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Does Google Use Theming to Group Together Similar Sites?
Jan 28, 2008 • 9:49 am | (1) by | Filed Under Google Search Engine Optimization
A HighRankings Forum thread discusses the possibility that Google themes sites. That is, Google groups sites together because of the relevancy of the link. So, for example, if you got 300 links to your blue widget site from a bunch of humor sites, wouldn't Google think that the blue widget site is actually about humor (and not so much about blue widgets)?
If you do a Google search for related:www.mysite.com and find similar sites, wouldn't that be theming?
As Randy says, "[I]t's more than just about the words on the page. You'd also need to factor a broader range of linking relationships between multiple sites into the equation."
Ian McAnerin mentions that the related: search operator doesn't really theme sites as we'd expect. It's based on the type of backlinks received.
However, in the end, people agree that some sort of theming exists:
I think Google does actually Theme sites. This may split a site as covering a number of related themes.
The discussion spans three pages (so far) and there appears to be no end in sight. What are your thoughts on Google's "theming?" Share your thoughts at HighRankings Forum.
Previous story: A Suggestion for a More Scalable Reinclusion Request Procedure
blog comments powered by Disqus
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Place:Lower Merion, Montgomery, Pennsylvania, United States
Watchers
NameLower Merion
Alt namesLower Merionsource: WeRelate abbreviation
Merionsource: Columbia Lippincott Gazetteer (1961)
TypeTownship
Coordinates39.983°N 75.267°W
Located inMontgomery, Pennsylvania, 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
Lower Merion Township is a township in Montgomery County, Pennsylvania and part of the Pennsylvania Main Line. As of the 2010 census, the township had a total population of 57,825. Lower Merion has the 5th highest per-capita income and the 12th highest median household income in the country with a population of 50,000 or more.
The name Merion originates with the county of Merioneth in north Wales. Merioneth is an English-language translation of the Welsh Meirionnydd.
History
the text in this section is copied from an article in Wikipedia
Lower Merion Township was first settled in 1682 by Welsh Quakers who were granted a tract of land (the Welsh Tract) by William Penn. In 1713, Lower Merion was established as an independent Township with about 52 landholders and tenants. In 1900, the Township was incorporated as a Township of the First Class. Lower Merion is home to the oldest continuously used place of worship in the United States, the Merion Friends Meeting House, used continuously since 1695.
The Mill Creek Historic District, and Seville Theatre are listed on the National Register of Historic Places. Green Hill Farms was added in 2011.
Research Tips
This page uses content from the English Wikipedia. The original content was at Lower Merion Township, Pennsylvania. 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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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 built a tool for myself and some relatives. It's a windows keyboard tool that allows someone to instantly type accent marks, other diacritics and often used special characters. No key combinations to remember, no keyboard switching in the regional settings.
I am a french expat in Canada and really created it for my own daily use. Starting from there I wanted to test if there would be some interest by others, so I purchased a web template and quickly setup.
My problem is that I don't know where to promote it. When I google some key keywords like "clavier qwerty accents" (this is in french because my beta first targets french people), the results I get usually are forums where people need help typing their accent marks. I can't simply go there, register and say "use keyxpat, it solves your problem". It's understood as spam.
Note that I will also need to target people from other countries (norwegians, germans, ...) and I can only do it in english since I don't speak these languages.
Something that could help thinking about it: a buddhist organization, which translates texts to from sanskrit (with a specific font under MS Word), would like me to add all accentuated sanskrit characters (because it's a nightmare for them), which is something keyxpat can do.
So, where would you go to talk about this tool?
share|improve this question
show 5 more comments
4 Answers
I live in Montreal too and an expat!
I like your software, there are several ways to promote it actually. If you don't want your post to sound like spam (and you're right, it would be perceived as such), you might consider asking the moderators of the forums to allow you to post on their website. In the end, if you're providing them a solution, they shouldn't say no.
Alternatively, if you're willing to spend a little bit of money, you can always track Google AdWords and see if there is demand and if there is, you can advertise there.
My experience is in marketing, and if you need help, let me know, my phone is 514 995 5147.
*PS: I am not profiting out of this, I am just trying to help.
share|improve this answer
Though I don't know French language, you software seems nice for any French living in North America.
The audiences are general. And, most likely they won't search such keywords but they will find your software useful once you told them.
I suggest you to test AdWords for Content Network with some geo limitation. For example, targeting French sites/forums but only show ad for IPs from US and CA.
You can also try Facebook Ads with similar targeting, and more specific targeting after generating some user data. Some hypothetical examples, unmarried men might be more interested in your software than aged women, man knows little English rather than fluent English might be a better customer.
P.S. Revised "AdSense" to "AdWords for Content Network" according to Jame's correction.
share|improve this answer
While you're waiting for an answer more decent than mine, you could start by going to the mall, or at your local cafe.
Spend for 25 coffee drinks (or what budget you can afford) and ask people to spend 3-4 minutes with you (or less, if you can compress your entire presentation) to present and ask what they think.
See what word-of-mouth can help you (if this method works where you reside)
Although it might be construed as stalking where you are (I am uncertain) but if you just ask people coming in -- or near or even just wear a shirt or signboard saying "Stand with me for 3 minutes and get a coffee" -- It might be less of a hassle for others.
Have a netbook or a really small laptop and just talk to people; ensure you won't ask anything personal -- and just ask them how they deal with character accents and other stuff, and ask them to try what you have - no strings attached. The coffee is like a complementary token for their precious 3-4 minutes.
share|improve this answer
Just to clarify here folks, AdSense is advertisement service by Google in which you enter a code into a website which will then generate ads whereby people can click them and you earn a few cents (depending) per click.
AdWords is the service where you pay money to have your advert appear on Google platforms.
You're looking for Adwords, not Adsense.
share|improve this answer
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1. Skip to navigation
2. Skip to content
3. Skip to sidebar
Source link: http://archive.mises.org/11707/the-correct-theory-of-probability/
The Correct Theory of Probability
February 22, 2010 by
While probability theory is thought of as a branch of mathematics, its foundations are purely philosophic, and Richard von Mises, in his great work, developed the correct, objective, or “frequency” theory of probability. FULL ARTICLE by Murray N. Rothbard
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Connexions
Sections
You are here: Home » Content » Hoe lyk ek? - 04
About: Hoe lyk ek? - 04
Module by: Siyavula Uploaders. E-mail the author
View the content: Hoe lyk ek? - 04
Metadata
Name: Hoe lyk ek? - 04
ID: m26913
Language: English (en)
Subject: Humanities
License: Creative Commons Attribution License CC-BY 3.0
Authors: Siyavula Uploaders (support@siyavula.org.za)
Copyright Holders: Siyavula Uploaders (support@siyavula.org.za)
Maintainers: Siyavula Uploaders (support@siyavula.org.za)
Latest version: 1.1 (history)
First publication date: Jul 4, 2009 8:16 am -0500
Last revision to module: Jul 4, 2009 8:24 am -0500
Downloads
PDF: m26913_1.1.pdf PDF file, for viewing content offline and printing. Learn more.
XML: m26913_1.1.cnxml XML that defines the structure and contents of the module, minus any included media files. Can be reimported in the editing interface. Learn more.
Version History
Version: 1.1 Jul 4, 2009 8:24 am -0500 by Siyavula Uploaders
Changes:
Add solid lines
How to Reuse and Attribute This Content
If you derive a copy of this content using a Connexions account and publish your version, proper attribution of the original work will be automatically done for you.
If you reuse this work elsewhere, in order to comply with the attribution requirements of the license (CC-BY 3.0), you must include
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• the title of the work: Hoe lyk ek? - 04
• the Connexions URL where the work can be found: http://cnx.org/content/m26913/1.1/
See the citation section below for examples you can copy.
How to Cite and Attribute This Content
The following citation styles comply with the attribution requirements for the license (CC-BY 3.0) of this work:
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Uploader S. Hoe lyk ek? - 04 [Connexions Web site]. July 4, 2009. Available at: http://cnx.org/content/m26913/1.1/.
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Uploader, Siyavula. Hoe lyk ek? - 04. Connexions. 4 July 2009 <http://cnx.org/content/m26913/1.1/>.
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Why Microsoft can't ship open source code
0
kicks
Why Microsoft can't ship open source code (Unpublished)
I've suggested a few times that Microsoft could go beyond just cooperating with the open source community and actually ship open source code. For instance, Paint.NET is a great alternative to MS Paint, so not just bundle it? Tonight I had a very long conversation with someone who is in a position to really understand both Microsoft and open source. Now I understand why my suggestion - though well intentioned - was hopelessly naive.
Kicked By:
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BURN3
From eLinux.org
Revision as of 04:52, 3 December 2009 by Wmat (Talk | contribs)
Jump to: navigation, search
BURN3 is a firmware for the ZipIt that contains a basic Linux distribution that is mainly useful for loading other, more feature-rich firmwares (such as OpenZipIt) onto the ZipIt.
BURN3 is pretty much exactly what was on the zipit when you got it, but instead of going to the messenger app by default it goes to a Linux console terminal instead. Login as root, and once you're in, type in zrun then hit enter and it's the same as an unmodded zipit. As far as what can it do, its an embedded linux box (w/ 802.11) but honestly, not too much more. If you then install OpenZipIt or "Adam's Alternate ROM load" then you'll have a small wireless ssh client (see ZipIt Software for more info).
Contents
Installing BURN3 from Windows using serial connection
(requires serial port hardware mod see: Zipit Hardware Mods)
detailed instructions to be written here
Download the following file and unzip it to a directory on your Windows PC: zipit_reflash_kit03.zip you should also get: zipit_tool_extras.zip
Original sources:
www.aibohack.com/zipit/zipit_reflash_kit03.zip www.aibohack.com/zipit/zipit_tool_extras.zip
Installing BURN3 from Windows via WiFi
Only works if your Zipit has firmware earlier than Ver 2.01
Download the following file and unzip it to a directory on your Windows PC: zipit_reflash_kit03.zip
In order to install BURN3 using Windows XP, one first has to configure Windows to be an ad-hoc networking node. For instructions on this, please see: ZipIt WinXP Setup Alternatively you may connect via an access point that is disconnected from the Internet and has WEP disabled.
Once this is done, follow the original instructions from the heading "Instructions (Windows PC)"
Installing Burn3 from Linux via serial connection
(requires serial port hardware mod see: Zipit Hardware Mods)
Download the following file and unzip it to a directory on your Linux box: zipit_reflash_kit03.zip
My linux port of the upl utility should work with the 3-wire mod. It can be found at:
http://stoa.dhs.org/~cvs/zipit/
(look for zipit-flash)
Although I have the 5-wire mod myself, I never did get this linux port correctly reading data from the zipit. I use it regularly to flash my zipit. Here's a little transcript:
$ ./upl /dev/ttyS1 zpm.bin
Connected
Turn on the Zipit (press button, wait for green, release)
Wait 10 seconds, then press ENTER to start transfer
(DBG pin must be grounded)
Transfering bootstrap program
Transfer complete
Switch to 57.6kbps
Echo + upload commands
Decide what to upload
'A' - allrom.bin upload (2MB)
'a' - loader.bin upload (8K max)
'k' - zimage.dat upload (581K max)
'u' - ramdisk.gz upload (1.5MB max)
Follow changes with 'WYes' to write
A <-- press ENTER
//Uploading 2097152 bytes from allrom.bin
// done upload: csum=ffffffff (363s)
WYes <-- press ENTER
^C
$
After entering WYes, go for a coffee or something. I'm not sure how long the flashing takes, but I've interrupted it too early a few times and had to do it again. Someone said they figured the orange LED turns on solid during flashing. I've been reading the zpm source code and I can't see where it does that and I've never observed that behaviour.
Chris.
Installing BURN3 from Linux over WiFi
Only works if your Zipit has firmware earlier than Ver 2.01
Download the following file and unzip it to a directory on your Linux box: zipit_reflash_kit03.zip
In order to install BURN3 using Linux, one first has to configure Linux to be an ad-hoc networking node. For instructions on this, please see: Zipit Linux Setup
Once this is done, follow the original instructions from the heading "Instructions (Windows PC)" all the way down to the bullet that states "Before you press the "NEXT" button, start the ZRS server". Those instructions deal exclusively with the ZipIt device, and are independant of your PC's operating system.
In order to use the zrs utility in Linux, we will make use of WINE. If you're using Ubuntu or another Debian based distribution, you can install WINE by typing:
sudo apt-get install wine
Packages for most other popular distributions are available at the official WINE website.
Now, open up a terminal and a create a new directory to store some stuff. Download and extract BURN3 and zrs by typing:
wget http://aibohack.com/zipit/zipit_reflash_kit03.zip
unzip zipit_reflash_kit03.zip
Now we can fire up zrs with:
wine zrs burn3 10.0.1.9
Push "Next" on your ZipIt, and it should now connect to the wireless network, and detect that "An update for the Zipit Wireless Messenger is available." Pressing "Next" again will report:
• Retrieving Update...
• Verifying Update...
• Installing Update...
This will take several minutes, and the device will reboot when it is finished.
On your PC, push Ctrl-C to stop the ZRS program, as it is no longer needed.
Finally, put your network settings back by going back to Networking, deactivate "Wireless connection", set the default gateway device back to eth0. If you find that your internet/ethernet connection isn't working right away, a reboot should fix the problem.
Now what?
Now that BURN3 is installed on your ZipIt, you can find out more about what you can do with it here, under the "Try it out" heading. At this time you may also want to setup an NFS server using windows or linux
Try it out
The device should reboot showing the Hacked by Zipit Pet and eventually the penguin logo.
• login as "root", no password
• As you know already: when running the Zipit IM app, the shift keys are a prefix (press shift key first, let go, then press the other key) The Linux keyboard driver acts differently. Hold down the SHIFT (up arrow), Alt or Ctrl shift keys and press the other key at the same time (ie. like a normal keyboard). The P1, P2, P3 keys are mapped to F1, F2, F3
• Alt+P1/P2/P3 will switch virtual consoles.
• To run the regular Zipit IM app, type the command "zrun" at the command prompt. NOTE: the regular 'Zipit' program run, it will attempt to connect to the real Internet and download the latest firmware. When an update to the official version is released (currently 2.01), reflashing will replace the hacked firmware with something new. Stop it before it gets that far if you want to keep your hacked version. (Note that if you allow it to upgrade to version 2.01, you won't be able to use ZRS to put back a hacked firmware.)
• When done, be sure to turn off the device (press and hold power switch). If you leave it on and un pluged the battery will run down (ie. there is no auto power off timer when running regular Linux unless you add the zipit tools with these options)
• The file system on the Zipit device is temporary, extracted from the Flash ROM contents at boot. If you copy over files, they will be lost when the power is turned off.
• If using a DHCP server, the command "udhcpc" will connect to an open access point (without a WEP) and assign an IP address using DHCP You can then 'telnet' to the Zipit device from your PC.
• If you have a WL-HDD device configured as recommended (see below), the "n1" command will assign a static IP, and connect to the nfs server.
Also, now you can install OpenZipIt, and do even cooler things with your ZipIt.
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LeapFrog Pollux Platform: File Format CBF
From eLinux.org
Revision as of 10:03, 27 October 2011 by Peter Huewe (Talk | contribs)
Jump to: navigation, search
Description
The LeapFrog Leapster Explorer and LeapPad Explorer both use the CBF file format for the kernel firmware and Surgeon. This is a rather basic format, that contains some summary information about the kernel, size, load address, etc. This information is all rather easy to obtain out of the file, with a hex editor. You can also extract the zImage or Image of the kernel if desired. LeapFrog includes the Python script to turn a kernel image into a cbf file <Sources>/scripts/make_cbf.py.
Versions
There are two versions of the make_cbf.py script, starting with source release 20110602 for the LeapPad, the cbf is built with an uncompressed kernel Image, instead of a gunzip compressed zImage. There is no indicator of this, other than a change to the Python script. There is a reference to a different version in this release's Surgeon script, referring to a make_compressed_cbf.py script. Which would seem to indicate Surgeon is built with the older version.
File Structure
There are three basic components of the CBF file, the summary, the kernel image, and padding. The Summary occupies the first 20 bytes of the file, which is followed by the summary CRC checksum. Directly after this starts the kernel image, which can vary in size depending on the options compiled in. It is then followed by the kernel image CRC checksum. This concludes the data portion, the file is then filled with 0xFF bytes until it is aligned to 16384 byte blocks of data.
Summary Summary CRC Kernel Kernel CRC Padding
[0:3] [4:7] [8:11] [12:15] [16:19] [20:23] [24:K end] [K end+1:+4] [..EOF]
Magic Number CBF Version Kernel Load Kernel Jump Kernel Size CRC32 Checksum Kernel Image CRC32 Checksum 0xFF
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Beaty's Company, Tennessee Independent Mounted Scouts (Union)Edit This Page
From FamilySearch Wiki
United States U.S. Military Tennessee Tennessee Military Tennessee in the Civil War Beaty's Company, Tennessee Independent Mounted Scouts
Brief History
"This company was organized in Fentress County early in 1862 by David Beaty, or Beatty, better known as Tinker Dave." It was apparently never mustered into the regular U.S. Service, but Major General Ambrose E. Burnside authorized it to act as scouts, and operate in the regions of Overton and Fentress Counties in combating Confederate guerrillas. Captain Beaty stated his men never drew any pay, but were supplied with arms and ammunition by the Federal authorities." [1]
"Compendium of the War of the Rebellion" by Frederick H. Dyer contains no history for this unit.[2]
Other Sources
• Beginning United States Civil War Research gives steps for finding information about a Civil War soldier or sailor. It covers the major records that should be used. Additional records are described in 'Tennessee in the Civil War' and 'United States Civil War, 1861 to 1865' (see below).
• National Park Service, The Civil War Soldiers and Sailors System, is searchable by soldier's name and state. It contains basic facts about soldiers on both sides of the Civil War, a list of regiments, descriptions of significant battles, sources of the information, and suggestions for where to find additional information.
• Tennessee in the Civil War describes many Confederate and Union sources, specifically for Tennessee, and how to find them.. These include compiled service records, pension records, rosters, cemetery records, Internet databases, published books, etc.
• United States Civil War, 1861 to 1865 describes and explains United States and Confederate States records, rather than state records, and how to find them. These include veterans’ censuses, compiled service records, pension records, rosters, cemetery records, Internet databases, published books, etc.
• O'Neal, Michael R., The Civil War on the Cumberland Plateau in Tennessee, (accessed 29 Jan 2012). (EDITOR’S NOTE— This article, on the Civil War in Scott and surrounding counties, was completed in May 1982 as part of a history course at Middle Tennessee State University. it represents a rare glimpse of how America’s most bitter struggle touched the lives of those who resided in one of the most isolated areas of the country. For the purpose of ease in reading and with the author’s permission, some 140 footnotes have been omitted from this article. O’Neal‘s paper was first published in the Winter and Spring 1986 Newsletters of the Scott County Historical Society and is reprinted here with permission.)
References
1. Tennesseans in the Civil War, Miscellaneous Federal Organizations, (accessed 29 Jan 2012).
2. National Park Service, The Civil War Soldiers and Sailors System, (accessed 6 December 2010).
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• This page was last modified on 30 January 2012, at 03:25.
• This page has been accessed 316 times.
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Eaton County (Michigan) Genealogical SocietyEdit This Page
From FamilySearch Wiki
Eaton County Genealogical Society
Established 1988
Contact Info
Address 100 W. Lawrence St,
P O Box 337, Charlotte, MI 48813
Telephone 517-543-8792
Website www.miegs.org
Society Officers
President Marcy Cousino
Vice-President Shirley Hodges
& Sher Brown
On the Eaton County Michigan Genealogical Society website, you will find:
• A list of our library holdings.
• Many name lists from our Index System database of various holdings.
• Name index lists of the majority of our cemeteries.
• Our Civil War Project information.
• Our Pioneer Family Project information.
Contents
Benefits
• What are the benefits for becoming a member of the society?
• What are the benefits the society has to offer for those who are not members?
History of the society
Society Officers
Society Projects
Current Projects
• Indexing Probate Packets on Line. Finished Packets viewable on computer in Eaton County Genealogical Society Library.
Current Projects
FamilySearch Wiki Projects
FamilySearch Wiki Page Adoptions
Past Projects
Publications
Newsletters
Collections
Events
Society Meetings
Workshops
Board Meetings
Training Meetings
Frequently Asked Questions
Q. What are the directions to the society?
A. Located main floor,1885 Court House, 100 Lawrence Ave, Charlotte, Michigan
Q. What are the society's hours of operation?
A.
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• This page was last modified on 15 November 2012, at 04:02.
• This page has been accessed 414 times.
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Rising Sun, Cecil County, MarylandEdit This Page
From FamilySearch Wiki
(Redirected from Rising Sun)
United States > Maryland > Cecil County > Rising Sun
Contents
Histories and Tidbits
Neighboring Communities
Family History Resources
Cemeteries
Community Web Sites
• Rising Sun, Maryland
• Nottingham Lots : 37 lots of approximately 500 acres each given by William Penn to his colonists in 1702 although they lay in Maryland and were part of George Talbot’s “Susquehanna Manor” of 32,000 acres granted him in 1680 by Lord Baltimore. Map
• Brick Meeting House - William Penn set aside lot no. 30 (500 acres) of the “Nottingham Lots” in 1702 for a “common” and site of a “meeting house” as a bold move in the boundary line dispute with Lord Baltimore. It has been continuously used since the first log meeting house was erected in 1709. Map
Historical and Genealogical Societies
Historical Newspapers
Histories, Biographies, And Genealogies
Libraries
Family History Web Sites
References
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• This page was last modified on 28 August 2010, at 01:54.
• This page has been accessed 573 times.
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Dorchester County, MarylandEdit This Page
From FamilySearch Wiki
Revision as of 22:19, 24 May 2010 by DSGurtler (Talk | contribs)
United States > Maryland > Dorchester County
Dorchester County, Maryland in green.
Dorchester County Boundary Map
Contents
County Courthouse
Dorchester County Courthouse, Cambridge, Md.
Dorchester County Office Building
501 Court Lane
Cambridge, MD 21613
History
Parent County
• Created 27 May 1668 from Colonial lands.
Boundary Changes
• 15 June 1773, Caroline County was set off.
Record Loss
Places/Localities
Populated Places
City
• Cambridge
Towns
• Brookview
• Church Creek
• East New Market
• Eldorado
• Galestown
• Hurlock
• Secretary
• Vienna
Communities
• Algonquin
• Bishops Head-Toddville
• Crapo
• Crocheron
• Elliott-Salem
• Fishing Creek
• Hoopersville
• Linkwood
• Madison-Woolford
• Rhodesdale
• Taylors Island
• Wingate
Neighboring Counties
Calvert| Caroline| St. Mary's| Somerset| Talbot| Wicomico| Deleware Counties: Sussex
Resources
Cemeteries
Dorchester County cemetery transcriptions in the US Genweb Project and other sources. http://www.idreamof.com/cemetery/md/dorchester.html
Census
• 1776 Transcription and Index
• 1778
• 1790
• 1800
• 1810
• 1820
• 1830
• 1840
• 1850
• 1850 Slave
• 1860
• 1860 Slave
• 1870
• 1880
• 1890
• 1900
• 1910
• 1920
• 1930
Church
Maryland State Archives' Guide to Maryland Religious Institutions identifies all churches known to have existed in Dorchester County, Maryland. It covers all denominations and includes record descriptions.
Court
Family Histories
It is anticipated that this bibliography will eventually identify all known family histories published about residents of this county. Use this list to:
• Locate publications about direct ancestors
• Find the most updated accounts of an ancestor's family
• Identify publications, to quote Elizabeth Shown Mills, about an ancestor's "FAN Club" [Friends, Associates, and Neighbors]
Bibliography
• [Wright] Wright, Charles W. The Wright Ancestry of Caroline, Dorchester, Somerset and Wicomico Counties Maryland. Baltimore: Baltimore City Printing and Binding Co., 1907. Available at FHL; digital versions at BYU Family History Archives and Google Books (full-view).
Gazetteers
Immigration
The New Early Settlers of Maryland database is a great place to start searching for immigrants who had arrived in the colony by the 1680s. The database "comprises 34,326 entries from Gust Skordas' Early Settlers of Maryland and Carson Gibb's Supplement to the Early Settlers of Maryland." Available online, courtesy: Maryland State Archives.
Other Dorchester County immigration resources include:
• Coldham, Peter Wilson. "Intercepted Letters Relating to America 1777-1811," The Genealogist, Vol. 14, No. 2 (Fall 2000):184-200; Vol. 15, No. 1 (Spring 2001):53-74. [Overseas correspondence of a resident of Vianna [Vienna, Dorchester County] with the following surname: Dennis.]
• List of imported servants and convicts from Europe who served labor terms in Colonial Dorchester County, Maryland (work in progress), courtesy: Immigrant Servants Database. [Includes Richard J. Cox's abstracts of Maryland Gazette runaways.]
Land
Through a Joint eGovernment Service of the Maryland Judiciary and the Maryland State Archives, free images and indexes of the complete series of Dorchester County Deed Books (1669-present) have been uploaded to their website: MDLandRec.Net: A Digital Image Retrieval System for Land Records in Maryland. (Requires free registration.)
Local Histories
Maps
Military
Newspapers
Dorchester County, Maryland Old Newspapers are available online.
Private Papers
• Coldham, Peter Wilson. "Intercepted Letters Relating to America 1777-1811," The Genealogist, Vol. 14, No. 2 (Fall 2000):184-200; Vol. 15, No. 1 (Spring 2001):53-74. [Overseas correspondence of residents of Vianna [Vienna, Dorchester County] with the following surname: Dennis.]
Probate
Taxation
Vital Records
Death
Other Dorchester County death record resources include:
• Dorchester County, Maryland Cemeteries, Death Certificate Indexes, Death Certificate Abstracts, Abstracts of Obituaries are available online.
Societies and Libraries
Web Sites
References
Cite error: <ref> tags exist, but no <references/> tag was found
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lillylosanz's bookmarks
"Life is not a problem to be solved, but a reality to be experienced."
Kierkegaard, Søren on life
12 fans of this quote
"Life can only be understood backwards, but it must be lived forward."
Kierkegaard, Søren on life
16 fans of this quote
"Life must be lived forward, but can only be understood backwards."
Kierkegaard, Søren on life
14 fans of this quote
"Life has its own hidden forces which you can only discover by living."
Kierkegaard, Søren on life
14 fans of this quote
"Once the game is over, the king and the pawn go back into the same box."
Proverb, Italian on death
20 fans of this quote
"The person who lives by hope will die by despair."
Proverb, Italian on despair
9 fans of this quote
"Speak of the Devil and he appears."
Proverb, Italian on evil
3 fans of this quote
"He that flatters you more than you desire either has deceived you or wishes to deceive."
Proverb, Italian on flattery
4 fans of this quote
"Hasty climbers have sudden falls."
Proverb, Italian on ambition
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"The person who lives with cripples will soon learn to limp."
Proverb, Italian on influence
3 fans of this quote
"The right man comes at the right time."
Proverb, Italian on leadership
3 fans of this quote
"Never do that by proxy which you can do yourself."
Proverb, Italian on leadership
"The best way to get praise is to die."
Proverb, Italian on praise
"If the secret sorrows of everyone could be read on their forehead, how many who now cause envy would suddenly become the objects of pity."
Proverb, Italian on pity
5 fans of this quote
"He who knows little knows enough if he knows how to hold is tongue."
Proverb, Italian on speakers and speaking
"After the ship has sunk, everyone knows how she might have been saved."
Proverb, Italian on solutions
"Faith may be defined briefly as an illogical belief in the occurrence of the improbable."
Mencken, H. L. on faith
4 fans of this quote
"I should have no use for a paradise in which I should be deprived of the right to prefer hell."
Rostand, Jean on paradise
3 fans of this quote
"A few great minds are enough to endow humanity with monstrous power, but a few great hearts are not enough to make us worthy of using it."
Rostand, Jean on power
"Stupidity, outrage, vanity, cruelty, iniquity, bad faith, falsehood -- we fail to see the whole array when it is facing in the same direction as we."
Rostand, Jean on prejudice
4 fans of this quote
"Nothing leads the scientist so astray as a premature truth."
Rostand, Jean on science
"Beauty in art is often nothing but ugliness subdued."
Rostand, Jean on beauty
"The nobility of a human being is strictly independent of that of his convictions."
Rostand, Jean on belief
"One must credit an hypothesis with all that has had to be discovered in order to demolish it."
Rostand, Jean on theory
"Truth is always served by great minds, even if they fight it."
Rostand, Jean on truth
"To love an idea is to love it a little more than one should."
Rostand, Jean on ideas
3 fans of this quote
"Remember that a government big enough to give you everything you want is also big enough to take away everything you have."
Crockett, Davy on government
11 fans of this quote
"The world's a forest, in which all lose their way; though by a different path each goes astray."
Villiers, George on world
4 fans of this quote
"Opportunity is missed by most people because it comes dressed in overalls and looks like work."
Edison, Thomas A. on opportunity
10 fans of this quote
"Our greatest weakness lies in giving up. The most certain way to succeed is always to try just one more time."
Edison, Thomas A. on perseverance
19 fans of this quote
"I am not discouraged, because every wrong attempt discarded is another step forward."
Edison, Thomas A. on failure
12 fans of this quote
"When I have fully decided that a result is worth getting I go ahead of it and make trial after trial until it comes."
Edison, Thomas A. on perseverance
"Many of life's failures are people who did not realize how close they were to success when they gave up."
Edison, Thomas A. on perseverance
12 fans of this quote
"Ninety-nine percent of the failures come from people who have the habit of making excuses."
Carver, George Washington on failure
9 fans of this quote
"Just because something doesn't do what you planned it to do doesn't mean it's useless."
Edison, Thomas A. on failure
7 fans of this quote
"I have not failed. I've just found 10, 000 ways that won't work."
Edison, Thomas A. on failure
27 fans of this quote
"Genius is one percent inspiration and ninety-nine percent perspiration."
Edison, Thomas A. on genius
15 fans of this quote
"The first requisite for success is the ability to apply your physical and mental energies to one problem incessantly without growing weary."
Edison, Thomas A. on ability
25 fans of this quote
"The value of an idea lies in the using of it."
Edison, Thomas A. on ideas
11 fans of this quote
This quotation can be viewed in the context of a book
But wait... my book has more: prev 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 next
Lilliana Lopez's quote collection
I'm female, single from Puerto Rico and made my book on 4th March 2007.
My book as a pdf
My feed
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Quotation added by staff
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Love's greatest gift is its ability to make everything it touches sacred. Angelis, Barbara De
This quote is about love · Search on Google Books to find all references and sources for this quotation.
A bit about Angelis, Barbara De ...
Barbara De Angelis Ph.D. is an influential teacher in the field of relationships and personal growth. For the past twenty-five years, she has reached tens of millions of people throughout the world with her positive messages about love, happiness and the search for meaning in our lives. As a best-selling author, popular television personality and sought after motivational speaker, Barbara has been a pioneer in the field of personal transformation as one of the first people to popularize the idea of self-help in the 1980's, and as one of the first nationally recognized female motivational teachers on television.
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My esoteric doctrine, is that if you entertain any doubt, it is safest to take the unpopular side in the first instance. Transit from the unpopular, is easy... but from the popular to the unpopular is so steep and rugged that it is impossible to maintain it. Melbourne, Lord
This quote is about policy · Search on Google Books to find all references and sources for this quotation.
A bit about Melbourne, Lord ...
Viscount Melbourne, of Kilmore in the County of Cavan, was a title created for Peniston Lamb, 1st Baron Melbourne in 1781 in the Peerage of Ireland. He had previously been created Lord Melbourne, Baron of Kilmore in the County of Cavan, in the Peerage of Ireland, in 1770, and was further created Baron Melbourne, of Melbourne in the County of Derby, in the Peerage of the United Kingdom, in 1815. The 2nd Viscount was Prime Minister of the United Kingdom, while his brother, the 3rd Viscount, was a diplomat who was created Baron Beauvale, of Beauvale in the County of Nottingham, in the Peerage of the United Kingdom, in 1839, before succeeding to the Viscountcy. All the titles became extinct on the death of the 3rd Viscount.
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Quotation added by staff
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...or experienced before it can be rejected.[80] But the greater number of them are quite clear and present no difficulty, as for instance the following:--
A fool sees not the same tree that a wise man sees.
He whose face gives no light shall never become a star.
No bird soars too high, if he soars with his own wings.
What is now proved was once only imagined.
As the air to a bird or the sea to a fish, so is contempt to the contemptible.
Exuberance is beauty.
Everything possible to be believed is an image of truth.
There are two tendencies of Blake's mind, both mystical--that is, rooted in unity--the understanding of which helps, on the one hand, to clear much in his writing that seems strange and difficult; and, on the other, reveals a deep meaning in remarks apparently simple to the point of silliness. These are his view of the solidarity of mental and spiritual as compared with physical things, and his habit of concentrating a...
Blake, William
Excerpt from Mysticism in English Literature · This quote is about beauty · Search on Google Books to find all references and sources for this quotation.
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Sorrow for a husband is like a pain in the elbow, sharp and short. Proverb, English
This quote is about widowhood · Search on Google Books to find all references and sources for this quotation.
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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.
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The stars are constantly shining, but often we do not see them until the dark hours. Unknown, Source
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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°
Click here to buy this »
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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.
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The wise man realistically accepts as part of life and builds a philosophy to meet them and make the most of them. He lives on the principle of nothing attempted, nothing gained and is resolved that if he fails he is going to fail while trying to succeed. Peterson, Wilferd A.
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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°
Click here to buy this »
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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.
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See everything, overlook a great deal, correct a little. Pope John XXIII
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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°
Click here to buy this »
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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.
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Keep a mid course between two extremes. Ovid
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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°
Click here to buy this »
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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.
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The most gifted natures are perhaps also the most trembling. Gide, Andre
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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°
Click here to buy this »
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NBA FInals
This should end some of the conspiracy talk
A lot of people watched Game 7 According to numbers released Tuesday by the Nielson Co., Game 7 of the NBA finals drew an audience of 28.2 million people, ranking it as the most-watched basketball game since Michael Jordan’s last championship-clinching win in 1998. Not including the Olympics, Thursday’s game between the Celtics and Lakers [...]
June 22, 2010 RedsArmyAdmin Uncategorized 54
A pick-me-up, courtesy of Doc Funk
Just two of the always hysterical captions from the genius that is Doc Funk. Head on over to the Game 7 recap and have a good laugh… cuz we all know we need it. [...]
June 18, 2010 RedsArmyAdmin Uncategorized 7
Enemy Chatter: A lot of stupid, stupid people
I often wonder what opposing teams, their beat reporters and bloggers are saying about the Celtics after playing the Celtics. Here's a dose of 'enemy chatter' from Los Angeles. Crowds broke windows of storefronts, jumped on cars, set at least 15 small fires and threw objects at police. The LAPD reported 38 arrests. There were [...]
June 18, 2010 Chuck - Red's Army Uncategorized 73
Thanks, Doc
Hey Doc, I don't know what you're going to do. You might not know what you're going to do yet either. But, at the risk of peppering this site with a ton of post-season "thank yous"… I just wanted to take a minute to say thanks. I haven't agreed with all of your decisions. But [...]
June 18, 2010 RedsArmyAdmin Uncategorized 13
Your Morning Dump… Where that might have been it for Sheed
Every morning, we compile the links of the day and dump them here… highlighting the big storyline. Because there's nothing quite as satisfying as a good morning dump. “You know, I don’t know if Rasheed will ever play again,” Rivers said. “You know, he’s one of them. I think he took that out on the [...]
June 18, 2010 RedsArmyAdmin Uncategorized 27
So close…
Credit to the Lakers for winning a hard-fought, hideously played Game 7, 83-79. Crazy Ron Artest (who thanked his psychiatrist in the post game interview) was the hero for Los Angeles. Ron had 20 points and 5 steals while playing lock down defense on Paul Pierce (18 points, 5-15 FG). His three-pointer with one minute [...]
June 17, 2010 Chuck - Red's Army Uncategorized 153
NBA Finals Game 7 Open Game Thread
(Mildly NSFW printed language in video) This is it folks. Scal's the secret weapon. And these guys are right… this is exactly like having sex with a supermodel on the death star while eating ice cream. It's that awesome. Meanwhile, those assholes in LA think having Christina Aguilera sing the national anthem again will bring [...]
June 17, 2010 RedsArmyAdmin Uncategorized 58
I trust Rasheed Wallace
I trust Rasheed Wallace. There, I said it. I know damn well what he did this regular season. I know damn well how much he's coasted and how old he is and how he's not what he used to be. But dammit, I trust him tonight. Here's the thing about Rasheed Wallace. He knows damn [...]
June 17, 2010 RedsArmyAdmin Uncategorized 2
We’re gaining momentum!
When we showed you this sports nation poll yesterday, Vermont, Connecticut and the rest of the country were showing Lakers. But New Englanders have stepped up… as have the Rondo-lovers in Kentucky and the Derek Fisher-haters in Utah. So thanks, New England, for showing up to the party. I'll just randomly assume Red's [...]
June 17, 2010 RedsArmyAdmin Uncategorized 11
Game 7 Motivation: Part 4
I so want to see Doc giving the pregame speech on ABC's "wired" segment and see Kevin Garnett do the slow clap thing. That would be awesome. [...]
June 17, 2010 RedsArmyAdmin Uncategorized 3
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7 Jul 2008 JamesBruton » (Master)
A robot I built a while ago but never finished made it onto Engadget, HackedGadgets, Makezine and Digg. This meant I've had 22,658 visitors to my XRobots website in the last 5 days (so far) consuming 46Gb of bandwidth, which is more than I usually do in two years.
I might take the time to finish that project after my Star Wars party is all done with.
Latest blog entries Older blog entries
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Restaurants/Areas
Info
Search:
The Areas page of Restaurants organizes the restaurants in Rochester by area within each jurisdiction. In the city of Rochester they are broken down by neighborhood. In other jurisdictions they may be broken down by the shopping plaza where they are located. In some cases, the plaza or street may already have the restaurants listed, and we just put the link to the plaza in that case.
It is intended to be a comprehensive list, across categories, so listing chain restaurants, local sub shops, pizzerias, etc, is not discouraged. If you are looking for bar food note that the bars listing is indexed by town and shows which serve some sort of food. Listing restaurants without a RocWiki page will also help people who live in those areas to fill out a page for those restaurants.
1. Brighton
2. City of Rochester
1. 19th Ward
2. Charlotte
3. Corn Hill
4. Changing of the Scenes and Susan B. Anthony
5. Culver-Merchants
6. Downtown
7. East Avenue
8. East End
9. Highland Park and Swillburg
10. Lyell-Otis
11. Maplewood
12. Monroe Village
13. Neighborhood of the Arts
14. North Winton Village
15. Park Avenue Area
16. Plymouth-Exchange
17. South Wedge
18. Upper Monroe
19. Upper Mt. Hope
20. Wadsworth Square
3. Chili
1. Ace Swim & Leisure Plaza
2. Chili Paul Plaza
4. East Rochester
5. Fairport / Perinton
6. Gates
7. Greece
1. Elm Ridge Center
2. The Mall at Greece Ridge
3. Stoneridge Plaza
8. Henrietta
1. Frontier Commons
2. Henrietta Plaza
3. Jefferson Plaza
4. Marketplace Square
5. Park Point at RIT
6. Southtown Plaza
7. Suburban Plaza
8. Win-Jeff Plaza
9. Honeoye Falls
10. Irondequoit
11. Macedon
12. Penfield
1. Baytown Plaza
2. Panorama Plaza
13. Pittsford
1. Northfield Common
2. Pittsford Plaza
3. Pittsford Village
4. Schoen Place
14. Scottsville
15. Spencerport
1. Barefoot Landing Plaza
16. Webster
1. Towne Center Webster
2. Webster Plaza
3. Webster Woods Plaza
4. Village of Webster
17. Victor
1. Cobblestone Court
2. Eastview Mall
Brighton
City of Rochester
19th Ward
Charlotte
Corn Hill
Changing of the Scenes and Susan B. Anthony
Culver-Merchants
Downtown
East Avenue
East End
Highland Park and Swillburg
Lyell-Otis
Maplewood
Monroe Village
Neighborhood of the Arts
North Winton Village
Park Avenue Area
Plymouth-Exchange
South Wedge
Upper Monroe
Upper Mt. Hope
Wadsworth Square
Chili
Ace Swim & Leisure Plaza
Chili Paul Plaza
East Rochester
Fairport / Perinton
Gates
Greece
Elm Ridge Center
The Mall at Greece Ridge
Stoneridge Plaza
Henrietta
Frontier Commons
Henrietta Plaza
Jefferson Plaza
Marketplace Square
Park Point at RIT
Southtown Plaza
Suburban Plaza
Win-Jeff Plaza
Honeoye Falls
Irondequoit
Macedon
Penfield
Baytown Plaza
Panorama Plaza
Pittsford
Northfield Common
Pittsford Plaza
Pittsford Village
Schoen Place
Scottsville
Spencerport
Barefoot Landing Plaza
Webster
Towne Center Webster
Webster Plaza
Webster Woods Plaza
Village of Webster
Victor
Cobblestone Court
Eastview Mall
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Help Wikitravel grow by contributing to an article! Learn how.
Kayes (city)
From Wikitravel
(Redirected from Kayes)
Jump to: navigation, search
Kayes is a city in the Kayes Region on the river Senegal in the West African country of Mali.
[edit] Understand
The city is told to be the hottest town in Africa. Until 1908 it was the colonial capital of French Sudan. The town is a stop of the Dakar-Bamako railway. The area is rich in iron and gold.
[edit] Get in
[edit] Get around
[edit][add listing] See
[edit][add listing] Do
[edit][add listing] Buy
[edit][add listing] Eat
[edit][add listing] Drink
[edit][add listing] Sleep
[edit] Get out
Take a truck to Keniéba, in southwest Mali. One hell of a journey!
This article is an outline and needs more content. It has a template, but there is not enough information present. Please plunge forward and help it grow!
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Saint-Malo
From Wikitravel
(Redirected from Saint Malo)
Jump to: navigation, search
Boats in the harbor, with Intramuros in the background
Saint-Malo is a small walled coastal town in Brittany, France.
[edit] Understand
Once the feared base of pirates (corsairs), heavily fortified against Norman (or English) attack, today's Saint-Malo is one of the top tourist draws in Brittany. The star of the show is the atmospheric walled city (intramuros), largely destroyed in the Second World War but painstakingly reconstructed. The modern towns of Parame and Saint-Servan lie outside the walls.
[edit] Get in
[edit] By train
Saint-Malo's train station is located over a kilometer south of the intramuros area, but it's an easy 20-min walk straight down Avenue Louis Martin. There are a few direct TGV services daily from Paris (Gare de Montparnasse), which take about three hours. Most travellers, however, will end up connecting in Rennes, from where there are hourly commuter services (50 min, €12) to Saint-Malo.
[edit] By ferry
From the UK you can arrive from Poole and Weymouth on Condor Ferries. Leaving from Portsmouth with Brittany Ferries. From Jersey & Guernsey you can take Condor Ferries which offers direct routes from both islands.
[edit] By bus
There are two buses daily to Pontorson (line 17, 1 hour, €2,5), which depart from the train station and stop at the city walls. The buses are timed to connect to onward buses to Mont Saint Michel (15 min, €2), allowing a fairly comfortable day-trip.
[edit] Get around
Saint-Malo has a good bus system, with the main terminals located at the train station and just outside the walls(St Vincent). Get a booklet with maps and times from any bus driver. A one and a half hour ticket costs €1.15. Unfortunately there are no bus services late in the evening.
The walled city is easily covered on foot, but you can also opt for a dinky "Tourist Train" that takes you and your wallet for a ride (€5.50).
[edit][add listing] See
• Ramparts (Remparts).
• The walled city (La Ville Intra-Muros)
• The Chateau
• The walled city view from the "Memorial 39-45"
• World's first tidal power station, [1]. The tidal power plant reportedly attracts 200,000 visitors per year. A canal lock in the west end of the dam permits the passage of 16,000 vessels between the English Channel and the Rance. The display centre is looking a bit tired and there isn't much to see from the barrage wall. Getting there is a bit tricky, bus routes C1 and C2 get you to within a kilometer walk. edit
[edit][add listing] Do
• Watch the impressive tide.
• Walk (or jog) along the beach.
• Walk around the walls of the walled city(free).
• Visit the Festival des Folklores du Monde (World Folklores), which takes place at the beginning of July. There are dance and music performances from around the world. You can also dance when Celtic Breton bands play music in the main square of Parame district.
• Look at the many hundreds of sailing boats of all sizes and ages in the harbour/s.
[edit][add listing] Buy
La cale aux trésors 2 passage de la grande hermine, intra-muros. website [2] French delicatessen shop.Wineshop.
Shops in the city center usually close by 19 hrs, but most of them now (as of 2010) stay open every Sunday. -Including high street cloth stores, which before 2010 were not allowed to open on Sunday and now are allowed-
[edit][add listing] Eat
Cancale Bay oysters
Saint-Malo is a great place to sample Breton specialties.
• Breton Pancakes: not just the world-famous sweet crêpes, but also savoury galettes.
• Kouing Aman: this is a delicious Breton cake made with butter and sugar. Try to sample them piping hot, especially the ones with apple added in.
• Mussels (moules): fished in the place and available in any restaurants.
• Oysters (huitres): the best are from Cancale, a village near to Saint-Malo. In France, they are eaten raw.
The Intramuros area has what is quite possibly France's highest concentration of creperies and seafood restaurants. Most cater solely to tourists and are effectively identical.
• Cafe de Saint-Malo, just inside Grande Porte. The restaurant here is unspectacular, but what makes this the best deal in Intramuros is the window selling fresh seafood to go. For €5, you can get a dozen large oysters, preshelled, on ice and with a quartered lemon.
• Petit Crêpier, Rue Ste Barbe, tel. +33-299409319, [3]. True to the name, this restaurant is small and has crepes, but their daily selection of seafood galettes is a cut above the pack. €10.
• Coté brasserie, 8, rue des Cordiers (intra-muros), tel. 2-99568340. New proprietary. . seafoods and chips. Well separated smoking and non-smoking areas. €20-40.
• Captain-Ice, Rue Jacques Cartier, Intra-Muros. This may well be the best ice cream place in town. Try Amour de Glace (Love of Ice cream) for something really yummy. Prices are slightly high, but you get big quantities and very high quality!
• In St Malo you can eat at any time of day. In smaller towns nearby, tip: look out for the lunchtime menu ouvrière (workers' menu}; often there is little or no choice of dishes, but what you get is genuine French home cooking (love those fries!) for half the price, if that, of what you'll pay in a tourist centre like St Malo or Mont St Michel. (French lunchtime is sacred. Every French person observes it religiously.)
• Crêperie le Tournesol, 4 rue des marins (Saint-Malo), 2-99403623, [4]. Brunch in St-Malo means only one thing: a galette washed down with a cup of local cider – no it's never too early. Try the Crêperie Le Tournesol (16) at 4 Rue des Marins (00 33 2 99 40 36 23), with its terrace spilling out on to cobbled streets, from 11.30am Sunday. Its speciality galettes start at €5.50 and come with a huge variety of fillings, from smoked Breton sausage and egg to goats' cheese and Camembert. If you still have room, finish with something sweet – a crêpe with hot chocolate sauce is €3.50. edit
[edit][add listing] Drink
Brittany is not a renowned region for its wine. Otherwise, there are other specialities:
• Breton beer
• Cider
• Calvados: apple brandy
• Chouchen: mead (it's a blend with alcohol and honey; it is very sweet)
• Muscadet: dry white wine, perfect with local seafood; true, it doesn't come from Brittany, but is from the nearest vineyard area, Pays de la Loire
[edit][add listing] Sleep
There are many accommodation options in Saint-Malo, including over 20 hotels within the walls, but they can fill up very fast in season — book ahead.
[edit] Budget
• Matthews Holidays, 0044 1483 285213, [5]. Mobile Home holidays to 4* & 5* beachside campsites throughout France. Camping Chateau des Ormes, situated 20 miles from St Malo is an all action campsite. Activities here include fishing, golf, horse riding, treetop adventure course, swimming pools and more. edit
• Le Centre Patrick Varangot, 37 avenue du R.P. Umbricht (near the beach, 30-40 minutes by foot from the walled city), tel. 02 99 40 29 80, E-mail : info@centrevarangot.com, [6].
[edit] Mid-range
• Best Western Central, 7 Grande Rue, +33-2-99408770, [7]. Superb location just inside the main gate of the walled town, but lower floors can be noisy. Rooms are small but clean, some with views out onto the street, some with shower, others with bath. Wifi available (separate charge). No parking. €98. edit
• San Pedro, 1 rue Sainte Anne, +33-2-99408857, [8]. Comfortable small nautical-themed hotel within the walled city. Rooms have shower, WC, TV, and Wifi. Daily changing themed breakfast available (€7.50 extra). Internet bookings unreliable, so call to confirm. €55/67 without/with sea view. edit
[edit] Splurge
[edit] Get out
• Visit nearby Mont Saint Michel - a monastery and town built on a tiny outcrop of rock in the sand, which is cut off from the mainland at high tide. It is one of France's major tourist destinations, and as such gets very busy in high season. Check the times of the tides before you visit!
• Cross the Rance Tidal Dam (Barrage de la Rance) and see Dinard; especially in October when the town hosts its annual English Film Festival (lots of US films, too). Casino, sandy beaches, high cliffs studded with quaint, Victorian-era houses, many with conical tower tops; covered market.
• Venture west beyond Dinard to the Côte d'Emeraude (Emerald Coast) to find even more luscious sandy beaches and little-known towns such as St-Lunaire and St-Cast (first French town to liberate itself from Nazis by own efforts, 1944) and the lonely, craggy, atmospheric Cap Fréhel, where in spring you can see gannets, the superb large seabird that never otherwise comes within sight of shore.
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Karimunjawa
From Wikitravel
Java : Central Java : Karimunjawa
Revision as of 13:19, 12 September 2012 by 125.163.210.203 (Talk)
Jump to: navigation, search
Karimunjawa is a chain of 27 islands north of Semarang, off the coast of Central Java, Indonesia.
Understand
Designated as a national marine park. Karimunjawa consists of many small islands, with the main ones being Karimunjawa island, Kemujan island, Menjangan Besar island, and Menjangan Kecil island.
History
Karimunjawa was originally settled by Sunan Nyamplungan, the son of Sunan Muria, one of the Muslim Saints (Sunan) who introduced Islam to Java.
Landscape
Mostly low lying islands with sandy beaches. There is some fringing mangrove around Kemujan island.
Flora and fauna
One can find various kinds of sea animals, like turtles, sharks, and fishes, in the watery territory of Karimunjawa. In the land, especially in Karimunjawa island and Kemujan island, one can find many kinds of birds, deer, and even snakes.
Climate
Tropical. It is very hot here in the dry season (approximately April to October) and wet and humid in the rainy season.
Get in
There are chartered planes from Semarang that fly from Semarang to Dewandaru Airport in Kemujan island. There also a regular ferry that sails from Tanjung Emas port in Semarang and Jepara port to Karimunjawa island.
Get around
In Karimunjawa and Kemujan island, you can rent a car or motorcycle. To get to the other islands, you can use a local boat or motorboat. Inter-island transportation can be booked at the following link, where you can also view timetables.[1] Note: It might be a good idea to book a rental car before you arrive in Karimunjawa because there are few cars there.
See
The island beaches and beautiful coral reefs.
Do
Many resorts in Karimunjawa, such as Kura-kura resort, provide diving activities. There are many interesting local spots for diving, like Taka Panyawangan and Gosong Cemara. There are some shipwrecks that attract many fish and divers alike. You can also go hiking around the island to find many places where there is a beautiful panorama
Buy
The best known handicrafts in Karimunjawa are its wood carvings, and many shops sell them.
Many people also go to Karimunjawa to find the dewandaru plant. They believe that dewandaru plants can make their life longer.
Drink
Alcoholic beverages are served in the hotels, and Bintang (Indonesian beer) can be purchased at some 'warungs.' Bottled water is a must and can be bought readily. At meals, seasonal fresh fruit juice is a treat (mango, orange, avocado).
Eat
Surrounded by seas, Karimunjawa provides lots of sea food. Fresh fish and prawns are staples in the island diet. Restaurants are located within hotels. Other eateries, or 'warungs', provide decent cheap food like fried rice, fish, or an assortment of veggies. Be flexible and you'll do fine.
Sleep
There are various kinds of accommodation there, from the four star hotels to homestays. There are also camping sites.
Lodging
• Roemah Emak Villa[2], a relax home for family, next to the beach
Moderate
• Melati hotel
• Blue Lagoon hotel
• Dewandaru hotel
• Wisma Apung floating hotel
• Escape Beach hotel
Splurge
• Kura-kura Resort [3], in Menyawakan island. Covered by coconut trees and surrounded by white sandy beaches and pristine coral reefs. It's a high class hotel with scuba facilities.
• Nirwana Laut Resort [4], a luxury resort with many facilities.
• Paradise Resort[5], private time share and holiday home. With a private entrance from the main road you experience the most amazing views high above the tree line overlooking the bay, national park and outer islands.
Camping
Backcountry
Stay safe
rent is very cheap local houses with full amenities
Get out
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Zaandam
From Wikitravel
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Zaandam is a medium-sized city just north of the Dutch capital of Amsterdam. It is just a short journey from Amsterdam. Zaandam is part of the municipality of Zaanstad (consisting of 7 towns of which Zaandam is the biggest), in the Zaan Region.
Understand
Directly outside the train station Zaandam is a shopping esplanade (currently being completely rebuilt), bike rental, taxis and a hotel. It takes a ten minutes walk through the rather dull shopping esplanade (called Gedempte Gracht) to get to the slightly more atmospheric area where you can find the pubs and restaurants. That area, with streets like the Zuiddijk and Prins Hendrikkade, is located at the waterfront of the river Zaan.
In all honesty, the centre of Zaandam is not very special, except for a few nice pubs and a venue with live music. The centre is currently a big construction site, as the town council is putting a big effort in reconstructing and rebuilding the city centre under the name "project Inverdan". This project consists of the building of a complete new town hall adjecent to the railway station, a brand new hotel which looks like a pile of wooden houses from the Zaan Region, a shopping mall/apartment complex (Hermitage) and bringing the water back in the Gedempte Gracht shopping mall.
You can explore the typical Dutch landscape with completely flat meadows and windmills around the city. The Zaan Region is possibly the oldest industrial area in the world (as it was not driven by steam but by wind), and it is shown in many old buildings.
• VVV Agentschap Zaandam, Ebbehout 31 (near the railway station), +31 20 201-8800. 24 hours. This tourist information centre has cycling maps, hiking paths and advice on where to go in the region.
Get in
By plane
Direct trains to Zaandam run twice every hour from Schiphol Airport. (These trains have destination Hoorn). In all other cases you can take any train with destination Amsterdam Centraal that stops at Amsterdam Sloterdijk and change there for Zaandam.
By train
Zaandam is just two stops from Amsterdam Central Station. You pass through station Amsterdam Sloterdijk. Trains leave regularly 4-8 trains per hour) until 1 am.
If you are on to visit the Zaanse Schans open air museum, take the "Sprinter" train with destination Uitgeest (runs 4x per hour on weekdays, half-hourly on Saturdays and Sundays) and get off at Koog-Zaandijk railway station (4th stop). From here it is about 10 min.walk to the Zaanse Schans.
By car
Take from the northern part of the circular road of Amsterdam (Ringweg A10) the A8 to Zaanstad/Zaandam, and just follow the signs.
By bus
Connexxion bus lines 92 and 94 run at least 4x per hour to Zaandam Centre (Peperstraat Bus Station) and Zaandam Railway Station. Bus line 91 runs from Amsterdam Central station to the Zaanse Schans open air museum.
Get around
See
Do
The whole area around the river Zaan, to be explored biking, walking, driving around or even boating [1] over the Zaan River. You will see a great mix of old style industry unusual for the Netherlands, old wooden houses and windmills, together with open green pastures (grass land) in the span of just a few miles. It will be like different epochs clash. This journey has to be arranged on an individual basis, as outside the Zaanse Schans tourism is not very well developed.
Buy
Eat
Drink
• Blacksmith, Hogendijk 46, +31 6 150-719-02. Small pub in the old workplace of a blacksmith. On the Hogedijk near the old harbour. A truly local pub with beer-tasting.
• Fishline, Zuiddijk 39, +31 75 615-86-12. W-Th 19:00-01:00, F-Sa 19:00-03:00, Su 12:30-01:00. Blues/rock pub at the waterfront, often with live music and jam sessions. They also have outdoor seating available.
• De Kade, Zuiddijk 9-11, +31 75 617-6972, [2]. Locally well known pop, rock and dance stage, with both DJs and bands performing live. In the centre of Zaandam at the Zuiddijk.
Sleep
• Inntel Hotel, Provincialeweg 102 (close to Zaandam railway station), +31 75 681-0171, [3]. Probably one of the weirdest buildings in the country. It's a new building, designed by architects Molenaar en van der Winden, that resembles about a dozen traditional Zaan houses plopped on top of each other. It looks odd, to say the least, but makes an impressive sight as you walk out of the railway station. It is a four-star hotel that has 160 rooms available. Free WiFi. €85-151.
Contact
Get Out
The Zaanse Schans is north of Zaandam, but still in the Zaan Region. It is an open air museum that consists of old windmills and the original wooden houses. These windmills have approximately 1 million visitors each year.
Routes through Zaandam
Amsterdam S N PurmerendGroningen
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
8771.0 - Private Sector Construction Industry, Australia, Preliminary, 1996-97
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 07/09/1998
Page tools: RSS Search this Product
Help for : Adobe PDF.
Publications
8771.0 - Private Sector Construction Industry, Australia, Preliminary
© 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
The Drosophila IKK-related kinase (Ik2) and Spindle-F proteins are part of a complex that regulates cytoskeleton organization during oogenesis
Dikla Dubin-Bar, Amir Bitan, Anna Bakhrat, Rotem Kaiden-Hasson, Sharon Etzion, Boaz Shaanan and Uri Abdu*
• * Corresponding author: Uri Abdu abdu@bgu.ac.il
• † Equal contributors
BMC Cell Biology 2008, 9:51 doi:10.1186/1471-2121-9-51
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This article is part of the supplement: Selected articles from the Tenth Asia Pacific Bioinformatics Conference (APBC 2012)
Proceedings
A mixture framework for inferring ancestral gene orders
Yiwei Zhang2, Fei Hu2 and Jijun Tang1,2*
Author affiliations
1 Center for Computational Biology, Beijing Forestry University, Beijing 100083, China
2 Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208, USA
For all author emails, please log on.
Citation and License
BMC Genomics 2012, 13(Suppl 1):S7 doi:10.1186/1471-2164-13-S1-S7
Published: 17 January 2012
Abstract
Background
Inferring gene orders of ancestral genomes has the potential to provide detailed information about the recent evolution of species descended from them. Current popular tools to infer ancestral genome data (such as GRAPPA and MGR) are all parsimony-based direct optimization methods with the aim to minimize the number of evolutionary events. Recently a new method based on the approach of maximum likelihood is proposed. The current implementation of these direct optimization methods are all based on solving the median problems and achieve more accurate results than the maximum likelihood method. However, both GRAPPA and MGR are extremely time consuming under high rearrangement rates. The maximum likelihood method, on the contrary, runs much faster with less accurate results.
Results
We propose a mixture method to optimize the inference of ancestral gene orders. This method first uses the maximum likelihood approach to identify gene adjacencies that are likely to be present in the ancestral genomes, which are then fixed in the branch-and-bound search of median calculations. This hybrid approach not only greatly speeds up the direct optimization methods, but also retains high accuracy even when the genomes are evolutionary very distant.
Conclusions
Our mixture method produces more accurate ancestral genomes compared with the maximum likelihood method while the computation time is far less than that of the parsimony-based direct optimization methods. It can effectively deal with genome data of relatively high rearrangement rates which is hard for the direct optimization methods to solve in a reasonable amount of time, thus extends the range of data that can be analyzed by the existing methods.
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"url": "www.familysearch.org/learn/wiki/en/index.php?hidetrans=1&title=Special%3AWhatLinksHere%2FCategory%3AAbitibi_County%2C_Quebec",
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Pages that link to "Category:Abitibi County, Quebec"
From FamilySearch Wiki
What links here
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In the FamilySearch Research Wiki, you can learn how to do genealogical research or share your knowledge with others.
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Washington
From Grand Theft Wiki
Jump to: navigation, search
Vehicle
Washington
(Rear quarter view)
A Washington in GTA Vice City.
Appearance(s) GTA Vice City
GTA San Andreas
GTA Vice City Stories
GTA V
Vehicle type Civilian car
Body style 4-door sedan
Capacity 4 (driver and three passengers)
Manufacturer Albany (GTA IV)
The Washington is a 4-door sedan found in Grand Theft Auto: Vice City, Grand Theft Auto: San Andreas, Grand Theft Auto: Vice City Stories, Grand Theft Auto IV, and, tentatively, Grand Theft Auto V. It can be found fairly widely throughout cities and in mostly the residential area in GTA Vice City and GTA San Andreas, and is available in many colors throughout the games except gray and white, which are reserved for the FBI Washington in GTA Vice City and GTA Vice City Stories, respectively.
Contents
Design
GTA Vice City — GTA Vice City Stories
"Rich man's sedan, import from UK."
- Official Vice City Bureau of Investigation file description, GTA Vice City.[1]
Depictions of the Washington prior to GTA IV bear a similarity to a 1984-1987 Lincoln Continental, with the rear more alike a Lincoln Mark VII.
The Washington features a generally boxy but then contemporary design resulting in the car being one of the newest cars at the time of GTA Vice City's and GTA Vice City Stories' 1980s settings. The colors of the car are varied, with up to eight sprayable colors. For GTA San Andreas, the car remains largely similar, with the exception of wider headlight clusters, a modified front grille and rear light clusters that light up as a whole at night. While similar to the GTA Vice City rendition, the GTA Vice City Stories Washington sports additional side trims derived from the FBI Washington, implying the FBI Washington's vehicle model was used in place of GTA Vice City's original Washington model.
GTA IV — GTA V
In GTA IV, the Albany Washington is based on the 2003-2011 Lincoln Town Car while the headlights and grille have a slight resemblance to a 2008-2009 Ford Taurus. The body style is based off of the Ford "Panther" platform, which the Lincoln Town Car, Ford Crown Victoria, and Mercury Grand Marquis were built on. It features "Executive" badging, much like some Town Cars. The rear portion of the car mainly represents the 1998-2011 Ford Crown Victoria, evidenced by the shape of the trunk lid with the taillights being a slight hint to the car as well. The rim design is taken from those of the 1998-2002 Crown Victoria LX.
The GTA V rendition of the Washington is slated to be identical in design to the GTA IV rendition.
Performance
GTA Vice City — GTA Vice City Stories
Pre-GTA IV Washingtons are generally regarded as having only moderate performance, being RWD, it is largely attributed to its bulky design. Its longer wheelbase and weight, often results in understeer and poor cornering, while its size may also be a factor in its moderate acceleration, and its top speed is also estimated to be moderate. Nevertheless, its superior size and weight allows the Washington to ram aside other sedans more easily.
GTA IV
The Washington in GTA IV is powered by a V8, coupled to a five-speed gearbox in a RWD layout. Acceleration is good, but due to the bulk of the vehicle it leaves much to be desired. Top speed is also good, but again due to the Washingtons weight, is limited: 135 km/h (84 mph). Braking is very good, and ABS is standard across the line up. The suspension is very soft, designed to flatten out bumps in a road; not high speed cornering, leaving the Washington fishtailing and spinning out of control when cornering at speed. Accident deformation is superb, making the Washington ideal for ramming vehicles. The engine build quality is also above average, and will sustain multiple impacts before failing.
Variants
GTA Vice City
The FBI Washington is a specialized version of this vehicle (only appearing in GTA Vice City and GTA Vice City Stories), and is the only version of the Washington in GTA Vice City that sports a dark gray paint job. Its acceleration is quite impressive, which becomes useful for catching up to distant criminals when on a Vigilante mission. In GTA Vice City Stories the car is much more harder to get however because stealing it from the FBI is more challenging rather then finding one. Also the FBI Washington can be the same color as a regular one as there are white regular Washingtons.
Similarly, two uniquely black Washingtons may be seen driven by the French in GTA Vice City during "All Hands on Deck!" in GTA Vice City. While it is possible to reach the cars and enter them, it is impossible to drive them during the mission (as the mission immediately ends and the car is lost). It is possible to push one of them to where the mission would start as an alternative, jump in, leading to mission failure which warps the player back to the nearby mission trigger with the car hopefully waiting there.
GTA IV
The requested Washington in Stevie's Car Thefts in GTA IV.
A special wagon version of the Washington is used for the game's rendition of the Romero hearse. A Washington is also requested as part of Stevie's Car Thefts; unlike most vehicles in the side mission, the Washington appears with a black body color that is not unique, as many black Washington's can be seen around Algonquin.
Customization in GTA San Andreas
The Washington in GTA San Andreas can be modified at a TransFender. However, the garage only offers a fairly limited range of parts for the car:
Italicized pricing denotes prices at the Las Venturas TransFender, which charges 20% more except Colors.
• Colors
• Car Color 1 (primary body color): $150
• Exhausts
• Large Exhaust: $250 ($300)
• Medium Exhaust: $200 ($240)
• Twin Exhaust: $300 ($360)
• Upswept Exhaust: $350 ($420)
• Nitro
• 2x Nitrous: $200 ($240)
• 5x Nitrous: $500 ($600)
• 10x Nitrous: $1,000 ($1,200)
• Spoilers:
• Champ: $400 ($480)
• Fury: $350 ($420)
• Worx: $200 ($240)
• Pro: $400 ($480)
• Wheels
• Import: $820 ($984)
• Atomic: $770 ($924)
• Ahab: $1,000 ($1,200)
• Virtual: $620 ($744)
• Access: $1,140 ($1,368)
• Off Road Wheel: $1,000 ($1,200)
• Mega: $1,030 ($1,236)
• Grove: $1,230 ($1,476)
• Twist: $1,200 ($1,440)
• Wires: $1,560 ($1,872)
• Car Stereo
• Bass Boost: $100 ($120)
• Hydraulics: $1,500 ($1,800)
Trivia
• The name is mostly always meant to be a parody of a full-size luxury Lincoln sedan (Abraham Lincoln and George Washington having both been Presidents of the United States).
• On the GTA Vice City website, it is claimed that the car is an import from the United Kingdom, which would contradict its similarities to Lincoln vehicles.
A cutscene-only Washington in the opening cutscene of "Outrider", GTA San Andreas, sporting a higher-than-usual greenhouse.
• In GTA San Andreas, an alternate, cutscene-only version of the Washington appears in the opening cutscene of "Outrider", with a heightened greenhouse. This is presumably done as the greenhouse on regular Washington's may have been too short for scenes within the car. The variant also features lower ground clearance and a steering wheel model that can be rotated.
• Like the Blista Compact and Mesa Grande, the Washington has different engine sounds in each third generation game.
• After collecting all thirty cars for Stevie in GTA IV, a Washington may be sold at his garage for $2,200.
• The GTA IV rendition of the Washington will make an audible "door ajar" dinging noise if the player exits the vehicle but leaves the door open. It can be heard clearly in quiet areas with the volume turned up.
• In its appearances in GTA San Andreas and GTA IV, the Washington plays the following radio stations by default when entered:
Locations
GTA Vice City
GTA San Andreas
GTA Vice City Stories
GTA IV
Reference
1. Vice City Crime Tree. Rockstar Games. official GTA Vice City website
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BioMed Research International
Volume 2013 (2013), Article ID 161687, 16 pages
http://dx.doi.org/10.1155/2013/161687
Review Article
Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence
1Center for Structural and Functional Neurosciences, The University of Montana, 32 Campus Drive, Skaggs Building 287, Missoula, MT 59812, USA
2Departamento de Investigación, Hospital Central Militar, Secretaria de la Defensa Nacional, 11649 México, DF, Mexico
3Departamentos de Radiología y Patología Experimental, Instituto Nacional de Pediatria, 04530 México, DF, Mexico
4Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico
Received 7 November 2012; Revised 1 January 2013; Accepted 1 January 2013
Academic Editor: Tim Nawrot
Copyright © 2013 Lilian Calderón-Garcidueñas 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
Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer’s and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.
1. Introduction
Air pollution is a significant health problem in megacities around the world [13]. In a scenario where the projected world population will have a further increase of 2 to 4.5 billion in the first 50 years of this century [4], the issue of deteriorating environments and their health impact is critical. The problem of air pollution is not confined to large urban centers, it also affects small cities and rural areas. Particulate matter (PM) air pollution is a public health problem affecting millions of people worldwide.
Recent works have shed new light on the etiology of Alzheimer’s and Parkinson’s diseases (AD and PD), with a growing body of evidence that oxidative stress and neuroinflammation are at the core of their etiopathogenesis and that there is a close interplay between environmental factors and neurodegeneration [58]. We also know the most beneficial neuroprotective effects might only be achieved in the very early stages of the detrimental processes. As such, a great effort has been made in establishing the associations between particulate air pollution, neuroinflammation, and neurodegeneration in highly exposed megacity children and young adults. The first part of this paper deals briefly with the current state of air pollution in Mexico City Metropolitan Area (MCMA) and with the several areas of investigation in our laboratory that exemplify how seemingly clinically healthy children are responding to the sustained exposures to air pollutants. The second part of the paper turns to a more troublesome challenge. How do you formulate the neuropathology and gene brain expression findings in clinically healthy children and young adults and establish the links with the current mainstream concepts of neurodegeneration. This principled problem thus addresses the relation between neuroinflammation, neurodegeneration, and air pollution exposures with an emphasis on compensatory responses. Dealing with this problem invites the development of linking hypotheses between the domains and the need for intervention, issues addressed in the third part of the paper.
2. Air Pollution Background and Clinical Issues in Metropolitan Mexico City Clinically Health Children
2.1. Air Pollution in Mexico City Metropolitan Area (MCMA)
Although there is significant air pollution associated with ozone in MCMA, in this work, we will focus on particulate matter (PM) broadly defined by the diameter of the aerodynamic particles and classified into coarse particles (<10 μm; PM10), fine particles (<2.5 μm; PM2.5), and ultrafine particles (<100 nm; UFPM). Fine and ultrafine PM are of particular interest given their capability to reach the brain [9]. The smaller the particle, the greater its penetration, diffusion, and deposition into the respiratory tract and its direct translocation into the brain [911].
MCMA, the largest urban center in North America, is an example of extreme urban growth and environmental pollution [12]. The metropolitan area of over 2000 square kilometers is home to over 20 million inhabitants including 8 million children. The energy demand of this population and over 40000 industries and 4 million vehicles consumes more than 40 million liters of petroleum fuels per day resulting in an annual emission of approximately 2.6 tons of pollutants including coarse and fine particulate matter, gaseous pollutants, polycyclic aromatic hydrocarbons, and lipopolysaccharides [12]. The MCMA is located in the southwestern portion of an elevated basin 2240 m above sea level that is surrounded on three sides by mountain ridges at 19° N 99° W. The high altitude and tropical insolation of the basin facilitate ozone production all year and contribute to the formation of secondary PM. Air quality is generally worse in the winter when thermal inversions are more frequent [13].
Even with the substantial reductions in the concentrations of some criteria pollutants (such as lead, CO, and SO2) achieved during the past fifteen years, MCMA residents remain exposed to concentrations of airborne pollutants exceeding current ambient air quality standards for PM and ozone [14]. High concentrations of PM2.5 as well as significant levels of PM10 associated with lipopolysaccharides (PM-LPS) have been registered historically in Mexico City’s air, and marked regional differences in the air pollutants concentrations and composition have been reported within MCMA [12, 1519].
Figure 1 shows the trend of 24-hour average PM10 concentrations for MCMA (1995–2011). PM10 concentrations had shown a clear reduction up to 2007; however, concentrations have been slowly back on the rise in the last 5 years. PM2.5 data from the monitoring network [20] in Figure 2 show the 90th percentile of the 24-hour average concentrations per year have been above the respective air quality standard of 35 μg/m3. MCMA residents are also exposed to UFPM from ambient air and workplaces. These nano sized PM include combustion sources (e.g., diesel exhaust particles, welding fumes) and manufactured or engineered nanoparticles (NPs). It is not widely appreciated that nano-sized materials are also present in many consumer products to which large segments of the population are exposed (e.g., toothpastes, cosmetics, sunscreens, food additives, and laser printer emissions) [21, 22].
Figure 1: Trend of the PM10 24-hour average concentrations from all monitoring stations in the MCMA from 1995 to 2011. The dashed line shows the U.S. EPA PM10 24 hr average air quality standard (data from the SMA-GDF).
Figure 2: Trend of the PM2.5 24-hour average concentrations from all monitoring stations in the MCMA from 2004 to 2011. The dashed line shows the U.S. EPA PM2.5 24 hr average air quality standard (data from the SMA-GDF).
In this massive exposure chamber, 8 million children and teens <18 y are receiving the impact of the involuntary exposure to the polluted air.
2.2. Detrimental NonCNS Effects in Exposed Children
It is important to emphasize that PM exposure has been epidemiologically associated to a wide spectrum of cardiovascular, pulmonary, and CNS effects [10, 11, 2325]. Exposure to fine PM over a few hours to weeks can trigger cardiovascular disease-related mortality and nonfatal events [10]. Longer-term exposure increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days [10]. In the cardiovascular literature “credible pathological mechanisms have been elucidated that lend biological plausibility to (detrimental) findings” [10]. Two mechanistic pathways applied to the cardiovascular and lung effects fit precisely the detrimental pathways in place in MCMA children [8]. These pathways include: pulmonary and systemic oxidative stress, and inflammation and direct effects of PM or its constituents on the vasculature and/or blood elements after translocation from the lung [10].
The pediatric studies from our laboratory cited in this work were performed in Mexico City clinically healthy children with no known risk factors for pulmonary, cardiovascular, and CNS pathology or cognitive deficits. MCMA children are selected from nonsmoking families and their results compared to age, gender, and socioeconomic status (SES) matched children residing in low polluted places. The detrimental nonCNS effects associated to residency in MC include the following.(i)Systemic inflammation with increased concentrations of proinflammatory cytokines, chemokines, and potent vasoconstrictors (i.e., endothelin-1, ET-1). The concentrations of inflammatory mediators and ET-1 correlate positively with cumulative exposures to PM2.5 and outdoor exposure hours [26]. Chronic inflammation involving the upper and lower respiratory tracts has been identified as a link between air pollution and brain damage [2633]. Continuous expression of inflammatory mediators capable of reaching the CNS promotes the formation of reactive oxygen species (ROS) [8]. Activation of innate immune responses within the brain may follow the interactions between circulating cytokines and the constitutively expressed cytokine receptors of brain endothelial cells. Such responses may, in turn, be followed by activation of cells involved in adaptive immunity [30, 34, 35]. Monocytes are the main innate immune response mediator cells, producing and secreting TNF-α, interleukin-6 (IL-6), and IL-1β, which in turn recruit and increase the activity of other immune cells [34]. Sustained exposures to fine and ultrafine PM likely start a chain of events leading to brain endothelial cell activation, disruption of the neurovascular unit, altered response of the innate immune system, neuroinflammation, and neurodegeneration [8, 30, 3436].(ii)Altered immune responses include significant decreases in the numbers of natural killer cells and increased numbers of mCD14+ monocytes and CD8+ cells. The reduction in the number of NK cells goes along with the low concentrations of interferon gamma (IFN-γ) [28]. MCMA children have monocytic mCD14 upregulation—a key membranous receptor involved in lipopolysaccharide (LPS) binding. The CD14 upregulation represents the early step in cell activation by LPS involving the innate immune initial host response to Gram negative bacterial infections [37]. MCMA children are historically exposed to endotoxin associated with PM [17, 28, 32, 38]. The issue is very important because we have shown there is a significant frontal upregulation of inflammasome-associated genes in MCMA children and young adults [30]. Moreover, particle exposure has been associated to pathogen sensors and the signaling by ROS drives inflammasome intracellular signaling complexes activation [3941]. Even very low doses of LPS elicit an augmented response to subsequent endotoxin challenge with a violent immune response [42]. The priming phenomenon could play a role in the neuroinflammatory responses observed in MCMA children [30, 35]. (iii)Pulmonary changes in MCMA children living in tobacco free homes include bilateral hyperinflation and increased linear markings observed in chest radiographs and mild bronchial wall thickening, prominent central airways, air trapping and pulmonary nodules identified by computed tomography scans. Abnormal lung function tests based on predicted values are seen in 7.8% of MCMA children. Higher concentrations of endothelin-1 correlate with elevations of mean pulmonary artery pressure, average hours per day spent outdoors, and 7 day cumulative concentrations of fine PM2.5 [26, 27]. (iv)Cardiovascular effects include a significant right ventricle upregulation of IL-1β, TNF-α, IL-10, and CD14, and a left ventricle difference in TNF-α, and IL-10 in South versus North Mexico City residents, a key point in relation to the marked difference in pollutant profiles determined by the residence MCMA location [43].
2.3. Detrimental CNS Effects in Exposed Children
MCMA children with no known risk factors for neurological or cognitive disorders exhibit significant deficits in a combination of fluid and crystallized cognition tasks versus control children [29]. Fifty-six percent of MCMA children showed prefrontal white matter hyperintense (WMH) lesions by MRI and similar lesions were observed in MCMA dogs (57%) [29]. One control child out of 13 tested exhibited a single white matter lesion, and this child was an APOE 3/4 carrier [29]. Critical to this paper, MC breed animal facility dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition [29]. The dogs MRI findings were the same as the children, including their prefrontal location [29]. The data suggested the prefrontal cortex was a target anatomical region in exposed children and its damage could have contributed to their cognitive dysfunction. We next tested whether patterns of brain growth, cognitive deficits, and WMH were associated with exposures to MCMA air pollution [44]. Baseline and 1-year followup measurements of global and regional brain MRI volumes, cognitive abilities (Wechsler Intelligence Scale for Children-Revised, WISC-R), and serum inflammatory mediators were collected in 20 MCMA children (10 with white matter hyperintensities, WMH (+), and 10 without, WMH (−)) and 10 matched controls (CTL). There were significant differences in white matter volumes between CTL and MCMA children—both WMH (+) and WMH (−)—in right parietal and bilateral temporal areas. Both WMH (−) and WMH (+) MC children showed progressive deficits, compared to CTL children, on the WISC-R Vocabulary and Digit Span subtests. Interestingly, the cognitive deficits in MCMA children matched the localization of the volumetric differences detected over the 1 year followup [44].
When we analyzed the WMH lesions in relation to the profile of cytokines and chemokines [32], MCMA WMH (−) children displayed the profile of classical proinflammatory defensive responses: high interleukin 12, production of powerful proinflammatory cytokines, and low concentrations of key cytokines and chemokines associated with neuroprotection. In contrast, MC WMH (+) children exhibited a response involved in resolution of inflammation, immunoregulation, and tissue remodeling. The MC WMH (+) group responded to the air pollution-associated brain volumetric alterations with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to MC WMH (−).
These findings suggest a complex modulation of cytokines and chemokines influencing children’s white matter hyperintensities, volumetric white matter responses and cognitive outcomes as a result of environmental pollution exposures.
3. Neuroinflammation and Neuropathology in Mexico City Children and Young Adults and Comparative Studies
In 2002, we published a dog study pointing to the nasal cavity as a major portal of entry of xenobiotics to the brain [45]. The study evaluated 32 healthy mongrel MCMA dogs, versus 8 dogs from Tlaxcala, a low polluted control city. MCMA dogs exhibited expression of nuclear neuronal NF-kappa B and iNOS in cortical endothelial cells at ages 2 and 4 weeks with subsequent damage to the blood-brain barrier (BBB), deposition of Apolipoprotein E (APOE)-positive lipid droplets in smooth muscle cells and pericytes, diffuse amyloid plaques, and neurofibrillary tangles [45]. Nasal respiratory and olfactory epithelium were clearly found to be early pollutant targets, as evidenced by the significant apurinic/apyrimidinic (AP) sites in MCMA dogs versus controls [46]. Moreover, olfactory bulb and hippocampal AP sites were also significantly higher in MCMA animals and nickel (Ni) and vanadium (V) were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex [46]. Striking findings in our canine studies included the presence of diffuse amyloid plaques in 11-month-old dogs and the presence of oil combustion PM-associated metals Ni and V in brain target areas. The dog studies are critical as they showed Alzheimer pathology beginning early in life with air pollutants playing a crucial role. Healthy young dogs exhibit a striking acceleration of Alzheimer’s pathology when they live in a highly polluted place. It is well known that dogs are a good aging model and AD-type pathology and cognitive deficits are seen in older animals [4749].
3.1. Neuroinflammation and Vascular Damage in MCMA Children and Young Adults
A very critical component of air pollution exposure is neuroinflammation [8, 5052]. MCMA young urbanites exhibit an important frontal imbalance in genes essential for inflammation, innate and adaptive immune responses, oxidative stress, cell proliferation and apoptosis, when compared to age-matched residents in low pollution cities [30]. Measurements of mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from 12 controls and 35 MC residents aged years showed upregulation of cyclooxygenase-2, IL-1β, and CD14 in supra, and infratentorial regions and cranial nerves including: olfactory bulb, frontal cortex, substantia nigrae, and the vagus nerve [35].
The entry of activated lymphocytes, mast cells, and macrophages into the brain parenchyma is a hallmark of chronic inflammatory processes [34, 5356]. Clusters of mononuclear cells around blood vessels and activated microglia in the frontal and temporal cortex, subicular area, and the brain stem (Figure 3(a)) were present in all MCMA children and were extremely rare in control children [30, 35]. These mononuclear cells are positive for CD68, CD163, Iba-1 (Figure 3(a)), and HLA-DR (Figure 3(b)) [57]. Intact and degranulated mast cells identified by means of tryptase monoclonal antibodies are seen in perivascular locations in frontal (Figure 3(c)) and temporal cortices, as well in trigeminal ganglia, and in peripheral autonomic nerves innervating the lungs and hearts in MCMA subjects, whereas in the controls mast cells were rare and intact. Blood vessels exhibit vacuolated endothelial cells and marginal WBCs, both indicative of endothelial damage and activation (Figure 3(d)). While the presence of abundant lipofuscin in endothelial cells (Figure 3(e))—usually associated with aging and indicative of a highly oxidized and covalently cross-linked aggregate of proteins—is evidence of a dysfunctional lysosomal degradation not expected in children or young adults.
Figure 3: (a) Eleven year old MCMA girl with abundant ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglia. Approximately 50% of the perivascular cells are Iba-1+ (Iba-1 antibody with DAB + brown product). (b) Eleven year old MCMA girl with brainstem perivascular accumulation of HLA-DR positive cells (HLA-DR antibody and DAB + brown product). (c) Frontal cortex in a MCMA 24 y old male with perivascular partially degranulated tryptase positive cells (Tryptase Ab with DAB + brown product). (d) Olfactory bulb blood vessel in a 14 year old MCMA boy. Notice a vacuolated endothelial cell and a polymorphonuclear leucocyte (PMN) attached to the vessel wall. Two glomeruli are adjacent to the damaged vessel. H&E. (e) Olfactory bulb blood vessel in a 14-year-old MCMA male APOE 3/3. Endothelial cells in the delicate vessel exhibit abundant lipofuscin, a highly oxidized and covalently cross-linked aggregate of proteins associated with aging. H&E. (f) Frontal cortex white matter from a MCMA 33 year old healthy subject with a cluster of blood vessels displaying perivascular numerous macrophages with lisosomal bodies and lipofuscin. The larger vessel displays abundant cell debris within the wall. One micron toluidine blue section. (g) Fourteen year old MCMA girl prefrontal white matter with an abnormal blood vessel displaying perivascular macrophages with lisosomal bodies and lipofuscin, abundant cell debri within the wall, apoptotic nuclei and focal enlargement of the Virchow-Robin space. One micron toluidine blue section. (h) Vascular lesions are also seen in young MCMA dogs. This 19 month dog exhibits a frontal white matter arteriole with hyperplastic endothelial cells partially reducing the lumen. One micron toluidine blue section. (i) The prefrontal cortex exhibits extensive vascular white matter damage, illustrated in this 13 y old MCMA girl. The arteriole shows extensive perivascular accumulation of macrophages with abundant lisosomal bodies. A striking enlargement of the Virchow-Robin space is seen with focal white matter damage. One micron toluidine blue section. (j) Seventeen year old MCMA teen brainstem blood vessel with extensive leaking expanding the Virchow-Robin space. (k) Same child as (j), the breakdown of the neurovascular unit also affects smaller blood vessels. (l) Electron micrograph of an olfactory bulb arteriole in a 17 y old MCMA boy. There is marked focal thickening of the vessel wall, numerous perivascular macrophages with lisosomal bodies and lipofuscin and vacuolization of endothelial cells. (m) Nanosized particles are seen in endothelial cells in many brain regions. This electron micrograph from a 17 y old MCMA male shows an arteriole in the olfactory bulb with two sharply defined particles in the endothelial cell cytoplasm and its basement membrane. The particles are 16 to 20 nanometers. EM ×50,000.
There was extensive vascular damage in the olfactory bulb and in the frontal cortex. In the prefrontal cortex, the vascular damage affects predominantly white matter (Figure 3(f)). The main vascular findings included thickened walls, abundant perivascular macrophages, and focal enlargement of the Virchow-Robin spaces (Figure 3(g)). Young dogs show similar lesions to children with significant endothelial cell hyperplasia markedly reducing the vessel lumen (Figure 3(h)). The extensive prefrontal vascular damage is accompanied by white matter focal damage that in some children is significant (Figure 3(i)). Extensive leaking of blood vessels involves supra and infratentorial regions (Figures 3(j) and 3(k)). Olfactory bulb arterioles also show marked focal thickening of the vessel walls, indicative of a chronic reparative process (Figure 3(l)).
Ultrafine particles are likely players in the endothelial cell activation and are found in various CNS regions, including the Olfactory bulb (Figure 3(m)). UFPM are also seen in erythrocytes with the formation of patterned discrete contact points between endothelial cells and RBCs in the CNS, trigeminal ganglia, and lung capillaries of highly exposed people [35].
3.2. Alzheimer’s and Parkinson’s Diseases Hallmarks
A growing body of epidemiologic and experimental data point to particulate matter components of air pollution as well as nanoparticles in the environment as risk factors for neurodegenerative diseases [51, 52, 5863]. Indeed, exposure to different size and composition PM produce molecular hallmarks of neurodegeneration, including the production and deposit of misfolded protein aggregates (amyloid, alpha synuclein, hyperphosphorylated tau), oxidative stress, cell damage and death in susceptible neuronal populations [51, 52, 6466]. Neuronal oxidative stress is prominent even in small MCMA children [35]. Extensive cytoplasmic accumulation of 8OHdG in key neuronal complexes (Figure 4(a)) correlates with oxidative stress and damage to DNA. Nitrotyrosine, a marker for inflammation and nitric oxide (NO) production, is also present in frontal neurons and infratentorial neuronal groups (Figure 4(b)). Nitrotyrosine positive inclusions are also seen in glial cells, microglia, and perivascular macrophages [35].
Figure 4: (a) Eleven year MCMA girl dorsal motor nucleus of the vagus stained with anti-8-OHdG showing immunohistochemical staining of oxidized nucleoside in neurons. 8-hydroxyguanosine is a modified base that occurs in DNA due to attack by hydroxyl radicals that are formed as byproducts and intermediates of aerobic metabolism and during oxidative stress. 8-OHdG immunohistochemistry red product. (b) Same 11 y old girl as in Figure 4(a) showing caudal pontine reticular nucleus neuronal protein oxidation marked by nitrotyrosine immunoreactivity. (c) Frontal cortex in an APOE 3/3 17 y old MCMA teen. A diffuse amyloid plaque (red product) is seen surrounded by glial cells negative for reactive astrocytes as detected by their reaction to the glial fibrillary acidic protein (GFAP). Dual immunohistochemistry for amyloid beta 1–42 and GFAP (DAB + brown product). (d) Frontal cortex in a 36 y old MCMA male APOE 3/4. This subject shows numerous diffuse and mature amyloid beta 1–42 plaques. (e) Frontal cortex in a 15 y old MCMA APOE 3/3 boy. Abnormal tau protein positive with the Tau 8 antibody (Innogenetics, Belgium), both in the neuronal body and in neuritis. (f) Frontal cortex in a 15 y old MCMA APOE 3/4 boy. A clear Tau 8 positive neurite is seen.
3.2.1. Cortical Neurodegeneration Hallmarks
In young MCMA residents, amyloid beta42 (Aβ42) frontal (Figure 4(c)), olfactory bulb, and/or hippocampal immunoreactivity was observed in 58.8% of Apolipoprotein E (APOE) 3/3 <25 y, and 100% of the APOE 4 subjects (Figure 4(d)), whereas α-synuclein was seen in 23.5% of <25 y subjects [29]. In a different MCMA cohort, aged years, 40% exhibited tau hyperphosphorylation with pretangle material (Figures 4(e) and 4(f)) and 51% had Aβ42 diffuse frontal plaques compared with 0% in controls [30]. Thus, diffuse amyloid plaques and pretangle hyperphosphorilated tau are common frontal findings in highly exposed children, while low pollution controls are negative.
3.2.2. Brainstem Neurodegeneration Hallmarks
Infratentorial involvement is also present in exposed children thus neuropathology is seen in the brainstems of children age months from highly polluted () versus a low polluted city () [67]. Figure 5(a) shows medial superior olivary neurons with strong oxidative stress as evidenced by their 8-hydroxyguanosine immunoreactivity. MC children have auditory and vestibular abnormal findings [67]. The pathology involves every level of the brainstem from the midbrain to the lower medulla. The substantia nigrae pars compacta displays IBA-1 microglia. The number of activated microglia also varies significantly between control and MCMA children (Figures 5(b) and 5(c)). Activated microglia are found throughout the brainstem in exposed children (Figures 5(c), 5(d), and 5(e)), along with reactive glial fibrillary acidic protein (GFAP) positive astrocytes, indicative of responsive glia to cell damage (Figure 5(f)). Accumulation of α-synuclein, activated microglia, extracellular neuromelanin, and pigment-laden macrophages are seen from the dorsal motor nucleus of the vagus level (Figure 5(g)) to the substantia nigrae midbrain sections (Figures 5(h) and 5(i)). There is a punctuated cytoplasmic accumulation of α-synuclein in affected neurons, while α-syn positive neurites are also seen in the neuropil.
Figure 5: (a) Medial superior olive neurons from an 11 year old MCMA girl exhibit strong positivity for 8-hydroxyguanosine indicative of oxidative stress. 8-OHdG immunohistochemistry DAB brown product. (b) Substantia nigrae, pars compacta in a 17 y old Control teen. The section has been stained for the ionized calcium binding adaptor molecule 1 (IBA-1). There are very few positive cells. IBA-1 antibody with red product. (c) In contrast, this is the substantia nigrae, pars compacta in a 14 y old MCMA teen stained for IBA-1. Numerous positive cells are seen among the pigmented neurons and in perivascular locations. IBA-1 antibody with red product. (d) The same child has numerous positive IBA-1 activated microglia in her vestibular nuclei. IBA-1 antibody with brown product. (e) Same child as previous picture. Positive IBA-1 activated microglia in her dorsal motor nucleus of the vagus. IBA-1 antibody with brown product. (f) Reactive astrocytes are part of the response of glial cells to cell damage. Reactive astrocytes positive for GFAP surround the dorsal motor nucleus of the vagus neurons in this MCMA teen. GFAP with DAB brown product. (f) The dorsal motor nucleus of the vagus displays positive α synuclein neurons in the same child as 5F. α-Synuclein with red product. (h) The substantia nigrae is an early target in highly exposed teens. In this 11 y old girl there are partially degranulated pigmented neurons with a few macrophages containing the pigmented granules. An elongated microglia-like cell contains such brown granules in the vicinity of a neuronal shadow. H&E. (i) Substantia nigrae pigmented neuron is positive for alpha-synuclein in this 14 y old MCMA girl. α-Synuclein with red product.
3.2.3. Olfactory Bulb Neurodegeneration
The olfactory bulb pathology deserves special attention because large segments of the world population are exposed to a myriad of toxic substances on a daily basis that have the potential for harming the olfactory system and penetrating the brain via the olfactory epithelium (OE) [6871]. Extreme instances of such exposures in the USA include the massive dust cloud following the September 11, 2001, terrorist attack in New York City, smoke and debris from wildfires, exposures to airborne herbicides and pesticides in farming communities, and pollutants from vehicle exhaust and manufacturing enterprises in major metropolitan areas. The issue is very important because olfactory dysfunction is among the earliest “preclinical” features of AD and PD, occurring in ~90% of early onset cases [7276].
In MCMA residents, the severe pathological changes in the nasal respiratory epithelium go hand and hand with a marked decrease in olfactory neurons, significant changes in Bowman’s glands, and pathologic Alzheimer and Parkinson’s early stage changes within the olfactory bulbs (OBs) [77]. In one study comparing the OBs of 35 young MCMA residents versus 9 controls ( years) from a minimally polluted city, the MC residents exhibited significant amounts of particles in OB glomerular neurons (Figure 6(a)), while reactive astrocytes were prominent in young children (Figure 6(b)). Immunoreactivity to alpha-synuclein, a hallmark of Parkinson’s disease was present in OB neurons of MCMA teens and young adult (Figures 6(c), 6(d), and 6(e)) [77]. While neuronal accumulation of Aβ42 was present in young children regardless of APOE genotype (Figure 6(f)). The basic laminar OB organization of the glomerular, external plexiform, mitral cell, internal plexiform, and granular cell layers of the controls were generally intact (Figure 6(g)). In contrast, ill-defined and fragmented organization of the olfactory bulb layers, including small acellular glomeruli characterized MCMA youngsters (Figure 6(h)). The changes were extreme in APOE 4 carriers (Figures 6(i) and 6(j)). The early olfactory deficits appear to be associated with the aforementioned presence of beta amyloid, alpha synuclein, particulate matter in glomerular structures and the massive distortion of the OB organization.
Figure 6: (a) Fourteen year old MCMA boy with abundant particulate material in neurons in the glomerular region. The insert shows a close-up of one such neuron with abundant particles and positive red cytoplasmic stain for Aβ42. Aβ42 immunohistochemistry and hematoxilin counterstain. (b) Reactive astrocytes are seen in the olfactory bulbs of MC children and teens. This is a 14 y old MCMA boy with reactive olfactory bulb astrocytes strongly staining for GFAP. GFAP immunohistochemistry with red product. (c) Olfactory bulb in an 11 y old MCMA boy APOE 3/3. Numerous neurons display positive cytoplasmic granular staining. α-Synuclein with red product. (d) A close-up of an olfactory bulb neuron with abundant α-Synuclein. (e) A close-up of a Lewy neurite is seen. α-Synuclein with red product. (f) Eleven year old MCMA male with β-amyloid 1–42 in olfactory bulb neurons. Aβ42 immunohistochemistry and hematoxilin counterstain. (g) This is the olfactory bulb of a control 20 year old male from a low polluted city. The glomerular structures are organized and exhibit normal cellular components. H&E. (h) In contrast, this is the olfactory bulb of an 11 year old MC boy APOE 3/3 with abnormal, loose and low cellular glomeruli. H&E. (i) Even more striking changes are seen in this 32 y old MC APOE 4/4 female. There are no remaining normal glomeruli, the few structures remaining are ill-defined with very few cells o no cells at all. It is expected this individual had significant olfactory deficits. H&E. (j) Same case as (i). The olfactory bulb shows extensive premature accumulation of corporae amylacea: glycoproteinaceous inclusions in astrocytic processes associated with astrocytic injury and gliosis. Premature accumulation of corpora amylacea plays an important role in the sequestration of toxic cellular metabolites. H&E.
3.3. The Role of the APOE Genotype in the Brain Effects of Air Pollution
The Apolipoprotein E (APOE) 4 polymorphism influences aging and age-related diseases including the risk for Alzheimer’s disease [7880]. The differential effects of ApoE isoforms on AD risk are given at least in part by the ability to affect Aβ aggregation and clearance in the brain, effects on synaptic plasticity, cell signaling, lipid transport and metabolism, and neuroinflammation [78]. APOE receptors influence both the CNS effects of APOE as well as Aβ metabolism and toxicity. The APOE 4 genotype (in contrast to APOE 3) is associated with oxidative stress and chronic inflammation [78]. In traumatic brain injury, APOE 4 carriers may be more predisposed to brain cellular damage as measured by S-100B and NSE concentrations [79]. APOE4 also influences plasma lipid concentrations, increases the risk of type 2 diabetes mellitus (particularly among obese subjects and smokers), conditions associated with high oxidative stress, neuroinflammation, and brain vascular damage [80]. In keeping with the current literature suggesting APOE 4 carriers have disadvantages in terms of brain repair, management of Aβ metabolism and toxicity and increased oxidative stress and chronic inflammation, we have shown MCMA APOE4 carriers have greater hyperphosphorylated tau and diffuse Aβ plaques versus E3 carriers (, ) [30]. This observation is important because based on our data, air pollution moderates the association between APOE genotype and neurodegenerative changes, that is, an APOE 4 carrier residing in a highly polluted environment will have an acceleration of neurodegenerative changes towards AD [35]. This information is critical when planning the neuroprotection of susceptible populations exposed to air pollutant components.
4. Compensatory Responses versus Neurotoxic and Neurodegenerative Changes. Friend or Foe?
In our pediatric studies, the early clinical olfactory deficits appear to be associated with the presence of misfolded proteins, reactive gliosis and vascular damage in the olfactory bulb and the frontal cortex [77]. There is no doubt the extensive olfactory bulb pathology likely affects OB proteins with critical functions [81]. Likewise, the prefrontal cortex differential regulation of key gene networks; that is, IL1, NFκB, TNF, IFN, and TLRs are likely players in the significant cognitive deficits observed in children with no risk factors for neurological or cognitive deficits, other than their residency in a highly polluted megacity [29, 32, 33, 77]. In the same stream of thought, the central delay in the brainstem auditory evoked potentials and the significant white matter volumetric changes described after 1-year followup of MCMA versus control children could be related to the accumulation of abnormal proteins in key neuronal groups and the significant neuroinflammation involving both gray and white matter [30, 35, 67].
In view of the cognitive, olfactory, auditory, vestibular, and volumetric white matter changes described in exposed children, a series of critical questions arise: (1)What is the role of PM in the neuroinflammatory process described in highly exposed children? (2)What is the relationship between clinical and electrophysiological changes and the described neuropathology? (3)How to interpret the neuropathology hallmarks of AD and PD in a 10 year old child with no family history of neurological diseases?
Let us begin with the issue of particulate matter: Mexico City residents have been chronically exposed to concentrations of particulate matter above the USA standards for the last 26 years [1, 12, 13, 16]. A considerable fraction of the PM2.5 consists of organic compounds including biologic components from bacteria and fungi, and transition metals with neurotoxic properties [1719]. Environmental endotoxins—from open field waste areas, waste water treatment plants, open sewer channels, and daily outdoor deposits of 500 metric tons of animal and human fecal material—are an important part of the organic portion of PM2.5.
Why is PM important for MCMA children? Because fine and ultrafine particles reach their brain by uptake through olfactory neurons and cranial nerves, trafficking of macrophage-like cells loaded with PM from the lung capillary bed to the systemic circulation, and by a direct transfer of ultrafine particles from the systemic circulation and/or red blood cells to brain endothelial cells [30, 35]. Our data and those of others suggest that exposure to PM can activate pathogen sensors, and that signaling by ROS can drive inflammatory processes [8286]. Asbestos and silica activate the NALP 3 inflammasome and NALP3 deficient mice have a significant reduction of their lung inflammatory responses [41]. The innate immune system rapidly detects invading pathogenic microbes and eliminates them. We have shown an upregulation of 27/84 frontal inflammasome associated genes, including NOD-like receptors and proinflammatory caspases [30], so it is biologically plausible that PM with lipopolysaccharides (PM-LPS) initiates an inflammatory brain response. Toll-like receptors sense “extracellular microbes” (e.g., PM-LPS) and trigger anti-pathogen signaling cascades [84]. Both LPS responses and systemic inflammation are important for the understanding of how the sensing of “microbial invaders” could translate into signaling pathways that culminate in the transcriptional regulation of immune responsive genes and how the activation of inflammasomes [84] could be a contributing factor for CNS inflammatory responses. The inflammasome activation results in caspase 1 activation leading to processing and secretion of proinflammatory cytokines like IL1β to engage innate immune defenses [86]. Indeed, this pathway is clearly active in MCMA children: the activation of inflammasomes turns on the protease caspase-1. Caspase-1 cleaves prointerleukin-1β into an active form. We have repeatedly shown IL-1β in frontal cortex, olfactory bulb, hippocampus, and the dorsal vagal complex is upregulated in highly exposed children, dogs and mice compared to low pollution controls [30, 35, 87]. There is a clear need for better understanding of the role of inflammasome activation in urban children’s brains and the defense against pathogens that do not really exist (only components of them, e.g., PM-LPS), and neuroinflammation. This is of particular importance as neuroprotective strategies are being explored.
The relationship between clinical and electrophysiological changes and the described neuropathology is of deep interest to pediatricians working in polluted urban centers. We mentioned olfaction deficits and abnormal UPSIT (University of Pennsylvania Smell Identification Test) scores present in 35.5% of the MCMA teens versus 12% of age matched controls [77]. Moreover, highly exposed APOE 4 carriers failed of the 10 UPSIT items identified in one study as being most strongly related to AD [88], while APOE 2/3 and 3/3 subjects failed only such items (). The olfactory bulb neuropathology associated with urban exposures is very similar to the one described in early stages of AD and PD [8996].
The central delayed brainstem auditory evoked potentials (BAEPs), auditory impairment and vestibular dysfunction could relate to the extensive brainstem inflammation with accumulation of β amyloid and alpha synuclein in key olfactory nuclei [67]. Neurodegenerative changes in the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, arcuate nucleus, raphe midline, and extra-raphe medial and lateral tegmental neurons [67] are similar to the PD stages I and II of Braak et al. [90, 91, 96].
It is difficult to establish the association between cognitive deficits, frontal tau hyperphosphorylation, and amyloid-β diffuse plaques in the absence of cognitive and brain MRI data in the demised children. However, we have shown a strong relationship between residency, brain structural changes and cognitive deficits [32]. MCMA children with WMH (+) are responding to the air pollution exposures with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to WMH negative children [32]. WMH in elderly people are associated with clinical symptoms related to disruption of fiber tracts, cognitive impairment risk, cerebral ischemia, neurodegeneration, cardiovascular, and metabolic diseases [97106]. WMH partially identify underlying white matter pathology and may be associated with widespread white matter changes, the novel concept of white matter hyperintensities penumbra [107]. Disruption of fiber tracts in the developing brain could result in cortical cholinergic and monoaminergic deafferentation and impact attention, emotion and goal-directed behavior [99]. The characterization of WMH in young urbanites is critical and knowledge about the complex modulation of cytokines and chemokines in the setting of air pollution are important because they may shed light into the etiopathogenesis of well-characterized risk factors for neurodegeneration, vascular, and cognitive disorders and disability [106, 107].
A difficult question to answer is how to interpret the early neuropathology hallmarks of Alzheimer’s and Parkinson’s diseases in children with no family history of neurological diseases.
In the Alzheimer’s brain, tau is abnormally hyperphosphorylated and it is aggregated into paired helical filaments forming neurofibrillary tangles, a histopathological hallmark of the disease [108]. Tau phosphorylation could be protective (e.g., hibernation) or toxic (e.g., hyperphosphorylation and aggregation of tau) [109]. Hyperphosphorylated tau in epitopes characteristic of AD has been identified by immunohistochemistry in 62.5% of APOE 4 and 33% of APOE 3 young MCMA carriers [30].
Is tau phosphorylation in children detrimental or protective in the setting of severe air pollution? [109114]. The aggregation of HP tau species has been proposed to represent a compensatory neuronal response against oxidative stress and to serve at least initially as a protector against cell death [111, 113]. The tau protective or toxic function could be related to different conformational molecular changes [109]. The formation of tangles is a quick process as it was demonstrated by De Calignon et al. [112] using in vivo multiphoton imaging in living tau transgenic mice. Caspase activation precedes tangle formation by hours to days, tangles form quickly but persist apparently indefinitely, thus cleavage of tau is enough to cause misfolding of tau followed by nucleation and recruitment of additional tau molecules to the neuronal cell body. Is our description of HPτ in MCMA children’s brains an isolated observation in the literature? The answer is no, Braak and Del Tredeci [93] examined 42 young brains (4–29 years) with a wide range of pathologies described pretangle HPτ using AT8 in 38/42 cases with no extracellular amyloid β protein deposition or neuritic plaques with the 4G8 antibody. Although these subjects were not healthy, there was no APOE genotyping or a recorded history of environmental exposures, we fully agree with Braak and Del Tredeci [93] that these findings may indicate Alzheimer’s disease-related pathological process leading to neurofibrillary tangle formation start quite early, before puberty or in early young adulthood.
There are very few arguments about the role of abnormal tau hyperphosphorylation in AD, related tauopathies and under experimental conditions [108, 109, 114118]. A subject to be explored in air pollution animal models ought to be the characterization of the HPτ and if indeed represents a compensatory neuronal response against oxidative stress. At this time, however, we are of the opinion that given the factors (chronic oxidative stress, neuroinflammation, presence of nanosize particles in critical brain units and anatomical regions) potentially accounting for the aggregation of tau, tau phosphorylation could represent an early sensor of oxidative stress with all the subsequent detrimental effects if the exposure persist.
Likewise, Aβ42 is capable of aggregation and misfolding leading to progressive neurodegeneration that develops insidiously over a lifetime. A key issue has to be addressed in this scenario: APOE4 carriers not only have HPτ, but also exhibit significant numbers of Aβ 6E10 diffuse plaques () in comparison to APOE 3 carriers. Recent work by Cerf et al. [119] suggests that APOE4 strongly stabilizes Aβ oligomers, the pathological species responsible for AD; thus we suggest APOE4 carriers are potentially at a higher risk of developing AD if residing in a highly polluted environment. This information is critical given that ~18% of the MCMA population carries an APOE 4 allele [30].
Alpha-synuclein aggregation is associated to the pathogenesis of Parkinson’s disease and exposure to a myriad of environmental agents, including agrochemicals increases the PD risk [120, 121]. Mitochondrial dysfunction and oxidative stress constitute key PD pathogenic events. Alpha-synuclein prevents cytochromec release and apoptosis through inhibition of the MAPK signaling pathway, suggesting that endogenous concentrations of α-synuclein confer resistance to oxidative stress downstream of free radical production and scavenging [122]. Recent evidence also suggests misfolded α-synuclein directly activates microglia inducing the production and release of the proinflammatory cytokine, TNF-α, and increasing antioxidant enzyme expression [123]. Béraud et al. emphasized the importance of protein misfolding, oxidative stress, and inflammation in PD as a potential locus for the development of novel therapeutics focused on induction of the Nrf2-directed antioxidant pathway and inhibition of protein misfolding [123].
It is important to note that α-synuclein in MCMA children is present in key regions associated with PD pathology including olfactory bulb, the midbrain, and the lower sections of the brainstem, for example, the medulla oblongata [67, 77]. MCMA teens exhibit already olfactory disturbances [77] and autonomic dysfunction (syncope in MCMA children personal communication of Dr. Maricela Franco-Lira), the latter severe enough to require pediatric care. The issue of MCMA children already showing symptoms seen in the premotor stages of PD has to be well thoughtout [73, 74] given the neurodegenerative process begins earlier in the olfactory bulb and lower brain stem and the fact there is a delay of several decades between the onset of dopaminergic denervation and the appearance of motor signs [96]. There is no question olfactory dysfunction is an early “preclinical” sign of Parkinson’s disease [73, 74]. Damage to cholinergic, serotonergic, and noradrenergic components of the olfactory pathway likely involved to explain the olfactory dysfunction [73, 74]. The presence of up-regulated inflammatory cytokines, α-synuclein- and HPπ-related olfactory bulb pathology in young highly exposed children is an ominous sign possibly associated with a number of other nonmotor symptoms related to PD, such as dysautonomia and sleep disturbances. Epidemiological studies addressing nonmotor PD symptoms in highly exposed young urbanites are warranted.
4.1. Looking Forward and Limitations
Despite controversy regarding the mechanistic pathways involved in the CNS damage associated with exposure to air pollutants, specifically fine and ultrafine particles of diverse origin, animal models and tissue culture studies have greatly improved our understanding of the mechanistic processes [39, 41, 42, 4852, 5866, 6971]. We are looking forward to bridging the gap between early neuroinflammation and neurodegeneration observed in childhood and early adulthood and experimental air pollution animal models. There is a strong need for collaborations between those who investigate humans and those who study experimental animal models to derive therapies that may be neuroprotective. There is also a need for looking into the neuropathology in diverse populations residing in megacities across the globe and sharing the results of the investigations. This is critical since the responses to air pollutants depend not only on the components of air pollution and concentrations, but also on the genetic background of the exposed populations and on a large list of environmental factors including dietary risk factors, obesity, alcohol intake, and lifelong experiences for example, educational and occupational attainment [124]. Our results are potentially limited by the characteristics of the air pollutants in MCMA and the populations we are studying, namely ethnic groups with a complex admixture of ancestral populations as seen with Mexican mestizos. Nevertheless, the significant differences in clinical and neuropathology findings between high and low pollution exposed subjects warrants extensive investigations in exposed populations from countries around the world.
5. Summary
MCMA children experience a chronic, intense state of oxidative stress resulting from lifelong exposures to a severely polluted environment. Children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses, cell proliferation and apoptosis. Neuroinflammation, endothelial activation, endothelial cell hyperplasia, the attachment of white blood cells to the endothelial damaged walls with the reduction of the lumen vessel, high blood concentrations of endothelin-1, and the breakdown of the BBB clearly contribute to cognitive impairment and pathogenesis and pathophysiology of neurodegenerative states [125, 126]. Environmental and genetic factors play a key role in their CNS responses as evidenced by the acceleration of neurodegenerative AD pathology in children carrying an APOE 4 allele.
The neuronal accumulation of misfolded proteins in exposed children coincides with the anatomical distribution observed in the early stages of both AD and PD with early clinical evidence of olfactory and cognitive deficits, brain volumetric changes, white matter hyperintense lesions, altered brainstem evoked auditory potentials and autonomic disbalance. There is a complex modulation of cytokines and chemokines influencing structural and volumetric brain responses and cognitive deficits.
We contend that misfolding of critical proteins could be a defensive early response to the sustained systemic and CNS inflammation. However, the sustained oxidative stress associated with dysregulated inflammation, both systemic and in the CNS contribute to the establishment of neurodegenerative processes with clinical early counterparts. We strongly support the contention that the nasal (olfactory and trigeminal), cardiorespiratory and gastrointestinal (vagus) pathways-along with the systemic direct transport of particles to the brain and the dysregulated systemic inflammation are critical in explaining the brain pathology in highly exposed MCMA children. Moreover, these children are at risk of developing Alzheimer’s and Parkinson’s diseases as adults.
We have a 50-year window of opportunity between the early brain changes observed in children and the time when the patient with mild cognitive impairment or dementia will show up at the neurologist’s door. Facing the current pediatric clinical and pathology evidence is imperative if we are aiming our efforts to identify and mitigate environmental factors that influence AD and PD pathogenesis.
One thing is clear: early implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes in children is warranted [43, 87]. Identification of biomarkers associating systemic inflammation to brain growth is also critical for detecting children at higher risk for cognitive deficits and neurodegeneration.
It is important to remember there is a severe and woeful deficit of progress in the development of both AD and PD-modifying therapy [127, 128]. Since fine and ultrafine PM likely play a key role in the development of neuroinflammation and neurodegeneration, it is very noteworthy that in the US alone, as of December 2012, more than 74 million people are being exposed to concentrations of PM2.5 above the 2006 standards (PM2.5 annual standard of 15 μg/m3) [129]. An appeal to research supporting institutions may be made to strongly invest in defining the CNS pathology associated with exposure to air pollutants in children and young adults and as Castellani and Perry suggested, consider a systems biology approach and an early preventive pathway [128].
Epidemiological, cognitive, and mechanistic studies into the association between air pollution exposures and the development of CNS damage in children are of pressing importance for public health and quality of life.
Acknowledgments
This work was supported in part by ITHS UL1RR025014, P20RR015583 and Canada-Latin America and the Caribbean Research Exchange Grants Program (LACREG 2011).
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Engineering » Electrical and Electronic Engineering » "Fourier Transform - Materials Analysis", book edited by Salih Mohammed Salih, ISBN 978-953-51-0594-7, Published: May 23, 2012 under CC BY 3.0 license
Chapter 2
High Resolution Mass Spectrometry Using FTICR and Orbitrap Instruments
By Paulo J. Amorim Madeira, Pedro A. Alves and Carlos M. Borges
DOI: 10.5772/37423
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Barrett & Files - Series Bibliography
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Nano Express
Fabrication of ordered nanoporous anodic alumina prepatterned by mold-assisted chemical etching
Kuan-Liang Lai1, Min-Hsiung Hon1 and Ing-Chi Leu2*
Author Affiliations
1 Department of Materials Science and Engineering, National Cheng Kung University, Tainan 701, Taiwan
2 Department of Materials Science, National University of Tainan, Tainan 700, Taiwan
For all author emails, please log on.
Nanoscale Research Letters 2011, 6:157 doi:10.1186/1556-276X-6-157
The electronic version of this article is the complete one and can be found online at: http://www.nanoscalereslett.com/content/6/1/157
Received:2 October 2010
Accepted:21 February 2011
Published:21 February 2011
© 2011 Lai et al; licensee Springer.
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
In this article, a simple and cost-effective method to create patterned nanoindentations on Al surface via mold-assisted chemical etching process is demonstrated. This report shows the reaction-diffusion method which formed nanoscale shallow etch pits by the absorption/liberation behaviors of chemical etchant in poly(dimethylsiloxane) stamp. During subsequent anodization, it was possible to obtain the ordered nanopore arrays with 277 nm pitch that were guided by the prepatterned etch pits. The prepatterned etch pits obtained can guide the growth of AAO nanopores during anodization and facilitate the preparation of ordered nanopore arrays.
Introduction
In recent years, nanoporous anodic aluminum oxide (AAO) has become a popular template system for the synthesis of various functional nanostructures which have extensive applications in scientific and commercial fields [1-4]. In the syntheis of template-based materials, the template with long-range-ordered nanostructure is attractive, in order that structurally well-defined materials can be consequently produced. In general, Al anodization processes, highly regular arrangement of pores, however, occurs only within a small process window, and the domain size (ordering length) is usually limited to a micrometer scale on Al foils [5,6]. In order to achieve an ordered pore arrangement over a larger area, Masuda et al. [5,7] developed a pretexturing process of Al using nanoimprinting with a SiC mold. Shallow indentations on an Al substrate initiate pore nucleation during anodization and lead to a long-range-ordered pore arrangement within the stamped area.
Self-ordered and prepatterned guided growths are two kinds of anodization technology, which are competing in the aspects of product quality and production cost. For prepatterned guided anodization, imprinting methods have been used by several author groups to prepare ordered AAO, wherein nanoindentations are created by transferring patterns from hard master stamp onto the Al surface under a high pressure (5-25 kN cm-2) before anodization [8-10]. Despite the ideally ordered patterns obtained, this method is limited by the pattern transfer protocol, and pattern transferred by imprint lithography directly onto metallic substrates such as Al foils or Al films requires 50-2000 times higher pressures in comparison with imprint lithography on polymer layers [11]. The applied pressure for pattern transfer tends to crack the substrates underneath the Al films, such as silicon and glass with brittle property, and leads to substrate fracture. Otherwise, damage to the imprint stamp often occurs after several runs of imprinting because of the high mechanical stresses.
In the reported literatures, some outstanding methods, such as focused ion beams [6], optical diffraction gratings [12], colloidal lithography [13], block-copolymer self-assembly [14], and metal mask [15] were also used to achieve prepatterning of Al substrates, thus avoiding fabrication of the expensive hard imprint stamp. However most of them have limitations in scalability or size of ordered domains. Consequently, a simple and economic method for realization of a long-range-ordered AAO over very large areas (cm2 to wafer size) still faces challenges. Recently, some methods, such as guided electric field method [16], and step and flash imprint lithography [17], have been developed to fabricate wafer-scale-ordered AAO.
Ideally, a simple and cost-effective process for preparing ordered AAO should combine with a high-throughput method to create patterned nanoindentations on Al surface. It should also be substrate-friendly to avoid damaging the substrate such as thin Al film-deposited Si.
The reaction-diffusion wet stamping (RD-WETS) method uses a nanopatterned agarose stamp such as poly(dimethylsiloxane) (PDMS) in soft lithography. An agarose stamp soaked with an appropriate chemical reactant can etch/dissolve the desired hard material by simply contacting with the substrate (e.g., HF for SiO2 or HCl/FeCl3 for Cu) [18-20]. Localized etching is mediated by a mold-assisted chemical etching initiated from the stamp microfeatures, and excellent uniformity over areas of several square centimeters can be achieved.
In this study, a simple and reliable method for substrate prepatterning by soft imprinting, using a diffusion-reaction-controlled wet chemical etching method, is developed thus avoiding the use of sophisticated device fabrication procedures. In addition, the highly ordered porous alumina on Al foils with the help of prepatterned indentations by the above-mentioned wet stamping were fabricated.
Experimental section
The master molds for PDMS stamp fabrication were sub-micromter gratings (for 1D pattern) and Si wafers with regular pit arrays (for 2D pattern). The membrane stamp was made by pouring a mixture of PDMS prepolymer (Dow Corning Sylgard 184) and its curing agent (10:1 by weight) into the masters, which was cured for 1 h at room temperature and then for 4 h at 60°C in an oven. The PDMS stamps about 2 mm in thickness were replicated from straight line diffraction grating surface (Thorlabs, Inc. 3600 and 1800 lines/mm), and Si mold with regular pit arrays of 277-nm pitch. The flexible agarose membrane has a better attachment to solid surface. Al samples with a total surface area of 2 × 2 cm2 were cut from an aluminum sheet (99.99%, Alfa Aesar), degreased in acetone and dried.
The Al sheet was electropolished at a constant voltage in perchloric acid/ethanol (1:4 V/V ratio) at 4°C for 30 s, to diminish the roughness of Al foil surface. Patterns on Al substrate were etched using a mold previously soaked in a diluted solution of mixed acid (2%) in alcohol (mixed acid composition: 0.15 M HNO3, 0.6 M H3PO4, and 0.2 M CH3COOH). The nitric acid consumes some of the aluminum material to form an aluminum oxide layer. This oxide layer is then dissolved by the phosphoric acid, and more Al2O3 is formed to keep the oxidation/dissolution cycle going. The diluted etchants moderated the condition of etching reaction and contributed to the formation of nanopatterns. The PDMS stamp was soaked in etching solution for 10 min and absorbed in the latter, and the time period for etching process was within 5 min. After nanoindentation by the RD-WETS process with PDMS membrane stamps, anodization was conducted under a constant voltage in phosphoric acid solution. The ordered AAO structures were examined by scanning electron microscopy (SEM, Hitachi S3000) and atomic-force microscopy (AFM, Digital Instrument Nanoscope LFM-3).
Results and discussions
The RD-WETS approach can be extended to structuring hard materials by chemical etching reaction. Regardless of the substrate type, the mechanism of localized microetching relied on the diffusive transport of chemicals within a stamp [18-20]. Figure 1 shows the scheme of mold-assisted microetching of substrate. The PDMS stamp was soaked in etching solution (2% mixed acid in alcohol) for 10 min and absorbed approximately 4% etching solution, and the residual solution on the surface of stamp was removed by N2 flow. Then, the wet stamp was set on Al substrate with a slight loading (0.01 MPa) to ensure a conformal contact with substrate. The etchant-contained alcohol liberated from stamp reacted with Al metal, and the reaction products diffused into PDMS along the concentration gradient as the arrows indicated. Compared with the conventional RD-WETS process, this method used alcohol in place of water because the alcohol in agarose mold has a higher absorptivity than water [21]. It helps to adjust the degree of reaction-diffusion by the solvent liberation/absorption process and this two-way chemical "pump" increases the work efficiency. From this point of view, the parameters of RD process should be adjusted to meet the requirements of imprinting nanopatterns on Al surface. In general, the shallow nanoscale concave (just 3 nm in depth is sufficient) can guide the ordered growth of AAO effectively [9].
Figure 1. Scheme of the experimental procedures for reaction-diffusion wet etching.
The photograph of sample after RD-WETS is shown in Figure 2a, where the Al surface with grating prepattern appears under visible diffractive light and results in a uniform prepattern over large areas (up to 2 × 2 cm2). A detailed investigation of the film topography was performed by AFM as Figure 2b,c shows. The pitches of grating patterns are 555 and 277 nm with pattern heights of 40 and 25 nm, respectively. Overall, the reaction-diffusion process allowed the PDMS to cut into the Al substrate, in particular, with retention of the stamp's topography.
Figure 2. The photograph and AFM images of the aluminum substrate with grating prepatterns (a) sample after RD-WETS. (b) procedure with pitch of 555 nm; (c) 277 nm.
After the RD process, anodization was conducted under a constant voltage of 110 V in 0.3 M H3PO4 at 5°C. The anodization voltage for the prepatterned aluminum substrate was chosen to satisfy the linear relationship between the interpore distance and the anodization potential (2.5 nm/V-1) reported for the common anodization process [22]. Figure 3 shows SEM micrographs of alumina pores obtained from aluminum foils, half of which (left-hand side) were obtained on Al pretextured by RD-WETS. Pores arranged in a 1D grating configuration were observed only in the pretextured area, while the disordered pores were found in the untreated area. In addition, it was found that the PDMS stamp can well tolerate the dilute acid etchant, which implies that the soft stamp can be reused multiple times without noticeable decrease in patterning quality [18].
Figure 3. SEM micrographs of anodization sample (a) alumina pores obtained from aluminum foils. (b) alumina pores grown in the 1D grating-patterned area. (c) alumina pores grown in the unpatterned area. Anodization conducted in 0.3 M H3PO4 at 110 V and 5°C.
Furthermore, the 2D periodic prepattern on Al was fabricated using a PDMS mold with square dot arrays, as Figure 4a shows. Shallow etched pits in the prepattern (approximately 40-nm depth) serves as nucleation sites for the development of a pore in the early stage of anodization [5-7], and results in the eventual growth of a pore channel. The results shown in Figure 4b confirm that the predetermined pattern can act as initiation points and guide the growth of channels in the oxide film. Straight oxide nanochannels (Figure 4c) with uniform-sized pores are obtained.
Figure 4. AFM and SEM images of Al prepattern and AAO (a) 2D Al prepatten after RD-WETS. (b, c) 2D prepattern-induced regular AAO array. Anodization conducted in 0.3 M H3PO4 at 110 V and 5°C.
Furthermore, the two-step imprinting was used to fabricate multiple patterns from a single master. The two-step imprinting can be used to selectively etch Al at established primary structure because the etchant only acts at the contact site between the mold and substrate [18]. After the first mold-assisted etching, a second etching step was performed using the same grating rotated by approximately 85° around the axis perpendicular to the surface to discriminate this multiple case from one-step imprinting method. A parallelogram profile of etched pit arrays was obtained, as illustrated in Figure 5a,b. From the AFM images, the intersects of grating pattern show shallow indent arrays which resemble point-like depressions [5,12] and have just several nanometers in depth relative to the local surface around them. In addition, the double-etching sites serve as the nucleation sites, and the ordered AAO growth can be maintained as shown in Figure 5c,d. A single pore just appears on double-etching site and the notches of multiple etching remain on the AAO surface and parallelogram (i.e., non-right angle) patterns of pore arrays are obviously different from the directly imprinted 2D square prepatterns (Figure 4b). All of these experimental findings suggest that this mold-assisted etching method is industrially applicable to a large-scale production of nanopatterning and has the potential of achieving the aim of fabricating nanostructured functional AAO with required design geometry.
Figure 5. AFM and SEM images of Al prepattern and AAO (a, b) Al prepattern featuring a second grating on a primary structure with ~85° rotation and pitch of 277 nm. (c, d) prepattern-induced regular AAO array. Anodization conducted in 0.3 M H3PO4 at 110 V and 5°C.
Conclusions
In conclusion, a novel method for fabricating prepatterned Al foil was developed, which used the reaction-diffusion process mediated by a PDMS template. By means of using the diluted (2%) mixed acid solution as a chemical etchant, the wet soft stamp can indent nanoscale shallow concaves on aluminum without the need of excessive loading. Furthermore, based on the phenomenon of multiple RD-WETS imprinting, 2D prepattern by multiple etching could be made using simple stripe-patterned stamps with selected orientation. After anodization, a uniform, ordered AAO array with 277-nm interpore distance guided by the prepattern was obtained. Combining mold-assisted chemical etching and anodization reaction, this process provides a simple and efficient route to obtain ordered nanostructures for further nanodevice applications.
Abbreviations
AAO: anodic aluminum oxide; PDMS: poly(dimethylsiloxane); RD-WETS: reaction-diffusion wet stamping.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MHH and ICL planned and supervised the research project. ICL, KLL and MHH conceived and designed the experiments. KLL carried out the experiments, analyzed the data, and drafted the manuscript. ICL participated in the analysis of experimental data and the writing of manuscript. All authors discussed the results and commented on the manuscript.
Acknowledgements
The financial support of this study from the National Science Council, Taiwan ROC (NSC 97-2628-E-006-122 and NSC 99-2221-E-024-004) is gratefully appreciated.
References
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4. Wang Z, Brust M: Fabrication of nanostructure via self-assembly of nanowires within the AAO template.
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15. Zhao X, Jiang P, Xie S, Feng J, Gao Y, Wang J, Liu D, Song L, Liu L, Dou X, Luo X, Zhang Z, Xiang Y, Zhou W, Wang F: Patterned anodic aluminium oxide fabricated with a Ta mask.
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16. Nasir ME, Allsopp DWE, Bowen CR, Hubbard G, Parsons KP: The fabrication of mono-domain highly ordered nanoporous alumina on a wafer scale by a guided electric field.
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Levon Aronian to participate in Grand Slam Masters Final
PanARMENIAN.Net - Armenian grandmaster Levon Aronian will participate in Grand Slam Masters Final due September 24th-October 13th in Sao Paulo (Brazil) and Bilbao (Spain.)
To rival Aronian are Vishy Anand, Magnus Carlsen, Fabiano Caruana, Sergey Karjakin and Francisco Vallejo Pons.
Partner news
Top stories
Armenian grandmaster Levon Aronian is currently 3rd with 4 points, Bulgaria’s Veselin Topalov is 7th with 3 points.
European Individual Chess Championship ended in Polish town of Legnica, with 24 chess players winning World Cup qualifications.
Gor Minasyan won silver medal, Andranik Karapetyan and Izabella Yalyan both won bronze at Junior World Championships in Lima.
The chief coach noted that the Greco-Roman wrestlers will participate in Mariupol-hosted tournament in June.
Partner news
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[189] About the same time king Agrippa built himself a very large dining-room in the royal palace at Jerusalem, near to the portico. Now this palace had been erected of old by the children of Asamoneus. and was situate upon an elevation, and afforded a most delightful prospect to those that had a mind to take a view of the city, which prospect was desired by the king; and there he could lie down, and eat, and thence observe what was done in the temple; which thing, when the chief men of Jerusalem saw they were very much displeased at it; for it was not agreeable to the institutions of our country or law that what was done in the temple should be viewed by others, especially what belonged to the sacrifices. They therefore erected a wall upon the uppermost building which belonged to the inner court of the temple towards the west, which wall when it was built, did not only intercept the prospect of the dining-room in the palace, but also of the western cloisters that belonged to the outer court of the temple also, where it was that the Romans kept guards for the temple at the festivals. At these doings both king Agrippa, and principally Festus the procurator, were much displeased; and Festus ordered them to pull the wall down again: but the Jews petitioned him to give them leave to send an embassage about this matter to Nero; for they said they could not endure to live if any part of the temple should be demolished; and when Festus had given them leave so to do, they sent ten of their principal men to Nero, as also Ismael the high priest, and Helcias, the keeper of the sacred treasure. And when Nero had heard what they had to say, he not only forgave 1 them what they had already done, but also gave them leave to let the wall they had built stand. This was granted them in order to gratify Poppea, Nero's wife, who was a religious woman, and had requested these favors of Nero, and who gave order to the ten ambassadors to go their way home; but retained Helcias and Ismael as hostages with herself. As soon as the king heard this news, he gave the high priesthood to Joseph, who was called Cabi, the son of Simon, formerly high priest.
2
1 We have here one eminent example of Nero's mildness and goodness in his government towards the Jews, during the first five years of his reign, so famous in antiquity; we have perhaps another in Josephus's own Life, sect. 3; and a third, though of a very different nature here, in sect. 9, just before. However, both the generous acts of kindness were obtained of Nero by his queen Poppea, who was a religious lady, and perhaps privately a Jewish proselyte, and so were not owing entirely to Nero's own goodness.
2 CONCERNING ALBINUS UNDER WHOSE PROCURATORSHIP JAMES WAS SLAIN; AS ALSO WHAT EDIFICES WERE BUILT BY AGRIPPA.
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adCenter 2+ Month Data Bug
Jan 18, 2012 • 8:16 am | (1) by | Filed Under Microsoft Bing adCenter
I believe we reported this in November 2011, where advertisers using Microsoft adCenter haven't seen updated search volume data since early November.
The issue is specifically with the Excel Ad Intelligence plugin, where there is no new data since November and the November and October data was "questionable" to many advertisers. Since then, Microsoft said they are working on the problem, but two months later, still no fix.
Ricky Poole from Microsoft updated several forum threads saying:
I will reach out to the engineers and try to get an ETA. Please note, they are working on this fix and it is definitely a priority to have MAI functioning correctly.
More info to come.
Thank you for your patience :-)
How much longer do they have to wait? Who knows but not a good thing for advertisers looking for more ways to spend their budgets with adCenter.
Forum discussion at Microsoft Advertising Help.
Previous story: Daily Search Forum Recap: January 17, 2012
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Off to Search Engine Strategies San Jose 2004
Aug 1, 2004 • 10:26 am | (0) by | Filed Under Search Engine Strategies 2004 San Jose
I am leaving soon to San Jose for the Search Engine Strategies conference. You can expect live coverage to be posted here with my notes on the sessions I attend. I will try to stay away from the basic sessions for you pros out there. I will also be going to the Google Dance 2004, where I hope to speak to some interesting people. The SEMPO controversy is hot right now, and Monday night I will be attending the members only session, so expect coverage of that as well. I hope to post pictures, and if allowed some audio.
If you will be attending the SES San Jose conference and you see me in the hall, feel free to check me into the wall and then say hello. Only legal hockey checks, none of that cheap stuff :).
I hope the wifi is strong, if its not, then I will do my best to run back and forth to my room to post the live coverage. Never been to this hotel or convention center, so I am not sure about its wifi and distance from hotel to convention center. Speak to you all soon.
Previous story: Bruce Clay Announces New SEO Toolset Web Site with SEO Code of Conduct
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(Text) Recap of Weekly Search Buzz :: February 26, 2010
Feb 26, 2010 • 4:04 am | (0) by | Filed Under Search Buzz Video Round Recap
This week, I am currently in Jerusalem, Israel, so I won't be producing a video. Here is a text recap instead of the video recap.
The European Union has opened an investigation to make sure Google isn't stepping over their boundaries by penalizing potential competitors in the web results. Google said they will launch the Caffeine index in the upcoming months. Google had a Webmaster Tools bug in the index URL report. Google may verify your web site in Webmaster Tools without you specifically requesting it. Google has updated the Jazz interface slightly and more people are seeing it. MySpace (and also Facebook) is now in Google's real-time search results. Bing is having trouble with their spiders again. Twitter users don't click on AdSense. Google AdWords has a new "target" CPA feature. AdWords is closing their old API in less than 60 days. Yelp was sued for allegedly removing negative reviews. SMX West is next week, I won't be there, but we got the coverage for you. That was this past week at the Search Engine Roundtable.
Select Topics For This Past Week:
Please do subscribe via iTunes or on your favorite RSS reader. Don't forget to comment below with the right answer and good luck!
Previous story: Google May Verify Your Sites in Webmaster Tools Without You Clicking Verify
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Place:Somerset (township), Somerset, Pennsylvania, United States
Watchers
NameSomerset (township)
Alt namesSomerset Township
Somersetsource: WeRelate abbreviation
TypeTownship
Located inSomerset, Pennsylvania, United States
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Somerset Township is a township in Somerset County, Pennsylvania, United States. The population was 12,122 at the 2010 census. It is part of the Johnstown, Pennsylvania Metropolitan Statistical Area and encompasses the census-designated place (CDP) of Friedens, Pennsylvania.
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This page uses content from the English Wikipedia. The original content was at Somerset Township, Somerset County, Pennsylvania. 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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Source:Indiana, United States. Indiana Census, 1790-1890
Watchers
Source Indiana Census, 1790-1890
Coverage
Place Indiana, United States
Publication information
Type Government / Church records
Citation
Indiana, United States. Indiana Census, 1790-1890.
Repositories
Ancestry.comhttp://www.ancestry.com/Paid website
Source Information
Jackson, Ronald V., Accelerated Indexing Systems, comp. Indiana Census, 1790-1890 [database on-line]. Provo, UT, USA: The Generations Network, Inc., 1999. Original data: Compiled and digitized by Mr. Jackson and AIS from microfilmed schedules of the U.S. Federal Decennial Census, territorial/state censuses, and/or census substitutes.
About Indiana Census, 1790-1890
This collection contains the following indexes:
1790 (Northwest Territory) Federal Census Index;
1807 State Census Index;
1810 Wayne County Census Index;
1812 Census Index;
1820 Federal Census Index;
1830 Federal Census Index;
1840 Federal Census Index;
1840 Pensioners List;
1850 Federal Census Index;
1860 Federal Census Index;
1870 Federal Census Index;
1890 Veterans Schedule.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
3201.0 - Population by Age and Sex, Australian States and Territories, Jun 2000
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NPCs
Many of the Non Player Characters are non-essential to the main storyline, however most of them have small quests or functions of their own.
Alvina of the Darkroot Wood
Anastacia of Astora
Black Iron Tarkus
Crestfallen Warrior
Dark Sun Gwyndolin
Darkstalker Kaathe
Dusk of Oolacile
Everlasting Dragon
Gravelord Nito
Gwynevere, Princess of Sunlight
Hawkeye Gough
Kingseeker Frampt
Kirk, Knight of Thorns
Knight Lautrec of Carim
Lady of the Darkling
Lord's Blade Ciaran
Maneater Mildred
Marvellous Chester
Oscar, Knight of Astora
Paladin Leeroy
Petrus of Thorolund
Quelaag's Sister
Quelana of Izalith
Rhea of Thorolund
Vince and Nico of Thorolund
Sieglinde of Catarina
Siegmeyer of Catarina
Sif, the Great Grey Wolf
Solaire of Astora
Witch Beatrice
Xanthous King, Jeremiah
Phantom Information
Some of the NPCs in the game will make themselves available to the player at bosses as helpful phantoms if the player is in human form.
Conversely, there are also NPCs that will also invade the player's world through scripted events.
Note: Black Phantoms will only spawn if the player is in human form and the area boss has not been defeated.
Therefore if the area boss is defeated before being invaded by a particular NPC Black Phantom, that NPC will not become available until the next playthrough.
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License
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Error!
Success!
Golf Tracker Series - Part 1 - Overview
0
kicks
Golf Tracker Series - Part 1 - Overview (Unpublished)
The Golf Tracker series is a series where I build a complete n-Tier ASP.NET MVC v2.0 application from the ground up, while you watch. The application will contain many best-practices including: Dependency Injection using Unity, n-Tier infrastructure, Linq-To-Sql, Service Layer, jQuery, and more.
Kicked By:
Drop Kicked By:
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Difference between revisions of "BeagleBoard/DSP Howto"
From eLinux.org
Jump to: navigation, search
(Kernel driver)
m (Kernel driver: Update Hiroshi's patches.)
Line 12: Line 12:
git clone http://www.kernel.org/pub/scm/linux/kernel/git/tmlind/linux-omap-2.6.git
git clone http://www.kernel.org/pub/scm/linux/kernel/git/tmlind/linux-omap-2.6.git
cd linux-omap-2.6
cd linux-omap-2.6
wget http://4869037.web.fc2.com/tidspbridge-20081010.tgz
+
wget http://4869037.web.fc2.com/tidspbridge-20081021.tgz
tar xvzf tidspbridge-20081010.tgz
+
tar xvzf tidspbridge-20081021.tgz
git am *.patch
git am *.patch
make omap3_beagle_defconfig
make omap3_beagle_defconfig
Revision as of 14:48, 22 October 2008
This article explains how to use the DSP in OMAP3 at BeagleBoard with TI's deliverables. For DSP tool chain see C64x+ DSP.
Contents
Setup
Kernel driver
In order to use the DSP you would need TI's bridgedriver module on the kernel. For that you would need Hiroshi's patches on top of linux-omap:
git clone http://www.kernel.org/pub/scm/linux/kernel/git/tmlind/linux-omap-2.6.git
cd linux-omap-2.6
wget http://4869037.web.fc2.com/tidspbridge-20081021.tgz
tar xvzf tidspbridge-20081021.tgz
git am *.patch
make omap3_beagle_defconfig
Then make menuconfig and add the following options in the menuconfig:
CONFIG_FB_OMAP_CONSISTENT_DMA_SIZE=14 #in Device Drivers->Graphics support->Support for frame buffer devices->Consistent DMA memory size
CONFIG_MPU_BRIDGE=m #in Device Drivers->DSP Bridge driver
TI binaries
In order to get the DSP binaries for multimedia processing you need to download TI's OpenMAX IL package. Once you have extracted the tarball you'll have to run the installer TI-OMX-Sample-Firmware-0.3-Linux-x86-Install and accept the license agreement.
You would end up with a bunch of binaries in lib/dsp, copy them to your root filesystem at the same location (/lib/dsp).
ping test
If you want to test the DSP you can try the simple ping test provided in this package.
Just:
./ping.out
Running
On the board use this to load the module:
modprobe bridgedriver base_img=/lib/dsp/baseimage.dof
Developing
In order to develop dynamic dsp nodes you'll need a C6x compiler and doffbuild tools.
doffbuild tools
The only relevant tool is DLLcreate, which can be found in TI's omapzoom site, on the dspbridge_dsp package.
mkdir -p tmp
tar -xf dspbridge_dsp.tar.gz -C tmp
mv tmp/dsp/bdsptools/packages/ti/dspbridge/dsp/doffbuild /opt/doffbuild
rm -rf tmp
libdspbridge
This library is used by the user-space applications.
git clone git://github.com/felipec/libdspbridge.git
cd libdspbridge
make DESTDIR=$rootfs install
Example dsp node
Here is an example dsp node that is simply passing buffers back and forth.
git clone git://github.com/felipec/dsp-dummy.git
make DSP_TOOLS=/opt/dsptools DSP_DOFFBUILD=/opt/doffbuild BRIDGE_DIR=../libdspbridge
As a result you'll have two binaries; dummy.dll64P for dsp-side, and dummy for arm-side.
To load the dynamic node:
/dspbridge/dynreg.out -r /lib/dsp/dummy.dll64P
Now you can run the dummy test application.
More information
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Difference between revisions of "Linux Tiny Patch Details"
From eLinux.org
Jump to: navigation, search
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|CONFIG_INLINE_THREADINFO
|CONFIG_INLINE_THREADINFO
|bgcolor="#ffe4e1"|patch doesn't apply (bitrotted?)
|bgcolor="#ffe4e1"|patch doesn't apply (bitrotted?)
|In discussion between Thomas Petazzoni and Ingo Molnar
+
|In discussion between Thomas Petazzoni and Ingo Molnar. See [http://selenic.com/pipermail/linux-tiny/2008-February/000525.html this thread].
|-
|-
|slob-accounting.patch
|slob-accounting.patch
Revision as of 14:05, 13 February 2008
This page has a table of patches that are part of the Linux-tiny project.
patch type description kernel option 2.6.22 status/notes mainline inclusion status
use-funit-at-a-time.patch compiler flag Add -funit-at-a-time to the gcc compilation flags for building the kernel None OK
config-net-small.patch add option Add CONFIG_NET_SMALL configuration option Adds CONFIG_NET_SMALL OK
cache_defer_hash.patch smaller data Reduce RPC cache hash table size from PageSize to 512 Uses CONFIG_NET_SMALL OK
unix_socket_table.patch smaller data Reduce AF_UNIX socket hash table from 256 to 16 entries Uses CONFIG_NET_SMALL OK
inet_protos.patch smaller data Reduce number of internet protocols supported from 256 to 32 Uses CONFIG_NET_SMALL OK
flow-cache-small.patch smaller data Reduce flow cache hash table from 2^10 (1024) to 2^3 (8) Uses CONFIG_NET_SMALL OK
tg3-oops.patch bugfix Handle tg3 ring allocation correctly None mainlined
namei-inlines.patch smaller code Uninline various functions in namei.c None OK
buffer-inlines.patch smaller code Uninline function in buffer.c None OK
ext2namei-inlines.patch smaller code Uninline ext2_add_nondir function None OK
kmalloc-accounting.patch measurement feature Add kmalloc accounting feature CONFIG_KMALLOC_ACCOUNTING (replaced)
cache-accounting.patch measurement feature Add slab accounting feature CONFIG_DEBUG_SLAB_ACCOUNT OK
slab-analysis-scripts.patch measurement feature Add slabalyze and casort CONFIG_DEBUG_SLAB_ACCOUNT OK
audit-bootmem.patch measurement feature Cause bootmem code to print callers and sizes for allocations CONFIG_AUDIT_BOOTMEM OK
deprecate-inline.patch measurement feature Add system for counting inline usage by generating deprecation warnings CONFIG_MEASURE_INLINES OK
deprecate-inline-kconfig-move.patch measurement feature Fixup a kconfig entry for measuring inlines CONFIG_MEASURE_INLINES OK
func-size.patch measurement feature Adds a script to count inline function sizes None OK
tiny-panic.patch reduced debug feature Add option to use smaller panic code CONFIG_FULL_PANIC OK
nopanic.patch omit debug feature Make code for kernel panic configurable CONFIG_PANIC OK
tiny-crc.patch smaller data Allow using function instead of table for CRC32 calculations CONFIG_CRC32_TABLES OK
threadinfo-ool.patch smaller code Inline current() and current_thread_info() on UP (configurable) (x86 only?) CONFIG_INLINE_THREADINFO patch doesn't apply (bitrotted?) In discussion between Thomas Petazzoni and Ingo Molnar. See this thread.
slob-accounting.patch measurement feature Add kmalloc accounting to SLOB allocator Uses CONFIG_SLOB, CONFIG_DEBUG_SLOB_ACCOUNT?? patch applies, but has no effect (missing config item), patch not completed|
mempool-shrink.patch reduced feature Allow disabling mempool allocator feature CONFIG_MEMPOOL OK
no-translations.patch omit feature Allow omitting support for console charset translation CONFIG_CONSOLE_TRANSLATIONS OK
sysenter.patch omit feature Allow disabling syscalls via sysenter (x86-only) CONFIG_SYSENTER OK
no-aio.patch omit feature Allow disabling Asynchronous IO syscalls and support CONFIG_AIO OK
no-xattr.patch omit feature Allow disabling Extended Attributes syscalls and support CONFIG_XATTR OK
fslock.patch omit feature Allow disabling POSIX file locking syscalls and support CONFIG_FILE_LOCKING OK
direct-io-core.patch omit feature Allow disabling directIO syscalls and support DIRECTIO patch doesn't apply (bitrotted?)
ethtool.patch omit feature Allow disabling support for configuring network devices with ethtool program CONFIG_ETHTOOL OK
inetpeer.patch omit feature Allow disabling INET peer data tracking CONFIG_INETPEER OK
net-filter.patch omit feature Allow disabling old-style packet filtering support CONFIG_NET_SK_FILTER OK
dev_mcast.patch omit feature Allow disabling netdev multicast support CONFIG_NET_DEV_MULTICAST OK
igmp.patch omit feature Allow disabling IGMP (Internet Group Management Protocol) support - used for multicasts CONFIG_IGMP OK
binfmt-script.patch omit feature Allow disabling support to run shell scripts via standard "#!" syntax CONFIG_BINFMT_SCRIPT OK
elf-no-aout.patch omit feature Allow disabling support for ELF programs with a.out format loader or libraries CONFIG_BINFMT_ELF_AOUT OK
max-swapfiles.patch smaller data Make the number of swapfiles configurable CONFIG_MAX_SWAPFILES_SHIFT OK
ldiscs.patch smaller data Make the number of tty line disciplines configurable CONFIG_NR_LDISCS OK
max_user_rt_prio.patch smaller data Make the number of RT priority O(1) scheduling queues configurable CONFIG_MAX_USER_RT_PRIO OK
ide-hwif.patch smaller data Make the number of supported IDE interfaces configurable CONFIG_IDE_HWIFS OK
sbf.patch omit feature Allow disabling simple bootflag support (x86-only) CONFIG_BOOTFLAG patch doesn't apply (bitrotted?) Patch updated by Thomas Petazzoni. Space-savings are very small, in discussion with x86 maintainers.
serial-pci.patch omit feature Allow disabling support for PCI serial devices CONFIG_SERIAL_PCI OK
dmi_blacklist.patch omit feautre Allow disabling DMI scanning (x86-only) CONFIG_DMI_SCAN patch doesn't apply (bitrotted?) Patch updated by Thomas Petazzoni and included in -mm by Andrew Morton
pci-quirks.patch omit feature Allow disabling of workarounds for various PCI chipset bugs and quirks CONFIG_PCI_QUIRKS OK
tsc.patch omit feature Allow disabling use of TSC as kernel timer (x86-only) CONFIG_X86_TSC_TIMER patch doesn't apply (bitrotted?)
cpu-support.patch omit feature Allow disabling vendor-specific x86 CPU features (x86-only) CONFIG_PROCESSOR_SELECT, CONFIG_CPU_SUP_* (many) patch doesn't apply (bitrotted?) Michael Opdenacker has updated the patch, in discussion with x86 maintainers for inclusion
mtrr.patch continuation patch Make MTRR support depend on vendor-specific CPU selection (x86-only) None patch doesn't apply (bitrotted?) Need to wait for cpu-support to be included
no-doublefault.patch omit feature Remove double faut exception handler None Already included, CONFIG_DOUBLEFAULT
movsl-mask.patch continuation patch Make movsl mask usage depend on vendor-specific CPU selection (x86-only) None OK
do-printk.patch reduced feature Allow fine-grained control of printk message compilation CONFIG_PRINTK_FUNC, uses CONFIG_PRINTK OK
inflate-*.patch (multiple patches) eliminate redundant code Allow ARM boot code to re-use existing lib/inflate code None patches don't apply (bitrotted!)
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Dan Gillmor
DirecTV Reins in the Legal Attack Dogs
In one of the uglier "intellectual property" abuses, DirecTV has been suing people for possession of tools it claims can be used to get TV shows without paying for them. The Electronic Frontier Foundation and Stanford Law School's Center for Internet and Society have challenged the satellite TV company on this conduct, and on Monday DirecTV agreed to modify its approach, according to this press release, which says in part:
The company will no longer pursue people solely for purchasing smart card readers, writers, general-purpose programmers, and general-purpose emulators. It will maintain this policy into the forseeable future and file lawsuits only against people it suspects of actually pirating its satellite signal. DirecTV will, however, continue to investigate purchasers of devices that are often primarily designed for satellite signal interception, nicknamed “bootloaders” and “unloopers.”
DirecTV also agreed to change its pre-lawsuit demand letters to explain in detail how innocent recipients can get DirecTV to drop their cases. The company also promised that it will investigate every substantive claim of innocence it receives. If purchasers provide sufficient evidence demonstrating that they did not use their devices for signal theft, DirecTV will dismiss their cases. EFF and CIS will monitor reports of this process to confirm that innocent device purchasers are having their cases dismissed.
Perhaps DirecTV saw some writing on the wall. On Tuesday, a federal appeals court has ruled that the company can't sue solely because someone possesses such equipment.
These are the kinds of stories that make me sometimes wish I lived in America. Good job EFF and Stanford Law School.
4 TrackBacks
Listed below are links to blogs that reference this entry: EFF and Stanford Law School to the rescue against DirecTV.
TrackBack URL for this entry: http://joi.ito.com/MT-4.35-en/mt-tb.cgi/1653
About this Archive
This page is an archive of recent entries in the Business and the Economy category.
Books is the previous category.
Computer and Network Risks is the next category.
Find recent content on the main index.
Monthly Archives
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Feb 192011
A fundamental item for those who work according to ITIL best practices is definitely CMDB.
A configuration management database (CMDB) is a repository of information related to all the components of an information system. Although repositories similar to CMDBs have been used by IT departments for many years, the term CMDB stems from ITIL. In the ITIL context, a CMDB represents the authorized configuration of the significant components of the IT environment. A CMDB helps an organization understand the relationships between these components and track their configuration.
There are many commercial products that offer solutions that should cover every aspect of a company, but than you discover that these software are huge, difficult to manage and impossible to use and customize without the help of a consultant.
That is why today I will propose some open source software for create your CMDB. Continue reading »
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[maemo-users] Headset plugged in disables ringtones
From: Henrik Frisk frisk.h at gmail.com
Date: Fri Nov 28 12:49:59 EET 2008
On Fri, Nov 28, 2008 at 9:58 AM, Eero Tamminen <eero.tamminen at nokia.com> wrote:
> Hi,
>
> ext Luca Olivetti wrote:
>> El Thu, 27 Nov 2008 17:48:35 +0200
>> Eero Tamminen <eero.tamminen at nokia.com> escribió:
>>
>>> So, in which all situations it in your opinion should switch?
>>
>> Always route the alarms to the loudspeakers and route "normal"
>> audio to the headphones if connected or to the loudspeakers if not?
>> Or make the alarm output configurable ("always loudspeakers", "always
>> headphones", "auto switch")
>
> Well, it goes to one place at the time. So, you're proposing that
> music would switch to loudspeakers when alarm comes and after alarm
> it would switch back to headphones? That could sound wierd...
>
In this case, this is the aspect I'm missing. If I understand you
correctly the routing of audio is at system level rather than at
application level? IOW switching the audio for one application
switches it for all? Anyway, when I started this thread, my intention
was to bring forth a problem that I have experienced that could
perhaps be addressed in a future hardware (despite the fact that the
routing can be software controlled the limitation is apparantly in the
hardware) release.
Having said that,knowing what I know now, I still think the built in
SIP client could have a more sensible logic behind where it's playing
its alarm than simply always playing it through the headphones if
these are connected. For example, returning to Eero's example and in
addition to Luca's suggestion: if there is audio in the headphones at
the time of the alarm route the alarm to the headphones, else to the
speakers. On the other hand, if you are listening to music while the
phone is ringing, you will want to turn it off before answering the
phone which somewhat eliminates the problem...
/h
More information about the maemo-users mailing list
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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
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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°
Click here to buy this »
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LeBron and Bosh should hire these people
RedsArmyAdmin August 1, 2010 Uncategorized 12 Comments
Thanks to "The Decision" of LeBron James, Miami Heat season tickets are sold out. That means the team doesn't really need the people whose job it is to sell the tickets. The Heat fired its ticket sales staff Friday, cutting an estimated 30 positions.
"Now that the supply for season tickets has been exhausted, we no longer
require a season ticket sales team," said the Heat in a statement
issued Friday afternoon.
Fanhouse
"Hey, thanks for tirelessly pushing our season tickets while we sucked. Now that everyone is jacking off to our logo and offering their significant others into indentured servitude in exchange for tickets… you guys can hit the bricks."
LeBron James and Chris Bosh should find positions for these people. You've got almost 3 dozen people who were probably living paycheck-to-paycheck that are suddenly collecting unemployment… all because these two guys came to town for a combined $30 million or so per year.
Wade can chip in a little too. If they all combined to provide $2 million… all 30 of these people would get around $60,000. Even if they gave them the cash just as a severance… the goodwill generated by the move would help repair some of the damage done by the way LeBron and Bosh left town.
What the hell? Why not? These guys have the cash and their arrival is directly responsible for these people losing their jobs. Why not give something to hard working 9-to-5'ers when you're a young megastar about to get a total of $100 million dollars and that contract is the reason why they're out of work?
I don't know…. I'd feel bad for them.
Like this Article? Share it!
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ServoMaster Servo Control Software
Posted 24 Jul 2005 at 14:44 UTC by steve
According to a Freshmeat.net announcement, a new version of the ServoMaster servo control software library has been released. Among other new features the software now includes support for the Polulu USB and serial servo controller boards. The library also supports the Scott Edwards SSC, FerretTronics FT639 and F649, and the PhidgetServo boards, as well as other PIC-based servo controller boards. The only downside for robotics users is that ServoMaster is written in Java which is not commonly used in robotics and relies on Sun's proprietary Java implementation. ServoMaster itself, however, is Free Software licensed under the GNU GPL.
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18 Jun 2009 jkkroll » (Master)
Welcome to the Mazetrix
So, I just got an email from BatchPCB that my board has been shipped, so it looks like I’m switching gears again.
My board is for a project based on the Tiletoy, and incidentally not unlike the Space Invaders Button, the Awesome and 64Pixels.
Many moons ago I managed to score several 8×64 Red-Green matrix displays salvaged, evidently, from a casino display. Even though I had managed to reverse engineer them and figure out how to display nifty messages, they were just too large and too COTS for me. I removed the 8×8 LED matrices (matrixes?) and designed a small board to run them. The display is run directly from an ATMega128, using a half-H bridge on each column so I can use the entire matrix as a sensor. Additionally, I have added a MMA7260 triple axis accelerometer. Last but not least is an IR LED pointed in each of the cardinal directions, also connected to be used as an input and an output, for communicating to neighbor modules(PDF link).
The ultimate goal is to create tiles with a red maze and a green “ball” than you can manipulate by tilting, just like the good old labyrinth game. When you get to the edge of a tile, you can connect another, which will attach magnetically, and the maze will continue on the new tile.
I’ll add more updates when I start building.
Here’s a few images to satisfy the curious:
schematic
Mazetrix Layout
Syndicated 2009-06-18 04:55:24 from robotguy.net/Blog
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
1371.0 - Book Retailers, Australia, 2002-03
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 21/09/2004
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Help for : Adobe PDF.
Publications
1371.0 - Book Retailers, Australia
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Australian Bureau of Statistics
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ABS Home > Statistics > By Release Date
9303.0.40.003 - New Motor Vehicle Registrations, Australia, Aug 1999
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 08/10/1999
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• About this Release
ABOUT THIS RELEASE
This product has been discontinued and is replaced by 9303.0.55.001.
Tables contain details of new motor vehicles registered in the reference month. These details include State of registration, vehicle type, make of vehicle, top makes and models for passenger vehicles, fuel used and tare weight, gross vehicle mass or gross combination mass.
See also 9311.0.
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Australian Bureau of Statistics
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1301.0 - Year Book Australia, 2002
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Contents >> Crime and Justice >> Expenditure on public order and safety
The Steering Committee for the Review of Commonwealth/State Service Provision, in its Report on Government Services 2001, estimated that approximately $330 per person was spent by governments on justice. This figure is based on recurrent expenditure and does not include spending by governments on items such as capital works (i.e. new police stations, prisons or court facilities). Of the total recurrent expenditure of over $6b, the majority ($4b) was spent on police services, followed by expenditure on corrective services of over $1b.
Between 1995-95 and 1999-2000 expenditure grew fastest in real terms for corrective services (annual average growth rate of 12%), and most slowly for criminal courts administration (annual average growth rate of 4%).
11.2 GOVERNMENT EXPENDITURE ON JUSTICE(a)(b)
Justice sector
1995-96
$m
1996-97
$m
1997-98
$m
1998-99
$m
1999-00
$m
Growth(c)
%
Police services
3,498
3,645
3,688
4,036
4,197
7.6
Court administration - criminal
351
337
363
389
388
4.0
Court administration - civil(d)
364
418
420
456
479
11.6
Corrective services(e)(f)
1,021
1,096
1,085
1,193
1,345
11.7
Total justice system
5,235
5,495
5,555
6,074
6,409
8.4
(a) In 1999-2000 dollars.
(b) Recurrent expenditure plus depreciation less revenue from own sources.
(c) Average annual growth rate over the period 1995-96 to 1999-2000.
(d) Excludes the costs of probate hearings.
(e) Includes costs of prisoner transport and escort services. For all years, the expenditure on corrective services is the same as that reported in the corresponding Report on Government Services.
(f) Excludes WA community corrections expenditure during 1996-97. NT prison and community corrections did not deduct revenue from own sources between 1995-96 and 1996-97.
Source: Report on Government Services 2001.
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< Previous
Thoughtcrime Experiments >
Christmas Chiptunes: This year everyone is a-twitter (and a-Twitter) about 8-Bit Jesus, the excellent album of Christmas carols done in the style of NES games, an album that has doubled in size since the last time I looked at its webpage. But if you can't bear to listen to music not synthesized by a 6502, it's not your only option.
A few years ago the twittering was about The 8bits of Christmas (that really does seem to be the best way to link to it; scroll down to "8bp038"). And this guy puts out a Christmas album every year. There's also this "8 Bit XMAS 2008" which actually comes on an NES cart. If you ask me the first two albums I linked to are the best, but nobody asks me these things.
Sumana listened to some of the music and said, "You won Christmas!"
Filed under: ,
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< Doggy Bag
Next >
(3) : How To Write Telegrams Properly.
Officials felt that the vital orders of the Government must be definite and clear cut, and they therefore used not only the word "stop," to indicate a period, but also adopted the practice of spelling out "comma," "colon," and "semi-colon." The word "query" often was used to indicate a question mark. Of all these, however, "stop" has come into most widespread use, and vaudeville artists and columnists have employed it with humorous effect, certain that the public would understand the allusion in connection with telegrams...
"Stop" is of course never necessary at the end of a message.
What's the standard science fiction term for densely packed computing matter, the stuff you use to build an upload civilization? I thought it was "computanium" but that only gets a handful of search results, and I know there's a standard term for it.
Filed under:
Comments:
Posted by Tim May at Mon Oct 26 2009 18:39
Computronium?
Posted by Leonard at Mon Oct 26 2009 20:07
That's it, thanks.
Posted by Nathaniel at Mon Oct 26 2009 23:45
You should check out Unicode (that's version 6, published 1889).
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SIM Cards
From Forensics Wiki
Revision as of 07:57, 29 September 2008 by Fripberg (Talk | contribs)
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A typical SIM card.
Contents
SIM-Subscriber Identity Module
The UICC (Universal Integrated Circuit Card) is a smart card which contains account information and memory that is used to enable GSM cellular telephones. One of the applications running on the smart card is the SIM, or Subscriber Identity Module. In common parlance the term "UICC" is not used an the phrase "SIM" is used to describe the smart card itself.
Because the SIM is just one of several applications running on the smart card, a given card could, in theory, contain multiple SIMs. This would allow multiple phone numbers or accounts to be accessed by a single UICC. This is seldom seen, though there is at least one "12-in-1" SIM card being advertised at present.
Early versions of the UICC used full-size smart cards (85mm x 54mm x 0.76mm). The card has since been shrunk to the standard size of 25mm x 15mm x 0.76mm.
Although UICC cards traditionally held just 16 to 64KB of memory, the recent trend has been to produce SIM cards with larger storage capacities, ranging from 512MB up to M-Systems' 1GB SIM Card slated for release in late 2006.
ICCID
Each SIM is internationally identified by its ICC-ID (Integrated Circuit Card ID). ICC-IDs are stored in the SIM card and can also be engraved or printed on the SIM card’s body during a process called personalization. The number is up to 18 digits long with an addition of a single “check digit” that is used for error detection. This single digit allows us to detect an input error of digits, mistyped digits or a permutation of two successive digits. This digit was calculated using the Luhn algorithm.
A typical SIM (19 digits) example 89 91 10 1200 00 320451 0, provide several details as follows:
• The first two digits (89 in the example) refers to the Telecom Id.
• The next two digits (91 in the example) refers to the country code (91-India).
• The next two digits (10 in the example) refers to the network code.
• The next four digits (1200 in the example) refers to the month and year of manufacturing.
• The next two digits (00 in the example) refers to the switch configuration code.
• The next six digits (320451 in the example) refers to the SIM number.
• The last digit which is separated from the rest is called the “check digit”.
These digits can be further grouped for additional information:
• The first 3 to 4 digits represents the Mobile Country Code (MCC. Some cards only have 3 digits to represent the Telecom ID and country code.)
• The next 2 digits represent the Mobile Network Code (MNC, AKA the mobile operator)
• The next 12 digits is the number represent the Home Location Register
• And mentioned above, the “check digit”
Location Area Identity
Operation networks for cell phone devices are divided into area locations called Location Areas. Each location is identified with its own unique identification number creating the LAI (Location Area Identity). A phone will store this number on its SIM card so it knows what location it’s in and to be able to receive service. If a phone were to change to a new Location Area, it stores the new LAI in the SIM card, adding to a list of all the previous LAIs it has been in. This way if a phone is powered down, when it boots back up, it can search its list of LAIs it has stored until it finds the one its in and can start to receive service again. This is much quicker than scanning the whole list of frequencies that a telephone can have access on. This is a real plus for forensic investigators because when a SIM card is reviewed, they can get a general idea of where the SIM card has been geographically. In turn this tells them where the phone has been and can then relate back to where the individual who owns the phone has been.
SIM Security
Information inside the UICC can be protected with a PIN and a PUK.
A PIN locks the SIM card until correct code is entered. Each phone network sets the PIN of SIM to a standard default number (this can be changed via handset). If PIN protection is enabled, the PIN will need to be entered each time phone is switched on. If the PIN is entered incorrectly 3 times in a row, the SIM card will be blocked requiring a PUK from the network/service provider.
A PUK is needed if the PIN is entered incorrectly 3 times and the SIM is blocked (phone is unable to make and receive calls/texts). The PUK can be received from the network provider, or possibly the GSM cell phone manual. Caution: if PUK is entered 10 times incorrectly, the SIM card is permanently disabled and must be exchanged.
SIM Forensics
The data that a SIM card can provide the forensics examiner can be invaluable to an investigation. Acquiring a SIM card allows a large amount of information that the suspect has dealt with over the phone to be investigated.
In general, some of this data can help an investigator determine:
• Phone numbers of calls made/received
• Contacts
• SMS details (time/date, recipient, etc.)
• SMS text (the message itself)
There are many software solutions that can help the examiner to acquire the information from the SIM card. Several products include 3GForensics SIMIS [1], Inside Out's SIMCon, or SIM Content Controller, and Paraben Forensics' SIM Card Seizure.
The SIM file system is hierarchical in nature consisting of 3 parts:
• Master File (MF) - root of the file system that contains
DF’s and EF’s
• Dedicated File (DF)
• Elementary Files (EF)
Data Acquisition
These software titles can extract such technical data from the SIM card as:
• International Mobile Subscriber Identity (IMSI): A unique identifying number that identifies the phone/subscription to the GSM network
• Mobile Country Code (MCC): A three-digit code that represents the SIM card's country of origin
• Mobile Network Code (MNC): A two-digit code that represents the SIM card's home network
• Mobile Subscriber Identification Number (MSIN): A unique ten-digit identifying number that identifies the specific subscriber to the GSM network
• Mobile Subscriber International ISDN Number (MSISDN): A number that identifies the phone number used by the headset
• Abbreviated Dialing Numbers (ADN): Telephone numbers stored in sims memory
• Last Dialed Numbers (LDN)
• Short Message Service (SMS): Text Messages
• Public Land Mobile Network (PLMN) selector
• Forbidden PLMNs
• Location Information (LOCI)
• General Packet Radio Service (GPRS) location
• Integrated Circuit Card Identifier (ICCID)
• Service Provider Name (SPN)
• Phase Identification
• SIM Service Table (SST)
• Language Preference (LP)
• Card Holder Verification (CHV1) and (CHV2)
• Broadcast Control Channels (BCCH)
• Ciphering Key (Kc)
• Ciphering Key Sequence Number
• Emergency Call Code
• Fixed Dialing Numbers (FDN)
• Forbidden PLMNs
• Local Area Identitity (LAI)
• Own Dialing Number
• Temporary Mobile Subscriber Identity (TMSI)
• Routing Area Identifier (RIA) netowrk code
• Service Dialing Numbers (SDNs)
• Service Provider Name
• Depersonalizatoin Keys
This information can be used to contact the service provider to obtain even more information than is stored on the SIM card.
USIM-Universal Subscriber Identity Module
A Universal Subscriber Identity Module is an application for UMTS mobile telephony running on a UICC smart card which is inserted in a 3G mobile phone. There is a common misconception to call the UICC card itself a USIM, but the USIM is merely a logical entity on the physical card.
It stores user subscriber information, authentication information and provides storage space for text messages and phone book contacts. The phone book on a UICC has been greatly enhanced.
For authentication purposes, the USIM stores a long-term preshared secret key K, which is shared with the Authentication Center (AuC) in the network. The USIM also verifies a sequence number that must be within a range using a window mechanism to avoid replay attacks, and is in charge of generating the session keys CK and IK to be used in the confidentiality and integrity algorithms of the KASUMI block cipher in Universal Mobile Telecommunications System (UMTS).
In Mobile Financial Services, USIM seems to be a mandetory Security Element for user authentication, authorization and stored credentials. With the integration of NFC Handset and USIM, users will be able to make proximity payments where the NFS handset enables contactless payment and USIM enables independent security element. This is the evolution of the SIM for 3G devices. It can allow for multiple phone numbers to be assigned to the USIM, thus giving more than one phone number to a device.
Service Provider Data
Some additional information the service provider might store:
Service Providers that use SIM Cards in the United States
• T-Mobile
• Cingular/AT&T
Sim Card Text Encoding
Originally the middle-European GSM network used only a 7-bit code derived from the basic ASCII code. However as GSM spread worldwide it was concluded that more characters, such as the major characters of all living languages, should be able to be represented on GSM phones. Thus, there was a movement towards a 16-bit code known as UCS-2 which is now the standard in GSM text encoding. This change in encoding can make it more difficult to accurately obtain data form SIM cards of the older generation which use the 7-bit encoding. This encoding is used to compress the hexadecimal size of certain elements of the SIMs data, particularly in SMS and Abbreviated Dialing Numbers.
Authentication Key (Ki)
The authentication key or Ki is a 128 bit key used in the authentication and cipher key generation process. In a nutshell, the key is used to authenticate the SIM on the GSM network. Each SIM contains this key which is assigned to it by the operator during the personalization process. The SIM card is specially designed so the Ki can't be compromised using a smart-card interface. However, flaws in the GSM cryptography have been discovered that do allow the extraction of the Ki from the SIM card, and essentially SIM card duplication.
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Invasive contributor
27Jan2012,20:51 #31
Quote:
Originally Posted by jamesadam432
Directory submission is normally used as a technique for doing search engine optimization of a website. I heard recently that this method is not much useful now. Is it right?
any suggestions for new techniques please.
Thanks
I don't think it is directory submission per sey that has been devalued, rather that many of the directories themselves have been devalued.
It can still be a part of a wider link building strategy, but avoid the low PR ones, find niche directories if you can, submit manually, and don't submit if a reciprocal link is required. As in all things, it is quality rather than quantity that is important.
As far as I am aware there is nothing new that has come along to replace directories, but there are already many other ways of building links.
Invasive contributor
7Feb2012,15:12 #32
Quote:
Originally Posted by axissoftech
Very descriptive and informative share.
I think this comment makes the same contribution to this thread as some of your comments on others have done, such as:
Nice informative share. Useful post for readers.
Thanks for a very descriptive summary
Nice post..learn things from this post thanks for sharing.
Appreciate for this post..very beneficial for users.
i.e. not very much really.
Invasive contributor
21Apr2012,20:05 #33
Quote:
Originally Posted by sachinseo
very nice stuffs collection by you. but i missing the question how we can find the blacklisted site and how we can remove the url from it.
I think you are asking that if you have a link to your site from one that you do not want to be linked from, how can it be removed?
If so, that is a subject for a different thread.
Ambitious contributor
23Apr2012,11:43 #34
These questions are really helpful from interview perspective and also gives a permanent idea and knowledge on the techniques and principles of SEO.
Newbie Member
8Jan2013,00:25 #35
Its Really good post.
Newbie Member
8Jan2013,16:29 #36
Thank you very much for posting it.
Banned
4Apr2013,16:40 #37
Shabbir your really having a great stuff in this field exactly your master in it thanks man for the sharing this info.
Go4Expert Founder
4Apr2013,16:52 #38
Quote:
Originally Posted by ramiszaro
Shabbir your really having a great stuff in this field exactly your master in it thanks man for the sharing this info.
Use the thanks button rather.
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Bioinorganic Chemistry and Applications
Volume 2012 (2012), Article ID 649640, 10 pages
doi:10.1155/2012/649640
Research Article
Sensitive Marker of the Cisplatin-DNA Interaction: X-Ray Photoelectron Spectroscopy of CL
State Key Laboratory Breeding Base of Photocatalysis, Research Institute of Photocatalysis, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China
Received 30 July 2012; Revised 27 September 2012; Accepted 29 September 2012
Academic Editor: Nicholas P. Farrell
Copyright © 2012 Fangxing Xiao 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
The development of cisplatin and Pt-based analogues anticancer agents requires knowledge concerning the molecular mechanisms of interaction between such drugs with DNA. However, the binding dynamics and kinetics of cisplatin reactions with DNA determined by traditional approaches are far from satisfactory. In this study, a typical 20-base oligonucleotide (CGTGACAGTTATTGCAGGCG), as a simplified model representing DNA, was mixed with cisplatin in different molar ratios and incubation time. High-resolution XPS spectra of the core elements C, N, O, P, and Cl were recorded to explore the interaction between cisplatin and DNA. From deconvoluted Cl spectra we could readily differentiate the covalently bound chlorine from ionic chloride species in the cisplatin-oligo complexes, which displayed distinct features at various reaction times and ratios. Monitoring the magnitude and energy of the photoelectron Cl 2p signal by XPS could act as a sensitive marker to probe the interaction dynamics of chemical bonds in the reaction of cisplatin with DNA. At 37°C, the optimum incubation time to obtain a stable cisplatin-oligo complex lies around 20 hrs. This novel analysis technique could have valuable implications to understand the fundamental mechanism of cisplatin cytotoxicity and determine the efficiency of the bonds in treated cancer cells.
1. Introduction
Cis-diamminedichloroplatinum (cisplatin) has become the most frequently used drugs in the chemotherapy treatment of most malignant cancers [14]. The enhancement of DNA damage by cisplatin in concomitant chemoradiation therapy further stresses the application of the cisplatin analogues drug in cancer treatment [5, 6]. Cisplatin kills cancer cells via apoptosis caused by its binding and cross-linking to nuclear DNA, in which different intermediate adducts formed when cisplatin binds to DNA are thought to be responsible for its cytotoxicity. Therefore, probing the molecular basis of such underlying interactions could have significant implications for the optimum clinical application of cisplatin and platinum-based antitumor drugs.
The process of Pt binding to nucleobases involves complex pathways which are kinetically controlled, rendering accurate identification of the reaction rates and products rather difficult. In this regard, a myriad of analyzing technologies to date have been harnessed to investigate the manifold of adducts from the cisplatin—DNA reactions, including ionic exchanged chromatography [7], capillary electrophoresis (CE) [811], high-performance liquid (HPLC) [12, 13], X-ray diffraction [1418], NMR spectroscopy [12, 1921], extended X-ray absorption fine structure (EXAFS), Fourier transform infrared (FTIR) [22], a collection of mass spectroscopy (MS) techniques [8, 16, 17, 2332], and time-resolved femtosecond laser spectroscopy [33]. These series of combinatorial studies have revealed that the reaction initiates predominantly from the aquation process of cisplatin to the monofunctional and bifunctional adducts on the time scale of days to weeks. The major configurations are the GpG and ApG intrastrand adducts that together account for 80–90% of the bound Pt. Despite the above joint techniques used for the determination of the products deriving from cisplatin binding to DNA, the challenge for elucidating the intermediate binding mechanism has met with limited success. Meanwhile, many other factors such as DNA sequence types and buffer can also affect the observed adduct profile. Hence, the interaction of cisplatin with DNA at the molecular scale was found to be fairly intricate in addition to its significance in cancer therapy. In practice, the application of Pt-based chemotherapeutic drugs requires a simple and direct method to monitor such interaction process.
Previous studies revealed the cisplatin aquation and subsequent reactions to be mainly oriented toward the Pt binding process. Nonetheless, important information regarding the chloro ligands released from cisplatin is generally neglected because it is difficult to obtain via conventional HPLC-based techniques. Moreover, reports on the interaction of cisplatin with DNA, by monitoring the chlorine signal with X-ray photoelectron spectroscopy (XPS), have not yet been reported. In the present study, new insights into the interaction of cisplatin with DNA are obtained by monitoring chlorine instead of the more conventional Pt signal with XPS. XPS is one of the most powerful techniques of chemical characterization. Compared to traditional analytical methods mentioned above, not only does it allow quantitative elemental analysis of various sample films, but also, more significantly, provides relatively precise information with regard to the modification of chemical bonds and elemental chemical state.
XPS characterization of cisplatin-DNA interaction has not been reported apart from the tentative work performed by Millard et al. in 1975 [34]. Depending on the sensitive binding energy (BE) shift of DNA constituent elements, including N 1s, O 1s, and P 2p, the authors concluded that the cisplatin—DNA reaction was initiated by the attack of Pt at the N7 position and neighboring O6 sites of guanine (G). Compared to the result of other techniques, which showed that cisplatin preferentially bonds to N7 sites of purine [4, 14, 15, 35], it thus appears highly desirable to systematically compare the cisplatin—DNA to pure DNA by XPS again with current improved sensitivity and resolution. With respect to the discrimination between aqua and chloroligands XPS is particularly well suited to detect the chemical changes of chlorine, which would be a powerful signal to monitor the kinetic interaction between cisplatin and DNA.
Herein, in order to simply elucidate the general chemistry scenario of cisplatin and DNA, a typical 20-base oligonucleotide, that is, the “oligo,” CGTGACAGTTATTGCAGGCG, with 8 sites of G is devised and used as a proof-of-concept model to represent cellular DNA. Cisplatin-oligo complexes are prepared with different ratios of cisplatin and reaction time at 37°C, as it does in most in vitro reactions [36, 37]. High-resolution spectra of the principal elements of oligonucleotide (C, N, O, P and Cl) with and without binding to cisplatin are accurately measured by XPS to probe the detailed chemical bond transformation of oligo in the dynamic process of cisplatin binding to DNA as compared with pure DNA. The significant differences of high-resolution spectra of Cl demonstrate that monitoring the chloro ligand by XPS could provide an easily accessible and effective way to disclose the detailed reaction dynamics of cisplatin. More significantly, the technique may be extended to other Pt-relating anticancer drugs used in chemotherapy. We also specifically discuss for the first time the compositional alterations of DNA in relation to its binding with cisplatin. It is hoped that our current work could motivate explorations focused on the mechanical analysis between platinum-based antitumor drugs and DNA with XPS.
2. Materials and Methods
2.1. Materials
The HPLC purified 20-mer oligo (CGTGACAGTTATTGCAGGCG, molecular weight 6063) was purchased from Invitrogen. The amount of oligo was determined by measuring its UV absorption at 260 nm of 28.5 μg/OD provided by Invitrogen. Cis-diammineplatinum (II) dichloride (cisplatin) was obtained from Sigma Aldrich and used without any further purification. The tantalum substrates (Alfa Aesar, 99.95%) were cleaned by ultrasonic with ethanol and deionized water (ddH2O, Milipore, 18.2 MΩ·cm resistivity) for three times and dried in glove box at room temperature prior to each deposition of DNA.
2.2. Preparation of Oligo and Cisplatin-Oligo Films
10 μL of oligo solution (100 μM) were deposited on the tantalum foil forming a drop with 2 mm radius and dried in glove box under nitrogen atmosphere at room temperature. Assuming a uniform distribution of the oligo on the substrate and a density of 1.7 g cm−3, the thickness of the film was estimated to be 50 molecular layers (ML).
0.1 mg of cisplatin was dissolved in 500 μL dd H2O at 55°C for 30 minutes to obtain the cisplatin solution. Subsequently, the cisplatin solution was mixed with oligos to prepare the cisplatin-oligo complexes with different ratios (), where is defined as the molar ratio of platinum atom to oligo molecule. In brief, 5.2 μL of 100 μM oligo were mixed with 1.56 μL of cisplatin with different concentration (from 100 to 2000 ng/μL) to get the final cisplatin-oligo complexes with molar ratios of 1 : 1, 2 : 1, 4 : 1, 8 : 1, 10 : 1, 12 : 1, 20 : 1, respectively. The cisplatin-oligo complexes were simultaneously incubated at 37°C in the dark for 4 h in PCR (GeneAmp PCR System 9700). Finally, the aqueous cisplatin-oligo solution was deposited on a tantalum substrate and dried in glove box with nitrogen atmosphere at room temperature to form the films of cisplatin-oligo complexes with different ratios. With the same amount of oligos in the complexes the thickness of all the cisplatin-oligo films was estimated to be 26 ML.
For the experiment of various incubation times, similarly, cisplatin-oligo complexes with ratio of 8 : 1 were incubated at 37°C from 0 to 24 h with 4 h time interrupt in between. Each sample was immediately removed from PCR at given time and formed the corresponding films for further XPS analysis.
2.3. XPS Measurement
XPS measurements were conducted using a commercial XPS system (Thermo Scientific ESCALAB 250) equipped with a dual anode X-ray gun, a concentric hemispherical electron energy analyzer, and a magnetic electron lens. The apparatus was operated with a monochromatic Al K beam as the excitation source ( eV) with the energy resolution of 0.45 eV. The emission current was kept at 6 mA under a base pressure of 3.8 × 10−10 mbar. The XPS spot size and analyzer field were below 1 mm2. The neutralizing electron gun was turned on in the low energy mode with emission current of 100 mA to eliminate the charging of the samples during X-ray irradiation. Before the measurements each film was first etched by Argon ion operated at 2 KV and 1 μA for 30 s. The material removed was estimated to be approximately 1.2 nm (0.4 Å/s × 30 s = 1.2 nm). No difference is observed in the P 2p spectra before and after Ar etching, while three monitored spots are randomly chosen on each sample surface (See Supporting Information Figure S1 in Supplementary Material available online at doi:10.1155/2012/649640). It indicates that the applied Ar etching does not affect the chemical composition of oligo and oligo-Pt complex on the Ta substrate under the present conditions. Instead it can helpfully remove surface contaminants and expose the fresh sample particularly for C, O, and N spectra. Since the XPS probing length is approximately 10 nm (3–5 ML) on a sample surface [38], the thickness of oligo and cisplatin oligo films with profile of 50 and 26 ML in the present study is found to be sufficient for the XPS characterization.
The hemispherical electron energy analyzer input axis was normal to the sample surface. XPS survey spectra from BE of 0 to 1200 eV were recorded in the fixed analyzer transmission mode with a pass energy of 100 eV and energy steps of 1 eV. The typical peaks of elements, C 1s, N 1s, O 1s, P 2p, Cl 2p, and Pt 4f, were recorded separately with pass energy of 50 eV and energy steps of 0.05 eV. The energy scale of XPS spectra was calibrated according to the standard C 1s BE line of 285.0 eV, which corresponds to standard hydrocarbon energy of C–H and C–C bonds. The work function of the system was 4.38 eV.
2.4. XPS Peak Analysis
Commercial XPS analysis software (Advantage 4.37) was used to calculate the peak area and deconvolute the peaks of high-resolution spectra. The atomic ratios of composition elements in the film were calculated according to the corresponding fitted peak area and corrected by the instrument sensitivity factors (SF), leading to the more reliable result with error of 5%. The convolution of Lorentzian and Gaussian line shapes were employed to fit the core-level spectra of individual peaks as well as the Shirley function to model the background.
3. Results and Discussion
3.1. The Reaction Process of Cisplatin with Oligos during the Incubation Time
Generally, two chemical states of chlorine exist in any compound, that is, the covalent-bound and the ionic states [39]. Figure 1(a) exhibits the core-level Cl 2p spectra of cisplatin in the solid phase (top curve) and in H2O (bottom curve). The individual Cl 2p peaks could be deconvoluted according to the chemical characteristics of chlorine. With the angular momentum coupling the 2p orbital of each type of chlorine consists of the spin-orbit-split doublet, that is, 2p3/2 and 2p1/2 [40]. Thus, the spectra of Cl 2p are curve fitted to two doublet subpeaks assigning to covalent (dashed upper curve in Figure 1(a)) and both covalent and ionic chlorine (dashed curves in lower Figure 1(a) and in Figure 1(b)).
Figure 1: (a) High-resolution XPS spectra of Cl 2p for cisplatin in solid phase and in H2O. (b) Cl 2p spectra for cisplatin-oligo complex at ratio of 8 : 1 with the increasing incubation time. The peaks are deconvoluted to covalent and ionic Cl (two coupled dashed lines), respectively. The straight line is used to point out the relative position of covalent Cl. (c) The binding energy of ionic Cl 2p3/2 corresponding to (b) as a function of incubation time.
For cisplatin in the solid, without the perturbation of aquation all chlorine is expected to be covalently bound to Pt. In other words, the spectrum of solid state cisplatin represents the characteristic covalent Cl with BE of 199.6 and 201.1 eV (Figure 1(a)). When cisplatin is dissolved in H2O, it is known that the kinetic of the aquation process involves the replacement of Cl by H2O subsequently in two steps, resulting the coexistence of two types of Cl: ionic and covalent, around the bulk of cisplatin [25, 41]. The ionic Cl arises from the release of covalently bound chlorine from cisplatin and exists owing to the remaining electrostatic interaction, indicating that the BE of ionic chlorine is smaller than that of covalently bonded. This scenario is demonstrated in Figure 1(a) for cisplatin in water, where a strong signal of ionic Cl is observed and the covalent Cl signal remains. The latter is evidently seen with the identical BE as that of in solid cisplatin. The similar assignation of Cl is applied to the spectra of cisplatin-oligo complex.
Figure 1(b) shows the core-level Cl 2p spectra of the cisplatin-oligo complex at molar ratio of 8 : 1 as a function of incubation time, ranging from 0 to 24 h at interval of 4 h. The high-resolution spectra of Cl 2p display dramatically different features with reaction time prolonging. At 0 h, which means that cisplatin is only mixed with oligos without the incubation at 37°C, two main peaks are observed corresponding to covalent and ionic Cl with characteristic BEs of 200.15 and 198.48 eV, respectively. The feature of the two main peaks remains after incubation for 4 h with the shift of related BEs to lower energies of 199.24 eV and 197.71 eV, respectively. With longer reaction time, the Cl spectra appear as a prominent broader peaks except at 24 h where the feature of the two peaks could be observed again to some extent. Applying the same principle of peak deconvolution, two types of Cl could be assigned in each spectrum with respect to various incubation times. The result clearly displayed that the BE of covalent Cl remained almost the same from 4 to 24 h, whereas the BE of ionic Cl decreased with a final relative increase of 0.27 eV at 24 h. The BE of ionic Cl as a function of incubation time is specified in Figure 1(c).
When cisplatin is mixed with oligos, the reaction channel of cisplatin directly interacting with oligos is expected to be competitive with the simultaneous aquation of cisplatin. In the process of hydrolysis, the chloride ions are progressively replaced by water (H2O) ligand, resulting in the production of cationic monofunctional and bifunctional adducts [41]. NMR studies have determined the half-time of cisplatin hydrolysis is ca. 2 h with cis-[Pt(NH3)2Cl(H2O)]+ as the dominant species which compromise ca. 8% of the total platinum complex within 2 h [41]. As revealed in Figure 1(a), the Cl spectrum of cisplatin-oligos at 0 h is similar to that of pure cisplatin, indicating a similar initial status of the reaction system. For pure cisplatin after 4 h of incubation the covalent component in the Cl spectra could be mainly assigned to the cis-[Pt(NH3)2Cl(H2O)]+ species with featured BE of 199.82 eV. Under identical reaction conditions, however, the Cl spectrum of the cisplatin-oligo complex varies substantially from the pure cisplatin with a pronounced BE shift of covalent-bound Cl (i.e., 199.18 eV versus 199.82 eV). Although it could not be accurately determined whether the formation of cis-Pt(NH3)2Cl-oligo adduct was due to the direct replacement of Cl ligand in cisplatin by oligos or replacement of water in cis-[Pt(NH3)2Cl(H2O)]+ by oligos, the significant difference of the spectra along with substantial BE shift simultaneously suggest that in the cisplatin-oligo system formation of cis-[Pt(NH3)2Cl (oligo)]+ adduct is the main pathway as compared with hydrolysis. In other words, cisplatin could react easily with oligos leading to irreversible DNA binding.
Notably, the full width at half-maximum (FWHM) for covalent and ionic Cl peaks at 4 h is approximately 1.0 and 1.1 eV, respectively. With the reaction time processing, the broadening of the Cl peaks, especially for the ionic Cl, is obvious in Figure 1(b). The enlargement of the peak reflects the increase of the inelastic electron scattering with the longer reaction time, which further demonstrates the formation of chemical bond between Pt and oligo bases as well as the release of ionic Cl. Evidence of ionic Cl release is reflected by the gradual decrease of BE for the ionic Cl 2p3/2 from 0 to 20 h (Figure 1(c)). The negative BE shift of ionic Cl indicates that Cl could be increasingly released with the binding of cisplatin to oligo. Around 20 h, it is expected that nearly all Cl ligands of the Pt species are replaced by oligo forming the cis-Pt(NH3)2(oligo) adducts such as cis-Pt(NH3)2GG, giving the major feature of ionic Cl in the spectra. At 24 h, the increase of the Cl BE and the recovered feature of two main peaks with characteristic BEs of 199.47 eV and 197.38 eV suggests that the interaction of cisplatin with oligos stabilizes around the incubation time of 20 h. Another explanation of the two-peak reappearance is the possible formation of bridged dinuclear platinum adducts, as reported by Davies et al. [41]. They reported that indication of the formation of bridged dinuclear platinum adducts is around 26 h [41].
The present result of high-resolution Cl spectra as a function of reaction time is consistent with the well-known cisplatin-DNA reaction schemes. In addition, it discloses that the process of cisplatin binding to DNA at a temperature of 37°C over a time scale of 24 h is more kinetically than thermodynamically controlled. Compared to previous studies focused on the Pt bonding, the signal of Cl by XPS technique could be a sensitive marker to directly reflect the dynamics of cisplatin reaction with DNA.
3.2. The Effect of the Molar Ratio of Cisplatin to Oligo
The Cl spectra of the complexes with various cisplatin/oligo ratios are illustrated in Figure 2 together with the pure cisplatin under the identical incubation time of 4 h. For better comparison, the amount of oligos was kept the same in the measurement; that is, only the amount of cisplatin increases. Accordingly, the amount of cisplatin with ratio of 2 is equal to 1 nmol, which is close to the detection limit of the XPS signal thereby leading to a broad Cl peak with relatively high signal-to-noise. Thus, with the exception of the ratio of 2 each Cl spectrum could be deconvoluted into two doublet 2p peaks assigned to covalent and ionic Cl, respectively (Figure 2). The Cl spectra of cisplatin-oligo complexes with ratios of 4, 8, and 10 exhibit similarly two main 2p3/2 peaks with BE of 199.2 and eV for covalent and ionic Cl, respectively. The assignment is consistent with the previous studies on the Cl containing compounds [4251]. Moreover, the integrated peak area of each type of Cl indicated a relative percentage of ionic to covalent Cl of approximately % for ratios of 4, 8, and 10.
Figure 2: High-resolution XPS spectra of Cl 2p for cisplatin-oligo complexes with ratios () from 2 to 20 with identical amount (3.1 μg) of oligo. All samples are taken after incubation at 37°C for 4 hrs. The three straight lines are used to assign the position of covalent and ionic (I) Cl bond position of cisplatin-oligo complexes as well as the ionic (II) Cl of cisplatin, respectively.
When the ratio increased to 12 and 20, a broader peak with higher BE is displayed. The result of reaction time has indicated that the BE of ionic Cl to the oligo is around 197.7 eV or lower. Compared to the spectra of cisplatin-oligos with lower ratios, it is surprising to find that the peak which could be resolved to similar ionic Cl (ionic I) does not exist in the cisplatin-oligo complex with ratios of 12 and 20. With such high BE, the broad peaks of cisplatin-oligo complex with ratios of 12 and 20 could only be assigned to covalent bond Cl. This assignment seems contrary to the previous result, indicating that cisplatin could react easily with oligos leading to the release of ionic Cl. How can we understand the apparent disappearance of the ionic Cl in Figure 2?
Noteworthily, the 20-base oligo (CGTGACAGTTATTGCAGGCG) used in this study has 11 purines (G, A) indicating there are a total of 11 interaction sites for one cisplatin. Thus, in the case of mole ratio of cisplatin to oligo lower than 11, cisplatin could react completely, that is, binding to one of G or A bases and release Cl as indicated in Figure 1. When the ratio increases beyond 11, there is an oversupply of cisplatin with respect to the reaction sites. In other words, the system contains more cisplatin which cannot react with oligos and has to follow the aquation process. The increase in the amount of cisplatin results in the change of chemical environment in the cisplatin-oligo complex, leading to shift of the Cl spectra to higher BE. In fact, the Cl spectrum of pure cisplatin under identical conditions is resolved to covalent and ionic Cl with BE of 199.82 and 198.37 eV, respectively. Thereby, it is reasonable to deconvolute the spectra of Cl with ratio of 12 and 20 to the ionic Cl in pure cisplatin, as ionic (II) Cl shown in Figure 2. Moreover, multiple reactions could also occur in the system with ratios of 12 and 20 which is demonstrated by the broader peaks of Cl spectra compared to that of ratios lower than 11.
Determination of the platination of DNA with Pt-based drugs is usually confined to complicated inductively coupled plasma mass spectroscopy (ICPMS) which may not provide sufficient information on the specific interaction process [52]. Our results strongly evince that peak intensity and detailed chemical compositions deconvoluted from the Cl spectra are well correlated with the ratio of cisplatin to oligo. The covalently bound chlorine (−Cl) and ionic chloride (Cl) species in different reaction procedures and in the presence of varied molar ratios of cisplatin could be readily differentiated solely from the high-resolution Cl spectra. That is, the Cl XPS spectrum could exhibit distinct features at different molar ratio levels, thus, making it an alterative in situ approach to trace the platination process of DNA. It also suggested that the characterization of Cl by XPS could be applied to monitor the interaction of chemotherapeutic agent cisplatin with DNA.
3.3. Chemical Bond Transformation of DNA Induced by Cisplatin
In addition to the Cl spectrum, XPS could also be used to characterize the chemical bond transformations of DNA induced by cisplatin. The high-resolution spectra recorded for the four principal elements, C, N, O, and P of DNA (C 1s, N 1s, O 1s, and P 2p regions of cisplatin-oligo and oligo) are presented in Figure 3. A number of peaks are chosen to fit each elemental region corresponding to particular chemical bonding. The assignment of the spectral peaks is carried out according to the known substituent effects of core electron binding energies [53]. The XPS characterization of thymus DNA [54] and self-assembled monolayer DNA [55, 56] has also been reported previously. Due to structural similarity of oligo to DNA and for better comparison, we apply the same peak assignments referring to the work of Ptasińska et al. [54]. The specific chemical bond species relating to C, N, and O in the framework of oligonucleotide are displayed in the supporting information.
Figure 3: High-resolution XPS spectra of C 1s, N 1s, O 1s, and P 2p regions for pure oligos and cisplatin-oligo complexes at a ratio of 10 with the same amount of oligos in the films. The incubation time for the cisplatin-oligo complex is 4 hr. The peaks (solid curve) were deconvoluted into specific components of the oligo (dashed line) including (a) C 1s, urea (peak 1), amide (2), C–N/C–O–C/C–OH/N=C–C (3), and hydrocarbon (4); (b) N 1s, amino (1) and imino (2); (c) O 1s, C–OH (1), C=O/N=O (2), and phosphate group (3); (d) P 2p, the phosphate group. Note that the spectra in each figure are on the same scale, but offset for clarity.
The C 1s spectra of cisplatin-oligo and oligo (Figure 3(a)) are curve-fitted to assign four types of carbon species: (1) urea [N–C(=O)–N], (2) amide (N–C=O), (3) alcohol/cyclic ether/carbon bond to nitrogen (C–OH/C–O–C/C–N/N=C–C), and (4) hydrocarbon (C–C/C–H). In the present study, the samples are sputtered with Ar ions before each measurement to obtain minimum carbon contamination in the XPS spectra. Thus, the C 1s spectra exhibit features uniquely due to the different contributions of carbon species in the bulk sample. The XPS C 1s spectrum of oligo shows faithful agreement with the previously reported single-strand DNA [55]. From the convoluted peak areas of the different carbon species, the percentage of corresponding 1–4 carbon components is found to change from 7.13%, 17.73%, 38.19%, and 36.95%, to 3.18%, 15.24%, 29.77%, and 51.18%, respectively, with the ratio of cisplatin to oligo increasing from 0 to 10. The constituent of C 1s spectrum varies appreciably for component 4 and the intensities greatly increase with the addition of cisplatin to oligo. It suggested that the binding of cisplatin may violently perturb the regular structure of oligonucleotides leading to the alternation of chemical environment. More specifically, with the inter- and intrastrand binding of cisplatin to DNA bases, greater effect of structural change, such as the perturbation of hydrogen bonding between bases, is expected to occur in the well-defined double-strand DNA.
The principal N 1s core-level peak consists of two-component structure for DNA with BE of 400.8 and 399.3 eV, respectively, consistent with published results [55]. The higher energy peak is attributed to amino N sites connected with single bonds, and the peak at the lower BE is assigned to imino species that include a double N=C bond. The N 1s spectrum of cisplatin-oligo displays different features in comparison with pure oligo: the increase of the intensity to a narrower peak and the shift of the peak to higher BE. It is known that cisplatin binds preferentially to the N7 sites of G or A yielding cisplatin-DNA adducts, and moreover, in vitro studies have shown that cis-Pt(NH3)2GG and cis-Pt(NH3)2AG intrastrand cross-link adducts account for 65% and 25%, respectively, in the total Pt-DNA species [57, 58]. Hence, it is expected that the peak 1 of N 1s for cisplatin-oligo includes the new contribution of the Pt–N bond. Compared to oligos, BEs of the amino and imino for cisplatin-oligos increased to 401.8 and 400.1 eV, respectively, indicating the formation of stronger chemical bond.
The O 1s spectrum of oligo is consistent with the previous report, including two main peaks and a relatively small peak with BE of 534.3, 532.8, and 531.1 eV, respectively. The small peak is deconvoluted according to the procedure of Dinsmore and Lee and assigned to the C–OH bond [55]. Nevertheless, for oligos, the alcohol is the smallest component in all the O species, which is negligible as indicated in [55]. A relative symmetric peak is observed in the O 1s spectrum of cisplatin-oligos. Similarly, it can be deconvoluted to three peaks having BE of 534.5, 533, and 532 eV. One possible explanation in terms of the change of O 1s spectra is that cisplatin could also react with carbonyl group near the N7 sites of guanine, as suggested by Macquet and Theophanides [59], which may contribute to the change of carboxyl/carbamido (2) species. Furthermore, it is noticeable that peak 3, which is assigned to oxygen in the phosphate group, is substantially shifted to higher BE by 0.9 eV. Since there is no bonding of cisplatin to the backbone, it is speculated that cisplatin binding to DNA bases may exert influence on the chemical bond environment of sites neighboring the backbone. In the case of P 2p spectra, a peak with increased BE of 0.2 eV is observed for cisplatin-oligo. In this regard, we speculate that the binding of cisplatin may authentically affect the backbone in that P 2p spectra can only be attributed to the phosphate of backbone; this result is in agreement with the interpretation of the result of O 1s spectra.
To recapitulate, significant changes are clearly observed in the XPS survey spectra of cisplatin-oligo complexes compared to that of pure oligo (Figure S5). It was explicitly demonstrated that the BEs and peak intensity in oligos with regard to the C 1s, N 1s, O 1s orbitals were perturbed with the addition of cisplatin, a phenomenon which lies at the basis of the mechanism for the cytotoxicity of cisplatin in cell.
3.4. DNA Chemical Bond Transformation during the Incubation Time
In addition to Cl spectra, chemical bond transformation during the incubation time could be related to the C, N, O, and P spectra. Applying the similar Gaussian curvefitting shown in Figure 3, the relative peak percentage of different components for C, N, and O species at various incubation times could be obtained. The relative percentage of O in phosphate (O 1s-3), N in imino (N 1s-2), and C in urea (C 1s-1) as a function of incubation time from 8 to 24 h is illustrated in Figure 4. The peak percentage of the typical three bonds of C, N, and O displays a similar trend, that is, decreasing dramatically from incubation time of 8 to 12 h along with relative saturation from 16 to 24 h. It indicates that no matter to what extent cisplatin binding influences the O, C, and N bonding in DNA, the chemical bond is more stable with the incubation time longer than 16 h. Thus, to get better equilibrium of chemical reaction between cisplatin and DNA and obtain stable cisplatin-DNA complexes for further radiation study, we suggest an optimum incubation time for cisplatin of about 20 h. The result also implies that for concomitant chemoradiation therapy involved Pt-based drugs the optimum uptake of cisplatin could occur within one day after injection.
Figure 4: The relative percentage of O–P (■), N=C (●), and C–N (▲) bonds for a cisplatin-oligo complex with ratio of 10 deconvoluted from the corresponding O 1s, N 1s, and C 1s peaks as a function of incubation time. The percentages were obtained from a similar Gaussian deconvolution procedure as shown in Figure 3.
4. Conclusion
The dynamics of cisplatin interaction with a 20-mer oligo have been systematically monitored by XPS technique. High-resolution XPS spectra of Cl in cisplatin-oligo complexes showed characteristic features with respect to different reaction time and ratios of cisplatin to oligo. The result indicated that characteristic Cl signal obtained by XPS could be employed as a sensitive marker to disclose the reaction dynamics of cisplatin binding with DNA, which at 37°C mimics the process in chemotherapy. By accurate measuring the spectra of other principal compositional elements of oligo (i.e., C, N, O, and P), the shift of the BE as well as peak intensity with the binding of cisplatin were, for the first time, observed. Since the structural and chemical bond modifications may provide information related to the cytotoxicity of cisplatin in cell, our results would point to promising vistas on XPS as a novel characterization platform to investigate the dynamics of specific processes in the reaction of cisplatin with DNA, along with complementary results from traditional methods. In fact, the technique may have widespread applications to monitor the reaction dynamics of other Pt-based chemotherapeutic agents, such as carboplatin and oxaliplatin. Recently, engineering of cisplatin nanoparticles with glycol-functionalized copolymer exhibit improved antitumor efficacy [60], indicating the continuous opening of the development of novel cisplatin drugs. Further systematic work along this line on interaction between Pt-anticancer drugs and DNA is in progress in our lab.
Acknowledgments
The support by the National Natural Science Foundation of China (20973039), the Award Program for Minjiang Scholar Professorship, Program for Changjiang Scholarship and Innovative Research Team in University (PCSIRT0818), and the National Basic Research Program of China (973 Program: 2007CB613306) is greatly acknowledged.
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About this Journal Submit a Manuscript Table of Contents
Computational and Mathematical Methods in Medicine
Volume 2012 (2012), Article ID 761901, 11 pages
doi:10.1155/2012/761901
Research Article
Diabetic Retinopathy Grading by Digital Curvelet Transform
1Biomedical Engineering Department, Medical Image & Signal Processing Research Center, Isfahan University of Medical Sciences, Isfahan 81745319, Iran
2Ophthalmology Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Received 24 May 2012; Accepted 30 July 2012
Academic Editor: Jacek Waniewski
Copyright © 2012 Shirin Hajeb Mohammad Alipour 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
One of the major complications of diabetes is diabetic retinopathy. As manual analysis and diagnosis of large amount of images are time consuming, automatic detection and grading of diabetic retinopathy are desired. In this paper, we use fundus fluorescein angiography and color fundus images simultaneously, extract 6 features employing curvelet transform, and feed them to support vector machine in order to determine diabetic retinopathy severity stages. These features are area of blood vessels, area, regularity of foveal avascular zone, and the number of micro-aneurisms therein, total number of micro-aneurisms, and area of exudates. In order to extract exudates and vessels, we respectively modify curvelet coefficients of color fundus images and angiograms. The end points of extracted vessels in predefined region of interest based on optic disk are connected together to segment foveal avascular zone region. To extract micro-aneurisms from angiogram, first extracted vessels are subtracted from original image, and after removing detected background by morphological operators and enhancing bright small pixels, micro-aneurisms are detected. 70 patients were involved in this study to classify diabetic retinopathy into 3 groups, that is, (1) no diabetic retinopathy, (2) mild/moderate nonproliferative diabetic retinopathy, (3) severe nonproliferative/proliferative diabetic retinopathy, and our simulations show that the proposed system has sensitivity and specificity of 100% for grading.
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Bibliography: Wake for the Living
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Title: Wake for the Living
Author: Ray Bradbury
Year: 1947
Variant Title of: The Coffin (by Ray Bradbury ) [may list more publications, awards and reviews]
Type: SHORTFICTION
Storylen: shortstory
ISFDB Record Number: 64843
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Copyright (c) 1995-2011 Al von Ruff.
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Symmetry 2010, 2(1), 272-283; doi:10.3390/sym2010272
Article
Time-Symmetric Boundary Conditions and Quantum Foundations
Department of Physics and Astronomy, San Jos´e State University, San Jos´e, CA 95192-0106, USA
Received: 1 January 2010 / Accepted: 4 March 2010 / Published: 8 March 2010
(This article belongs to the Special Issue Feature Papers: Symmetry Concepts and Applications)
Download PDF Full-Text [110 KB, uploaded 8 March 2010 15:00 CET]
Abstract: Despite the widely-held premise that initial boundary conditions (BCs) corresponding to measurements/interactions can fully specify a physical subsystem, a literal reading of Hamilton’s principle would imply that both initial and final BCs are required (or more generally, a BC on a closed hypersurface in spacetime). Such a time-symmetric perspective of BCs, as applied to classical fields, leads to interesting parallels with quantum theory. This paper will map out some of the consequences of this counter-intuitive premise, as applied to covariant classical fields. The most notable result is the contextuality of fields constrained in this manner, naturally bypassing the usual arguments against so-called “realistic” interpretations of quantum phenomena.
Keywords: time symmetry; Hamilton’s principle; classical field theory; quantum foundations
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Cite This Article
MDPI and ACS Style
Wharton, K. Time-Symmetric Boundary Conditions and Quantum Foundations. Symmetry 2010, 2, 272-283.
AMA Style
Wharton K. Time-Symmetric Boundary Conditions and Quantum Foundations. Symmetry. 2010; 2(1):272-283.
Chicago/Turabian Style
Wharton, Ken. 2010. "Time-Symmetric Boundary Conditions and Quantum Foundations." Symmetry 2, no. 1: 272-283.
Symmetry EISSN 2073-8994 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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Cronn Lab:Research
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Contents
Douglas-fir Transcriptome Observatory
The basis of climatic adaptation in Douglas-fir (Pseudotsuga menziesii) - possibly the most ecologically and economically important conifer in western North America - is poorly understood. This limits our ability to predict population changes to climate and offer science-based prescriptions for management. The Transcriptome Observatory merges a large-scale translocation study with expressed gene (transcriptome) sequencing to define seasonal leaf transcriptomes, and differences in gene expression that define trees from different geographic region. Our goal is to identify genes that contribute to climatic sensing and adaptation in Douglas-fir.
Conifer Evolutionary Genomics
We contribute to the Gymnosperm Tree of Life, a collaboration between scientists at 15 universities, state and federal institutions who seek to document the complete evolutionary record of gymnosperms. Our group works with Aaron Liston and Chris Campbell to define chloroplast genomic diversity in members of the pine family (Pinaceae).
Conifer Transcriptome Analysis
The basis of climatic adaptation in conifers is poorly understood, and this limits our ability to predict population changes to climate and offer science-based prescriptions for management. We have initiated transcriptome analyses to define seasonal variation in gene expression for a number of important conifers. The Douglas-fir (Pseudotsuga menziesii) Transcriptome Observatory merges a large-scale translocation study with expressed gene sequencing to define seasonal leaf transcriptomes and differences in gene expression that relate to climatic variation. Similarly, the (Western Forest Transcriptome Survey) is a collaboration to identify climate-responsive genes from diverse forest species.
Conservation Mitogenomics
Mitochondrial DNA sequences are among the most commonly-used molecules for assessing animal biodiversity. Our group has adapted Multiplexed Sequencing-by-Synthesis to enable high-throughput genetic analysis of complete animal mitochondrial genomes. This work is being conducted with the USFS Wildlife Genetics Laboratory , with primary focus on Fisher (Martes pennanti) and other regionally rare carnivores, as well as West-Slope Cutthroat Trout (Martes pennanti) .
Development of DNA tools to aid genetic conservation and restoration in false cypresses
In western North America, Port Orford-cedar and Yellow-cedar both show evidence of decline due to biotic and abiotic stresses. These species have exceptional ecological and economic value, and conservation of genetic resources is a focus of USFS activities. We are developing microsatellite markers for these species using Multiplexed Sequencing-by-Synthesis. Our experience shows this to be an efficient, inexpensive, and rapid way to identify tens of thousands of microsatellite-containing sequences. Microsatellites are being used to define spatial genetic structure and characterize valuable resistant breeding materials in these species.
Restoration Landscape Genetics
We are working to understand how key restoration species respond to climate, with the goal of defining seed transfer guidelines. Efforts to date include Antelope bitterbrush , Big Sagebrush , and a number of grass species.
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Designing primers
From OpenWetWare
Revision as of 14:10, 23 May 2005 by Jason R. Kelly (Talk | contribs)
Jump to: navigation, search
This needs more work, but wanted to get it started.
Some general rules:
• Avoid runs over 3 nucleotide (AAAA)
• 18-30bp in length (what about tails?)
• 3’ end should be G or C (stronger bond)
• primer melting temp (Tm) should be 50-60C w/ low FIR difference (<5C, 2C better)
• 30-80% GC (>50% is better)
• avoid palindromes
• check for dimer binding and hairpins in Vector NTI
• want to avoid structures with ΔG < -5kcal/mol
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CMD sent two reporters to track ALEC in Oklahoma
Click here to help support our future investigations.
Peter Saunders (CIS)
From SourceWatch
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Professor Peter Saunders is the Social Research Director at the Centre for Independent Studies a free market think tank based in Sydney, Australia.
"Professor Peter Saunders is an Honorary Senior Fellow at the Centre for Independent Studies. He was the Centre's Director of Social Policy from 2002 until 2008, was Professor of Sociology at the University of Sussex in England and was Research Manager at the Australian Institute of Family Studies (2000-02). His work at the CIS has focused mainly on issues of poverty, social inequality and welfare reform. Before joining CIS, Saunders published major works on topics including meritocracy, contemporary capitalism, privatisation and home ownership. He is author of Social Foundations of a Free Society (2001), Poverty in Australia: Beyond the Rhetoric (2002), A Self-Reliant Australia (2003) and Australia's Welfare Habit: And how to kick it (2004) and The Government Giveth and the Government Taketh Away (2007). In 2006, Peter edited Taxploitation. The Case for Income Tax Reform." [1]
Saunders research at the CIS is largely aimed at justifying decreases in Australian government spending on welfare. He has also argued that recipients of welfare in Australia should have to repay the welfare support they receive. [1]
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1. Staff, Centre for Independent Studies, accessed September 21, 2008.
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Place:Billingsley, Shropshire, England
Watchers
NameBillingsley
TypeUnknown
Located inShropshire, England
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Billingsley
Billingsley is a small village and civil parish in Shropshire, England. It is located 6 miles (9.7 km) south of Bridgnorth and lies in the diocese of Hereford.
The Village
The village is situated on the B4363 road, south of Deuxhill. Between the two parishes flows the Horsford Brook. The village itself is in an area covering approximately 1302 acres. The eastern boundary of the village is formed by the Borle Brook. The parish is directly above coal measures that belong to the Wyre Forest Coalfield.
History
The name ‘Billingsley’ is a Saxon name and is said to mean ‘the clearing of the sword’. It is argued that it was called this due to the shape of a wood clearing by Saxons who first settled there in the 7th century. Billingsley is not named in the Doomsday Book because it was actually a detached portion of the Manor of Morville. It was granted to the Abbey of Shrewsbury by Earl Roger de Montgomery. Then in 1147, it passed hands from Shrewsbury Abbey to the Abbey of Seez in Normandy After this it passed to the Morehall family, the Clopton family and the Harewell family. Billingsley was predominately an agricultural village whose inhabitants led a fairly relaxed rural life. However, there is evidence to show of iron working.
In the 17th century, the woods were being occupied for the making of charcoal. In the 18th century, coal and ironstone were being mined. In the mid-1790s, Billingsley was exchanged hands to Sir William Pulterney who was the MP for Shrewsbury. He owned many estates throughout the country and was particularly interested in exploiting the mineral reserves that lay in Billingsley. The colliery struggled and in 1802, MacNab (one of Pulterney’s associates) fled the country for fear of his creditors. Then in 1811, Billingsley’s industrial period ended with the bankruptcy of George Stokes. A brick works opened in Billingsley in the late 1860s and this continued until the First World War. There were further prospects for coal and as a result, some housing was built for the miners. However, most of the miners were housed in Highly. This was the beginning of the Billingsley Colliery Company but this also suffered from ill-success and closed in 1921.
St. Mary’s Church
The church is located on the B4363 which runs through the village. The Church is about 2.5 km along the B4363, North West of Billingsley village. Billingsley Church was originally built in around 1140 and is classed as a Grade II listed building. The Churchyard alone is the home to two incredibly old yew trees. Both are mentioned in the National Register of Ancient Yews and are also mentioned in Andrew Morton’s ‘Trees of Shropshire’. According to the Church of England, Billingsley Church has an ‘unusual’ Jacobean double pulpit from around 1620. However the front of the Church contains mainly original Norman stonework. The Easter Sepulchre dates from around 1320. The register of the parish in the Church dates back to 1627. The Church was rebuilt in 1875 after a fire and at the time cost around £1000 for the renovation work to be carried out. Billingsley Church, as it currently stands, is dedicated to St. Mary and is made up of a south porch, chancel, nave and a bell tower containing two bells.
Occupations
This is a chart showing the occupational structure of the parish of Billingsley in 1881 – comparing men and women. It gives a valuable insight into the village at this time. It uses the ’24 orders’ that were used for the original published reports in 1881 plus an ‘unknown’ category. From the chart, it can be seen that the majority of men work in agriculture which suggests that it is a predominantly agricultural and working class village. From the graph it can be seen that there are more men working than women. However there are more women than men working in domestic services or offices.
Below is a pie chart showing the percentage of males aged 20 and over in 9 occupational categories in the village of Billingsley in 1831. Agriculture stands out again as the major occupation in the parish, with over half of the males in the village aged 20 and over taking up this occupation.
Population
According to the most recently published (2001) census Billingsley has a population of 181. This consists of 69 households, containing 86 females and 95 males. In 1801, the population was around 320 and rose to just over 425 by 1811. The population then decreased rapidly between 1811 and 1821 to just below 180 people. The population slowly decreased again to just over 100 by 1901. It then increased to just below 180 again but then began to decrease slowly again until 1961 when it was just below 90 people.
Housing
The chart below shows the total number of houses in the village of Billingsley from 1830 to 1960. In 1831 there were 32 houses in the village. This gradually decreased until 1941 to 29 houses. This rose again over the next 10 years and then started to decrease again until 1901 when there were 21 houses. The amount of houses increased a lot until 1931 to 32 (the same as 100 years earlier) and has been gently fluctuating around 30 since then. There was a small housing estate built in Billingsley in the 1960s however the village does still remain small and rural.
Research Tips
This page uses content from the English Wikipedia. The original content was at Billingsley, Shropshire. 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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Place:Byron, Alfalfa, Oklahoma, United States
Watchers
NameByron
TypeTown
Coordinates36.902°N 98.295°W
Located inAlfalfa, Oklahoma, United States
source: Getty Thesaurus of Geographic Names
the text in this section is copied from an article in Wikipedia
Byron is a town in Alfalfa County, Oklahoma, United States. The population was 45 at the 2000 census.
Research Tips
This page uses content from the English Wikipedia. The original content was at Byron, Oklahoma. 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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Place:Haddon, Huntingdonshire, England
Watchers
NameHaddon
Alt namesAdonesource: Domesday Book (1985) p 141
TypeVillage
Coordinates52.517°N 0.333°W
Located inHuntingdonshire, England
source: Getty Thesaurus of Geographic Names
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Haddon – in Huntingdonshire (now part of Cambridgeshire), England – is a village near Chesterton west of Yaxley.
Research Tips
This page uses content from the English Wikipedia. The original content was at Haddon, Cambridgeshire. 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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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
5306.0 - International Investment Position, Australia, Dec 1994
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 03/03/1995
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• About this Release
Provides a complete international investment position statement, including a detailed analysis of international investment. Covers foreign investment in Australia and Australian investment abroad, including details of the level of investment, investment flows and associated income. Detailed information is provided on Australia's foreign debt. Series are classified by institutional sector and type of investment. For foreign investment in Australia, some country and industry detail are also provided. For foreign debt, further details are included on drawings and repayments, currency, and maturity structure.
This publication has been converted from older electronic formats and does not necessarily have the same appearance and functionality as later releases.
© 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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Posts
Comments
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Sal Khan On 60 Minutes
Sanjay Gupta, introducing Khan Academy:
Take a moment and remember your favorite teacher. Now imagine that teacher could reach, not thirty kids in a classroom, but millions of students all over the world. That's exactly what Sal Khan is doing on his website Khan Academy.
If your favorite teacher did anything other than lecture for 10-20 minutes continuously, though, Khan Academy may seem like several steps in a different direction.
Students Don't Like The Videos
60 Minutes reported the quantity of videos Khan has produced and the time and effort it took to make them. It didn't report the efforts some students take to avoid watching them. Here's a white paper from Stanford's d.school:
We were surprised to find that students preferred to teach themselves or each other through the practice problems and hints rather than watching the Khan videos.
My own classroom observations confirm theirs and a Khan Academy employee confirmed both: kids watch videos as a last resort after exhausting other efforts, some of which don't look much like "learning."
Pivoting From The Flipped Classroom
That is a critical design challenge for Khan and his team as they put distance between themselves and the "flipped classroom" model he promoted in his TED talk a year ago.
Then:
And the teachers would write, saying, "We've used your videos to flip the classroom. You've given the lectures, so now what we do … " — and this could happen in every classroom in America tomorrow — " … what I do is I assign the lectures for homework, and what used to be homework, I now have the students doing in the classroom."
Last night:
I kind of view [the flipped classroom] as a step in the direction. The ideal direction is using something like Khan Academy for every student to work at their own pace to master concepts before moving on and then the teacher using Khan Academy as a tool so that you can have a room of 20 or 30 kids all working on different things but you can still kind of administrate that chaos.
This is a enormous expansion of the Khan Academy vision. No longer is the message, "Do the basic skills with Khan Academy outside the classroom to free up time for projects and higher-order thinking inside the classroom." That message raised a lot of interesting questions which are now moot. (eg. "Why are video lectures the best way to learn basic skills? Why are we separating basic skills and higher-order thinking? Who decides which is which?") Now Khan Academy is the classroom. Kids come into class, sit in front of a laptop, put on headphones, and pick up where they left off from the last class. The teacher monitors the class dashboard and offers coaching when necessary. If you think I'm extrapolating too much from Khan's remarks, the same Khan Academy employee confirmed that vision to my Stanford team a few months ago.
We could argue whether or not that kind of future for our math classrooms is depressing and dystopian but all available evidence indicates that kids won't put up with it. I'm curious what changes, if any, Khan will make in response to the evidence that kids don't like watching his videos.
BTW: The strangest editing decision CBS made last night.
BTW: Edtech Hulk has the vibe surrounding Khan Academy and the just-announced TED-Ed exactly right.
2011 Mar 13. Sue Van Hattum e-mailed to suggest that the middling student reception to his videos explains Sal Khan's hiring of Vi Hart and Brit Cruise, both of whom do good work with video. I think that's plausible.
2011 Mar 14. I Would Have Loved Khan Academy In Eighth Grade.
2011 Mar 14. Welcome, EdSurge readers. Let me point out that EdSurge rebuts [amended below] the d.school's report that kids make efforts to avoid watching Khan's videos (confirmed by a Khan employee and my own observation) with no stronger evidence than a) an iPad app released by Khan Academy this week and b) a Gates Foundation op-ed. We're all playing on Team Student Learning here. It does nobody any good to paper over bad news. Let's figure out the nut of the problem and fix it. Take it as a design challenge for EdSurge's design-minded readership.
2011 Mar 14. I misinterpreted EdSurge as rebutting my case. According to their editor, that wasn't their intent. Here is the item in its entirety:
THE FUTURE OF EDUCATION: That's how CBS 60 Minutes–like so many others–billed the Khan Academy in its feature of Salman Khan last weekend. Such great PR has Dan Meyers on his feet, pointing to studies that say students don't actually like watching Khan videos. Dan also notices a discourse shift from emphasis on flipped classrooms to a model where the Academy is the classroom. His take: "all available evidence indicates that kids won't put up with it." Khan clearly feels otherwise, particularly as it is now offering a collection of ipad apps. A cogent argument in favor of blended learning is set forth by Stacey Childress of the Gates Foundation in the Harvard Business Review. It's among the most read pieces in the issue. Full disclosure: EdSurge has received support from the Gates Foundation for our beta website.
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Category:Mediaserver
From NAS-Central Buffalo - The Linkstation Wiki
Jump to: navigation, search
A media server is a computing device storing various digital media. A media server acts as an aggregator of information: video, audio, photos, books, etc. These different types of media (whether they originated on DVD, CD, digital camera, or in physical form) are stored on the media server's hard drive.
This can then be read from another computer or a digital media receiver, a home entertainment device used to connect a home theatre system to a computer network in order to retrieve media files (music, pictures, video). A Digital media receiver is capable of browsing file trees and using metadata to organize media files. It can connect wirelessly (802.11b, g) or through an Ethernet connection, allowing people to play music, pictures, and video through their home entertainment system.
Pages in category "Mediaserver"
The following 49 pages are in this category, out of 49 total.
A
C
D
F
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G cont.
J
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P cont.
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Pozzolanic Properties of Micronized Biomass Silica in Enhancing Compressive Strength and Water Permeability of Concrete
Suraya Hani Adnan, Ismail Abdul Rahman, Hamidah Mohd Saman, Fetra Venny Riza
Abstract
This study presents the analysis and the benefits from using Micronized Biomass Silica (MBS) of rice husk which comprises of high content of silica. MBS was generated from controlled burning of the husk into off-white biomass silica ash and crushing the ash into micronized size. Concrete samples containing various percentages of MBS were tested for workability, compressive strength and also water permeability performances. It was found that the optimum percentage of MBS added to the concrete that lead to good performance of concrete in terms of compressive strength and water permeability was 12%. The compressive strength increased up to 43% when 12% of MBS was added to the concrete after 90 days period. Increasing the content of MBS exceeding the optimum percentage showed inferior performance of the concrete. It indicates that the pozzolanic reaction properties of MBS could improve the compressive strength and water permeability of concrete.
Full Text: PDF DOI: 10.5539/mas.v6n11p1
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Modern Applied Science ISSN 1913-1844 (Print) ISSN 1913-1852 (Online)
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Category:Harnett County, North CarolinaEdit This Page
From FamilySearch Wiki
Pages in category "Harnett County, North Carolina"
This category contains only the following page.
H
Media in category "Harnett County, North Carolina"
The following 2 files are in this category, out of 2 total.
• This page was last modified on 25 November 2012, at 21:44.
• This page has been accessed 370 times.
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Maryland Marriages (FamilySearch Historical Records)Edit This Page
From FamilySearch Wiki
Revision as of 18:59, 6 April 2011 by HawkBlade124 (Talk | contribs)
Contents
Collection Time Period
This collection includes the years 1650 through 1995.
Record Description
This index is an electronic database of information compiled from a variety of sources including the following:
• Family Records
• Church Records
• Civil Registration
This index is not complete for any particular place or region.
Record Content
The key genealogical facts found in marriage index entries may include:
• Name of the bride and groom
• Names of the parents
• Marriage date
• Marriage place
• Family History Library Microfilm and item numbers for the source materials
Coverage Table
This collection is a partial index of records for the localities listed below as of April 2010. The table below shows the number of records by locality. Localities not listed may not have any records in this collection.
Most of these records date from the time period indicated in the columns below; however, there may be records before and after these dates. Record counts where the locality information was incomplete are included below under the country name. Because of this, you may wish to search only by state.
As this is an index of records compiled from various sources, it is strongly recommended that you verify the information in original records. Due to privacy laws not all records may be displayed.
Locality Births and Christenings, 1650-1995 Marriages, 1666-1970 Deaths and Burials, 1877-1992
Allegany 0 7,055 0
Anne Arundel 15,054 14,418 0
Baltimore 44,117 139,129 8,031
Baltimore (Independent City) 9,203 3,102 0
Calvert 594 0 0
Caroline 124 4,553 0
Carroll 6,599 5,171 0
Cecil 2,651 2,447 0
Charles 2,777 799 0
Dorchester 2,747 12,051 0
Frederick 44,259 15,138 0
Harford 2,226 16,583 0
Howard 317 444 0
Kent 3,015 971 0
Maryland 21,261 233 3,655
Montgomery 2,322 221 0
Prince George's 5,491 7,250 0
Queen Anne's 1,095 968 0
Somerset 7,347 4,235 0
St. Mary's 5,560 11,927 0
Talbot 2,659 1,757 0
Washington 26,718 5,275 0
Worcester 152 0 0
Total 206,288 253,727 11,686
How to Use the Record
Use this index to help you learn more about your ancestors. The information could help you identify family relationships and lineages as well as direct you to original records of your ancestors, which may contain additional information.
Finding the Original Source for an Entry in This Collection
Each entry in this index has a source listed which includes a batch number. You will need to trace the batch number for the individual entry to learn its source. Please see the following wiki articles for more information on batch numbers:
If an FHL film number is given in the entry for your ancestor, search for it in the Family History Library Catalog.
Record History
For over 30 years, volunteer indexers extracted this information from microfilm copies of the original records. In 1998, a few of the entries were published on 7 CDs by the Family History Department of The Church of Jesus Christ of Latter-day Saints as the "North America Vital Records Index." This index is an index of some marriages throughout Maryland. The index is not necessarily complete for any particular place or region.
Why This Record Was Created
The Church of Jesus Christ of Latter-day Saints sponsored this index to help individuals find information about their ancestors.
Record Reliability
Church records and civil registration were official records and are some of the most reliable sources of information available for those who were born, married, or died in Maryland
Related Web Sites
This section of the article is incomplete. You can help FamilySearch Wiki by supplying links to related websites here.
Related Wiki Articles
Maryland Vital Records
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.
Sources of Information for This Collection
"Maryland Marriages, 1666-1970," database, FamilySearch (http://familysearch.org/). Index entries derived from digital copies of original and compiled records.
Citing FamilySearch Historical Collections
When you copy information from a record, you should also 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: How to Cite FamilySearch Collections.
Examples of Source Citations for a Record in This Collection
• "'Maryland Marriages, 1666-1970.'" database and images, FamilySearch: : accessed March 25, 2011. Entry for William A. Barton and Sadie Whittington, married 26 March 1896; citing Marriage Record, FHL film 893707 Index entries derived from digital copies of original and compiled records.
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Waccamaw County, South CarolinaEdit This Page
From FamilySearch Wiki
Revision as of 17:03, 5 May 2011 by DiltsGD (Talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
United States South Carolina Waccamaw County
Waccamaw County was a tentative name given to what officially should have been Kingston County on the 1800 federal census.[1]
Neither Kingston nor Waccamaw ever became a real, functioning county.
Kingston/Waccamaw County was renamed Horry County in 1801.[1]
For documents of people who lived in this area around 1800, look in All Saints Parish records, Georgetown District records in Georgetown, or for papers in Charleston, South Carolina.
Sources
1. 1.0 1.1 A History of Kingston District (County) in Carolana at http://www.carolana.com/SC/Counties/Kingston_county_sc.html (accessed 5 May 2011).
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Asbestos
Asbestos is a fibrous form of mineral silicates belonging to the serpentine and amphibole groups of rock-forming minerals, including actinolite, amosite (brown asbestos), anthophyllite, chrysotile (white asbestos), crocidolite (blue asbestos), tremolite, or any mixture containing one or more of the mineral silicates belonging to the serpentine and amphibole groups.
Asbestos soft and pliant and has the ability to withstand heat. It can be very toxic if inhaled.
Related Pages
External Links & References
1. Code of Practice for the Management and Control of Asbestos in Workplaces
2. Wikipedia
3. Asbestos Management and Control Policy for (Queensland) Government Buildings
4. Inspectapedia
5. Asbestos - removal of, and work on asbestos containing materials (Workplace Health & Safety Queensland)
Page tags: a definitions whs
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License
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University students, administrators are anxious over possible tuition hikes
April 24, 2012 at 12:21 am
By Justin Snow
Justin@MarylandReporter.com
With still no word on a special session two weeks after the General Assembly adjourned having failed to pass a revenue bill to fund the full state budget, higher education officials and students alike have begun to worry.
On Friday, dozens of students at the University of Maryland urged lawmakers to return to Annapolis and rallied against tuition hikes that would likely result if the “doomsday budget” is implemented.
Friday’s rally followed a unanimous vote by the Student Government Association calling on Gov. Martin O’Malley to order a special session. O’Malley has delayed ordering lawmakers back to Annapolis until a consensus can be met on the issues that derailed the legislation two weeks ago.
Legislators have until June 1 to reconvene and pass the remainder of the budget package in order to avoid $50 million in cuts to the university system budget that could result in as much as a 13% increase to in-state tuition. Such a hike would be the largest since the Ehrlich administration, which saw tuition increase by about $2,000 over four years.
Students who attend the 12 institutions overseen by the University System of Maryland have been plunged into uncertainty in the wake of the budget inaction. Although in-state students have faced cost increases over the years, they have been relatively modest.
Tuition up $400 in O’Malley years
Under the O’Malley administration since fiscal 2008, tuition for in-state undergraduates at the state’s flagship university in College Park has increased $400, thanks largely to a four-year tuition freeze lifted by O’Malley at the end of his first term.
Separate from tuition costs, which are dictated by the legislature and approved by the Board of Regents, student fees are decided at the university level. These mandatory fees vary from institution and go toward a variety of services, such as healthcare, athletics, and shuttle buses.
But for students, the technical differences between the two costs are irrelevant — they appear on the same bill. Although student fees at the University of Maryland have seen small increases over the years, they too spiked after the end of the tuition freeze in 2010. That same year saw furlough days for faculty and reductions in aid.
Overall, the cost of attendance for College Park undergraduates has increased by about $1,000 since 2008, not counting textbooks, housing and living expenses, which continue to rise.
Tokunbo Okulaja, a junior at the University of Maryland who spoke at the unveiling of a doomsday countdown clock last week, said that she and others have been faced with the prospect of losing legislative scholarships as a result of the budget.
“It’s unfair to students,” Okulaja said, noting that some students have been forced to drop out in the face of decreasing financial aid.
For university administrators, steep tuition hikes are a reminder of an era many wish to forget. Under the Ehrlich administration, tuition increased by 40%, making Maryland colleges the 6th most expensive in the country. That ranking has decreased to around 26th, with universities around the country increasing tuition as state aid has fallen. The University of Maryland is often more affordable than public universities in Virginia, Pennsylvania, and Delaware.
Kirwan: Cuts would break compact on affordability
William “Brit” Kirwan, who has served as chancellor of the University System of Maryland for both Ehrlich and O’Malley, said in an interview Monday that the doomsday budget would not only mean a dramatic hike in tuition of more than $800, but also a reduction in services and fewer classes.
“It would really break the compact we’ve had in the state on affordability in higher education,” said Kirwan. “Double digit or near double digit increases to tuition may become the easy way out for the state in the future.”
Kirwan said he fears Maryland could go down a path similar to California, which in recent years has reduced state funding for higher education by about half in the face of dramatic budget cuts. As a result, public universities established for the primary purpose of serving Californians have been forced to turn away in-state students for out of state and international students who pay a higher tuition rate.
O’Malley is scheduled to meet with House Speaker Michael Busch and Senate President Mike Miller over breakfast on Tuesday — apparently the first time Busch and Miller have met since a tense bill signing ceremony the morning after the session ended. Kirwan said he remains unsure what the final product of a special session could be.
“I still have some anxiety about the final outcome even if there is a special session,” Kirwan said, adding that the budget package they expected may not be what is finally approved. “If this doesn’t get fixed then who knows where we go in the future.”
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CH391L/S13/In vitro Selection of FNAs
From OpenWetWare
(Difference between revisions)
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(Ribozymes)
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===Ribozymes===
===Ribozymes===
-
As previously mentioned ribozymes fall under the category of enzymes. Most of the ribozymes studied up until recently in living organism fall into 9 classes.
+
As previously mentioned ribozymes fall under the category of enzymes. Most of the ribozymes studied up until recently in living organism fall into 9 classes. Of this most perform some type scission and ligation reaction. In the case of ''in vitro'' selected ribozymes their function has been expanded.
+
+
Natural Ribozymes <cite>Patel2007</cite>
*Cleaving Ribozymes
*Cleaving Ribozymes
**1 Self-cleaving i.e. The Hammerhead family (satellite RNA)
**1 Self-cleaving i.e. The Hammerhead family (satellite RNA)
Line 27: Line 29:
**8 Metabolites
**8 Metabolites
**9 Magnesium
**9 Magnesium
-
===Deoxyribozymes===
===Deoxyribozymes===
Revision as of 09:53, 11 February 2013
Contents
Introduction
Although the vast majority of such ligand binding activities or enzymatic activities known are performed by proteins a secondary subset of these fall under the category of Functional nucleic acids (FNAs. FNAs are RNA, ssDNA, or XNA(nucleic acid analogues) that perform an activity such as binding or catalyzing a reaction. FNAs are grouped into three main categories Aptamers, Ribozymes, and Deoxyribozymes that are further classified into either natural or artificial depending on their origin. The exception being Deoxyribozymes as they have yet to be discovered in a living organism. Still, It was only in the 1980s that the 1st ribozyme was discovered that we started to study FNAs and have allowed for the discovery of new methods, such as the SELEX or In vitro selection process that we are expanding their potential both as tools for exploring biology and real world problem solving.
<!Note to self: mention RNA World>
Functional Nucleic Acids
[1],[2],[3],[4]
Ribozymes
As previously mentioned ribozymes fall under the category of enzymes. Most of the ribozymes studied up until recently in living organism fall into 9 classes. Of this most perform some type scission and ligation reaction. In the case of in vitro selected ribozymes their function has been expanded.
Natural Ribozymes [5]
• Cleaving Ribozymes
• 1 Self-cleaving i.e. The Hammerhead family (satellite RNA)
• 2 Trans-cleaving i.e. RNase P
• Splicing Ribozymes
• 3 Group I
• 4 Group II
• Riboswitches
• 5 Thermosensors
• 6 sRNAs
• 7 T-Boxes
• 8 Metabolites
• 9 Magnesium
Deoxyribozymes
Aptamers and Riboswitches
The word aptamer from the latin aptus and translates as the past participle of to fit were originally identified by employing the protocol SELEX. Therefore the word Aptamer describes their basic function as RNA or single stranded DNA (ssDNA)that can bind a ligand by assuming an specific structure.[6, 7] Yet, it would take several years until the discovery of the first in vivo aptamer or riboswitch [8]. See the following page to get a better understanding of aptamers and riboswitches.
In vitro Selection of Functional Nucleic Acids
The image presented describes the basic method for performing a SELEX or In vivo selection experiment using single stranded nucleic acids (RNA,ssDNA,XNA) that are chemically synthesizedan have a constant region (CR) and a random region. Having the CR allows later amplification using PCR. The first step is subjecting the population of single stranded nucleic acids to specific selective condition in which function is possible. Then a (2) diverse subset of the population will perform the desired function and will be then (3) PCR amplified to make double stranded nucleic acids with the use of the CR introduced previously. Therefore the selection can continue to a following round, while at the same time a sample is obtained and can be sequenced. [9]
New Methods and Tools that assit In vitro selections
Computational Methods
• Mfold - originally developed as a GUI or graphical user interface server for the prediction of the secondary structure of single stranded nucleic acids. The core algorithm predicts structures based on minimum free energies necessary to fold a structure. This algorithm can be used initially as a step to predict possible secondary structures of active sequences [10].
FRET
• Fluorescent analogues
Next Generation Sequencing
New Applications of FNAs
1. Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, and Cech TR. . pmid:6297745. PubMed HubMed [Cech1982]
2. Guerrier-Takada C, Gardiner K, Marsh T, Pace N, and Altman S. . pmid:6197186. PubMed HubMed [Altman1983]
3. Ellington AD and Szostak JW. . pmid:1697402. PubMed HubMed [Ellington1990]
4. Tuerk C and Gold L. . pmid:2200121. PubMed HubMed [Gold1990]
5. Functional Nucleic Acids for Analytical Applications. Dordrecht: Springer, 2009. isbn:978-0-387-73711-9. [Silverman2009]
6. Wilson DS and Szostak JW. . pmid:10872462. PubMed HubMed [Wilson1999]
7. Winkler W, Nahvi A, and Breaker RR. . pmid:12410317. PubMed HubMed [Winkler2002]
8. Emilsson GM and Breaker RR. . pmid:12022469. PubMed HubMed [Breaker2002]
9. Zuker M. . pmid:12824337. PubMed HubMed [Zucker2003]
All Medline abstracts: PubMed HubMed
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IGEM:Virginia 2012/Protocols/Preparing a Pertussis Culture
From OpenWetWare
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Contents
Overview
Below is the procedure for preparing a Bordetella pertussis culture. First, the frozen stock is streaked onto a sheep blood agar plate. This plate is then incubated for ~3 days, until it produces pertussis colonies which are gray/white and dull rather than shiny. These colonies are then used to inoculate a liquid culture. Since pertussis is aerobic, the liquid culture must have a high amount of surface area. This liquid culture can then be diluted so that it is in the logarithmic growth phase in time for manipulation. Pertussis can't be stored in the fridge, so the liquid culture can be used to start new cultures for a limited period of time, so that mutations do not accumulate.
Materials
Procedure
Note: This procedure should be done in a hood to prevent aerosolization.
1. Using a sterilized stick, streak the entire surface of the BG Agar plate. Discard the stick in the biohazard container.
2. Put the plates in a plastic bag to prevent drying out and incubate at 37°C for three days.
3. Using 10 mL of SSM media in a 50 mL flask, inoculate the liquid culture.
4. Incubate at 35.5°C for a day.
5. Dilute the liquid culture.
Notes
Please feel free to post comments, questions, or improvements to this protocol. Happy to have your input!
References
Contact
• Who has experience with this protocol?
or instead, discuss this protocol.
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Quotation added by staff
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Life is a dream walking death is a going home. Proverb, Chinese
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A lie can run around the world six times while the truth is still trying to put on its pants. Twain, Mark
This quote is about lies and lying · Search on Google Books to find all references and sources for this quotation.
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Samuel Langhorne Clemens (November 30, 1835 April 21, 1910), better known by his pen name Mark Twain, was a famous and popular American humorist, novelist, writer and lecturer.
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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.
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Understand that most problems are a good sign. Problems indicate that progress is being made, wheels are turning, you are moving toward your goals. Beware when you have no problems. Then you've really got a problem... Problems are like landmarks of progress. Alexander, Scott
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{
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Quotes by Ciardi, John
John Anthony Ciardi (June 24, 1916 - March 30, 1986) was an American poet, translator, and etymologist..
"The Constitution gives every American the inalienable right to make a damn fool of himself."
Ciardi, John on america
3 fans of this quote
"Every parent is at some time the father of the unreturned prodigal, with nothing to do but keep his house open to hope."
Ciardi, John on hope
8 fans of this quote
"Love is the word used to label the sexual excitement of the young, the habituation of the middle-aged, and the mutual dependence of the old."
Ciardi, John on love
6 fans of this quote
"There is nothing wrong with sobriety in moderation."
Ciardi, John on moderation
"Modern art is what happens when painters stop looking at girls and persuade themselves they have a better idea."
Ciardi, John on art
"You do not have to suffer to be a poet. Adolescence is enough suffering for anyone."
Ciardi, John on suffering
"A neighborhood is a residential area that is changing for the worse."
Ciardi, John on life
"A university is what a college becomes when the faculty loses interest in students."
Ciardi, John on colleges and universities
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Hacking the Human Body By Daniel Kraft, MD
Daniel Kraft, MD had a great talk about the future of medicine at the recent Pioneers Festival. Click on the image to watch the video on UStream.
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Posts: 7 | Thanked: 0 times | Joined on Apr 2012 @ Netherlands
#1
Hello, I have already used search but I cant figure this out.
I want to install NITDroid on my n900's EMMC with the 8gb EMMC becouse I have no Micro SD card, an I heard it will be faster if I put it in the EMMC.
So first I tried to flash the n900 with flasher 3.5 and the 8gb EMMC. When I rebooted all the images of the UI where gone, so I connected it with PC suite and restored the firmware, when I rebooted again I found out the the flashing of the EMMC worked.( this EMMC: http://wiki.maemo.org/NITDroid_FAQ#M...at_can_I_do.3F)
Do you need to Reflash the kernel to If you have flashed the EMMC?
Then I tried to Install NITDroid, I first tried this way: http://wiki.maemo.org/Nitdroid_easy_install_on_EMMC
but the multiboot just didnt work.
I deleted NITDROID again (I think I didn't did that properely) and tried another installer. When I booted the device again it showed Multiboot but with no options, not to boot maemo and not to boot nitdroid. when you press "0" (zero) it will try to boot in maemo but fails and then shuts down.
So I want to reflash my device with new firmware and again with the 8gb EMMC, so I have a fresh device to start again, can anybody tell me how to do that?
and then how to install NITDroid preperely?
(sorry for my bad english, it is not my main language.)
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Posts: 791 | Thanked: 767 times | Joined on Sep 2007 @ /Canada/Ontario/GTA
#1
I am trying to install a PHP app (eyeOS), and the installer tells me that my PHP installation does not have gzip support. Would anyone know how I could enable it?
I am running the nginx http server, and php5-fastcgi.
Many thanks!
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Tarifa
From Wikitravel
Europe : Iberia : Spain : Andalusia : Cadiz : Tarifa
Revision as of 06:21, 5 April 2012 by Youploi (Talk | contribs)
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Tarifa is in the province of Cadiz in the Andalucia region of Spain. It is located on the southernmost point of the European continent, only 14 km from the coasts of North Africa.
Known throughout the world as a Mecca for Windsurfing this charming white Andalusian town has only been mildly spoiled by the mass touristic developments which have ravaged the coasts of most of Spain. Much of the surrounding coastline is still protected by Spanish law and a few kilometres to the west of the town are two of Spain's most beautiful beaches.
How to get to Tarifa
Local coaches run to Cadiz and Algeciras, where you can connect with buses for the Andalucian cities of Cordoba, Seville and Granada.
High speed ferries make the 35 minute trip to Tangier, Morocco.
There are many fast hydrofoils daily on FRS Ferry Serice from Tangiers for about 37 Euros one way or 67 Euros round-trip (as of November 2010). As you go through customs, there are free buses waiting in the parking lot to Algeciras
Get around
Tarifa is situated between the best golfcourses of Europe, at the Atlantic side you find Dehesa Montenmedio and Benalup golf & country club(www.benalupgolf.com) . Both courses are set in a natural envoirement. At the Mediterranea side you find the only links course here in the south, Alcaidesa Golf club. The world famous Valedrrama en Sotogrande.
See
• Castle
• the Beach with views of Morocco and either side of the Atlantic and Mediterranean
• Go for a whale-watching tour! Resident species (can be seen all year) include the Common dolphin, Striped dolphin, Bottlenose dolphin and Pilot Whale. Semi-resident species (presence related to feed periods) include the Killer whale - Orca (between July and September), Sperm whale (mostly between March and July). Migratory species (cross the strait in their migratory routes) include the Fin whale (mostly between May and July).
• Abandoned Militairy buildings
Tarifa before digital times was one of the most strategic points in the world and still is. The Strait of Gibraltar was this time guarded by large, heavy guns from various military batteries here on the coast of Tarifa. In those days the soldiers on duty had a lot of fun in Tarifa and their green uniforms were a nice contrast to the vibrant colors of the first windsurfers. Today these military batteries are overgrown with plants and trees, the walls decorated with graffiti, broken windows, roofs far from waterproof, sun playing with the shadow and a lot of mistery. The work noises have been replaced by silence (except the wind) but if you listen carefully they will tell you their story.
Do
Strong winds and good waves make Tarifa an attractive spot for water and wind sports. You can also take Spanish lessons.
• Windsurf
Te best combination of services and wind, Tarifa is well known as a test center or training place for most of the brands and pro riders, but is good to for beginners too, you will find windsurf centers from Los Lances beach to Valdevaqueros and Bolonia, depending on the wind direction you will have to choose the one that suits better your level, the conditions can vary from 3 kms distances so ask the locals, the will friendly recommend the best spot for the day. Most of the centers open from March to October but you will find some, like the Surf Center in Hotel Arte Vida, that open all year around. Some days windsurfing in Tarifa can become unforgettable for you, cruising in the Strait of Gibraltar waters, with such beautiful views of the African Continent, thinking in the history of this channel and even feeling the magical enviroment and ambient, mix of African-Flamenco fusions... I Promise you will become an addict of this town, well known is that from that day you always want to come back.
• Kitesurf
For sure the best spot in Europe for practicing this sport, the mix of good winds, kilometers of perfect beaches and a full service of professional schools and rental centers makes Tarifa that place, from flat waters for begginers or freestylers to waves for kite - surfing adicted, everybody is suited in this waters just choose your spot... from Tarifa town to Caños de Meca you will find a beautiful spot that suits your needs, but only in Tarifa Shops ussing the take away service or closer spots like Dos Mares, Arte Vida, or Valdevaqueros were you will find Centers with all the services you can need. You can even find places with kindergarden service.
• Mountainbike
An absolute mountain bike paradise hidden in the inland of Tarifa with many trails for all kind of levels where you can ride all year. Long up hills, challenging down hills, easy and rough trails, beautiful nature and incredible views over the Atlantic ocean and the strait of Gibraltar. Within easy reach of Tarifa there are many more trails to explore in the extensive nature reserve of Los Alcornocales.
• Surfski
A new sport in Tarifa. Paddling between two continents “The Strait of Gibraltar”. Like Oscar Chalupsky (11 x time winner of the Molakai)said . Tarifa is probably the best downwind spot in the world.
• Surf
Hotspot Balneario near the town.
• Dive
Around the clear waters of the isla de las palomas
• Swim
In both the Atlantic and Mediterranean.
• Windsurfingclasses
Along the coast you will find many windsurfing schools.
• Spanish Lesson
With other travellers (www.hispalense.com) Special youth bilingual summer camps
Transition of a fishing industry to tourism industry.
Tarifa resident and personality Henk Post has taken the initiative to clean up the town. The fish industry is finished and tourism will be the only income for the habitants of Tarifa. Using social media like Facebook, he rallied together a group of friends and on Tuesday, 14th of February at eleven in the morning 2012, they met at the castle wall with buckets of white paint, rollers and paintbrushes. Their aim was to repaint the wall by the end of the day. All of the materials have been supplied by local business people,’ explains Henk. ‘This is a real local initiative. Too many people complain about their towns but it’s too easy to complain. Now is the time to come with some solutions. That’s what this initiative is about.’ Before embarking on the project, Henk secured the support of Tarifa’s new mayor Juan André Gil Garcia. Garcia’s new administration recognises that the future of Tarifa lies in the success of its tourism industry and that’s why he is giving his full support to the project.
Eat
• Food is generally good in Tarifa- especially fish. Try going for the places filled with locals. They are generally easy to pick out from tourists (both Spanish and foreign). Some of the best places in Tarifa also happen to be the cheapest. Don't forget to try the local Tuna, swordfish and, especially, the "Tortillas de camarón", typical of the coast of Cadiz. "Ortigas" (sea nettles) are another local specialty.
• The best restaurant in the old city is called Mandragora, located on Independencia (a small alleyway between the city wall and the Cathedral). It is not cheap, but the food was the best we had in Spain, and it is filled with locals.
• There is a restaurant near a village Facinas, a few kilometres to the north from Tarifa. Just follow the road to Cadiz and in about 10-12 km there will be a right turn to Fasinas (which is in turn a beautiful one spread on a foothills in the form of a cross) with a hardly noticeable sign. This restaurant is located just before the village i.e. a kilometre or two away from the main road. It is a meat restaurant with extremely delicious dishes, especially meat ones, and very friendly waitstaff. The portions are rich and generous. Prices are about 25-30 euros with wine (35 tops to full you completely), for two persons. The place is sometimes (mainly at weekends) crowded with locals watching football matches on TV or having talks to each other. One of the best restaurant in this region. Nobody speaks English there, so be prepared.
Drink
• Cerveza
• Jazz
• Mojitos The best Mojitos you got at the Beach Club of Hotel Arte Vida,
• Bar la Tribu Playa
Sleep
A variety of medium priced hostels by (cheap) Spanish standards. Touts work around the bus station and port offering various accommodations, including sleeping space on rooftops!
• Camping is available outside of town, but you'll need a car.
• Hostal Alameda [1] Situated in the centre of Tarifa, this comfortable cosy hostal offers all services you expect from an Hostal. Near the harbour and all facilities.
• Hotel La Mirada [2] Nice English-speaking staff, new construction, decent location. 40 euros a night for a single room with a good en suite bathroom and flat-screen TV when I stayed there. Calle San Sebastian 41.
• Dos Mares Apartment [3] A stylish two bedroom apartment in Tarifa, with balcony amazing views, swimming pool, storage for equipment, close to town and windsurf/ kitesurf beaches. Visit English Owned and managed
• Hotel Arte Vida, CN 340 km 79.3, 956684652, [4]. This cosy hotel is Situated at the most spectaculair beach of Europe, Los Lances. Great views over the Strait of Gibraltar. The restaurant of Arte Vida is well known for the fresh fish and the ambient. Don`t mis the sunset celebration parties at the beach [5] club
• Pension Facundo. Great hostel to accomodate backpackers and travellers on a budget. €20/night for a bed in the dorm or more for a nice private room (14/07/10). The hostel cares for hygiene and maintains cooking facilities and free internet for travellers. Staff has problems speaking English but that's a part of the charm in travelling.
Get out
• The port of tarifa [6] gathers every year more and more passengers.Tanger is often seen as an extension of the Costa del Sol. One day trips to Tanger are very popular and many travel agents offer guided tours. Tanger is a magical city, living the adventure feeling.
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Toronto/Cabbagetown
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Once one of Toronto's poorest neighbourhoods, Cabbagetown is now a distinct neighbourhood populated with elegantly renovated Victorian homes. Cabbagetown gets its name from the large cabbages planted in their front lawns by Irish immigrants in the 19th century.
Get in
See
• Allan Gardens located at the south side of Carlton Street between Jarvis and Sherbourne Streets, is a conservatory containing six greenhouses on large landscaped grounds. Admission is free and the greenhouses are open to the public year-round. The greenhouses contain plants native to many different countries and from different climactic regions of the world. Countries represented include Australia, Brazil, China, Mexico, and many others. On any given day one is likely to come across frolicking squirrels or birds that have found their way in through the doors. The ponds are home to turtles and fish and, if you look up, you just might see a snoozing raccoon. Allan Gardens is wheelchair accessible.
• Riverdale Farm located in the heart of Cabbagetown, is a turn of the century, that would be the twentieth century, Ontario farm and the site of Toronto's first zoo. Riverdale Farm is located in the Old Cabbagetown at 201 Winchester Street, east of Parliament St., near Carlton St. There is no parking on the grounds, but street parking is available near by. Attractions include demonstrations of milking, cream separating, butter-making, egg collecting, sheep sheering, wool spinning and dying, amongst others. Admission is free.
Do
Buy
Eat
• JAMcafe is located in a historic building at 195 Carlton Street west of Parliament. They feature fine bistro dining, a nice wine list, a summer patio and free parking. [www.jamcafe.ca] Cranberries Restaurant on Parliament, north of Wellesley, serves good, reasonably priced meals, heavy on the comfort food. They also have great nightly specials.
Drink
Sleep
• The Toronto Townhouse B&B 213 Carlton Street; +1 416 323-8898 [1] Toronto Tourism award winners, they offer suites and rooms from $79 and up and are just 4 city blocks from Yonge & College subway. Big pluses are free wi-fi and local & long distance calling.
Budget
Mid-range
Splurge
Contact
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6201.1 - Labour Force, New South Wales and Australian Capital Territory, May 2001
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