar
Since July of 2004 [http://www.turquia.org.br/vpsfiles/NewsPage.aspx?IDProject
[edit] De avião
The main door of entrance of international flights is international airport Atat�rk (IST), located 23km of the center of Istambul. The airport Sabiha G�k�en (SAW) has been increasingly used for the company aerial of low cost. He is 30km of Istambul.
The airports of Ancara and Antalya less are put into motion, but they receive some flights important.
Between the company aerial that operates flights of the Europe for Turkey are: AtlasJet, Fly Air, Onur Air, beyond economic the Easyjet and Germanwings.
[edit] De barco
It has ferries connecting Turkey to several other countries, as Greece and Italy. Marmara Lines operates regular lines of the Italian cities of Ancona and Brindisi to the Turkish port of [[�eşme]]. Of islands Greeks as Rodes, also has frequent linkings with Turkey, especially for the city of [[Bodrum]
[edit] De carro
To enter in the Turkey of car the Green Card of international insurance is necessary. Symbol TR does not have to be marked, that is, the card must be valid for Turkey. In case that contrary, it will be necessary to acquire a Turkish insurance policy in the border. It confirms if its insurance is valid also for occurrences in the Asian side of the country.
[edit] De ônibus
It has many lines of bus between important europ�ias cities and Turkey. They normally arrive at at the country passing for Greece or Italy (she saw ferry) and are relatively cheap, beyond well faster e comfortable of that the trains.
Company that operates international lines includes Varan (de/para Greece and Austria) and Ulusoy.
[edit] De trem
The golden times of the Express of the East had passed and today the access of train to Turkey suffers with the slowness and the competition from the modern buses and cheap flights. Still thus, it is possible to arrive at the train country. Of the Europe, it is arrived Istambul of Belgrade (23 hours of trip), Bucharest (20 hours) and Tessalonica (15 hours), of where it is possible to change of train for other parts of the continent.
The pricipais connections with countries of the Middle East come of the Syrian and the Ir�. The trip of train of Tehran the Ancara can lead about 60 hours.
The company of Turkish Railroads is the national authority of railroad transport.
[edit] Circular
Turkey is a great country, with more than 1500km of east the west, and valley the penalty to take in account these dimensions when planning the form of if moving for the country.
[edit] De avião
The cities most important are served by airports and, in bigger distances, the prices and the comfort to fly can compensate in relation to the buses. The biggest Turkish aerial company is T�rk Hava Yolları (Turkish Airlines), that it flies for all the regions of the country. Its main competitor is Onur Air, that she has lower tariffs. Other company of low cost [includes the Turk-German http://www.sunexpress.de/ Sun Express], Atlases Jet and Fly Air, that also vende tickets in the agencies of the post offices connected to the InterNet.
Some localities do not have daily flights for Ancara or Istambul. The tickets normally can be bought by the InterNet, in the domestic terminal of the airports or in the store of the proper companias.
In any trip, it also considers the value of the transport of the airport for the city, therefore they can significantly increase the cost of its day.
[edit] De barco
Hizli feribot is boats in the style catamaran, that connect some cities, as for example, Istambul with the other side of the Sea of M�rmara. They are sufficiently fast (50-60 Km/h) and can reduce the trip times sufficiently. For example, leaving of p�er of Yeni Kapi in Istambul (soon the southwest of the Blue Mosque), you can reach to less otogar (terminal road) of Bursa in two hours, being of one dedicated hour to the maritime trip the Yalova. Sevi�os similar operates more binding to some parts of Istambul to the Asian side or the places above in the B�sforo. The presence of this type of fast boat if has spread for all the country, where it wants that if it can sail.
[edit] De carro
The minimum age to direct is 21 years and is necessary to carry, beyond the passport, the international permission to lead, the documents of the automobile (if they will not be in the name of the conductor, is necessary a power of attorney) and the policy (automobile insurance) of insurance with visible symbol TR. To who it comes of the Middle East, she is necessary also to have the call ticket license ("Carnet of passage"). The vehicles can remain in the country for up to 6 months.
The circulation rules are sufficiently similar to the ones of Brazil and the Europe, but frequent they are disrespected by the local inhabitants. It is not uncommon to see changes sudden of band and, in the cities, 4 rows of cars stopped in a signal of transit with only 2 bands. You alert short with the horn they are frequent and they only serve to inform to the other drivers whom somebody has there. The speed limits are of 50 km/h in urban perimeter and 90 km/h in the roads. The use of the security belt is obligator for the driver and all the passengers.
The highways, in general, are tarred, conserved and served for ranks of fuel and restaurants well. The signalling, however, is not frequent, the illumination is imperfection and the amount of accidents is high. In the interior of the country, it is common to have that to divide the slow roads with the local population, wagons and other vehicles and without illumination, what it increases the risk of nocturnal accidents.
For who it prefers to rent an car, it has offices of the main companies of alguel in the airports and the cities most important.
[edit] De táxi
They are obliged to use the taximeter. Normally tip for the taxistas is not left - convenient, to round off the value for top.
[edit] Em dolmush
Dolmush was, originally, taxis shared, but today they remain few of these in some cities. Most common they are vans (turkey hens, micron-bus) that they operate in fixed routes and they charge in accordance with in the distance that you will cover. It ahead informs to the driver its destination and pass the money with the contribution of the other passengers, who will be able to ask for the same of you. In the hour to go down, the driver alerts so that she stops.
[edit] De autocarro/ônibus
Turkey has an excellent net of bus interurban calls. The buses are comfortable, have conditional air, private armchairs e, in the generality, good services, especially in great the company.
To otogar (road station) of the main cities they have bus frequently leaving for practically any destination. Beyond the driver, the buses have ��oecomiss�rios of bordo”. In the trips longest, as a driver it assumes the direction when the first one if tires. During the trip, they are offered drunk gratis, snacks and are made stops to each two hours and stocking, approximately, in good restaurants to the long one of the roads.
The more the east of the country, less frequent the buses if become, but exactly places more remote as Dogubeyazit or Van has lines for localities the hundreds of kilometers of distance. A village has of being really very small not to have a bus for Istambul or Izmir at least one time to each two days.
To find the bus correct can require aid. People in charge offering the services are always gifts and can help in the purchase of a ticket, but attention: to the times alone she has a line for the desired destination, but in some occasions, you she can finish seated while other buses for the same local leave while you wait. Therefore, if you she will have available time, she verifies the grating of arrivals and exits of other company. You also can say that she needs to leave immediately (uses the words "hemen" or "shimdy", or the expression "adjelem to var" �� "has haste), and the people will understand that you need to leave soon.
In the case to have some companies operating for the same locality, it looks for to know the size of the buses that cover the line. Generally, the greaters are more comfortable and some lines arrive to place discomforted vans (dolmus) operating in these lines. Another tip is to compare the size of the signboards normally �� "the companies with more bus and routes also have the biggest signboards. If it does not surprise if, the way for some strange and more distant destination, you has that to go down of the bus, to apanhar its luggage and being transferred to another bus, what ��oediretas” or ��oeexpressas” can occur even though in routes. In these cases, the other bus goes ��oecomprar” you and to take it it its destination.
To the times the buses of long distance will be able to release it in some next road ring to a city, instead of taking it it the center, therefore, it does not leave to ask if the final destination is in the center of the city. On the other hand, much company has "arac servile", vehicles that lead to the center when the Otogar is in the periphery of a city, what nowadays it occurs frequently. In the cities as Ancara these vehicles are shared by some company, and a fleet of them, leaving for the some parts of the city, will be to the wait. It would be useful to keep by hand its ticket to prove that you it was in a bus (the majority of these services operates, however, in the base of the good-faith).
The seat inside of the buses is determined, in part, for "koltuk numarası" - the number of the seat in its ticket �� "and part for the custom to seat together the women, the couples and thus for ahead. If it does not annoy, therefore, if to ask for to change to it of place. Generally, being an foreigner, you it will have the best seats.
A tip: although the last row of seats can be private driver-reserve to sleep it, normally it is better to catch a seat in the deep ones, any that is the number of its koltuk, and thus not to be importunado in the biggest part of the trip. This is especially useful when if it travels alone and if it wants to continue thus.
[edit] De comboio/trem
Turkey has an extensive railroad net. Although the tickets are cheap, the trains are extremely slow and normally they are not race for the competition of the comfortable buses of the country and the just-arrivals economic airlines.
[edit] Fale
The official language is the Turk, who uses the Roman alphabet with some modifications. The Kurd also is said in determined areas. The German is popular as second language and many young has some knowledge of English.
The pronunciation of the Turkish words is almost total phonetic - all the letters are sharp, except the Ğ that prolongates the sound of the preceding vowel. The sounds also correspond, in the generality to the ones of the Portuguese, with some exceptions:
• ı - similar � in the Portuguese (and not i)
• � - as in the German, a sound between and the e
• � - as the French, sharp u with the contracted lips
• c - sound of dj (as the j of jump in English)
• � - sound of tch (as in Czech)
• h - always sharp, has sound of rr
• r - as the r of the word brightness
• s - always as s and never as z
• ş - as ch (key, animal etc)
• y - always sharp (as in the word iyi, "good")
The gestual language is always very useful and to the times most efficient of the one than the words. To say "not", the Turks simply move the head stop backwards raising the eyes and estalando slightly the language. To say "yes", they lower the head and the eyes.
[edit] Compre
The costs in Turkey, in general, are well cheaper of the one than the European standards and many times even though of that the Brazilian prices.
The Turks are a mercadora people of soul e, in general, negotiating ex�mios. Therefore, except in the case of firm prices, the word of order is to negotiate. This form of negotiation is part of the local culture of purchase and venda and can cause a little of estranhamento to the travellers who are not accustomed (and that many times leave paying more the one than they would have). The insistence of the salesmen to the times also can be irritating. Still thus, it is possible to all make excellent purchases for the country.
[edit] Produtos
• Carpets - four main types, all facts Exist by hand: kilim, the cicim (djidjim is pronounced), sumak and Hal;
• Leather - the city of Malatya is a great article producer in leather;
• Ceramic - produced in Avanos and [[K�tahya]] is interesting and uses old Ottoman reasons;
• Typical musical instruments
• Narguil�s
• Antiguidades - Important to notice that, in order to prevent the illicit traffic of cultural goods, the Turkish authorities do not allow the exit of the object country, especially the archaeological ones, of more than 100 years.
[edit] Taxa de câmbio
In May of 2006, the quotation of 1 new lira Turkish is of, approximately:
• �'� 0,60
• USS 0,75
• R$ 1,59
[edit] Coma
The Turkish kitchen is excellent e, except for the vegetarians, has an immense amount of plates to give water in the mouth. In accordance with the Islamic rules, the consumption of pig meat is forbidden.
The coffee of the morning (kahvaltı) served in the hotels and pensions normally consists of a buffet contends bread, torradas, cheese, ham, honey, olives, tea and coffee.
B�rek or the puddle ("potcha" is said) salty stuffed with meat, cheese or potato, or simit (rosquinhas of sesame) is vendidos in tents and stands in the streets and consumed by many people soon of morning.
Fast snacks include:
• Lahmacun - pizza species with meat covering
• Pide, Turkish pizza, a Syria bread with coverings that are served in specialized establishments called pideci.
• Tava, shellfishes to the milanesa, common in the coastal cities
• Mantı - ravi�lis of meat with yoghurt gravy
The restaurants, in turn, serve hot plates substanciosos as the Kebap:
• İskenderkebap - meat in the Syria bread with gravy of spiced, yoghurt and salada tomatoe
• K�fte (alm�ndegas)
• šiš(grilled meat)
• ��p šiš(of lamb)
Very popular they are the mezes, entered that to the times they substitute a complete meal and normally are folloied by rakı(ver section Drinks, below)
The desserts most common include baclavas (crayons candies, watered the honey), s�tla� (type of rice-candy) and lokum, the Turkish delight that consists of sugar bullets of gum.
[edit] Beba e saia
• Coffee (kahve) - the Turkish coffee is served in small x�caras and strong and is encorpado. Attention not to drink the grains that are in the deep one of x�cara. Sade kahve is served pure. Already şekerli, orta şekerli and �ok şekerli take sugar.
• Tea (�ay) also is very popular in the country and, when prepared for the places, it is strong. The apple tea (elma �ayı) is imperd�vel.
• Ayran - a refreshment to the yoghurt base
• Boza, originary drink of Central Asia, is made to the base of wheat, sugar and water. For being leavend, it has a lightly alc�olico text. Its thick consistency and is consumed frozen. Vefa Bozacisi is the known mark more of Istambul.
• Sahlep - another traditional, however hot drink. It is made of milk, root of orqu�dea and sugar and typically decorated with cinnamon. More it is consumed in the winter and served in coffees and patisseries (pastane).
[edit] Bebidas alcóolicas
Although it is an Islamic country, drunk alc�olicas easily they are found by the country. However, to be drunk can cause serious recriminations. The alc�olicas drink consumption all prevents the cost in public during the month of the Ramad�.
• Rakı - a alc�olica drink derivative of the grape and with flavor of anise, fellow creature to arak. The national drink of Turkey is considered. Normally it is served mixed the water and/or ice.
• Wine - the encorpado wine of the Capad�cia is aged in barrels of concrete and has a distinctive flavor
[edit] Durma
It has an enormous amount of options of lodging in Turkey. Still thus, it is recommendable to reserve in the high season (July and August, Anzac Day etc.). Of November to the April start (except in the Christmas and New Year), many hotels offer reduced tariffs. Some of the best hotels of the world are in the country, but it also has economic hotels, pensions and shelters. Also the charm hotels are common, installed in old houses and with a more traditional environment and decoration "retr�" that it retraces to the past. Although they cost a little more expensive, they are an interesting experience.
The prices, in the majority of the times, are quoted in euros or dollar. Amongst the cities of the country, Istambul is certainly most expensive and the daily ones of comparable establishments can many times cost the double in the city of that in the remaining portion of Turkey.
Normally men and women are not placed in the same room. To the couples that teethe to be together, one sends regards to use alliances of same marriage that are not married, or at least to fill a date of marriage in the fiche of entrance in the place where they will take up quarters.
Campings, cujoa localization is indicated in maps distributed for the services of tourist information, they are only common in the coastal region and the national parks. Compared with the prices of the pensions most economic, the encampment to the times is not advantageous.
[edit] Aprenda
The students normally need a special visa. He in such a way has chances of studies for how much informal formal education.
Hardly lessons in Portuguese will meet. Many universities have lessons in English and/or preparatory courses of Turk for the students.
[edit] Trabalhe
Although many people work in the illegality, the visa of work to be able is necessary to work legally in the country.
The chance most common for foreigners is to work in the education of languages, especially the English and, it is clearly, the native falantes of this language more are valued. The activities related to the foreign commerce also present many chances.
It still has programs of periods of training, works during the vacations, service of au to pair (bab�) and chances of voluntariado.
[edit] Segurança
The historical spite do of earthquakes, terrorist attacks and horrible (and false) the presented image no classic has filmed the Express da midnight, Turkey is more insurance do that many countries of Europe and the register of violent crimes is sufficiently rare. The robberies also are not common and the local authorities treat the visitors with courtesy.
The policemen use blue-marine clothes and caps.
[edit] Mulheres
The travelling women must attempt against to some peculiar questions to the Islamic countries, especially in that she says respect to the siege. A series of badly-understood takes the Turkish men to imagine "easy" the women occidental as. If on the other hand, the Turkish women know to get rid themselves of the inopportune boardings with more naturalness (also keeping a necessary level of formality), the occidental women, especially if they travel alone, can be felt importunadas. It prevents of looking at the Turkish men in the eyes, it does not smile for strangers and it prevents to leave to the night in quarters where it has prostitution (Beyazit and Aksaray in Istambul, for example). To use marriage alliance also can discourage some attempts. If necessary, a group of Turkish women is joined it and part helps.
[edit] Saúde
Although the water is treated in some places, it always drinks bottled water (it prevents the ice).
Despite the occurrences of the avi�ria grippe in the country, it does not have immediate risk of cont�gio between human beings. Not frequent places where it has contact with birds and excrements (farms, markets of birds etc.) e eats only cooked foods well. She also prevents plates with vendidos shellfishes to the outdoors, over all in Istambul - they can have been washed with the polu�da water of the B�sforo.
Although he is not obligator, vaccine against diphtheria, hepatitis, t�tano and the p�lio one sends regards to it (normally already applied universally in other countries). Visitors who if dirigem to the coastal regions of M�rmara or the Black Sea can take the due precautions against the malaria. Those that they will be long periods in agricultural areas can be vacinar against the tif�ide fever.
The indispensable medicines widely are found in the country and vendidos without prescription. Solar filter and repellent of insects also can be bought in the country.
[edit] Respeite
• The local religion and customs - It uses appropriate clothes and it keeps an adjusted behavior to visit the mosques. It does not imitate or makes favour of sings it of call for conjunct repeated for muezins, has an important religious content.
• Atat�rk - the governor who revolutionized the Turkish politics, customs and the language is admired by almost all and the Turks are little tolerant to the critical ones to its image.
[edit] Mantenha contato
The telem�veis use technology GSM, offered for three operators (Avea, Telsim and Turkcell - sites in Turk and English). The covering of the country is ample and roaming, including of services of data, costuma to function without problems.
Many bigger hotels offer to InterNet connections without-wire, generally without additional cost.
[[de:T�rkei]] [[es:Turqu�a]] [[ja:ト��"�'�]] [[sv:Turkiet] [[Dmoz:�sia/Turquia]
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Yosemite National Park
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Half Dome from the Half Dome trail
Yosemite National Park [1] is a United States National Park and a UNESCO World Heritage Site located in the Sierra Nevada mountains in east-central California. Yosemite is internationally recognized for its spectacular granite cliffs, waterfalls, clear streams, giant sequoia groves, and biological diversity. The 750,000-acre, 1,200 square-mile park contains thousands of lakes and ponds, 1600 miles of streams, 800 miles of hiking trails, and 350 miles of roads. It is currently the third most visited national park in the United States, with an annual visitation of nearly 4 million.
[edit] Understand
[edit] History
Efforts to protect Yosemite Valley began as far back as June 30, 1864 when President Abraham Lincoln signed a bill granting Yosemite Valley and the Mariposa Grove of Giant Sequoias to the State of California as an inalienable public trust. This was the first time in history that a federal government had set aside scenic lands simply to protect them and to allow for their enjoyment by all people. The area became a national park on October 1, 1890 following several years of struggle by John Muir against the devastation of the subalpine meadows surrounding Yosemite Valley.
Despite its national park status, California controlled the initial grant area until 1906. Prior to ceding control, the city of San Francisco became embroiled in a bitter political struggle over the Hetch Hetchy Valley, in which the city wanted to dam the Tuolumne River as a source of drinking water and hydroelectric power. In 1913, conservationists led by John Muir lost the battle when Congress passed the Raker Act, authorizing the construction of O'Shaughnessy Dam. To this day crusades to restore Hetch Hetchy are ongoing.
Yosemite has grown from a little visited, yet historically significant, park to one of the "crown jewels" of the US National Park System. With this stature comes difficulties; current visitation numbers roughly 4 million visitors per year, with a majority visiting 12 square miles within Yosemite Valley (about 1% of the total park land). The dual role of the park service -- protection of the resource and provide for the enjoyment of the visitor -- makes sure that Yosemite continues to be an important breeding ground for management ideas about US National Parks.
[edit] Landscape
The Flood of 1997
Warm winter temperatures, a late-season tropical rainstorm, and a heavy snow pack combined to produce the greatest flooding on record in Yosemite Valley in January of 1997. A highly unusual winter rainstorm arrived in January, and the rainfall caused tremendous melting of the existing High Sierra snowpack. The resulting flood of rain and melted snow caused the Merced River to rise nearly ten feet above its normal level, producing over $178 million in damage in Yosemite Valley. As a result the Valley was closed for over three months, and vast changes were made to the area's management plan. Today numerous structures have been relocated, roads have been re-routed out of the flood plain, and nearly fifty percent of campsites have been removed. Signs indicating the floodwater height are posted throughout the Valley.
Yosemite is best known for the massive granite cliffs and domes found within the park. The landscape began forming about ten million years ago when the Sierra Nevada was uplifted and then tilted to form its relatively gentle western slopes and the more dramatic eastern slopes. The uplift increased the steepness of stream and river beds, resulting in formation of deep, narrow canyons. About one million years ago, snow and ice accumulated, forming glaciers at the higher alpine meadows that moved down the river valleys. Ice thickness in Yosemite Valley may have reached 4,000 feet during the early glacial episode. The downslope movement of the ice masses cut and sculpted the U-shaped valley that attracts so many visitors to its scenic vistas today.
The park is also home to the Yosemite Falls, at 739m (2425ft), the highest waterfall in North America.
[edit] Flora and fauna
Yosemite has more than 300 species of vertebrate animals, and 85 of these are native mammals. Black bears are abundant in the park, and are often involved in conflicts with humans that result in property damage and, occasionally, injuries to humans. Visitor education and bear management efforts have reduced the bear-human incidents and property damage by 90% in the past few years. Ungulates include large numbers of mule deer. Bighorn sheep formerly populated the Sierra crest, but have been reduced to only a few remnant populations. There are 17 species of bats, 9 of which are either Federal or California Species of Special Concern. Over 150 species of birds regularly occur in the parks. Other species that are found within the park include bobcat, gray fox, mountain beaver, great gray owls, white-headed woodpeckers, spotted owls, golden-mantled ground squirrel, martens, Steller's jays, pika, yellow-bellied marmot, white-tailed hare, and coyotes.
The vegetation in the park is primarily coniferous forest. Most notable among the park's trees are isolated groves of giant sequoias, the largest trees in the world, which are found in three groves in Yosemite National Park.
[edit] Climate
Climate Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
Daily highs (°F) 49 55 59 65 73 82 90 90 87 74 58 48
Nightly lows (°F) 26 28 31 35 42 48 54 53 47 39 31 26
Precipitation (in) 6 6 5 3 1 0 0 1 2 5 6
The above measurements are for Yosemite Valley. Note that temperatures outside the valley can be dramatically cooler.
Check Yosemite Valley's 7 day forecast at NOAA
Check Tuolumne Meadows's 7 day forecast at NOAA
Weather can change rapidly during all seasons of the year, and will also vary greatly with elevation. When visiting it is wise to pack for any season with clothing that can be layered, ready to peel off or add on as conditions dictate. Always include some kind of rain gear; the park receives most of its precipitation in the months of January, February and March, but storms are common during the transitional spring and fall seasons, and spectacular thunderstorms may occur during summer.
For Yosemite Valley and Wawona (subtract 10-20°F (5-10°C) for Tuolumne Meadows), average weather is as follows:
• Summer: Typically dry, with occasional thunderstorms; temperatures from 50°F (10°C) to the low 90°F (30°C) range.
• Fall & Spring: Highly variable, with typical high temperatures ranging from 50-80°F (10-27°C) , with lows from 30-40°F (-1 to 4°C). Rain is less likely early in fall/late in spring and rain or snow is likely late in fall/early in spring.
• Winter: Snowy, rainy, or (sometimes) even sunny days are possible, with highs ranging from 30-60°F (-1 to 16°C) and lows in the high 20°F (-4 to 0°C) range. Winter Storm Warnings indicate a significant storm is impending or occuring.
[edit] Get in
Yosemite National Park roadmap
[edit] By car
Warning: There are no gas/petrol stations in the Yosemite Valley!
There are four major entrances into the park. All of these routes are relatively windy mountain roads and appropriate time should be budgeted for them. Be advised that the above can pose a safety risk, so when driving, stay alert and focused throughout the ride. Also, don't confuse the town of Oakdale to the west, with Oakhurst to the south.
• State Route 120 from the west from Oakdale. This is the fastest route from locations west (Bay Area) and northwest (Sacramento). Route 120 is a bit steep, so RVs and trailers should consider Route 140 instead. In winter, snow makes the lower elevations of Route 140 more attractive.
• State Route 140 west from Mariposa and Merced. This route mostly travels up the Merced River Canyon into Yosemite Valley and is the most scenic western entrance. RV and tour bus traffic used to congest this road a bit too much in summer. However, two new bridges to bypass a recent rock slide in the Merced River Canyon now limit vehicles to 45 feet. Many visitors are still unaware of the new bridges over the Merced River and assume State Route 140 is still closed. Highway 140 is now pleasantly less congested and the bridges afford an excellent view of the massive rock slide.
• State Route 41 north from Fresno and Los Angeles/Southern California. Be sure to fill your gas tank in Oakhurst (several stations along highway), or pay dearly as you get closer to the park. Note that many businesses (including two more gas stations) are located on the first half mile of ajoining State Route 49 in Oakhurst.
• State Route 120 from the east (Tioga Pass Road) from Lee Vining and points east. This road is only open from June through October, although heavy snow may force closure in late September and push opening back to late July.
A secondary entrance exists to Hetch Hetchy Reservoir exclusively (no Yosemite Valley access) off of State Route 120 from the west. It requires taking a side road near the main Route 120 west entrance of Yosemite. Please note that Hetch Hetchy has restricted hours for access due to security for the Reservoir. Please check with Yosemite National Park information before heading out to Hetch Hetchy.
During the snow season, usually November through March, snow chains may be required. Chain requirements are strictly enforced in Yosemite with potential fines being as much as $5,000, so chains should be carried during those months.
Note: During summer months traffic becomes heavily congested in Yosemite Valley, and parking can be nearly impossible to find. Summer visitors to Yosemite Valley are therefore highly encouraged to use the YARTS shuttle system (see below) to get into the park.
[edit] By plane
There are no landing strips within the park. Airports in surrounding communities include:
• Fresno-Yosemite International (FAT), Fresno. Located approximately 1.5 hours (by car) south of the park's entrance on Highway 41.
• Merced Airport (MCE), Merced. Located approximately two hours (by car) from Yosemite Valley on Highway 140.
• Modesto City-County Airport (MOD), Modesto. Located approximately 1.5 hours (by car) from the park's east entrance on Highway 120.
Stockton Municipal Airport has commercial flights. Bay Area airports including San Francisco International (SFO), Oakland International (OAK), and San Jose International (SJC) are larger and offer more flights. Driving distance from the Bay Area is approximately four hours. However, landing at SFO requires crossing one of the San Francisco Bay bridges which are usually congested during the late afternoon and early evening commute. (Likewise, in the morning for the return flight, and this direction includes a toll booth.) Sacramento International airport (SMF), north of Sacramento, is another large airport option that is also about a four-hour drive from the park. Visitors arriving from the east may choose Reno/Tahoe International (RNO) in Reno, which is approximately 3.5 hours (by car) from the Tioga Pass Entrance (summer only).
Small private aircraft land at Mariposa-Yosemite Airport (KMPI) about 5 mi/8 km northwest of the town of Mariposa on State Route 49. There is no control tower, and car rentals in the area are very limited. The YARTS shuttle (see below) is another possibility. Park entrance is an additional 27 mi/44 km via State Route 140.
[edit] By train
Amtrak offers service to Yosemite by means of a motorcoach bus that meets its San Joaquins trains in Merced. The San Joaquins provide several departures each day along its route from Bakersfield in the south, Sacramento in the north, and the San Francisco Bay Area in the west. With ample motorcoach connections to and from the trains, this train service serves most of the state, allowing quick and easy access to Merced from most places within the state. However, by driving from San Francisco to Yosemite, it will take 4 1/2 to 5 hours. By train, it will take closer to six hours.
[edit] By bus
Many tour bus companies run tours from the Bay Area. Some will just take you to Yosemite Valley; others provide full tours to see the Giant Sequoias and/or Glacier Point.
[edit] By shuttle
The Yosemite Area Regional Transportation System (YARTS) [2] offers reasonably-priced transportation into Yosemite Valley from towns east and west of the park including Merced, Mariposa, El Portal, Lee Vining and Mammoth Lakes. Tickets can be purchased ahead of time or from the shuttle driver, and round-trip fares are between $7 (from El Portal) to $20 (from Merced and Mammoth Lakes) into Yosemite Valley. When combined with the free shuttle service that operates within Yosemite Valley, YARTS can eliminate many hassles for summer visitors. YARTS is now providing service on Hwy 120 beginning in Sonora(Dec 2012).
[edit] Fees/Permits
Park entrance fees are $20 for private vehicles and $10 for individuals on foot, bike and motorcycle. All entrance fees are valid for seven days. The Yosemite Annual Pass is available for $40, allowing park entry for one year. Alternatively, The National Parks and Federal Recreational Lands Annual Pass can be purchased for $80, allowing free entry to all park and recreation lands controlled by the US Department of the Interior for one year.
[edit] Get around
The Yosemite Park Tram
[edit] By car
In general a car is a great way to tour the park, although during the summer Yosemite Valley can be so crowded that a shuttle bus is a vastly better option. Be aware that the Tioga Pass Road and the road to Glacier Point are seasonal and close as soon as the first major snow falls. Other park roads may close during storms, but in general are always open. Note that the speed limit in all areas of the park is fairly slow, and is strictly enforced by rangers with radar guns; the speed limits are for your own safety on the twisting mountain roads, as well as for the safety of pedestrians and the many animals that use the area.
The loop road through Yosemite Valley is now one-way. For many years this was a two-lane road, but motorists travelling slowly to admire the scenery often created a long backup of annoyed drivers, so the Park Service converted most of the roads in the valley into one-way roads to allow passing. As a result, when driving in the valley be aware that a wrong turn can send you on a one-way five-mile detour.
The one-way routing affects those entering from Oakdale on Hwy 120 the most. You will have to cross over to Southside Drive at the Pohono Bridge. Likewise upon leaving the park, those taking the south exit on Hwy 41 to Fresno also cross the Pohono Bridge, backtrack one mile, before turning right onto Wawona Road.
[edit] By shuttle
To limit traffic congestion the park service runs several free shuttle buses throughout the park (note that these are not the YARTS system):
• Yosemite Valley. Shuttles operate from 7AM until 10PM in the eastern portion of Yosemite Valley year-round, stopping at or near all accommodations, shopping areas, and major sights.
• Wawona-Mariposa Grove. Between spring and fall a free shuttle operates between Wawona and the Mariposa Sequoia Grove. Parking is often full at the grove, so the shuttle then becomes the only option for visiting.
• Badger Pass Bus. During the ski season a free bus travels twice daily between Yosemite Valley and the ski area.
• Tuolumne Meadows Shuttle Bus. During the summer season this bus provides access to points in and around Tuolumne Meadows.
• Tuolumne Meadows Hikers' Bus (fee charged). This bus travels in summer between Yosemite Valley and Tuolumne Meadows, dropping hikers off along the way. To guarantee seating tickets should be purchased one day in advance by calling (209) 372-1240.
• Glacier Point Hikers' Bus (fee charged). This bus provides service between Yosemite Valley and Glacier Point, making stops along the way. To guarantee seating tickets should be purchased one day in advance by calling (209) 372-1240.
[edit] By bicycle
Yosemite Valley has a network of bicycle paths along its north and south sides. Bikes can be rented for the day at Curry Village & turn a thirty minute walk into a five minute ride.
[edit] By foot
Although the road network covers the most popular sights in Yosemite, the vast majority of the park's area can only be accessed using the park's network of trails. Trails including the John Muir Trail and the Pacific Crest Trail lead to areas outside of the park's north and south borders.
[edit][add listing] See
The park is extremely large with more than can be seen in just a one or two day visit. The peak seasons for Yosemite are generally Spring, when the waterfalls in the Valley are strongest, and Summer, when the Tioga Pass and Glacier Point roads are open, giving visitors access to the higher meadows and to views of the Valley from above.
[edit] Yosemite Valley
Yosemite Falls
Yosemite Valley is world famous for its impressive waterfalls, meadows, cliffs, and unusual rock formations. Yosemite Valley is accessible by car all year, but during the summer months traffic can feel like a city rush hour rather than a national park, making shuttle bus usage highly recommended.
Perhaps the most famous sight in the valley is the granite monolith of Half Dome, a mountain whose sheer face and rounded top looks like a giant stone dome that has been split in half. The imposing vertical face of El Capitan is legendary among climbers, and numerous lesser-known features line the valley.
Equally famous for its waterfalls, Yosemite Falls is one of the highest waterfalls in the world at 2425 feet (782 m), and is most impressive during the spring months. Bridalveil Fall is another easily accessible waterfall, while Nevada Fall and Vernal Fall can be reached by those willing to do some hiking.
Another popular viewpoint is the Tunnel View. The spot gives visitors a view of the Yosemite Valley with El Capitan on the left, Bridalveil Fall on the right and Half Dome in the center. The view point is on the 41 at the western end of the Wawona tunnel. There is a small parking lot near the lookout.
[edit] Wawona
Wawona is the home to the historic Wawona Hotel, dating from the late nineteenth century. The Pioneer Yosemite History Center, a collection of historic buildings, is located just over the covered bridge from the hotel. Wawona is accessible by car year-round.
The Mariposa Grove is south of Wawona near the entrance station. The Mariposa Grove is the largest stand of giant sequoias (also known as Sierra redwoods or big trees) in Yosemite. The road to the Mariposa Grove is not plowed in winter and is often closed from sometime in November through March.
[edit] Glacier Point and Badger Pass
Glacier Point, an overlook with a commanding view of Yosemite Valley, Half Dome, and much of the Sierra Nevada mountain range, is located 30 miles (one hour) from Yosemite Valley. The road ends at Glacier Point and a quarter mile long paved walkway leads to one of the most spectacular viewpoints in the park. The road is closed from sometime in November through early May or late June. From mid-December through early April the road is plowed only as far as the Badger Pass ski area and Glacier Point can be reached via skis or snowshoes only. Both downhill and cross-country skiing are available at Badger Pass from mid-December through early April.
Washburn Point, another overlook on the same road, appears about half a mile before Glacier Point. This overlook gives a view of the southern side of the Yosemite Valley.
[edit] Tuolumne Meadows
The Tioga Road (Highway 120 East), is generally open to vehicles from late May or early June through sometime in November. It offers a 39 mile scenic drive between Crane Flat and Tuolumne Meadows through forests and past meadows, lakes, and granite domes. Many turnouts offer broad and beautiful vistas.
Tuolumne Meadows is a large, open sub-alpine meadow graced by the winding Tuolumne River and surrounded by majestic peaks and domes. From sometime in November through late May or early June, this area is only accessible by cross-country skis or snowshoes. One of the easiest ways to explore the Meadows is to take the dirt road past the Dog Lake trailhead (along Tioga Rd.) for a quarter mile. There you'll find a metal gate and a fire road behind it. The road you're driving on curves sharply to the right here. Park and follow the road past the gate. The first mile of this road provides you with up-close views of the Meadow's beauty, particularly toward the left (south).
[edit] Crane Flat
Crane Flat is a pleasant forest and meadow area located 16 miles (30 minutes) from Yosemite Valley. Nearby are the Tuolumne and Merced Groves of Giant Sequoias, which are only accessible by foot. Crane Flat is accessible by car all year. Bears can be spotted in the meadows in this area regularly, so keep your eyes open and don't block traffic if you see one!
[edit] Hetch Hetchy Valley
Hetch Hetchy, a lesser known twin to Yosemite Valley (perhaps because its river has been dammed), is home to spectacular scenery and is the starting point for many less-used wilderness trails. Although the road to Hetch Hetchy is open year-round, on a day to day basis it has restricted hours due to security for the reservoir. It may close periodically due to snow in winter and spring. During the spring and early summer, impressive water falls flow into the reservoir, making hiking in Hetch Hetchy even more spectacular.
[edit][add listing] Do
[edit] Hiking
Physically-fit travelers will enjoy hiking the Park's many trails and footpaths. Check with rangers for trail conditions; snow and hazards from falling rock close many trails in winter, and the cables on the Half Dome trail are only up from late May through early October (ascending Half Dome when the cables are not erected is possible but is dangerous and strongly discouraged). No permits are required park-wide for day hikes, with the exception of the Half Dome Summit.
[edit] Yosemite Valley
Many of the meadows have short trails, some of which are handicap accessible. For those staying in the valley, walking to get around is easy, scenic, and avoids the stresses of car travel in the valley.
The cables on the Half Dome trail
• Lower Yosemite Fall (0.5 mi (0.8 km) round-trip), Starts at the Lower Yosemite Fall shuttle bus stop. This easy paved trail provides a good view of the falls with a close-up view of the lower fall. (Note: this waterfall is often dry from August through October.) Since the trailhead falls on the Northside Dr, it's better to see the falls on your way out of the Yosemite Valley. edit
• Bridalveil Fall (0.5 mi (0.8 km) round-trip), Starts from the Bridalveil Fall parking area. Another easy paved trail that leads to the bottom of Bridalveil Fall. The trailhead to this fall falls on the Southside Dr. So, it's best to visit it on your way to the Valley. edit
• Mirror Lake/Meadow (2 mi (3.2 km) to Mirror Lake, 5 mi (8 km) around the lake), Starts from the Mirror Lake trailhead shuttle bus stop. The trail leads along an old road to what is a large pond in spring and a meadow the rest of the year. The largely dry lake is mostly a meadow that is at the bottom of Half Dome and provides excellent views. Those who are interested can also hike around the lakebed. edit
• Valley Floor Loop (6.5 mi (10.5 km) round-trip with cutoff, 13 mi (21 km) without). The loop trail around Yosemite Valley can be hiked in pieces or in full. Following the road in places, the trail can be shortened by crossing the bridge just east of El Capitan Meadow. edit
• Vernal Fall (Mist Trail) (3 mi (4.8 km) round-trip), Starts from the Happy Isles shuttle bus stop. This strenuous hike leads to the top of Vernal Fall. From the Vernal Fall footbridge onwards the trail offers excellent views of the 317 foot (97 m) high Vernal Fall. Past the footbridge the trail becomes steep and may be slippery and the spray from the falls will get you quite wet as it traverses 600 granite steps to the top of the waterfall. edit
• Nevada Fall (Mist Trail) (7 mi (11.2 km) round-trip), Starts from the Happy Isles shuttle bus stop. Nevada Fall is located further along the Mist Trail, past Vernal Fall. This strenuous hike leads to the top of Vernal Fall, up more granite steps, and to the top of Nevada Fall. edit
• Panorama Trail (8.5 mi (13.7 km) one-way), Starts from Glacier Point. The Panorama Trail offers panoramic views of the valley and close-up views of three waterfalls (including lesser known Illilouette Fall) before continuing down the Mist Trail and ending at Happy Isles. From late May or early June through October, a fee-based hikers bus will take you up to Glacier Point. edit
• Four Mile Trail to Glacier Point (9.6 mi (15.5 km) round-trip), Starts from the Four Mile Trailhead just west of Swinging Bridge picnic area. This strenuous trail follows switchbacks up to Glacier Point. The trail offers spectacular views up and down Yosemite Valley. Visitors interested in a long day hike can return to Yosemite Valley via the Panorama Trail. edit
• Upper Yosemite Fall (7.2 mi (11.6 km) round-trip), Starts near the Camp 4 shuttle bus stop. This extremely strenuous trail switchbacks to the top of the 2,425 foot (739 meter) high Yosemite Falls. The trail provides great views of Half Dome and eastern Yosemite Valley. Those without the time (or energy) to make it to the top can hike about one mile to the railed-in Columbia Rock, which itself has great views. In summer, the trail is hot and dusty, so bring lots of water. edit
• Half Dome (17 mi (27.4 km) round-trip), Starts at the Happy Isles shuttle bus stop. One of the most spectacular trails in the world, the Half Dome trail travels past Vernal Falls, and Nevada Falls, and then continues rising through a pine forest before opening up near the summit of Half Dome. The final mile is a grueling trek up granite steps, followed by wire cables that lead up the steep ascent to the top of Half Dome. Hikers should bring leather work gloves to protect their hands from the cables; some gloves are often available in a pile at the bottom of the cables. While it is possible to ascend Half Dome while the cables are down (between approximately October 15 and May 15), hikers do so at their own risk. Views and scenery are unforgettable, but hikers should be aware that the final climb up the back side of Half Dome via the cables can be exhausting and, for those with even a mild fear of heights, frightening. Starting in 2011, permits are required for day hikes of the Half Dome summit seven days a week, and rangers stationed on the trail turn away hikers without permits. [3] edit
[edit] Glacier Point
• McGurk Meadow, Bridalveil Creek, & Dewey Point (7 mi (11.2 km) round-trip), Starts at the McGurk Meadow trailhead parking area (west of the Bridalveil Creek Campground turnoff). This trail leads downhill to an old cabin built by John McGurk and a large meadow. Continue east (right) at the trail junction to get to Bridalveil Creek (4 mi / 6.4 km) or continue west to a Dewey Point (7 mi / 11.2 km), which has a spectacular view of western Yosemite Valley. edit
• Ostrander Lake (12.7 mi (20.3 km) round-trip), Begins at the Ostrander Lake trailhead parking area (1.3 mi / 2.1 km east of Bridalveil Creek Campground). The first half of this hike gains little elevation; the second half gains about 1,500 ft (450 m). As the trail rises it offers views of the Clark Range before eventually arriving at Ostrander Lake. edit
• Mono Meadow (3 mi (4.8 km) round-trip), Starts from the Mono Meadow trailhead parking area (2.5 mi / 4 km east of Bridalveil Creek Campground). From its start this trail descends steeply to Mono Meadow, an area which is wet, particularly early to mid summer (be sure to stay on the trail, even if it is muddy). Shortly after leaving Mono Meadow, the trail passes through an unmarked clearing with views of the Clark Range, Mount Starr King, and Half Dome. edit
• Taft Point (2.2 mi (3.5 km) round-trip), The trailhead is located at the Sentinel Dome/Taft Point trailhead parking area (6 mi / 9.6 km east of Bridalveil Creek Campground). This relatively easy trail leads to the edge of Yosemite Valley. As the trail approaches Taft Point watch for fissures, which are deep cracks extending hundreds of feet downwards. The railed-in Taft Point offers a breathtaking view of Yosemite Valley, 2,000 feet (600 m) below. edit
• Sentinel Dome (2.2 mi (3.5 km) round-trip), Starts at the Sentinel Dome/Taft Point trailhead parking area, (6 mi / 9.6 km east of Bridalveil Creek Campground). The Sentinel Dome trail is an easy hike that leads to the base of Sentinel Dome, where you can scramble up the granite slope of the dome (it is not especially steep on its northeast side). From the top, you have a spectacular 360° view of Yosemite Valley (including Yosemite, Vernal, and Nevada Falls) and parts of the high country. A loop including Taft Point is a nice addition, but the climb from Taft Point to the top of the dome goes up several hundred feet. edit
[edit] Tuolumne Meadows
• Soda Springs & Parson's Lodge (1.5 mi (2.4 km) round-trip), Begins at the Lembert Dome parking area. The trail follows the gravel road northwest past a locked gate. The Soda Springs are protected within a log enclosure. Carbonated water bubbles up through the ground, but drinking the water is not recommended due to possible surface contamination. Further along the trail is the historic Parson's Memorial Lodge, which offers exhibits. edit
• Dog Lake (2.8 mi (4.5 km) round-trip), Starts at the Dog Lake/John Muir Trail parking area. The trail goes up steeply and crosses the Tioga Road, then continues up for 0.75 mi (1.2 km) to a signed junction. Continue straight to Dog Lake. Enjoy fishing and picnicking from this high country lake. edit
• Lembert Dome (2.8 mi (4.5 km) round-trip), Begins at the Dog Lake/John Muir Trail parking area. A strenuous hike that goes up steeply for 0.75 mi (1.2 km) to a signed junction. The trail to the left goes to the top of Lembert Dome. Expect a spectacular panoramic view of Tuolumne Meadows, Cathedral Peak, and Unicorn Peak. The top of the dome can be windy and quite a bit cooler than down below. edit
• Dog Lake and Lembert Dome (5.0 (8 km) mi loop). These two hikes can be combined in a loop that delivers some of the best scenery from any five-mile hike in the park. Do the lake first, before you get tired from the dome climb. edit
• Glen Aulin (11 mi (17.7 km) round-trip), Starts from the road near Tuolumne Meadows Stables. A moderately difficult trail that follows the gravel road as it loops behind Soda Springs and drops to Glen Aulin. The route is noted for scenic cascades, particularly Tuolumne Falls, located 4 miles from the trailhead. edit
• Elizabeth Lake (4.8 mi (7.7 km) round-trip), Starts near the Tuolumne Meadows Group Campground. This moderately difficult hike climbs steadily to the glacier-carved lake at the base of Unicorn Peak. To reach the trailhead, drive past the group campsites to where the road ends. There are restrooms there. edit
Lower Cathedral Lake
• Cathedral Lakes (7 mi (11.3 km) round-trip). From the Cathedral Lakes Trailhead the trail climbs steadily (1,000 ft / 305 m) to Upper Cathedral Lake. Near the top, it passes a spur trail to Lower Cathedral Lake. edit
• John Muir Trail through Lyell Canyon (8 mi (12.9 km) one-way). From the Dog Lake/John Muir Trail parking area this relatively flat trail (only 200 ft / 61 m elevation gain over 8 mi / 12.9 km) wanders through Lyell Canyon, mostly alongside the Lyell Fork of the Tuolumne River. edit
• Mono Pass (8 mi (12.9 km)), Starts at the Mono Pass Trailhead (6 mi / 4.4 km east of Tuolumne Meadows). A moderately difficult trail that climbs gently at first (1,000 ft / 304 m elevation gain) to a junction with Spillway Lake. The left fork then steeply climbs to Mono Pass, at 10,500 ft / 3,200 m. From the pass, Upper Sardine Lake is another 0.75 / 1.2 km down the pass to the east. edit
• Gaylor Lakes (2 mi (3.2 km)), Starts from the Gaylor Lakes Trailhead (at the Tioga Pass Entrance Station). A strenuous trail that climbs steeply in the first 0.5 mi / 0.8 km (1,000 ft / 304 m elevation gain) to a ridge with views to both sides. At the ridge, the trail drops 200 ft / 61 m to a lake and meadows, which can be explored with side trails. edit
• Vogelsang High Sierra Camp, Lake, and Pass (15.8 mi (25.5 km)), Starts from the Dog Lake/John Muir Trail parking area. The trail's first 2 mi / 3.2 km, along the John Muir Trail, are relatively level. The Rafferty Creek Trail then splits off and begins a 1,200 ft / 366 m ascent to Tuolumne Pass, followed by a 160 ft / 49 m climb to the High Sierra Camp. You can continue to Vogelsang Lake (0.5 mi / 0.8 km further) and spectacular Vogelsang Pass (1.5 mi / 2.4 km further). edit
[edit] Wawona & Mariposa Grove
• Wawona Meadow Loop (3.5 mi (5.6 km) round-trip), Starts at the golf course across the street from the hotel. The trail is a pleasant stroll on a fire road around the Wawona Meadow. edit
• Swinging Bridge Loop (5 mi (8 km) round-trip). A moderate hike leading from the Wawona Store to the swinging bridge, the trail follows the paved Forest Drive 2 mi (3.2 km) upstream from the history center and then continues on the dirt road for a short distance to the swinging bridge (which really does swing). Cross the bridge and bear left onto the dirt road, which soon becomes paved Chilnualna Falls Road. When you reach the Wawona Stable, walk into it towards the Covered Bridge, where you started this hike. edit
• Chilnualna Fall (8.2 mi (13.1 km) round-trip), Starts in the Chilnualna Fall trailhead parking area. This strenuous hike leads past the cascades of Chilnualna Fall and all the way to the top of the fall. For the hearty day-hiker, the trip can be extended 18 miles (round-trip) to reach Crescent Lake. edit
• Alder Creek (12 mi (18.7 km) round-trip), Begins at the Alder Creek trailhead parking area. This strenuous trail climbs through an open pine forest with abundant manzanita on the drier slopes. edit
• Wawona to Mariposa Grove (6 mi (9.6 km) one-way), Starts near the Moore Cottage at the Wawona Hotel. This generally viewless hike leads to the Mariposa Grove of Giant Sequoias. From late April through September, you can take the free shuttle bus from the grove back to Wawona. edit
• Mariposa Grove of Giant Sequoias (6 mi (9.6 km) round-trip). There are numerous trails leading through this grove of giant trees, all starting from the Mariposa Grove parking area. To reach the Grizzly Giant and California Tunnel Tree, follow the trail that begins at the far end of the parking area. To reach Wawona Point, continue on the trail past the Grizzly Giant into the upper grove. The old road ascends to Wawona Point from near the Galen Clark Tree. edit
[edit] Hetch Hetchy
• Wapama Falls (5 mi (8 km) round-trip), Starts from the O'Shaugnessy Dam. This easy trail leads to the bottom Wapama Falls (and Tueeulala Falls in spring). edit
• Rancheria Falls (13.4 mi (21.4 km) round-trip), Starts from the O'Shaugnessy Dam. A moderately difficult hike that provides numerous views of the Hetch Hetch Valley. edit
• Poopenaut Valley (3 mi (4.8 km) round-trip). This oddly named trail begins four miles from the Hetch Hetchy Entrance Station and provides quick access to the Tuolumne River, descending 1,229 feet (735 m) to the river below O'Shaugnessy Dam. edit
• Smith Peak (12.5 mi (20 km) round-trip). A strenuous trail from the Hetch Hetchy Ranger Station to Smith Peak. Forests and meadows eventually give way to great views of the Hetch Hetchy area. edit
[edit] Rock climbing
Yosemite Valley from Tunnel View
The Valley also offers some of the most challenging and spectacular rock climbing in North America, with vertical faces 3,000 and more feet tall. At the current time, wilderness permits are not required for nights spent on a wall, but it is illegal to camp at the base of any wall in Yosemite Valley. Additional regulations:
1. Fight litter! Don't toss anything off a wall, even if you intend to pick it up later. Don't leave food or water at the top or on ledges "for future parties". Set a good example by picking up any litter you see, including tape wads and cigarette butts.
2. Don't leave fixed ropes as permanent fixtures on approaches and descents. These are considered abandoned property and will be removed.
3. Minimize erosion on your approach and descent. If an obvious main trail has been created, use it. Go slow on the way down to avoid pushing soil down the hill. Avoid walking on vegetation whenever possible.
4. If you need to build a fire for survival during an unplanned bivouac on the summit, use an existing fire ring. Building a new fire ring or windbreak is prohibited. Make sure your fire is completely out before you leave.
5. Clean extra, rotting slings off anchors when you descend. Bring earth-toned slings to leave on anchors.
6. Check the Camp 4 Kiosk or the Mountain Shop for the current Peregrine Falcon closures.
7. On first ascents: Please think about the impacts that will be caused by your new climb- Is the approach susceptible to erosion? Is there a lot of vegetation on the rock? "Gardening", e.g. killing plants, is illegal in Yosemite. Can the climb be done with a minimum of bolts? Motorized drills are prohibited.
Commercial guided climbing trips are also available:
• Yosemite Mountaineering School and Guide Service, (in Curry Village by the Mountain Shop), +1-209-372-8344 (), [4]. Offers guided hikes and backpacking trips in Yosemite of varying lengths and difficulty in addition to climbing outings ranging from beginner instruction to multi-day ascents of El Cap. edit
[edit] Horseback riding
There are still commercial horseback-riding concessions in the Yosemite Valley, Wawona and Tuolumne Meadows areas.
• DNC Parks & Resorts at Yosemite, +1-209-372-8427 (Tuolumne) or +1-209-375-6502 (Wawona), [5]. Offers two-hour ($59), half-day ($79) and full-day ($119) trail rides. Custom guided trips are also available. edit
[edit] Golf
• Wawona Golf Course, +1 209-375-6572, [6]. A championship 18-hole golf course in Wawona Meadow in the South end of the Park, right next door to the Wawona Lodge and stables. $18.50 for 9 holes and $29.50 for 18 holes. edit
[edit] Skiing
Badger Pass is the oldest ski area in California, and offers both downhill and cross-country trails. For cross-country skiers the park offers over 350 miles of trails, with 90 miles of marked trails and 25 miles of groomed trails originating at Badger Pass. Downhill skiing options include ten runs at Badger Pass, with lifts operating daily from 9AM-4PM during the ski season. Note that the majority of these runs are for beginners and moderate skiers, so thrill seekers may wish to ski elsewhere. Lift tickets cost $5 for a single run or $35 for a full-day ticket. Both downhill and cross-country lessons are available.
Due NPS regulations in place to ensure the area remains as natural as possible, the Badger area has no artificially-lighted skiing and cannot make its own snow.
Most years Badger Pass is open around Dec 15th and closes around April 1st.
[edit][add listing] Buy
Gift shops abound in Yosemite. Stores are run by the park concessionaire (DNC), the Yosemite Conservancy, or the Ansel Adams Gallery, with a few smaller family stores. DNC, YC, and the Ansel Adams Gallery offer some form of mail order. The Yosemite Conservancy stores specialize in educational materials about Yosemite, many of which are published by the organization; membership offers a 15% discount on most purchases.
Gas is available for purchase at Crane Flat, Tuolumne Meadows, Wawona, and in towns located outside of the park. Gas prices tend to be 60 cents to 1 dollar higher than communities like Fresno, Merced, and Modesto.
[edit] Yosemite Valley
• The Ahwahnee Gift Shop/Sweet Shop, +1-209-372-1409. Two sister stores located inside the Ahwhanee Hotel. The Gift Shop has mostly high-end merchandise (including some of the best jewelry in Yosemite), and the sweet shop sells sundries, food, and more inexpensive items. The Sweet Shop also sells postage stamps. edit
• Ansel Adams Gallery. Store for the famous nature photographer, also has unique items, and one of the most diverse book selections in Yosemite. Not only do they offer a variety of affordable Ansel Adams Special Edition Prints, but other great selections from landscape photographers of Yosemite. Also unique selection of Native American and contemporary jewelry, and handcrafted pottery. Best for book shopping after the Yosemite Valley Visitor Center Bookstore. Offers a 10% discount for Yosemite Conservancy donors. Store is regarded as the photography "experts" of Yosemite. edit
• Art Center. Seasonal. Operated by the Yosemite Conservancy. edit
• Curry Village Gift Shop. Serving as a "camp store", you can find gifts as well as numerous items to make camp life easier. edit
• Curry Village Mountain Shop. The best sport shop in Yosemite, and one of the best rock climbing gear stores in the world. edit
• The Green Store. Located in the Degnan's building in Yosemite Village, the store specializes in environmentally friendly products. edit
• Housekeeping Camp Store. Seasonal. Best described as a combination between Curry Gift and the Village Sport Shop. edit
• Museum Store. Operated by the Yosemite Conservancy. edit
• The Nature Shop. All merchandise has a "natural" bent but relatively low prices compared to the Ahwahnee Gift Shop. Low visitation to this store makes it desirable for quiet shopping. edit
• Village Store, +1-209-372-1253. The largest store in Yosemite, with the largest grocery selection as well. If you need something for your visit, check here first. edit
• Village Sport Shop. One of the two camping goods stores in Yosemite Valley. edit
• Visitor Center Bookstore. Operated by the Yosemite Conservancy. edit
• Yosemite Lodge Gift Shop. Extremely similar to the Curry Village Gift Shop. Caters mostly to Lodge guest, camp 4 campers, and tour groups. edit
[edit] Other locations
• Big Trees Store, Mariposa Grove. Seasonal. Snacks and gifts for Mariposa Grove visitors. Located near the entrance to the Grove. edit
• Crane Flat Gas Station, Crane Flat. One of the few gas stations in Yosemite, it has merchandise you would expect to find in a well stocked mini-mart, but also includes camp supplies. Gas Pumps remain open all year, but store may close in winter. edit
• Hill Studio, Wawona. Operated by the Yosemite Conservancy. edit
• Mariposa Grove Museum, Wawona. Seasonal. Operated by the Yosemite Conservancy. edit
• Tuolumne Meadows Store, Tuolumne Meadows. Seasonal. Well visited by long-distance hikers, as the PCT and the JMT go right by the store, it has camp supplies, gifts, and snacks. edit
• Tuolumne Meadows Mountain Shop, Tuolumne Meadows. Seasonal. Home of the TM mountain school, smaller version of the Curry Mountain Shop. edit
• Tuolumne Meadows Visitor Center, Tuolumne Meadows. Seasonal. Operated by the Yosemite Conservancy. edit
• Wawona Store and Gift Shop, Wawona. Servicing the southern end of Yosemite, this store as groceries and gifts for local campers and Wawona Hotel guests edit
• White Wolf, White Wolf. Seasonal. Camp Store. edit
[edit][add listing] Eat
Groceries can be purchased in Yosemite Village, Crane Flat, Curry Village, Wawona, and Tuolumne Meadows.
[edit] Yosemite Valley
• Ahwahnee Dining Room, +1-209-372-1489, [7]. An upscale restaurant in Yosemite Valley serving breakfast, lunch and dinner. Famous also for its Sunday Grand Buffet. Be aware that there is a "resort casual" dress code for dinner service, meaning shorts and jeans are not acceptable attire, and that dinner reservations are recommended. Breakfast and Lunch attire remain regular casual. edit
• The Mountain Room, [8]. Reservations are not taken for groups of eight or less edit
• Yosemite Lodge Food Court. Serving cafeteria-style meals in Yosemite Lodge. Offers breakfast, lunch and dinner year-round. edit
• Degnan's Deli. Open year-round and offering standard deli fare, located in Yosemite Village. edit
• Degnan's Loft. Open to the public from April to October from 12PM to 9PM, offering pizza, salads and soups in Yosemite Village. Open only to park employees and residents November through March from 5PM to midnight (last call at 11:30PM). Pizzas and salads are available only from 5PM to 9PM. They also add pool tables and video games during the winter. They are removed during tourist season to maximize seating. edit
• Degnan's Cafe. Next to Degnan's Loft, serving "grab-and-go" food like sandwiches and chips, coffee and soft-serve ice cream. Open Summer Season. edit
• Village Grill. Fast food in Yosemite Village. Open from Spring through Fall. Closes for the day if weather is poor. edit
• Curry Village Pavilion Buffet. Located in Curry Village, this buffet offers both a breakfast and a dinner buffet. edit
• Curry Village Taco Stand. Burritos, tacos, nachos, ice cream and beverages. Open Seasonally from April to October. edit
• Curry Village Pizza Deck. Pizza and salads. Open March through December. The food offered is nearly identical in quality and price as the Loft, but if crowds aren't your cup of tea then it might be best to avoid this establishment. edit
• Curry Village Ice Cream & Coffee Corner. Open March through December. edit
• Happy Isles Snack Stand. Offering drinks and snacks during the summer. Located near the Happy Isles nature center. Handy when you come off the trail, and want something. edit
[edit] Wawona
• Wawona Dining Room. Fine dining, serving breakfast, lunch and dinner daily, with a brunch served on Sundays. edit
• Wawona Lawn Barbecue. (summer) Sa 5PM-7PM. On Saturday evenings in summer the lawn outside of the Wawona Lodge hosts a barbecue featuring steak, chicken, hamburgers and corn-on-the-cob. edit
• Wawona Golf Shop Snack Stand. Snacks, beer, and other beverages on the golf course. Open daily from spring through fall. edit
[edit] Tuolumne
• Tuolumne Meadows Lodge, +1-209-372-8413. Family-style meals served in a tent setting. Reservations are required for dinner. edit
• Tuolumne Meadows Grill. To-go food for breakfast, lunch and dinner. Open daily in summer. edit
• White Wolf Lodge, +1-209-372-8416. Located near the Tioga Pass Road (about half way between Tuolumne Meadows and Crane Flat) and serving breakfast and dinner. Reservations are advised for dinner. edit
[edit] Glacier Point
• Glacier Point Snack Stand. Ice cream, sodas, and other nutritious fare. edit
[edit][add listing] Drink
• The Ahwahnee Lounge, (Ahwahnee Hotel). An upscale lounge in Yosemite Valley, offering cocktails, wine, beer, and bar food (sandwiches, appetizers, salads) with seating available both inside and on the terrace. Opens at 11:00AM daily, with live piano music most Friday and Saturday evenings. edit
• Mountain Room Lounge, (Yosemite Lodge), [9]. Located in Yosemite Lodge, this lounge offers cocktails and bar food. Televisions are also placed around the room for those who have escaped to Yosemite but can't bear to miss the game. edit
• Pavilion Bar, (Curry Village). Located in Curry Village, this bar serves cocktails, beer, wine and fast food with both inside and deck seating. Extremely popular among employees. Seasonal. edit
• Wawona Cocktail Service, (Wawona Hotel). Within the Wawona hotel a cocktail service is available in both the lounge and on the veranda. Singing piano player performs certain nights. edit
[edit][add listing] Sleep
Demand for lodging in Yosemite Valley in both the hotels and the campgrounds is extremely heavy (despite the very high prices), so you need to book well ahead of time during the late spring, summer and early fall, although there are often vacancies during the winter, late fall and early spring. Cancellations occur on a random basis, so it is also advised to call back frequently for a desired reservation date.
The least expensive lodging option is to stay outside the park itself and drive in each day. The nearby towns of El Portal, Mariposa, Groveland, Fish Camp, and Lee Vining have lodging. In addition, the community of Yosemite West borders the park and offers numerous rentals; it is accessible only from within Yosemite and provides a convenient option to visitors planning to stay near Wawona or Yosemite Valley. Be aware that despite names like "Yosemite View", no lodging outside the park has a view of the Valley. Lodging is particularly close to the park near the Route 140 entrance and the Route 120 East entrance; for those approaching from the Route 41South entrance, there are many affordable lodging options in Oakhurst, but at the cost of a longer commute distance. In addition, Yosemite is surrounded by national forests that offer numerous campgrounds.
[edit] Lodging
[edit] Park Lodging
The following lodging options are "official" park lodgings, operated by the National Park Service through a concessionaire.
• The Ahwahnee, (801) 559-4884, [10]. 99 luxury hotel rooms and 24 cottages in Yosemite Valley. The lodge is a national historic landmark and the most upscale lodging in the park, with rooms facing Half Dome, Glacier Point or the West Valley. There is a small heated outdoor pool. Rooms and cottages start at about $500 per night, with suites running up to and above $1000 per night. edit
• Curry Village, (801) 559-4884, [11]. Located in Yosemite Valley, Curry Village offers a wide range of lodging options ranging from "hotel" accommodations to tent cabins. Be aware that tent cabins and some wooden cabins are primitive and do not have private baths. There are five bathroom buildings and one shower building in the camp. No cooking is allowed at Curry Village and tent cabins also come with a bear locker to store food. There is an outdoor pool, which is free to people lodging there and open to the public for $5. Rates for tent cabins are from $109 per night, while cabins and motel rooms are from $115 to $190 per night. edit
• High Sierra Camps, (801) 559-4884, [12]. The five High Sierra Camps are villages of tent cabins located in Yosemite's backcountry, with most of the tent cabins holding four people (be prepared for mixed gender sleeping arrangements). Due to their remote locations the High Sierra Camps are normally visited as part of a horseback package tour or a hiking trek, with each camped spaced a day's hike apart. All of the High Sierra Camps include gourmet breakfast and dinner, and eat-in only reservations may be possible for those not needing accommodation. The High Sierra Camp cooking is widely regarded by locals as some of the best food in Yosemite. Some lodges may have hot showers, and all require that you bring your own linens. Demand for the High Sierra Camps is so high that reservations are handled by a lottery held from October 15 to November 30 (call for an application) with final assignments decided by March 31. Be aware that it is sometimes possible to get a High Sierra Camps reservation later if someone cancels. $145 to $151 per night for adults and $87 to $91 per night for children (age 7-12). edit
• Housekeeping Camp, (801) 559-4884, [13]. Despite its name, Housekeeping Camp (located near Curry Village) offers 266 sturdy tents for visitor lodging. The "tents" have a concrete floor, three concrete walls, canvas tops, and sleep six in bunk beds and double beds. Linen is not provided but may be rented for $2.50 per night. Open during the summer season only. Housekeeping Camp is the only lodging in the Valley that allows for a fire and cooking. $94 per night. edit
• Tuolumne Meadows, (801) 559-4884, [14]. Open from mid-July through September, Tuolumne offers 69 tent cabins in Tuolumne Meadows. These tent cabins have wooden frames, a concrete floor, and canvas walls. Bunks beds, linens, candles, and a wood stove are provided, while bathrooms and showers are located in a central facility. $107 per night. edit
• Wawona, (801) 559-4884, [15]. This historic lodge overlooks Wawona Meadow in the south part of the park along Route 41. Of the 104 rooms only 50 have a private bath. The lodge is rustic, with no telephones or televisions. In the winter months the lodge is only open on select weekends and holiday periods. Rooms rates are $225 for a room with a private bath, and $151 without. Rates are slightly lower in the winter. edit
• White Wolf, (801) 559-4884, [16]. Located along the Tioga Pass Road, White Wolf is open from July through September and offers 24 tent cabins and 4 cabins with private bath. The tent cabins are wood frame on a raised wooden platform and include beds, linen, and a wood stove. Rates are $67 per night for tent cabins, and $91 per night for cabins with bath. edit
• Yosemite Lodge at the Falls, (801) 559-4884, [17]. Located near the base of Yosemite Falls, this lodge offers 245 rooms, but be aware that no rooms have air conditioning. Internet access (in-lobby kiosks and WiFi in guest rooms) is now also available. There is an outdoor pool located on the premises, as well as the main activities desk for the park. Room rates are $219 per night, with slightly lower prices during the winter. edit
[edit] Private cabins
In addition to the lodging operated through the park service, there are also a handful of private cabins located within the park boundaries that can be rented.
• The Redwoods in Yosemite, +1-209-375-6666 (), [18]. There are over 130 private cabins in the Wawona area that may be rented from their owners. Ranging from log cabins to spacious vacation homes, all homes are completely furnished, including linens, cookware, dishes, and a barbecue grill. Prices vary by cabin style and date, with economy cabins from $150 per night during low times, and premium cabins as much as $500 per night on holiday weekends. edit
• Yosemite Vacation Homes, [19]. Yosemite Vacation Homes offers 11 unique homes and cabins for nightly rent in the Foresta area. Foresta is inside the gates of Yosemite National Park and only 7 miles from Yosemite Valley. Prices vary by cabin type and range from $230 to $400 per night. edit
[edit] Camping
Camping is by far the cheapest way of staying within the park, but campgrounds fill quickly during summer months and may require making reservations months in advance. Reservations can be made through the National Park Service from 7AM-7PM PST, or by calling 1-877-444-6777 or +1 518-885-3639 from outside the United States. Written reservation requests can be made by including desired location, type of equipment you will be camping in (i.e.,tent, RV,etc.), as well as method of payment. Send written requests to NPRS, P.O. Box 1600, Cumberland, MD 21502.
All campgrounds offer bear-safe food storage containers, tap water (except where noted), and flush toilets. Pay showers and laundry are located in Curry Village in Yosemite Valley. During summer, showers are also available afternoons at Tuolumne Meadows Lodge.
For backpackers, North Pines in Yosemite Valley and the Tuolumne Meadows campground both have "backpacker camps". These are walk-in sites offered for people with valid wilderness permits to stay the night before and the night after their backcountry trips. For more information contact the Yosemite Valley Wilderness Center or any park campground office.
[edit] Yosemite Valley
In the main section of Yosemite Village, you cannot go further east than the parking area, as Northside Drive becomes one-way at this point. Turn at Sentinel Road (0.1 mi/0.2 km) to the west of the parking lots, cross the bridge, then turn left and continue on Southside Dr. along the Merced River to the Pines Campgrounds (1.6 mi/2.5 km). If staying in the North Pines, re-cross the river at Clarks Bridge. Getting in via the Ahwahnee Hotel is not possible either, except on foot or bicycle. Some GPS units do not handle routing to the Pines Campgrounds correctly, and direct you to go the wrong way on Northside Dr. (Tip: make the south end of Sentinel Bridge an intermediate stop.)
• Camp 4. This walk-in campground is in Yosemite Valley, open year-round, and offers 35 sites on a first-come, first-served basis. All sites are tent only. Note that with six people assigned to every site this isn't the quietest of campgrounds, so light sleepers may want to bring earplugs. Campground is world famous among the rock climbing community and as such can be EXTREMELY popular during the peak season. Prospective campers can expect to see people waiting in line for sites as early as four o'clock in the morning. As of 2011 all campers wishing to stay at Camp 4 need to hold their own place in line. $5 per person per night. edit
• Lower Pines. Located in Yosemite Valley, and closest to the Half Dome hike, this campground is open from March through October, requires reservations, and offers 60 sites for both tents and RVs. Three larger sites are also available for groups of up to 12 people for $30 per night. $20 per night. edit
• North Pines. Located in Yosemite Valley, this campground is open from April through September, requires reservations, and offers 81 sites for both tents and RVs. $20 per night. edit
• Upper Pines. Located in Yosemite Valley and open year-round, this campground requires reservations and offers 238 sites for both tents and RVs. $20 per night. edit
[edit] Wawona
• Wawona. Wawona campground is open year-round, requires reservations April-September, and offers 93 sites for both tents and RVs. $20 per night. edit
[edit] Glacier Pass
• Bridalveil Creek. The Bridalveil Creek campground is located along the road to Glacier Pass and is open from July through early September. The campground's 110 sites are first-come, first served, and sites are available for both tents and RVs. $14 per night. edit
[edit] Crane Flat
• Crane Flat. Crane Flat is open from June through September, requires reservations, and offers 166 sites for both tents and RVs. $20 per night. edit
• Hodgdon Meadow. This campground is located north of Crane Flat near the park entrance and is open year-round. Reservations are required from April through September, and offers 105 sites for both tents and RVs. Four group sites are available for 15-25 people. $20 per night. edit
[edit] Tioga Pass Road
• Porcupine Flat. Porcupine Flat is located off of the Tioga Pass Road and offers 52 tent and RV sites from July through early September on a first-come, first-served basis. Creek water only $10 per night. edit
• Tamarack Flat. Open from June through September, this campground is located off of the Tioga Pass Road near Crane Flat and offers 52 tent sites on a first-come, first-served basis. Creek water only. $10 per night. edit
• Tuolumne Meadows. The Tuolumne Meadows campground is open from July through September and offers 50% of its sites as reservation only, while 50% are first-come, first-served. 304 sites are available for both tents and RVs. Be prepared for chilly nighttime temperatures. $20 per night. edit
• White Wolf. White Wolf is open only from July through early September and is located along the Tioga Pass Road. The 74 sites are first-come, first-served for tents and small RVs only. $14 per night. edit
• Yosemite Creek. Open from July through early September, this campground is located off of the Tioga Pass Road and offers 75 sites on a first-come, first-served basis for tents only. Creek water only. $10 per night. edit
[edit] Backcountry
Backcountry permits are free and are required year-round for all overnight trips into Yosemite's wilderness. Wilderness areas operate under a quota system that limits the number of people who may begin overnight hikes from each trailhead, each day. While permits may be reserved for $5 per party plus $5 per person, at least 40% of each trailhead quota is available on a first-come first-served basis the day of, or one day prior to, the beginning of your trip.
Permits can be obtained in person from the wilderness stations in Yosemite Village, Big Oak Flat, Tuolumne Meadows, Badger Pass, Hetch Hetchy and Wawona. In addition, permits can be reserved up to 24 weeks in advance for a fee. There are three ways to reserve a wilderness permit [20]:
1. By fax. Faxes to (209) 372-0739 are processed before phone calls. See Yosemite's web site for the appropriate form.
2. By phone. Reservations for summer trips are accepted from 2 days to up to 24 weeks in advance by calling (209) 372-0740. You must know your entry and exit trailheads prior to calling.
3. By mail. Reservation requests for summer trips are accepted from 2 weeks to 24 weeks in advance by writing to Wilderness Permits, PO Box 545, Yosemite, CA, 95389. See Yosemite's web site for the reservation form to include with written requests. If your requested trailhead and dates are available, you will receive a confirmation letter in the mail. A payment method must be provided with all written requests.
All backcountry campers are expected to leave the wilderness in the same condition as they find it, meaning no trash, fire scars, or other evidence of your visit should be left behind. Backcountry campsites must be at least four trail miles from Tuolumne Meadows, Yosemite Valley, Glacier Point, Hetch Hetchy or Wawona, or at least one trail mile from any road. Groups are limited in size to 15 people. Pets, weapons, bicycles, strollers, and mechanized vehicles of any kind are not allowed in the wilderness areas, while fires are only allowed in existing fire circles, and are not allowed above 9600 feet elevation.
Bear canisters are required in all areas of the Park and highly recommended in areas close to Yosemite's borders. These canisters must be used for food storage, as well as for storing scented toiletries such as soap, deodorant and toothpaste, and should be stashed at least 100 meters from your campsite. Canisters can be rented from the ranger station where you pick up your backcountry permit for $5, good for up to two weeks.
[edit] Stay safe
For any emergency in Yosemite National Park, dial 911 from most phones (hotel and retail phones may require 9+911). Yosemite NPS runs its own dedicated emergency dispatch. If you dial from a cell phone, first mention that you are in Yosemite as many cell phones route to a call center in your number's area code
[edit] Medical
• Yosemite Medical Clinic, Ahwahnee Drive in Yosemite Valley, +1 209-372-4637. Drop-in and urgent care: 9AM-7PM, 7 days per week, May-September; 9AM-5PM Monday-Friday, October-April. Appointments 8AM-5PM M-F. Routine and emergency medical care, 24-hour paramedic/ambulance services, lab, and Mountain Crisis Services for victims of domestic violence. edit
[edit] Wildlife
Over the years the park's bears have become accustomed to scavenging trash and food left out by humans, and will even break into cars and tents to get it. While not the larger grizzly bears that once roamed California, black bears are strong enough to tear a door off of a car with ease. Luckily they usually prefer to avoid humans, so they'll most likely do their work on vehicles left at trailheads or in parking lots. Prevention is remarkably simple: never leave food or scented items (deodorant, air fresheners) in your car or bring them into your tent. Heed this advice! Leaving even just a tube of toothpaste or empty food wrappers in a car may result in thousands of dollars of damage to your vehicle should a bear choose to investigate the smell! Bear-resistant storage units are provided at park campgrounds and overnight parking areas: use them.
To avoid bear encounters while hiking, make noise so that the animal knows you are coming. This approach will also help to avoid encounters with mountain lions, which also inhabit the park. Other animals, such as the herds of deer which can be found in the park's meadows, can be equally dangerous; a young boy was killed by a deer in Yosemite Valley several years ago. Give all animals their space, and never feed any park wildlife.
[edit] Light
Yosemite Lodge (and possibly other accommodation areas) has no outside lighting. This is to reduce light pollution and allow the stars to shine down. If moving about the area at night (even to go to the reception office or restaurant) ensure that you have a flashlight (torch), as walking in the dark can be quite hazardous.
[edit] Weather
Other natural dangers in the park come from the weather. Hypothermia can be a concern at higher elevations where temperatures can drop below freezing throughout the year. Dress in layers, and be prepared for storms and rapid changes in temperature. When storms are approaching avoid open areas such as the summits of the park's many granite domes; lightning strikes these areas regularly. If a storm does approach, get off of high, open ground. When hiking wear sturdy footwear and drink plenty of water - if you are thirsty that is an early sign of dehydration. Be aware that the sun can be intense at higher elevations and when reflected off of snow, so sunscreen is important. In the winter, take the weather term "Winter Storm Warning" very seriously as it means a significant storm is definitely coming.
[edit] On the trails
Hikers should follow all posted signs - if a trail is closed due to ice, landslide, or some other reason do not ignore the closure as doing so endangers both the hiker and any area that must be traversed to go around the closure. On the Half Dome trail hikers should ALWAYS remain inside the cables for both their ascent and descent - people have died on this section of trail as recently as Summer 2009.
The park's waterfalls pose another potential hazard. Do not attempt to get close to the waterfalls, especially in the spring. This includes swimming above the waterfalls at a distance of less than 1 mile (about 1600 meters) The force of the water will easily sweep a person off their feet and over the falls. Being swept over any of Yosemite's waterfalls is invariably fatal.
[edit] Other Concerns
Currently, the greatest danger in the park comes from the thousands of park visitors. Petty thieves and traffic accidents are two issues to be aware of. Follow park speed limits, lock your vehicle, and be aware of your belongings, especially in Yosemite Valley. Violent crime is extremely rare in Yosemite, but given the numbers of people that visit you should expect that a few unsavory characters will be visiting too.
The National Park Service provides the primary law enforcement and fire protection in the park. NPS is supplemented by DNC Security, who handle a number of calls for service on DNC land assignments. DNC Fire is paged out along with NPS Fire, and handles a large number of calls in Yosemite Valley.
Lost and Found
There are two major Lost and Found operations in Yosemite. One is run by the National Park Service. It can be reached at 209-379-1001. The other is run by DNC, and can be reached at: 209-372-4357. They coordinate as best as possible, considering they are a half-hour away from each other. They process thousands of items each year, and surprising, get a number of items back to the rightful owner. Because of the thousands of items lost or found, generally, you will not get a return call unless your item has been found and turned in correctly.
Items that are found that cannot be returned to the owner are generally turned over to recognized charities. So, if you don't get your item back, and if it is turned in by the finder, at least you can rest easy that it will eventually go to a good cause.
[edit] Get out
The towns of El Portal (west on SR140), Mariposa (west on SR140), Groveland (west on SR120), Fish Camp (south on SR41), Lee Vining (east on SR120) and Yosemite West (midway between Yosemite Valley and Wawona) are all within a few miles of the park border. Other nearby destinations include:
• Devils Postpile National Monument. This monument is located south of Yosemite off of highway 395 and protects unusual geologic features while also providing an access point to the High Sierra wilderness.
• Sequoia and Kings Canyon National Parks. Located south of Yosemite, these two parks are managed as a single unit and protect vast groves of giant sequoia trees as well as a backpacker's wonderland of pristine areas in the High Sierra. Within Sequoia NP is Mount Whitney, the highest summit in the contiguous United States with an elevation of 14,505 feet (4,421 m). There is no vehicle access to these parks via US Highway 395, though it's much easier to get a good view of Mt. Whitney this way. To enter, take State Highway 41 (south exit) to Fresno, then State Highway 180 (in downtown Fresno) to Kings or State Highway 198 (via Visalia) to Sequoia.
• Tuolumne County, California's historic gold mining country of the mid-1800's. Towns include Jamestown, Sonora, and Columbia. The latter was the first capital of the state. Take State Highway 120 west to State Highway 49 north (turn at Parrott's Ferry Rd. [E-18] for Columbia).
• Mono County, includes the large Mono Lake and Bodie State Park, a well-preserved, gold-mining ghost town. In the wintertime, Bodie often has the lowest overnight temperatures in all of California.
• Manzanar National Historic Site The most well-known and best preserved of the Japanese internment camps during World War II which operated from 1942-1945. Manzanar is located between the towns of Independence and Lone Pine off US Highway 395. A bit far from Yosemite, the park is still the closest major tourist location from the site, and the best chance many will ever have to visit Manzanar. (No direct access from Sequoia/Kings Canyon Parks.) About 120 mi (200 km) from the Tioga Pass (east) exit, with a right turn (going south) on US Highway 395. This is one of the more isolated spots of California, and the climate can be quite extreme at times with heat, dust, and in the wintertime, cold (elevation 3850 ft).
Routes through Yosemite National Park
FresnoFish Camp S N END
MantecaGroveland W E Lee ViningBenton
MercedEl Portal W E END
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Q4sales voted on the following stories on BizSugar
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Carnosine Treatment for Gulf War Illness: A Randomized Controlled Trial
James Nicholas Baraniuk, Suliman El-Amin, Rebecca Corey, Rakib Rayhan, Christian Timbol
Abstract
About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (B-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment.
Full Text: PDF DOI: 10.5539/gjhs.v5n3p69
This work is licensed under a Creative Commons Attribution 3.0 License.
Global Journal of Health Science ISSN 1916-9736(Print) ISSN 1916-9744(Online)
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The Concept ‘Development’ Revisited towards Understanding: in the Context of Sub-Saharan Africa
Brian-Vincent IKEJIAKU
Abstract
There has been lingering contention on what development means in the African context. The meaning of development in the African context is crucial in order to know whether Africa is developing or not, particularly since 1970. This debate becomes critical when it is appreciated that Africa appears as the least developed continent in the world. This paper conceptualises ‘development’; in doing this, the paper considers both economic and political development, and looks into the complex question: Must economic development precede political development in Africa or vice-versa? In an attempt to address these issues, the paper considers and examines the views of many scholars and studies on these subject matters. While the paper recognises the rise and importance of recent global development paradigms, such as feminism, and green-environmentalism, it however, applies the long traditional approaches – modernisation, liberalism, dependency and Marxism in analysing the meaning of development in Sub-Saharan African context. This is because this paper is concerned with the real development stage of this Sub continent of Africa, and not merely an intellectual exercise. The paper finally proffers a definition of development, which it believes to be germane in the context of real developmental stage of Sub-Saharan Africa.
Full Text: PDF
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PennFuture Pittsburgh works to create a just future where nature, communities and the economy thrive. We enforce environmental laws and advocate for the transformation of public policy, public opinion and the marketplace to restore and protect the environment and safeguard public health. PennFuture advances effective solutions for the problems of pollution, sprawl and global warming; mobilizes citizens; crafts compelling communications; and provides excellent legal services and policy analysis.
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Pamlico County, North CarolinaEdit This Page
From FamilySearch Wiki
Revision as of 16:55, 13 March 2013 by Murphynw (Talk | contribs)
United States North Carolina Pamlico County
Guide to Pamlico County North Carolina genealogy. Birth records, marriage records, death records, census records, family history, and military records.
North Carolina
Online Records
Pamlico County, North Carolina
Map
Location in the state of North Carolina
Location of North Carolina in the U.S.
Facts
Founded 1872
County Seat Bayboro
Courthouse
Adopt-a-wiki page
This page adopted by:
NCGenWeb Project
who welcome you to contribute.
County Coordinator
Pamlico Co. NCGenWeb
Adopt a page today
Contents
County Courthouse
Pamlico County Courthouse
202 Main St P O Box 423
Bayboro, NC 25815
Phone: 252-745-4421
Registrar of Deeds has birth records from 1913
marriage and death and land records from 1872
Clerk Superior Court has divorce and probate and court from 1872[1]
History
Parent County
1872--Pamlico County was created from Beaufort and Craven Counties.
County seat: Bayboro [2]
History
Record Loss
Places/Localities
Populated Places
Neighboring Counties
Resources
Ncpamlico.png
Cemeteries
Census & Tax Records
For tips on accessing Pamlico County, North Carolina census records online, see: North Carolina Census.
Land
Lookups
Maps
Military
Civil War
Civil War Confederate units - Brief history, counties where recruited, etc.
Miscellaneous
Newspapers
Obituaries
Organizations & Addresses
Queries
Surnames
Vital Records
Wills & Estates
Societies and Libraries
Family History Centers
Web Sites
• USGenWeb project. May have maps, name indexes, history or other information for this county. Select the state, then the county.
• Family History Library Catalog
References
1. Handybook for Genealogists: United States of America, 10th ed. (Draper, Utah: Everton Pub., 2002), Pamilco County, North Carolina. Page 511 At various libraries (WorldCat); FHL Book 973 D27e 2002.
2. The Handybook for Genealogists: United States of America,10th ed. (Draper, UT:Everton Publishers, 2002).
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Parsing & Formatting Date/Time in Python
This is an article on Parsing & Formatting Date/Time in Python in Python.
Being in the era of instant updates & notifications one would at some point or the other would need to parse/format date & time, be it any language. Here, we'll see how we can parse & format date/time with Python.
Python is natively equipped with the functions to make our job easier, the function we would look at are strftime() & strptime(), both functions are available in the Python package time.
Parsing Date/Time
strptime(string[, format]) requires the date/time string as the first argument and the second argument (optional, it defaults to "%a %b %d %H:%M:%S %Y") is the format string and returns a time_struct object. Go through the example code below for a demo.
Code: Python
#!/usr/bin/python
import time
t = time.strptime('2 Jun 2012 11:15:29','%d %b %Y %H:%M:%S')
print "parsed time_struct: %s " % t
## this will print year
print t[0]
Here's the output:
Code:
parsed time_struct: (2012, 6, 2, 11, 15, 29, 5, 154, -1)
2012
Now, you may work with the returned object and use the required data in it, like you may only need the year as I've used in the example.
Formatting Date/Time
strftime(format[, t]) outputs the data passed as time_struct object into the format specified, if t is not passed the current value that'd be returned by localtime() will be used. Again, a code example to play with & understand.
Code: Python
#!/usr/bin/python
import time
start_t = time.localtime();
print time.strftime('Started : %d %b %Y %H:%M:%S',start_t)
## imitate some work, let's sleep
time.sleep(5)
end_t = time.localtime();
print time.strftime('Ended : %d %b %Y %H:%M:%S',end_t)
## incase you have an unix timestamp
unix_timestamp = 1339074642
unix_t = time.localtime(1339074642)
print time.strftime('Unix TS : %d %b %Y %H:%M:%S',unix_t)
Here we have just touched the basics of date/time formatting, let the internet be your guide. Happy coding!!
Format Strings For strftime/strptime
• %a => Locale’s abbreviated weekday name.
• %A => Locale’s full weekday name.
• %b => Locale’s abbreviated month name.
• %B => Locale’s full month name.
• %c => Locale’s appropriate date and time representation.
• %d => Day of the month as a decimal number [01,31].
• %H => Hour (24-hour clock) as a decimal number [00,23].
• %I => Hour (12-hour clock) as a decimal number [01,12].
• %j => Day of the year as a decimal number [001,366].
• %m => Month as a decimal number [01,12].
• %M => Minute as a decimal number [00,59].
• %p => Locale’s equivalent of either AM or PM.
• %S => Second as a decimal number [00,61].
• %U => Week number of the year (Sunday as the first day of the week) as a decimal number [00,53]. All days in a new year preceding the first Sunday are considered to be in week 0.
• %w => Weekday as a decimal number [0(Sunday),6].
• %W => Week number of the year (Monday as the first day of the week) as a decimal number [00,53]. All days in a new year preceding the first Monday are considered to be in week 0.
• %x => Locale’s appropriate date representation.
• %X => Locale’s appropriate time representation.
• %y => Year without century as a decimal number [00,99].
• %Y => Year with century as a decimal number.
• %Z => Time zone name (no characters if no time zone exists).
• %% => A literal '%' character.
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About this Journal Submit a Manuscript Table of Contents
International Journal of Forestry Research
Volume 2012 (2012), Article ID 263953, 16 pages
doi:10.1155/2012/263953
Research Article
Structural Equation Modeling: Theory and Applications in Forest Management
1Department of Forest Engineering, Resources and Management, College of Forestry, Oregon State University, 204 Peavy Hall, Corvallis, OR 97331, USA
2Division of Forest Management, Department of Forest and Climate Change, Korea Forest Research Institute, 57 Hoegiro, Dongdaemun-gu, Seoul 130-712, Republic of Korea
Received 18 October 2011; Accepted 27 January 2012
Academic Editor: Hubert Sterba
Copyright © 2012 Tzeng Yih Lam and Douglas A. Maguire. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Fantasy Tales (UK) - Series Bibliography
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ISFDB Record Number: 26765
Bibliographic Comments: View/edit existing Series comment
Copyright (c) 1995-2011 Al von Ruff.
ISFDB Engine - Version 4.00 (04/24/06)
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User:Lorrie LeJeune
From OpenWetWare
Revision as of 13:29, 12 July 2008 by Lorrie LeJeune (Talk | contribs)
Jump to: navigation, search
Contents
Contact Info
Lorrie LeJeune (an artistic interpretation)
I'm the managing director of OpenWetWare.
Education
• 1994-1995, Graduate program (incomplete), Library and Information Science, University of Michigan
• 1982, BS, Animal and Veterinary Sciences, University of Maine
Professional and Research interests
• Web-based publishing models
• Disruptive technology
• Graphic Design, Illustration, Photography
Publications
• “The Role of the Scholarly Press in the Electronic Environment.” Paper presented at Literary Texts in an Electronic Age, the 31st Annual Clinic on Library Applications of Data Processing, University of Illinois at Urbana-Champaign, April 1994.
• "Before Its Time: The Internet Public Library." vol. 3, no. 2, The Journal of Electronic Publishing, December, 1997 (http://hdl.handle.net/2027/spo.3336451.0003.205)
• “What If Gutenberg Had a T-1 Connection?” Joseph Janes and Lorrie LeJeune. The Serials Librarian, ISSN: 0361-526X, Volume 36 Number 3/4, 1999. (Paper presented at the 13th Annual Conference of the North American Serials Interest Group, University of Colorado at Boulder, June 1998.)
• “Who Owns What? Intellectual Property, Copyright, and the Next Millennium.” Guest editor, volume 4, no. 3, The Journal of Electronic Publishing, March 1999 (http://hdl.handle.net/2027/spo.3336451.0004.301).
Short Bio
Lorrie LeJeune is Managing Director of OpenWetWare, an open-access web-based resource that promotes the sharing of information, know-how, and wisdom among researchers in biology & biological engineering. In previous professional incarnations Lorrie was a molecular biologist, an editor at O'Reilly Media, a program manager for mobile applications at Orange, and an illustrator of O'Reilly book covers. A B.S. in Animal and Veterinary Science helps her make those illustrations more realistic. You may contact her at lorrie at openwetware dot org.
Random nonsense
Construction of the Koch Institute for Integrative Cancer Research at MIT
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McKinney:Research
From OpenWetWare
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McKinney Lab, The Rockefeller University
About Us Lab Members Materials and Methods Lab Business Useful Links
"Following infection, the incubation period of tuberculosis ranges from a few weeks to a lifetime." This remark from a leading epidemiologist encapsulates the chief mystery and challenge of tuberculosis (TB): the ability of the pathogen to persist in the tissues indefinitely in the face of the host-immune response. Although in most cases infection is effectively contained by host immunity, failure to eliminate the “enemy within” means that TB can flare up again if the immune system is weakened. Nearly 2 billion individuals worldwide, including 10 to 15 million in the United States alone, are asymptomatically infected with Mycobacterium tuberculosis. Over the course of a lifetime, 100 to 200 million of these latent infections will reactivate and develop into full-blown TB — an enormous burden of future disease arising from infections that are already established. At present, virtually nothing is being done to reduce this vast and pervasive reservoir of vances that permit the direct analysis of M. tuberculosis in its natural environment, the mammalian lung. A long-term goal of our research is the development of new and more effective strategies for TB control. With 10 million new cases and 2 to 3 million deaths each year attributed to TB, the need could hardly be greater.
In Vivo Drug Tolerance of M. tuberculosis. One of the key obstacles to TB control is the inadequacy of current drug therapies. Effective treatment of TB requires administration of multiple drugs for at least six months, a regimen that many patients are unwilling or unable to complete without close supervision. Prophylactic therapy of latent TB, when the patient has no clinical signs or symptoms, is especially problematic. Why is TB so difficult to cure? Our recent studies indicate that during later stages of infection mycobacteria may be in the stationary phase of growth. This could explain the recalcitrance of in vivo mycobacteria to conventional antimicrobials, which target cellular growth processes such as DNA replication and cell wall biogenesis. If correct, then development of “better, faster, cheaper” therapies for TB will hinge on the elucidation of bacterial pathways that are essential for nondividing persistence in the lungs.
In Vivo Metabolism of Persistent Mycobacteria. The term “parasite” is derived from the Greek parasitos, meaning, “One who eats at another’s table.” This definition underscores a central but poorly understood feature of the parasitic lifestyle: the exploitation of the host as a substrate to fuel the pathogen’s metabolism and growth. We have undertaken a systematic analysis of the in vivo metabolism of M. tuberculosis. Our analysis to date indicates that mycobacteria switch to a diet of fatty acids at late stages of infection in vivo. This switch is triggered by the host-immune response, and mutant bacteria that cannot make the switch fail to persist. One of the pathways involved, the glyoxylate cycle, is an attractive target for drug development because it is absent in human cells. Current efforts are focused on elucidation of the host mechanism that forces the switch in bacterial metabolism and on development of glyoxylate cycle inhibitors as potential anti-TB drugs.
Mycobacterial Persistence Factors. TB infection is biphasic: an early acute phase of exponential bacterial growth in the lungs leads into a prolonged chronic phase in which bacterial numbers are stabilized by the emergent host-immune response. The ability to persist indefinitely in the lungs is the key feature of TB pathogenesis, yet little is known about the mechanisms involved. Our studies on the glyoxylate cycle indicate that genetically distinct pathways are required for early-stage growth and late-stage persistence. Building on this conceptual foundation, we have initiated genetic screens to identify other pathways that are specifically required for late-stage persistence of M. tuberculosis in the lungs. The “persistence factors” identified in these screens may also be attractive targets for development of novel anti-persistence drugs.
Immune Evasion. The ability to persist indefinitely in the lungs of healthy individuals indicates that M. tuberculosis has evolved effective mechanisms of defense against the onslaught of the immune response. We have initiated genetic screens to identify mycobacterial “defense factors” by comparing the growth and persistence of transposon-induced mutants in normal mice versus mice with specific immune deficiencies. These studies will elucidate the biology of the host-pathogen interface and could point the way to new strategies to enhance the immune system’s ability to kill persistent mycobacteria.
In Vivo Gene Expression of M. tuberculosis. We are currently analyzing M. tuberculosis gene expression in mouse and human tissues via quantitative real-time RT-PCR with fluorescent probes ("molecular beacons"). Our studies indicate that adaptation of M. tuberculosis to life in the lung involves induction of pathways for alternative carbon metabolism (including the glyoxylate cycle, fatty acid â-oxidation cycle and gluconeogenesis), iron scavenging and hypoxic stress response. We have uncovered significant differences in M. tuberculosis gene expression in mouse versus human lungs, which underscores the importance of studying the pathogenesis of infectious diseases in the natural host. Our current efforts are focused on the comparative analysis of M. tuberculosis gene expression in the lungs of humans with latent infection versus active disease. Our aim is to identify mycobacterial correlates of protection and pathogenesis, respectively, as a powerful new tool for evaluation of candidate TB vaccines.
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Main Page
From SmashWiki, the Super Smash Bros. wiki
This is an old revision of this page, as edited by Toomai (Talk | contribs) at 22:30, 2 April 2012. It may differ significantly from the current revision.
Jump to: navigation, search
Welcome to SmashWiki,
2,163 articles since July 2006
Featured Article
Like many games, there are many beta elements in the games of the Super Smash Bros. series. Beta elements come in two forms. The first form is the "pre-release" form, where early screenshots and trailers of a game showcase content that is eventually changed or removed in the final version of the game. The second form is the "unused data" form, where a game's final release contains unused information, such as unused textures, models, sounds, and so on; in some cases evidence can be found for scrapped stages or even characters. (more...)
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April 25, 2013
The eighth version of the Super Smash Bros. Brawl tier list has been released.
January 23, 2013
A Nintendo Direct presentation has confirmed that the next Smash Bros. game will appear in some capacity at E3 2013. This was later clarified via Twitter that the Nintendo 3DS and Wii U versions of the game would be shown.
January 13, 2013
Apex 2013 has concluded, with Salem, Armada, and Kikoushi winning Brawl, Melee, and SSB64 singles respectively, and Nairo/ADHD and Armada/Mew2King winning Brawl and Melee doubles respectively.
Did you know...
• ...that Zap Jyks produce a water sound on impact while Hydro Jyks have an electric one?
• ...that there are two types of Tail stickers: those that can only be worn by Star Fox characters, and those that can only be worn by characters of other series?
• ...that smash attacks in Melee launch themselves one frame before they can reach full charge?
• ...that according to the Project M backroom, Brawl can take up to two frames to process known inputs?
• ...that Charizard's up special shows fire but doesn't actually do any fire damage?
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Place:Northwood, Rockingham, New Hampshire, United States
Watchers
NameNorthwood
Alt namesOld Northwoodsource: AAA: Maine (1988)
TypeTown
Coordinates43.183°N 71.15°W
Located inRockingham, New Hampshire, United States
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Northwood is a town in Rockingham County, New Hampshire, United States. The population was 4,241 at the 2010 census.
History
the text in this section is copied from an article in Wikipedia
First settled in 1763, Northwood was incorporated on February 6, 1773 by Colonial Governor John Wentworth, when a large tract of land called "North Woods" was separated from Nottingham. Around 1800, the Portsmouth to Concord Turnpike was built, and the town began to prosper. Numerous taverns accommodated sledge and stage passengers. At one time, there were some twelve sawmills in the town, five of which were replaced by shoe factories during the latter half of the 19th century. By 1920, however, the last shoe factory had closed. More recently, the town has been a popular vacation spot, being home to nine lakes and many antique shops.
Four Northwood districts along Route 4 are considered historic sections of town. They are, from east to west, East Northwood, Northwood Ridge, Northwood Center and Northwood Narrows. The town is home to Coe-Brown Northwood Academy, founded in 1867.
Research Tips
This page uses content from the English Wikipedia. The original content was at Northwood, New Hampshire. The list of authors can be seen in the page history. As with WeRelate, the content of Wikipedia is available under the Creative Commons Attribution/Share-Alike License.
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OpenID Economics Centers on Relying Parties
Tim Bray has written a post saying that OpenID seems pretty useless and then points out some problems and possible solutions. The ironic thing is I can't argue with many of his points, but come to a very different conclusion.
I don't intend to respond point by point. He's spot on, for example, in what he says about TLS. While the OpenID spec tries to stay away from specific authentication mechanisms and has been subjected to considerable security analysis over the months, there's not reason not to require HTTP transport happen over TLS. In practice, however, I doubt any serious OpenID identity providers (IdPs) wouldn't use TLS.
That leads to the primary point. While it's true that anyone can throw up an OpenID server and start offering IdP services (Tim's "what's it mean" point), I think we'll see a limited set of trusted IdPs in practice. After all, AOL offers it now. If a few more of the big players offered with their services (come on, Yahoo! and Google), everyone on the 'Net would have an OpenID from a trustworthy IdP.
A few big players would be sufficient since what OpenID provides is authentication. Simple, plain-old authentication. When you accept an OpenID as a relying party, all you know is that the IdP is saying that the person in control of the password for that OpenID entered at their site. So, as long as you trust the IdP to verify the identity of the user, that's all you need.
What's the value? Just that. I don't have to do authentication and mess with password reset, and so on. If I were building a Web applications today, I'd certainly allow OpenID authentication and might even consider only accepting OpenID. There's not much time savings at build time, but it cuts the operational complexity. You still have to associate attributes with that identity and build authorizations around it.
OpenID 1.0 doesn't include attribute exchange, but OpenID 2.0 does. With attribute exchange, I might start caring which OpenID provider someone uses even more. Amazon might be able to send me attributes (with the user's permission) that Google can't. As a relying party, I might get more picky based on what I need to know.
Much of the talk is about user convenience and "single sign-on" (SSO) but that's not what will drive OpenID acceptance and use. For that to happen relying parties have to see value in (a) account management simplicity and (b) attribute exchange. The first is a reality today, the second will come.
With attribute exchange, some niche OpenID providers are likely to spin up based on specific attributes or features. But wait, if I've got multiple OpenIDs and IdPs, doesn't the negate the SSO value? Yes, but for the announcement that OpenID will interoperate with CardSpace. Now, I can have multiple OpenIDs and manage them in my card selector from my desktop, choosing which to send based on what I want to reveal and what the replying party needs.
So, I don't think OpenID is useless. To the contrary, I think there's real value to relying parties now and more to come.
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Wednesday, 16 April 2008
South Africa - new article on trade-mark use
The Comparative and International Law Journal of Southern Africa (CILSA for short) is not the first point of reference for trade-mark matters. However, the November 2007 issue (vol XL no 3), now out in print form, contains an article titled 'Limiting the trade-mark monopoly: the nature of infringing use' written by South Africa's most respected trade-mark academic, Professor Brian Rutherford from the department of Mercantile Law, UNISA. Non-subscribers can contact the journal editor at bothanj@unisa.ac.za for a pdf version of the article. The abstract reads as follows:
"Motivated by the concern of creating an unwarranted monopoly, recent decisions in Europe and South Africa have imported certain restrictions into the current trade-mark infringement provisions. These restrictions are intended to limit the infringement rights of trade-mark proprietors. This is particularly evident from the definition of infringing use adopted by the courts. This article compares the approaches adopted in Europe and South Africa. Like the British House of Lords, the South African Supreme Court of Appeal has adopted a narrow traditional approach in defining infringing use which is at variance with European jurisprudence and the TRIPS Agreement. Also in line with developments in the United Kingdom, onerous requirements for establishing trade-mark dilution have been imposed".
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Tell me more ×
Answers OnStartups is a question and answer site for entrepreneurs looking to start or run a new business. It's 100% free, no registration required.
I assume that some people on here have defined terms and conditions on their websites. How did you come to define it? Did you hire a lawyer to help draft one up or go online and find a template that you leveraged?
Any input is greatly appreciated.
share|improve this question
4 Answers
I'm a lawyer who works for a small start up. Before last summer, I had never drafted any T&C's, so I was in a similar position as you (albeit with a legal education).
I found 3-4 other companies that do similar things to mine, and used theirs to draft my own. If there were clauses that I wasn't sure about, then I used Google/Wikipedia to get a better understanding. This is what attorneys do, and you can do it yourself as well.
Better to paraphrase and mix and match so that you don't get accused of copyright infringement. This isn't a big risk as attorneys are constantly borrowing from existing documents and there isn't much creativity in drafting legal terms.
Since you are asking here, I'm assuming you don't have a lot of cash to spend on attorneys. That also means you don't have a lot to risk so it is probably ok if your T&C's are not perfect. If you start making money, then hire an attorney to look them over.
share|improve this answer
This is a little open ended, as a lot will determine what the terms and conditions cover, if we are talking about a brochure site for your company then their are loads of boiler templates which when combined with your privacy policy should work well enough.
If you are running a site with a free or paid for service and expect users to sign up and the TOC are for both the site and this service then it's a different ball game. There are lots of templates out their but it's worth running anything like that past a lawyer, especially if you are unsure of small changes from jurisdiction to jurisdiction. Also rarely are two services alike so changes will have to be made, again this is something you can do, or pass it to a lawyer to look at.
If you site is a pure E-commerce store then again their are hundreds of templates out there and assuming your TOS do not outline any after sales or warranty conditions should be straight forward and a boiler template should cover it, but again it comes back to any doubts or worries and assuming you have the money to consult a lawyer.
When I was first starting up I had a friend who had just completed law school and bartered for his time to help look over documents, if you know someone in a similar position even if you decide to go down the template route it's worth letting them read it. This is not a substitue for getting a lawyer to draft anything, but at least is better then having a sit around and dreaming up legalease sounding words.
n.b I am not a lawyer.
share|improve this answer
The folks at Automattic (makers of WordPress) have a very useful Terms of Service template here:
http://en.wordpress.com/tos/
It's available under a liberal Creative Commons license. We use it for status.net, in a slightly modified form.
share|improve this answer
There are several legal aspects to be considered to ensure that a website runs legally and securely, and that best interests of the business are served. From my experienceone needs to have is very diligently drafted legal documentation on your website. Your website shall have all the required disclaimers of regulating Acts and/or agencies, and in the right format.
The legal documentation for every website is specific depending on particular governing law and functionality. Mere copy paste of legal documentation can be a vulnerable threat to your web based business. You should also include clauses which most of them ignore like Notification Changes, Refund Policy etc.
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101 reputation
2
bio website meronymy.blogspot.com
location Oslo, Norway
age 41
visits member for 1 year, 3 months
seen Jan 30 '12 at 9:13
stats profile views 2
I'm a software developer at Webnodes ( http://www.webnodes.com ) with a ASP.Net CMS solution, and the Founder of Meronymy ( http://www.meronymy.com ).
All my code that I post here is distributed under a MIT license.
More about me here: http://about.me/ingehenriksen
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1. Skip to navigation
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Source link: http://archive.mises.org/10757/joseph-secretary-of-agriculture/
Joseph, Secretary of Agriculture
October 2, 2009 by
It occurred to Pharaoh, however, that a mind that had all the answers ought not to languish in Potiphar’s jail. So, on the very spot — confirmation by the Senate was quite unnecessary in those days — he appointed the surprised Joseph to be his secretary of agriculture. There being no Constitution to swear by, and no Bible to kiss, Pharaoh made the appointment stick by putting his own signet ring on Joseph’s hand and a solid gold chain around his neck. For lack of an automobile, an official chariot was assigned to the new dignitary. No doubt, though the chronicle does not record it, Joseph must have had a big office to work from, with a lot of assistants and secretaries, for mention is made of many overseers. FULL ARTICLE by Frank Chodorov
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Connexions
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You are here: Home » Content » Willie kom kuier - 02
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Name: Willie kom kuier - 02
ID: m26411
Language: English (en)
Subject: Humanities
License: Creative Commons Attribution License CC-BY 3.0
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Latest version: 1.1 (history)
First publication date: Jul 1, 2009 10:36 am -0500
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Wikia
UA:Bell Curve Rolls
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Revision as of 16:26, August 14, 2009 by Surgo (Talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
This material is published under the OGL
Contents
Bell Curve Rolls Edit
Here's perhaps the most fundamental variant to the d20 rules: Don't use a d20! Instead, roll 3d6 whenever you would roll a d20, applying bonuses and penalties normally. The possible results when rolling 3d6 (or any other multiple dice) form a bell curve- that is, a range of odds that favor average results much more than extreme results.
Rules for RollingEdit
This system requires several changes to how rolls are made.
Automatic successes and failures: Automatic successes (for attack rolls and saves) happen on a natural 18, and automatic failures on a natural 3. Neither occurs as often as in standard d20 (less than 1/2% of the time as opposed to 5% of the time).
Taking 20 and taking 10: You can't take 20 using the bell curve variant. Instead, you have two new options: You can take 16, which makes the task take ten times as long, or you can take 18, which makes the task take one hundred times as long. As with the rules for taking 20, you can only take 16 and take 18 when you have plenty of time, when you aren't distracted, and when the task carries no consequences for failure. For a check that normally requires a standard action, taking 16 uses up 1 minute and taking 18 uses up 10 minutes.
The rules for taking ten remain unchanged.
Threat range: Because it is no longer possible to roll a natural 19 or 20, the threat ranges of weapons change in the bell curve variant. Refer to the following table.
Table: Armor and Damage Reduction
Old threat range New threat range
20 16-18
19-20 15-18
18-20 14-18
17-20 14-18
15-20 13-18
With the bell curve variant, the narrowest threat range becomes slightly more narrow (4.6% rather than 5%) and the new 14-18 range (16%) falls between the old 18-20 and 17-20 ranges. But because the Improved Critical feat and the keen edge spell double threat ranges, characters still improve their weapons in every case, despite the flat spot on the table.
There's no table entry for a threat range of 16-20 because no combination of weapons, feats, and magic can attain it in the standard d20 rules.
Monster Challenge RatingsEdit
Any time creatures are encountered in groups of four or more, reduce their CR by 1. For example, a single troll is CR 5, and two trolls are CR 5 each (and thus a EL 7 encounter). But four trolls are only CR 4 each (making a EL 8 encounter).
Monsters with fractional CRs move down to the next lowest fraction when encountered in groups of four or more; the goblin (ordinarily CR1/2) becomes CR 1/3, for example.
The Luck DomainEdit
The granted power of the Luck domain changes, because simple rerolls aren't as useful in the bell curve variant as they are in the standard rules. When electing to reroll a standard result, a cleric with access to the Luck domain rolls 4d6 for the reroll (instead of 3d6), dropping the lowest die. For example, if you rolled 2, 5, 6, and 6, you would drop the 2 for a total of seventeen.
The Luck domain spells change as well, with auspicious odds replacing protection from energy at 3rd level, and mass auspicious odds replacing break enchantment at 5th level.
Behind the Curtain: Bell Curve Rolls Edit
In general, this variant leads to a grittier d20 game, because there will be far fewer very good or very bad rolls. Not only can you no longer roll 1, 2, 19, or 20, but most rolls will be clustered around the average of 10.5. With a d20, every result is equally likely; you have a 5% chance of rolling an 18 and a 5% chance of rolling a 10. With 3d6, there is only one possible combination that results in an 18 (three sixes, obviously), but there are twenty-four combinations that result in a 10. Players used to the thrill of rolling high and the agony of the natural 1 will get that feeling less often--but it may be more meaningful when it does happen. Good die rolls are a fundamental reward of the game, and it changes the character of the game when the rewards are somewhat stronger but much less frequent.
Game balance shifts subtly when you use the bell curve variant. Rolling 3d6 gives you a lot more average rolls, which favors the stronger side in a combat. And in a d20 game, that's almost always the PCs. Many monsters--especially low-CR monsters encountered in groups-- rely heavily on a lucky shot to damage the PCs. When rolling 3d6, those lucky shots are fewer and farther between. In a fair fight in which everyone rolls a 10, the PCs should win almost every time. The bell curve variant adheres more tightly to that average (which is the reason behind the reduction in CR for monsters encountered in groups.
Another subtle change to the game is that the bell curve variant rewards bonuses relatively more and die rolls relatively less, simply because the die roll is almost always within a few points of 10. A character's skill ranks, ability scores, and gear have a much bigger impact on successes and failures than they do in the standard d20 rules.
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RPi Expansion Boards
From eLinux.org
Revision as of 20:55, 23 June 2012 by Malcolmlear (Talk | contribs)
Jump to: navigation, search
Contents
Back to the Hub.
Hardware & Peripherals:
Hardware and Hardware History.
Low-level Peripherals and Expansion Boards.
Screens, Cases and Other Peripherals.
Introduction
On the Raspberry Pi, there are several connections which can be used for expansion:
• The Rpi GPIO (General Purpose Input/Output) pins are exposed, that means that expansion boards are able to talk directly to the CPU.
• The DSI connector will allow low-level interfacing with LCDs and other displays.
• The CSI connector will allow camera modules to be added in future.
Current expansion boards
GertBoard
main page: RPi Gertboard
This board is a buffer between your Rpi and the real world, use it to flash LEDs on and off, drive motors, run sensors and all that other fun stuff.[1]
rpi_serial
BitWizard has a Raspberrypi serial breakout board. It breaks out four serial buses from the GPIO port.
BitWizard then has a series SPI (or I2C) expansion boards that can be daisy-chained off the SPI (or I2C) buses of the expansion board. A virtually unlimited number of expansion boards can be connected. Expansion boards are available that drive a simple 16x2 text LCD, more general purpose IOs, servos, temperature sensors, relays, optocouplers etc.
Piface
Piface is simpler than the RPi Gertboard (it's aimed at less experienced users), but also intended to connect to PCs and Android to be platform agnostic
CJE/4D RTC
On 2nd January 2012, CJE/4D announced that they have a real-time clock (RTC) expansion board in the works: [1]
Pi-Wire
Pi-Wire Homelabs are developing options for connection of a 1-wire bus to the RaspberryPi. Boards include SPI breakout connections for future boards.
Slice of Pi
Slice of Pi Ciseco have produced a convienient small break out board for the Raspberry PI. XBee style connector for XRF / XBee / RN-XV / XBT / RF-BEE etc. Has the SPI and I2C pins on one standard 8 way header and the Raspberry PI's 8 general purpose I/O pins on another for easy access. Comes as a kit of parts that needs to be soldered. Construction is very easy and suitable for children with basic soldering skills.
GPIO isolated expansion/RTC
UT Electronics is developing a expansion board containing a fully isolated 16-I/O I2C GPIO expander and RTC, with extensive options for further expansion. C and Python libraries will be available at launch. The board will probably be sold as a kit, with SMT components already in place.
Buffer Board
Buffer Board How to make a Pi Buffer on Veroboard. Each of the 14 outputs can drive up to 500mA using a Darlington array.
PiDuino
Youtube video showing prototype board
Arduino Shield and Raspberry Pi
a little board with Arduino socket and Raspberry Pi socket you can power the boards with 12Volt or 5Volt http://www.progetti-hw-sw.it/raspberry.htm
Relay board and Raspberry Pi GPIO
a board with 8 relays and 8 input with a Raspberry Pi socket you can power the boards with 12Volt, the board has a DIN rail container http://www.progetti-hw-sw.it/raspberry.htm
Pi Plates
Announcement
Prototyping plate announcement
RPi Protoboard
RPi Protoboard is a simple prototype board for the Raspberry Pi
another link to the same project?
RPi "UserPort"
RPi UserPort is a digital and analogue I/O board for the Raspberry Pi. UserPort replicates the original BBC Micros digital User Port and Analogue Port but uses more modern components such as the MCP23S17 16-ch GPIO and MCP3204 4-ch 12-bit ADC.
RPi MIDI Breakout Board
RPi MIDI Breakout Board is a simple MIDI breakout board for the Raspberry Pi using the hardware UART from the RPi's expansion interface
RPi RS232 Breakout Board
RPi RS232 Breakout Board is a simple RS232 breakout board for the Raspberry Pi
Quick2Wire GPIO Expansion Board
Quick2Wire GPIO board and experimenters kit is an extension board for the Raspberry Pi that has level converters to allow the driving of TTL and real world devices such as LED's and switches. It will also provide an experimenters kit, a software framework and a number of tutorials.
Raspberry Pi IO Interface
forum thread showing 'paper mockup'. Another buffered IO expander.
Buzzberry Buzz-Board Interface
Buzzberry is a interface board enabling expansion using the Buzz-Board modular system designed primarily for educational use.
Ponte
PONTE initial post An arduino shield bridge from Omer and SKPang
aLaMode
“À la mode” is an Arduino clone specifically designed to interface with the Raspberry Pi. You can of course connect a standard Arduino to a Pi USB port using a cord, but when you want a turnkey solution, how about an Arduino compatible “plate” (shield) that fits right on top of the Raspberry Pi with direct access to GPIO port? The Linux side handles all of the displays, human interfaces, and number crunching. The low power Arduino compatible “à la mode” board handles sensors, servos/motors, and provides a highly accurate real time clock.
XBee ZB SMT Backpack
The Raspberry Pi XBee ZB SMT Backpack by bootc is a carrier board for Digi XBee ZB SMT modules. These are different to the normal XBee modules because they are surface mount and additionally can interface to a host using SPI as well as serial. The backpack also features 3 LEDs for status signals as well as two FTDI headers (one for the RPi and one for the XBee), as well as being able to host a 'normal' XBee module (though of course you can't use SPI with those).
References
1. http://www.raspberrypi.org/archives/411
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Murray Utah South Family History CenterEdit This Page
From FamilySearch Wiki
Revision as of 12:00, 15 April 2011 by Cottrells (Talk | contribs)
This article describes the services and resources available at a Family History Center, a branch facility of the Family History Library.
(Add a brief paragraph about your center here and the area it serves. Information in italics below is guidance for you and should be deleted as you fill out the page. Remove italics from other text by selecting the text and clicking the "I" box in the Toolbar above.)
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Center Resources
Collections
• Family History Library Catalog: This center has the ability to order any of the films and fiche available through the Family History Library Catalog.
• (List additional collections you have such as the types of books and microfilm you have on indefinite loan; though you will not want to list every single item you have. Just give visitors to this page a general idea of your resources.)
Databases and Software
• FHC Portal: This center has access to the Family History Center Portal page which gives free access in the center to premium family history software and websites that generally charge for subscriptions. (Note to FHC: Not all FHCs have access to this portal. If you do not, you will want to remove this entire bullet. If you do have access to it, just remove this text in italics.)
Hardware and Equipment
• (Include the resources you have to help individuals do their research - computers, microfilm readers, printers, etc. )
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For the half-year to 30 June 2013, the IPKat's regular team is supplemented by contributions from guest bloggers Stefano Barazza, Matthias Lamping and Jeff John Roberts.
Two of our regular Kats are currently on blogging sabbaticals. They are Birgit Clark and Catherine Lee.
Wednesday, 16 July 2003
NAMED AND SHAMED
The UK Patent Office, concerned by certain cases where the loser in inter partes trade mark opposition cases has failed to pay his share of the winner’s costs, has published a list of defaulting losing parties in an attempt to encourage them to pay up without the need for further legal action. The Registrar doesn’t actually have the power to enforce the cost orders but can impose security for costs on parties engaged in proceedings if he believes that they will not honour any costs orders made against them. A survey to investigate the extent of the unpaid costs problem has also been launched.
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Aug 212012
This is an article of mine, first published on Wazi
Every organization must monitor its infrastructure’s uptime and performance. While the popular Nagios application is a good general-purpose monitoring program that you can extend with plugins to handle just about any task, you may do even better by employing Cacti as a graphical front end to RRDTool‘s data logging and graphing functionality. Cacti was developed specifically to monitor and collect performance information, while Nagios is more oriented toward state changes, such as noting whether a daemon is up or down.
RRDTool stores all of the necessary information to create graphs and populate them with data in a MySQL database. Cacti provides templates to gather and show information such as system load (CPU, RAM, disks), users connected, MySQL load, and Apache load, all of which can affect the performance of your site.
Cacti’s front end is completely PHP-driven. It supports data gathering via different methods such as scripts in any language and SNMP.
Continue reading »
Oct 112011
I’m usually for the old school methods: go down to the terminal and get all the information you need from there, terminal don’t tells lies.
But i also understand that with the cheap price that i see around for the VPS more people are starting to use Linux VPS for their service, and a graphical dashboard can be really useful for many VPS owner.
In a former article i’ve wrote about 4 software that can help you in the management of your Linux server, today we’ll see a simple tool that can be used to know via your browser the status to all of your servers.
The software it’s Status2K
Continue reading »
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Thursday, January 28, 2010
Antizionism Blogs A Haven for Antisemites
I know that antizionists claim not to be antisemites.
But...
But their sites attract them nevertheless.
For example, here:-
"There's nothing magical about the 'success' of jews -- they're simply a highly organized and networked gang of thieves and murderers that have been perfecting their craft for over 2,000 years."
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ISISBio:Protocols/Sortase mediated ligation/Small molecule ligation
From OpenWetWare
< ISISBio:Protocols/Sortase mediated ligation(Difference between revisions)
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Current revision (06:13, 7 November 2008) (view source)
m
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*Target protein: 5 – 200 µM
*Target protein: 5 – 200 µM
*Ligation partner: 100 µM – 1 mM (at least 20-fold excess over protein)
*Ligation partner: 100 µM – 1 mM (at least 20-fold excess over protein)
-
*Sortase A: 50 nM (although sometimes poor yields can be overcome by higher concentrations see the [[ISISBio:Protocols/Sortase_mediated_ligation|main Sortase page]] for details.
+
*Sortase A: 50 nM (although sometimes poor yields can be overcome by higher concentrations see the [[ISISBio:Protocols/Sortase_mediated_ligation|main Sortase page]] for details).
==Procedure==
==Procedure==
Current revision
Contents
Overview
We [1] and others [2] have used Sortase to attach small molecules fluorophores to proteins but there is no reason why similar constructs shouldn't work for a very wide range of small molecule labels. Ligation of amino sugars has been demonstrated (using much higher Sortase concentrations than we generally do) [3] and other obvious possibilities include azides, alkynes, alkenes, biotin, and cysteine. We generally carry the reaction out overnight at room temperature and have not examined the effect of temperature extensively.
Design of the small molecule ligation partner
We have investigated the rate and yield of reaction for substrates of the form H-GGnK(Fluor)-OH which are straightforward to synthesise and relatively cheap to purchase from general peptide suppliers. We have observed no difference in rate of reaction or yield for n=1-3 and would therefore advise the use of substrates of the form H-GGK(Fluor)-OH on the grounds of ease and price. We have used fluorescein amine exclusively. Others have reported the use of similar constructs with three glycines and rhodamine but we see no reason why other fluorophores and other molecules should not work with two glycines. We recommend using as high a concentration of ligation partner as is feasible (or affordable) to obtain the highest yield.
Materials
• Sortase A
• LPETGG-tagged protein target
• Small molecule construct
• Sortase buffer (50 mM Tris-HCl, 150 mM NaCl, 5 mM CaCl2, pH 7.5)
Standard Ligation Conditions
• Target protein: 5 – 200 µM
• Ligation partner: 100 µM – 1 mM (at least 20-fold excess over protein)
• Sortase A: 50 nM (although sometimes poor yields can be overcome by higher concentrations see the main Sortase page for details).
Procedure
1. Mix reactants together and incubate overnight at room temperature. Yes, it really is that simple (see here for an example).
2. Run gel to confirm labeling reaction if appropriate
3. Purify product
Notes
The small molecule ligation partner can be readily removed by gel filtration and residual Sortase can be removed if required by gel filtration (if the sizes are sufficiently different) or nickel affinity chromatography. Remember the desired product is in the flow through.
The yield of desired product generally follows the ratio of protein to ligation partner. Reducing the concentration of ligation partner will therefore reduce the yield. It also tends to slightly increase the amount of hydrolysis product observed. Increasing the Sortase concentration will speed up the reaction but will also increase the amount of hydrolysis product. Reactions are probably complete in 4-6 hours depending on target protein concentration but we have found overnight incubation convenient.
References
Relevant papers and books
1. Cameron Neylon, Chemtools LaBLog, 29 August 2007 http://chemtools.chem.soton.ac.uk/projects/blog/blogs.php/bit_id/2709 [neylon07]
2. Popp MW, Antos JM, Grotenbreg GM, Spooner E, and Ploegh HL. . pmid:17891153. PubMed HubMed [popp07]
3. Samantaray S, Marathe U, Dasgupta S, Nandicoori VK, and Roy RP. . pmid:18229923. PubMed HubMed [samantaray08]
All Medline abstracts: PubMed HubMed
Contact
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User:TheLarry/Notebook/Larrys Notebook/2009/11/21
From OpenWetWare
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Generating Data Main project page
Previous entry Next entry
Creating a Trajectory
I have a pretty good way to make a trajectory now. The user can put his trajectory together piece wise. They can add a horizontal line, vertical line, or circle in any order they want. And make each one of those as long as they want. I can add more geometries to create more intricate trajectories like a slanted line, but for right now this can do what i want. This .vi can also calculate the distances between adjacent points as well. It does this through
So i have everything i need now to make any trajectory and then make a microtubule of a certain length move along it. I still have to worry about the width of the microtubule, but for right now i'll go with it being a line and get this working. Then i'll add width.
This works decent, but i have a hard time transitioning from the horizontal line to the circle. I think it is the abrupt change that does it. The points around the change from line to circle have a shorter length than all the other points. This might be ok to work with. i can take these points our or since i know the actual answers this can sill be used to show if the tracking software is working alright. So i'll just go ahead with this.
Here is a movie of the trajectory i made. I think everything is working well. I am happy with this. Now i have to take this image and send it through my convolution sub.vi and i think i'd have a good looking simulation of the movie we get.
oh wait i gotta get this width right first. Alright let me see how badly i can screw this up. hmm maybe i don't have to worry about screwing this up since the width of the microtubule is so small if keep the high res image pixel higher than the width of the microtubule i should be golden.
Maybe the next thing i gotta do is automate the convolution .vi. But i am getting tired so maybe i'll do that tomorrow.
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Quotation added by staff
Why not add this quote to your bookmarks?
Look for a long time at what pleases you, and a longer time at what pains you. Colette, Sidonie Gabrielle
This quote is about pleasure · Search on Google Books to find all references and sources for this quotation.
A bit about Colette, Sidonie Gabrielle ...
Colette was the pen name of the French novelist Sidonie-Gabrielle Colette (January 28, 1873 August 3, 1954).
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Quotes by Roosevelt, Theodore
We don't have a biography. Please consult wikipedia.
"In any moment of decision the best thing you can do is the right thing, the next best thing is the wrong thing, and the worst thing you can do is nothing."
Roosevelt, Theodore on decisions
16 fans of this quote
"I wish to preach, not the doctrine of ignoble ease, but the doctrine of the strenuous life."
Roosevelt, Theodore on dedication
3 fans of this quote
This quotation can be viewed in the context of a book
"At sometime in our lives a devil dwells within us, causes heartbreaks, confusion and troubles, then dies."
Roosevelt, Theodore on evil
7 fans of this quote
"The first requisite of a good citizen in this republic of ours is that he shall be able and willing to pull his weight."
Roosevelt, Theodore on duty
4 fans of this quote
"A man who has never gone to school may steal from a freight car; but if he has a university education, he may steal the whole railroad."
Roosevelt, Theodore on education
5 fans of this quote
"To educate a man in mind and not in morals is to educate a menace to society."
Roosevelt, Theodore on education
12 fans of this quote
"Freedom from effort in the present merely means that there has been effort stored up in the past."
Roosevelt, Theodore on effort
3 fans of this quote
"There has never yet been a man in our history who led a life of ease whose name is worth remembering."
Roosevelt, Theodore on effort
6 fans of this quote
"No man is above the law, and no man is below it."
Roosevelt, Theodore on equality
3 fans of this quote
"No man is justified in doing evil on the ground of expediency."
Roosevelt, Theodore on expediency
4 fans of this quote
"The boy who is going to make a great man must not make up his mind merely to overcome a thousand obstacles, but to win in spite of a thousand repulses and defeats."
Roosevelt, Theodore on failure
4 fans of this quote
"It is hard to fail, but it is worse never to have tried to succeed. In this life we get nothing save by effort."
Roosevelt, Theodore on failure
9 fans of this quote
This quotation can be viewed in the context of a book
"The things that will destroy America are prosperity-at-any-price, peace-at-any-price, safety-first instead of duty-first, the love of soft living, and the get-rich-quick theory of life."
Roosevelt, Theodore on america
9 fans of this quote
"The American people abhor a vacuum."
Roosevelt, Theodore on america
"The government is us; we are the government, you and I."
Roosevelt, Theodore on government
"I think there is only one quality worse than hardness of heart and that is softness of head."
Roosevelt, Theodore on art
3 fans of this quote
"Some men can live up to their loftiest ideals without ever going higher than a basement."
Roosevelt, Theodore on ideals and idealism
3 fans of this quote
"Every immigrant who comes here should be required within five years to learn English or leave the country."
Roosevelt, Theodore on immigration
6 fans of this quote
"It is only through labor and painful effort, by grim energy and resolute courage, that we move on to better things."
Roosevelt, Theodore on labor
8 fans of this quote
"It is difficult to make our material condition better by the best law, but it is easy enough to ruin it by bad laws."
Roosevelt, Theodore on law and lawyers
"People ask the difference between a leader and a boss. The leader works in the open, and the boss in covert. The leader leads, and the boss drives."
Roosevelt, Theodore on leadership
4 fans of this quote
"The best executive is the one who has sense enough to pick good men to do what he wants done, and self restraint to keep from meddling with them while they do it."
Roosevelt, Theodore on leadership
"It is better to be faithful than famous."
Roosevelt, Theodore on loyalty
12 fans of this quote
"The men with the muck-rake are often indispensable to the well-being of society, but only if they know when to stop raking the muck."
Roosevelt, Theodore on media
"All the resources we need are in the mind"
Roosevelt, Theodore on mind
"The man who makes no mistakes does not usually make anything"
Roosevelt, Theodore on mistakes
10 fans of this quote
"There can be no fifty-fifty Americanism in this country. There is room here for only 100 % Americanism, only for those who are Americans and nothing else."
Roosevelt, Theodore on multiculturalism
"Obedience of the law is demanded; not asked as a favor."
Roosevelt, Theodore on obedience
"I care not what others think of what I do, but I care very much about what I think of what I do! That is character!"
Roosevelt, Theodore on opinions
12 fans of this quote
"A man who is good enough to shed his blood for his country is good enough to be given a square deal afterwards. More than that no man is entitled to, and less than that no man shall have."
Roosevelt, Theodore on patriotism
5 fans of this quote
"The pacifist is as surely a traitor to his country and to humanity as is the most brutal wrongdoer."
Roosevelt, Theodore on peace
6 fans of this quote
"Peace is normally a great good, and normally it coincides with righteousness, but it is righteousness and not peace which should bind the conscience of a nation as it should bind the conscience of an individual; and neither a nation nor an individual can surrender conscience to another's keeping."
Roosevelt, Theodore on peace
"I am only an average man but, by George, I work harder at it than the average man."
Roosevelt, Theodore on averages
"The old parties are husks, with no real soul within either, divided on artificial lines, boss-ridden and privilege-controlled, each a jumble of incongruous elements, and neither daring to speak out wisely and fearlessly on what should be said on the vital issues of the day."
Roosevelt, Theodore on politics
"When they call the roll in the Senate, the senators do not know whether to answer present or not guilty."
Roosevelt, Theodore on politics
4 fans of this quote
"The most successful politician is he who says what everybody is thinking most often and in the loudest voice."
Roosevelt, Theodore on politics
"Speak softly and carry a big stick; you will go far."
Roosevelt, Theodore on power
8 fans of this quote
This quotation can be viewed in the context of a book
"No people is wholly civilized where a distinction is drawn between stealing an office and stealing a purse."
Roosevelt, Theodore on public office
But wait... There are more: 1, 2, 3 next
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Skip to content
Webicina iPhone app won the 2011 Medical App Awards!
One of my favourite blogs focusing on medical applications, Scrubdin, held the 2011 Medical App Awards and it’s a great pleasure to announce that the free Webicina iPhone app that curates medical social media resources won the Most Innovative App category. Thank you very much for the support! We will keep on improving the application.
Please see more information about the free Webicina iPhone app here.
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Help Wikitravel grow by contributing to an article! Learn how.
Difference between revisions of "Subic"
From Wikitravel
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(Please do not provide blog listings unless they are the only source of info for this activity.)
(updated listing The Pub Hotel Subic)
Line 183: Line 183:
*<sleep name="Palm Tree Resort" alt="" address="116 National Highway, Barrio Barretto, Olongapo City" directions="" phone="" url="http://www.palmtreesubic.com" checkin="2:00pm" checkout="12:00nn" price="Php2200.00" lat="" long="">Palm Tree Resort has sea view rooms and suites overlooking the mountains. Also has an in house restaurant that serves Filipino and English cuisines.</sleep>
*<sleep name="Palm Tree Resort" alt="" address="116 National Highway, Barrio Barretto, Olongapo City" directions="" phone="" url="http://www.palmtreesubic.com" checkin="2:00pm" checkout="12:00nn" price="Php2200.00" lat="" long="">Palm Tree Resort has sea view rooms and suites overlooking the mountains. Also has an in house restaurant that serves Filipino and English cuisines.</sleep>
*<sleep name="The Pub Hotel Subic" alt="" address="National Highway, Barrio Barretto" directions="" phone="" url="http://www.thepubhotel.com" checkin="1:00pm" checkout="11:00am" price="Php1,080.00" lat="" long="">The Pub is located right amidst the nightlife district of Barretto. Just seconds walk away from beachfront restaurants and bars as well as the famous GoGo bars of Subic.</sleep>
+
*<sleep name="The Pub Hotel Subic" alt="" address="National Highway, Barrio Barretto" directions="" phone="" url="http://www.thepubhotel.com" checkin="1:00pm" checkout="11:00am" price="Php1,500.00" lat="" long="">The Pub is located right amidst the nightlife district of Barretto. Just seconds walk away from beachfront restaurants and bars as well as the famous GoGo bars of Subic.</sleep>
*<sleep name="RK Hotel" alt="" address="SBIP Phase 1 Commercial Complex, Subic Bay Gateway Park Rizal Highway" directions="" phone="" url="http://www.rkhotelsubic.com" checkin="2:00pm" checkout="12:00nn" price="Php2500.00" lat="" long="">The hotel has 64 well-appointed rooms, private KTV rooms, a sports bar, swimming pool, conference and meeting facilities and its own Oriental Spa. The hotel's location is very accessible to guests as it is located near Duty Free shops, spas and restaurants that serve international cuisines.</sleep>
*<sleep name="RK Hotel" alt="" address="SBIP Phase 1 Commercial Complex, Subic Bay Gateway Park Rizal Highway" directions="" phone="" url="http://www.rkhotelsubic.com" checkin="2:00pm" checkout="12:00nn" price="Php2500.00" lat="" long="">The hotel has 64 well-appointed rooms, private KTV rooms, a sports bar, swimming pool, conference and meeting facilities and its own Oriental Spa. The hotel's location is very accessible to guests as it is located near Duty Free shops, spas and restaurants that serve international cuisines.</sleep>
Revision as of 13:21, 3 January 2013
This article or section does not match our manual of style or needs other editing. Please plunge forward, give it your attention and help it improve! Suggested fixes: None specified. Please use the article's talk page to ask questions if you are not sure why this tag was added and whether it is safe to remove it.
Subic is a sea side area on the western side of Luzon island in Zambales province within the region of Subic Bay. Subic Bay is a former US naval base that was converted into a beach town in the broader proximity of Manila. The main industry is the free port and the airport which is utilized by logistic companies.
Contents
Get in
• Subic Bay International Airport (SBIA) - The gateway to Subic Bay Freeport-, a modern, international airport with 10,000 sqm passenger terminal. It's capable of handling 700 passengers at any given time and works according to international standards. There are few regular flights to Subic other than random flights by South East Asian Airlines [1]. The airport used to be the Asian hub for FedEx - however, they have since moved their hub to China.
• Olongapo City - Surrounding Subic Bay is the city of Olongapo. This small city contains many transport routes to other Philippines destinations. Regular bus services run to Manila, IPA, Bagio, Clark and Angeles.
• Subic Bay Freeport (SBF) - It is 110 kilometers North of Manila, facing the South China Sea and is surrounded by Olongapo City and the towns of Subic and Morong. It is Northwest of the Bataan Peninsula and Southwest of the Zambales Province. It has long been recognized for its strategic location, being at the center of the fastest growing markets in the Philippines. It is at the hub of the region, and all major cities in Asia are within easy reach either by sea or by air. (3 to 4 days by sea, 2 to 3 hours by air). Aside from its strategic location, SBF has a deepwater seaport that is capable of handling the largest ships ever built, manifested when it once supported the mighty US 7th Fleet.
• Subic Bay Seaport - A major alternative port for importers and exporters in the Northern and Central Luzon areas of the country to decongest the Manila International Container Terminal. It has a total of 15 operational piers and wharves capable of servicing all kinds of sea vessels. Subic’s seaport and container handling facilities were recently enhanced with the operation of the Subic Bay International Container Terminal Services at the Sattler pier. The Freeport also has two operational port terminals: the fertilizer bulk terminal at the Boton Wharf and the grain bulk terminal at the Leyte Wharf.
Get around
• TAXI - Taxis are available at the main SBMA/SFZ gates with Olongapo. They can also be booked by telephone for collection anywhere inside Subic.
• JEEPNEYS - Jeepneys are not permitted to operate within Subic Freeport.
• TRIKES - Trikes are not permitted to operate within Subic Freeport
See
• Subic Bay Ocean Adventure [2] - See dolphins and tropical fish.
• Le Man's Go Kart - Beside Bicentennial Park, Rizal Highway, Subic Bay Freeport Zone, Zambales Tel No: (6347) 252-2272, Open from 10:00 A.M. to 7:00 P.M.
• Pamaulaklakin Trail, Pamulaklakin forest, Binictican heights (Taxe a taxi from SBMA to Pamulaklakin). 3 hours. There are very good guided treks in Pamulaklakin forest. 15 minutes taxi ride from Subic SBMA, there are 2 trails - for 30 minutes and for 3 hours. the trail takes you inside the Pamulaklakin forest, along the Pamulaklakin river. A great way to see the local fauna and flora - birds, medicinal plants,and nature. 300 Pesos.
Do
Scuba Diving
The tourism office for the area calls Subic Bay the “Pearl of the Orient” and much like a pearl inside an oyster, its true value is hidden unless you know where to look.
Scuba diving is incredibly popular throughout the Philippines and more international divers are arriving each year. The growth of diving in Subic Bay, whilst increasing, is doing so at a slower rate - so this area still remains a hidden gem, with unspoilt sites and lack of crowding.
Subic Bay offers some of the world's best shipwrecks, all within recreational diving depths, as well as tranquil coral and artificial reefs that explode with marine life. Unlike Coron, and other international wreck diving locations, where you ride for hours to get to a wreck site, the majority of Subic Bay dive sites are a quick 15 minutes boat trip from the dive centres.
The bay is a unique 'wreck heaven' because its sheltered waters allow calm year-round diving (except in the strongest Typhoons), with short duration transits to the dive sites and a fantastic collection of exceptionally well-preserved historical wrecks.
Just how many wrecks are there in Subic Bay and around its entrance? That is a very difficult question. Unlike Coron or Truk, whose wrecks occurred over a relatively short period, Subic’s WWII wrecks covered almost the entire war period. No less than 25 Japanese ships were reported sunk during the war years. Some of these may have been removed in the late fifties as salvage operations were done to open up the bay for shipping Additional ships were sunk after the war either as targets or victims of mother nature. It is widely believed that an additional ten large ships may lie within the Bay. The area is not limited to WWII wrecks, at the entrance to the bay alongside Grande Island, is the remains of the Spanish American war wreck San Quintin. Outside the bay in deep water lie the remains of a Spanish Galleon as well as a 16th century Chinese Junk (beyond diving range).
The eruption of Mount Pinatubo in 1991 did an enormous amount of damage to Luzon and the Zambales/Subic Bay area was very hard hit. A meter of ash covered the area including homes and business. Within days, a typhoon entered the area turning the ash into mud. Many homes and business collapse under the weight. One resident stated that the river looked just like the cement coming out of a cement mixer. A large percentage of the coral was killed lying under the ash.
When the Navy occupied the naval base at Subic, many of the wrecks were closed to diving. Divers however had the advantage of diving in water that was crystal clear with 40 or more meters of visibility on the wrecks that were open. The bay was the home of different varieties of sharks, dolphins, and turtles. While a few turtles still nest on the beaches the visibility, sharks and dolphins are no longer here. The visibility is returning slowly and the coral is recovering. Hopefully the turtles, sharks and dolphins will return in abundance also. More turtles and rays have been seen this year than last and the number of sharks just outside the bay also seems to be on the rise
In recent years, there have been increasingly more common spottings of Bull Sharks around the deeper wreck sites, along with Eagle Ray around the USS New York, LST and El Capitan... and Black Tip Reef Sharks around the outside of Grande Island.
Underwater Photographers have been reporting success with Macro critters, such as Harlequin Ghost Pipefish and many species of Nudibranch
The last few years have seen a dramatic growth in the number of dive operators in the Bay area. In 1998 there was only one fledgling full time operator at Subic - today there are more than 10. These dive operators serve a variety of scuba training agencies, including; PADI, SSI, ANDI, PSAI, BSAC and DSAT. They provide a collection of entry-level and specialist scuba training courses, including (of course!) basic and advanced/technical wreck diver training.
• Scuba Tech Philippines [[3]]runs PADI and TecRec technical courses [[4]] from a luxury dive boat based in Subic Freeport Zone. The instructor, Andy Davis[[5]], is a highly qualified and experienced UK-trained instructor with PADI, SSI, BSAC and DSAT TecRec. Daily scuba diving trips are offered to the wrecks and reefs of Subic Bay. These trips can be tailored to fulfil divers requirements at any level. Accomodation can be booked at any hotel inside SFZ, with pick-up/drop-off included.
• Boardwalk Divers is located on the free port so benefits from quick access to the wrecks. It is run be George AngDyPay an experienced TDI and PSAI technical rebreather instructor. Set up to cater to both recreational and technical divers it has quickly become the dive center of choice for most tech divers. Guding is done by local staff members who are all trained as divemasters and technical wreck guides. [[6]] Accommodation is at the nearby hotels - Herbie's Mansion, Boardwalk Inn and Mango Valley
• Johan’s on Baloy Long Beach, Barrio Barretto, Olongapo has very nice simple rooms to service it dive clients and their friends. Located on the beach you are just steps away from the beach to your rooms
• 2N2 dive center in Olongapo. This center with its hotel caters mostly to Korean Divers
• Inside the Subic Freeport, Vascos, a restaurant and hotel combination. They purport to be the most experienced wreck divers in the Philippines and have a museum (free entry) of artifacts to prove it.
• Ocean Adventure also has a dive center. Grande Island has just opened a dive center
Area Wrecks
• USS NEW YORK - A 120m-long hull. 27m of water between Alava Pier and the northern end of Cubi Point runway.
• EL CAPITAN - A 3,000-ton freighter, about 130m long that crashed down the mouth of Ilanin Bay.5m below the surface.
• SAN QUENTIN - The oldest known wreck in Subic, a wooden gunboat scuttled by the Spanish in 1898.
• LANDING SHIP TANK (LST) - Situated between Grande Island and the southern tip of the runway. 32m deep.
• ORYOKU MARU - Located 400m off Alava pier. 20m (60ft) deep.
• PATROL BOAT - In Triboa Bay at a depth of 20-25m (60-75ft).
• LANDING CRAFT UTILITY (LCU) - Triboa Bay. 5-20m (25-60ft).
Further details of Subic Bay Wreck Sites can be found at:
• Subic Bay and Its Wrecks by Scuba Tech Philippines [[7]]
Area Dive Shops
• Boardwalk Divers - The Boardwalk, Subic Bay Freeport - [[8]]
• Blue Rock Dive Center - Baloy Long Beach.
• Scuba Tech Philippines - Subic Bay Freeport - [[9]]
Dive Vacations
• Seahorse Tours & Souvenirs- Times Square Cinema Complex, CBD, SBFZ (6347) 252-5617 info@seahorsetours.com provides dive and vacation packages using the areas leading hotels and dive operators. [[10]]
Beach
• Kamayan beach - beach beside Ocean Adventure. Entrance fee: P275
Zoobic Safari
Zoobic Safari is one attraction you will find at Subic Bay Freeport's Forest Adventure Park. Embracing a 25 hectare land - local and foreign guests can expect an astonishing sight of diverse exotic animals roaming and frolicking in their natural habitat. It features a wide range of habitats present in the forest due to the terrain, presence of streams and fringing grasslands. These represent the major habitats for varied exotic animals featured in Zoobic Safari Forest Adventure Park.
Zoobic Safari has the following attractions to look forward namely:
The Zoobic Park - a Petting Zoo area in a walk through tropical jungle like were you can have a live interaction with deers, ostrich, albino carabao, bear, monkey, eagle, miniature horse, ducks and a lot more.
Savannah - A sanctuary of the wild that features a wide range of ostriches, potbellies, wild boars and guinea fowls.
Serpentarium - A real view of snakes, lizards, iguanas, turtles and a lot more cold blooded animals.
Honey Bee Farm - See how honey is produced by hard working bees.
Rodent World - An amazing collection of rodent animals. Be amaze in Mice Surprise trick in the area and watch guinea pigs being groomed in a Rodent Salon.
Egg-Ziting Story - An area showcasing the cycle of the eggs.
Animal Bone Museum - A collection of various real animal bones.
Close Encounter - An exciting close encounter (2 ft away) with Siberian and Bengala tigers and be a witness to their huge appetite while the tour guide feeds them.
Tiger Safari - A once in a lifetine adventure experience riding in a safari jeep were you will enter in a close fence structure and be fascinated to see the live tigers roaming around as they thrilled you with their vibrating appetite.
Zoobic Safari also has an educational show featuring live animals, jungle survival with Aetas and the newest Mini Moe Show were you can have fun as you see unique mini animals perform live!
Added attractions to the Croco Loco section is the guided tour which gives visitors a trek through an Aeta Village (Aetas are native Filipinos), a Hip-hop Bayawak (Bayawak is Filipino for Gecko) area and a view of the Garden of Adam which features an Aeta Adam.
One of the highlights of Croco Loco area is a brief stunt show of a man dressed as a chicken walking over the crocodiles in a small walkway above them.
The crocodiles section of the Safari is set to complement the other animal attractions in the25-hectare wildlife sanctuary which includes tigers, a serpentarium, ostriches and other exotic animals that can be viewed along with entertaining and informative animal shows presented by animal experts.
For more information, visit their website at [www.zoobic.com.ph]
Buy
Shopping Malls
Subic has several malls
Royal Subic: The biggest department store in Subic. They carry imported and local housewares, cooking items, and snacks. Royal Subic also carries branded clothes. Most of are surplus so they're actually cheaper. Has an extensive selection of cigarettes and perfumes.
Freeport Exchange: They are mostly the same as Royal Subic. However, they also carry some electronics (All are set for 220 volts). Freeport also carries Subic's largest supply of candy (but it's a close competition with Royal Subic)!
Pure Gold: Has recently (Early 2010)opened a huge warehouse type store with a very large selection of goods. Across the intersection from the Royal Subic.
Value City: Value City has a lot of things that other stores don't. They have a lot of quick snacks, and an extensive supply of cat food.
National Bookstore: Books, magazines, and a cafe. They are also very popular for getting school supplies.
American Hardware: A hardware stores that carries lots of useful things. All their products are imported from the United States. They have lots of items that are very rare in the Philippines. American Hardware also runs the only car wash in Subic Bay.
Bretto's: This is actually in Olongapo, not in Subic, but it's very useful. It is a meat shop. They sell lots of good meats, such as steaks, chicken saugage, and ground beef. Many FedEx people go there, as it is one of the few places that has imported US meat.They close at a early time at 11:00
Uncle Ed's: Uncle Ed's is a small convenience store in Binictican (where most FedEx people live). They have a lots of basic things and are useful if you suddenly run out of cold soft drinks, milk, or some other must-have item. Recently, they have gotten a lot of good sweets and candies, such as M&Ms, Dr. Pepper, Tootsie Rolls, and lots of other treats like that.Uncle eds is very nice store but they close at a early time, at 11:00
Island Souvenirs: Buy your Subic souvenir shirts in Seahorse Tours and Souvenirs. They very funky island shirts for as low as US $8.
Seahorse Tours & Souvenirs: you will find them located directly next to the cinema with ample of free parking in the front or the side parking lot.The majority of our items have been selected from livelihood programs and sole artist. Livelihood programs are projects originally sponsored by local government or non profit organizations with the intent of helping those in need to develop skills and a means to earn, to supplement their current income or in many cases to provide a means of support. We have found that many of the items produced as the results of these programs are of very high quality and we are proud of showcases these items.
Eat
There are several great locations for food from many cultures:
• Blue Rock resort. Good for western food. Great prices, quantity and quality.
• Texas Joe's House of Ribs, Watrerfront Rd, Subic Bay Freeport Zone, 047 252 3189, [11]. 11am -10pm. Authentic Smoked meats and ribs. Numerous different barbecue sauces. Attentive service
Drink
Sleep
• All Hands Beach Subic, All Hands Beach, San Bernardino Road, Subic Bay Freeport Zone, (+6347) 250-2270, [12]. All Hands Beach Resort in Subic offers air-conditioned beachfront rooms and cottages. Bamboo huts, function rooms and pavilions are also available for family, business or special events. Php3500.00.
• Arizona International Hotel , 47 National Highway, Barrio Barretto, Olongapo City, Tel 047 224 4557 or 4559, [13]. It is minutes away from Subic. Online reservation at best rates with instant confirmation starts at PHP 1,562.50+.
• Asiana Hotel, No. 48 Gordon Avenue, Barangay Asinan, Olongapo City, [14]. The hotel has a touch of Asian architecture and delicacies. Php1,200.00.
• Bayfront Hotel, Blk. 19 Lot 1 Moonbay, Marina Waterfront Road, Subic Bay Freeport Zone, Tel: 63-47 252-3148-49/1948 Fax Number: 63-47 252-2591, Email bayfront@subictel.com [15]. Mediterranean-inspired hotel with villa set-up. Clean, comfortable accommodations. Online reservation at best rates with instant confirmation starts at USD $51.
• Casablanca Hotel Subic, Lot 14 Agronaut Highway, Subic Bay Freeport Zone, [16]. Casablanca Hotel is a fully furnished condo-hotel that has a pool side bar, jacuzzi and restaurant that serves International cuisines. Php2100.
• City View Hotel, Magsaysay Drive, New Asinan, Olongapo City, +6347 2529978, [17]. Php1800.00.
• Court Meridian Hotel, Waterfront Road, SBMA, +63 (47) 252-2366, [18]. A/C rooms equipped with cable TV, private toilet and bath with hot and cold running water. Some of its facilities and services are business center, jetski, bar and restaurant. From USD 72.00.
• Elmolina Beach Resort, 135 National Highway, Barrio Barretto, [19]. The resort offers budget accommodation beachfront of Subic's calm beach. Activities like kayaking, banana boating, snorkeling and jetskiing can be enjoyed at Elmolina Beach Resort. Php2,100.00.
• Hotel Interpark, Bldg. 663 Dewey Ave. Corner Sta. Rita Road, Subic Bay Freeport Zone (one block from the Waterfront Road and the Oriental Paradise Casino), [20]. checkin: 2:00pm; checkout: 12:00nn. Php2500.00.
• Lighthouse Marina Resort, Moonbay Marina Complex Waterfront Road, CBD Subic Bay Freeport Zone, (047)252-9978, [21]. The Lighthouse Marina Resort is a three-floor, 34-room boutique hotel capped by a lighthouse.
• Ocean View Beach Resort, Lower Kalaklan, Olongapo City, [22]. checkin: 2:00pm; checkout: 12:00nn. Ocean View Beach Resort has complete amenities for beach outings and company events. It has 40 newly renovated rooms and a spacious conference facility. The beach is safe for swimming and water sport activities like, aqua bikes, jetski and banana boat all at a very affordable price. Php2,500.00.
• Olongapo Travel Lodge, Magsaysay Drive, Olongapo City, [23]. checkin: 14:00; checkout: 13:00. Olongapo Travel Lodge offers modern-designed rooms in a budget-friendly hotel. Php1,600.00.
• Palm Coast Inn, Baloy Long Beach, Bo. Barretto, [24]. checkin: 2:00pm; checkout: 12:00nn. Palm Coast Inn offers standard rooms overlooking the beach and mountains of Subic. Php1,199.00.
• Palm Tree Resort, 116 National Highway, Barrio Barretto, Olongapo City, [25]. checkin: 2:00pm; checkout: 12:00nn. Palm Tree Resort has sea view rooms and suites overlooking the mountains. Also has an in house restaurant that serves Filipino and English cuisines. Php2200.00.
• The Pub Hotel Subic, National Highway, Barrio Barretto, [26]. checkin: 1:00pm; checkout: 11:00am. The Pub is located right amidst the nightlife district of Barretto. Just seconds walk away from beachfront restaurants and bars as well as the famous GoGo bars of Subic. Php1,500.00.
• RK Hotel, SBIP Phase 1 Commercial Complex, Subic Bay Gateway Park Rizal Highway, [27]. checkin: 2:00pm; checkout: 12:00nn. The hotel has 64 well-appointed rooms, private KTV rooms, a sports bar, swimming pool, conference and meeting facilities and its own Oriental Spa. The hotel's location is very accessible to guests as it is located near Duty Free shops, spas and restaurants that serve international cuisines. Php2500.00.
• Sanjaha Inn, 64 Gordon Ave. New Asinan Olongapo City, [28]. checkin: 2:00pm; checkout: 12:00nn. Php1,500.00.
• Subic International Hotel, Labitan and Sta. Rita Roads, Subic Bay Freeport Zone, Tel +047-252-22-22 Fax +047-894-55-79, [29] This hotel used to be the US Naval Base's barracks. Rates start at around PHP2000/night.
• Subic Grand Seas Resort, 83 National Highway, Barrio Barretto, Olongapo City, +6347-222-8541, [30]. Offers 22 Deluxe rooms, all of which have an air-conditioning, an LCD television with cable connection, and a telephone with NDD and IDD accesses. Some of its amenities include an infinity and kiddie pools, and a massage service. Best rates on official website start at PHP 2,500.
• Subic Oceanview Hotel, 202 Purok 6, National Highway, Calapandayan, [31]. checkin: 2:00pm; checkout: 12:00nn. All the guest rooms are equipped with a work area. Php1800.00.
• Subic Park Hotel, Moonbay Marina, Waterfront Road, Subic Bay Freeport Zone, Tel +047-252-2092 +047-252-2093 +047-250-2039, [32] 30 comfortable rooms offer views of the bay and the forested mountains surrounding it. Online reservation at best rates with instant confirmation starts near US$33.
• Terrace Hotel, Blk 1 Lot 2 & 3 Moonbay Marina, Waterfront Road, Subic Bay Freeport Zone, +63 (47) 250-2730 to 32 (fax: +63 (47) 252-2733), [33]. Studio, Junior Deluxe and Executive, Terrace Suite all equipped with TV with cable channels, coffee/tea maker and mini-bar. It also has a business center, rooftop patio and swimming pool.
• Vista Marina Hotel and Resort Subic, Waterfront Road, Blk 3 Lot 2, Moonbay Marina Area, Subic Bay Freeport Zone, [34]. A Mediterranean inspired hotel situated along the beach.
• Win Hotel Olongapo, #27 18th St. Corner Brill St. West Bajac Bajac Olongapo City (at Victory Liner Terminal), [35]. checkin: 2:00pm; checkout: 12:00nn. New hotel. Rooms are cozy with warm lighting fitted with wooden furniture and modern decor. Php1600.00.
• Grand Hoyah Hotel, Lot Nos 5B and 6, Block B, Manila Ave., cor. Canal Rd. CBD Area, Subic Bay Freeport Zone, [36]. checkin: 2:00pm; checkout: 12:00nn. Grand Hoyah is a 3-star hotel located in the Central Business District of Subic Bay Freeport Zone. The hotel offers Deluxe accommodation in its Superior, Family Rooms and Suites.
• Sheavens Seafront Resort, Baloy Long Beach Bo. Baretto, Olongapo City, [37]. checkin: 1:00pm; checkout: 11:00am. Sheavens Seafront Resort has 45 modern hotel rooms. Choose from Standard, Deluxe and Family guestrooms overlooking Subic Bay. Php900.00.
• Boardwalk Inn, Bldg 664 Waterfront Road, Subic Bay Freeport Zone, [38]. checkin: 1:00pm; checkout: 12:00nn. Boardwalk Inn Subic is located along Waterfront Road at the heart of Subic Bay Freeport Zone's business district. The hotel is walking distance from the beachfront, restaurants, bars and nightlife of Subic Bay. Php1,950.00.
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Difference between revisions of "Talk:Chicago"
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(Lead needs more color)
(Lead needs more color)
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:"Color" is not more important than truth, and your edits were nothing but vandalism. Besides, if someone were to visit based on their love of "pubic art" and the "ambiguous sexuality" of Midwesterners and Subway Restaurant employees, they would likely be highly disappointed and they'd go home and tell their countrymen that Chicago is overrated and not worth the visit. [[User:ChubbyWimbus|ChubbyWimbus]] 04:24, 28 February 2011 (EST)
:"Color" is not more important than truth, and your edits were nothing but vandalism. Besides, if someone were to visit based on their love of "pubic art" and the "ambiguous sexuality" of Midwesterners and Subway Restaurant employees, they would likely be highly disappointed and they'd go home and tell their countrymen that Chicago is overrated and not worth the visit. [[User:ChubbyWimbus|ChubbyWimbus]] 04:24, 28 February 2011 (EST)
+
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I agree that truth is more important than color. But legitimate concerns about the lead's bombastic claims were repeatedly brought up and shouted down by people who said "we need color, your edits are boring." Some of the people round here think its dull writing if it doesn't have a bunch of meaningless color that isnt based on reality.
+
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Satire, not vandalism.
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We need to calm down the lead and bring it in line with the helpful, informativie, and interesting nature of the rest of this site. Not a "Chicago is awesome" banner.
Revision as of 20:12, 28 February 2011
How to help the Wikitravel Chicago project
The Chicago article is a showcase for Wikitravel. The coverage is extensive, perhaps more so than for any other city. Updating and refining existing content is still needed, but before adding new content check that the information is not already in the article, and that there aren't already some examples of what you are adding. We want to avoid a guide that is too bloated or crowded, and we don't need to list every hotel, bar or restaurant to have a excellent guide. In addition the maps are so saturated that it may be difficult to add further listings to them.
If you are seeking to help, check the to do list. We need help to keep information current, so if you have current knowledge of a section of town, please scan the appropriate district article for out of date information, e.g., listings for businesses that have closed, outdated contact information, CTA station closures, etc.
If there is something important that is omitted, feel free to raise it on the discussion page, if you have found a hidden gem in your Chicago travels, let us know about it.
But above all, please do join the effort to keep this the best travel guide to Chicago there ever was.
Contents
Archives
To Do List
Here's what I think we need:
• Itineraries for districts outside the city center
• Improved coverage of Little Village shopping
• Improved coverage of "do" activities in the Southwest Side
Suburbs
Many suburbs are covered on the Chicagoland page and have only one attraction of note. However, there are a few that deserve fuller coverage as a complement to the Chicago set of articles, and need work accordingly. Post 'em here (but only if you're willing to work on them).
Last updated by Peter Talk 04:04, 20 May 2009 (EDT)
Article status
lead
Re: [1], my guess is that the IP thought that the word "idea" was a little bland after using such evocative phrases as "truth of jazz" and "heart of comedy". (But at least it keeps the parallel construction, so I agree that it's better than having nothing there at all.) Is there a loftier noun that could be used to describe the skyscrapers? Engage a pun by saying "height of architecture" or something like that?
(On a related note, the lack of a descriptor before "blues" also rubs me the wrong way as it sounds clunky when it's followed by those "___ of ___" constructions.)
-- LtPowers 08:37, 5 January 2010 (EST)
It's the home of the blues? That's actually the adage from which the following metaphors are inspired.
I rather like "idea," and Marc's nicely built some continuity with that phrase elsewhere in the guide. If I were going to try and find fault with one of the descriptors, it would be "truth," but I think we should resist the urge to wikittack the few turns of phrases on site that aspire to "speak above a whisper." It's extremely easy to do, but I don't think we'll benefit from it. (Lest I be misunderstood, I'm not at all pointing fingers, just making a point.) --Peter Talk 14:49, 5 January 2010 (EST)
I was reading it as "is the home of the blues and [the home of] the truth of jazz" rather than "is the home of the blues and [is] the truth of jazz." Honestly, I don't even know what the latter would mean. =) As for "idea", it's fine if you like it; it just strikes me as more pedestrian than the abstractions that precede it. LtPowers 15:47, 5 January 2010 (EST)
Summer
Chicago's summers are not disgustingly hot. They are hot and humid at times. "Disgustingly hot" would be more identifiable with Phoenix, or pretty much any South Texas city or South Florida city, like Houston and Miami. I have been in Chicago in the summer when it was just 81 degrees, and I have been there when it was 91. But every day or every summer in Chicago is not like that, so by definition that does not make their summer's disgustingly hot. Phoenix, Miami, and Houston, however, ARE like that every day of the summer for every year. Therefore, their articles should have the term "disgustingly hot". This needs to be changed. —The preceding unsigned comment was added by 66.192.176.30 (talkcontribs)
I'm inclined to agree that it should be changed. The lake keeps things pretty nice for people used to far worse summers. The fact that swimming is a good cool off option makes it all the more an appealing part of the year from my perspective. (I can't believe, btw, that you are still pushing that taxi madness—you need to explore the city a bit more, my friend.) --Peter Talk 21:39, 12 January 2010 (EST)
The fact that this anonymous user keeps trying to insert false and frankly dangerous information about taxis casts aspersions over the worth of everything else he or she has to say. Nevertheless, while this article need not be married to the term "disgustingly hot" if there's a better descriptive, there is more to climate than 'degrees' — the reason all the old folks go to Phoenix is because it's a dry heat, cool in the shade, low humidity. And the argument that Chicago can't be called hot because other cities are hotter is absurd. If that's true, why would we describe Miami as hot when Mexico City is so much hotter? Why would we describe Mexico City as hot when Vientiane is so much hotter? Answer: because the articles are independent of each other. Gorilla Jones 23:13, 12 January 2010 (EST)
It should also be noted that the anonymous user has employed inaccurate terms above — the article does not say that "Chicago's summers are disgustingly hot." It says that "Many days in July and August are disgustingly hot." So the anonymous user has built an argument on a false premise and is arguing against a phrasing that does not actually exist. Gorilla Jones 23:21, 12 January 2010 (EST)
Hmm, you are correct as usual. I'm tempted to add a little non-weather-related plug for the summer in that section, though. Summer, especially late summer, is the one time of the year when I feel unambivalently happier to be in Chicago than anywhere else in the world. --Peter Talk 23:48, 12 January 2010 (EST)
First of all, I never insert false information. If you walk away with nothing else, at least walk away with that. I did not say Chicago cannot be called hot in summer. It can be called "hot and humid at times in the summer", that phrasing would be better. I said it shouldn't be called "disgustingly hot" because if you use that term, you have nowhere else to go when describing the summers of cities like Phoenix, Houston or Miami, which are actually "disgustingly hot" in the summer (dry heat or not for Phoenix).
And as far as the taxi situation, ok here we go: The article states "outside of the downtown, North Side, Near West, and Near South sides you will likely have greater difficulty hailing a taxi directly from the street". Well look at a map of the city of Chicago. All those aforementioned areas added together constitute roughly half of the city's land area! Then add to that several upper-class and middle-class neighborhoods on the South Side and Southwest like Hyde Park, Kenwood, Chatham, and Beverly, to name a few, where hailing taxis are easy too. Plus the upper and middle class sections of the Northwest Side and you technically have covered almost the entire city. Now of course, there will be several lower class areas where taxis themselves may not be as numerous in numbers, but when they do ride through the streets of those lower class areas, they still will sometimes stop if hailed. This is no different than New York City where taxis can be hailed, and are more numerous in Manhattan but less so in the Bronx, Queens, or Staten Island. New York City's article doesn't state "outside of Manhattan taxis may be more difficult to hail from the street", so there should be no reason Chicago's article should have wording stating its difficult to hail a cab outside what really is a large portion of Chicago. In fact, it may be easier to hail a cab in the entire city of Chicago versus the entire city of New York because taxis are freely hailed in about half of Chicago's land area, and in New York City taxis concentrate on Manhattan only, which is not half of New York City's land area. Chicago, New York City, and Washington D.C. are considered American cities where taxis can be hailed from the street. Sorry for the long reply, but you asked.
As usual, your arguments seem irreconcilable with reality as I understand it. I've made a map of the city (about 30, actually), you can view it here. What you are calling roughly half the city is actually less than a tenth of it... And did you miss my story on your talk page? To recap: taxis won't come pick you up even if you call in vast portions of the city! It has nothing to do with the "class" of the neighborhood, it's just a matter of fact that you won't see a taxi drive by in most of the city outside the center, even waiting half an hour on a main thoroughfare. And yes, that goes for Hyde Park and Beverly too. I'm really bewildered that you are still pushing this, and that you continue to edit war to try and reinsert it. --Peter Talk 22:44, 27 January 2010 (EST)
Indeed, it's wildly inaccurate to claim those areas constitute half or even a quarter of the city, which calls into question the writer's basic familiarity with the city. And, once again, there are presently no plans to describe Miami's weather in the Chicago article, just as there are no plans to describe Jakarta's weather in the Miami article, which would require us to describe Miami's weather as mild. The terminology has no relationship. I fully expect that a complete New York article would say that city has the best pizza in the nation. So does this one. Doesn't matter. Gorilla Jones 23:45, 27 January 2010 (EST)
If you are looking at your Chicago maps correctly, you will see that the downtown area, the North Side, Near West, and Near South sides added together do not constitute just a tenth of the city's land area. The Near North Side and the North Side stretch from Division all the way to the Howard border at the city's northern limits with Evanston. The Near South Side would go as far south as 35th Street and the Near West Side as far west as Western Ave. That entire land mass added together is not just a tenth of Chicago. Look again. An area that large doesn't deserve the terminology "outside the downtown, North Side, Near West, and Near South sides you may find it difficult to hail a cab" because, although that may be true, you are giving the reader an inaccurate perception of hailing cabs off the streets of Chicago. It is not hard to do; anyone in Chicago will tell you that. Look at it this way: New York City's article -doesn't- state "outside of Manhattan (or perhaps some areas of Brooklyn) you may find it difficult to hail a taxi off the street", although that statement is true. People who live in the Bronx, Staten Island, or Queens find it more difficult hailing a taxi off the streets than people in Manhattan. So if you want to keep that terminology in Chicago's article, New York's article should have the same terminology. If you didn't find it necessary to state it's harder to hail a cab off the streets in the Bronx, Staten Island, or Queens versus Manhattan, there was no need to put that type of terminology in Chicago's article when referring to the South or West Sides. Keep it consistent.
Good gracious man, that map is labeled. You can click on any of the individual district articles to view the district maps, and thus see that what you are stating is the opposite of what is fact. This discussion is surreal.
With regards to taxis, my inclination is to think that you haven't really spent any time in the areas you are talking about. You are just as likely to be able to hail a cab in Chatham (as you assert) as you are to find MLK Jr. Highway in NYC (as you invented). Statements like "several upper-class and middle-class neighborhoods on the South Side and Southwest like Hyde Park, Kenwood, Chatham, and Beverly, to name a few, where hailing taxis are easy too" make it very clear to me that you are making assertions about areas you know next to nothing about, and likely have never been to. --Peter Talk 17:21, 28 January 2010 (EST)
Point blank. It is not hard to hail a taxi off the streets of Chicago. In most American cities, you must call a taxi to come pick you up. Chicago and New York City are exceptions to that rule. But both cities have areas where it's easier to hail a cab and areas where it may be somewhat more difficult yet not impossible to hail a cab off the street. For Chicago, the easier areas are downtown, North Side, Near South, and Near West Sides. The harder areas in Chicago may be the West Side, and some parts of the South Side. In New York City, the easier area is Manhattan. The harder areas are the Bronx, Staten Island, and parts of Brooklyn and Queens. So if they both are comparable in that regard, my arguement is that when you read the Chicago article it gives the reader the impression that it's virtually impossible outside a small area, whereas the New York article doesn't give that impression, yet the same is true for both cities. That's what I'm saying.
I don't know why you persist in thinking the New York article is a model for this one, since that article is (generously) at 'usable' status, two levels below this one. (Also, nobody from Chicago gives a crap how New York does anything.) Nevertheless, I have 25 years of experience of not being able to hail a taxi off the street up by Howard Street or anywhere in the vicinity of it. So you're objectively wrong. Gorilla Jones
Lede (again)
I found the lede to this article to be misleading. Chicago is not the birthplace of jazz and the blues; those are from the South. Moreover, the local music scene isn't really the most important thing to the city's identity. My suggested rewrite was reverted; no particular objection to the content was specified. It is reproduced below. -- Beland 01:08, 18 May 2010 (EDT)
Chicago [2] is the hub of the American Midwest, its identity partly formed as a gateway to the agricultural heartland of the country, and partly as a teeming metropolis of cultural expression and innovation. Economically, it has thrived as a central North American transportation nexus, whether in the age of ships, railroads, or airplanes.
The city is easy to find — its picturesque skyline calls across the waters of Lake Michigan, a first impression that soon reveals world-class museums of art and science, miles of sandy beaches, huge parks and public art, and perhaps the finest downtown collection of modern architecture in the world.
Culturally, Chicago has become the adopted home of jazz and the blues, and a center of comedy and theater. It has shopping of an international caliber, while maintaining a local flair in architecture and food. The hustle and bustle of big city life have barely put a dent in real Midwestern friendliness.
What's a lede?--Burmesedays 01:15, 18 May 2010 (EDT)
Read back to the discussion above. Apparently the argument goes that "home of" does not equate to the "birthplace of". Apparently the blues, like a petulant teenager, has found its true home distant from its birth. --inas 01:26, 18 May 2010 (EDT)
That's... pretty boring, overall. The current version is interesting to read, whereas "teeming metropolis of cultural expression and innovation" feels like a jumble of buzzwords saying nothing about Chicago in particular. — D. Guillaime 01:33, 18 May 2010 (EDT)
wikipedia:wikt:lede#English defines "lede". It's a variant spelling of "lead" that is used only to refer to the opening section of a written work, like an encyclopedia article or a news article. And yes, I reverted Beland's contribution because it was dry and encyclopedic instead of lively travel writing. And because this is a star article, and reached star status with its current lede, I felt that any changes to the lede ought to be discussed here first, especially when they change the Tone so much. LtPowers 08:57, 18 May 2010 (EDT)
OK, here's another try, avoiding misleading claims (not the birthplace of jazz and the blues, meat packing is no longer a big industry) while trying to keep a livlier style. -- Beland 13:39, 19 May 2010 (EDT)
As the hub of the Midwest, Chicago [3] is easy to find — its picturesque skyline calls across the waters of Lake Michigan, a first impression that soon reveals world-class museums of art and science, miles of sandy beaches, huge parks and public art, and perhaps the finest downtown collection of historic and modern architecture in the world. Here, the age of railroads found its center and spawned a huge meatpacking industry; in more recent decades, airplanes have swooped in to connect the city to the world and carry its faith in social progress.
Known for its blues, jazz, comedy, theater, shopping, and fine dining, the hustle and bustle of life in America's "Second City" (a title now contested with Los Angeles) have barely put a dent in its genuine Midwestern friendliness.
I'm a little confused regarding what exactly is "misleding." The article neither claims Chicago is the birthplace of jazz or blues, nor that meat packing is currently a major industry.
Marc's version is one of the most dynamic intros we have on the site—it's about the last one I think would be worth much effort tinkering with, when there are so many lifeless "X is in Y" bits floating around. It's possible to quibble endlessly about originality in writing, especially in a collaborative wiki environment. But I think we should resist the urge to eye "the neck of any author who dares to speak above a whisper or write above a nursery rhyme," and instead focus on improving the vast quantities of legitimately poor writing on the site. --Peter Talk 14:01, 19 May 2010 (EDT)
Well, as a tourist visiting Chicago, I read that lede and I interpreted it as saying that Chicago was the birthplace of jazz and the blues. I had to do my own research before I was certain this was factually incorrect. I don't think this travel guide should sacrifice factual accuracy in the name of being "dynamic". I tried to fix only that part of the intro, but that change was also reverted. It was requested that I discuss the issue here, so that's what I'm doing. -- Beland 14:30, 20 May 2010 (EDT)
I just don't see what's misleading about calling it the Home of the Blues (and actually, it says nothing about it being the home, much less the birthplace of jazz). It's not a Wikitravel coinage—it's a well-known city slogan. And regardless, if I say I'm going "home," I mean to my house, not to a hospital in New York. Further down the article at Chicago#Jazz and blues, the process by which the blues came to live in Chicago is explained.
And you're most certainly not doing anything wrong in discussing it here. I just disagree with you ;) --Peter Talk 18:19, 20 May 2010 (EDT)
Well, I was personally misled, because I thought the article was claiming that Chicago was the birthplace of the blues and jazz. I'm sure it reads differently to people who live in Chicago vs. those who don't know anything about it. If it's a well-known city slogan, the article should make that clear to people who have never heard it, as in "Chicago calls itself 'The Home of the Blues'". -- Beland 15:12, 24 May 2010 (EDT)
Sometimes clarity and poetry are mutually exclusive. The minor negative effects of a misunderstanding (one which, frankly, I don't expect a large number of people to have) are not worth disrupting the flow of the lede, IMO. Is it really a big deal if you were momentarily confused about the true birthplace of the blues? The rest of the article makes it clear that the blues migrated from the South along with several other cultural elements. LtPowers 18:47, 24 May 2010 (EDT)
I stopped reading before I got to the full explanation, and so walked away from the article with the wrong impression. Isn't the whole point of Wikitravel to give people accurate information about the places they visit? After having a discussion on the road, I concluded that this article was simply wrong, which undermines the site's credibility. -- Beland 19:52, 23 June 2010 (EDT)
Sorry, but that's your mistake, not the article's. Home ≠ birthplace. If it did, we'd all live in hospitals. Gorilla Jones 20:04, 23 June 2010 (EDT)
Hyperbole in the lead
The lead sounds like it was written by the Chicago Tourism Bureau. It is not the "home of the blues," only electric or Chicago-style blues. I don't know what "the truth of jazz" means. New York has a stronger association with skyscrapers. It's midwestern friendliness is noted, so no need to insult other cities as surly in the next sentence. The first sentence should note that Chicago is the third biggest city in America and the capital of the midwest. The features of the city should be noted without sounding so cheesy. Hyperbole destroys an articles credibility. —The preceding comment was added by 67.52.80.198 (talkcontribs)
Yeah, and dry encyclopedic writing destroys an article's readability. I agree that "the truth of jazz" is a pretty meaningless phrase, but it sounds good and fits with what you'd find in any good travel article. LtPowers 13:30, 26 July 2010 (EDT)
"any good travel article" doesn't need to exagerate to be colorful. Look at the articles for New York, London, Paris, Tokyo, Los Angeles, or Berlin. They lead with the information a traveller would want, not meaningless praise. We can have a readable lead that people will like. There have been many changes, but the Chicago Tourism Bureau keeps changing it back.
FYI, a good half of the Chicago Tourism Bureau has moved to D.C., but does miss his 26th St style pizza at Connie's quite dearly. --Peter Talk 17:06, 15 August 2010 (EDT)
I just think it's a shame that the New York Tourism Bureau chooses to keep conducting itself like this. Gorilla Jones 23:33, 15 August 2010 (EDT)
You betray your bias. I was citing the other cities not to bring conflict, but to show that Chicago's lead is in no way typical. It is an off-putting, over-exciting lie. I'm sorry your "book" contains the hyperbole lead, but lets make this online article easier to read and use. We don't need Chicago-patriots screaming their cities praise. Travel is about putting prejudices aside. —The preceding unsigned comment was added by 67.52.80.198 (talkcontribs)
There clearly isn't any consensus to tone down the lead, so I've reverted the latest changes until there is some agreement. While I'd tend to agree that the current lede does stray a bit into hyperbole, trimming it down to cold, boring facts is IMHO going too far in the opposite direction. Wikitravel:Tone encourages lively writing, so given the choice between the current version or a stark recitation of fact I'd prefer the status quo. -- Ryan • (talk) • 17:35, 21 August 2010 (EDT)
The other cities cited were at guide status, while this was the first huge city star article. Just for fun, lets quote the top of Wikitravel:Tone right here:
Every dimwit editor who sees himself as the source of all dreary blanc-mange plain porridge unleavened literature, licks his guillotine and eyes the neck of any author who dares to speak above a whisper or write above a nursery rhyme. -Ray Bradbury
--Peter Talk 17:42, 21 August 2010 (EDT)
I agree. This whole article reads like a travel brochure. People don't go to wikitravel to be convinced to go to a place. They've already decided to go and want clear, no-nonsense information about everything city related. Great cities speak for themselves. —The preceding comment was added by 207.229.139.182 (talkcontribs)
Don't tell us what people come here for. I think everyone here would agree this may be the best article on the site. It is the article to which the rest of us aspire when writing our own articles. It has been turned into a book that has a perfect review score on Amazon and sells better than Frommer's Chicago and Chicago for Dummies. We are writing travel guides both for people who want to know where to go and what to do, as well as people who already know where they're going and what they're doing. We cater to both markets; deal with it. LtPowers 11:49, 31 January 2011 (EST)
Willis / Sears Tower
There have been numerous edits to the Chicago articles in the past year to change "Sears Tower" to "Willis Tower", most of which have been reverted. At some point "Willis Tower (formerly Sears Tower)" is going to be the most common name. If we aren't there yet, then "Sears Tower (officially Willis Tower)" might be a decent compromise that will stave off further well-meaning edits. I don't know Chicago well enough to know which is better, so can anyone provide some input so that those of us watching this article know what to do with edits to the tower's name? -- Ryan • (talk) • 10:52, 24 August 2010 (EDT)
I think it is important to call it both "Sears Tower" for historical recognition and "Willis Tower" for the sake of being completely up-to-date (and for interesting trivia). I agree that "Sears Tower (officially Willis Tower)" accomplishes this perfectly.
The name appears many places throughout the Chicago pages though, most notably in Architecture, Buildings, and Skydeck. I would suggest noting the name change only in its first appearances on the Architecture and Buildings sections to avoid unnecessary confusion. By the time someone navigates to the Skydeck listing hopefully it will already be apparent to them. --Jtesla16 11:48, 24 August 2010 (EDT)
I suppose that's a reasonable compromise; the edits I made earlier today were merely to enforce what I saw as the existing consensus, that the building is still called the Sears Tower. I don't claim to be an expert. LtPowers 15:37, 24 August 2010 (EDT)
There is an infobox explaining the name change in the main article, but I think it would be fine to put the parenthetical after the first mention in the architecture section, for anyone who is confused, and missed the infobox. It's anecdotal, of course, but I was talking about the Sears Tower today (comparing it to the height of the ridiculously high Burj Khalifa) with people who neither familiar with Chicago nor terribly interested in skyscrapers or architecture, and it never even crossed my mind or theirs to refer to it as anything else.
I don't think that the Willis name is catching on, nor do I think it will, as the Sears Tower, unlike, say, Chicago's Standard Oil Building, is an icon with worldwide name recognition. Similarly, if the Eiffel Tower was whored out under corporate naming rights as the GazProm Tower, people would keep on calling it the Eiffel Tower. The notable exception, of course, is Wikipedia, where I'd say they are violating their own policies, by asserting without much evidential basis that Willis will become the more widespread usage. --Peter Talk 16:40, 24 August 2010 (EDT)
This edit to the Skyline guide, as well as one to the USA article, are actually what prompted the discussion, since I've seen such edits reverted and was curious whether we had an agreement on this. It sounds like the parenthetical is a decent compromise to ward off those trying to "fix" the name. As to "Sears" vs "Willis", it sounds very similar to when San Francisco tried to claim that "Candlestick Park" was actually "3Com Park" or "Monster.com Park" - aside from the guys in the broadcast booth I can't recall ever hearing anyone utter the new names, and if they had the scorn directed in their direction would have been fast and heavy. It got to the point that in 2004 there was actually a ballot measure passed to prevent the city from trying to rename the park again. -- Ryan • (talk) • 16:50, 24 August 2010 (EDT)
I'm not sure what policies Wikipedia is violating by calling their article wikipedia:Willis Tower. They have wikipedia:WP:COMMONNAME, of course, but it's my opinion that the plainest reading of it doesn't necessarily mean "what do most people on the street call it", especially for things that do have official names. Most of the most reliable sources -- such as news articles and official sources -- will call it the Willis Tower, so that's a perfectly reasonable name for the article's title. (Our purposes, of course, are different; in our case, we definitely should prefer what most people call the building, so that travelers can better find it.) LtPowers 17:03, 24 August 2010 (EDT)
I'd be happy to wager that most official sources and news articles still call it the Sears Tower. --Peter Talk 17:05, 24 August 2010 (EDT)
I'm fine with 'Sears Tower (officially Willis Tower)' at the first mention. I spoke to a Chicago Architecture Foundation docent recently, and he said that they refer to it as the Sears Tower on their tours, but usually include a brief (and derisive) reference to Willis. As for Wikipedia, they had the name change in place the day the contract called for it, before any meaningful reading of wikipedia:WP:COMMONNAME had been met. To be fair, though, it's obvious from their talk page that it was a small group of users who rammed it through, not the result of any consensus. Gorilla Jones 18:38, 24 August 2010 (EDT)
Bus table
I'm moving this here for discussion — I'm not sure we should devote this much space to bus transit between Chicago and a scant two cities. Gorilla Jones 18:20, 26 September 2010 (EDT)
A summary of bus fares to Milwaukee and Minneapolis frequencies and services including the lowest internet fare, the walk-up ticket price and how often the buses run:
Milwaukee lowest Milwaukee walkup Milwaukee frequency Minneapolis lowest Minneapolis walkup Minneapolis frequency wifi 110v outlets
Amtrak² $22 $22 7x day $56 $56-$74 1x day No Yes
Greyhound $6 $16 8x day $27 $65 5x day No No
Ind. Trails ? ? 1x day Yes Yes
Megabus $1 $20³ 4x day $1 $24³ 3-4x day Yes Some
Wisconsin $26 $26 14x day No No
²Train. AAA, ISIC, SA, Senior (walk-up) discounts: Milwaukee $18, Minneapolis from $47. ³Tickets must be purchased via internet or telephone($3 fee).
Coyotes downtown?
Not sure whether or where this might fit it in the article. Seemed worth posting, though: http://blogs.discovermagazine.com/discoblog/2010/11/16/let-loose-the-coyotes-chicago-embraces-rat-hunting-predators/ Pashley 05:37, 25 November 2010 (EST)
Heh, that article mentions "nuisance problems, like mice, rats, and rabbits." Chicago does have an unusually large number of weird nocturnal urban bunnies, but I never thought of them as a nuisance. --Peter Talk 11:27, 25 November 2010 (EST)
Lead needs more color
The lead was so boring before. Everyone knows that blues and jazz are centered in Chicago, that people are super-friendly there unlike every other city that size, and that there is days weeks and months of stuff to see in Chicago.
But there might be some foreigners reading this and we need to convince them to come to Chicago! We should add more color to the lead. I added some real colorful stuff. It's not all true, mind you, but color is more important than truth. Chicago!
"Color" is not more important than truth, and your edits were nothing but vandalism. Besides, if someone were to visit based on their love of "pubic art" and the "ambiguous sexuality" of Midwesterners and Subway Restaurant employees, they would likely be highly disappointed and they'd go home and tell their countrymen that Chicago is overrated and not worth the visit. ChubbyWimbus 04:24, 28 February 2011 (EST)
I agree that truth is more important than color. But legitimate concerns about the lead's bombastic claims were repeatedly brought up and shouted down by people who said "we need color, your edits are boring." Some of the people round here think its dull writing if it doesn't have a bunch of meaningless color that isnt based on reality.
Satire, not vandalism.
We need to calm down the lead and bring it in line with the helpful, informativie, and interesting nature of the rest of this site. Not a "Chicago is awesome" banner.
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Number of dwelling units and value of residential buildings (houses and other residential), value of alterations and additions to residential buildings and value of non-residential building by class of building (eg. hotels, offices, etc.),for private and public sectors, stage of construction (commenced, under construction, completed), value of work done during period and value of work yet to be done. Number of new houses by class of builder. Seasonally adjusted series show number of dwelling units commenced and completed and value of work done. Value of work commenced and work done at average 1989-90 prices.
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CONTENTS
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Migration in context
Net overseas migration (NOM)
Australia's diverse population
Interstate migration
Household mobility in Australia
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International comparison
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Australia's Diverse Population
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History of overseas-born in Australia
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
6250.0 - Characteristics of Recent Migrants, Australia, Nov 2010 Quality Declaration
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 24/05/2011
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Research article
Socio-economic and lifestyle factors associated with overweight in Flemish adult men and women
Nathalie Duvigneaud1*, Katrien Wijndaele2, Lynn Matton3, Peter Deriemaeker1, Renaat Philippaerts2, Johan Lefevre3, Martine Thomis3 and William Duquet1
Author Affiliations
1 Department of Human Biometry and Biomechanics, Faculty of Physical Education and Physical Therapy, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussel, Belgium
2 Department of Movement and Sports Sciences, Ghent University, Watersportlaan 2, B-9000 Gent, Belgium
3 Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, K.U.Leuven, Tervuursevest 101, B-3001 Leuven, Belgium
For all author emails, please log on.
BMC Public Health 2007, 7:23 doi:10.1186/1471-2458-7-23
Published: 26 February 2007
Abstract
Background
Changes in lifestyles and in the environment over the last decades are probably the most important cause of the overweight epidemic, but the findings are inconsistent among studies. The purpose of this study was to investigate the association of several socio-economic and lifestyle factors with overweight in Flemish adults, using BMI ≥ 25 kg/m2, waist circumference (WC) ≥ 94 cm (men) or ≥ 80 cm (women) and the combination of BMI and WC for identifying overweight.
Methods
This cross-sectional epidemiological study was conducted by the Flemish Policy Research Centre Sport, Physical Activity and Health between October 2002 and February 2004 in 46 Flemish communities. A total of 4903 Flemish adults (2595 men and 2308 women), aged 18 to 75 years, from a population-based random sample were included in the analysis. Body weight, height and WC were measured, and socio-economic and lifestyle factors were reported by means of validated questionnaires.
Results
The results of the logistic regressions revealed that age is positively associated with overweight in both genders. Alcohol consumption is associated with overweight only in men. Men smoking in the past and watching TV >11 h/week have significantly higher OR's for overweight, while men who participate in health related sports >4 h/week have significantly lower OR's for overweight. In women, watching TV >9 h/week was positively associated with overweight. Women who are current smokers or participate in health related sports >2.5 h/week or with a higher educational level have significantly lower odds for overweight. Different results are observed between the first (BMI) and the second model (WC) in both genders. In men, the models differ for education and health related sports, while in women they differ for smoking status and leisure time physical activity.
Conclusion
The present study confirms the contention that overweight is a multifactorial problem. Age and TV viewing are positively associated with overweight, while educational level and health related sports are negatively related to overweight in both genders. In men, alcohol consumption and smoking in the past are also among the lifestyle factors associated with overweight. This study also indicates that BMI and WC do not have the same discriminative function regarding different lifestyle factors.
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Personal Information
Username: lonelybiz
User Stats
Joined: 2012-08-29
Submitted Stories: 100
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Published Votes: 6
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"url": "www.globalsiteplans.com/environmental-non-profit/the-environmental-justice-movement-in-sunset-park-brooklyn-new-york/",
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March 12 2012
The Environmental Justice Movement in Sunset Park, Brooklyn, New York
Here in Sunset Park, Brooklyn, we have 200,000 cars a day going through the Gowanus Expressway. Our community complains about asthma, cancer, respiratory disease … but the excuse for neglecting us is that it is too expensive to mitigate”
-Elizabeth Yeampierre, Executive Director of the Labor/Community Strategy Center
Elizabeth Yeampierre’s words highlight a number of the environmental justice issues that burden the residents of Sunset Park, Brooklyn in New York and how these problems are linked to the the legacy of industrial uses in the area. Community-based organizations and environmental non-profits like the New York City Environmental Justice Alliance (NYC-EJ) have proposed innovative solutions encourage the sustainability of Sunset Park’s waterfront and inland areas.
Sunset Park contains zones called Significant Maritime and Industrial Areas (SMIA’s) — zoning distinctions which are designed to encourage the clustering or concentration of heavy industrial and polluting infrastructure uses. There are only six SMIA’s in New York City (in the South Bronx, Sunset Park, Red Hook, Newtown Creek, Brooklyn Navy Yard & North Shore of Staten Island) — all located in predominantly low-income communities of color. This cluster of industrial uses combines with Sunset Park’s proximity to the Gowanus Expressway to pose serious health risks to the workers and residents of Sunset Park.
In 2010, NYC-EJ launched its Waterfront Justice Project to encourage city officials, architects, engineers, and urban planners to focus attention on the decontamination of New York City’s SMIA areas. Further, as the project states, “In the event of flooding, sea level rise, hurricanes and storm surge, toxic materials in the water will migrate to other parts of the waterfront and vast acreage upland.”
The Waterfront Justice Project proposes a number of potentially sustainable solutions including the prohibition of open chemicals along the water’s edge and requiring that waterfront industrial facilities be equipped to handle storm surge.
Many towns and municipalities contain cluster industrial uses along the waterfront.How have similar issues been successfully addressed in other areas?
Credits: Images and data linked to sources.
Christine Camilleri
Christine Devon Camilleri blogged for the GRID from October 2011 to May 2012. She is a Graduate student studying City and Regional Planning at Pratt Institute in Brooklyn, New York. She also holds a B.S. in Human Development from Cornell University. She has lived in New York City for the majority of her life, and currently resides in Brooklyn, N.Y. Prior to joining Global Site Plans she worked as a grassroots political organizer. She is especially interested in New York City’s post-industrial waterfronts and the implications of participatory planning processes for community development initiatives.
More Posts - Website - Twitter - Facebook
This entry was posted on Monday, March 12th, 2012 at 2:36 pm and is filed under Community/Economic Development, Environment, Environmental Non-Profit, Infrastructure, Land Use, Social/Demographics. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.
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New Bing "Disavow Links" tools
Invasive contributor
30Jun2012,12:30 #1
There is much discussion going on about Google's proposed tool to disavow links, but Bing is a step ahead and has already launched theirs.
Sign into Bing Webmaster Tools, click on the "configure my site site" tab and then select
"Disavow Links".
There are options to discount links from a domain, a directory or a page. All you need to do is indicate which you want, and then enter the url and click "Disavow".
I feel sure that Google will now follow with their own tool very soon.
Go4Expert Founder
30Jun2012,12:42 #2
I am sure Google will not follow that because it would mean they are following Bing. Google has to come up with something better than that.
Actually I think with announcement of Google Paid Inclusions its high time for Bing anyways.
I am actively looking into Bing optimization because I always believe it is Google only who can de-thrown Google and they are stepping towards de-throwning themselves
Invasive contributor
30Jun2012,12:57 #3
Sorry, when I said Google would follow I did not mean with exactly the same thing but with their own version of a disavow tool. I could have worded it better.
I agree completely that if Google are to be overtaken it will be by their own doing. They have moved so far away from the original concept and at some point users will have had enough and will look for something offering simpler organic search results (as was Google's original intent).
Go4Expert Founder
30Jun2012,13:21 #4
Bing I think has a long way to make search results relevant because at times Bing is not able to rank official sites above the other spammy sites.
See http://imtips.co/google-vs-bing.html
Invasive contributor
30Jun2012,13:40 #5
Your article makes some good points, not least that it is users who decide the popularity of an SE not webmasters, and that Bing is not delivering the best possible results either.
But I do feel that Bing's apparent willingness to work more openly with webmasters may provide the opportunity to help improve the results situation.
Go4Expert Founder
30Jun2012,13:56 #6
Yes and that is where Google rules. No matter how badly it treats webmasters, they do good to users who uses them. As a webmaster you have to accept that fact as well.
Bing does not drive lot of traffic to websites and so webmaster's are not very keen on looking into Bing. If I look at June 1 2011 to June 30 2012 for Go4Expert, the stats are as follows.
• google / organic - 84.08%
• (direct) / (none) - 10.26%
• bing / organic - 0.64%
And if I look for only June 2012, I see that ratio as 0.46% only which does not reveal much but I conclude is traffic from Bing is not picking up either and so it does not excite me to visit Bing Webmaster central either.
Invasive contributor
30Jun2012,14:40 #7
The problem with stats are that they are site specific, and although my Bing traffic is relatively low, it is still there.
Over the same period, 70% of my traffic came from search, 18% by referral and 12% was direct.
Looking at the search traffic, 87.23% was from Google, 4.43 Yahoo and 4.26 was Bing (previous month Bing was 4.03).
So while I fully appreciate that as far as Go4expert is concerned Bing is insignificant, it isn't necessarily so across the board.
A further consideration is that my total monthly traffic would only represent a small percentage of that which visits this forum, but e.g. I come here on a regular basis and am involved in real estate, and others from different fields will also visit because it has a fairly wide appeal. But there is no real reason for anyone to go to a site which features property for sale in a small town in a foreign country unless they have a specific interest in buying or selling real estate there.
What I mean is that even one visit can be significant for me, because it could result in my selling a home to someone, and I do not need to sell very many each year to cover the bills.
Go4Expert Founder
30Jun2012,18:48 #8
No I still think that Bing traffic is valuable because you may have conversions but what I meant is Google still enjoys large % of search volume and so Webmasters don't get good percentage of Bing traffic.
Something to look at:
from http://www.seobook.com/meta-thoughts
Invasive contributor
30Jun2012,18:57 #9
Very good
shabbir likes this
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Bibliography: Robur the Conqueror (Part 1 of 2)
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Title: Robur the Conqueror (Part 1 of 2)
Author: Paul
Year: 1927
Type: INTERIORART
ISFDB Record Number: 1349603
User Rating: This title has fewer than 5 votes. VOTE
Current Tags: None Add Tags
Publications:
Copyright (c) 1995-2011 Al von Ruff.
ISFDB Engine - Version 4.00 (04/24/06)
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