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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
8635.1.40.001 - Tourist Accommodation, Small Area Data, New South Wales, Jun 2001
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 21/09/2001
Page tools: Print Page Print All RSS Search this Product
• About this Release
ABOUT THIS RELEASE
Contains the results from the on-going quarterly Survey of Tourist Accommodation. Data provide information on the supply of, and demand for, tourist accommodation facilities. Data include number of establishments, capacity and employment for the quarter and occupancy and takings from accommodation for each month; by type of establishment and by star grading. This data report includes information for selected small areas and for Tourism Regions. This is a useful reference for policy makers and tourism industry monitors and advisers.
Since March quarter 1998 all hotels, motels and guest houses and serviced apartments with 15 or more rooms/units have been included in the survey. Every third year, beginning in 2000, the survey also includes caravan parks with 40 or more powered sites or cabins, visitor hostels with 25 or more bed spaces and holiday flats and units operated by owners, managers or real estate agents with sole letting rights to 15 or more units.
The State and Territory Tourist Accommodation publications, from 8635.1.40.001 to 8635.7.40.001, have been discontinued.
These have been continued by Data Cubes, in Excel format, from 8635.1.55.001 to 8635.8.55.001
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
4183.0 - Cultural Funding by Government, Australia, 2006-07 Quality Declaration
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 08/07/2008
Directory of Statistical Sources
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
6411.0 - Price Indexes of Materials Used in Manufacturing Industries, Australia, Dec 1994
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 20/02/1995
Page tools: Print Page Print All RSS Search this Product
• About this Release
These indexes measure price movements of materials and fuels used by establishments classified to each defined ASIC manufacturing 'sector' which has sources from establishments outside that 'sector' or from overseas. Index numbers are published for the Manufacturing Division (ASIC Division C); for 14 manufacturing 'sectors' that are defined in terms of ASIC Subdivisions, ASIC Groups or combinations of ASIC Groups; for 20 selected categories of materials and for selected metallic materials used in the fabricated metal products industry (ASIC Subdivision 31).
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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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
8752.7 - Building Activity, Northern Territory, Sep 1993
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 07/01/1994
Page tools: Print Page Print All RSS Search this Product
• About this Release
Number of dwelling units and value of residential buildings (houses and other residential), value of alterations and additions to residential buildings and value of non-residential building by class of building (eg. hotels, offices, etc.), private and public sectors, stage of construction (commenced, under construction, completed), value of work done during period and value of work yet to be done. Number of new houses by class of builder. Value of work commenced and work done at average 1989-90 prices.
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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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
6321.0 - Industrial Disputes, Australia, Sep 2002
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 18/12/2002
Page tools: Print Page Print All RSS Search this Product
• About this Release
ABOUT THIS RELEASE
Continued by 6321.0.55.001
The March 2004 edition will be the first quarterly publication and first electronic publication.
Number of disputes, employees involved, working days lost and working days lost per 1,000 employees in industrial disputes involving stoppages of work of 10 working days or more, classified by State, industry, duration, cause and method of settlement.
More detailed data are released on request.
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home
External Debt Statistics
The table below presents Australia's external debt according to the External Debt Statistics: Guide for Compilers and Users formulation. Financial derivative liabilities are shown as a memorandum item to reconcile external debt with foreign debt liabilities presented in Table 31 of Balance of Payments and International Investment Position, Australia (cat. no.5302.0).
Download this entire document
in Acrobat format
If you do not have reader software...
$m
Q4/12
© 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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How To Be A More Interesting Blogger
Posted by jonrhodesuk2 under Public Relations
From http://www.affiliatehelp.info 77 days ago
Made Hot by: seobromino on March 5, 2013 12:33 pm
Here's how you can become a more interesting blogger. Get people compelled with your content and wanting more with these top tips.
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The smile on Mike Abasov's face reflects the joy he feels every time he helps entrepreneurs reach their … More
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< Previous
Next >
: Leonard's [my uncle's] computer now has Debian on it. I don't know why I was afraid of an install-over-dial-up. Maybe it was just making all those floppies for the base system.
Also, the tiny 486 laptop now has Minix on it.
[Main] [Edit]
Unless otherwise noted, all content licensed by Leonard Richardson
under a Creative Commons License.
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This article is part of the supplement: New trends in digital pathology: Proceedings of the 9th European Congress on Telepathology and 3rd International Congress on Virtual Microscopy
Proceedings
Implementation of the Business Process Modelling Notation (BPMN) in the modelling of anatomic pathology processes
Marcial G Rojo*, Elvira Rolón, Luis Calahorra, Felix Ó García, Rosario P Sánchez, Francisco Ruiz, Nieves Ballester, María Armenteros, Teresa Rodríguez and Rafael M Espartero
Diagnostic Pathology 2008, 3(Suppl 1):S22 doi:10.1186/1746-1596-3-S1-S22
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You are here: Home / News / More effort needed to reduce summer ozone
More effort needed to reduce summer ozone
Published : Mar 19, 2012 Last modified : Mar 20, 2012 03:12 PM
Ground level ozone causes health problems, decreases crop yields and damages the environment. Ozone levels exceeding certain targets in Europe were less frequent in summer 2011 than in any year since monitoring started in 1997. However, the long-term objective was exceeded in all EU Member States and it is likely many of them will not meet the target value, applicable as of 2010.
Image © Luis Garcia
In summer 2011, exceedances of ozone targets were lower than average. But it is still one of the most serious air pollutants in Europe. Air pollution affects people’s quality of life.
EEA Executive Director Jacqueline McGlade
"In summer 2011, exceedances of ozone targets were lower than average," EEA Executive Director Jacqueline McGlade said. "But it is still one of the most serious air pollutants in Europe. Air pollution affects people’s quality of life."
Ozone can cause respiratory problems and other severe health problems.
Ground level ozone production depends on weather conditions such as solar intensity and temperature, and is a result of chemical reactions between other pollutants in the air. These include nitrogen oxides, carbon monoxide, methane and non-methane volatile organic compounds. These substances are emitted by industry, transport, agriculture and other sources.
The European Environment Agency (EEA) publishes an annual report on summer ozone levels. The 2012 report, covering April to September 2011, was based on data from 2 186 monitoring sites across Europe.
Main findings of the report
• In the summer of 2011, the ‘information threshold’ and the ‘long term objective’ (LTO) for the protection of human health were both exceeded in the lowest proportion of air monitoring stations since the start of comprehensive Europe-wide data reporting in 1997. This reduction was mainly due to unusually low temperatures and increased rainfall during the summer months, although there have also been some reductions in the emissions of ozone-precursor pollutants.
• The information threshold (a one-hour ozone concentration of 180 μg/m3) was exceeded at monitoring sites in 16 EU Member States and four non-member countries. The information threshold was exceeded at approximately 18 % of all operational stations. Only northern Italy and several more isolated locations reported a substantial number of exceedances.
• As in previous years, the LTO for the protection of human health (maximum daily eight-hour mean concentration of 120 μg/m3) was exceeded in all EU Member States. These exceedances were registered at approximately 84 % of all operational stations. This limit was exceeded on more than 25 days in a significant part of Europe.
• The alert threshold (a one-hour average ozone concentration of 240 μg/m3) was exceeded 41 times. Concentrations of 300 µg/m3 or more were measured three times in 2011, in Bulgaria, Italy and Spain.
Ozone pollution – not only a local air quality issue
In Europe, ozone concentrations in a particular country are also influenced by emissions in other northern hemisphere countries and by sectors such as international shipping and aviation. Thus, ozone pollution is not only a local air quality issue but also a hemispheric and global problem.
Data sources on emissions of ozone precursor gases
The EEA ground-level ozone viewer provides interactive access to provisional unvalidated ozone data in near real-time. Moreover, the Agency recently published preliminary emissions data on the air pollutants that contribute to the formation of ground-level ozone.
The EEA website includes a table of exceedences across Europe in 2011.
European Environment Agency (EEA)
Kongens Nytorv 6
1050 Copenhagen K
Denmark
Phone: +45 3336 7100
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Rate This Article
Average: 0/5
Tunisia country profile
Tunisia country profile
This article has been reviewed by the following Topic Editor: Lakhdar Boukerrou
Map of Tunisia. (Source: EIA)
Terracing prevents further gully erosion and stores surface runoff for olive production (Tunisia). (Source: Millennium Ecosystem Assessment)
1. General overview
2. Water in Tunisia
3. Energy in Tunisia
4. Human Development Index
5. National parks and preserves:
1. Ichkeul National Park
6. Ecoregions:
1. Mediterranean conifer and mixed forests
2. Mediterranean dry woodlands and steppe
3. Mediterranean woodlands and forests
4. North Saharan steppe and woodlands
5. Sahara desert
6. Saharan halophytics
7. Regional biodiversity hotspot (Mediterranean Basin)
More African country profiles
Return to the Africa Collection
Citation
Maggie Surface (Lead Author);Lakhdar Boukerrou (Topic Editor) "Tunisia country profile". In: Encyclopedia of Earth. Eds. Cutler J. Cleveland (Washington, D.C.: Environmental Information Coalition, National Council for Science and the Environment). [First published in the Encyclopedia of Earth August 26, 2008; Last revised Date August 26, 2008; Retrieved May 18, 2013 <http://www.eoearth.org/article/Tunisia_country_profile>
The Author
Maggie Surface, originally from Nashville, TN, graduated in May of 2007 from Allegheny College with a double B.S. in physics and environmental studies. Her senior thesis at Allegheny focused on bringing solar energy to campus. She interned with American Rivers in the summer of 2006, helping plan River Lobby Day, and with the Meadville Area Local Growers and the Meadville Redevelopment Authority in the summer of 2005. Maggie served as the Earth Portal Program Coordinator for the National Counc ... (Full Bio)
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Changes related to "Japan Calendars"
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Cherry Popper Ice Cream Company
From Grand Theft Wiki
Jump to: navigation, search
Cherry Popper Ice Cream Company's logo in GTA Vice City.
The Cherry Popper Ice Cream Company, or simply Cherry Poppers, is an ice cream company first featured as a front for drugs distribution in Grand Theft Auto: Vice City. The company's name has since resurfaced many times in subsequent games.
Contents
Description
GTA Vice City and GTA Vice City Stories
Cherry Popper is first featured in GTA Vice City based at the Cherry Popper Ice Cream Factory located in Little Havana, Vice City, and owned by Maude Hanson. After "Shakedown", the factory can be purchased by the player for use as an asset and savepoint, but is also revealed during the purchase cutscene that the factory is merely a front for more illicit activities, mainly drug dealing. Thus the factory is central to the "Distribution" side-mission, which involves selling drugs out of the Cherry Popper factory's Mr. Whoopee ice cream trucks.
The building in which the Cherry Popper factory is based in GTA Vice City is retained in the GTA Vice City Stories rendition of Vice City, but lacks any decorations or signage indicating it is based at that time.
GTA San Andreas
In GTA San Andreas, Cherry Popper stalls selling ice cream can be found in various urban locations for the player to replenish their health and stave off hunger. The stalls also depict what appears to the the mascot of the company, Whoopee the Clown, a character first seen on Mr. Whoopees in GTA III.
Boxes of "Chocolate Chunk" and "Raspberry Ripple" Cherry Popper ice cream can also be found in 24-7 stores, and Cherry Popper logos can been be seen on a handful of crates in the game, which texture is also, unusually, used on dumbbells in gyms.
GTA IV
In GTA IV, the Cherry Popper logo is featured on the side of the Mr. Tasty ice cream truck.
Trivia
• The phrase "Cherry Popper" is a take on a girl's first sexual experience (losing virginity).
Gallery
See also
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Bibliography: Second Nature
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Title: Second Nature
Author: Cherry Wilder
Year: 1982
Type: NOVEL
Series: Rhomary Land
ISFDB Record Number: 13979
User Rating: This title has fewer than 5 votes. VOTE
Current Tags: None Add Tags
Publications:
Reviews:
Copyright (c) 1995-2011 Al von Ruff.
ISFDB Engine - Version 4.00 (04/24/06)
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World 9 (New Super Mario Bros. Wii)
From the Super Mario Wiki
Jump to: navigation, search
Platformer World
World 9
Appearance New Super Mario Bros. Wii
Levels 8
<< List of Worlds >>
World 9 is a bonus world from New Super Mario Bros. Wii, unlocked by defeating the final boss of World 8. Each of the eight levels in this world are unlocked by getting all of the Star Coins in the world of the corresponding level number (e.g. All Star Coins in World 1 unlocks World 9-1). World 9 also has Star Coins, but the player doesn't unlock any new stages for collecting them all. There is a total of 24 Star Coins in World 9. Regardless, they're still needed if the player wants to get all five stars on his or her profile on the file select screen. None of the levels have any Checkpoint Flags in them which adds to the challenge of the world, which may be a reference to the Special World from Super Mario World, which, along with the Star World, provides the inspiration for this world. The rainbow theme of the world is also similar to the Rainbow Road courses in the Mario Kart series, and the theme of Mario Kart 64's Rainbow Road can even be heard at some point in World 9's map theme. However, despite being a rainbow-themed world, the levels take place in places other than rainbow-themed ones.
[edit] Levels
Level Preview Description
World 9-1 There are lots of spinning rectangle platforms around the level. Read more...
World 9-2 This stage takes place at a beach setting. The player must get to the goal avoiding a Porcu-Puffer and many Koopas. Read more...
World 9-3 This course has the background of World 6. It features Missile Bills and Missile Banzai Bills. Read more...
World 9-4 World 9-4 involves a desert landscape, which has many pipes and auto-scrolls. Read more...
World 9-5 A snow level where the player must get to the top of the Icy Mountain, while avoiding Cooligans, Fuzzies, and Mega Fuzzies. Read more...
World 9-6 A lava level, where platforms emerge and descend into the lava. Read more...
World 9-7 The penultimate course is obnoxiously difficult. The level takes place in a snowy forest, with floors made of ice blocks, and pipes. Almost the most difficult level in the game,Read more...
World 9-8 The last stage of the game is a sky level. Read more...
[edit] Level Previews
[edit] New Enemies
Personal tools
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Information 2013, 4(1), 1-30; doi:10.3390/info4010001
Article
Complexity over Uncertainty in Generalized Representational Information Theory (GRIT): A Structure-Sensitive General Theory of Information
Center for the Advancement of Cognitive Science, Ohio University, 318 Porter Hall, Athens, OH 45701, USA
Received: 9 August 2012; in revised form: 12 November 2012 / Accepted: 12 December 2012 / Published: 20 December 2012
(This article belongs to the Special Issue Information: Its Different Modes and Its Relation to Meaning)
Download PDF Full-Text [350 KB, Updated Version, uploaded 7 January 2013 16:00 CET]
The original version is still available [336 KB, uploaded 20 December 2012 16:26 CET]
Abstract: What is information? Although researchers have used the construct of information liberally to refer to pertinent forms of domain-specific knowledge, relatively few have attempted to generalize and standardize the construct. Shannon and Weaver (1949) offered the best known attempt at a quantitative generalization in terms of the number of discriminable symbols required to communicate the state of an uncertain event. This idea, although useful, does not capture the role that structural context and complexity play in the process of understanding an event as being informative. In what follows, we discuss the limitations and futility of any generalization (and particularly, Shannon’s) that is not based on the way that agents extract patterns from their environment. More specifically, we shall argue that agent concept acquisition, and not the communication of states of uncertainty, lie at the heart of generalized information, and that the best way of characterizing information is via the relative gain or loss in concept complexity that is experienced when a set of known entities (regardless of their nature or domain of origin) changes. We show that Representational Information Theory perfectly captures this crucial aspect of information and conclude with the first generalization of RIT to continuous domains.
Keywords: information theory; representational information; categorization; concepts; invariance; complexity; information measure; subjective information
Article Statistics
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Cite This Article
MDPI and ACS Style
Vigo, R. Complexity over Uncertainty in Generalized Representational Information Theory (GRIT): A Structure-Sensitive General Theory of Information. Information 2013, 4, 1-30.
AMA Style
Vigo R. Complexity over Uncertainty in Generalized Representational Information Theory (GRIT): A Structure-Sensitive General Theory of Information. Information. 2013; 4(1):1-30.
Chicago/Turabian Style
Vigo, Ronaldo. 2013. "Complexity over Uncertainty in Generalized Representational Information Theory (GRIT): A Structure-Sensitive General Theory of Information." Information 4, no. 1: 1-30.
Information EISSN 2078-2489 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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Scary Google Patent Application & Some Gmail Patent Apps
Oct 7, 2005 • 8:55 am | (0) by | Filed Under Other Google Topics
Msgraph, known for his postings of complex patent applications, posted two new threads at Search Engine Watch Forums.
The first I want to share with you is one that might make you cringe. The thread is titled, Patent App For Behavioral Monitoring Desktop Application. Msgraph explains that this is really scary stuff;
Imagine all of your actions being constantly monitored in order to build personalized search queries. Those last words you typed in a Word document or IM window. The e-mail you just sent. What words your cursor is next to. The text you copied to the clipboard. All of it constantly monitored and processed, in real-time, locally and/or using Google's search engine in order to build search results for you in case you need them at a moment's notice.
Little brother. :)
The next thread msgraph started is on Gmail patent application requests, he titled the thread GMail Patent Application Bundle. It is a bundle of patent applications, because he linked to six different applications in that one thread. Here they are;
There is your light weekend reading for you.
Previous story: AdWords Customers to Target Specific AdSense Pages (Not Just Sites)
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Seasonal Based Fluctuations in Search Rankings
Dec 30, 2005 • 8:22 am | (0) by | Filed Under Search Engine & SEO Theory
Two days ago dazzlindonna over at SEO Scoop wrote Update to Kooky Theory a year later where she explains a new theory she has. The theory basically stats that seasonal popularity is a factor in search rankings at Google and the other engines. She explains;
I have a handful of seasonal sites. These sites are ones that people generally don't go to unless the time is right - and of course the searches are seasonal too. The odd thing I've noticed is that when the season hits, and I start getting traffic to them (say, from yahoo and msn), my google rankings for those sites go up too. As soon as the season is over, the google rankings fall to barely nothing. The backlinks don't change appreciably during the season (maybe a handful more than usual). And yahoo and msn rankings don't fluctuate the same way. Only google. It almost feels like Google is using alexa traffic ranks in its algo. If a lot of people are going to a site, then let's rank it better. If no one is going to a site, then let's drop it. Now, I realize this is a kooky theory, and I'm sure it could be shot down in any number of ways, but for the last 3 holidays, I've seen this exact same pattern with Google. Of course, my non-holiday sites don't have such big spikes during the year, so I can't evaluate them the same way. Anyway, just thought I'd throw out the kooky theory for the day for everyone to poke holes in.
Now, she has seen this exact pattern happen again for this Christmas season. She uses a WebmasterWorld post (message # 138) has support. Seems like a nice theory to me.
Forum discussion at a new forum named SEO Refugee
Previous story: Blogger's AdSense Integration Way Outdated
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Place:Kane Basin, Nunavut, Canada
Watchers
NameKane Basin
TypeCommunity
Located inNunavut, Canada
the text in this section is copied from an article in Wikipedia
Kane Basin is an Arctic waterway lying between Greenland and Canada's northernmost island, Ellesmere Island. It links Smith Sound to Kennedy Channel and forms part of Nares Strait. It is approximately 180 kilometres in length and 130 km at its widest.
It is named after Elisha Kane, whose expedition in search of the lost Franklin expedition crossed it in 1854. Kane himself had named it "Peabody Bay," in honor of philanthropist George Peabody, the major funder of Kane's expedition.
Research Tips
This page uses content from the English Wikipedia. The original content was at Kane Basin (waterway). 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:Otto, Oceana, Michigan, United States
Watchers
NameOtto
Alt namesOttosource: WeRelate abbreviation
TypeTownship
Located inOceana, Michigan, United States
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Otto Township is a civil township of Oceana County in the U.S. state of Michigan. The population was 662 at the 2000 census.
Research Tips
This page uses content from the English Wikipedia. The original content was at Otto Township, Michigan. 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:Peckham, Surrey, England
Watchers
NamePeckham
TypeDistrict
Coordinates51.480207°N 0.056477°W
Located inSurrey, England ( - 1889)
Also located inLondon, England (1889 - 1965)
Greater London, England (1965 - )
source: Family History Library Catalog
the text in this section is copied from an article in Wikipedia
Peckham is a district in Southeast London, England, located in the London Borough of Southwark. It is situated south-east of Charing Cross. The area is identified in the London Plan as one of 35 major centres in Greater London. The 2001 Census recorded a population of 11,381 in the Peckham ward of Southwark and the Office for National Statistics estimated 19,500 residents in the Peckham Community Council area in 2005.
Contents
History
the text in this section is copied from an article in Wikipedia
'Peckham' is a Saxon place name meaning the village of the River Peck, a small stream that ran through the district until it was enclosed in 1823. Archaeological evidence indicates earlier Roman occupation in the area, although the name of this settlement is lost.
Peckham appears in Domesday Book of 1086 as Pecheham. It was held by the Bishop of Lisieux from the Bishop of Bayeux. Its Domesday assets were: 2 hides. It had land for 1 plough, of meadow. It rendered £1 10s 0d (£1.50).
The manor was owned by King Henry I who gave it to his son Robert, Earl of Gloucester. When Robert married the heiress to Camberwell the two manors were united under royal ownership. King John probably hunted at Peckham and local anecdotes suggest that the right to an annual fair was granted to celebrate a particularly good day's sport. The fair grew to be a rowdy major event lasting three weeks until its abolition in 1827.
Peckham became popular as a wealthy residential area by the 16th century and there are several claims that Christopher Wren had local links. By the 18th century the area was a more commercial centre and attracted industrialists who wanted to avoid paying the expensive rents in central London. Peckham also boasted extensive market gardens and orchards growing produce for the nearby markets of London. Local produce included melons, figs and grapes. The formal gardens of the Peckham Manor House, rebuilt in 1672 by Sir Thomas Bond were particularly noticeable and can be seen on the Rocque map of 1746. The manor house was sacked in 1688, as its then owner Sir Henry Bond was a Roman Catholic and staunch supporter of James II. The house was finally demolished in 1797 for the formation of Peckham Hill Street, as the Shard family developed the area. Today Shard's Terrace, the block that contains Manze's Pie and Mash shop, and the western side of Peckham Hill Street represent this Georgian planned expansion.
The village was the last stopping point for many cattle drovers taking their livestock for sale in London. The drovers stayed in the local inns (such as The Red Cow) while the cattle were safely secured overnight in holding pens. Most of the villagers were agricultural or horticultural workers but with the early growth of the suburbs an increasing number worked in the brick industry that exploited the local London Clay.
In 1767 William Blake visited Peckham Rye and had a vision of an angel in a tree. In 1993, at the request of the Dulwich Festival, artist Stan Peskett painted a mural of Blake's vision next to the Goose Green playground in East Dulwich.
19th century
At the beginning of the 19th century Peckham was a "small, quiet, retired village surrounded by fields". Since 1744 stagecoaches had travelled with an armed guard between Peckham and London to give protection from highwaymen. The rough roads constrained traffic so a branch of the Grand Surrey Canal was proposed as a route from the Thames to Portsmouth. The canal was built from Surrey Commercial Docks to Peckham before the builders ran out of funds in 1826. The abbreviated canal was used to ship soft wood for construction and even though the canal was drained and backfilled in 1970 Whitten's timber merchants still stands on the site of the canal head.
In 1851 Thomas Tilling started an innovative omnibus service from Peckham to London. Tilling's buses were the first to use pre-arranged bus stops, which helped them to run to a reliable timetable. His services expanded to cover much of London until his horses were requisitioned for the Army in World War I.
Before Peckham Rye railway station was opened in 1865 the area had developed around two centres: north and south. In the north, housing spread out to the south of the Old Kent Road including Peckham New Town built on land owned by the Hill family (from whom the name Peckham Hill Street derives). In the south, large houses were built to the west of the common land called Peckham Rye and the lane that led to it.
With the arrival of the railway and the introduction of horse-drawn trams about ten years later, Peckham became accessible to artisans and clerical staff working in the City and the docks. Housing for this socio-economic group filled almost all the remaining fields except the Rye. In 1868 the vestry of Camberwell St Giles bought the Rye to keep it as common land. Responding to concerns about the dangerous overcrowding of the common on holidays the vestry bought the adjacent Homestall Farm (the last farm in the area) in 1894 and opened this as Peckham Rye Park.
With the influx of younger residents with money to spend Rye Lane became a major shopping street. Jones & Higgins opened a small shop in 1867 (on the corner of Rye Lane and Peckham High Street) that would become the best known department store in South London for many years. It closed in the 1980s. In 1870 George Gibson Bussey moved to Peckham and set up a firm described as "Firearms, Ammunition & Shooting” at the Museum Works, Rye Lane, Peckham. The Museum of Firearms was built in 1867. The Ordnance Survey Map of 1868 shows the Museum building with a rifle range at the rear extending along the side of the railway embankment for 150 yards.
The late 19th century also saw the arrival of George Batty, a manufacturer of condiments, whose main business stood at Finsbury Pavement. The company's Peckham premises occupied 19 railway arches. It was acquired by the H. J. Heinz Company in 1905 as their first UK manufacturing base.
The southern end of Peckham was the location for the railway line that once served The Crystal Palace in Sydenham. Though the line was eventually dismantled due to the collapse of the embankment into the gardens of Marmora Road it is still possible to see large sections of it. The flats on Wood Vale and the full length of Brenchley Gardens trace its route.
Marmora, Therapia, Mundania and Scutari Roads, built in the 1880s, all derive their curious names from locations now in modern day Turkey, possibly from associations with the stationing of British forces there during the Crimean War. Close by is the Aquarias Golf Club which is located over the cavernous Honor Oak Reservoir constructed between 1901 and 1909. When it was completed it was the largest brick built underground reservoir in the world and is still one of the largest in Europe. The reservoir now forms part of the Southern extension of the Thames Water Ring Main.
Camberwell Old Cemetery, on Forest Hill Road, is a later example of the ring of Victorian cemeteries that were built to alleviate the overcrowding of churchyards that was experienced with the rapid expansion of London in the 19th century. The Stone House at its main entrance was used in the filming of Joe Orton's Entertaining Mr. Sloane (released 1970). It was gutted by fire in the mid-1970s and rebuilt some years later. Camberwell Old Cemetery did not have the grandeur of nearby Nunhead Cemetery, which was one of the original London necropolis', and once nearing capacity it was replaced by Camberwell New Cemetery on Brenchley Gardens.
Brenchley Gardens Park follows the route of the old line to the Crystal Palace culminating at the High Level station. The park runs behind Marmora Road and the remains of the embankment then continues along Wood Vale where flats were built on it. The line was closed in 1954 following a decline in its use after the destruction of the Crystal Palace in 1936 and due to slippage in the structure of the embankment.
20th century
In the 1930s George Scott Williamson and Innes Pearse opened the Pioneer Health Centre in Queens Road. They planned to conduct a large experiment into the effect of environment on health. 'The Peckham Experiment' recruited 950 families at one shilling (5p) a week. The members joined something like a modern sports club with facilities for physical exercise, games, workshops and socialising with no mandatory programme. The centre moved into a purpose built modernist building by the architect Sir Owen Williams in 1935.
North Peckham was heavily redeveloped in the 1960s, consisting mainly of high-rise flats to rehouse people from dilapidated old houses. It was popular on its completion for offering a high quality and modern standing of living. However, high unemployment and a lack of economic opportunities led to urban decay and a period of decline in the late 1970s. The North Peckham Estate became one of the most deprived residential areas in Western Europe. Vandalism, graffiti, arson attacks, burglaries, robberies and muggings were commonplace, and the area became an archetypal London sink estate. As a result, the area was subjected to a £290 million regeneration programme in the late 1990s and early 2000s. After the beginning of the regeneration, the estate gained nationwide notoriety in the media when 10-year-old Nigerian resident Damilola Taylor was stabbed to death on the estate on 27 November 2000. By 2002, 90% of the redevelopment was complete. The new homes were better laid out and offered improved security, though few local people were convinced that better housing would equate to a better area. A gang operating in the area is the Peckham Boys.
In the early 1990s Peckham was a centre of underground music, partly due to a large squat in a disused, 2 floor DHSS building in Collyer Place near Peckham High Street. The building was already known for having featured in the cover shot of a 1980s pictorial biography of 1960s' mods, featuring them on their customised scooters outside the then Camberwell Labour Exchange. In 1989 the squatters adopted the name Dole House Crew and along with another local group of squatters called the "Green Circus", held regular gigs/parties in the building. Upstairs was a large live gig room and downstairs was a rave music DJ set up. There were also two bars, a vegan cafe and a chill out lounge. During the week, any empty rooms were utilised for bands or artists. Some notable bands who regularly played gigs at the Dole House were: The Levellers, Citizen Fish, and Radical Dance Faction. Up to 1,000 people could be squeezed into the squat and from February 1990 it was regularly filled to capacity. Those involved provided music at various free festivals in the 1990s and also assistance to the then budding Deptford urban free festival (later the Fordham Park urban free festival). They moved on to many other South East London venues after the Peckham Dolehouse was evicted in late October 1990. A squatted social centre called the Spike Surplus Scheme ran from 1998 until being evicted by the council in 2009.
Peckham was one of the areas where riots took place during the 2011 England riots.
Research Tips
This page uses content from the English Wikipedia. The original content was at Peckham. 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 Catalogue Number
4123.2 - Victoria's Young People, 1996
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 14/12/1998
Page tools: Print Page Print All RSS Search this Product
INTRODUCTION
This publication provides a comprehensive range of statistics on young people aged 12-25 years in Victoria, using data from the 1996 Census of Population and Housing. The report is one of a series produced for each Australian State and Territory, jointly published by the National Youth Affairs Research Scheme (NYARS) and the Australian Bureau of Statistics (ABS). NYARS was established in 1985 as a cooperative funding arrangement between the Commonwealth and State and Territory Governments to facilitate nationally based research into current social, political and economic factors affecting young people. NYARS is administered under the auspices of Youth Ministers through a working group of the Ministerial Council on Education, Employment, Training and Youth Affairs. Research undertaken assists in the formulation, implementation and assessment of policy by Commonwealth, State and Territory Ministers for Youth.
A similar series, using 1991 Census data, was jointly published by the ABS and NYARS during 1992 and 1993.
The publication features summary tables of selected characteristics of young people at national and local government area levels. More detailed information is presented in five subject-based chapters: population, cultural diversity, living arrangements, education and working life.
Within these broad subject headings, the publication also considers young people in the context of age, sex, and cultural diversity. Comparative data from the 1986 and 1991 Censuses are also included in some tables to provide a time dimension.
CHAPTER 1 SELECTED CHARACTERISTICS
NATIONAL SUMMARY-Main findings
On census night 1996, 3,636,900 12-25 year-olds were counted in Australia, representing 21% of Australians of all ages.
In New South Wales, the most populous State, they numbered 1,201,800, representing one-third of Australia's young people. The Australian Capital Territory had the highest proportion of young people (24%).
Young males outnumbered young females in all States and Territories. Nationally, there were 48,800 more 12-25 year-old males than females.
Cultural diversity
Almost 3% (99,500) of Australia's young people were of Indigenous origin. In the Northern Territory, people who reported that they were of Indigenous origin comprised 32% of all 12-25 year-olds, but in Victoria, they made up fewer than 1% of young people.
Just over 14% of young people in Australia had been born overseas. For 5%, their country of birth had been one of the main English-speaking countries (Canada, Ireland, New Zealand, South Africa, the United Kingdom and the United States of America). The other 9% had been born in other countries.
A high proportion of young people (15%) spoke languages other than English. More than 28% of the Northern Territory's 12-25 year-olds, and 20% of young people in Victoria, reported speaking a language other than English at home.
Living arrangements
Over 42% of young people in Australia were living with their parents as dependent children-either children aged 15 years or under, or dependent students aged 15-24 years. Another 20% lived with their parents as non-dependent children.
Almost 24% of young people had formed families or partnerships, or were living independently, alone or in group households.
Education
Over 87% of 12-17 year-olds, and almost 30% of 18-25 year-olds, were attending schools or other educational institutions. The highest levels of educational participation were reported in the Australian Capital Territory (92% of 12-17 year-olds, and 43% of 18-25 year-olds), and the lowest, in the Northern Territory - 75% and 14% respectively.
New South Wales had the highest proportion (32%) of any State or Territory of young people (18-25 years) with post-school qualifications. Nationally, the proportion was 29%.
Working life
There were 48% of Australian 15-19 year-olds, and 78% of 20-25 year-olds, who were in the labour force, that is, they were employed, or looking for work.
Among young people aged 15-19 years, the highest proportion (23%) were working part-time, compared with 14% in full-time work. For 20-25 year-olds, these positions were reversed - 47% were working full-time, and 19% part-time.
Unemployment
Unemployment rates among young people were at 19% for 15-19 year-olds, and 13% for 20-25 year-olds.
An alternative measure of unemployment levels is the percentage of unemployed in the whole age group. In 1996, this proportion was 9% for 15-19 year-olds, and 10% for 20-25 year-olds. This measure is particularly useful for young people, as it takes into account the number of people not participating in the labour force because of their education commitments.
Income
The median weekly income for 15-25 year-olds in 1996 was $181. The highest median incomes were reported in the Northern Territory ($193), Queensland and Western Australia (both $192).
CHAPTER 2 POPULATION
Main findings
On census night (6 August 1996) 891,624 young people aged 12-25 years were counted, constituting 20% of all people in Victoria.
1986 to 1996
Between 1986 and 1996, Victoria's census count increased by just over 345,300 (9%) to 4,354,126. The number of young people fell by 68,761 or 7% over the same period.
As a result, young Victorians represent a declining proportion of the total, falling from 24% in 1986 to 22% in 1991, and then to 20% in 1996. This trend can be expected to continue, since the proportion aged 0-11 years has also declined, from 18% in 1986 to 17% in 1996.
YOUNG PEOPLE, Proportion of All Persons
Sex and age
There were slightly more males than females in the 12-25 years age group (451,872 compared with 439,752). Males slightly outnumbered females at all ages up to 23 years, after which the number of females began to exceed the number of males. Among all people counted in Victoria, females outnumbered males by 71,736.
Geographic
Most of Victoria's young people live in Melbourne. The 1996 Census counted 651,943 12-25 year-olds in the Statistical Division of Melbourne. The next largest numbers of young people were counted in the Statistical Divisions of Barwon (46,287) and Goulburn (33,654).
Melbourne and Central Highlands Statistical Divisions recorded the highest proportions of young people (21%) In the rural Statistical Division of Wimmera 12-25 year-olds comprised only 17% of all people.
Movement
Young people reported being more mobile than older people. In 1996, 38% of 12-25 year-olds reported living at a different address five years previously, compared with 32% of older people. A similar pattern was evident for residential movement within the previous twelve months, with 20% of young people and only 11% of older people reporting that they were living at a different address.
Most of this movement had taken place within Victoria. Among people who had moved within the previous five years, 91% of 12-25 year-olds and 92% of older people had moved within the State.
People who had a Different Address Five Years previously
Young females were more likely to have moved than young males with 41% of young women reporting living at a different address from five years ago, compared with 35% of young men. Among persons aged 26 years and over, similar proportions of males and females were living at a different address five years ago (32% and 31% respectively).
CHAPTER 3 CULTURAL DIVERSITY
Main findings
Indigenous people
In 1996, 82% of 12-25 year-olds (734,782) in Victoria were Australian-born, compared with 65% of people aged 26 years and over. Fewer than 1% (5,735) of young Victorians reported that they were of Indigenous origin. This was the lowest proportion among all of the States and Territories.
Overseas-born
Just over 14% (127,533) of 12-25 year-olds in Victoria were born overseas, compared with more than twice this proportion among older people (32%).
Countries of birth
Just under 23% of young people born overseas were from the main English-speaking countries (Canada, Ireland, New Zealand, South Africa, the United Kingdom and the United States of America). The largest number (12% or 15,370 people) of overseas-born young people in Victoria were from Viet Nam, followed by young people from the United Kingdom (11%), and New Zealand (7%).
Among people aged 26 years and over born overseas, more than 29% originated from the main English-speaking countries. Almost 23% had been born in the United Kingdom, 11% were born in Italy, and 7% in Greece.
OVERSEAS-BORN, Leading Countries of Birth
Among overseas-born young people who arrived in Australia between 1986 and 1990, the highest proportion were born in Viet Nam (14%), followed by the United Kingdom (9%) and New Zealand (7%). Of those who arrived between 1991 and 1996, 11% had migrated from Viet Nam, 10% from Malaysia and 8% from Indonesia.
Birthplace of parents
Among Australian-born Victorians aged 26 years and over, 76% had both parents born in Australia. Among 12-25 year-olds born in Australia, a lower proportion (61%) had both an Australian-born mother and father. Almost 38% (277,671) of Australian-born young people in Victoria had at least one parent who had been born overseas, and 16% had both parents born in a non-main English-speaking country.
Languages spoken at home
Just over 20% (179,783) of young Victorians spoke a language other than English at home. The predominant languages they reported speaking were Italian and Greek (almost 15% for each) and Chinese languages (just under 14%). Twice the proportion (40%) of older people reported speaking a language other than English at home. The languages most commonly spoken were also Italian, Greek and Chinese languages, although in different proportions (21%, 15% and 10% respectively).
Proficiency in English
The majority (77%) of young Victorians spoke English only. Another 19% spoke another language, and reported that they spoke English well or very well. A similar proportion (76%) of those aged 26 years and over reported speaking English only. However, 5% of older people reported speaking English not well or not at all, compared with just over 1% of young people.
CHAPTER 4 LIVING ARRANGEMENTS
Main findings
Marital status
Just over 12% of 15-25 year-olds in Victoria were married - 7% in a registered marriage, and 5% in a de facto marriage. Young females were more likely than young males to be in a partnership (16% compared with 9%).
Living arrangements
Over 45% of 12-25 year-olds were living with their parents as dependent children. This was the highest proportion of all States and Territories. Another 25% of young males, and 17% of young females, were living as non-dependent children with their parents. Young females were more likely than young males to have moved from the family home, forming partnerships and their own families (15% compared with 7% respectively).
Young People-Living Arrangements
Among Indigenous young people, higher proportions of females (25%) than males (10%) had formed partnerships, or their own families.
For young people born in non-main English-speaking countries, about 43% were living as dependent children with their parents. Another 14% lived in the family home as non-dependent children, while 9% were living in group households.
Type of dwelling
About 3% (23,723) of 12-25 year-olds in Victoria had spent census night in a non-private dwelling. The majority of these young people were in boarding schools or residential colleges (11,194), or staying at hotels and motels (6,258). Another 2,702 young people reported having no usual address.
Type of tenure
About 65% of young people occupied dwellings which were owned or being purchased, compared with 74% of people aged 26 years and over.
The proportion of young people living in rented dwellings was just under 28% compared with 17% of older people (aged 26 years and over). More than 56% of Indigenous young people, and 42% of those born overseas in non-main English-speaking countries, were in rented dwellings.
CHAPTER 5 EDUCATION
Main findings
Attendance at educational institutions
Slightly more than 57% (508,751) of all 12-25 year-olds were attending an educational institution in 1996. This compares with 53% in 1991. There was a similar overall participation rate for both males (56%) and females (58%).
The proportions of young people attending schools in 1996 (38%) and Technical or further educational institutions and other higher education institutions (18%) were slightly higher than in 1991 (36% and 16% respectively).
ATTENDANCE AT EDUCATIONAL INSTITUTIONS,
Persons Aged 12-25 Years
Given the compulsory nature of school attendance, education participation rates in Victoria were highest for the younger age groups and, overall, exceeded the national average. Almost all (95%) of those in the 12-14 years age group reported that they were still at school, with the majority (63%) attending government schools. Among 15-17 year-olds, educational participation was lower, with 80% at school and 3% attending a Technical or further education institution or a higher education institution.
Education participation continued to decline with age, with 57% of 18-19 year-olds and 27% of 20-25 year-olds remaining in education.
Non-main English-speaking birthplace
Participation in education was very high among young people born overseas in a non-main English-speaking country. Almost 69% were attending an educational institution. Much of this participation was among older youth, with 80% of 18-19 year-olds and 51% of 20-25 year-olds remaining in education.
Indigenous people
Among Indigenous youth aged 12-25 years, 2,536 (44%) were attending an educational institution in 1996. However, most of the participation was in the younger age groups, with 89% of 12-14 year-olds and 61% of 15-17 year-olds in education. Just 14% of 20-25 year-olds remained in education.
Education and labour force status
Among 15-25 year-olds who were attending an educational institution in 1996, 38% were employed; 27% part-time and 10% full-time. A lower proportion (34%) were employed in 1991 (20% part-time and 12% full-time).
In 1996, 44% of young people attending a tertiary or other institution full-time were either working part-time or seeking part-time work. In 1991 this proportion was 38%, reflecting a general increase in part-time work.
Qualifications
In the five years from 1991 to 1996, the proportion of 15-25 year-olds with post-secondary qualifications increased from 16% to 20%. Among persons aged 26 years and over, the proportion increased from 30% to 34% over the same period.
Young Victorians were also more likely to hold higher levels of qualifications in 1996 than five years earlier. Among those young people holding post-school qualifications, the proportions who had attained a bachelor degree or higher increased from 28% to 38%.
While the same proportions of young females and males held post-school qualifications (20%), the level of qualification varied between the sexes. The most common qualifications held by young females were bachelor degrees (8%), followed by associate diplomas (4%). For young males, the most common qualifications held were skilled vocational qualifications (9%) followed by bachelor degrees (5%).
HIGHEST QUALIFICATION, Persons Aged 15-25 Years
CHAPTER 6 WORKING LIFE
Main Findings
Labour force status
In 1996 there were 450,427 young Victorians in the labour force; that is, either employed or looking for work. They made up 22% of the total labour force (2,081,069 people). The majority (85%) of these young people were employed.
Participation rates
The labour force participation rate for young people in 1996 was 64%. Participation among Indigenous young people was lower at 55%. However, among young people born overseas in a non-main English-speaking country, the participation rate was 42%. This reflected the much higher level of educational participation by this group.
In 1996, fewer young females were in the labour force than young males (62% compared with 65%). A similar pattern existed in 1991, with 63% of young females and 68% of young males in the labour force.
Full-time work
The proportion of young people employed in full-time work fell between 1991 and 1996 from 34% to 32%. This decrease was experienced by both young males (from 38% to 36%) and females (from 30% to 27%). Over the same period the proportion of older people (aged 26 years and over) who were employed full-time remained relatively unchanged at about 39%.
Part-time work
The proportions of both young and older people employed in part-time work have increased. Between 1991 and 1996, the proportion of young Victorians who were employed part-time increased from 15% to 21%. The percentage point increase for older people was much lower (1%). Of employed young females, 47% were employed part-time compared with 30% of young males.
Unemployment
In 1996, Victoria's unemployment rate for young people was 15%. The age group with the highest rate of unemployment (21%) was 18-19 year-olds. In the 15-17 year-old age group the rate was 17% and among 20-24 year-olds it was 14%. Among all young Victorians, 10% were unemployed.
Industry
In 1996, the largest proportions of young people were employed in Retail trade (27% or 104,591); Manufacturing (14%); and Property and business services (9%). For older people, the largest industries of employment were similar: Manufacturing (17%) and Retail trade and Property and business services (both 10%).
EMPLOYED YOUNG PEOPLE, Leading Industries of Employment
Occupation
In 1996, 76,312 or 20% of young Victorians were employed as Elementary clerical, sales and service workers. The largest proportion (20%) of older people were employed as Professionals. For young males, the most common occupations were Tradespersons and related workers (28%); Labourers and related workers (14%); and Intermediate production and transport workers (12%). Young females were most commonly employed as Intermediate clerical, sales and service workers (29%); Elementary clerical, sales and service workers (28%); and Professionals (12%).
Income
The highest proportion (15%) of young people reported receiving no income. In general, there were proportionally more young females at lower income levels and fewer at higher income levels. A partial explanation for this is females' higher participation in part-time work.
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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 have recently approached my business partner with a request to buy out his membership in our LLC. His involvement as of late is declining and a buy out was something we had planned on from day 1. I was very "young and dumb" when we started the business 4.5 years ago, so nothing regarding the buyout amount was set in stone.
He has given me his requested number and it seems a bit high. Keep in mind he has not entered our office in six months and simply handles accounts payable and makes deposits. He has brought in a few clients, but nothing more than what our existing clients already refer.
I feel the amount is a bit high. Is there are simple formula to determine what the buyout price should be for our business. We are equal 50/50 members in the LLC.
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2 Answers
Ask an accountant to put a value on your business. It will be something along the lines of the value of your assets less liabilities, plus some multiple of your annual profitability on your sales.
So if your company has $50K of equipment, a lease worth $20K, and no other assets or liabilities, then your company would be worth $30K, plus your income factor. If you had an average of $100K profit in each of the last 3 years, then your business would be worth between $130K and $500K, depending on your industry.
Don't forget to calculate in any salaries drawn before looking at the bottom line.
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Your company is worth what you can sell it for. A valuation based on assets and income is fine, but only relevant if you have a serious prospect.
In your case, I would tell your partner you are going to each get 3 bids, and then take the middle of each, (middle from your 3, and middle from his). Then take the average of both for a fair figure.
The valuations are what prospects will look at.
Typically, i feel a company is worth 3 to 4 times it yearly net profits.
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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 am a US citizen currently living in Poland (EU state) and would like to register a US based LLC from here.
Is this possible?
If so:
1. How?
2. How much is the cost?
3. What are the positives & negatives?
I ask because I thought one had to be there in person to sign the documents. Also I heard there are services that can do this for you via mail/online.
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1 Answer
up vote 0 down vote accepted
This is absolutely possible.
I've setup companies in other countries remotely and I've setup companies in the US in person and remotely. All you need to do to register a company is to file the proper paperwork. If you want to create a LLC or other limited structure then just draw up your articles of incorporation and send them off. The issue is that most states (perhaps all) require a registered agent who has a physical address in that state. I believe there are firms which will act as your registered agent for you. This is so the state can send you official notices and things like that. Fail to file a simple annual report with your state or registration and they'll shut down your company. So, its important but trivial stuff.
If you have a little money (should not be much, maybe $1,000 - $2,000) hire an attorney to do this for you. Most of them have the process quite automated.
You might need to give a power of attorney but better to give this to a licensed profession rather than someone who has nothing to lose from abusing the power you are giving them.
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Source link: http://archive.mises.org/5587/competition-european-style/
Competition, European Style
September 8, 2006 by
The New York Times reports that the European Commission has “ordered Microsoft to disclose secret code in Windows XP needed by rivals to allow them to write programs that work properly with Windows. And it required the company to introduce a second version of Windows XP with its audio and video player removed.”
The European Commission is also reported to be drafting a ruling that will require the world tennis champion Roger Federer to share the secrets of his play with rivals, to enable them, for example, to better integrate their returns with his serves.
In still another development, the European Commission is reported to be contemplating barring the sale of automobiles and other motor vehicles equipped with radios, CD players, or video players. The ruling is held to be necessary to preserve the separate markets of the suppliers of these devices and not allow them to be monopolized by automakers.
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Email this article to a friend
Glucocorticoid receptor gene polymorphisms and disease activity during pregnancy and the postpartum period in rheumatoid arthritis
Rogier AM Quax*, Yaël A de Man, Jan W Koper, Elisabeth FC van Rossum, Sten P Willemsen, Steven WJ Lamberts, Johanna MW Hazes, Radboud JEM Dolhain and Richard A Feelders
Arthritis Research & Therapy 2012, 14:R183 doi:10.1186/ar4014
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User talk:Paweł
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Welcome to eLinux.org! We hope you will contribute much and well. You will probably want to read the help pages. Again, welcome and have fun! Wmat (talk) 00:39, 25 January 2013 (UTC)
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COIN
Unique ID: WILT-C0AA33
Object type certainty: Certain
Workflow status: Awaiting validation
A Medieval cut halfpenny of Henry III (1216-72), long cross coinage class 5g. Measures 16.5mm, weighs 0.50g, exceedingly worn.
Obverse: Crowned bust facing
Reverse: Long cross with three pellets in each quarter
RIC ARD [...] AR are ligatured
Mint: Canterbury, class 5g
Moneyer: Ricard
Date: 1251-72
Reference: North 997
Subsequent actions
Subsequent action after recording: Returned to finder
Chronology
Broad period: MEDIEVAL
Period from: MEDIEVAL [scope notes | view all attributed records]
Date from: Circa AD 1251
Date to: Circa AD 1272
Dimensions and weight
Weight: 0.5 g
Diameter: 16.5 mm
Quantity: 1
Discovery dates
Date(s) of discovery: Wednesday 30th November 2011 - Wednesday 29th February 2012
Personal details
Found by: This information is restricted for your login.
Recorded by: Ms Katie Hinds - [ view all attributed records]
Identified by: Mr David Algar - [view all attributed records]
Other reference numbers
Other reference: Salisbury Museum Entry Form No. 3822
Materials and construction
Primary material: Silver [scope notes | view all attributed records]
Completeness: Complete [scope notes | view all attributed records]
Coin data (numismatics)
Denomination: Cut halfpenny [ scope notes | view all attributed records]
Ruler/issuer: Henry III of England [ scope notes | view all attributed records]
Mint or issue place: Canterbury [scope notes | view all attributed records]
Category: English coin short and long cross period 1180 - 1278 [ scope notes | View all attributed records]
Type: Long cross class 5g (N 997) [scope notes | view all attributed records]
Obverse description: Crowned bust facing
Reverse description: Long cross with three pellets in each quarter
Reverse inscription: RIC ARD [...] AR are ligatured
QR barcode
The barcode on the right is a unique identifier for this record. If your phone has scanning software installed, then this can be used for sharing or you can print it off and attach it to the object.
Spatial metadata
Region: South West
County: Wiltshire
District: Swindon
To be known as: Swindon
Spatial coordinates
Grid reference source: From finder
Unmasked grid reference accurate to a 100 metre square.
Discovery metadata
Method of discovery: Metal detector [scope notes]
General landuse: Cultivated land[scope notes]
Specific landuse: Operations to a depth less than 0.25 m[scope notes]
Similar objects
Find number: WMID-F9DD16
Object type: COIN
Broadperiod: MEDIEVAL
Silver cut halfpenny of Henry III (1216-72); long-cross coinage; class 5 (1251-72); moneyer: Ricard; London mint.
Workflow: Awaiting validation
Find number: WMID-C21946
Object type: COIN
Broadperiod: MEDIEVAL
An incomplete silver long-cross type penny of Henry III (1216-72). Canterbury mint, moneyer Ricard, class 5g (1251-72), probably (Coin ref. No…
Workflow: Awaiting validation
Find number: WILT-A08695
Object type: COIN
Broadperiod: MEDIEVAL
A Medieval silver long cross penny of Henry III (reigned 1216-72), class 3a, 17-19mm in diameter and weighing 1.30g (20.2gn). It is worn with…
Workflow: Awaiting validation
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Friday, February 08, 2013
A Fuzzy Fashion Quiz
All of the women pictured b elow are wearing a dress that is know as sheer and lacey.
Two of them are Israeli but only one is the wife of Israel's Prime Minister:
1.
2.
3.
4.>br />
5.
6.
And the answer is...?
______________
The Uriel Sinai / Getty Images pic:
^
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Library Camp UK 2012
The creative energy unleashed by an unconference is a wonderful thing. I attended LibCamp2012 recently and was surprised that a disparate bunch of people can self-assemble such a varied and interesting programme, all in one day.
I went to the first LibCamp last year. It grew out of something called GovCamp, a local government unconference. The public librarians who had attended GovCamp thought that a library version might work well, so they organised LibCamp2011 in Birmingham. That went very well and inspired several local libcamps (I went to the Brunel libcamp in January). The 2012 event, also in Birmingham, attracted a similar mix of people from public, academic and other libraries – about 200 attendees.
The energy comes from the immediacy, the informality and the level of participation in discussion, cross-fertilised by the broad cross-section of types of libraries represented. The sessions are interactive. Rather than a long lecture followed by a few questions, the sessions I attended comprised a short exposition followed by an extensive round-table discussion, where we shared our experiences. I think the unconference is second cousin to the blog: a home for half-baked ideas (in the nicest possible way) and lively comments. Talking of baking, LibCamp also has a fully-baked component in the shape of cakes brought along by delegates.
The programme was eclectic, assembled by means of a pitching session at the beginning of the day (and a wiki for idea-sharing in advance of the event). I didn’t hear most of the pitches as one of the organisers thrust a camera into my hands and instructed me to take photos. I didn’t cope very well with the unfamiliar camera and I suspect they all came out poorly composed and blurry. Luckily the battery ran out so I was able to hand the camera back after a few minutes.
This is the post-it note version of the programme:
And this was a readable (but incomplete) version circulated later:
With five parallel sessions at any one time there was a good deal of choice. One session on how to cope with swearing attracted some interest and there was apparently some disagreement in the session on What is a Library for? The five sessions I attended were less dramatic, but thought-provoking nevertheless.
The session on Living libraries, as pioneered by Malmo public library in Sweden, was fascinating. It was led by someone Anna Brynolf, who had lived for some years in Sweden. The idea of “lending” living people was envisaged as a way to lessen differences between cultures – you could confront your prejudice about a particular group by “borrowing” and talking to someone from that group for 45 minutes. For instance, you could meet with someone who was an animal rights activist, or a Muslim, or a vegan, and talk to them about their beliefs or experiences. The idea started at a music festival in Denmark but it developed further in Sweden and has since spread elsewhere. One person at the session told us she had worked in a library in Dublin that had a similar project. Someone tweeting about the session discovered that in the UK it had also been done at the WOMAD festival, and at Anglia Ruskin University. The Human Library website has more background about the idea and mentions projects in various countries around the world:
The Human Library enables groups to break stereotypes by challenging the most common prejudices in a positive and humorous manner. It is a concrete, easily transferable and affordable way of promoting tolerance and understanding.
Another unusual library was described in a session by someone hoping to establish the UK’s first tool library. He explained that there are several of these in the USA and a handful elsewhere. One of the earliest established is in Berkeley, which is where he had come across the concept. Now living in Dudley he decided to set up a tool library there. He has funding and some space and we gave him a few more ideas about how the library might be set up.
My favourite session was on roaming libraries, presented by the remarkable and brilliant Itinerant Poetry Librarian, aka Sara Wingate Gray. I think she was keen to encourage us to discuss roaming libraries more broadly. She mentioned the Mile High Ref Desk, which provides library services to passengers on airline flights, and Radical Reference, which is “dedicated to information activism to foster a more egalitarian society”. However I found her descriptions of her own project much more interesting and was happy just to hear her talk about that. Sara has taken The Itinerant Poetry Library (TIPL) to more than 20 cities in the USA and Europe. She sets it up in bars or coffee shops, registers readers and then lets them borrow poetry books. If you want to know more about TIPL, there is a nice article about it in VarsityThere is an element of performance to TIPL which gave me food for thought. I have been doing some background reading on science busking which also involves a significant degree of performance, and attention-grabbing. Perhaps we need a new breed of librarian to grab people’s attention and thrust books under their noses.
The most hard-core session I attended was on classification. The session leader set out the dichotomy between the philosophical approach (the right class mark) and the pragmatic approach (the right classmark for my library) to classification. I always assume that most libraries use sensible classification schemes – the major schemes like Library of Congress or Dewey. A quick survey of the room revealed a wide range of schemes in use, from major global schemes, to very old (obsolete) schemes, hybrid schemes, multiple schemes, and weird local schemes. Someone commented that library users did not all understand what classification was for and were pleasantly surprised to find that books on a similar subject were all in the same place on the shelf. But some academics complained vociferously if ‘their’ books were (as they saw it) classified wrongly. On the plus side, we heard reports that reclassification could be effective, increasing the number of library users who could find books.
The most interesting question raised was whether classification was necessary at all for electronic resources. The answer must surely be “No”, since classification is all about physical books on the shelf. That set me thinking about the benefits of browsing at the shelf, and wondering whether there could be a way to create a life-size electronic shelf search/browse that combined the advantages of the old and new technologies. It would be a giant vertical touch-sensitive screen in the Library that allowed you to search and view full-text content, and mark items that you wanted to read later.
I will draw a modest veil over the session on iPads in libraries that I co-facilitated with Sarah Barker but I think it went down well. There was less sharing of experiences than I had hoped for, perhaps because it is still not that common for libraries to lend iPads.
The session on mental health in libraries was remarkable for the way that people shared their experiences, good and bad, very openly. Not much of the discussion was specific to libraries, but applied to the workplace more generally. The most useful thing I learned was that an organisation called Mental Health First Aid offers free training in “how to recognise the signs and symptoms of common mental health issues, provide help on a first aid basis and effectively signpost towards support services”. A number of people in the session said the courses were very good.
So, that was my Library Camp UK 2012. I enjoyed the day – it went very quickly. I would have liked to have gone to more sessions, but I enjoyed those I did attend. It was a shame that the venue’s wifi was not up to scratch but that meant I listened and talked more freely instead of trying to tweet all the time so perhaps it was for the best. For me the benefit was in hearing a wide range of ideas from well outside my comfort zone, from people I wouldn’t otherwise meet as we are in different parts of the library world.
Note: thanks to Andrew Preater for giving me Anna Brynolf’s namE, as the leader of the living libraries session.
About Frank
I am a librarian in a biomedical research institute. I've been around a few years, long enough to know that exciting new things fall into the same familiar patterns. I'm interested in navigating a path for libraries as we slip from print through to electronic information resources.
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trauet's bookmarks
"The eagle has ceased to scream, but the parrots will now begin to chatter. The war of the giants is over and the pigmies will now start to squabble. "
Churchill, Winston on uncategorised
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"In war you can be killed only once. In politics, many times."
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"Solitary trees, if they grow at all, grow strong."
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"If you have an important point to make, don't try to be subtle or clever. Use the pile driver. Hit the point once. Then come back and hit it again. Then hit it a third time; a tremendous whack."
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"Some people regard private enterprise as a predatory tiger to be shot. Others look on it as a cow they can milk. Not enough people see it as a healthy horse, pulling a sturdy wagon."
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"The inherent vice of capitalism is the unequal sharing of blessings; the inherent vice of socialism is the equal sharing of miseries."
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"To improve is to change; to be perfect is to change often."
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"Too often the strong, silent man is silent only because he does not know what to say, and is reputed strong only because he has remained silent."
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"If I was your wife Sir, I'd poison you! Madam, if you were my wife, I'd let you!"
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"There is no finer investment for any community than putting milk into babies."
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"Once upon a time all the animals in the zoo decided that they would disarm, and they arranged to have a conference to arrange the matter. So the Rhinoceros said when he opened the proceedings that the use of teeth was barbarous and horrible and ought to be strictly prohibited by general consent. Horns, which were mainly defensive weapons, would, of course, have to be allowed. The Buffalo, the Stag, the Porcupine, and even the little Hedgehog all said they would vote with the Rhino, but the Lion and the Tiger took a different view. They defended teeth and even claws, which they described as honourable weapons of immemorial antiquity. The Panther, the Leopard, the Puma, and the whole tribe of small cats all supported the Lion and the Tiger. Then the Bear spoke. He proposed that both teeth and horns should be banned and never used again for fighting by any animal. It would be quite enough if animals were allowed to give each other a good hug when they quarreled. No one could object to that. It was so fraternal, and that would be a great step towards peace. However, all the other animals were very offended with the Bear, and the Turkey fell into a perfect panic. The discussion got so hot and angry, and all those animals began thinking so much about horns and teeth and hugging when they argued about the peaceful intentions that had brought them together that they began to look at one another in a very nasty way. Luckily the keepers were able to calm them down and persuade them to go back quietly to their cages, and they began to feel quite friendly with one another again. "
Churchill, Winston on uncategorised
6 fans of this quote
"The whole history of the world is summed up in the fact that, when nations are strong, they are not always just, and when they wish to be just, they are no longer strong."
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"Many forms of Government have been tried, and will be tried in this world of sin and woe. No one pretends that democracy is perfect or all-wise. Indeed, it has been said that democracy is the worst form of Government except all those others that have been tried from time to time."
Churchill, Winston on government
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"Golf is a game whose aim is to hit a very small ball into an even smaller hole, with weapons singularly ill-designed for the purpose."
Churchill, Winston on golf
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"It has been said that Democracy is the worst form of government except all those other forms that have been tried from time to time."
Churchill, Winston on democracy
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"We are happier in many ways when we are old than when we were young. The young sow wild oats. The old grow sage."
Churchill, Winston on age and aging
14 fans of this quote
"In those days he was wiser than he is now -- he used frequently to take my advice."
Churchill, Winston on advice
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"He is a modest little man who has a good deal to be modest about."
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3 fans of this quote
"There are few virtues that the Poles do not possess and there are few errors they have ever avoided."
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"The pessimist sees difficulty in every opportunity. The optimist sees the opportunity in every difficulty."
Churchill, Winston on opportunity
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"Some men change their party for the sake of their principles; others their principles for the sake of their party."
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"Any 20 year-old who isn't a liberal doesn't have a heart, and any 40 year-old who isn't a conservative doesn't have a brain."
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"When the eagles are silent the parrots begin to jabber."
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"He has all the virtues I dislike and none of the vices I admire."
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"When pygmies throw long shadows, it is late in the evening."
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"All men make mistakes, but only wise men learn from their mistakes."
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Johan Hancke's quote collection
I'm male from Norway and made my book on 12th March 2010.
My book as a pdf
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Quotation added by staff
Why not add this quote to your bookmarks?
The theater, bringing impersonal masks to life, is only for those who are virile enough to create new life: either as a conflict of passions subtler than those we already know, or as a complete new character. Jarry, Alfred
This quote is about theater · Search on Google Books to find all references and sources for this quotation.
A bit about Jarry, Alfred ...
Alfred Jarry (September 8, 1873 November 1, 1907) was a French writer born in Laval, Mayenne, France, not far from the border of Brittany; he was of Breton descent on his mother's side.
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sa5ohyenykcrbmmdhbr25tw23r46ifrz
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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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Love is a conflict between reflexes and reflections. Hirschfield, Mangnu
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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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Sculpture is the best comment that a painter can make on painting. Picasso, Pablo
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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 possible you've erased this fact from your memory, but Michael Olowokandi did play a couple of seasons in Boston. Olowokandi was born on April 3, 1975 in Lagos, Nigeria. His father was a diplomat who eventually moved to London. Michael was an athlete in cricket and rugby among other random sports not called basketball. [...]
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
4842.0.55.001 - Overweight and Obesity in Adults in Australia: A Snapshot, 2007–08
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 27/05/2011 First Issue
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Contents >> Excess weight and risk factors >> Excess weight and risk factors
Excess weight and risk factors
Certain lifestyle behaviours can increase the risk of a number of health conditions, but unlike factors such as age and sex, individuals can take action to alter these behaviours. For instance, healthy diet and regular exercise can prevent the onset of obesity, diabetes and cardiovascular disease. Conversely, smoking and excessive alcohol consumption are risk factors for obesity.
In the 2007-08 NHS, people were asked to report whether or not they smoked, their usual alcohol, fruit and vegetable consumption, the amount of exercise they do, and the fat content of the milk they usually drink. As data was self-reported, people may have provided responses that were perceived to be more socially desirable, such as understating the amount of alcohol they consumed.
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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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Changes related to "Allamakee County, Iowa"
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GeoLogi and Top GeoShot winners announced
17 October 2012
Geoscience Australia’s 2012
Top GeoShot winner. Aerial photo
of flood waters in Central
Queensland taken in 2009 by
Hayley Anderson.
The winners of Geoscience Australia’s 2012 Top GeoShot photo and GeoLogi short film competitions were announced at an award ceremony in Canberra today.
The GeoLogi short film competition, which is co-hosted annually by Geoscience Australia and the Australian Science Teachers Association, is open to primary and secondary schools across Australia.
The films were judged on promotion of the theme Discovering geoscience as well as their science content and creativity.
The winners are:
Primary Category (Year K-6)
• Winner: Free hot showers: Geyser by Asmita Deonath, Kaleen Primary School, ACT
• Runner-up: Earthquake Explorers by Maribyrnong Primary School, ACT
• Highly commended: Earthquakes and Tsunami by Fraser Primary School, ACT
• Highly commended: What influences the speed of erosion? by Taryn Abbott, Blackwood Primary School, SA
Junior Category (Year 7–10)
• Winner: 3112 AD by Wauchope High School, NSW
• Runner-up: Tectonic plates and continental drift by Amaroo School, ACT
• Highly commended: Finding Fossils with Dr T-Rex by Macarthur Anglican School, NSW
A total of 191 entries were received from all over Australia for this year’s Top GeoShot photo competition. The overall winner was Hayley Anderson with her aerial photo of flood waters in central Queensland taken in 2009. The People’s Choice award was taken out by Andy Marshall with his photo "Nature’s Window".
View the winning GeoLogi and Top GeoShot entries.
Geoscience Australia is hosting Australia's Earth Science Week celebrations from 14 – 20 October 2012, aligning with the international Earth Science Week theme of 'Discovering careers in Earth sciences'.
Topic contact: media@ga.gov.au Last updated: October 23, 2012
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You are here: Home > Free Data Downloads
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Which is the best one page website builder?
Team Leader
21Mar2012,20:58 #1
I have a myname.com domain and want one page website where I can create my portfolio page and write about me.
An HTML Page would also do and I don't need any front end. Can you recommend me a simple one page website building.
Is blogger a good choice?
Go4Expert Founder
21Mar2012,21:40 #2
According to me flavors.me should be your best choice
Newbie Member
1Apr2012,13:10 #3
I use only joomla and wordpress for page building as they are user friendly and don’t have to put so much time in thinking about design of page.
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About this Journal Submit a Manuscript Table of Contents
Case Reports in Pulmonology
Volume 2012 (2012), Article ID 108672, 3 pages
doi:10.1155/2012/108672
Case Report
Chronic Thromboembolic Pulmonary Hypertension: Treat the Patient Not the Haemodynamics
1Advanced Lung Disease and Transplant Unit, Royal Perth Hospital, Perth, WA 6000, Australia
2Erasmus University, Rotterdam, The Netherlands
3Women's and Children's Hospital, Adelaide, SA 5006, Australia
4Department of Cardiothoracic Surgery, Royal Perth Hospital, Perth, WA 6000, Australia
Received 4 September 2012; Accepted 2 October 2012
Academic Editors: M. Berman and J. Murchison
Copyright © 2012 Ben Dunne 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 thromboembolic pulmonary hypertension (CTEPH) is a disabling condition that is being increasingly recognised. It is unique as a cause of pulmonary hypertension in that it is surgically curable. We wish to highlight the importance of recognition and early referral of any patient who may have CTEPH even in the absence of resting pulmonary hypertension as excellent results can be achieved by restoring pulmonary vascular anatomy, reducing exercise-induced pulmonary hypertension, and reducing dead-space ventilation. We present a case that illustrates these points and discuss our experience as a referral centre for CTEPH.
1. Introduction
We report the case of a 15-year-old boy, heterozygous for the antithrombin mutation, who developed chronic thromboembolic pulmonary hypertension (CTEPH) secondary to recurrent pulmonary emboli and was successfully treated with pulmonary thromboendarterectomy.
This case highlights a number of points relevant to both primary care physicians and those working in specialist centres. In particular, we wish to emphasise that significantly symptomatic CTEPH can present with only borderline abnormal resting pulmonary haemodynamics and that it probably remains significantly underdiagnosed. Recognition of this complex condition allows the consideration of curative surgery and a return to normal life for the patient.
2. Case Report
Our patient presented at the age of 15 to the ED of an Adelaide hospital with a several-month history of breathlessness, nausea, and dull bilateral chest pain, which worsened over 7 days. He had presented on several occasions in the preceding few months to primary care doctors without an apparent diagnosis. By the time of presentation to the ED, he was noted to be hypoxaemic and had clinical signs of right heart dysfunction (tender hepatomegaly and elevated jugular venous pressure) without dependent oedema.
He was known to have antithrombin deficiency due to a heterozygous mutation, being diagnosed at the age of 7 after screening in view of a strong family history on his maternal side. His AT III levels were recorded at 38% predicted, which is lower than the generally reported range of 40–60% associated with heterozygosity [1]. He had no other known risk factors for venous thromboembolism.
CTPA demonstrated evidence of acute bilateral submassive pulmonary emboli extending from both left and right pulmonary arteries to the subsegmental level involving all lobes of the lungs. Further, there was evidence of chronic thromboembolism with webs and cutoffs in both segmental and subsegmental arteries suggesting previous pulmonary thromboembolic events.
Despite therapeutic anticoagulation, and an initial improvement, he failed to progressively improve over the following 6 months. He remained breathless on minimal exertion, was unable to attend school, and had difficulty performing activities of daily living due to intense nausea and breathlessness.
A 6-minute walk test was attempted but abandoned as he desaturated to 80% on air after just 20 meters accompanied by severe dyspnoea.
A V/Q scan demonstrated evidence of incomplete improvement in pulmonary clot burden with bilateral asymmetric mismatched defects worse on the left. Echocardiography revealed a right ventricular systolic pressure (RVSP) of 45 mmHg.
As pulmonary endarterectomy is not offered in South Australia, he was referred to Royal Perth Hospital for consideration. Repeat CTPA as well as formal pulmonary angiography revealed evidence of residual left worse than right upper and lower lobar arterial clot. Echocardiography confirmed the mildly elevated RVSP.
Right heart catheterisation was performed confirming mild resting precapillary pulmonary hypertension (Figure 1 and Table 1).
Table 1: Right heart catheter results.
Figure 1: Coronal CT Image Demonstrating Pulmonary Arterial Thromboembolic Disease.
In view of the (only) mild elevation in pulmonary vascular resistance, which appeared out of keeping with the degree of symptomatic impairment, exercise pulmonary haemodynamics were attempted but unfortunately, the patient became extremely unwell on only minimal exertion and before stable reliable exercise haemodynamics could be recorded, and the procedure was abandoned.
After discussion at the Royal Perth Hospital Advanced Lung Disease and Pulmonary Vascular Unit Multidisciplinary meeting, a consensus was reached to proceed with pulmonary endarterectomy. The decision was made due to our view that the patient’s marked symptomatology and exercise desaturation reflected a significant worsening of cardiopulmonary haemodynamics and dead space ventilation with exercise.
Pulmonary endarterectomy was carried out in the standard fashion through a median sternotomy, with cardiopulmonary bypass and circulatory arrest. The left upper lobe was successfully endarterectomised, however, the left lower lobe was only partially endarterectomised as the disease was very distal. Unfortunately there was no surgically resectable disease in the right pulmonary arterial tree.
He recovered well, with a postoperative ICU stay of 18 hours and a total post-operative stay of 6 days without complication.
His anticoagulation was managed perioperatively with daily IV antithrombin replacement (Thrombotrol) and intravenous heparin until he was reestablished on warfarin with a target INR of 3–3.5.
Six months postoperatively he is well. He has been able to return to school as well as normal activities and sports. His six minute walk test is normal (predicted for age) at 690 metres and exercise oximetry has shown no desaturation even after strenuous exercise. He continues on warfarin with a target INR of 3–3.5.
3. Discussion
Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon condition that is being increasingly recognised. Once thought to occur in less than 1% of patients who suffer from an acute pulmonary embolus, its incidence is now estimated as at least 3.8% [2] and is still probably underdiagnosed. It is unique as a cause of pulmonary hypertension as it is amenable to complete cure with a surgical procedure other than lung transplantation. Pulmonary endarterectomy affords these patients the opportunity to return to a normal level of physical functioning and quality of life [3].
This case illustrates several issues. Significant symptoms especially on exercise may develop in patients with CTEPH even in the absence of widespread clot burden. We have previously reported our experience in measuring exercise haemodynamics in patients with mild or borderline resting elevation in pulmonary vascular resistance [4]. Performing exercise haemodynamics, especially in patients with symptomatology that appears “out of keeping” from resting pulmonary haemodynamics can “uncover” significant abnormalities with exercise. This may be especially relevant to patients with CTEPH [5].
It is our view that the presence of exercise-induced pulmonary hypertension resulting from chronic thromboembolic disease may be an indication for surgery even in the absence of abnormal resting haemodynamics provided the patient is sufficiently symptomatic and where there is sufficient surgically accessible clot burden.
There is evidence that without surgery, the degree of pulmonary hypertension will worsen with time [6] and that the same functional outcome can be achieved for the patient without waiting for resting pulmonary hypertension to develop. Further, there is a lower operative mortality rate in patients with lower resting pulmonary vascular resistance (PVR) [5].
This case also highlights the importance of fully investigating unexplained breathlessness in a young patient, which in our experience is too often dismissed. This is of particular importance in the setting of a family history of thrombophilia, PAH, or cardiac disease. Pulmonary hypertension of any cause can often present with little abnormalities on examination or on basic investigation and CTEPH in particular can often present in the absence of a history of venous thromboembolism [6].
A common but underappreciated presentation of pulmonary hypertension in young patients is nausea and early satiety caused by right heart failure and gastric congestion. This is often present before the more traditionally described physical signs of right heart failure are apparent.
Most importantly, any patient suspected of potentially having CTEPH should be referred to a specialist centre with significant experience in its management. The decision to proceed with endarterectomy is complex and involves consideration of symptoms, the presence and burden of apparent surgically resectable disease, and the presence of abnormal pulmonary haemodynamics at rest and/or on exercise.
We believe that the symptomatic improvement in the subgroup of patients with mildly raised resting pulmonary pressures is often due not only to the reduction in pulmonary vascular resistance on exertion but to restoration of normal (or near-normal) pulmonary vascular anatomy and reduced dead-space ventilation as evidenced by the improved exercise oximetry in this patient.
In conclusion, we believe that this case not only highlights the importance of earlier recognition of CTEPH as well as other causes of pulmonary hypertension but also the importance of referral to a specialist centre experienced in the assessment and surgical management of this potentially curative disease. The decision to proceed with surgery involves consideration of the patient’s symptoms and pulmonary arterial anatomy and not only the haemodynamics.
References
1. D. A. Lane, T. Bayston, R. J. Olds et al., “Antithrombin mutation database: 2nd update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis,” Thrombosis and Haemostasis, vol. 77, no. 1, pp. 197–211, 1997. View at Scopus
2. V. Pengo, A. W. A. Lensing, M. H. Prins et al., “Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism,” The New England Journal of Medicine, vol. 350, no. 22, pp. 2257–2264, 2004. View at Publisher · View at Google Scholar · View at Scopus
3. C. J. Archibald, W. R. Auger, P. F. Fedullo et al., “Long-term outcome after pulmonary thromboendarterectomy,” American Journal of Respiratory and Critical Care Medicine, vol. 160, no. 2, pp. 523–528, 1999. View at Scopus
4. R. M. Fowler, A. J. Maiorana, S. C. Jenkins, K. R. Gain, G. O'Driscoll, and E. Gabbay, “Implications of exercise-induced pulmonary arterial hypertension,” Medicine and Science in Sports and Exercise, vol. 43, no. 6, pp. 983–989, 2011. View at Publisher · View at Google Scholar · View at Scopus
5. S. W. Jamieson, D. P. Kapelanski, N. Sakakibara et al., “Pulmonary endarterectomy: experience and lessons learned in 1,500 cases,” Annals of Thoracic Surgery, vol. 76, no. 5, pp. 1457–1464, 2003. View at Publisher · View at Google Scholar · View at Scopus
6. C. J. Wray and W. R. Auger, “Evaluation of patients for pulmonary endarterectomy,” Seminars in Thoracic and Cardiovascular Surgery, vol. 18, no. 3, pp. 223–229, 2006. View at Publisher · View at Google Scholar · View at Scopus
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Bibliography: Cover: The Men from P.I.G. and R.O.B.O.T.
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Title: Cover: The Men from P.I.G. and R.O.B.O.T.
Author: Peter Jones
Year: 1983
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• A Dictionary of Greek and Roman Antiquities (1890), LACUS
• Dictionary of Greek and Roman Geography (1854), IDU´BEDA
• Dictionary of Greek and Roman Geography (1854), SALO
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Minor Rhetoricians
The contemporaries of Isocrates are overshadowed by his genius; nevertheless there were in his time other speakers and teachers of ability. The only one of them who deserves serious consideration is Alcidamas, a pupil of Gorgias or of his school, who, though a rival of Isocrates, had come under the influence of the latter's style. We possess under his name a sophistical exercise, the Accusation of Palamedes by Odysseus, which is of no importance, and may be spurious, and a declamation On the Sophists, which is probably genuine; at least we may say that it is the work of an able critic and a graceful writer. His other works included two rhetorical exercises, the Praise of Death and the Praise of Nais, and a Messenian Oration, which was apparently a counterblast to the Archidamus of Isocrates.
The Sophists is really an attack on the methods of Isocrates, and is directed against the practice of laboriously composing written speeches, which are no real help to a man who wishes to be an orator, whether in the assembly or the law-courts. Certain so-called Sophists, he contends, who, while quite incapable of speaking, have practised writing, pride themselves on this accomplishment, and though they can call only one small department of rhetoric their own, claim to be masters of the complete science. He would not disparage the art of writing, but he considers it of secondary importance, while other accomplishments deserve far more attention. Any man of ability, given the time, can learn to write moderately well; but in order to speak well you must apply a careful training to the development of certain special gifts. To be able to speak extemporaneously is a very important gift; a man who possesses it can adapt himself to the mood of his audience, while one who relies on prepared orations must often miss a great opportunity, for it is beyond human powers to learn by heart enough speeches to be ready at a moment's notice to speak on any subject and to any kind of audience. A man accustomed to the use of written speeches, when forced to speak ex tempore, will not maintain his proper level of performance.1 Many arguments, of more or less value, are adduced; in all of them there is a certain cleverness.
Dionysius thought the style of Alcidamas coarse and trivial; 2 Aristotle says that he used his epithets ‘not as seasoning but as meat.’ (Rhet., iii. 3. 3). These strictures do not apply to the one surviving work. He seems to have been raised above the dead level of rhetoricians by possessing ideas; in the speech advocating the freedom of the Messenians occurred the sentence, ‘God has made all men free; nature has made no man a slave’; and his description of the Odyssey as ‘a noble mirror of human life,’ is a fine expression in itself, though Aristotle objects that such ornaments detract from the value of a speech, as giving the impression of over-preparation (Arist., Rhet., iii. 3. 4).
Polycrates, a rhetorician of the same period, is known to have composed a fictitious Accusation of Socrates, to which Isocrates refers.3 His Encomium of Busiris, the cannibal king of Egypt, stirred Isocrates to write his own Busiris, in order to show how such a theme ought to be treated. Dionysius found his style inane, frigid, and vulgar (de Isaeo, ch. xx). Lycophron, an imitator of Gorgias, is quoted several times by Aristotle; and Cephisodorus, the best known rhetorician of the school of Isocrates, wrote an admirable defence of his master against the attacks of Aristotle.4
These minor teachers, who are mentioned only as offshoots from the prominent schools, had no permanent influence on the growth either of rhetoric or of oratory.
1 The truth of this maxim is illustrated by our records of the impromptu performances of Demosthenes; see below, p. 190.
2 de Isaeo, ch. xix.,παχύτερον ὄντα τὴν λέξιν καὶ κοινότερον”.
3 Busiris, §§ 5-6. He endeavoured to make Socrates responsible for the misdeeds of Alcibiades.
4 Dion., de Isocrate, ch. xviii.: “τὴν ἀπολογίαν τὴν πάνυ θαυμαστὴν ἐν ταῖς πρὸς Ἀριστοτέλη ἀντιγραφαῖς ἐποιήσατο”.
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• Aristotle, Rhetoric, 1406b
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• Isocrates, Busiris, 5
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• A Dictionary of Greek and Roman Antiquities (1890), DIADE´MA
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• Smith's Bio, M. Favo'nius
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7/16/10
Obama Cool With Cutting Food Stamps To Pay For Education (We're Doomed)
Obey: White House Suggested Cutting Food Stamps to Pay for Education Program
By ANNIE LOWREY 7/16/10 5:04 PM
This entire interview with Rep. Dave Obey (D-Wis.), the head of the House Appropriations Committee and a powerful veteran member of Congress, who is retiring this year, is worth a read. But one passage is particularly striking. Obey is discussing his proposal to divert funds from the Obama administration’s Race to the Top education program to save teachers’ jobs. Due to the states’ fiscal crises, as many as 200,000 local government employees, many of them teachers, might lose their jobs in the coming year.
The proposal made it in to the House war-funding bill, which needs a Senate vote. The White House has threatened to veto the war-funding bill if it contains Obey’s change. Here is the quote, from an interview with The Fiscal Times:
The secretary of education [Arne Duncan] is whining about the fact he only got 85 percent of the money he wanted .… [W]hen we needed money, we committed the cardinal sin of treating him like any other mere mortal. We were giving them over $10 billion in money to help keep teachers on the job, plus another $5 billion for Pell, so he was getting $15 billion for the programs he says he cares about, and it was costing him $500 million [in reductions to the Race to the Top program]. Now that’s a pretty damn good deal. So as far as I’m concerned, the secretary of education should have been happy as hell. He should have taken that deal and smiled like a Cheshire cat. He’s got more walking around money than every other cabinet secretary put together.
It blows my mind that the White House would even notice the fight [over Race to the Top]. I would have expected the president to say to the secretary, “Look, you’re getting a good deal, for God’s sake, what this really does is guarantee that the rest of the money isn’t going to be touched.” We gave [Duncan] $4.3 billion in the stimulus package, no questions asked. He could spend it any way he wants. … I trusted the secretary, so I gave him a hell of a lot more money than I should have.
My point is that I have been working for school reform long before I ever heard of the secretary of education, and long before I ever heard of Obama. And I’m happy to welcome them on the reform road, but I’ll be damned if I think the only road to reform lies in the head of the secretary of education.
We were told we have to offset every damn dime of [new teacher spending]. Well, it ain’t easy to find offsets, and with all due respect to the administration their first suggestion for offsets was to cut food stamps. Now they were careful not to make an official budget request, because they didn’t want to take the political heat for it, but that was the first trial balloon they sent down here. … Their line of argument was, well, the cost of food relative to what we thought it would be has come down, so people on food stamps are getting a pretty good deal in comparison to what we thought they were going to get. Well isn’t that nice. Some poor bastard is going to get a break for a change.
If Obey is right about this, it is, in a word, horrifying. Food stamps are not particularly generous. They help families that are often desperate. They are just about the last thing that should get cut in the midst of a horrific employment crisis in the wake of a job-sapping recession.
The New Guy Will Vote To Keep Millions Out Of The Poor House
Rockefeller: Goodwin Will Vote for Unemployment Benefits Extension
Sen. Jay Rockefeller (D-W.Va.) just answered the question on the minds of all the people who have lost their unemployment benefits in recent weeks: Senate appointee Carte Goodwin (D-W.Va.) will vote in favor of the unemployment benefits extension bill that the Senate will take up shortly after he is sworn in at 2:15 p.m. on Tuesday. That means there will be 60 votes in favor of the bill, enough to overcome a Republican filibuster.
Rockefeller announced Goodwin’s anticipated vote for him as he made remarks during a press conference today. West Virginia Gov. Joe Manchin (D) announced during the presser that Goodwin will replace the late Sen. Robert Byrd (D).
Friday Cartoon Fun: Bob Reich Edition
...Although the financial reform bill may have clipped some of Goldman’s wings — its lucrative derivative business may require Goldman to jettison its status as a bank holding company, and the access to the Fed discount window that comes with it — the main point is that the Goldman settlement reveals everything that’s weakest about the financial reform bill.
The American people will continue to have to foot the bill for the mistakes of Wall Street’s biggest banks because the legislation does nothing to diminish the economic and political power of these giants. It does not cap their size. It does not resurrect the Glass-Steagall Act that once separated commercial (normal) banking from investment (casino) banking. It does not even link the pay of their traders and top executives to long-term performance. In other words, it does nothing to change their basic structure. And for this reason, it gives them an implicit federal insurance policy against failure unavailable to smaller banks — thereby adding to their economic and political power in the future. [emphasis mine]
The bill contains hortatory language but is precariously weak in the details. The so-called Volcker Rule has been watered down and delayed. Blanche Lincoln’s important proposal that derivatives be traded in separate entities which aren’t subsidized by commercial deposits has been shrunk and compromised. Customized derivates can remain underground. The consumer protection agency has been lodged in the Fed, whose own consumer division failed miserably to protect consumers last time around.
On every important issue the legislation merely passes on to regulators decisions about how to oversee the big banks and treat them if they’re behaving badly. But if history proves one lesson it’s that regulators won’t and can’t. They don’t have the resources. They don’t have the knowledge. They are staffed by people in their 30s and 40s who are paid a small fraction of what the lawyers working for the banks are paid. Many want and expect better-paying jobs on Wall Street after they leave government, and so are shrink-wrapped in a basic conflict of interest. And the big banks’ lawyers and accountants can run circles around them by threatening protracted litigation....
From Robert Reich
7/15/10
The Oil Gusher Is Capped And Undergoing Testing
Apparently the cap is in place and BP is testing to make sure the pressure won't blow up the floor of the sea. My BP feeds here, BP's actual feeds page (now updated with all feeds on one page) is here.
7/13/10
Dylan Ratigan: "Thanks For Nothing!"
h/t digby
George Steinbrenner: R.I.P.
New York Yankees owner George Steinbrenner died this morning, Tuesday, July 13, 2010, at the age of 80. Steinbrenner suffered from a heart attack and passed away at St. Joseph's Hospital in Tampa, Fla.
From HuffPo
7/12/10
Those Greedy, Mortgage Defaulting, Rich Bastards!
I am one of those homeowners who is underwater. I am not one of the rich ones. My mortgage is about 280K for a condo worth about half that. Eat the rich.
Monday Bonus Cartoon Fun: Things Change Edition
h/t Diane Ravitch
Monday Cartoon Fun: Jobless Edition
Dance Of A Survivor
This video of a family dancing at Auschwitz with their survivor grandpa is stirring up some controversy. As an atheist Jew (oxymoron?) I have to side with the folks who think it's very cool he lived long enough to celebrate his survival, life, children and grandchildren.
What do you think?
The Achievement Gap: It's About Poverty. Still
Hopefully one day, probably long after I am dead and gone, folks will realize what we have (or have not) done to make a better world for our children. We could start by acknowledging simple truths, but this too is a problem.
Left Ed: Race, Income and School Reform
...In 1966, the Coleman Report revealed the Inconvenient Truth that the correlation of low student achievement to race and poverty is so strong that "schools generally can not overcome" the inequalities imposed on them by the society at large. [emphasis mine] Children born to families with socio-economic advantages in our society will continue to have their advantages reinforced in the schools they attend, while children born to families with more challenging circumstances will chronically lag behind.
Today, merely pointing this fact out often gets you labeled by the reformist crowd as "making excuses" for bad schools. But when one wants to understand the weather outside, it makes sense to start by recognizing how clouds make rain. Complex systems such as schools have multiple inputs, which should all be considered in policy making....
h/t Open Left
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Place:Herbaijum, Franekeradeel, Friesland, Netherlands
Watchers
NameHerbaijum
Alt namesHerbayumsource: Family History Library Catalog
Hjerbeamsource: Fryslân-Fryske Akademy
TypeVillage
Coordinates53.18473°N 5.49498°E
Located inFranekeradeel, Friesland, Netherlands
Contents
General Info
• Herbaijum, a village in the gemeente (municipality) of Franekeradeel.
Research Tips
Maps and Gazetteers
Images
Kerken/Churches
• Herbaijum (Hjerbeam), Hervormde kerk
Burial Information
Links
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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'm a qualified software engineer and I've been reading some articles about start ups.
So my question is when it comes to making a start-up all these different websites refer to the fact that it is "okay to have competitors". My question is how many successful start ups? start with a singular developer with large already situated competitors?
share|improve this question
1 Answer
up vote 2 down vote accepted
It's perfectly okay to have competitors. In fact, you should think extra hard about your idea if it doesn't look like there are any competitors out there. Maybe you're the first one, but probably not.
There's plenty of startups that had competitors when they bootstrapped. Air B&B had couchsurfing, Thumbtack had Angie's list and Red Beacon.
And Facebook had MySpace.
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1. Skip to navigation
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Source link: http://archive.mises.org/15372/lecture-on-bank-mechanics/
Lecture on Bank Mechanics
January 20, 2011 by
As part of the Mises Academy’s continuing efforts to provide ever higher quality service to students, in Robert Murphy’s Anatomy of the Fed class, in addition to the live lectures, we are trying out providing separately-recorded, higher video-quality versions of each lecture.
In the lecture below (click here for the slides), Robert Murphy walks you through an analysis of bank mechanics to be found in Rothbard’s Mystery of Banking (the main textbook for the course). The book, published for the first time not so long ago by the Mises Institute, is itself a wonderful pedagogical accomplishment. And now, to be able to be guided through it, step by step, by an economist and educator like Dr. Murphy, is truly marvelous. The opportunities for the public to educate itself regarding the science that Mises called “the pith of civilization” are expanding and deepening with every passing week, which hopefully bodes well for civilization itself.
This online course, as well as 5 other winter courses, are still open for enrollment at the Mises Academy.
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Add a Serial port to the PowerPC Linkstation
From NAS-Central Buffalo - The Linkstation Wiki
Revision as of 11:45, 15 November 2009 by Marcaureleii (Talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to: navigation, search
Originally by frontalot and nix from linkstationwiki.org
The console is the text output device for system administration messages. These messages come from the kernel, from the init system and from the system logger. On modern small computers the console is usually the computer's attached monitor and keyboard. The LinkStation, however, doesn't have monitor output; instead, it uses a serial connection for console output. Not only does the serial console provide valuable debugging output, it also allows root access!
Most of this information courtesy of http://www.type-g.com, http://www.kurobox.com, http://www.tldp.org, http://www.larwe.com, and John Taylor.
Also look at: How to attach a serial port to the Kurbox/KuroboxHG
Contents
Prerequisites
• (1)Electronic-grade soldering iron
• (1) 0.015", 1 oz silver-bearing solder
• (1) Desolder braid, solder sucker, or Servisol Soldamop
• (1) 0.1” series PCB header plug, 4-way
• (1) Serial converter (or build your own - see Stage 4)
• (1) Tweezers
• (1) Anti-static wrist strap
Stage 1 - Access the Board
• Disassemble the LinkStation.
• Remove the main circuit board by removing the 4 mounting screws:
• Place the circuit board on a static-free work area:
The Circuit Board
Stage 2 - Attach Header to the Board
• The console header needs to be attached to the J1 pad:
• Remove the preexisting solder from J1:
• Solder the PCB header to J1 so that the pinouts face towards the IDE header
Solder the PCB header to J1 so that the pinouts face towards the IDE header
J1 Pinout
Pin Signal
1 Transmit (TX)
2 Receive (RX)
3 Power (3.3V)*
4 Ground (GND)
Stage 3 - Enable Full Serial Tx/Rx
Method 1 (easier)
• To enable write support across the serial port bridging r76 with a short piece of wire or just with some soldering
• IN SHORT, ALL THAT IS NECESSARY TO GET 2 WAY SERIAL COMMUNICATION ON THE KURO HG, HD, AND PPC LINKSTATIONS IS TO BRIDGE THE CONTACTS FOR THE SERIES RESISTOR AT R76.
http://forum.buffalo.nas-central.org/viewtopic.php?f=42&t=9186
Method 2 (original)
To enable write support across the serial port, remove the 10K ohm pullup resistor from R75 and install it , or another 10K ohm pullup resistor, to R76. From http://www.larwe.com
• To enable write support across the serial port, remove the 10K ohm pullup resistor from R75 and install it , or another 10K ohm pullup resistor, to R76.
HG hardware requires different procedure. Instead of adding 10K ohm, a short wire connecting two pads perpendicular to R69 worked for me (I replaced R69 with 10K ohms, you can keep the original part.)
Desoldering Tip
To desolder an SMD resistor you can apply the following trick:
• Take a short piece of blank wire and bend one end into a small U-shape using some small pliers. The U-shape should be as such that you can touch the sides of both ends of the resistor at the same time. The width of the U should basically be the length of the resistor.
• Wrap the other end of the wire around the tip of your soldering iron - while it is still cold. You now have a small U-shaped tool to remove the resistor.
• Heat up the iron. When the wire is hot enough, heat up the solder at both ends of the resistor and gently pull the resistor away from the pads with the U-shaped tip. Be careful, the resistor likes to end up on the floor.
Stage 4 - The Serial Converter
The serial port signals from the processor are only 3.3V. For proper RS-232 12V signaling, an RS-232 level shifter needs to be added. These are very common in PDA serial cables also, but can be purchased
Models other than KuroPro
If you are attaching a serial header pin onto the main board, you may want to consider:
• Using the header pin unit with a 90 degree bend, or you might not be able to close the case
• Soldering it with the pins toward the interior, rather than toward the case. This allows easier access, since if the pins face the case side they would be very close to the metal side. This would make access is so tight that one might end up taking the board out to get plug fitted on the pins.
Build your own LVTTL/RS232 or LVTTL/USB interface
Buy your own TTL Level Shifter
Usage considerations for the TTL-232R-3V3
TTL-232R-3V3 USB to TTL Serial Converter Cable
A very similar TTL/USB converter cable that uses a chip by FTDI (the same chip is used in the SCON-KIT ) can be obtained, but the pinout at the connector end would need to be reassigned: Spec Sheet w/ pinout, wire colors & other info
Mouser Part # 895-TTL-232R-3V3 $20.00
Mouser Part # 517-929400-01-04 $0.32
A working/tested pinout/wire-color scheme is:
Color Pin Number Signal
yellow 1 TXD
orange 2 RXD
unused 3 VCC
black 4 GND
• Solder the 4-pin header to the board. Make sure you don't have shorts.
• You will need to switch wires on the TTL-232R-3V3 cable. Use a sharp object to lift the plastic tabs and carefully pull the wires out. Rearrange them according to the table above (black, empty, orange, yellow, empty, empty) and slide those wires back in. Tape the other wires to make sure they don't short anything.
• When plugging in the cable, make sure black aligns with GND, yellow with TXD, and orange with RXD.
• Connect the USB cable to your computer, start a terminal program with the right settings.
• Turn on the device, you should see output from the bootloader in couple seconds.
Stage 5 - Using the Serial Console
• You may access the serial console using Windows HyperTerminal (included with Windows) or [TeraTerm Pro].
Serial Port Settings
Data Settings
Baudrate 57600
Data bits 8
Stop bits 1
Parity None
Flow Control None
External Links
Personal tools
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| Edit | | History |
From DDO wiki
(Redirected from Bound to Account)
Jump to: navigation, search
Definitions of various bind statuses of items. For resurrection location and its mechanism, see Bind point.
Contents
[edit] Unbound
Most randomly generated items are not bound to the character, and can freely be used, traded, mailed, and auctioned.
• By using these items, they will suffer consequential permanent durability damage from a wear-and-tear effect.
• By spending Khyber Dragonshard Fragments, players can bind their equipment at the Stone of Change .
• Unbound items become Bound to Character; Bound to Account items remain Bound to Account.
[edit] Bound to Character (BTC)
Items that are already bound to a character and thus cannot be traded, mailed, or auctioned.
• Bound items will not take permanent durability damage while repairing.
[edit] Bound to Account (BTA)
Items that are bound to a account can only be traded to a character on the same account and server, using the Shared Bank. Bound to Account items cannot be mailed, not even to characters on the same account base on the same server. Cannot be auctioned.
• Introduced with Module 9.
• Free to Play and Premium players must purchase Account Bank access to transfer these type of items.
• Like Bound to Character items, BTA items will not take permanent durability damage.
[edit] Binds on Acquire (BOA)
Items with this status become Bound (either to Character or Account), once taken from a chest or a reward list.
[edit] Binds on Equip (BOE)
Items on this status can be traded, mailed, and auctioned, but once they are equipped they become either Bound to Character (BTCOE) or Bound to Account (BTAOE).
Note: Upgrading a Green Steel item at an altar within the Shroud will also bind the item to the crafter.
[edit] See also
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Widow's Lotus
consumed
In-Game Descripton
The petal of a dark flower that floats on water. Removes plague from the user's body.
This flower was fastened to the corpses of those who died of plague during their burial, but later it became an emblem of the people claimed by the disease.
Use
Cures plague status effect
Availability
Location Cost Amount Comment
3-1 1000 unlimited Buy from the Once Royal Mistress
3-1 treasure 2 On the platform overlooking the approach to the Fool's Idol fight
3-1 treasure 1 As you exit the cell at the start of the level, turn left and it's in the second cell you pass
5-1 2000 unlimited Buy from the Filthy Woman
5-2 2000 unlimited Buy from the Filthy Woman
5-2 treasure 3 Just past the Filthy Woman, on a platform overhead
5-3 treasure 2 On the platform between the two sets of ladders as you enter the level from the Dirty Colossus arena
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-ShareAlike 3.0 License
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Error!
Success!
Enhancing VisualSVN Server to Allow Anonymous Access
0
kicks
Enhancing VisualSVN Server to Allow Anonymous Access (Unpublished)
I have been running VisualSVN Server for my repositories for a little while now and especially love how painless the setup is. Not to mention that VisualSVN Server is 100% free! One part that I especially liked was the part I have been missing and that is anonymous access to repositories.
Kicked By:
Drop Kicked By:
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Grim-N-Gritty (3.5e Sourcebook)/Called Shots
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Contents
Called Shots
Called Shots are attacks that a character tries to target at a specific location on your opponent’s body, in an attempt to inflict damage that is more severe, pierce a weak point in the target’s armor, or disable a limb.
Rather than having a body-part centered Called Shot system, the GnG uses an effect-based system. In other words, you do not specify the part of the body you wish to hit. Instead, you select a set of effects you desire to inflict upon your enemy.
Procedure
Called shots use the following procedure:
• You declare your intent to perform a Called Shot before you roll the dice for your attack.
• You select the effects of your Called Shot. (Each effect imposes a negative modifier to your attack roll.)
• You provoke an attack of opportunity from your target when you initiate the Called Shot.
• You make your attack, with the appropriate negative penalties.
• If your attack hits and you chose a Penetration Effect, your target makes a Reflex save to avoid having its armor penetrated.
• If your attack hits, you chose a Condition Effect, and you inflicted at least 1 HP damage to your target (after Protection, Damage Reduction, Energy Resistance, and similar attributes are applied), your target makes a Fortitude save against the condition.
• If your target fails the save, the effect takes place.
You may not perform Called Shots as attacks of opportunity.
You may not perform Called Shots against targets with any degree of concealment.
Effects
You may select multiple effects for a single Called Shot. The penalties to your attack roll are cumulative.
Called Shot effects are broken into two general categories: Penetration Effects and Condition Effects.
Penetration Effects
Penetration Effects attempt to bypass a portion of the target’s Protection score. You seek a vulnerable spot in the target’s armor and natural armor. Then, you strike at that point.
If your attack hits, your target makes a Reflex saving throw against 10 + the Relative Degree of your attack roll. If the save fails, you ignore one-half of your target’s Protection score.
The attack penalty for your Called Shot depends on the type of armor worn by your target. If your target wears mixed types of armor, choose the highest penalty.
• Light Armor: -4 attack penalty.
• Medium Armor: -6 attack penalty.
• Heavy Armor: -8 attack penalty.
• Natural Armor: -8 attack penalty.
• Force-based Armor: A Penetration Effect is impossible.
Penetration Effects cannot reduce the effectiveness of your target’s Damage Reduction or Energy Resistance.
Condition Effects
Condition Effects impose a particular penalty, condition, or damage modifier to the target.
If your attack hits and inflicts at least 1 HP damage to your target, your target makes a Fortitude save against 10 + the damage inflicted by your attack. If the save fails, your target suffers all of the conditions imposed by your Called Shot.
Condition effects include the following:
Blindness
Attack Penalty: -6.
Result: Your target is blinded for one round.
Special: Creatures with no nervous system are immune to this effect.
Daze
Attack Penalty: -4.
Result: Your target is dazed for one round.
Special: Creatures with no nervous system are immune to this effect.
Deafness
Attack Penalty: -4.
Result: Your target is deafened for 1d4+1 rounds.
Special: Creatures with no nervous system are immune to this effect.
Disabled Arm
Attack Penalty: -8.
Result: Your target suffers a –2 penalty to attack rolls, Strength checks, and all skill checks based on arm use, such as Climb, Craft, Disable Device, Escape Artist, Forgery, Alchemy, Heal, Open Lock, Pick Pocket, Swim, and Use Rope checks. If all arms are disabled, the victim cannot manipulate items. A disabled arm automatically drops any items it holds.
Note: The penalties for multiple disabled arms do not stack, though they do stack with other body parts.
Disabled Ear
You disable your target’s ear, not only disrupting his hearing, but also disturbing his equilibrium.
Attack Penalty: -4
Result: Your target suffers a –2 penalty to initiative rolls, Defense rolls, Reflex saves, and all skill checks based on the sense of hearing or equilibrium, such as Balance, Bluff, Climb, Diplomacy, Intimidate, Listen, Perform, and Tumble. If all ears are disabled, the victim is deafened.
Note: The penalties for multiple disabled ears do not stack, though they do stack with other body parts.
Disabled Eye
Attack Penalty: -8.
Result: Your target suffers a –2 penalty to Dexterity checks, attack rolls, Defense rolls, Reflex saves, and all skill checks based on vision, such as Appraise, Craft, Decipher Script, Disable Device, Forgery, Search, Sense Motive, Spot, and Survival (for tracking). If all eyes are disabled, the victim is blinded.
Note: The penalties for multiple disabled eyes do not stack, though they do stack with other body parts.
Disabled Head
You cause a concussion, brain damage, spinal damage, or similar effect.
Attack Penalty: -8.
Result: Your target suffers a –2 penalty to all rolls (except damage).
Special: Creatures with no nervous system, brain, or some centralized organ for cognition are immune to this effect.
Note: The penalties for multiple disabled heads do not stack, though they do stack with other body parts.
Disabled Leg
Attack Penalty: -6.
Result: Your target suffers a –2 penalty to Defense rolls, Reflex saves, Dexterity checks, and all skill checks based on leg use, such as Climb, Swim, Jump, Ride, Tumble, Balance, and Move Silently checks. The victim cannot run or charge. If all legs are disabled, the victim can only move by crawling and loses any Dexterity bonus to Defense.
Note: The penalties for multiple disabled legs do not stack, though they do stack with other body parts.
Severe Bleeding
You open a major artery in your opponent’s body and cause severe bleeding.
Attack Penalty: -8.
Result: One round after the attack, the victim makes a DC 12 Fortitude save. If he fails the save, he becomes fatigued from blood loss. If he succeeds, next round (and each round thereafter), he must make another Fortitude save with a cumulative +1 increase in the DC.
Once the victim becomes fatigued, the DC of the Fortitude save resets to 15. The consequence of failing the save is now exhaustion.
Once the victim becomes exhausted, the Fortitude save DC resets again. Now, the victim makes the save to avoid death from blood loss.
Binding the wounds or performing some other treatment to stop the bleeding causes the need for saves to end. The victim must recover from fatigue and exhaustion in the normal manner.
Special: Creatures with no circulatory system are immune to this effect.
Note: In real life, you would die in a matter of seconds from severe bleeding, without regard for your physical toughness.
Silent Kill
You kill your opponent without your victim uttering a sound.
Attack Penalty: -4.
Result: If your attack inflicts enough damage to disable, kill, or render your target unconscious, your target cannot make any noise to draw attention to its incapacitation. It is not possible for the victim to scream or groan. Nothing more than a slight, faint gasp escapes its lips.
Special: Creatures with no nervous system or sensitivity to pain are immune to this effect.
Stab and Grab
You stab your weapon through your opponent’s body (usually through an arm or leg). Then, with your free hand, you grab the weapon as it pokes out on the opposite side and twist. This initiates a grapple.
Special Requirements: To perform this Called Shot, you must meet the following requirements:
• You must have the Improved Grapple feat.
• You must wield a one-handed slashing or piercing melee weapon.
• You must have one hand free.
• If you use a slashing weapon, it must have a single edge. (Otherwise, you slice yourself.)
Attack Penalty: -4.
Result: The weapon punctures your target, and you grab it. You immediately perform a grapple check, with a +4 bonus on your roll, to initiate a grapple and inflict damage on your target. If you win the check, you are now grappling.
As long as the weapon remains lodged in your opponent’s body, you gain a +4 bonus on all grapple checks against that enemy.
Removing the Weapon: An opposed grapple check is necessary to remove the weapon from your opponent’s body. Either you or your opponent may initiate the check. When the weapon is removed, your victim suffers damage from the weapon. Do not count Strength modifiers, specialization bonuses, Relative Degree, skill-based damage modifiers, and the like when figuring the damage. Since the weapon already pierces your enemy’s flesh, the damage ignores Protection.
If the weapon is barbed, double the damage dice it inflicts when removed.
Stun
Attack Penalty: -6.
Result: Your target is stunned for one round.
Special: Creatures with no nervous system or sensitivity to pain are immune to this effect.
Vital Strike
You penetrate a vital organ to inflict severe damage.
Attack Penalty: -8.
Result: Double all damage inflicted upon the target after applying Protection, Damage Reduction, Energy Resistance, and similar defenses.
Special: Creatures with no discernible anatomy, oozes, undead, and the like are immune to this effect.
Recovery of Disabled Body Parts
If a nonlethal attack disables a body part, the part recovers in 2d4 minutes.
If a lethal attack disables a body part, the part takes a considerable time to heal.
Natural Healing: After a normal day’s rest, roll d%. If the result is equal to or less than your Constitution score, then your disabled body part recovers. (Make a separate roll for each disabled part.) Any significant interruption during your rest prevents you from healing that night. Any HP loss during a cycle prevents recovery.
If you undergo complete bed rest for an entire day, the d% chance that your body part will recover equals twice your Constitution score.
If a healer successfully tends your injuries, your chance of recovery equals twice your Constitution if you have normal rest and three times your Constitution score with complete bed rest.
If you cannot recover lost HP because you are dying and unstable, then you cannot recover disabled body parts.
Surgery: A DC 15 check with Heal skill can restore a disabled body part as a full-round action. (-5 penalty to do so as a standard action, -10 penalty to do so as a move action, -15 penalty to do so as a swift action)
Regeneration: Creatures with the regeneration special ability recover disabled body parts as soon as they recover all lost HP.
Extraordinary Healing: You may direct items, special abilities, and powers that heal a particular amount of HP to restore a disabled body part. Roll the dice to determine the amount of HP healed. Then, roll 1d20. If the d20 result is equal to or lower than the HP amount, the disabled part is restored.
Extraordinary healing methods used to restore disabled body part do not restore lost HP.
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Difference between revisions of "Android"
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=== Community Ports ===
=== Community Ports ===
[[OpenMoko Freerunner|OpenMoko]]
+
[[OpenMoko|OpenMoko Freerunner]]
Revision as of 02:20, 7 April 2009
Contents
Overview
Android (wikipedia entry) a software platform and operating system written by Google and the Open Handset Alliance, designed for use in small form factor devices and smartphones.
See Android Notes for miscellaneous notes on Android.
See Android on OMAP for tips for putting Android on OMAP-based platforms.
Stack
Android Stack
http://developer.android.com/guide/basics/what-is-android.html
Devices
Production
HTC Dream as the T-Mobile G1 and the Google ADP1 HTC Magic
Community Ports
OpenMoko Freerunner
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JuiceWare Xd Socket4
From eLinux.org
Revision as of 09:12, 14 July 2007 by Chris (Talk | contribs)
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This is a good point at which to test the unit. Plug it in without the xD card to make sure that the Juicebox powers up. Running the mem tests (hold play and rewind as you power it up) should indicate there is no MMC or cartridge detected. Now power down and put an xD card in the socket. The mem test should detect that there is a cartridge and will show a manufacturer ID and memory size. If everything is working properly you will get the same checksum each time the test is run.
Next build the JuiceWare Test Image. Use JuiceBox_JTAG interface to write the image to the xD card. Once the image is written power cycle the JuiceBox and you should see the "Juicebox demo #2" running.
At this point the unit should be fully functional. If there are any problems see the troubleshooting section JuiceWare Xd Socket5. Get everything working before proceeding.
You may want to glue the top half of the cartridge to the PCB for added strength. Don't get any glue into the socket or on the gold fingers. In case there is a problem in the future (loose wire etc.) it is best not to glue the back half on, the two screws will be enough to hold it together.
Next: JuiceWare Xd Socket5 - Troubleshooting Back to main JuiceWare Xd Socket menu.
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Ransom, Ralph on adversity
4 fans of this quote
"Am I willing to give up what I have in order to be what I am not yet? Am I able to follow the spirit of love into the desert? It is a frightening and sacred moment. There is no return. One's life is charged forever. It is the fire that gives us our shape."
Richards, Mary Caroline on adversity
4 fans of this quote
"Every man has a rainy corner of his life whence comes foul weather which follows him."
Richter, Jean Paul on adversity
"I have become my own version of an optimist. If I can't make it through one door, I'll go through another door -- or I'll make a door. Something terrific will come no matter how dark the present."
Tagore, Rabindranath on adversity
28 fans of this quote
"If we study the lives of great men and women carefully and unemotionally we find that, invariably, greatness was developed, tested and revealed through the darker periods of their lives. One of the largest tributaries of the RIVER OF GREATNESS is always the STREAM OF ADVERSITY."
Robert, Cavett on adversity
"In a dark time, the eye begins to see."
Roethke, Theodore on adversity
7 fans of this quote
"Over every mountain there is a path, although it may not be seen from the valley."
Rogers, James on adversity
4 fans of this quote
"The worst thing that happens to you may be the best thing for you if you don't let it get the best of you."
Rogers, Will on adversity
15 fans of this quote
"People are like stained -- glass windows. They sparkle and shine when the sun is out, but when the darkness sets in, their true beauty is revealed only if there is a light from within"
Ross, Elizabeth Kubler on adversity
10 fans of this quote
"To endure is the first thing that a child ought to learn, and that which he will have the most need to know."
Rousseau, Jean Jacques on adversity
5 fans of this quote
"Adversity is a great teacher, but this teacher makes us pay dearly for its instruction; and often the profit we derive, is not worth the price we paid."
Rousseau, Jean Jacques on adversity
3 fans of this quote
"When something an affliction happens to you, you either let it defeat you, or you defeat it."
Russell, Rosalind on adversity
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New Dutch Robot Pumps Your Gas
Posted 5 Feb 2008 at 18:48 UTC by steve
Reuters is carrying a story about a Dutch robot called TankPitStop that can pump your gas at the gas station. A video of the robot in action is avilable online. The inventor was inspired by seeing cow milking robots, which are now very common in dairy industry. He wondered, "if a robot can do that, then why can't it fill a car tank?". So he built the TankPitStop robot. It is said to work on any car provided the gas tank cover can be opened without a key and the robot has the car's contours and dimensions on file so it can avoid scratching the surface as it moves. As is always the case with the latest robot, they're claiming this is the first ever robot of it's kind but gas pumping robots have been around for at least a decade. Anyone have a link to an older one? The blogosphere seems fascinated by this story.
See more of the latest robot news!
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Musashi no Ken - Tadaima Shugyou Chuu
From StrategyWiki, the video game walkthrough and strategy guide wiki
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This page is a stub. Help us expand it, and you get a cookie.
Musashi no Ken - Tadaima Shugyou Chuu
Developer(s) Taito Corporation
Publisher(s) Taito Corporation
Japanese title 六三四の剣 ただいま修行中
Release date(s)
August 8th, 1986
Genre(s) Action
System(s) Famicom
Players 1-2
Neoseeker Related Pages
Musashi no Ken - Tadaima Shugyou Chuu (roughly translated, Sword of Musashi - Now in the Middle of Training) is a Famicom game developed by Taito in 1986. It is the Famicom adaption of an early 80s manga and anime known as Musashi no Ken, which its plot features the son of two Kendo champions named Musashi. He strives to become as great at Kendo as his parents. The entire story centers around the world of Kendo and its up and coming competitors. The anime is broken up in to two parts. The first part follows Musashi's early years in grade school while the second part follows his high school years. In the first episode, Musashi befriends an Akita puppy who is by his side throughout the series.
The Famicom title was originally planned as a home port of the 1984 weapon-based fighting game, Great Swordsman, developed by SETA and published by Taito, which in fact its vs. mode resembles the Kendo mode of Great Swordsman. The Famicom game has two modes. The single player mode depicts Musashi in the middle of his training. He must run through several obstacle courses collecting swords and other items along the way. At the same time, his pet Akita will be running the course behind him. Musashi must not fall too far behind his dog. After completing three courses, Musashi will be entered into a Kendo tournament. He must defeat five competitors to win the tournament. The swords that Musashi collects during the obstacle courses provide him with access to special strike moves if he has collected enough. If you succeed in winning, the game will continue from the beginning at a higher level of difficulty. After winning the championship a second time, the game is over.
The second mode is a two player vs. mode. Each player selects from a roster of competitors, and selects them secretly by pressing different inputs on the control pad. Once five selections have been made, the selections are revealed. Each player then squares off in a Kendo match with each of their selections. The winner is the player with three or more victories.
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Cocle
From Wikitravel
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Coclé is one of the provinces of Panama.
[edit] Regions
[edit] Cities
Penonomé — provincial capital
[edit] Other destinations
[edit] Understand
[edit] Talk
[edit] Get in
[edit] Get around
[edit][add listing] See
[edit] Itineraries
[edit][add listing] Do
[edit][add listing] Eat
[edit][add listing] Drink
[edit] Stay safe
[edit] Get out
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Haines
From Wikitravel
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Haines is a small port community (population about 2,000) in Southeastern Alaska. It is located on the shores of the Lynn Canal, the state's longest fjord, and surrounded by glacier-covered mountains of the Coast Range.
[edit] Understand
If you loved the TV show "Northern Exposure," you'll love the down-home feel of Haines. It's the kind of laid-back place you picture when you think about an Alaskan town. The first thing you'll notice when you arrive is how scenically beautiful Haines is.
Haines is blessed with surrounding natural areas and wildlife in what is known as the "Valley of the Eagles." The area is a magnet for bald eagles, drawn by the warm open water and abundant supply of salmon. More than 3,500 of the birds visit from October to February – during that time a dozen eagles may share a single tree limb.
[edit] Get in
There are three main ways to get to Haines, which makes Haines more accessible than most other southeast Alaskan communities of its size. First, you can drive to Haines from Haines Junction, Yukon, of the Alaska Highway. If this is your route, Haines is the very end of the Haines Highway, about 155 miles.
You can fly into Haines, but there are no large commercial flights. More likely you will fly into Juneau on Alaska Airlines, and from there catch a smaller bush carrier or charter a flight. The Haines Airport is on the Haines Highway about 4 miles west of town.
The third, and probably most popular, way to Haines is by boat. The primary mode of inter-Alaskan transportation is by the Alaska Marine Highway. The Lynn Canal route of the ferry system (Juneau-Haines-Skagway) receives a large amount of ferry traffic, especially in the summer. The Haines state ferry terminal at 2112 Lutak Road is about 4 miles north of town.
Recently, Haines became a port-of-call to cruise ships, only about 20 calls per season, mainly from the Holland-America Line. The cruise ship docks at the Port Chilkoot Wharf, at the foot of Portage St below Fort Seward. If you are on a cruise that visits Haines, you can rest assured that your ship will be the only ship in port and there won't be any large crowds to contend with in town.
[edit] Get around
Haines is small enough that you can easily walk around the town in an hour or two.
During cruise ship dockings, there is a Shuttle Bus service that runs every 30 minutes. It starts at the Port Chilkoot Dock, and makes a loop to the Sheldon Museum, Visitor Center, Library, Dalton City, Eagle Foundation, Fort Seward Historic District, and then back to the Dock.
There are no taxis in Haines. Occasionally there is one when someone tries to start a taxi business, but they don't survive. You will need a car, a bike, a shuttle service, or make a friend quick.
[edit][add listing] See
• Haines Convention and Visitors Bureau, 122 Second Ave S (near Willard St), 907-766-2234; 800-458-3579, [1]. Summer: M-F 8am-7pm, and weekends 9am-6pm. You can pick up the Haines Visitor's Guide, walking tour maps, e.g., for Fort Seward, and "Haines is for Hikers". edit
• Fort William H. Seward, House No. 1, Fort Seward Dr (above 2nd Ave S and Portage St). On the original Haines Mission grounds, Fort William H. Seward was Alaska's first US army fort, built during the gold rush era (1902). It is a nationally recognized historic site (declared National Historic Landmark in 1978). The Fort is also referred to as Port Chilkoot, a leftover from the Port Chilkoot Company, which was formed after World War II by a group of investors who purchased the Fort from the Federal Government. An increasing number of restaurants, lodges, and art galleries are utilizing the original buildings; e.g., the Fort's hospital is now the Alaska Indian Arts Center. Within the parade ground is Totem Village. Although not part of the original fort, it includes two tribal houses and totem poles and is the home of the Chilkat Storytellers Theater Show, an hour-long performance of Alaska Native dramatization. A walking-tour map of the Fort is available at the Visitors Bureau, or you can just read the historical panels that have been erected there. edit
• American Bald Eagle Foundation, 2nd Ave S and Haines Hwy, 907-766-3094, [2]. The American Bald Eagle Foundation contains a Natural History Museum featuring dioramas and (opened in 2010) a Live Raptor Center featuring live bird presentations. $10 to $3. edit
• Sheldon Museum & Cultural Center, 11 Main Street (near Front St on original Haines Mission grounds), (907) 766-2366 , [3]. Summer: M-F 10am-5pm, weekends 1-4pm.. The Sheldon Museum is a cultural and historical center for the Native Tlingit art and culture, Haines history (Mission, Eldred Rock Lighthouse lens, Army, local industries, people), and the work of local artists. Two stories. Gift shop. Admission: $5 adult, children less than 12 free. edit
• Kroschel Wildlife Center, 30 mile Haines Hwy; 1.8 mile Mosquito Lake Road (At approximately 30 miles northwest of Haines on the Haines Hwy, turn right onto Mosquito Lake Rd. Travel 1.8 miles down Mosquito Lake Rd; Center on the left.), (907)-767-5464, [4]. Guided tours feature opportunities for up-close experiences and photographic opportunities with over 15 species of Alaskan Wildlife, including grizzly bear, wolf, moose, lynx, fox, reindeer, porcupine, snowy owl, and wolverine. Easy walking on over 600 yards of groomed trail. edit
• Alaska Bald Eagle Festival. Five day celebration in mid November of the peak of the gathering of eagles, mostly within the Eagle Council Grounds at 19 mile Haines Highway. edit
[edit][add listing] Do
• Battery Point Trail, [5]. This short trail through the woods parallels shoreline to a pleasant beach, and provides access to Mt. Riley. edit
• Mountain Flying Service (Glacier Bay Flightseeing), 132 2nd Ave S (3 doors down from the visitors center), (907) 766-3007, [6]. Mountain Flying Service does charter flights and flightseeing mostly among Skagway, Haines, and Glacier Bay. They do glacier landings in winter, spring, and early summer, and also do remote beach landings in Glacier Bay. It's incredible. edit
• Southeast Alaska State Fair. Late July at the Southeast Alaska Fairgrounds in Dalton City edit
[edit][add listing] Buy
• Howsers IGA Supermarket, Main St near 2nd Ave. Mon-Sat 8am-9pm; Sun 10am-7pm. Locally owned full service supermarket in downtown Haines. edit
[edit][add listing] Eat
During summer there are a variety of restaurants open from sea food, wood fire cooked pizza, to Mexican. But in winter there can be times where no restaurants are open at all.
• Mosey's Cantina (Mosey's Cantina), 1 Soap Suds Alley (Go straight up the hill from the cruise dock.), (907) 766-2320, [7]. Authentic Mexican food. They go south each winter and hand select their ingredients. edit
• 33 Mile Roadhouse, 33 Haines Highway (Go 33 miles outside of Haines, west on the Haines Highway.), (907) 767-5510, [8]. 33 Mile is home to world famous burgers and world famous heliskiing. Great burgers and food and a great price. edit
[edit][add listing] Drink
• Haines Brewing Co, 108 White Fang Way, Dalton City (Southeast Alaska Fairgrounds), 907 766-3828. Mon-Sat 1-7pm. Freshly poured growlers at Haines own micro brewery. Can take the Shuttle Bus on cruise docking days. edit
[edit][add listing] Sleep
• Bear Creek Cabins and Hostel, Small Tract Rd (1 mile south of central Haines), +1 907 766-2259 (), [9]. checkin: 3PM; checkout: 11AM. Four small cabins (sleeps 4 each), one family/group cabin (sleeps 6), and two hostel cabins (sleeps 4 each, can be booked as a group cabin). Communal kitchen and bathroom facilities (the family cabin has a private bath). No lockout or curfew. Hostel bunk $20, small cabins $68, group cabin $120. edit
[edit] Contact
The Haines Borough Public Library[10], 113 Third Ave S (near Willard), has several computer workstations available free of charge on a first-come, first-served basis. The library, completed in 2003, is open Mon-Thurs 10am to 9pm, Fri 10am to 6pm, and Sat-Sun 12:30pm to 4:30pm.
[edit] Get out
Take a fast ferry from the Small Boat Harbor or the Port Chilkoot Dock (check the point of departure) to Skagway or Juneau via the Lynn Canal.
• Alaska Fjordlines, 1-800-320-0146
• Chilkat Express, 1-855-766-4001
• Fast Ferry, 1-888-766-2103
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
2901.0 - Census Dictionary, 2006 (Reissue)
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 17/11/2006 Reissue
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GNGP
Second release
Government/Non-Government Employer Indicator The employer's business name and the workplace address of the employed person is used to classify employed persons into government or non-government industry sectors. If the government sector cannot be determined, responses are coded to Private sector as the default code.
Applicable to: Employed persons
1 Commonwealth Government
2 State/Territory Government
3 Local Government
4 Private sector
& Not stated
@ Not applicable
V Overseas visitor
Total number of categories: 7
Not applicable (@) category comprises:
Unemployed persons, looking for either full-time or part-time work
Persons not in the labour force
Persons with Labour Force Status (LFS06P), not stated
Persons aged under 15 years
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
4130.0.55.001 - Housing Occupancy and Costs, Australia, 2003-2004
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 13/03/2006
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NOTES
ABOUT THIS PUBLICATION
This publication presents data from the Survey of Income and Housing (SIH) on Australian housing costs, and relates these to characteristics of occupants and dwellings such as tenure, family composition of household, dwelling structure, age, income and principal source of income. It also includes value of dwelling estimates, and information on recent home buyers.
CHANGES IN THIS ISSUE
Changes in the contents of this issue are:
• The replacement of the variable 'household composition' with the variable 'family composition of household'
• Housing stress data are not presented. Refer to the Explanatory Notes (paragraphs 17-21) for further information.
Changes in the SIH which are likely to have impacted on the data in this issue include:
• a larger sample of 22,315 persons for 2003-04 compared to 19,400 to 2002-03 (lower sample error)
• previous SIH cycles selected dwellings from those that had been respondents for eight months in the monthly population survey, whereas from 2003-04 the SIH sample is drawn from dwellings not recently included in an ABS household survey (possible change in response bias)
• interviewer use of a laptop computer instead of a paper form to collect information from respondents (possible improvement in data capture)
• an expanded range of questions to collect details about income - in particular, information was collected about expected income in the current financial year from own unincorporated business and investments, whereas previous "current period" estimates for these components of income were based only on information about reported income for the previous financial year (a significant impact on the coverage of such income streams in current income measures)
• a comprehensive range of questions to collect details about the assets and liabilities of the household, which may have improved the quality of reporting of associated income streams
• the integration of the SIH with the Household Expenditure Survey (HES), refer to Explanatory Notes for further information
• selection of household reference person no longer influenced by differing income unit tenure types within the household.
EFFECTS OF ROUNDING
Where figures have been rounded, discrepancies may occur between sums of the component items and totals. Published percentages are calculated prior to rounding of the figures and therefore some discrepancy may exist between these percentages and those that could be calculated from the rounded figures.
INQUIRIES
For further information about these and related statistics, contact the National Information and Referral Service on 1300 135 070 or Alan Wong in Canberra (02) 6252 5508. Alternative contact: John Forsey (02) 6252 7031.
SUMMARY COMMENTARY
SUMMARY OF FINDINGS
INTRODUCTION
For many people, the cost of providing shelter for themselves and their families is one of the largest expenditures that they will make. The recurrent aspects of housing costs reported in this publication, which cover the housing-related mortgage and rates payments of owner households, and the rent payments of renter households, are also often the largest expenditure items to be met from households' current incomes.
The data presented in this publication are compiled from the Survey of Income and Housing (SIH), with information for the years 1994-95 to 2003-04 (excluding 1998-99 and 2001-02, when the survey was not conducted). However, more extensive and more detailed housing costs information for 2003-04, including the split between the interest and capital components of mortgage repayments, is available from the Household Expenditure Survey (HES) - see Household Expenditure Survey, Australia: Detailed Expenditure Items (cat. no. 6535.0.55.001) for information available from the 2003-04 survey.
HOUSING OCCUPANCY
Changes since 1994-95
In 2003-04 there were approximately 19.6 million people or 7.7 million households living in private dwellings, up 11% on the number of people in private dwellings in 1994-95. There was a larger increase in the number of households over this period (up 18%), reflecting a decrease in the average household size from 2.69 to 2.53 persons per household. The average dwelling size increased over this period from 2.88 to 3.02 bedrooms per dwelling. The proportion of separate houses and dwellings that were either semi-detached houses or town houses remained the same at 80% and 8%.
Over this period there was a decrease in the proportion of households that owned their dwelling outright, from 42% in 1994-95 to 35% in 2003-04. There were increases in the proportion of households that had a mortgage on their homes (from 30% to 35%) and in the proportion of households that were renting privately (from 18% to 21%).
Housing Tenure, 1994-95 and 2003-04
Life cycle stages
The proportion of households that own their home outright increases as the age of the reference person increases. Only 3% of single and couple only households with a reference person aged under 35 years owned their home outright, compared to 85% of couples with the reference person aged 65 years and over (Table 16). Younger single people were most likely to be renting privately (61%) and also had the highest proportion of any group in flats and apartments (41%). Younger persons in a couple relationship were more likely to move into home ownership than younger single people, with 57% of younger couple households owning their home with or without a mortgage. When couples have children they are more likely than younger couple only households to own a home. For couples with their eldest child under 5 years, 72% owned their home with or without a mortgage. This rose to 76% for couples with their eldest child aged 5 to 14, and 87% for couples with dependent children only and the eldest aged 15 to 24.
HOUSING TENURE BY LIFE CYCLE - 2003-04
HOUSING UTILISATION
The Canadian National Occupancy Standard is widely used internationally as an indicator of housing utilisation (see explanatory notes). According to this measure, of the 7.7 million Australian households only a small proportion (3%) required one or more additional bedrooms. More than three quarters (77%) of households occupied dwellings which had more bedrooms than were needed to accommodate occupants (Table 14).
Households that owned their home without a mortgage were more likely than those with other tenures to have one or more bedrooms spare (89%). Households renting from a state or territory housing authority were the most likely tenure group (43%) to have the required number of rooms. Five percent of private renters and three percent of state or territory housing authority renters required one or more additional bedrooms.
Sixty five percent of couples living with dependent children had at least one spare bedroom, compared to 48% of one parent households with dependent children. Of the latter group, 8% required one or more additional bedrooms. Multiple family households and group households were the most likely to require additional bedrooms (27% and 9% respectively). On average, dwellings for couples with dependent and non-dependent children contained the highest number of bedrooms (3.9) and housed an average of 4.8 people.
HOUSING COSTS
The composition of housing costs differs depending on type of tenure. In this publication, housing costs of owners comprise rates, both general and water, and mortgage repayments if the mortgage was initially taken out primarily to purchase, build or alter the dwelling. Owners that have a mortgage where the purpose of the mortgage when initially taken out was not primarily housing related, are categorised as owners with a mortgage, but their mortgage repayments are not included in their housing costs. For renters housing costs comprise the amount of rent paid.
The mean (average) weekly housing costs for all households were $157 in 2003-04. There is, however, considerable variation in housing costs with 44% of all households paying $75 or less per week. For owners without a mortgage the average weekly housing costs were $25, which represented 3% of average gross weekly income for those households. Owners with a mortgage paid an average of $287 per week on housing costs, which represented 19% of their average gross income per week. Households renting from state and territory housing authorities paid an average of $84 per week, representing 19% of their average gross income. Households renting from private landlords paid an average of $198 per week.
However, some lower income households receive a refund of their private rental costs through the Commonwealth Rent Assistance (CRA) scheme. It is estimated that these refunds lowered the average housing costs of households renting from private landlords by about 10%. See paragraph 16 of the Explanatory Notes for more detail.
Changes since 1994-95
In real (2003-04 all groups CPI adjusted) terms average weekly housing costs across all households increased by 29% from $122 in 1994-95 to $157 in 2003-04. For owners without a mortgage, real average weekly housing costs decreased from $28 in 1994-95 to $25 in 2003-04. For owners with a mortgage, real average weekly housing costs rose by 19%, from $242 to $287. For private renters, real average weekly housing costs rose by 12%, from $177 to $198, before adjusting for CRA refunds.
REAL WEEKLY HOUSING COSTS BY TENURE TYPE, 1994-95 and 2003-04
VALUE OF DWELLING
In the SIH, owners were asked to estimate the value of their dwelling. The estimate they provided may differ from valuations made by accredited valuers or the actual sale price of the dwelling. The extent of the difference has not been measured and therefore some care needs to be taken when using these data.
In 2003-04 the median value of the 5.4 million owner occupied dwellings was $300,000, an increase of 17% on the Consumer Price Index (all groups) adjusted value of $256,000 in 2002-03, and a 70% increase on the corresponding value in 1994-95 (table 1). However, the CPI adjusted value of the median value of mortgage outstanding only increased by 3%, from $98,000 to $101,000, between 2002-03 and 2003-04, and by 42% between 1994-95 and 2003-04. The proportion of total households with a mortgage outstanding increased from 30% to 35% over the period 1994-95 to 2003-04, and the proportion of dwellings owned outright declined from 42% to 35% (table 3).
Dwelling values were highest for couple with dependent children only, where the eldest child was 15 to 24 years, couple with dependent and non-dependent children and couple with non-dependent children only (table 19). The median value of dwelling for these groups was $350,000. The life cycle group that reported the lowest median value of dwellings was lone persons under the age of 35 years. The median value for this group was $210,000.
The median value of dwellings for capital cities was $340,000 (table 26). The median value was highest in Sydney at $500,000, followed by Canberra at $359,000.
Value of dwelling, By capital city, 2003-04
RECENT HOME BUYERS
Almost 1.2 million households purchased their dwelling in the 3 years before the survey. These households are divided into first home buyers (34%) and changeover buyers (66%). The majority of recent home buyers bought an established house (83% of first home buyers and 79% of changeover buyers).
The median value of recently purchased dwellings was $250,000 for first home buyers and $310,000 for changeover buyers (table 34). Housing costs, on the other hand, were higher for first home buyers than for changeover buyers, at $330 and $251 per week respectively (table 32). This is consistent with a higher proportion of first home buyers having a mortgage (95%) than of changeover buyers (70%). New dwellings had both a higher median value ($350,000) than recently purchased established dwellings ($280,000) and higher housing costs, with average weekly housing costs of $286 for new dwellings and $276 for established dwellings.
DENDOGRAM OF SELECTED HOUSEHOLD CHARACTERISTICS
ABBREVIATIONS AND SYMBOLS
ABBREVIATIONS
ABS Australian Bureau of Statistics
ACT Australian Capital Territory
Aust. Australia
CPI Consumer Price Index
CRA Commonwealth Rent Assistance
HES Household Expenditure Survey
np not available for separate publication but included in totals where applicable, unless otherwise indicated
NSW New South Wales
NT Northern Territory
Qld Queensland
RSE Relative Standard Error
SA South Australia
SE Standard Error
SIH Survey of Income and Housing
Tas. Tasmania
Vic. Victoria
WA Western Australia
SYMBOLS
* estimate has a relative standard error of 25% to 50% and should be used with caution
** estimate has a relative standard error greater than 50% and is considered too unreliable for general use
- nil or rounded to zero (including null cells)
© Commonwealth of Australia 2013
Unless otherwise noted, content on this website is licensed under a Creative Commons Attribution 2.5 Australia Licence together with any terms, conditions and exclusions as set out in the website Copyright notice. For permission to do anything beyond the scope of this licence and copyright terms contact us.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
3101.0 - Australian Demographic Statistics, Jun 1983
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 18/11/1983
Future Releases
• Next Issue: Dec 2012 expected for release on 20/06/2013
Past Releases
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
1376.0 - Local Government and ABS, 2013
Latest ISSUE Released at 11:30 AM (CANBERRA TIME) 31/01/2013
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POPULATION CENSUS DEVELOPMENTS
2016 Census Planning
2011 Census Update (Updated - Apr 2013)
2016 CENSUS PLANNING
Planning for the 2016 Census of Population and Housing is underway, and the ABS invites you to have your say.
The ABS has released a publication proposing directions for Australia's 17th national Census, to be held in 2016.
The publication 2016 Census of Population and Housing: Consultation on content and procedures – ABS (cat. no. 2007.0) outlines initial ABS views on topics and procedures for the 2016 Census.
The ABS has begun a consultation process with Census data users and the general public. The consultation process includes:
• public information sessions where the ABS presented proposed directions for 2016. (These were held late 2012 )
• a submission period where interested parties can formally submit their feedback and suggestions to the ABS via an online submission form or they can be emailed to the ABS (see 'Making a submission' for more details).
Making a submission
Before making a submission it is important to:
Submissions can be made to the ABS up to 31 May 2013.
2011 CENSUS UPDATE
SEIFA 2011 now available
Socio-Economic Indexes for Areas (SEIFA) is a product developed by the ABS that ranks areas in Australia according to relative socio-economic advantage and disadvantage. The indexes are based on information from the five-yearly Census.
SEIFA 2011 is the latest version of this product and consists of four indexes:
• The Index of Relative Socio-Economic Disadvantage (IRSD)
• The Index of Relative Socio-Economic Advantage and Disadvantage (IRSAD)
• The Index of Education and Occupation (IEO)
• The Index of Economic Resources (IER).
Each index is a summary of a different subset of Census variables and focuses on a different aspect of socio-economic advantage and disadvantage. More information about SEIFA can be found on the Census/SEIFA webpage.
Mesh Block Counts now available
Mesh block counts for usual resident population and dwellings are now available to be downloaded from our website. You can download these as Excel or CSV files. For more information see the Mesh Block Counts page of the ABS website.
Remaining 2011 release schedule
The third release of Census 2011 data began on 28 March 2013, with products released progressively until the end of 2013. This will finalise all Census data output for the 2011 Census.
March to August: The data in QuickStats, Community Profiles, TableBuilder and DataPacks will be supplemented with data at Remoteness Area level.
September: Census Sample Files (1% and 5%) will be released as Confidentialised Unit Record Files (CURFs).
Final quarter 2013: 5% Statistical Longitudinal Dataset (SLCD) will be released as a CURF.
For more information see the Information Paper: Census of Population and Housing -- Products and Services, 2011 (cat. no. 2011.0.55.001), specifically Chapter 8 and Appendices 10 - 13.
© Commonwealth of Australia 2013
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
8501.0 - Retail Trade, Australia, Dec 2001
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 05/02/2002
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• About this Release
ABOUT THIS RELEASE
Contains monthly estimates of turnover for retail and selected service establishments. Original, seasonally adjusted and trend estimates are included for states and Australia in current price terms. Volume measures are published quarterly classified by state or industry.
© 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
Evidence for cervical cancer mortality with screening program in Taiwan, 1981–2010: age-period-cohort model
Shih-Yung Su1,2, Jing-Yang Huang1, Chien-Chang Ho3 and Yung-Po Liaw1*
Author affiliations
1 Department of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sec 1 Chien-Kuo N. Road, Taichung City 40201, Taiwan
2 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Rm. 536, No. 17, Xuzhou Rd, Taipei 100, Taiwan
3 Department of Health and Leisure Management, Yuanpei University, Hsinchu City, 30015, Taiwan
For all author emails, please log on.
Citation and License
BMC Public Health 2013, 13:13 doi:10.1186/1471-2458-13-13
Published: 8 January 2013
Abstract
Background
Cervical cancer is the most common cancer experienced by women worldwide; however, screening techniques are very effective for reducing the risk of death. The national cervical cancer screening program was implemented in Taiwan in 1995. The objective of this study was to examine and provide evidence of the cervical cancer mortality trends for the periods before and after the screening program was implemented.
Methods
Data from 1981 to 2010 of the causes of death registered were obtained from the Department of Health, Taiwan. Age-standardized mortality rates, age-specific rates, and age-period-cohort models that employed the sequential method were used to assess temporal changes that occurred between 1981 and 2010, with 1995 used as the separating year.
Results
The results showed that for both time periods of 1981 to 1995 and 1996 to 2010, age and period had significant effects, whereas the birth cohort effects were insignificant. For patients between 80 and 84 years of age, the mortality rate for 1981 to 1995 and 1996 to 2010 was 48.34 and 68.08. The cervical cancer mortality rate for 1996 to 2010 was 1.0 for patients between 75 and 79 years of age and 1.4 for patients between 80 and 84 years of age compared to that for 1981 to 1995. Regarding the period effect, the mortality trend decreased 2-fold from 1996 to 2010.
Conclusions
The results of this study indicate a decline in cervical cancer mortality trends after the screening program involving Papanicolaou tests was implemented in 1995. However, the positive effects of the screening program were not observed in elderly women because of treatment delays during the initial implementation of the screening program.
Keywords:
Cervical cancer; Age-period-cohort model; Mortality; Gynecologic oncology; Screening program
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You are here: Home / Celebrating Europe and its environment / Speaker's corner
Speaker's corner
Climate change the main environmental concern of European youth — Mar 22, 2007
More environmental education, alternative sources of energy and stricter transportation laws are some of the proposals put forth by Europe’s next generations of policy makers and voters.
European Environment Agency (EEA)
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You are here: Home / News / Major step in protecting the ozone layer
Major step in protecting the ozone layer
Published : Sep 28, 2007 Last modified : May 31, 2011 03:05 PM
Topics: ,
World governments meeting in Montreal last week agreed to freeze production of the ozone depleting substances hydrochlorofluorocarbons (HCFCs) in 2013 and bring forward the final phase-out date of these chemicals by ten years. Industrialised countries also pledged to provide 'stable and sufficient' funds to help developing countries meet the accelerated phase-out deadline.
The accelerated phase out is expected to restore the ozone layer, which filters out damaging levels of ultra violet light, a few years earlier than originally estimated.
'Governments from all countries, developed and developing, have achieved a major step forwards in protecting the ozone layer and at the same time combating climate change in an effective way', says Jacqueline McGlade, Executive Director at the European Environment Agency in Copenhagen.
HCFCs are chemicals replacing more ozone-damaging chemicals such as CFCs (chloroflurocarbons) in air conditioning and some forms of refrigeration equipment and foams. CFCs are already being phased out under earlier decisions. There is mounting evidence that HCFCs contribute to global warming. These gases are not covered by the Kyoto Protocol which does address all other main greenhouse gases from human activities. Thus apart from helping restoring the ozone layer the phasing out of HCFCs also reduces global greenhouse gas emissions and helps tackling climate change.
The agreement to accelerate the phase out happened under the 20 year-old UN Montreal Protocol, a treaty to protect the Earth’s ozone layer.
Developed countries agreed to reduce production and consumption by 2010 by 75 per cent and by 90 per cent by 2015 with final phase out in 2020. Developing countries have agreed to cut production and consumption by 10 per cent in 2015; by 35 per cent by 2020 and by 67.5 per cent by 2025 with a final phase-out in 2030. Governments also agreed an initial 2009 quota for critical use exemptions of the banned ozone-depleting pesticide methyl bromide.
For more information see the UNEP ozone secretariat website.
See also the EEA website on climate change.
European Environment Agency (EEA)
Kongens Nytorv 6
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Denmark
Phone: +45 3336 7100
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Biodiversity
Biodiversity is the variation in living organisms, viewed within a given habitat, ecosystem or in the world as a whole. The concept is usually applied to the species diversity, although the notion of genetic biodiversity is applied to the variation in genes within an individual species. While most people think of rainforests as loci of great biodiversity, biomes such as oceans and grasslands are the likely repositories for even greater variation. Retention of diverse biota is important, since intact ecosystems are thought to be essential for provision of ecosystem services to humans, including maintenance of a diverse foodbank, pollination, clean water, flood control, pest control, waste decomposition, biomass energy resources and climate stability. Biodiversity is presently critical since we live in the era of the Mass Holocene Extinction, a period of species loss caused by man, and unrivaled in rate of species loss. Although the number of total species numbers in the tens of millions, most have not yet even been described. The extinction of a species is almost always related to destruction of habitat or man-made pollution.
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The Burnt Cape is a limestone barren headland on the extreme northwest of the Northern Peninsula of Newfoundland, Canada. The prevailing harsh cold climate and calcareous...
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The seas in which corals and other calcifying species dwell are turning acidic, their pH slowly dropping as Earth's oceans acidify in response to increased carbon dioxide... More »
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Wrasses (the family Labridae) are the most abundant and conspicuous fishes on tropical reefs around the world. Wrasses also comprise an important element of the coldwater fish... More »
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Coral reefs are one of the most diverse, complex, aesthetically appealing and threatened ecosystems on earth. This collection will include information on a wide range of topics... More »
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Pollination in angiosperms and gymnosperms is the process that transfers pollen grains, which contain the male gametes (sperm) to where the female gamete(s) are contained... More »
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Cubozoans are astounding animals. They resemble basic jellyfish, but they can swim quite rapidly, maneuver with great agility, and have good vision despite not having a... More »
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About this Journal Submit a Manuscript Table of Contents
International Journal of Distributed Sensor Networks
Volume 2012 (2012), Article ID 686172, 12 pages
doi:10.1155/2012/686172
Research Article
Rendezvous Data Collection Using a Mobile Element in Heterogeneous Sensor Networks
Software School and State Key Lab of ISN, Xidian University, Shaanxi 710071, China
Received 11 January 2012; Accepted 20 February 2012
Academic Editor: Mo Li
Copyright © 2012 Junzhao Du 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
We study the rendezvous data collection problem for the Mobile Element (ME) in heterogeneous sensor networks where data generation rates of sensors are distinct. The link quality is instable in our network model and the sensory data cannot be aggregated when transmitting. The Mobile Element is able to efficiently collect network wide data within a given delay bound; meanwhile the network eliminates the energy bottleneck to prolong its lifetime. For case study, we consider the trajectory planning for both Mobile Relay and Mobile Sink on a tree-shaped network. In the Mobile Relay case where the ME’s trajectory must pass through a sink to upload sensory data for further processing, an ( lg ) algorithm named RP-MR is proposed to approach (1) the optimal Rendezvous Points (RPs) to collect global sensory data; (2) the optimal data collection trajectory for the Mobile Relay to gather the cached data from RPs. In the Mobile Sink case where the Mobile Element can process the sensory on its motion, we develop an ( lg2 ) algorithm named RP-MS to recursively investigate the optimal solution. Both the theoretical analysis and extensive simulations verify the correctness and effectiveness of proposals.
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Journal of Toxicology
Volume 2013 (2013), Article ID 956404, 11 pages
http://dx.doi.org/10.1155/2013/956404
Research Article
Differential Cytotoxicity Responses by Dog and Rat Hepatocytes to Phospholipogenic Treatments
1Disposition, Safety and Animal Research, Sanofi, 5 The Mountain Road, Framingham, MA 01701, USA
2Global Safety Assessment, AstraZeneca Pharmaceuticals, B2.86, 35 Gatehouse Drive, Waltham, MA 02451, USA
Received 22 December 2012; Accepted 28 January 2013
Academic Editor: Michael Cunningham
Copyright © 2013 James K. Morelli and Paul J. Ciaccio. 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
Dog and rat hepatocytes were treated with phospholipogenics to identify the more sensitive species and to determine whether lysosomal or mitochondrial changes were the primary cause of cytotoxicity. Endpoints included cell death, lysosome membrane integrity, mitochondrial membrane polarization, and fluorescent phospholipid (NBD-PE). Dog cells exhibited lower survival IC50 values than did rat cells with all phospholipogenic treatments and exhibited a lower capacity to accumulate NBD-PE in 4 of 5 phospholipogenic test conditions. The lysosomal modulator Bafilomycin A1 (Baf) rescued dog cells from cytotoxicity caused by 3 phospholipogenic 5HT1b antagonists and hydroxychloroquine, but not fluoxetine, and rescued rat cells from hydroxychloroquine and NMTMB, a 5HT1b antagonist. Following NMTMB treatment, rat mitochondrial membrane hyperpolarization was observed at modestly cytotoxic concentrations and depolarization at the highest concentration. At the highest test concentration, lysosomal loss of acridine orange occurred by 30 min, mitochondrial polarity changes by 1 hr, and NBD-PE accumulation by 2 hr, respectively. Baf shifted mitochondrial polarity from a depolarized state to a hyperpolarized state. These data demonstrate that (a) dog hepatocytes were generally less capable of mounting an adaptive, protective phospholipidotic response than rat hepatocytes, (b) effects on mitochondria and survival were preventable by lysosomal protection, and (c) destabilizing changes in both organelles are involved causally in cytotoxicity.
1. Introduction
Cationic amphiphilic drugs have chemical structures composed of hydrophilic and lipophilic regions, combined with a cationic amine group. Many cationic amphiphilic drugs are phospholipogenic (here defined as a compound that causes phospholipidosis (PLD)). A phospholipidotic response is characterized by the accumulation of phospholipids, lamellar bodies, and drug in cellular lysosomes and results from inhibited lysosomal phospholipase activity, either by binding of drug to phospholipids or by direct inhibition of phospholipases, and through alkalization of the normally acidic lysosomal mileu [1]. Lysosomotropic properties and accumulation potential of phospholipogenics are underscored by studies employing lysosomal modulators. The ionophore monensin, ammonium chloride (which causes direct lysosomal alkalinization), and the specific vacuolar sodium-potassium proton pump inhibitor Bafilomycin A1 (Baf) have been shown to abolish the pH gradient from cytoplasm (near neutral) to lysosome (low internal pH) and preclude accumulation of phospholipogenics in the lysosome and/or rescue cells in vitro from such treatments [26].
PLD can occur in multiple tissue types, often reflecting benign, adaptive and reversible changes in affected tissues without functional consequence [7, 8], but is sometimes associated with frank tissue degeneration including that for liver and neuronal tissue [914]. Drug-induced liver injury is an important source of attrition for pharmaceutical compounds. It does not necessarily result in abandonment of compound development, as toxicity responses across a dosing interval do not always translate across species, and the therapeutic windows may be sufficient. While cause and effect between PLD and degenerative changes has not been clearly established, mechanisms of degenerative concurrent injury caused by phospholipogenics and species response differences should be elucidated where possible to support compound progression into the clinic.
Select phospholipogenics cause liver toxicity in preclinical species such as rats [911, 13, 14] and dogs [14]. For example, at comparable plasma exposures in 1-month toxicology studies, a weak phospholipogenic 5HT1b antagonist compound A caused liver PLD in both dog and rat liver but only dog had concomitant centrilobular necrosis (unpublished observations). These findings led us to inquire whether the dog is a more sensitive species generally to phospholipogenic drug administration and whether the phospholipidotic response is a primary cause of cytotoxicity.
We report on in vitro investigations showing that, against a panel of such treatments and toxicity endpoints, dog hepatocytes profiled differently than rat hepatocytes as they were more sensitive to the phospholipogenics tested (including compound A) and generally exhibited a diminished capacity to mount protective phospholipidotic responses. Investigations with another 5HT1b antagonist, N-[(2R)-5-methyl-8-(4-methylpiperazin-1-yl)tetralin-2-yl]-4-morpholino-benzamide (NMTMB), suggested that both lysosome and mitochondria organelles are involved in early steps of cell stress. Baf cotreatment rescued hepatocytes from phospholipogenic-mediated cytotoxicity, suggesting that a lysosomal mechanism of cytotoxicity may be primary. Mitochondrial mechanisms of rat cell cytotoxicity, such as mitochondrial membrane depolarization, occurred coordinately with lysosomal membrane destabilization and earlier than detectable phospholipidotic responses.
2. Materials and Methods
2.1. Cell Culture
Primary rat hepatocytes were freshly isolated from Han Wistar rats at AstraZeneca, using the collagenase perfusion method (Selgen, PO, 1976). Primary dog hepatocytes were isolated at AstraZeneca, or purchased from CellzDirect Corp. (Durham, NC), which also uses a collagenase perfusion method. Cells were centrifuged and resuspended in hepatocyte culture media, consisting of Williams E basal media (Sigma-Aldrich, Inc., St. Louis, MO) 5% Hyclone fetal bovine serum (ThermoFisher Scientific Inc., Rockford, IL), 15 mM HEPES (Mediatech Inc., Manassas, VA), 100 units/mL penicillin/streptomycin, 200 M l-glutamine, 1X ITS (insulin, transferrin, selenium solution from Mediatech Inc.), and 30 nM dexamethasone (Sigma-Aldrich). Cells were suspended at cell/mL and added to BD Biocoat collagen I coated microtiter plates at 100 L/well, for a final count of 25,000 cells/well. Selection criterion for use of initial isolates was 85% minimal viability. Cells were incubated at 37°C in a CO2 incubator for 4 h to allow for cell attachment. Media was aspirated and replaced with hepatocyte culture media without fetal bovine serum and supplemented with 150 g/mL Matrigel collagen matrix (BD Inc.). Cells were incubated in a CO2 incubator for 24 h, the media was replaced with hepatocyte culture media, and the cells were incubated for an additional 24 h. Compounds were solubilized in DMSO, water, or ethanol to 1000X stock and then diluted to 1X in media. All conditions contained equal concentrations of vehicle. Cells were incubated with drug for the durations indicated in figure or table legends.
2.2. Compounds
Figure 1 shows the chemical structures of AstraZeneca Pharmaceuticals (AZ) 5HT-1b antagonist compounds NMTMB, A, and B. It also shows negative control compounds C and D. All AZ compounds employed in this study were prepared by the AstraZeneca CNS Chemistry Department (Wilmington, DE) and were of >95% chemical and isomeric purity. 5-HT1b receptor antagonists and synthetic steps are further described by Stenfors et al. [15] and Bernstein et al. [16]. NMTMB and compound A are confirmed multiorgan in vivo phospholipogenics as they were tested preclinically in both rat and dog models (data not shown). Compound B was tested independently in a splenocyte model in vitro [17] and was found to be phospholipogenic. Three compounds (Diclofenac, C, and D), which lack cationic amphiphilic properties, were also tested in this model and were found to be negative. They were therefore used as negative controls in this study. Compound D is the right hand side aniline of A. Diclofenac (obtained from Sigma-Aldrich) is not phospholipogenic in vivo. Additional positive controls, obtained from Sigma-Aldrich, were fluoxetine and hydroxychloroquine and are known to cause PLD (see summary reviews [1, 7, 9]). The vacuolar ATPase proton pump inhibitor Bafilomycin A1 (Sigma-Aldrich) has been shown to alkalinize lysosomes and prevent lysosomal membrane permeability and intrinsic apoptosis [18, 19]. PADK (Z-Phe-Ala-diazomethylketone) (Bachem Bioscience, Inc. King of Prussia, PA) is known to enhance intralysosomal cathepsin activity [20].
Figure 1: Chemical structures of select compounds used in this study.
The Baf concentration selection for these experiments was based upon several observations. At 30 nM Baf exhibited no effects on control (ATP levels, not shown) or survival. One hundred nM Baf caused 2-fold increases in dog and rat hepatocyte control NBD-PE fluorescent staining, but minimal changes at 30 nM. One hundred nM Baf but not 30 nM caused vacuolation of dog hepatocytes. Finally, 100 nM but not 30 nM Baf enhanced cell death in rat hepatocytes when cotreated with hydroxychloroquine and amiodarone treatments. This concentration selection and outcomes differ from that of the work of Boya et al. [18] who employed CHO cells, a cell line which possesses a very different phenotype than primary hepatocytes.
2.3. NBD-PE Accumulation Assay
In a modification of the procedure described by Morelli et al. [17], hepatocytes were treated with drugs diluted into culture media containing 12 g/mL NBD-PE (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt) for 24 hours. At the end of the treatment period, Sytox orange (100 nM Invitrogen Inc.) was added to cells for 20 minutes prior to fixation. This fluorescent dye stains only cells with compromised cell membranes thereby enabling their exclusion from NBD-PE cell quantitation by the Cellomics ArrayScan instrument. Media were aspirated, cells were washed with 1X PBS and fixed by the addition of 100 L PBS containing 3.7% formaldehyde, and 1 g/mL Hoechst dye. Fixation was allowed to proceed for 30 min at RT, and cells were washed three times with 1X PBS, and sealed for imaging. Labeled cells were analyzed using the Cellomics Arrayscan instrument (Cellomics Inc., Pittsburgh, PA) with version 3.5 equipment and software. The ArrayScan captures fluorescent images in the 3 channels relevant to this assay (Hoechst, TRITC for Sytox staining and FITC for NBD-PE staining) and performs automated image analysis to quantify cell nuclei, the number of dead cells, and NBD-PE dye fluorescent intensity. The analysis algorithms that enable cell versus well-based detection were purchased from Cellomics Inc. and are referred to as Cell Health Profiling (CHP) and Target Activation (TA) algorithms. Given bell-shaped concentration-response curves, accurate EC50 (half maximal effective concentration) values were difficult to obtain but were estimated from the left-hand portion of the concentration response curves. For time-course investigations with NMTMB, concentrations were selected to bracket the rat survival IC50 value and to approach the NBD-PE EC50 (~65 μM) value. NBD-PE peak signal was defined as the maximal response.
2.4. Acridine Orange Time Course
Acridine Orange (AO) (Invitrogen Inc.) was purchased at a concentration of 10 mg/mL in water, and diluted to 50 M final in Williams E media. Cells were preincubated for 1 h in 90 L complete Williams E media, or complete Williams E media containing 30 nM Bafilomycin A1 for 1 h. Ten L Acridine Orange was added to wells to reach a final well concentration of 5 M. Cells were incubated with AO for 10 minutes. The media were then aspirated, the cells rinsed once with PBS, and replaced with fresh media containing compounds of interest, plus or minus Baf. As above, labeled cells were analyzed using the Cellomics Arrayscan instrument (Cellomics Inc., Pittsburgh, PA).
2.5. Mitochondrial Membrane Potential
JC-1 fluorescent dye (Invitrogen Inc., Carlsbad, CA) is used to monitor mitochondrial health since it exhibits membrane potential-dependent accumulation in mitochondria reflected as a fluorescence emission shift from green (~529 nm) to red (~590 nm). Mitochondrial depolarization is indicated by a decrease in the red/green fluorescence intensity ratio (hyperpolarization exhibiting the opposite). JC-1 was added to cell cultures at a concentration of 5 g/mL for 30 minutes to allow for cellular accumulation. Media were then aspirated and replaced with fresh media containing drugs of interest without JC-1. Fluorescence was detected using a spectrofluorometer. The ratio of red to green signals was calculated and converted to % control for graphing and analysis.
3. Results
3.1. Differential Survival and NBD-PE Accumulation by Rat versus Dog Hepatocytes in Response to Phospholipogenic Compounds
To determine which species’ hepatocytes were more sensitive to phospholipogenic compounds, cells were treated for 24 hr with the potent phospholipogenic NMTMB, and endpoints of cell death and phospholipidotic response were monitored. Compared to rat hepatocytes, dog hepatocytes were more sensitive to treatment with this compound (Figure 2(a)). In this comparative experiment complete cell death occurred in dog hepatocytes at 100 M, whereas ~80% of rat hepatocytes typically survived at this concentration. Fluorescent phospholipid NBD-PE accumulation in live cells also differed markedly between the 2 species. Dog cells exhibited greater phospholipidotic response potency (illustrated by low test concentration responses that were not observed in rat cell conditions) but with a lower maximal response (% vehicle control). Figure 2(b) shows representative fluorescent images of NBD-PE containing hepatocytes illustrating these findings visually. At 10 M NMTMB, NBD-PE accumulation was lower in rat hepatocytes than in dog hepatocytes. At 50 M, rat cells exhibited significant NBD-PE accumulation (4-fold vehicle control), a majority of the cells were viable and NBD-PE responses were characterized morphologically by a punctuate-granular appearance. In contrast, at this concentration dog cell NBD-PE accumulation was diminishing, fluorescence was both punctuate-granular and diffuse in appearance, and ~70% cells were dead, accounting for the bell-shape of NBD-PE curves in these isolates (illustrated in Figure 2(a)).
Figure 2: (a) Differential effect of NMTMB on survival and NBD-PE accumulation in dog and rat hepatocytes. Cells were treated with compound in NBD-PE containing media. After 24 h cells were fixed with formaldehyde/Hoechst, and both survival and NBD-PE accumulation were quantified using the Cellomics Arrayscan instrument (as described in Section 2). Expressed as % control ±SD for 3 replicates from single isolations. Dog and rat hepatocytes were isolated for this experiment on the same day. (b) Differential effect of NMTMB on accumulation of NBD-PE in rat and dog hepatocytes. Cells were treated with NMTMB in NBD-PE containing media. After 24 h cells were fixed with formaldehyde/Hoechst and imaged using the Cellomics Arrayscan instrument. Image exposures were identical in all experiments (0.5 sec); background levels of NBD-PE accumulation were similar between dog and rat hepatocytes (approximately 50 mean average intensity units). Some artifactual accumulation of NBD-PE in dog preparations is apparent in the control sample. Dog and rat hepatocytes were isolated for this experiment on the same day.
To determine whether this species response differential was general, we tested a larger set of phospholipogenics, alongside a few nonphospholipogenic compounds (negative controls). This larger test set included compound A, a 5HT1b antagonist that caused in vivo multiorgan PLD in 1 month repeat-dose toxicology studies, including liver PLD in both dog and rat, and centrilobular loss in dog liver only (data not shown). Statistical comparisons across species were not applied in this particular instance since the data, while reflecting an average of three well replicates per experiment, only represent in some instances an average of or 2 individual (isolate) experiments (where histograms in the figure do not have error bars) (averages of 3 independent isolates have ±SEM error bars). Results however across independent experiments exhibit clear trends. Compared to rat hepatocytes, phospholipidotic responses by dog hepatocytes were more potent for 2 of 5 phospholipogenic compounds tested (NMTMB and Fluoxetine, Figure 3), but exhibited a lower capacity to accumulate NBD-PE compared to rat hepatocytes at higher concentrations for these two as well, compound A and hydroxychloroquine. Rat hepatocytes accumulated as much as 5-fold vehicle control levels of NBD-PE (% VC or maximal response), whereas dog hepatocytes never exceeded 3-fold vehicle control levels (Figure 3) (note: background NBD-PE levels detected by the Cellomics Arrayscan were similar between control dog and rat hepatocytes.). Compound A treatment did not yield a less potent NBD-PE response in rat hepatocytes compared to dog, but the maximal response in hepatocytes from this species was on average greater than 1.7-fold that for dog cells. In contrast to that for phospholipogenic treatment conditions, absolute levels of NBD-PE accumulation were minimal and differential effects in phospholipidotic potency or maximal response were not observed with negative control compounds in hepatocytes isolated from these two species (compound D exhibited 140% (dog) and 101% (rat) control activity at 300 M (, Figure 3); compound C exhibited 121% (dog) and 95% (rat) control activity at 300 M (, data not shown)).
Figure 3: Differential effects of phospholipogenic test articles on accumulation of the fluorescent phospholipid NBD-PE on dog and rat hepatocytes. Cells were treated with known phospholipogenic or nonphospholipogenic compounds in NBD-PE containing media. After 24 h cells were fixed with formaldehyde/hoechst, and NBD-PE accumulation was quantified using the Cellomics Arrayscan instrument. Image exposures were identical in all experiments (0.5 sec); background levels of NBD-PE accumulation were similar between dog and rat hepatocytes (approximately 50 mean average intensity units). Accumulation is expressed as % VC (vehicle control) at listed concentrations. Three replicates for each cell isolate were employed per experiment. Isolations occurred on separate days. The data are represented as an average of individual experiments where (where histograms do not have error bars) or an average of 3 independent isolates ±SEM.
Like responses to NMTMB, rat hepatocytes were more resistant to cytotoxicity caused by all other phospholipogenic compounds tested, including compound A (Table 1). Rat hepatocyte survival IC50 (half maximal inhibitory concentration) values were generally 2- to 3-fold greater than those for dog cells. For some rat treatment conditions, a convincing quantitative difference in survival could not be specifically determined given solubility limitations in DMSO, as concentrations required for IC50 (half maximal inhibitory concentration) interpolation would be above the highest concentrations tested (listed in Table 1 as >300 M or >450 M). It was thus clear that rat hepatocytes tolerated these compounds better than dog hepatocytes since rat cell survival was minimally affected at 300 or 450 M. Response differentials for either survival or NBD-PE accumulation were not evident with the nonphospholipogenic compounds, including compound D which consists of the right hand side aniline portion of the 5HT1b antagonist compound A and which does not contain a cationic phenylpiperazine moiety.
Table 1: Cell survival IC50 (half maximal inhibitory concentration) values of dog and rat hepatocytes treated with phospholipogenic or nonphospholipogenic compounds. Cells were fixed with formaldehyde/Hoescht, and survival was quantified using the Cellomics Arrayscan instrument (see Materials and Methods). Isolates were obtained on different days. The data are represented as individual experiments only ( = 1 or 2) or as an average of 3 individual (separate isolates, = 3) experiments ± SD.
3.2. Effect of Lysosomal Modulators on Survival Levels in Rat and Dog Hepatocytes Treated with Phospholipogenic Compounds
Lysosomes maintain their low pH via the proton transport activity of vacuolar ATPases. Baf is a macrolide antibiotic that acts as an inhibitor of vacuolar ATPases and therefore reduces lysosomal acidity. Baf was shown to prevent accumulation of the phospholipogenic compound hydroxychloroquine in Hela cells and reduced apoptosis caused by hydroxychloroquine treatment [18]. To address the question of whether phospholipogenic compounds are cytotoxic to hepatocytes by mechanisms involving lysosomes, effects of Baf on rat and dog hepatocytes were assessed in the presence of phospholipogenics. Results of experiments are shown in Figure 4. Dog hepatocyte survival in response to four of five phospholipogenics was significantly improved by cotreatment with 30 nM Baf. Rescue was conferred specifically against treatments of compounds from the same phenylpiperazine-containing AZ chemical series as well as hydroxychloroquine, but not for the more potent phospholipogenic fluoxetine in a singular experiment (or potent phospholipogenics amiodarone and perhexiline , data not shown). In contrast to dog conditions, Baf cotreatment improved rat hepatocyte survival only against hydroxychloroquine (marginally and may not be biologically significant since hydroxychloroquine was not very cytotoxic in the rat control condition (~25–35% change in survival)) and NMTMB.
Figure 4: Effects of lysosomal modulator Baf (30 nM) cotreatments on 24 h survival of phospholipogenic-treated rat and dog hepatocytes. Cell survival was measured using the Cellomics Arrayscan (see Section 2). The data are expressed as an average of 3 replicates (±SD) for a single cell isolate. Statistically significant (, -test) differences between dog phospholipogenic controls and modulator treatments occurred at the four top concentrations for NMTMB, top three concentrations for hydroxychloroquine, and top 2 concentrations for compounds A and B, and are illustrated by “”. For rat, statistically significant differences between phospholipogenic control and modulator treatments occurred at the top 3 concentrations for NMTMB and hydroxychloroquine and are illustrated by “”.
NMTMB was used subsequently for mechanistic investigations in rat cells as a representative tool to further probe common mechanisms mediated by the phenylpiperazine-containing AZ series because the phospholipidotic responses it caused in both species preparations were robust, and because cells treated with this compound were rescuable by Baf.
To confirm whether rescue is conferred by lysosomal modulation, rat hepatocytes treated with 300 M NMTMB were cotreated with a second lysosomal modulator, PADK, that operates differently than Baf. Butler et al. [20] showed PADK treatment upregulated active intralysosomal cathepsin D in hippocampal slices and to protect against chloroquine-mediated cytoxicity. In our experiment, PADK caused statistically significant rescue (average std dev % survival): 51 8.5 for NMTMB plus PADK versus 9.3 4% for NMTMB alone (, -test).
3.3. Effects of NMTMB Mitochondrial Polarization in Rat Hepatocytes
The work of Boya et al. [18] demonstrated that hydroxychloroquine-mediated Hela cell mitochondrial membrane permeabilization occurred secondary to lysosomal destabilization. Similarly, we sought to determine whether mitochondrial or lysosomal mechanisms were mediating phospholipogenic-induced hepatocyte cytotoxicity. Figure 5 shows an 8 hr time-course of mitochondrial polarization status (as indicated by JC-1 fluorescence measurement), NBD-PE accumulation and rat cell survival following NMTMB treatments at concentrations that bracketed the 24 h survival IC50 (159 M) and approached the approximate NBD-PE EC50 (half maximal effective concentration, ~65 M). At 100 M NMTMB, a mild but statistically significant (, -test) mitochondria hyperpolarization occurred within 1 h of treatment, before NBD-PE accumulation was evident. Hyperpolarization increased over time, reaching a maximum by 2 h. Cell survival during this time period variably dropped by 40%, that is, sixty % of the cells survived the 8 h treatment. At 300 M NMTMB statistically significant mitochondria depolarization was observed within the first hour and this preceded detectable NBD-PE signal elevation as well. By 2 h, there was a statistically significant increased NBD-PE accumulation and significant cell death (20% survival compared to control), and by 4 h cell death was complete.
Figure 5: Effect of NMTMB on cell survival, NBD-PE accumulation, and mitochondrial polarization (JC-1 fluorescence) over 8 hours. Rat hepatocytes were treated with NMTMB for 30 minutes, 1 h, 2 h, 4 h, or 8 h. The data are expressed as an average of 3 (±SD) replicates from a single cell isolate. A statistically significant difference in JC-1 and NBD-PE levels between corresponding control replicates and that for NMTMB conditions was achieved by 1 h and 2 h, respectively (, -test). As there was minimal survival observed for the higher test concentration beyond 2 h, NBDPE levels are not presented beyond 2 h.
Similarly, for other phospholipogenics employed, when using concentrations that bracketed both 24 h survival IC50 (half maximal inhibitory concentration) values and approximated NBD-PE EC50 (half maximal effective concentration) values, hyperpolarization occurred at the lower test concentrations and depolarization was evident only when the 24 h IC50 values were exceeded (data not shown). Treating rat cells with phospholipogenics having 24 h survival IC50 values >300 M yielded only hyperpolarization. In all cases, mitochondrial membrane polarity changes were evident by 30 min to 1 h and small NBD-PE increases were evident by 2 hr. Thus, for every phospholipogenic compound test condition, the mitochondrial changes occurred approximately 1 h or earlier than detectable phospholipidotic responses.
3.4. Baf Modulation of Mitochondrial Polarization State in NMTMB-Treated Rat Hepatocytes
To test whether lysosomal modulation affects mitochondrial membrane polarization, rat hepatocytes were cotreated with NMTMB and Baf, and JC-1 fluorescence was monitored over an 8 hr time-course (Figure 6). By 1 h Baf caused a marked shift from mitochondrial depolarization to a hyperpolarized state at the higher, 300 M NMTMB test concentration. Consistent with Baf cotreatment 24 h rescue shown in Figure 4, mitochondria from Baf cotreated cells never reached a depolarized state by 8 h.
Figure 6: Baf (30 nM) cotreatment shifted the mitochondrial polarization state of rat hepatocytes treated with NMTMB over an 8-hour time course. Rat hepatocytes were treated with NMTMB for 30 minutes, 1 h, 2 h, 4 h, 6 h or 8 h. Mitochondrial polarization status was monitored using JC-1 fluorescence on a Molecular Devices Flexstation instrument. The data are expressed as an average of 3 replicates (±SD) from a single cell isolate. Statistically significant differences between control replicates and that for all NMTMB conditions was achieved by 1 h (, -test).
3.5. Time-Course of AO Granular Staining Loss and Cell Death in NMTMB-Treated Rat Hepatocytes
The work by Boya et al. [18] suggested that hydroxychloroquine caused Baf-inhibitable lysosomal membrane destabilization, leading to cathepsin release and cell death. Since mitochondrial changes occurred prior to measurable phospholipidotic responses (elevated NBD-PE) in our experiments with NMTMB, we tested whether lysosomal membrane integrity was intact at early time points. To do this, we measured lysosomal staining with AO, a fluorescent dye that partitions into lysosomes. The fluorescent images in Figure 7 show robust/distinct, perinuclear, punctate staining of control cells and in cells from the lower concentration treatment throughout the time-course. In contrast, the higher, more cytotoxic, test concentration exhibited a combination of both diffuse cellular and punctuate AO fluorescence by 30 min. The spot count for the 100 M condition maintained or exceeded control levels of AO stained spots for up to 8 h. Within 30 minutes of treatment, the AO spot count in 300 M treated rat hepatocytes declined nearly 50% compared to control, and continued to drop to near 0% by 4 h. These early changes correlate with measures of cell death by 4 h (Figure 5) and suggest an early loss of lysosomal membrane integrity at 300 but not 100 M treatment. These effects occur concomitantly with mitochondrial membrane depolarization, but not hyperpolarization, and apparently prior to NBD-PE signal elevation.
Figure 7: NMTMB affected acridine orange (AO) staining of lysosomes of rat hepatocytes over an 8-hour time course. AO was added to hepatocyte media for 10 minutes, removed, and replaced with media containing compound. Treatment with NMTMB proceeded for 30 minutes, 1 h, 2 h, 4 h or 8 h. AO staining was monitored using the Cellomics Arrayscan instrument. The data are expressed as an average of 3 replicates (±SD) from a single cell isolate. A statistically significant difference between control replicates and that for the NMTMB high test concentration is achieved by 30 min (, -test) where marked cytotoxicity is evident by 4 hr (see Figure 5). Images from the Cellomics at the 30-minute time point are presented in (b).
4. Discussion
In this study dog and rat hepatocytes were treated with a variety of phospholipogenics to identify the more sensitive species and to test whether lysosomal or mitochondrial changes were the primary cause of cytotoxicity. We report that, against a panel of phospholipogenic treatments, dog hepatocytes exhibited lower 24 h survival IC50 (half maximal inhibitory concentration) values and generally exhibited a diminished capacity to accumulate NBD-PE, that is, dog hepatocytes appeared less able to process phospholipogenics and mount phospholipidotic protective responses across broad concentrations ranges. These differences appeared specific to phospholipogenic chemistries as they were not apparent following treatment with a limited test set of nonphospholipogenic (negative control) compounds, including compound D which consists of the right hand side aniline portion of the 5HT1b antagonist compound A and which does not contain a cationic phenylpiperazine moiety. Indeed, for negative control treatment conditions, NBD-PE did not accumulate significantly, dog and rat hepatocytes died at similar test concentrations, and cells treated with these agents were unresponsive to Baf cotreatment.
Rat hepatocyte data indicate that both lysosomal destabilization and mitochondrial toxicity played key roles in phospholipogenic-mediated cytotoxicity and that phospholipid accumulation does not. NMTMB-induced loss of AO punctate fluorescence and the appearance of diffuse AO fluorescence alongside mitochondrial membrane depolarization. Second, Baf, a macrolide antibiotic that acts as an inhibitor of vacuolar ATPases and reduces lysosomal acidity and drug accumulation, shifted rat mitochondria to a hyperpolarized state from a depolarized state that is more clearly associated with acute cytotoxicity. Third, an additional lysosomal modulator (PADK) known to cause upregulation of intralysosomal and protective enzymes, including cathepsins B, D and L [20, 21], also prevented rat cytotoxicity caused by NMTMB. (This proposed mechanism of protection does not contradict, and should not be confused with, a cathepsin proapoptotic property once cathepsins are released from the lysosome under membrane destabilizing conditions.)
Mechanisms of hydroxychloroquine-mediated cell death have also been hypothesized by Boya et al. [18] to include the lysosome. Hydroxychloroquine-induced lysosomal membrane permeabilization led to pivotal Hela cell release of the acid protease cathepsin B from lysosomes, which in turn caused mitochondrial membrane permeabilization, release of cytochrome c, and activation of the caspase 3-mediated apoptotic pathway. Under these circumstances cathepsin release is proapoptotic. Cotreatment of the cells with the lysosomal modulator Baf prevented these changes as well as accumulation of hydroxychloroquine in lysosomes. Finally, Baf-mediated rescue for other cell contexts was reported by Shacka et al [4]. They showed protection against chloroquine-induced, caspase 3-driven apoptosis of cerebellar granule cells.
When cotreated with lysosomal modulators known to confer protective biochemical responses, dog hepatocytes were generally more rescuable than rat hepatocytes from phospholipogenic-induced cytotoxicity, including that for the AZ phenylpiperizine series. Rescue conferred by Baf was observed in rat cells only when treated with hydroxychloroquine (marginally, as hydroxychloroquine was not very cytotoxic in the rat control condition) or NMTMB, the later being the most cytotoxic in the AZ phenylpiperazine series to both species preparations. As the weaker phospholopogenic AZ compounds were DMSO solubility-limited, it was not possible to determine whether Baf would prevent rat cell death at higher test concentrations of these compounds. The data otherwise suggest that this subset of compounds caused distinct mechanisms of cytotoxicity involving both lysosome and mitochondria, which can be abrogated by cotreatment with lysosomal modulation, and whose phenotypic responses were not fully shared by Fluoxetine.
Theoretically, if dog lysosomes have a diminished capacity to sequester phospholipogenics into lysosomes for cellular protection (so-called depot effect), they may accumulate high concentrations in the cytoplasm, be free for electrophoretic attraction to the mitochondrial inner membranous space and cause membrane polarization and subsequent ATP depletion. The greater lysosomal partitioning of NBD-PE in response to phospholipogenics in rat relative to dog hepatocytes suggests that the rat hepatocyte basal functional capacity may be larger. We do not know, however, whether these differences are driven by differences in morphology, levels or type of phospholipid substrates, or acidity. We did not observe differences between dog and rat hepatocyte control levels of the lysosomal markers Lysotracker, AO, or NBD-PE in short-term cultures (data not shown).
An important caveat on differences in dog versus rat cytotoxicity responses is that cytotoxicity could be a function of reactive metabolite generation. We did not profile microsomal capacity or metabolite generation from either dog or rat preparations and assume that cytotoxicity is driven primarily by parent molecules.
Baf exhibits additional biological activities, as exemplified by the recent work of Teplova et al. [22]. Using isolated rat mitochondria, they demonstrated that Baf is a mitochondrial potassium ionophore. It caused uptake of potassium by energized mitochondria, mitochondrial swelling, loss of membrane potential, uncoupling of oxidative phosphorylation, and inhibition of maximal respiration rates. The minimal concentration required to affect these changes were 50 nM, a level that falls in the effective range used for our whole cell experiments. However, since we do not know the intracellular Baf levels in our experiment, it is not possible to make a direct comparison to the data of Teplova et al. [22]. Furthermore, the effects on mitochondria described by them do not elucidate a mechanism of rescue for phospholipogenic treatment cell contexts in our study as they represent cytotoxic attributes, not protective ones.
In summary, our data add to the body of literature describing a complex picture of differences in phospholipogenic in vitro cytotoxicity relating to structure, phospholipogenic potency, and multiplicity of cellular effects in two species. We demonstrated that dog hepatocytes were with select compounds less capable of mounting an adaptive, protective phospholipidotic response than were rat hepatocytes, and both lysosomal and mitochondrial changes appear to be linked mechanistically to phospholipogenic-mediated cytotoxicity in vitro. It would be of interest to confirm in a comprehensive survey of in vivo toxicology studies whether the in vitro response profiles described here correlate with in vivo liver PLD and liver toxicity responses as they do for compound A. In addition, a comparison to hepatocytes from preclinical species to human is warranted in order to shed light on prediction/translatability of these cytotoxicity profiles.
Abbreviations
AO:Acridine orange
Baf:Bafilomycin A1
DMSO:Dimethyl sulfoxide
NBD-PE:N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-snglycero-3-phosphoethanolamine, triethylammonium salt
PLD:Phospholipidosis
NMTMB:N-[(2R)-5-methyl-8-(4-methylpiperazin-1-yl)tetralin-2-yl]-4-morpholino-benzamide.
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4. J. J. Shacka, B. J. Klocke, M. Shibata et al., “Bafilomycin A1 inhibits chloroquine-induced death of cerebellar granule neurons,” Molecular Pharmacology, vol. 69, no. 4, pp. 1125–1136, 2006. View at Publisher · View at Google Scholar · View at Scopus
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8. M. E. Cartwright, J. Petruska, J. Arezzo et al., “Phospholipidosis in neurons caused by posaconazole, without evidence for functional neurologic effects,” Toxicologic Pathology, vol. 37, no. 7, pp. 902–910, 2009. View at Publisher · View at Google Scholar · View at Scopus
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10. M. J. Reasor, C. M. McCloud, T. L. Beard et al., “Comparative evaluation of amiodarone-induced phospholipidosis and drug accumulation in Fischer-344 and Sprague-Dawley rats,” Toxicology, vol. 106, no. 1–3, pp. 139–147, 1996. View at Publisher · View at Google Scholar · View at Scopus
11. J. Willard, “FDA phospholipidosis working group preliminary results and developing opinions,” Presented at the Society of Toxicology (STP) Continuing Education Course on drug-induced phospholipidosis, 2008.
12. E. A. Tengstrand, G. T. Miwa, and F. Y. Hsieh, “Bis(monoacylglycerol)phosphate as a non-invasive biomarker to monitor the onset and time-course of phospholipidosis with drug-induced toxicities,” Expert Opinion on Drug Metabolism and Toxicology, vol. 6, no. 5, pp. 555–570, 2010. View at Publisher · View at Google Scholar · View at Scopus
13. P. R. Bernstein, J. Morelli, and P. Ciaccio, “Drug-induced phospholipidosis,” Annual Reports in Medicinal Chemistry, vol. 46, pp. 419–429, 2011.
14. L. R. Barone, S. Boyer, J. R. Damewood Jr., J. Fikes, and P. J. Ciaccio, “Phospholipogenic pharmaceuticals are associated with a higher incidence of histological findings than nonphospholipogenic pharmaceuticals in preclinical toxicology studies,” Journal of Toxicology, vol. 2012, Article ID 308594, 7 pages, 2012. View at Publisher · View at Google Scholar
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17. J. K. Morelli, M. Buehrle, F. Pognan, L. R. Barone, W. Fieles, and P. J. Ciaccio, “Validation of an in vitro screen for phospholipidosis using a high-content biology platform,” Cell Biology and Toxicology, vol. 22, no. 1, pp. 15–27, 2006. View at Publisher · View at Google Scholar · View at Scopus
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22. V. V. Teplova, A. A. Tonshin, P. A. Grigoriev, N. E. L. Saris, and M. S. Salkinoja-Salonen, “Bafilomycin A1 is a potassium ionophore that impairs mitochondrial functions,” Journal of Bioenergetics and Biomembranes, vol. 39, no. 4, pp. 321–329, 2007. View at Publisher · View at Google Scholar · View at Scopus
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Sea of death
pollution levels have reached alarming proportions in Mumbai, severely affecting the fish catch and other marine resources. B R Subramaniam, director of the Department of Ocean Development, blames population explosion and rising industrial activity along the coastline for the present situation. Estimates show that Mumbai contributes industrial effluents and 1,600 million litres of untreated sewage to the sea everyday.
Increased pollution load has mainly affected big cities as a huge amount of municipal waste is generated in these places. Oil spill by pipelines are also contributing to the rising pollution level in the sea. This has seriously affected several species of fish, mollusc, algae and other marine resources.
Most of the cities and towns along the coastline such as Mangalore and Kochi are also contributing to the pollution upsurge. Subramaniam points out that oil spill, industrial effluents and cutting down of mangrove forests such as the Sunderbans has also significantly contributed to the pollution.
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Bibliography: Castaway
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Title: Castaway
Author: Arthur C. Clarke
Year: 1947
Type: SHORTFICTION
Storylen: shortstory
Language: English
ISFDB Record Number: 65145
Note: First published under the name Charles Willis in the magazine Fantasy, The Magazine of Science Fiction, April 1947.
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Copyright (c) 1995-2011 Al von Ruff.
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Nano Perspectives
The Periodic Instability of Diameter of ZnO Nanowires via a Self-oscillatory Mechanism
Ye Zhang*, Youguo Yan and Feng Zhu
Author Affiliations
Key Laboratory of Materials Physics, Institute of Solid State Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, P.R. China
For all author emails, please log on.
Nanoscale Research Letters 2007, 2:492-495 doi:10.1007/s11671-007-9094-0
Published: 13 September 2007
Abstract
ZnO nanowires with a periodic instability of diameter were successfully prepared by a thermal physical vapor deposition method. The morphology of ZnO nanowires was investigated by SEM. SEM shows ZnO possess periodic bead-like structure. The instability only appears when the diameter of ZnO nanowires is small. The kinetics and mechanism of Instability was discussed at length. The appearance of the instability is due to negative feed-back mechanism under certain experimental conditions (crystallization temperature, vapor supersaturation, etc).
Keywords:
ZnO nanowire; Negative feed-back mechanism; Growth mechanism; Physical vapor deposition
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Preparing chemically competent cells
From OpenWetWare
Revision as of 16:14, 26 February 2007 by Jason R. Kelly (Talk | contribs)
Jump to: navigation, search
Contents
Materials
Glassware & Equipment
• Falcon tubes
• 500μl Eppendorf tubes, on ice
• 200ml conical flask
• 200μl pipetman or repeating pipettor
• 5ml pipette
Preparation
1. Grow a 5ml overnight culture of cells in LB media. In the morning, dilute this culture back into 25-50ml of fresh LB media in a 200ml conical flask. You should aim to dilute the overnight culture by at least 1/100.
2. Grow the diluted culture to an OD600 of 0.2 - 0.5. (You will get a very small pellet if you grow 25ml to OD600 0.2)
3. Put eppendorf tubes on ice now so that they are cold when cells are aliquoted into them later. If your culture is X ml, you will need X tubes. At this point you should also make sure that your TSS is being chilled (it should be stored at 4oC but if you have just made it fresh then put it in an ice bath).
4. Split the culture into two 50ml falcon tubes and incubate on ice for 10 min.
All subsequent steps should be carried out at 4oC and the cells should be kept on ice wherever possible
1. Centrifuge for 10 minutes at 3000 rpm and 4oC.
2. Remove supernatant. The cell pellets should be sufficiently solid that you can just pour off the supernatant if you are careful. Pipette out any remaining media.
3. Resuspend in chilled TSS buffer. The volume of TSS to use is 10% of the culture volume that you spun down. You may need to vortex gently to fully resuspend the culture, keep an eye out for small cell aggregates even after the pellet is completely off the wall.
4. Add 100 μl aliquots to your chilled eppendorfs and store at − 80oC.
• The original paper [1] suggests freezing the cells immediately using a dry ice bath. I (BC) have used liquid nitrogen quite successfully instead of dry ice. Simply placing the cells at − 80oC also seems to work well (Jkm)
• The Endy Lab is trying to use a standard positive control to better compare (and hopefully improve) the transformation efficiencies in the lab, you can check it out here.
Related topics & References
Based on a protocol from Kathleen McGinness, annotated by Josh Michener & Barry Canton. Original protocol published by Chung et al.[1] [2]
1. Chung CT, Niemela SL, and Miller RH. . pmid:2648393. PubMed HubMed [chung]
2. Chung CT and Miller RH. . pmid:8510550. PubMed HubMed [chung2]
All Medline abstracts: PubMed HubMed
Personal tools
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26 killed in China highway explosion
PanARMENIAN.Net - A truck carrying fireworks ahead of Chinese New Year celebrations exploded and destroyed part of an elevated highway Friday, February 1 in central China, killing at least 26 people as it sent vehicles plummeting 30 meters (about 100 feet) to the ground, state media said, according to AP.
The huge blast destroyed an 80-meter (80-yard) stretch of highway outside the city of Sanmenxia in Henan province, and was powerful enough to shatter windows of a nearby truck stop.
Emergency crews closed the highway at the accident site, said China National Radio, which reported the death toll of 26. The Xinhua News Agency reported four deaths but said search and rescue efforts were continuing. At least 15 people were injured and sent to nearby hospitals, the Henan Commercial Newspaper reported.
Photos posted on the popular news site Sina.com by Chinese netizens showed a stretch of elevated highway gone, with a truck perched precariously at the broken edge. Other photos showed wrecked trucks below and blackened chunks of scattered debris, including collapsed sections of highway, wrecked trucks and cargo containers.
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Jorge Rafael Videla, an austere former army commander, led Argentina during the bloodiest days of its Dirty War dictatorship.
According to the United Nations, April was Iraq's bloodiest month for almost five years, with 712 people killed.
Reports suggest the rebel fighters may have tried to blow up the walls of the prison, which holds some 4,000 inmates.
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[240] which was the point to be reached. It was expected that the Third corps, General French, would join the Second at Robertson's Tavern, but owing to General French having lost the road, this part of the programme was not carried out. General Hayes led the advance with his division, followed by General Webb's, then General Caldwell's division. At Robertson's Tavern, General Hayes met a large body of rebels and drove them back. General Webb happened to be near at hand, and at once deploying his forces to the right of the road, drove them back in confusion toward Raccoon Ford. It was in this spirited encounter that Lieutenant-Colonel Hesser, a gallant officer, fell mortally wounded. About this time, half-past 11 A. M., our skirmishers ascertained that the rebels were concealed in the thick woods, and were shrewdly extending their skirmishers to such an extent, that nearly all of the Second corps was required to check them.
At this time, rebel deserters and prisoners informed General Warren, that Johnston's rebel division was between him and Raccoon Ford, and that he was confronting Rhodes's rebel division.
General Meade was at once informed of this, and also that General Warren had received no tidings from General French on his right, and General Sykes on his left. General Warren notified General Meade that he was ready and willing to begin the attack, if he so desired, by advancing the centre, which was so weak as to be in a critical condition, and wholly unfit to cope with the superior forces of the enemy. It must be borne in mind that both wings of our army were then separated four or five miles from General Warren. General Meade instructed General Warren to wait until the right and left were heard from. Soon after, the roar of artillery was heard, and just then news came of the position of the left wing. The rapid cannonading came from General Gregg's cavalry division, who were engaging the enemy briskly on the plankroad. Heavy firing was heard shortly after at Morton's Ford, where General Custer's cavalry were skirmishing with Stuart's cavalry. During all this time, while General Warren was awaiting further orders and information, the enemy were artfully changing their lines, endeavoring to turn General Warren's right flank. While manaeuvring our forces, Lieutenant-Colonel Josselyn, commanding the Fifteenth Massachusetts volunteers, was seriously wounded, and fell into the hands of the enemy. This determination on the part of the rebels, induced General Warren to make a feint movement, as though about to offer battle for a general engagement. To do this, it was necessary to advance his line of skirmishers. He was entirely successful in deluding the wily foe, for, in the language of the F. F. V.'s, he fought “right smart” along the front of the Second corps. Colonel Carroll's brigade, composed of Western troops, conducted themselves in a manner that cannot be too highly praised. Colonel Carroll evinced considerable skill by drawing the enemy to his line of battle down she turnpike, where large numbers of Gordon's brigade, belonging to Early's division, were captured Colonel Carroll had a miraculous escape from instant death, his clothing having ten or twelve bullet-holes in it. Colonel Lockwood, of the same brigade, had his uniform pierced in several places by Minie balls.
In the afternoon, General Meade ascertained that General French had participated in an engagement, and the enemy had massed a force strong enough to successfully resist him. The exact position of the Third corps, at this time, still continued an uncertainty, although it was known to be four or five miles distant. At sundown General Warren ventured to advance his line of skirmishers, with a strong support. The enemy made a stubborn resistance, and retreated inch by inch, disputing his claim to the soil. Owing to the almost impenetrable woods, it was an impossibility to preserve a perfect line of battle, beside affording a subtle foe concealment, and an excellent opportunity to construct formidable earthworks in addition to those already there.
General Warren evinced his thorough military knowledge by using sufficient military caution in advancing so as to deceive the vigilant enemy, and thereby deter him from hurling his overwhelmingly strong numbers upon our lines. General Warren continued to maintain his position, although no other corps had formed a junction with him.
The First corps, General Newton, which had been ordered from the left in the afternoon, reached the rear of General Warren's command half an hour before dark, and, at daylight on the twenty-eighth, they were in line of battle on his left, a little south of the turnpike.
The Sixth corps, General Sedgwick, moved up and took position to the right of the Second corps, at daylight. At sunrise, the First, Second, and Sixth corps proceeded in line of battle simultaneously, but, to their great chagrin, they found the fleet-footed enemy had decamped during the night. By constant and rapid marching, our advance overtook their retreating rear-guard, and shortly after discovered the main body of the rebel army in a strong position on the west bank of Mine Run, which. is about one and three quarter miles from Robertson's Tavern.
Quite a number of deserters were picked up by our advance, and from them we learned that Hill's corps (rebel) had advanced from Orange Court-House down the plank-road, and there united with Ewell's corps, thereby concentrating the whole of Lee's army in a position naturally strong, and with formidable intrenchments to protect him.
To add to our numerous disadvantages, a heavy rain-storm set in early in the forenoon, accompanied with a thick fog, that foiled all our attempts, for a time, to continue a close inspection of the enemy's works and movements. Determined not to be balked by unpropitious weather, General Warren made a minute and personal reconnoissance
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[78] Vice-President Eve of this Association displayed conspicuous gallantry and rendered important service.
The venerable and brave Commodore Josiah Tattnall, commanding the naval forces at this station, afforded such assistance as the nature of the case and the means at hand justified.
It lies not within the compass of this address to enumerate the details of the siege, which, for ten days, was closely maintained. An incessant cannonade was supplemented at various points by sharp shooting and musketry firing. The artillery duels were particularly fierce at Battery Jones, at Pine-Point battery, at the redoubts crowning the high grounds of the plantations of Lawton and Daly, at the Central railroad crossing, and at Williamson's place. On more than one occasion the Federals demonstrated in force and attempted to carry the Confederate works, but suffered repulse. Protected by their entrenchments, the Confederates sustained comparatively few casualties.
On the afternoon of the 13th of December, Brigadier-General Hazen, with the second division of the 15th army corps, by a rapid assault, swept over the abattis and rear defenses of Fort McAllister and compassed its capture with a loss to his command of one hundred and thirty-four killed and wounded. In the language of this victorious officer, the fighting was desperate and deadly; and, when overwhelmed by the enveloping forces, the Confederates contested every inch of ground within the fort, finally retreating to the bomb-proofs, ‘from which they still fought, and only succumbed as each man was individually overpowered.’
Upon the fall of this work General Sherman acquired full control of the Great Ogeechee river, and was thus enabled to communicate freely with the Federal fleet and establish a convenient base of supplies for his army, then sadly in need of provisions for man and beast. The further retention of Savannah was rendered impracticable, and the salvation of its garrison became the problem of the hour. General Hardee's instructions from General Beauregard were to hold Savannah only so long as, in his judgment, it might be advisable to do so; and that whenever it became necessary to decide between a sacrifice of the garrison or the city, to preserve the former for operation elsewhere.
A conference between Generals Sherman and Foster and Admiral Dahlgren resulted in an agreement that the Admiral would speedily engage the Confederate batteries at Turner's Point, Rose Dew and Beaulieu, and furnish vessels suitable for the navigation of the Great
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Place:Berwick, Columbia, Pennsylvania, United States
Watchers
NameBerwick
TypeBorough
Coordinates41.057°N 76.248°W
Located inColumbia, 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
Berwick is a borough in Columbia County, Pennsylvania, 22.6 miles (36.4 km) southwest of Wilkes Barre. Berwick is one of two principal cities of the Bloomsburg–Berwick Micropolitan Statistical Area, a micropolitan area that covers Columbia and Montour counties and had a combined population of 82,387 at the 2000 census.
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Place:Remsenburg-Speonk, Suffolk, New York, United States
Watchers
NameRemsenburg-Speonk
TypeCensus-designated place
Coordinates40.82°N 72.701°W
Located inSuffolk, New York, United States
the text in this section is copied from an article in Wikipedia
Remsenburg-Speonk is a census-designated place (CDP) located in the Town of Southhampton, Suffolk County, New York. It consists of the hamlets of Remsenburg and Speonk. The population was 2,642 at the 2010 census. The population of this CDP and surrounding ones increases in the summer due to summer renters who come out for the beaches and scenery.
History
the text in this section is copied from an article in Wikipedia
As early as 1712, meadows in Speonk were leased to cattle owners from Southampton. Most of the early residents came west from Southampton and Bridgehampton in the 1740s, building farms and clearing the forests of wood. In the 1880s, duck farms thrived in Speonk, but few survived past the turn of the century. The name Speonk was inspired by a Native American word meaning "high place". An 1897 Long Island Rail Road catalog listed Speonk, noting that that name "certainly sounds like the call of a frog". Some residents pressed to change the name to "Remsenburg", after prominent resident Charles Remsen donated a new Presbyterian church. Today, both names remain in use, each covering different areas of the community.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Catalogue Number
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6. SMALL AREA DATA AVAILABLE FROM THE FIVE YEARLY AGRICULTURAL CENSUS
During the five yearly Agricultural Census, all in-scope agricultural businesses (155,000 in 2006) are approached for information. This coverage of the industry means data are suitable for release at the small area level for example, Local Government Areas. It is important that the Agricultural Census includes those questions which are required to inform users of agricultural statistics within a region.
The ABS holds discussions every five years with key users to identify any critical business, land or water management issues for which data can be collected in the Census and linked with small area commodity production data. As the number of questions which can be collected on Agricultural Census questionnaires is limited, and the collection opportunity occurs only once every five years, the ABS is keen to ensure that the most relevant and highest priority questions are included.
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Australian Bureau of Statistics
Celebrating the International Year of Statistics 2013
ABS Home > Statistics > By Release Date
8501.0 - Retail Trade, Australia, Jun 1996
Previous ISSUE Released at 11:30 AM (CANBERRA TIME) 31/07/1996
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• About this Release
Monthly; ISSN:1032-3651; Contains monthly estimates of turnover for retail and selected service establishments. Original, seasonally adjusted and trend estimates are included for Australia in current price terms. The original and trend estimates are disaggregated by State and by industry. Constant price data are published quarterly classified by State or industry.
This publication has been converted from older electronic formats and does not necessarily have the same appearance and functionality as later releases.
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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'm planning to incorporate in Delaware. But not sure If from the start I have to create an x amount of publications to be recognized in the state as an LLC.
I incorporated an LLC In NYC and it was a must from the start to have an x amount of publications to be recognized as an LLC by the state. It can be very expensive (it can easily be in the thousands).
If possible, I don't want to do any publications this time around. I just want to incorporate smoothly and just worry about my business.
share|improve this question
2 Answers
up vote 1 down vote accepted
Delaware does NOT have a publication requirement.
share|improve this answer
If you read Delaware State law on LLCs, you'll find that there is no publication requirement. http://delcode.delaware.gov/title6/c018/index.shtml
http://delcode.delaware.gov/title6/c018/sc02/index.shtml
NY State law has this requirement: http://law.justia.com/codes/new-york/2006/limited-liability-company-law/llc0206_206.html
You'll still have to pay annual renewal fees. Make sure to keep track of filing deadlines.
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Research article
Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection
Marijn Rutgers1, Daniël BF Saris1, Wouter JA Dhert1,2 and Laura B Creemers1*
Author Affiliations
1 Department of Orthopaedics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
2 Faculty of Veterinary Sciences, Utrecht University, Yalelaan 1, De Uithof, 3584 CL Utrecht, The Netherlands
For all author emails, please log on.
Arthritis Research & Therapy 2010, 12:R114 doi:10.1186/ar3050
See related letter by Moser, http://arthritis-research.com/content/12/6/410 and related letter by Rutgers et al., http://arthritis-research.com/content/12/6/411
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/12/3/R114
Received:24 October 2009
Revisions received:3 May 2010
Accepted:10 June 2010
Published:10 June 2010
© 2010 Rutgers et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction
Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration.
Methods
The effect of conditioned serum on PG metabolism of cultured OA cartilage explants was compared to unconditioned serum. The effect of serum conditioning on levels of interleukin-1beta (IL-1β), IL-4, IL-6, IL-10, IL-13, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG), oncostatin M (OSM), interleukin-1 receptor (IL-1ra) and transforming growth factor beta (TGF-β) were measured by multiplex ELISA. As TNF-α levels were found to be increased in conditioned serum, the effect of TNF-α inhibition by etanercept on PG metabolism was studied in cartilage explants cultured in the presence of conditioned serum. Furthermore, cytokine levels in SF were measured three days after intraarticular ACS injection in OA patients to verify their retention time in the joint space.
Results
PG metabolism was not different in the presence of conditioned serum compared to unconditioned serum. Levels of the anti-inflammatory cytokines IL-1ra, TGF-β, IL-10 as well as of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and OSM were increased. IL-4, IL-13 and IFN-γ levels remained similar, while OPG levels decreased. TNF-α inhibition did not influence PG metabolism in cartilage explant culture in the presence of condtioned serum. Although OPG levels were higher and TGF-β levels were clearly lower in ACS than in SF, intraarticular ACS injection in OA patients did not result in significant changes in these cytokine levels.
Conclusions
ACS for treatment of osteoarthritis contains increased levels of anti-inflammatory as well as pro-inflammatory cytokines, in particular TNF-α, but conditioned serum does not seem to have a net direct effect on cartilage metabolism, even upon inhibition of TNF-α. The fast intraarticular clearance of cytokines in the injected ACS may explain the limited effects found previously in vivo.
Introduction
Osteoarthritis (OA)-associated cartilage degradation is mediated in part by cytokines and growth factors, excreted into the intraarticular environment by synoviocytes, activated immune cells, or by the articular cartilage itself [1,2]. Therapies interfering with these cytokines may influence disease progression and improve the patient's quality of life.
A pivotal role in the progression of OA has been assigned to the pro-inflammatory cytokine interleukin-1β (IL-1β), which induces a cascade of inflammatory and catabolic events including the expression of cartilage degrading matrix metalloproteinases (MMP) [3], nitric oxygen (NO) production and prostaglandin E2 (PGE2) release [4], while inhibiting proteoglycan and collagen synthesis [5,6]. The number of type-1 IL-1 receptors is significantly increased in OA chondrocytes [7] and synovial fibroblasts [8], increasing the susceptibility for IL-1α and IL-1β mediated effects. In addition, it was suggested that in OA synovium, a relative deficit in IL-1ra-production exists [1]. As intraarticular administration of recombinant human interleukin-1 receptor antagonist has been shown to alleviate symptoms in several animal models of OA and rheumatoid arthritis [9-11], intraarticular treatment with IL-1ra was also suggested as a feasible treatment for patients with OA.
One example of a disease-modifying osteoarthritis-drug (DMOAD) based on blocking the intraarticular effects of IL-1 associated with OA, is autologous conditioned serum (ACS or Orthokine®; Orthogen, Düsseldorf, Germany). Autologous conditioned serum (ACS) treatment consists of six repetitive injections of ACS over a period of 21 days. ACS is prepared from whole blood that is incubated in the presence of glass beads to initiate monocyte activation [12,13]. The resulting conditioned serum (ACS), has been shown to contain increased levels of IL-1ra as well as IL-4 and IL-10 [12]. In horses with arthroscopically induced osteochondral defects, ACS treatment demonstrated a reduction in lameness and a decrease in synovial membrane hyperplasia [14]. ACS treatment of human OA patients, however, demonstrated limited to moderate clinical effects [15,16]. Despite the fact that this approach has already been introduced in the clinic, the mechanisms by which administration of this product may result in reduction of OA symptoms is not yet fully understood [14,16,17]. Although the primary goal of ACS treatment is alleviation of OA symptoms, one of the mechanisms may be enhancement of cartilage integrity through the inhibition of inflammatory activity, in particular with respect to Il-1 signalling. In fact, the direct effect of the entire blend of known and unknown factors present in ACS on cartilage metabolism in human OA cartilage has not been described. Moreover, only limited data are available on the actual composition of the conditioned serum. Besides IL-1ra, growth factors, such as transforming growth factor beta 1 (TGF-β1), which stimulates chondrocyte proliferation [18,19], are upregulated during incubation [17]. Of several pro-inflammatory cytokines like IL-1β, tumour necrosis factor-alpha (TNF-α) [20,21] and IL-6 [22], of the last of which also anti-inflammatory effects have been described [23], it is not entirely clear if their levels remain equal or are upregulated during incubation [12,17]. As a consequence of monocyte activation during incubation of blood, anti-inflammatory cytokines such as IL-13, which was shown to inhibit the production of IL-1β and enhance production of IL-1ra [24], and osteoprotegerin (OPG) [25], which protected cartilage in a murine model of surgically induced osteoarthritis from further degeneration [26], may be upregulated. Also pro-inflammatory cytokines oncostatin-M (OSM) [27] and interferon-gamma (IFN-γ) [28] which act synergistically with IL-1β to stimulate production of MMPs and aggrecanases, may be upregulated together with the anti-inflammatory cytokines. Even if the composition of ACS would be favourable to cartilage regeneration, it is still unknown to what extent the intraarticularly injected cytokines are present long enough in the knee joint to exert their actions. The intraarticular availability of adequate levels of IL-1ra is important, as IL-1β is considered to be active at low concentrations and relatively high levels of IL-1ra are required to inhibit the effects of IL-1β [29]. In vivo, increased IL-1ra levels were found in equine synovial fluid 35 days after the last (of four) injections with ACS [14].
The current study aims to evaluate the direct in vitro effect of conditioned serum on cartilage proteoglycan metabolism, to further evaluate the composition of ACS and to examine to what extent intraarticular injection of ACS is reflected in cytokine level changes in human osteoarthritic synovial fluid.
Materials and methods
Preparation of conditioned serum
To prepare conditioned serum, 35 ml of whole blood was acquired through venapunction and aspirated in six polypropylene syringes (5 ml) containing glass beads (Orthogen, Düsseldorf, Germany). The syringes were incubated at 37°C for six hours. After incubation, the blood was centrifuged at 1,000 × g for 10 minutes, and serum was aspirated and stored at -80°C until further use. Control syringes containing whole blood (5 ml without glass beads) were centrifuged and serum was stored at -80°C.
Effect of conditioned serum on proteoglycan metabolism
To measure the effects of conditioned serum on proteoglycan metabolism, 48 full thickness osteoarthritic cartilage explants were taken of the femoral condyles of OA patients undergoing a total knee arthroplasty (Kellgren-Lawrence grade III) and satisfying the OA criteria of the American College of Rheumatology [30]. The explants were cultured in the presence of conditioned serum (n = 24) or non-conditioned control serum (n = 24) of healthy serum donors. The cartilage was washed, cut into cubes of approximately 3 × 3 × 3 mm, weighed and cultured for 16 days in Dulbecco's Modified Eagles Medium containing 1% penicillin/streptomycin, 1% ascorbic acid (ASAP) and either 25% conditioned serum or 25% control (non-stimulated) serum. The experiment was repeated with two other OA cartilage and serum donor combinations (Table 1).
Table 1. Patient characteristics of cartilage explant experiments
Effect of TNF-α inhibition by etanercept on proteoglycan metabolism in the presence of conditioned serum
In another series of three experiments comparing the effect of conditioned serum and unconditioned serum on in vitro cartilage metabolism, Etanercept (Enbrel®, Wyeth Pharmaceuticals Inc., Collegeville, PA, USA) was added to full-thickness cartilage explants of femoral condyles of OA patients undergoing a knee replacement surgery and cultured in vitro. The explants were cultured with 25% control serum (n = 8), 25% conditioned serum (n = 8) and 25% conditioned serum with etanercept (1 μg/ml etanercept, n = 8). This concentration was based on a previous publication showing that this concentration was capable of inhibiting the activity of 40 ng/ml of TNFα [31].
35S incorporation was measured by means of a four-hour incubation with 35SO42-, on Day 4 for all conditions (see below). The medium released on Days 4, 8, 12 and on Day 16 was analysed for proteoglycan release, including release of newly synthesised PGs. The experiment was repeated with two other OA cartilage and serum donor combinations (Table 1).
35S incorporation
At Days 4, 8 and 12 of the culture, 35SO42-incorporation (Na2 35SO4, carrier-free; Perkin Elmer, Boston, MA, USA) was measured in order to quantify proteoglycan incorporation by means of a four-hour incubation in culture medium containing 20 μCi of 35SO42-. For the control as well as for the conditioned serum cultured cartilage explants, eight separate cartilage explants were used for each incorporation time point. Explants were then rinsed in plain culture medium during three 45-minute changes, and the culture of these explants was continued in isotope-free medium until the end of culture on Day 16. At Days 4, 8, 12 and 16, conditioned media were collected to quantify the release of newly synthesised PG. 35SO42- incorporation was quantified using a scintillation counter (Tri-carb 1900CA, Packard, Ramsey, MN, USA), and results were normalized to DNA content and weight of the sample.
Alcian blue immunoprecipitation and DNA assay
On Day 16, all cartilage explants were washed three times in phosphate-buffered saline (PBS) at 4°C. Explants were then digested in 2% papain (Sigma, St. Louis, MO, USA) in 50 mM phosphate buffer, 2 mM N-acetylcysteine, and 2 mM Na2-EDTA (pH 6.5) at 65°C for two hours. Part of the digest was used to measure DNA content and part was used for the quantification of the glycosaminoglycan content as a measure of proteoglycan content using an Alcian Blue precipitation assay (described below). Another part was used to measure 35SO42- activity.
Glycosaminoglycans (GAGs) were precipitated from the explant digests as well as from the culture medium and stained with an Alcian blue dye solution (Alcian blue 8GX, Sigma-Aldrich, Zwijndrecht, The Netherlands), saturated in 0.1 M sodium acetate buffer, containing 0.3 M MgCl2 (pH 6.2) for 30 minutes at 37°C [32]. The blue staining of the medium was quantified photospectrometrically from the change in absorbance at 620 nm, using chondroitin sulphate (Sigma) as a reference. DNA was stained with the fluorescent dye Hoechst 33258 (Sigma) and fluorescence was measured on the Cytofluor (MTX Lab Systems, Vienna, VA, USA) [33], using calf thymus DNA (Sigma) as a reference.
Composition of autologous conditioned serum (ACS)
Whole blood was obtained from 22 OA patients meeting the American College of Rheumatology criteria for OA (mean age 52 years, range 35 to 72). ACS for intraarticular treatment was prepared by whole blood incubation in the presence of ACS-specific glass beads. Unconditioned serum was taken as control.
Multiplex ELISA
Multiplex ELISA was used for measurement of cytokine levels in conditioned and unconditioned serum and in SF. Earlier validation studies showed high correlation of multiplex ELISA readings with conventional ELISA [34] and demonstrated that multiplex ELISA is suitable for SF analysis [35]. The cytokines measured were IL-1β, IL-4, IL-6, IL-10, IL-13, IFN-γ, OSM and OPG. Measurements and data analysis were performed using the Bio-Plex system in combination with the Bio-Plex Manager software version 3.0 using five parametric curve fitting (Bio-Rad Laboratories, Hercules, CA, USA). Coating antibodies for IL-1β, IL-6, IL-10 and TNF-α were provided by Strathman Biotec (Hannover, Germany); coating antibodies for IL-4, OPG and OSM by R&D Systems (Abingdon, UK), coating antibody for IL-13 by National Institute for Biological Standards and control (Potters Bar, UK) and coating antibody for IFN-γ by BD Biosciences (San Diego, CA, USA). The recombinant proteins for IL-1β, IL-6, IL-10 and IL-13 were provided by Sanquin (Amsterdam, The Netherlands), for IL-4 and IFN-γ by eBioscience (San Diego, CA, USA), for TNF-α by BD Biosciences, for OPG by R&D Systems (Abingdon, UK) and for OSM by Biocarta (Hamburg, Germany).
Preparation of recombinant cytokine mixes, covalent coupling of the captured antibodies to the microspheres and preparation of detection antibodies were performed as described previously [34,35]. For determination of cytokine profiles in SF, aliquots of 200 μl were first pre-treated with 20 μl of hyaluronidase (0.5 mg/ml, type IV-S, Sigma-Aldrich, Zwijndrecht, The Netherlands) for 30 minutes at 37°C, spun over 0.22 μm nylon membrane (Spin-X column; Corning, The Netherlands) and diluted with High-Performance ELISA-buffer (Sanquin Blood Supply Foundation, Utrecht, Netherlands) at a 1:2 dilution. Recombinant protein standards and calibration curves were prepared in serum diluents (R&D Systems). A mix containing 1,000 coupled microspheres per cytokine (total volume of 10 μl/well) was added to the standard, sample or blank, and incubated for 60 minutes. Next, a 10 μl mix of biotinylated antibodies (final concentration 16.6 μg/ml for each antibody) was added to each well and incubated for an additional 60 minutes. Beads were washed in PBS containing 1% BSA and 0.5% Tween 20 (pH 7.4) in order to remove residual sample and unbound antibodies. After incubation for 10 minutes with 0.5 μg/ml streptavidin R-phycoerythrin (BD Biosciences) and washing twice with 1% BSA and 0.5% Tween 20 (pH 7.4), the fluorescence intensity of the beads was measured in 100 μl High Performance ELISA buffer (Sanquin). Measurements and data analysis were performed using the Bio-Plex system in combination with the Bio-Plex Manager software version 3.0 using five parametric curve fitting (Bio-Rad Laboratories). To eliminate the possibility of inter-assay variability, control and conditioned serum samples were measured in duplo in the same assay.
ELISA
IL-1ra and TGF-β1 levels were measured using commercially available ELISA kits (Quantikine®, DRA00 and DB100B, R&D Systems), following the manufacturer's protocol.
Analysis of cytokines in synovial fluid after ACS injection
Twenty-two OA patients were treated with six consecutive injections of ACS at Days 0, 3, 7, 10, 14 and 21, according to the ACS treatment schedule. To this end, a 21 gauge needle was inserted into the knee joint through a lateral supra-patellar approach. After aspiration of the SF, 2 ml of ACS was injected into the joint through a 0.22 mm sterile nitrocellulose filter (Millex®, Millipore Express, Carrigtwohill, Co. Cork, Ireland). The knee was flexed and extended manually to ensure thorough distribution of the serum throughout the joint. Within 30 minutes after aspiration, the aspirated SF was centrifuged for 10 minutes at 1,000 × g and the aspirate and the residual serum samples were stored at -80°C until further analysis.
Treatment of patients with ACS was performed in compliance with the Helsinki Declaration. Written informed consent was given by all participants, and approval by the Medical Ethics Committee (University Medical Center Utrecht, The Netherlands; trial registration ID 03-232/G-O) was obtained before initiation of the trial.
Statistical analysis
SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for data analysis. Paired t-tests were used to compare cytokine levels in ACS and control serum of OA patients (n = 22 patients), and independent t-tests were used to compare PG content, DNA content and PG/DNA for each of the in vitro experiments. Analysis of variance (ANOVA) was performed on the pooled data of the experiments, with randomised block design to correct for inter-donor variability. Repeated measurement analysis was used to identify changes in SF cytokine levels during treatment. Comparisons between different treatments (control, ACS, Etanercept) were followed by a Bonferroni correction. P-values less than 0.05 were considered statistically significant. Graphs show mean values with standard deviation (SD).
Results
Proteoglycan metabolism of cartilage explant culture
An average of 40% of explant proteoglycan (PG) was released into the culture medium in 25% conditioned serum or in 25% control serum (Figure 1). PG release, PG content at the end of the culture, nor 35S incorporation on Days 4, 8 or 12 differed between OA cartilage explants cultured in either condition, measured with independent t-tests and ANOVA (Figures 1 and 2).
Figure 1. Proteoglycan incorporation and release during culture of cartilage explants (mean +/- SD). (a) Proteoglycan release during culture of cartilage explants. A similar amount of proteoglycans were released into the culture medium by explants cultured with unstimulated (n = 24) or conditioned serum (CS; n = 24). (b) PG incorporation rate on Days 4, 8 and 12 of the culture, measured using 35SO42- incorporation (n = 8 per timepoint). Results are representative of three separate experiments with different OA cartilage donor - serum donor combinations.
Figure 2. Proteoglycan and DNA content during culture of cartilage explants (mean +/- SD). Proteoglycan and DNA content of cartilage explants after culturing with unconditioned serum (n = 24) or conditioned serum (CS, n = 24 cartilage explants). (a) Proteoglycan content. (b) DNA content, (c) PG/DNA ratio.
Proteoglycan metabolism upon TNF-α inhibition by etanercept
Addition of etanercept to conditioned serum or control serum did not alter PG release, PG incorporation and final PG or DNA content after culture measured with independent t-tests and ANOVA (Figures 3 and 4).
Figure 3. Proteoglycan incorporation and release during culture in unconditioned, conditioned or conditioned serum with Etanercept (mean +/- SD). Proteoglycan release and incorporation (mean +/- SD) in the presence of unconditioned serum (control, n = 8), conditioned serum (CS, n = 8) or conditioned serum with etanercept (n = 8). (a) Proteoglycan release, (b) Proteogycan incorporation on Day 4, measured by 35SO42- incorporation (n = 8). Results are representative for three separate experiments with different OA cartilage donor - serum donor combinations.
Figure 4. Proteoglycan and DNA content during culture in unconditioned, conditioned serum or conditioned serum with Etanercept (mean +/- SD). Proteoglycan (PG) metabolism in the presence of unconditioned serum (control, n = 8), conditioned serum (CS, n = 8) or conditioned serum with etanercept (n = 8). (a) PG content, (b) DNA content, (c) PG/DNA ratio.
Cytokines in unconditioned serum and ACS
Serum levels of IL-10 and IL-1ra increased after conditioning (3.0-fold and 7.9-fold, respectively) (P < 0.01). Of the other anti-inflammatory cytokines, TGF-β1 was upregulated (14.9-fold) and OPG was downregulated (2.8-fold) (both P < 0.001). Pro-inflammatory cytokines IL-1β, OSM and TNF-α were upregulated (20.9-fold, 2.9 fold and 10.2-fold, respectively) (all P < 0.01) while IFN-γ levels did not change. IL-6 levels were upregulated 19.3 fold (P < 0.001). IL-4 levels and IL-13 levels were below detection limits in non-stimulated serum as well as in ACS (Figure 5).
Figure 5. Effects of whole blood conditioning on serum cytokine levels of 22 OA patients. Cytokine levels in serum of 22 OA patients, before incubation (control) and after six hours of incubation in the presence of glass beads (ACS). Note the increase in anti-inflammatory cytokines (IL-1ra, TGF-β1, IL-10) and pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, OSM, TNF-α) after incubation. OPG levels were decreased. All values are displayed as mean ± SD in pg/ml. * P < 0.01; ** P < 0.001.
Cytokines in synovial fluid before and after treatment
Sufficient amounts of SF for all treatment time points were available for analysis in 14 patients. To verify whether this implied a bias in the ensuing experiments, clinical grade of OA and baseline serum cytokine levels were compared between this group of patients and the eight patients from whom no SF could be aspirated. No statistically significant differences between these patients and the other group of eight patients were noted (Table 2).
Table 2. Clinical scores and serum cytokine levels in patients with sufficient and with non-sufficient SF for analysis
Levels of IL-1β, IL-4, IL-13, TNF-α, and IFN-γ were low or undetectable in SF before and during treatment with ACS. IL-6, OSM, OPG, IL-10, TGF-β and IL-1ra were detectable in synovial fluid, but only OPG and TGF-β levels differed significantly from ACS levels. The levels of OPG in SF at baseline were higher than in ACS (14,476 pg/ml vs. 134 pg/ml, P < 0.001), but had not changed significantly three days after injection of the serum. Baseline synovial fluid TGF-β levels were lower than in ACS (580.7 vs. 21,670.9 pg/ml, P < 0.001), but did not change significantly after ACS injection either (Figure 6).
Figure 6. Cytokine levels in control serum and ACS, and in synovial fluid during treatment. Control serum (control), autologous conditioned serum (ACS) and synovial fluid cytokine levels (mean +/- SD) of IL-1RA, TGF-β1, IL-10, IL-6, OSM and OPG during treatment with ACS in 14 OA patients. The large symbols next to the y-axis correspond to the levels of these cytokines in control serum and the injected ACS. TGF-β1 levels in SF were lower than in the injected ACS, and OPG levels in SF were higher than in ACS (P < 0.01). During the course of treatment, no significant changes in cytokine levels occurred despite repeated ACS injection (SF was aspirated before each of the six injections with ACS, at t = 0, Day 3, Day 7, Day 10, Day 14 and Day 21).
Discussion
Disease-modifying drugs for conservative treatment of osteoarthritis have proven effective in a variety of randomized controlled clinical trials [36,37]. Although autologous conditioned serum (ACS, Orthokine®) proved slightly to moderately effective for alleviation of OA symptoms up to two years after treatment in human OA patients [15,16], many aspects of this therapy have remained unclear so far.
In vitro, conditioned serum does not seem to have a direct effect on cartilage metabolism compared to unstimulated serum. In line with earlier studies, IL-1ra levels of ACS in the current study were upregulated, although the reported relative increases in conditoned serum differed an order of a magnitude with those from the current study [12,17]. Also IL-10 levels were upregulated two-fold as found earlier [4], but IL-4 was hardly detectable. It is not known to what extent this is related to the change in the manufacturer's protocol, in which the conditioning period is reduced to six hours [17], as opposed to the 24 hours initially included in the preparation protocol [14,15]. Allegedly, most of the cytokine production occurs after six hours. Moreover, although this has not been argued as such by the manufacturer, long incubation periods at body temperature are known to reduce the bioactivity of most cytokines, while their immunoreactivity as determined by ELISA is still retained [38]. In particular Il-10, one of the anti-inflammatory cytokines upregulated in ACS, has been shown to have a half-life of several hours under these conditions [39]. This may also represent another explanation for the limited effects found in vivo thus far. More important, however, pro-inflammatory cytokines, in particular IL-1β and TNF-α, were found to be significantly upregulated in the current ACS study, in contrast to previous results [17]. As, unlike for IL-1, the increased TNF-α levels were not counterbalanced by an increase in levels of natural inhibitors, and TNF-α has been postulated to have degenerative effects on cartilage [21,40], this may have explained the limited effects found in OA patients treated with conditioned serum. However, blocking the action of TNF-α [31] did not result in a net positive effect of conditioned serum on matrix metabolism in vitro, suggesting that, if any, in vivo effects of the TNFα in the injected ACS would have been indirect. It is not clear to what extent the increased levels of IL-6, OSM and lower levels of OPG in conditioned serum may have had a pro-inflammatory effect, but as conditioned serum addition did not result in decreased sulphate incorporation after four days of cartilage explant culture, or a lower PG content after 16 days of culture, conditioning of serum is not likely to have any effect on OA cartilage. These findings were strengthened by the large number of explants used per experiment, and by repeating both experiments in a total of six different OA donors. Nevertheless, it cannot be excluded that factors present in conditioned serum, either known or as yet undiscovered, play a role in vivo by inducing other mediators, not determined in the current study, in the joint space. With respect to the role of Il-1 signalling in OA, in the one human clinical study using recombinant IL-1ra as a treatment for OA, a single injection into the knee joint did not result in an improvement of OA symptoms [41]. This may have been due to fast clearance from the joint space. Injection of ACS led to an increase of IL-1ra SF levels in osteoarthritic equine knee joints during ACS treatment in vivo [14]. However, in the current study, IL-1ra levels did not increase during the course of the treatment, even though the interval between injection and measurement was shorter than in the former study (3 days vs 7 and 35 days [14]). The fast clearance of injected cytokines from the joint found in the current study suggests that any in vitro net effect would still have been difficult to reproduce in vivo. Continuous intraarticular availability of IL-1ra may be more effective. In vivo injection of synoviocytes transduced with the IL-1ra gene into a canine knee joint after sectioning of the anterior cruciate ligament [11] and intraarticular injection of IL-1ra plasmid into a rabbit knee joint after meniscectomy resulted in reduction of OA clinical symptoms (histological parameters, preservation of articular cartilage quality) [42]. Eventually these long term approaches may be more effective than the limited number of injections of this treatment, but currently they are not practically feasible in a clinical setting. Nevertheless, even if IL-1ra levels are increased in the synovial fluid in vivo, it is uncertain if these IL-1ra levels correlate with OA symptoms or disease progression, as the ratio of IL-1ra to IL-1β in the SF of human OA subjects were shown not to correlate with pain or with the Lequesne OA index [43].
With respect to the upregulation of IL-1β, its role in progression of OA may actually be disputed [44]. In our study, IL-1β levels in OA SF were extremely low, which is in line with previous reports [34,45,46]. Although there are studies in which IL-1β inhibited proteoglycan synthesis in vitro at concentrations as low as 10 pg/ml [47], commonly IL-1β concentrations of at least 1,000 pg/ml are used to induce detectable cartilage damage [48,49]. Studies demonstrating synergistic effects of IL-1β with IFN-γ, TNF-α, IL-17 or Oncostatin-M [50] also departed from IL-1β concentrations much higher than detected in OA synovial fluid and hence synergistic effects of low IL-1β levels with other cytokines in the current study do not seem likely. Moreover, the baseline IL-1ra levels in the SF of the currently studied OA patients were already in the effective range to block IL-1β [29]. Although it may be argued that the patients with sufficient amounts of SF may have differed from the group as a whole, this is contradicted by the observation that serum cytokine levels as well as the clinical response of the patients with sufficient amounts of SF were similar to the patients with insufficient amounts of SF.
A high standard deviation in synovial fluid cytokine levels was encountered, as is common in OA. Increasing the number of subjects may decrease this standard deviation and possibly enable subgroup analysis (for example, by progression of OA according to radiological parameters (dGEMRIC) or by clinical parameters (KOOS scores). However, as the group of patients was already small, this would have even further reduced the likelihood of finding statistically significant changes.
Future evaluation of intraarticular cytokine changes following ACS injection might include SF analysis earlier after injection, which would give further insight on intraarticular half-life. Also, effects of ACS on synovium, either alone or in coculture with cartilage explants may be studied. Even though multiplex ELISA showed good to excellent correlation with ELISA [34], separate ELISAs may give slightly more accurate information about absolute cytokine levels.
Although the present in vitro data show no effect of ACS and a short intraarticular half life, a recent clinical study demonstrated a two-year lasting improvement of ACS treatment compared to hyaluronic acid and placebo treatment [51]. However, it must be noted that the treatment regimens differed, with six injections of ACS being compared to three injections of hyaluronic acid or placebo. Moreover, as none of the clinical trials carried out so far included unconditioned serum as a placebo, it can actually not be excluded that injection of serum without prior conditioning per se has a beneficial effect on proteoglycan metabolism in vivo.
Conclusions
In conclusion, ACS is a mix of counteracting growth factors and cytokines that does not have a direct effect on cartilage metabolism and probably has a minimal influence in the joint space, given the fast disappearance of cytokines from the synovial fluid after injection. Development of new intraarticular therapies may focus on their prolonged presence in the joint space.
Abbreviations
ACS: autologous conditioned serum; ASAP: ascorbic acid; DMOAD: disease-modifying osteoarthritis-drug; GAGS: glycosaminoglycans; IFN-γ: interferon gamma; IL-1ra: interleukin-1 receptor antagonist; IL-1β: interleukin-1 beta; IL-4: interleukin-4; IL-6: interleukin-6; IL-10: interleukin-10; IL-13: interleukin-13; MMP: matrix metalloproteinases; NO: nitric oxygen; OA: osteoarthritis; OPG: osteoprotegerin; OSM: oncostatin M; PG: proteoglycan; PGE2: prostaglandin E2; SD: standard deviation; SF: synovial fluid; TNF-α: tumor necrosis factor alpha; TGF-β: transforming growth factor beta.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MR carried out the in vitro and in vivo experiments, analysed and interpreted the data and drafted the manuscript. DS participated in design and coordination of the study and revised the manuscript. WD was involved in design of the study and revised the manuscript. LC conceived of the study and participated in its design and coordination, aided with statistics and revised the manuscript. All authors read and approved the final manuscript.
Acknowledgements
The authors wish to thank the Anna Foundation for Musculoskeletal Research in The Netherlands, the Netherlands Organisation for Health Research and Development (NWO) and the Dutch Arthritis Association (Reumafonds) for their continuous support. The authors wish to thank W. de Jager, PhD for his assistance with the multiplex ELISA and P. Westers, PhD for his statistical advice.
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Firefox Debuts New Developer Toolbar
Mozilla
7
Firefox makes developing for the Web faster and easier with a unique Developer Command Line. The new tool provides easy keyboard control over Firefox Developer Tools and is intuitive, completing commands and parameters for you.
In addition, Firefox unprefixes a number of stable features including: CSS3 Animations, Transitions, Transforms, Image Values, IndexedDB and Values and Units. Firefox also unprefixes Battery API and Vibration API, two Web APIs that Mozilla helped create.
On mobile, Firefox for Android introduces Reader Mode to make it easier to view, read and share articles and stories from your mobile phone or tablet. Simply tap the “Reader” icon in the Awesome Bar to activate. This feature provides an enjoyable and clutter-free way to read online content by removing advertisements, reformatting pictures and increasing font size.
For more information:
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Isotope Technique (14C, 131I) for Safety Analysis of Domestic Solid Waste Disposal Site in Jakarta, Indonesia- A Case Study
Syafalni Syafalni, I. Abustan, M. Tadza Abdul Rahman
Abstract
Bekasi is one of city around Jakarta which has been developed for the last 10 years. In the south of Bekasi placed sanitary landfill area for domestic solid waste of Jakarta Metropolitan as a Disposal Site. The objective of the present study is to evaluate the location of Bantar Gebang Bekasi solid waste disposal site for safety analysis. The geohydrologycal parameters are determined by using isotopes techniques (14C, 131I) to study the shallow groundwater characteristics of the site. From the results of 14C the direction of groundwater movement is found to be from South to the North and turned to North West of Jakarta at Jakarta Center. From radiotracer method (131I) the direction of shallow groundwater in the rainy is observed to be from the disposal site to the surrounding area and the Ciketing canal which flows to the North. For the dry season from the disposal site to the surrounding area. The results from environmental isotopes and hydrochemistry analysis indicate that the pollutants from the site have given an impact to the surrounding area of disposal site which was shown by migration of nitrate. It is recommended that the decision maker should give high priority to the geology, geohydrology and environmental pollution studies for consideration of disposal site for the safety of sanitary landfill.
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Modern Applied Science ISSN 1913-1844 (Print) ISSN 1913-1852 (Online)
Copyright © Canadian Center of Science and Education
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Working With Connection Strings in ASP.NET 2.0
0
kicks
Working With Connection Strings in ASP.NET 2.0 (Unpublished)
If you work with data, then you need a way to connect to your data source and manipulate the information contained within. In .Net, as always, there are a number of ways to tackle this issue. This article provides an overview of the most common methods and links to further reading.
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NOTE: If you are a developer, please use a private wiki based on foswiki/trunk on a daily base ...or use trunk.foswiki.org to view this page for some minimal testing.
Use Item9693 for docu changes for 1.2 and 2.0.
Item1354: SEARCHDEFAULTTYPE causes confusing and the misspelling means that people think this is the problem
Priority: CurrentState: AppliesTo: Component: WaitingFor:
Normal Closed Engine
Item6217_2009_03_18T16_36_14Z
From TWikibug:Item6217
DEFAULTTYPE, not DEFAULTTTYPE.
And even if I corrected the spelling, it didn't work. After I change that setting to regex, in WebSearch Page, it still uses keyword search.
-- TWiki:Main/FengZhaolin - 18 Mar 2009
It is actually misspelled also in the code.
Fix or not fix? Piss of anyone that put it in SitePreferences by fixing it or not?
I think we should not fix it.
The problem Feng raised that "it does not work" is that he tries in the WebSearch page which has it own idea of default.
I choose to document what we have because
• The only time we have heard trouble is this one bug item
• The WebSearch works fine as it is and the default we have now was discussed and decided on some years ago
• The spelling correction will create more trouble than help
and I will not change any behavior at all.
-- KennethLavrsen - 22 Mar 2009
ItemTemplate edit
Summary SEARCHDEFAULTTYPE causes confusing and the misspelling means that people think this is the problem
ReportedBy KennethLavrsen
Codebase
SVN Range Foswiki-1.0.0, Thu, 08 Jan 2009, build 1878
AppliesTo Engine
Component
Priority Normal
CurrentState Closed
WaitingFor
Checkins Foswikirev:3239 Foswikirev:3240
TargetRelease patch
ReleasedIn 1.0.5
Topic revision: r5 - 25 Apr 2009, KennethLavrsen
The copyright of the content on this website is held by the contributing authors, except where stated elsewhere. see CopyrightStatement.
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For the half-year to 30 June 2013, the IPKat's regular team is supplemented by contributions from guest bloggers Stefano Barazza, Matthias Lamping and Jeff John Roberts.
Two of our regular Kats are currently on blogging sabbaticals. They are Birgit Clark and Catherine Lee.
Thursday, 24 January 2008
You're no gent, says Court of Appeal
In October 2006 Mr Justice Mann (Patents Court, England and Wales) gave ruling in Cinpres Gas Injection Ltd v Melea Ltd [2006] EWHC 2451 (Ch) which very greatly upset the IPKat (see here). In short, Cinpres sought a declaration that it was entitled to be registered as owner of a patent for gas injection moulding technology used in the plastics industry. But did the inventor, James Hendry, make the invention when working for Cinpres -- or was he then working for Ladney, an American businessman who set up Melea as a patent holding company? Hendry first worked for Cinpres but left the company after falling out with it in 1985. A year and a quarter later, after entering into a settlement agreement with Cinpres that contained a confidentiality clause, Hendry took up a consultancy with Ladney with whom he worked till 1991. In 2001 Hendry returned to Cinpres, this time as a consultant. Meanwhile in 1996 the UK Patent Office had ruled that Hendry had discovered the invention while working for Ladney, in consequence of which Melea was registered as proprietor. Hendry, who had given evidence before the Patent Office in support of Ladney, subsequently wanted to give evidence that he had discovered the invention while working for Cinpres. Cinpres said it was not barred by the earlier proceedings from seeking a fresh declaration that it was entitled to the patent, since Hendry was willing to admit that he had perjured himself when giving evidence in the earlier proceedings and to testify that Ladney had procured, or taken advantage of, his decision to do so.
Mann J dismissed Cinpres' application. He agreed that Hendry had lied on oath and had both acquired and deployed knowledge of the invention while working for Cinpres. Also, the use of the invention was something that Hendry should have kept confidential under the terms of the settlement agreement with Cinpres; his perjured evidence was therefore relevant to a material matter. However, since Ladney had not actually induced Hendry to commit perjury and did not know of it or take any advantage of it, the decision in the earlier proceedings could not be impeached and it governed the issue of the ownership of the patent. Said Mann J:
"I appreciate that that result might be considered by some as less than satisfactory – the entitlement to the patent is governed by a decision which was reached after receiving and accepting perjured evidence and which might have been different if the truth had been told. However, that is the effect of the requirements of the applicable principles, as to which there was no dispute between the parties".
The Court of Appeal today reversed this decision (text in full on BAILII). The Court (Sir Igor Judge, President of the Queen's Bench Division, plus Lords Justices Jacob and Richards) commented that the parties had taken so many new points that the case was scarcely recognisable as that upon which Mann J originally had to decide.
The anonymous judge giving the decision of the Court of Appeal (the BAILII transcript posted today doesn't mention names, but the IPKat suspects it might just be Jacob LJ -- even though para. 52 mentions him in the third person ...). Anyway, the Court had some interesting things to say about the manner in which an appellate court should consider a finding of dishonesty by a trial judge:
"It is one thing for the Court of Appeal to hold a man a perjurer for the first time on appeal but quite another to hold that an established perjurer was more extensive in his perjury than held by the judge. The real question here is simply whether the Judge was wrong in his evaluation of all the evidence".
In this regard, said the Court,
"We are not satisfied that he reached the wrong conclusion on the facts. Ladney is not shown to have been complicit in Hendry's perjury at the time. It does not follow, however, that he has not himself adopted and relied upon that perjury and Hendry's false story".
The Court then effectively pinned Hendry's evidence on Ladney:
" ... we have come to the conclusion that Hendry's evidence the first time round should be regarded as that also of Ladney and that Hendry's fraud should be treated as also that of Ladney. Both Hendry and Ladney were actually parties to the first proceedings. Hendry was seeking to justify his claim to be the inventor, to be named on the patent as such and to have had the right to have assigned the property in the invention to Ladney. Ladney was claiming to be the owner of the right to apply for the patent by virtue of assignment from Hendry. They had a common foe, Cinpres, and made common, and completely intermixed cause against it. One could not succeed without the other. True it is that Ladney's claim was much the more valuable commercially, but we do not see that value has anything to do with it. Besides even Hendry had a commercial interest in the patent belonging to Ladney for he would be entitled to royalties if that were so. Not so if the patent belonged to Cinpres.
Putting it another way it would be wrong to say that Hendry was a "mere witness" in the first proceedings. He was more than merely a witness for Ladney – he was Ladney's "comrade in arms". His fraud by way of perjury was being adopted by Ladney and should be regarded as Ladney's. Hendry himself clearly could not resist the earlier judgment being set aside on the grounds of his fraud. Given that, the whole judgment is unravelled and should be set aside".
The IPKat notes the genuine indignation of the Court, whose judgment opened with the stern comment that
"Mann J had the unenviable task of deciding, as between two liars and perjurers, what the truth was (or at least what was most likely) about the making and ownership of the invention the subject of the Patent. ... James Hendry was one of the liars. The other was Michael Ladney. Neither deserves the courtesy of a 'Mister'".
Merpel is delighted with the outcome of this appeal. A sensitive Kat, she has suffered for fifteen months from the notion that British patent law could operate in such a manner as to deprive Cinpres of a patent to which it was morally and, in her opinion legally, entitled.
The truth, the whole truth and nothing but the truth here
When truth is fiction here
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