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subset: commoncrawl


text:
Baltimore Orioles v Tampa Bay Rays
Outfielder Wil Myers of the Tampa Bay Rays runs through the bullpen... News PhotoAmerican League Baseball,Ball,Baltimore Orioles,Baseball - Sport,Baseball Bullpen,Catching,Florida - US State,Gulf Coast States,Horizontal,Major League Baseball,Outfielder,Sport,St. Petersburg - Florida,Tampa Bay Rays,Tropicana Field,USA,Wil MyersPhotographer Al MesserschmidtCollection: Getty Images Sport 2013 Getty ImagesST. PETERSBURG, FL - SEPTEMBER 22: Outfielder Wil Myers #9 of the Tampa Bay Rays runs through the bullpen after catching a ball near the right field line against the Baltimore Orioles September 22, 2013 at Tropicana Field in St. Petersburg, Florida. The Rays won 3 - 1. (Photo by Al Messerschmidt/Getty Images)


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Podesta Group
The Podesta Group is a lobbying and public affairs firm based in Washington, D.C.. It was founded in 1988 by brothers John Podesta and Tony Podesta and has previously been known as Podesta Associates, podesta.com and PodestaMattoon. The firm most recently reorganized in January 2007 after current Chairman Tony Podesta split with former business partner Dan Mattoon.
Source: Wikipedia
Some of this data may be out of date
State influence data from the National Institute on Money in State Politics changed in format and availability during the 2013-2014 election cycle. While we work to integrate their new style of data release, state-level campaign finance data for the 2014 cycle and beyond will be unavailable. We apologize for the inconvenience, but heartily recommend trying out their snazzy new site at FollowTheMoney.org!
Campaign Finance$3,466,019 Given
Figures are based on itemized contributions reported to the Federal Election Commission and state agencies. Please note that:
- contributions under $200 are not reported, and so are not included in totals.
- only contributions from individuals and organizations to candidates are included. Various accounting measures and more exotic contribution types are excluded.
- contributions are matched based on organization and recipient name reported within each election cycle. Contributions using an incorrect or non-standard version of the name may be missed.
- corporate name changes and mergers may cause figures to differ from those of the Center for Responsive Politics.
- organization totals include known subsidiaries of the organization.
For more information, please see our campaign finance methodology page. Lobbyist bundling data is described on our lobbyist bundling methodology page.
state-level data is not available in bulk for 2014. for current state data, browse http://followthemoney.org/
Top Recipients
- PAC Color Block
- Organization's PAC(s)
- Employee Color Block
- Associated Individuals
Republicans vs. Democratsin dollars. "Other" includes 3rd parties and organizations without official party affiliation.
State vs. Federalin dollars
Top PAC Recipients
- PAC Color Block
- Organization's PAC(s)
- Employee Color Block
- Associated Individuals
Bundled ContributionsMoney raised by the firm from multiple donors on behalf of the recipient. The firm's own contributions are not included.
Recipient Lobbyist Amount Democratic Senatorial Campaign Cmte Tony Podesta $420,300 Democratic Congressional Campaign Cmte Tony Podesta $351,400 Harry Reid Tony Podesta $123,350 Searchlight Leadership Fund Tony Podesta $35,500 Henry A. Waxman Tony Podesta $30,500 Charles E. Schumer $21,000 Patty Murray Tony Podesta $20,500 Robert Menendez Andrew Kauders $16,100
Lobbying$183,230,000 Income
Figures are based on lobbying activity reported to the Senate Office of Public Records. Reported dollar amounts are required to be accurate only to the nearest $20,000. For organizations whose primary business is lobbying, we display total income and top clients. For organizations that are not primarily lobbying firms, we display total amount spent on lobbying and top lobbying firms hired.
For more information, please see our lobbying methodology page.
Lobbying Carried Out by Podesta Group
Names of Lobbyists
Client Amount Google Inc $3,590,000 Lockheed Martin $3,520,000 Wal-Mart Stores $3,190,000 Wells Fargo $3,180,000 Alliance for Quality Nursing Home Care $2,990,000 General Dynamics $2,970,000 Reed Elsevier Inc $2,970,000 BP America $2,640,000 BP America $2,640,000 BAE Systems $2,640,000
Most Frequently Disclosed Lobbying Issues
- Fed Budget & Appropriations,
- Health Issues,
- Taxes,
- Medicare & Medicaid,
- Defense,
- Energy & Nuclear Power,
- Copyright, Patent & Trademark,
- Finance,
- Pharmacy,
- Trade
Most Frequently Disclosed Bills
Bill No. Title H.R.2454 American Clean Energy And Security Act of 2009 H.R.1 American Recovery and Reinvestment Act of 2009 H.R.3200 America's Affordable Health Choices Act of 2009 H.R.3590 Service Members Home Ownership Tax Act of 2009 S.1733 Green Taxis Act of 2009 S.2029 Physician Payments Sunshine Act of 2007 H.R.1260 Patent Reform Act of 2009 S.515 Patent Reform Act of 2009 H.R.3162 Children's Health and Medicare Protection Act of 2007 S.1213 Patient-Centered Outcomes Research Act of 2009
Recent Lobbying Contracts
Date Client Summary Sept. 11, 2015 Creative Associates International H.R. 2772 / S. 1725, Department of State, Foreign Operations, and Related Programs Appropriations Act, 2016. View registration July 21, 2015 West African Real Estate Holdings Limited Supporting urban development projects in Africa. View registration July 20, 2015 West African Land Holdings Limited Supporting urban development projects in Africa. View registration July 20, 2015 Orange County, FL FY 2016 appropriations. View registration July 20, 2015 Debevoise & Plimpton LLP International finance issues. View registration
RegulationsMentioned in 6 dockets
All data is based on documents downloaded from Regulations.gov. The first table shows mentions: all documents that include the name of the company anywhere in the document or document metadata. The second table shows submissions: all documents where the submitter metadata included the company name. Each table shows the top 10 dockets, ranked by number of occurrences.
Matches are based on a search for the company name. Variations in the company name, such as acronyms, nicknames or alternate names may cause documents to be missed. The mention of a company name in a document may be incidental and does not necessarily indicate that the company has any relevance to the document. Company names that are common English words may erroneously match with text that is not referring to the company.
Not all agencies submit public comments to Regulations.gov. For a list of participating and non-participating agencies see here. Agencies that do submit to Regulations.gov have varying levels of accuracy and completeness.
Regulations and public comments can be downloaded in bulk here.
The tables show occurrences of "Podesta Group" in public comments on proposed federal regulations.
Mentions in Document Text
- Mentions
- Agency
- Docket
- Date
View all mentions data for Podesta Group
- Toggle 3 EPA National Emission Standards for Hazardous Air Pollutants for Coal- and Oil-fired Electric Utility Steam Generating Units 2009
- Toggle 1 NHTSA Environmental Impact Statement for New Medium and Heavy Duty Vehicle Fuel Efficiency Improvement Program Standard 2014
- Toggle 1 NHTSA Environmental Impact Statement for Corporate Average Fuel Economy (CAFE)Standards, Model Years 2017-2025 2011
- Toggle 1 EPA 2014 Standards for the Renewable Fuel Standard (RFS) Program 2013
- Toggle 1 NHTSA Corporate Average Fuel Economy -- Model Years 2017-2025 2010
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From Yahoo Sports: The returning Velasquez ran out of gas in the Mexico City altitude as Werdum adds another chapter to his legacy. read news >>
Blasphemy! According to some mixed martial arts (MMA) experts, perhaps the most dangerous tool Cain Velasquez has in his arsenal is his legendary cardio. Ultimate Fighting Championship's (UFC) Heavyw read news >>
Khabib Nurmagomedov hasn't let his foot off the gas pedal in his war of words on Donald Cerrone, heading into UFC 187 on May 23rd. Now he's taking shots at Cerrone's affinity for drinking and "Cowboy read news >>
Grappling coach Ricky Lundell used to joke with friend Todd Place that there were so many CPR-certified people at Las Vegas' Bishop Gorman High school, there was little need to polish their life-savi read news >>
Following the viral video that showed the 'MMA gas station guy' pummelling assailants who were attempting an armed robbery, Mayura Dissanayake stepped back inside the ring and earned a quick stoppage read news >>
If three burly thugs couldn't stop Mayura Dissanayake, then what possible hope did lil' Jamie Garcia have? None, as you can see from the video above, and the latter was the recipient of a high-octane read news >>
After dishing out some beatings to would-be robbers, Mayura Dissanayake took his talents back to the ring. The results, though, were much the same.Filed under: News, Videos read news >>
Video: Mayura Dissanyake, the store clerk who beat down a few would-be thieves in Houston, Texas, has received an open invitation from wrestling mastermind Kenny Johnson (via YouTube) to train with h read news >>
Get a Big Gulp, a foot long, and an ass-whooping all in the same place. That's a lesson a couple of would-be robbers learned when they tried to ambush a store clerk in Houston, Texas, unaware that th read news >>
Phoenix Jones better move over. He's not the only crime-fighting MMA aficionado out there these days. Mayura Dissanyake, a cashier at a Houston convenience store and self-proclaimed semi-pro MMA figh read news >>
Build a bigger gas tank and ratchet up your strength with this three-pronged attack. read news >>
Demian Maia needs a win in the worst kind of way, but he's trying to not let the pressure of a big homecoming get to him.Filed under: News, UFC read news >>
The Joe Warren gas tank was there when he needed it. read news >>
UFC lightweight and title contender Gilbert Melendez admits the stress of negotiations with Bellator and UFC were intense, but they also helped him solidify his priorities. Now that he's resign read news >>


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Discussion Questions - Scott v. Harris
Use the discussion questions to help form your opinion on the case.
- Was the chase – and its outcome – a consequence of Harris breaking the law or did police use excessive force to end the chase?
- Did the police exceed the limits of the Fourth Amendment protection against unreasonable seizure?
- Two lower courts disagreed on the key issue. The Supreme Court determined the final outcome. How would you decide?


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Have you ever wanted to sneak something out of your child's dresser, give it to Goodwill and then pretend you don't know what happened to it?
Oh, that's just me?
I've done a lot of shopping with my tween and teen girls so I know they have a lot of cute, stylish clothes in their closets. But I see the same outfits all the time — and they're not my favorites.
I've made a gallery of my girls' clothes that I would take to the Goodwill if I could ever wrestle the items off their bodies. If you, too, have an item in your child's closet that you rue the day you ever purchased, e-mail a photo to me at firstname.lastname@example.com and I'll add it to the gallery.
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text:
Similar to other countries, Vodafone in UK using the same approach in retrieving your MMS pictures. Only the URL name is slightly different.
You may proceed to http://getmyphoto.vodafone.co.uk which later will be redirected to https://getmyphoto.vodafone.co.uk/mcp-vfg-prd_uk/front?cmd=defaultlogin&firstTime=true
Quoted from their website:
This service allows you to view multimedia messages (MMS) that have been sent to you. For every message you receive, you can reply with your own multimedia message, or forward it to someone else.
Multimedia Messages can be sent by people with camera-equipped mobile phones and may contain pictures, sounds or even video clips. If your handset cannot display the contents of the message, it is sent here where you will be able to view it. Please note that if you have a Vodafone live! Studio account you can still access your old messages and content on the live! Studio service in the usual way by going to www.vodafone.co.uk/livestudio.
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text: 23-year-old pole-vaulter Jillian Schwartz will represent Israel in the Olympic games. Schwartz immigrated to Israel from the United States. She will participate in the 2012 London Olympics.Tags: OlympicsRelated StoriesRegev: Being Quiet About PA Sports was a 'Mistake'Campaign Against Israel in 2016 Olympics?Asia's Olympic Chief Calls for Hijab to be AllowedCeremony Marks 40 Years Since Munich Massacre 'Jewish Star' to be Inducted into Hall of FameMaccabi Games Kick off with 'Minute for Munich''Jewish Star' Accepts Invitation to Visit IsraelJewish Gymnast Honors Israeli VictimsNazi Ties May Force Athletes to Take Democracy VowJewish American Gymnast Aly Raisman Takes Gold


text:
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ACE Fit Share
Add these shoulder exercises into your regular workout routine and increase your upper body strength, while strengthening and stabilizing your shoulders. From the stability ball dumbbell press to the medicine ball push-up, these exercises are a great way to strengthen your deltoids, rotator cuff and trapezius muscles. Browse through our large collection of detailed tutorials and step-by-step demonstrations from today's leaders in the health fitness industry. For full workout routines featuring these shoulder exercises, visit our Workouts section.
Fit Life Articles
A strong core is essential for a healthy back and a body that moves well in both sports and everyday life. This 10-minute workout strengthens the muscles of the torso through the use of static-hold exercises coupled with dynamic movements, all of which will challenge these...
Strong biceps are not just for show—they are responsible for bending the elbow and make it possible for you to lift and carry heavy objects—including your own body weight. This 10-minute biceps workout is a great way to strengthen these essential muscles.
There's never been a better time to upgrade your current workout playlist. ACE has partnered with Power Music to create three compilations to help make physical activity feel less strenuous. Whether you are a lunchtime walker or group fitness instructor looking to better...


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This issue of Reflections is intended to help us think through the value of art and beauty in various venues of faith in the 21st century and see its many applications. The essays take a measure of the role of art and music in a local church. They challenge us to reflect on the power and use of poetry not only for personal edification but for use in worship. They analyze the understanding of beauty in Kant, von Balthasar, and Jonathan Edwards. And they engage with the architectural significance of modern church structures. I hope that you find these essays as helpful and encouraging as I have.
Beauty provokes awe and wonder in us. Though we admire the creativity and skill of the artists, this beauty and creativity is really a reflection of the perfection and creative powers of God. Beauty enables us to experience the Creator God who exists beyond space and time of the sense-perceptible world we inhabit, whether we experience that beauty through our eyes, our ears, or multiple senses. Johann Sebastian Bach was right to sign his cantatas ad majorem Dei gloriam, not only to express his intent in composing each choral work, but to capture our reaction to the experience of hearing it.
Read more From the Dean's Desk


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This resource covers the history and culture of the United States and Canada, from prehistory to the present. With hundreds of full-text journals and books, and selective indexing for journals dating back nearly 60 years, this database is a key reference tool for students and scholars of U.S. and Canadian history.
Scholarly Full-Text Content
Strong English-language journal coverage is balanced by an international perspective on topics and events. Abstracts are available in English, which were originally published in a variety of languages.
America: History and Life with Full Text covers all key journals in the discipline, state and local history publications, and selected articles from scholarly journals in the social sciences and humanities. In addition to standard search features, this database allows for searching by time period, an essential lfeature given the extensive range of its coverage.
Advanced Search, with its elegantly laid-out tool set for crafting very precise search strategies, gives the user great control over the whole search process.– Library Journal


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Kaspersky Internet Security 2011
Kaspersky Internet Security 2011 : Virtual Keyboard To avoid the possibility that a keylogger might capture your password you can enter them using the virtual keyboard, shown here in its expanded format.
25 / 41
Bottom Line
This suite's firewall is smart enough to do its job without hassling you, its parental control tops almost all the competition, and it offers some unusual and useful bonus tools. Its performance in my anti-malware tests didn't come up to the glowing ratings from independent labs, though.


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Blepharospasm: The most common adverse reactions (incidence greater than or equal to 10% of patients and twice the rate of placebo) for XEOMIN were eyelid ptosis (19%), dry mouth (16%), visual impairment (12%), diarrhea (8%), and headache (7%).
DRUG INTERACTIONSConcomitant treatment of XEOMIN and aminoglycoside antibiotics, spectinomycin, or other agents that interfere with neuromuscular transmission (e.g., tubocurarine-like agents), or muscle relaxants, should be observed closely because the effect of XEOMIN may be potentiated.
USE IN PREGNANCYPregnancy Category C: There are no adequate and well-controlled studies in pregnant women. XEOMIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Please see full Prescribing Information for XEOMIN, including Boxed WARNING, available atwww.XEOMIN.com. About Merz Merz Pharmaceuticals, LLC is a part of the Merz Group of companies and was established in 1995 to develop and commercialize products for the Merz Group. Areas of therapeutic focus include Neurology, Physiatry, Dermatology, and Podiatry.
With over a century of heritage, the Merz Group is known worldwide for its development of original compounds and formulations for medical professionals and consumers in 90 countries. Globally, Merz is a leader in the development of pharmaceuticals for the treatment of neurological and psychological disorders as well as for aesthetic medicine. Global research is concentrated in fields that have a strong need for therapeutic innovation such as Alzheimer's disease, Parkinson's disease, tinnitus, chronic pain conditions, addictions, and neuromuscular disturbances.
XEOMIN is a registered trademark of Merz Pharma GmbH & Co KGaA.<
|SOURCE Merz Pharmaceuticals
Copyright©2010 PR Newswire.
All rights reserved


text: > View Product Details Please select the size of the product. Please enter valid quantity. Alberto Fermani black leather flat tall boots overview details Retail: $575.00 Reduced: $268.99 40% Off : $161.39 color : We're sorry. This style is currently unavailable. Black These gorgeous boots from Italian designer, Alberto Fermani, feature finely crafted natural leather and a chic design that's typical of the label's innovative creations. Color: Black Supple, soft leather upper Tapered almond toe Full side zip closure Leather lined Rubber sole Shaft measures 17�'' tall and 14�'' around widest point Leather / Rubber; Italy; style#312349201


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analog-to-digital converter
(n.) An analog-to-digital converter, or ADC as it is more commonly called, is a device that converts analog signals into digital signals. Analog information is transmitted by modulating a continuous transmission signal by amplifying a signal's strength or varying its frequency to add or take away data. Digital information describes any system based on discontinuous data or events. Computers, which handle data in digital form, require analog-to-digital converters to turn signals from analog to digital before it can be read. One example is a modem which turns signals from digital to analog before transmitting those signals over communication lines such as telephone lines that carry only analog signals. The signals are turned back into digital form (demodulated) at the receiving end so that the computer can process the data in its digital format.
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Press Releases
Our Sponsors
|DOMA Under Fire in Equal Benefits Case
Today Lambda Legal and Morrison & Foerster LLP filed an amended complaint challenging the constitutionality of the so-called Defense of Marriage Act (DOMA) in its case representing Karen Golinski, a federal court employee denied spousal health benefits for her wife.Anti-LGBT Rulings, Laws and Amendments | Employment and Rights in the Workplace | Marriage, Relationships and Family Protections
|DOMA Shift Not Reflected in Latest Government Filing in Lambda Legal's Golinski v. OPM
(San Francisco, February 28, 2011) The U.S. Department of Justice has announced that it will continue to deny spousal health insurance benefits to a lesbian federal employee, in spite of last weeks announcement that Attorney General Eric Holder has determined that the so-called Defense of Marriage Act (DOMA) is unconstitutional and that DOJ therefore will no longer defend it against court challenges.Marriage, Relationships and Family Protections
|DOMA Shift Leaves Government Out of Excuses, Lambda Legal, Morrison & Foerster Inform Judge
Lambda Legal and Morrison & Foerster LLP today told a federal judge that government attorneys have shown they have no further arguments and therefore no further legal barrier exists to a married lesbian federal employee receiving spousal health benefits already provided to her heterosexual co-workers. U.S. Department of Justice (DOJ) attorneys had argued that, among other reasons, the so-called Defense of Marriage Act (DOMA) prohibits the employer-provided medical insurance that Karen Golinski had requested for her spouse, Amy Cunninghis. Lambda Legal and Morrison & Foerster represent Golinski, a 19-year-employee of the U.S. Ninth Circuit Court of Appeals.Anti-LGBT Rulings, Laws and Amendments | Employment and Rights in the Workplace | Health Care Fairness | Marriage, Relationships and Family Protections
|DOJ Tells State Licensing Boards And Occupational Training Schools That It Is Illegal To Bar People With HIV
|DOJ Delivers Powerful Critique of DOMA in Lambda Legal Case
On Friday, the U.S. Department of Justice (DOJ) filed a brief strongly arguing that the Defense of Marriage Act (DOMA) is unconstitutional in a case brought by Lambda Legal and Morrison & Foerster LLP on behalf of Karen Golinski, a lesbian federal court employee denied medical coverage for her wife, whom she married when same-sex couples could do so in California. The DOJ had previously announced they would no longer defend DOMA, but this is the first legal filing in the country in which they have fully argued to a court that DOMA is unconstitutional. They asked the federal court not to dismiss Golinski's claim.Anti-LGBT Rulings, Laws and Amendments | Employment and Rights in the Workplace | Health Care Fairness | Marriage, Relationships and Family Protections
|Do the Boy Scouts of America Have a First Amendment License to Discriminate?
(NEW YORK, October 25, 1999) -- At a Washington, D.C., forum about the recent defeat of the Boy Scouts of America's anti-gay policy, Evan Wolfson, senior staff attorney at Lambda Legal Defense and Education Fund, will explain why New Jersey's highest court correctly ruled that there is no first amendment problem with requiring the BSA to comply with anti-discrimination law.
|Divided California Court of Appeal Rejects Challenge to Discriminatory Marriage Law
FOR IMMEDIATE RELEASEOctober 5, 2006(San Francisco, California, October 5, 2006) In a 2 – 1 decision that will be appealed to the California Supreme Court, a divided panel of the California Court of Appeal ruled today that California may continue to bar same-sex couples from marriage.
|Discriminatory Policy Raises Questions About Special Treatment for Boy Scouts
(NEW YORK, July 19, 2000) — Barely one month after the Boy Scouts of America established its right to discriminate against gay members, long-time Scouts supporters are questioning their continued involvement with the organization, and the special government treatment long accorded the youth group increasingly is coming under close scrutiny.
|Disappointment for Russian Lesbian Seeking Asylum
(NEW YORK June 6, 1997) -- Immigration officials Thursday refused to resolve a Russian lesbian's asylum case and instead ruled that Alla Pitcherskaia must prove to an immigration judge that she is likely to be persecuted if returned to her native country, Lambda Legal Defense and Education Fund said.Immigration
|Disappointing ADA Rulings Threaten Protections for Workers with Disabilities
(NEW YORK, June 23, 1999) -- Lambda Legal Defense and Education Fund expressed disappointment Wednesday over three United States Supreme Court decisions that substantially limit the scope of the Americans with Disabilities Act.HIV


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European Journal of Clinical Microbiology & Infectious Diseases
EJCMID is an interdisciplinary journal devoted to the publication of communications on infectious diseases of bacterial, viral and parasitic origin.
The journal welcomes full articles presenting original research results, invited editorials, and reviews on the following topics:
- General epidemiology and diagnostics of infectious agents
- Clinical infectious diseases research
- Genetics and phenotypes of host susceptibility towards infectious disease or colonization
- Use of animal models to study bacterial infections and the imaging of such infections
Studies should primarily be performed from a mechanistic point of view with emphasis on the inter-relatedness of molecular features with clinical presentation of infections. Papers on the translational application of basic research findings will be prioritized.
- 34 Volumes
- 367 Issues
- 7,510 Articles
- 181 Open Access
- 1982 - 2015 Available between
Latest Articles
Original Article
Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production
N. T. Mutters, S. Zimmermann, M. Kaase… (October 2015)
Original Article
Real-time polymerase chain reaction and culture in the diagnosis of invasive group B streptococcal disease in infants: a retrospective study
M. Meehan, M. Cafferkey, S. Corcoran… (October 2015)
Original Article
Triclosan-coated sutures and sternal wound infections: a prospective randomized clinical trial
S. Steingrimsson, L. Thimour-Bergström… (October 2015)
- Journal Title
- European Journal of Clinical Microbiology & Infectious Diseases
- Coverage
- Volume 1 / 1982 - Volume 34 / 2015
- Print ISSN
- 0934-9723
- Online ISSN
- 1435-4373
- Publisher
- Springer Berlin Heidelberg
- Additional Links
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Continue reading...
To view the rest of this content please follow the download PDF link above.


text: More from SI Report: Dodgers release pitcher Freddy Garcia Report: Dodgers release pitcher Freddy Garcia Marshawn Lynch sports gold cleats for Super Bowl Marshawn Lynch sports gold cleats for Super Bowl Louisville vs. FIU: Game time, live stream, TV coverage Louisville vs. FIU: Game time, live stream, TV coverage Pittsburgh-area high school football player dies after... Pittsburgh-area high school football player dies after... Close Tweet0 Share0 Comment0 Share0 Share0 Stumble It0 Print0 More SI Wire Sean Spence injury: Steelers LB suffers severe damage to left knee by alin0303 Email Posted: Fri Aug. 31, 2012 A promising 2012 draft for the Pittsburgh Steelers is quickly being torn asunder by injury. Just one week after losing first-round OG David DeCastro to a severe right knee injury (although DeCastro might be able to return late in the season), the Steelers apparently have also lost third-round LB Sean Spence to an even more devastating knee injury.Mike Florio of ProFootballTalk.com is reporting that Spence is believed to have a torn ACL, a torn LCL (lateral collateral ligament) and a dislocated knee cap. Spence was carted off the field with his leg in an air cast after his cleat appeared to get caught in the turf while he was pursuing Carolina Panthers quarterback Jimmy Clausen.Here's a screenshot of the injury:https://twitter.com/fsmikey/status/241344668745490433/ Spence's journey to becoming the next great Steelers linebacker will have to wait a year. He was listed as Lawrence Timmons' backup on Pittsburgh's official depth chart. Promoted Stories Comments


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The Escarpment Retreat provides luxury accommodation on Mt Tamborine and Hope Island. Our retreat on Mt Tamborine is set on four acres of botanical gardens and lush rainforest, complete with flowing stream, small waterfall and cliff views at the rear of the property through the surrounding valleys as far as the Gold Coast. Featuring romantic couple's only chalet style villas in a garden setting with a Balinese flavour, plus the 3-bedroom Edge Hose family accommodation an award-winning Day Spa, private Gold Class Cinema and a spectacular tree house common room in the rainforest.
In addition to this, we also have a newly refurbished 5-bedroom holiday rental in Sanctuary Cove featuring garden or water views from almost every room, a courtyard with a swing and an in-ground pool.
Our rainforest mountain sanctuary has 6 romantic villas, featuring sunken lounge rooms, cosy log fireplaces, luxurious couches, cedar floors, vaulted timber ceilings, private balconies, posturepedic king size beds, decadent deep spa baths, flat screen tv's, dvd, cd players and iphone chargers. Nestled in a beautiful rainforest garden setting.
This amazing 3-bedroom holiday rental in our property on Mt Tamborine is perched on a cliff with amazing views as far as the coast. Designed for self-catering, the Edge House has a fully equipped kitchen and a barbecue. Featuring 2 viewing deck including one with a fireplace, 2 bathrooms, a triple spa bath, open plan dining and living rooms, 2 viewing decks and luxury appointments. It is perfect for families who wish to escape and spend quality time in a rainforest setting, for girls getaways or accommodation for the entourage of your Mt Tamborine wedding.
Look inside our beautiful, 5 bedroom holiday rental in Sanctuary Cove. Located in the heart of the Northern Gold Coast on Hope Island, a short 15-min drive from popular attractions. Featuring garden or water views from almost every room in the house, a central courtyard and an inground pool. Ideal for those who wish to experience the laid-back lifestyle of a resort style community, families visiting the popular gold coast theme parks, and golf enthusiasts.
Laguna is our newest and most luxurious holiday home in Sanctuary Cove. This beautiful waterfront home features a glass-fenced pool, poolside covered entertaining area with huge built-in BBQ, broad waterfront terrace and 9m pontoon plus free use of inflatable boat and golf buggy.


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Police break up massive college party
Footage of hundreds of party-goers throwing projectiles at riot police in Bellingham, Wash. as they attempt to control a chaotic scene.
Join the discussion
PoliceOne top 5
- 1 Video: Md. cop shoots, kills man who 'aggressively' advances towards him
- 2 SC cop shot, killed by suspect in mall
- 3 Sheriff: 9 killed, 7 injured in shooting at Ore. college
- 4 Numbers talk: Officers killed in the line of duty, people fatally shot by police
- 5 Fla. officer's finger nearly bitten off, suspect fatally shot


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This comprehensive guide is for Plone website administrators and developers. Whether you are new to Plone, are already running Plone websites, or would like to be able to build custom Plone solutions, this is the book for you. With something for everyone, from complete beginners, to those with a working knowledge of Python and Zope, to seasoned experts, this book will help you gain a deep understanding of Plone.
J. Cameron Cooper has been playing around on the web since there wasn't much of a web with which to play around. He was introduced to Zope right around the time it came out and quickly saw the light, but only after graduating from Rice University in 2002 (a few years too late for the dot-com boom) did he begin to make any money from it. He has followed the CMF and Plone for most of their lives, too, and built most of the groups interface for Plone, under the sponsorship of the Connexions Project [cnx.rice.edu], among other contributions. He lives in Houston, Texas and wears many hats.
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This book was a little helpful, but it's not the books fault. The fact that we upgraded to Plone 4 and this book is for Plone 3 and the developers changed it so much between... Read morePublished on July 23, 2013 by Jason Taylor
I bought them both and find this one more complete with a more authoritative exposition.Published on June 26, 2007 by Jonathan
Yes, we need more books on Plone, in particular of the introductory kind. Unfortunately, this is not the one. Read morePublished on June 12, 2005 by Helge Skrivervik


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Determining the Critical Particle Size to Induce Enhanced Emission in Aggregates of a Highly Twisted Triarylamine
Article first published online: 2 OCT 2013
DOI: 10.1002/cphc.201300667
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 14, Issue 16, pages 3682–3686, November 11, 2013
Additional Information
How to Cite
Kokil, A., Chudomel, J. M., Yang, B., Barnes, M. D., Lahti, P. M. and Kumar, J. (2013), Determining the Critical Particle Size to Induce Enhanced Emission in Aggregates of a Highly Twisted Triarylamine. ChemPhysChem, 14: 3682–3686. doi: 10.1002/cphc.201300667
Publication History
- Issue published online: 31 OCT 2013
- Article first published online: 2 OCT 2013
- Manuscript Received: 20 JUL 2013
Funded by
- U.S. Department of Energy. Grant Number: DE-SC0001087
- US Department of Energy. Grant Number: DE-FG02-05ER15695
- aggregate fluorescence;
- aggregation-induced enhanced emission;
- photoluminescence;
- solvatochromism;
- triarylamine fluorescence
Towards highly luminescent aggregates: A highly twisted triphenylamine displays aggregation-induced enhanced emission. A solvent-specific critical molecular aggregate size, once reached, gives rapid onset of enhanced emission in polar solvent mixtures that favor quenching of solvated individual molecule excited states.


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Tel: (360)598-5954
Grades: 6-12 | 91 students
On of WSA's Jan Term 2014 classes was a course on restoring wooden boats. It wasn't all work! Students took a breaks from sanding and scraping for a ride in a sailboat and to go kayaking in Miller Bay.
Lunchtime! International students have come to WSA from twenty-five different countries, and those nation's flags hang on the wall of the Commons.
West Sound Academy: an International Baccalaureate World School offering a college preparatory curriculum for grades 6-12 on the Kitsap Peninsula in Poulsbo, Washington. West Sound Academy transforms the lives of students by respecting and supporting the individual, preparing them for college and life beyond through superior teaching, excellent curriculum, and high expectations, and providing a safe community in an inspirational setting in which to grow and learn.
The West Sound Academy campus resides on twenty pastoral acres overlooking Liberty Bay in Poulsbo, Washington.
With views of the Olympic Mountains, our four modern buildings have state of the art science labs, a technology center, dance, drama and music studios, a library and seminar rooms.
Outside there are sports fields, a picnic area and an outdoor amphitheater, all set amidst old fir and cedar trees.
It is an ideal setting for students to learn and explore. Small classes ensure individual attention to students.
The average class size is 11, with classes ranging from 7 students to 20 students. Since our first commencement in 2002, WSA graduates have been accepted to over 145 colleges and universities.
These include some of the most selective schools and programs: US Military Academy at West Point, Middlebury College, Vassar College, Rhode Island School of Design, Purdue University, University of Washington Honors Program and the Rhodes Scholarship Program at Oxford University.
Upcoming Events and News:
School Overview
|School Membership(s)School Assoc.
|Other school association(s)
International Baccalaureate (IB) World School
|Grades Offered
|Grades 6-12
|Year Founded
Student Body
|Total Students
|91 students
|Student Body Type
|% Students of Color
State avg.: 27%
|Students by Grade
Academics and Faculty
|Total Classroom Teachers
|17 teachers
|Student : Teacher Ratio
National avg.: 13:1
|% Faculty w/Advanced Degree
|Average Class Size
|11 students
|Number of AP Courses
|1 courses
|List of Courses Offered
|Link to List of Courses
|Advanced Courses
|AP Calculus AB, IB Biology HL/SL (Group 4), IB Chemistry HL/SL (Group 4), IB English (Group 2), IB French HL/SL (Group 2), IB Literature in English (Group 1), IB Mathematical Studies (Group 5), IB Mathematics HL/SL (Group 5), IB Spanish HL/SL (Group 2), IB Visual Arts (Group 6), IB War & Peace in the 20th Century (Group 3)
|Average SAT score
|Average ACT score
|Matriculation DataMatric. Data
|Link to Matriculation Data
|Classroom Dress Code
Finances and Admission
|Admission Deadline
|None / Rolling
|Yearly Tuition Cost
|Tuition Notes
|$14,600 for Middle School and $16,120 for Upper School
|% on Financial Aid
|Acceptance Rate
National avg.: 85%
|Admissions Director
|Lisa Gsellman
|Admissions Associate
|Susan Trower
|Total Sports Offered
|4 sports
|Bowling, Dance, Kayaking, Rock ClimbingBowling, Dance,
Kayaking, Rock Climbing,
|Total ExtracurricularsTotal Extra-curric.
|10 extracurriculars
|Crafting Club, Debate Club, Kayak Club, Knowledge Bowl, Literary Journal, Middle School Math Club, Middle School National History Bowl, Rock Climbing Club, Upper School National History Bowl, Yearbook Crafting Club, Debate Club, Kayak Club, Knowledge Bowl, Yearbook, Literary Journal,
Middle School Math Club,
Middle School National History Bowl,
Rock Climbing Club,
Upper School National History Bowl,
School Notes:
- Mission - West Sound Academy is a college preparatory school that graduates accomplished, creative, intellectually curious young adults prepared to contribute responsibly to the world.
- Type of School — West Sound Academy is an independent college preparatory school serving students in grades six through twelve. The International Baccalaureate Diploma Programme is offered for students in grades 11 and 12.
- Location and Campus — West Sound Academy is located on a wooded, twenty-acre campus overlooking Liberty Bay in Poulsbo, Washington. The school's four buildings include classrooms, a library, a computer lab, three science labs, three teaching studios (art, dance, and music), an art gallery, and a Commons. The outdoor setting and the magnificent views of the Olympic Mountains inspire students and staff. Outdoor facilities include an amphitheater, a playfield, and a sports court.
- Accreditation — IB World School, authorized to offer the International Baccalaureate Diploma Programme; Northwest Accreditation Commission (NWAC), and Subscriber School, Northwest Association of Independent Schools.
- Admissions — West Sound Academy admits students of any race, color, or national or ethnic origin. Qualified students are those who have sound academic records, a sense of individuality, are motivated toward discovery, demonstrate integrity, and have an abiding interest in their world.
- Students — West Sound Academy students typically come from all parts of the Kitsap Peninsula and Bainbridge Island, as well as from eastern Jefferson County. In line with our mission, approximately 20% of our student body is comprised of international students. West Sound Academy is a diverse community that affirms and values people's differences. We have a multiplicity of backgrounds and perspectives within our school family, and mutual appreciation and respect is encouraged in our students.
- Class Size — Class sizes vary according to grade level and course, but are always designed to insure individual attention to students. Average class size is 11, with classes ranging from 7 students to 18 students. Student to teacher ratio: 7 to 1.
- Faculty — West Sound Academy's faculty is comprised of seventeen full- and part-time teachers, with an administrative and support staff of seven. The Academy's enthusiastic faculty of talented professionals fosters curiosity and discovery and stress critical thinking and clear communication.
- Curriculum — Providing a rigorous
academic and art curriculum to prepare students for college, West
Sound Academy is an IB World School, authorized to deliver
the International Baccalaureate Degree Programme (IBDP) for
students in Grades 11-12. The curriculum for Grades 6- 9 is
centered on a pre-IBDP course of study, while Grades 10-12 have a
selection of challenging college preparatory courses in the six
academic areas of the Diploma Programme.
The curriculum stresses critical and disciplined thinking, effective communication and scientific analysis, and creative problem solving. Skills introduced and reinforced in the classroom, including critical reading, critical writing, and document analysis and evaluation, will prepare students for the rigors of the Diploma Programme and for success in college after their years at West Sound.
Graduates leave West Sound Academy with the intellectual, personal, emotional and social skills to live, learn and work in a rapidly globalizing world.
- Technology— A wide variety of hardware and software is available at West Sound Academy to assure that students learn appropriate use of technology to help them communicate effectively; collect, analyze, process, and present information; as well as master the technical skills necessary to succeed in college and later life. Technology resources include: Student to computer ratio: 2.5 to 1 The school has a state of the art 10 MB+ fiber connection to the Internet with a campus-wide LAN and WiFi service. Technology assets include an Apple file server for storage of student work, computer lab, mobile laptop cart, digital projectors, digital document cameras, digital still cameras and video Flip cameras. Software assets include applications from Microsoft (Office 2008), Apple (iWork, iLife,), and Adobe (CS3, Final Cut, Logic). Additionally, Upper School students are provided Google Apps accounts which include email and other online collaborative tools.
- College Placement — 100% of the Class of 2014 admitted to college; average merit scholarship per student applying to American colleges: $67,000.
- Leadership Opportunities — A host of leadership opportunities are available from serving as officers or grade representatives on the WSA Student Council to student leadership in community service, to performing arts, to publications (yearbook and literary journal), to recreational clubs, and more.
- Advocacy Program — West Sound Academy offers an Advocacy Program that pairs a small group of students with a teacher for one or more years. The advocacy groups meet on a weekly basis to discuss important issues and work together on service projects for the school. The advocate meets with students and their parents for occasional conferences during the school year.
- Experiential Learning and Outdoor Education — Fall and Spring Trips take West Sound Academy students into real world settings from remote wilderness sites, to working ranches, to urban museums all the while teaching leadership, environmental ethics, and technical skills. These challenging outdoor adventures are opportunities for both environmental education and personal growth. Trips in recent years have included: A sailing trip on a schooner across Puget Sound Biking and kayak trips through the San Juan Islands A rock climbing adventure at Smith Rock in central Oregon Canoe and raft trips down the rivers of Utah Canyoneering in the San Rafael Swell in Utah Working at a Habitat for Humanity site in Florida
- Annual Arts Events - Friday Sound events (live music performances in the Commons on Friday evenings) Monthly openings for exhibiting artists at the Frodel Gallery on campus Performances of the school play or premieres of the school film production.
Profile last updated: 04/14/2014
Nearby Schools:
Show me:
- School Location Miles Grades Students
PoulsboGrades: 1-7 | 20 students
2.3 miles
1700 Ne Lincoln Rd
Poulsbo, WA 98370
PoulsboGrades: K-6 | 51 students
2.6 miles
14000 Central Valley Rd NW
Poulsbo, WA 98370
PoulsboGrades: NS-K | 17 students
2.7 miles
Po Box 127
Poulsbo, WA 98370
PoulsboGrades: PK-12 | 485 students
3.1 miles
Po Box 2460 705 NE Lincoln
Poulsbo, WA 98370
Bainbridge IslandGrades: NS-6 | 144 students
3.4 miles
10994 Arrow Point Drive Ne
Bainbridge Island, WA 98110
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Recent Articles
September 20, 2015
It is easy to fall into the trap of not keeping your skill-set current. There's no time and no need anyway. We look at why you need to keep things current and offer some suggestions as to how to proceed.
September 07, 2015
Choosing the right school for your child is a major project. We look a five reasons why you might be looking at the wrong schools.
August 30, 2015
Scandals in private school are bound to raise questions for those of us thinking about sending our children to private school. Regardless of how sensational these scandals may appear, they are actually few and far between.


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A Piece of Peace
A Piece of Peace will help you to help yourself to greater health, happiness, and productivity. With compassion and sensitivity we combine the most effective massage, reflexology, and Reiki techniques. Located in Noe Valley, San Francisco, we are easily accessible via public transportation, bike, or car.
About Our Practice
At A Piece of Peace we touch people with awareness of physical, mental, emotional and spiritual well being. To relieve pain, release stress, and encourage happiness is our passion and purpose.
Tailored to individual needs and goals, custom bodywork sessions may include a combination of techniques. Read more about the techniques we use in our practice.
Introducing Zabet Gerber
Zabet Gerber has over 1,000 hours of massage training. She offers therapeutic and relaxation massage using primarily Deep Tissue, Myofascial Release, Swedish, Trigger Point, Shiatsu, Thai, Reiki (energy work), Acupressure, and Ortho-Bionomy to assist and support your body's unwinding of physical, emotional, and/or energetic holding.
Special Offers
Refer a Friend: Receive a $10 gift certificate when you refer a friend who schedules a session. Your recommendation is important to us.
Series Specials: Save $40 to $140 when you purchase a series.
Schedule an Appointment
We have recently changed appointment scheduling software. If you are a previous client, please search via name or email and update your information.
You may also call 415-647-2188.
Location and Hours
A Piece of Peace
3819 23rd St.
San Francisco, CA 94114
Mon Closed
Tue 12:30 - 7:30 pm Zabet
Wed 12:30 pm - 7:30 pm Lauren
Thur 12:30 - 7:30 pm Zabet
Fri 12:30 - 7:30 pm Lauren
Sat 10 am - 7 pm
Sun 10 am - 7 pm
We are in the process of hiring new therapists. Check back soon to see our expanded appointment schedule.
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What a generous thought! Order your gift certificate here.
Email Newsletter
Receive special offers and ideas for stress management and general happiness.


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Angelina "A" Villa
from £10 /night help Price for guests, Nights
from £10 /night help Price for guests, Nights
Estimated nightly price based on a weekly stay. Excludes fees (if applicable). Enter your dates to see the total cost.
Villa / 4 bedrooms / sleeps 8 Home 105719
Availability Your dates are available
Villa / 4 bedrooms / sleeps 8
|Key Info
A charming detached Villa with Private Pool and Beautiful Views situated in the foothills of the Babadag Mountains in the village of Ovacik.The ground floor is open plan offering a well-furnished living room with air conditioning and a fully equipped kitchen. Doors lead from the kitchen and living areas onto the large covered terrace offering mountain and sea views, an ideal dining area for al fresco eating. The Villa benefits from WiFi with internet access.Within easy walking distance there are many local restaurants, small shops and the much advertised Water Park, this has many slides and flumes providing an enjoyable day for both adults and children alike.The popular town of Hisaronu with its lively night life provides a larger selection of restaurants, entertainment and shops and is only a 5 min bus ride or 20 mins walk away. The stunning lagoon and bay of Oludeniz with its spectacular beach is located a 10 mins bus ride away with the lovely harbour and market town of Fethiye being a similar distance in the opposing direction.
|Sleeps up to 8, 4 bedrooms
|4 bedrooms, 3 bathrooms of which 2 Family bathrooms and 1 En suites
|Nearest beach
|Olu Deniz 5 km
|Car not necessary
|Nearest Amenities
|500 m
|Nearest travel links
|Nearest airport: Dalaman 55 km
|Family friendly
|Great for children of all ages
|No pets allowed, No smoking at this property
Features and Facilities
|Internet access, DVD player, Sea view
|Private outdoor pool (unheated)
|Air conditioning, TV, Safe, Wi-Fi available
|Kettle, Toaster, Iron
|Clothes dryer, Cooker, Microwave, Fridge, Freezer, Washing machine
|King Beds (2), Single beds (4), Dining seats for 8, Lounge seats for 8
|Linen provided, Towels provided, High chair
|Private outdoor pool (unheated), Balcony or terrace, Private garden
|Parking, Not suitable for wheelchair users
|Further details indoors
Bedrooms: Bedroom 1 has a balcony with A/C, King size bed and en suite.Bedroom 2 has a balcony with A/C, twin beds and adjoining shower room/WC.Bedroom 3 with A/C, King size bed adjacent to shower room/WC.Bedroom 4 with A/C, twin beds adjacent to shower room/WC.Bathrooms:1) En suite to bedroom 1 having shower, wash basin and W/C.2) Shower room with wash basin and W/C on 1st floor.3) Shower room with wash basin and W/C on lower ground floor.Kitchen:Hob, Oven, Large Fridge/Freezer, Microwave, Cooking Utensils and Cutlery etc.Washing Machine, Clothes Airer, Iron and Ironing Board.Living Room:Open plan lounge/dining room area with air conditioning and 2 French doors leading onto the large covered terrace offering mountain and sea views, the ideal dining area for al fresco eating, there is a TV for use with the DVD Player.Other:WiFi with internet access, a safety deposit box usable at no additional charge and a large utility/storage room on the lower ground floor for storing suitcases etc. during your stay to leave rooms clutter free.Cleaning/towels/linen/maid service: The villa will be cleaned prior to and after your stay and bed linen and towels are provided. Guests should bring their own towels for use around the pool and on the beach, the towels provided in the villa are strictly for use in the villa.All rooms with the exception of the utility/storage room are Air conditioned, the Air Conditioning can also be used for heating if necessary.There is a large wooden table with 8 Chairs, this typically located in the Terrace area but can be moved if desired.The accommodation is strictly non-smoking!
|Further details outdoors
The 2 first floor bedrooms have their own balconies.The South facing private pool benefits from a an open surrounding terrace area ideal for sunbathing. Their is an adjoining upper covered terrace area that leads into the Kitchen and Living areas, this being ideal for when it just gets too hot for bathing !The Pool measures 6m x 3m & is typically cleaned on a daily basis.There are 4 Sun beds, 2 reclining Sun Chairs, 2 Parasols, 1 Small Table and 4 Patio Chairs.
|Further details
Luxury Airport transfers can be arranged at competitive prices.
Welcome packs can be arranged on arrival at a nominal charge.
Swimming pool only available May to end October.
Free of charge English-speaking representative visit can be arranged to answer any questions.
The Turkish Aegean Coast region
The Turquoise coast is on the south west coast of Turkey and a region of outstanding natural beauty. Ovacik is located approx 300m above sea level making it more comfortable during the hot summer months than the coastal towns of Oludeniz or Fethiye
The stunning Blue Lagoon and bay of Olu Deniz with its spectacular beach is located a 10 minute bus ride away. The lovely harbour and market town of Fethiye is a similar distance in the opposing direction.
Within easy walking distance there are many local restaurants, small shops and a water park. You are welcomed at most local Hotels which are usually happy to let you use their facilties and entertainment during the daytime and evenings. The popular town of Hisaronu is only a 5 minute bus ride or 20 minute brisk walk away.
Ovacik is a quiet area situated just outside the lively area of Hisaronu and approx equi-distance from Oludeniz and Fethiye. There are many places of interest within easy reach. Trips to Saklikent Gorge, Ruins of Tlos, ghost town of Kayakoy, the picturesque harbour town of Gocek and the many island boat trips from Fethiye are just a few of those on offer.
The following are also locally available:
Horse Riding, Jeep Safari's, Scuba Diving and Paragliding.
Car hire is available at the airport and locally in Ovacik.
General Info:
Restaurants typically charge the equivalent of £7 to £10 for a 3-course meal, a full English breakfast for as little as £2.00. Bars charge around £2.00 for local beer and £3.00 for shorts, many bars have 2 for 1 happy hours during certain times.
Supermarket food is typically the same as the UK but produce from Turkey is cheaper. A loaf of bread around 25p, local beer around £1.30 per bottle. The markets in Hisaronu (Mondays) and Fethiye (Tuesdays) are the ideal places for good quality but inexpensive fresh fruit, vegetables, cheese, nuts and spices.
Currency exchange is locally available as are cash M/C's some dispensing a choice of Turkish Lira or £ Sterling. Exchange rate as of June 2015 is 4.0 TYL to £1.
Note: All prices quoted as of June 2015.
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Motivation: Recognition models for protein-DNA interactions, which allow the prediction of specificity for a DNA-binding domain based only on its sequence or the alteration of specificity through rational design, have long been a goal of computational biology. There has been some progress in constructing useful models, especially for C2H2 zinc finger proteins, but it remains a challenging problem with ample room for improvement. For most families of transcription factors the best available methods utilize k-nearest neighbor (KNN) algorithms to make specificity predictions based on the average of the specificities of the k most similar proteins with defined specificities. Homeodomain (HD) proteins are the second most abundant family of transcription factors, after zinc fingers, in most metazoan genomes, and as a consequence an effective recognition model for this family would facilitate predictive models of many transcriptional regulatory networks within these genomes.
Results: Using extensive experimental data, we have tested several machine learning approaches and find that both support vector machines and random forests (RFs) can produce recognition models for HD proteins that are significant improvements over KNN-based methods. Cross-validation analyses show that the resulting models are capable of predicting specificities with high accuracy. We have produced a web-based prediction tool, PreMoTF (Predicted Motifs for Transcription Factors) (http://stormo.wustl.edu/PreMoTF), for predicting position frequency matrices from protein sequence using a RF-based model.
Contact: ude.ltsuw@omrots
It is a long-standing goal to predict the DNA-binding specificity of a transcription factor (TF) based only on its protein sequence (Benos et al., 2002a). That ability would allow for the inference of regulatory networks from genome sequences alone as well as for the design of TFs with desired recognition sequences. Early hopes for a simple recognition code (Seeman et al., 1976) were dashed by the structures of the first few protein-DNA complexes (Matthews, 1988). As the structures of more DNA-protein complexes were determined it became apparent that there were definite preferences for interactions between particular amino acids and base pairs, and that those preferences might vary depending on the class of TF. C2H2 Zinc finger proteins, in particular, were heavily studied and a degenerate, qualitative recognition code was shown to be moderately successful at predicting their binding specificities (Choo and Klug, 1994a; Choo and Klug, 1994b; Choo and Klug, 1997; Wolfe et al., 1999; Wolfe et al., 2000). This general idea of class-specific, degenerate recognition codes was further developed into a quantitative probabilistic code for zinc finger proteins that was more predictive than previous models but sill less accurate than desired (Benos et al., 2002b; Kaplan et al., 2005; Liu and Stormo, 2008; Persikov and Singh, 2011; Persikov et al., 2009).
The homeodomain (HD) family is the second most abundant TF family in mammals and most metazoans (Tupler et al., 2001). The HD TF family was first discovered in Drosophila where mutations in some HD proteins caused severe 'homeotic' phenotypes (Lewis, 1978). Homeodomains typically span ~60 residues that fold into a stable bundle of three alpha helices (Gehring et al., 1994). The C-terminal helix, or recognition helix, binds in the major groove and an unstructured N-terminal arm binds in the minor groove. This domain provides a favorable family for construction of a predictive recognition model because of similarities in docking geometry for a number of family members (Pabo and Nekludova, 2000; Siggers et al., 2005) and the characterization of specificity for many members of this family present in the yeast, drosophila and mouse genomes (Table 1). Using specificity data for 263 HD proteins, mostly determined using new high-throughput methods (Stormo and Zhao, 2010), allowed us to test different machine learning approaches and to assess the ability of recognition models to accurately predict the specificity of HD proteins. Using a cross-validation methodology we demonstrate that both support vector machines (SVMs) and random forests (RFs) based methods produce recognition models that are significantly better than previously published methods.
Table 1 lists the number of HD proteins from each of five species (including 13 variants of fly HD proteins), the experimental method used to determine their specificity and the reference for the datasets. All wild type protein sequences were obtained from UniPROBE (Newburger and Bulyk, 2009) or FlyFactorSurvey (Zhu et al., 2011). The hmmsearch program from the HMMER suite (Bateman et al., 1999) was used to extract the DBD for every protein using the homeobox Pfam hmm model (Pfam ID: PF00046) (Finn et al., 2010).
Protein binding microarray (PBM) data are available for 168 mouse HD proteins, but 14 of these (Dbx1, Hoxb5, Hoxb6, Hoxc6, Irx5, Lhx5, Lhx9, Lmx1b, Obox2, Pax6, Phox2a, Six6, Titf1, Tlx2) were removed from the dataset because their scaled BEEML-PBM PWMs (position weight matrices; see below) had a total information content (IC) <3 std below the mean IC for the entire combined set of motifs.
The HD DBDs were aligned using MAFFT (Katoh et al., 2005), which gave higher quality alignments, with fewer gaps, than other programs. Perhaps the best studied HD protein is the Drosophila engrailed protein (Fraenkel et al., 1998; Kissinger et al., 1990; Liu et al., 1990; Sato et al., 2004). For consistency with previous studies, HD positions are numbered with respect to the engrailed HD and all columns in the multiple sequence alignment that contained insertions relative to engrailed were removed. Only a small minority of the proteins in the dataset had short insertions relative to engrailed. The majority of these insertions (26) correspond to the three residue (TALE) insertion between positions 21 and 22 (Burglin, 1997). Two other types of insertions only occur in the mouse proteins Hdx, Hmbox1, Tcf1 and Tcf2. Figure 1 displays a sequence logo for the set of aligned HD proteins used in this study (Crooks et al., 2004).
Specificities for each HD protein were initially represented by PWMs or position count matrices (PCMs; Stormo et al., 1982). For bacterial one-hybrid (B1H) datasets the PCMs were obtained from the FlyFactorSurvey database (Zhu et al., 2011) for fly proteins. The PCMs for human and mutant fly proteins were obtained from Noyes et al. (2008). For PBM datasets, PWMs were generated using the BEEML-PBM program which provides more accurate PWMs than other analysis methods (Zhao and Stormo, 2011). Although Alleyne et al. (2009) were not able to align motifs for HD proteins based on their analysis of PBM data, the PWMs that we obtained could be aligned confidently (see below). For purposes of alignment and recognition modeling the PWMs were converted to position frequency matrices (PFMs), where the elements at each position are the probabilities of each base occurring, using:
However, we noticed when comparing the PWMs from orthologous HD proteins between flies, obtained using the B1H method, and mouse, using the PBM method, that there was a difference in scaling. A set of close mouse and fly homologs was assembled for comparison. For each mouse HD protein, the fly protein that was identical at key recognition residues 5, 47, 50, 51, 54, 55 (Noyes et al., 2008) and that was the smallest Hamming distance away was chosen as the homolog likely to have the most similar motif. Only mouse and fly HD pairs with a Hamming distance <15 were used. For each of the 104 homologous pairs we determined the optimal scaling factor. The mean of all of the optimal scalar values for all pairs was 2.238. This scalar value was then used to scale up all of the BEEML-PBM PWMs before converting them to PFMs.
Mahoney et al. developed a multiple PFM alignment program, STAMP, that produces reliable motif alignments (Mahony et al., 2007a; Mahony et al., 2007b). They further showed a mutual information analysis between the motif alignments and the protein alignments could be used to determine some of the key interacting residues for various TF families (Mahony et al., 2007b). We implemented a similar multiple alignment program in MATLAB to test additional scoring metrics and methods of guide tree construction. After developing metrics which incorporated the per column IC, we found that the best metric was SSDs (sum of squared differences), also one of the two best metrics reported by Mahony et al. We also found that ungapped local alignments yielded the best PFM alignments and that it was important to perform motif core alignment, as outlined by Mahoney et al. when aligning the relatively short HD motifs to generate a multiple motif alignment (MMA). Motif cores are defined as consecutive positions in a motif having an IC above 0.3 bits, or if there were not at least four consecutive columns with IC >0.3 bits, then the four consecutive columns with the highest total IC were used. If the motif was <4 base pairs long, then the entire motif was designated as the motif core. The guide tree we used for progressive motif alignments was based on the Euclidian distances between PFMs, which is simpler than the p-value-based alignment trees used by STAMP and produces similar results. We trimmed flanking positions from the MMA that had a mean IC of <0.05. The final trimmed MMA consisted of nine positions. Figure 2 shows the logo for the average PFM for the entire HD dataset. The A at position 5 in the average HD PFM is almost completely conserved. This preference reflects the strong conservation of Asn at position 51, which effectively specifies the conserved A (Ades and Sauer, 1995; Fig. 1)
Machine learning methods like SVMs and RFs are relatively good at capturing both the non-linear and linear relationships between independent variables that give rise to the observed dependent variable. In our case the independent variables are the amino acids in the DBD of each protein. The dependent variables are the elements of the PFM for each protein, 27 free parameters for the 9 positions of the HD motifs (Stormo, 2011). The SVM and RF methods can both perform feature selection as part of the learning process, but we found that ranking features with an adjusted form of mutual information (MIp) (Dunn et al., 2008) led to faster training and resulted in more accurate models. To make each PFM matrix discrete, we used a profile alphabet (Wang and Stormo, 2005). Nineteen different multinomial probability distributions over the four bases A, C, G and T were defined and assigned to labels in an alphabet. This allowed us to convert each column of a PFM to a single discrete label. We began with an initial set of seed profiles chosen to cover the space of possible PFM columns and then iteratively refined those profiles. The Euclidean distance between every column from every PFM in the MMA and all 19 profile vectors was calculated. Each PFM column was assigned to the nearest profile. The mean of the set of column vectors assigned to each profile then became the new profile vector. This process was repeated until convergence.
MIp was used to rank the positions in the DBDs. The adjustment to the mutual information proposed by Dunn et al. (2008) is based on the idea that the average entropy of each position in an alignment gives each position a particular propensity toward mutual information. A simple correction to the MI, called the average product correction (APC), takes into account the average MI across all of the positions. The final corrected mutual information is MIp(a,b) = MI(a,b) − APC(a,b).
The MIp score was calculated for every possible protein and motif position pair. Using the maximum MIp score for each position in the protein alignment, the set of protein positions, or potential features, was then sorted according to max(MIp) resulting in a sorted set of features. The RF, SVM and K-nearest neighbor (KNN) methods (described below) were each used to train a set of models, one model per element of the PFM. WYK encoding (Stormo, 2011) was used so that only free parameters were predicted by the models, since each position of a PFM only has three free parameters due to the constraint that each PFM column sums to one. To avoid imposing an arbitrary MIp score cutoff to determine the feature set to use for training the recognition models, the sorted set of features was used to construct progressively larger feature sets. The first feature set contained just the single DBD position with the highest MIp score. The last feature set in the series contained all of the residues in the DBD.
KNNs is the best published approach for predicting the specificity of HD proteins (Alleyne et al., 2009; Noyes et al., 2008). We included that in our set of methods so that each approach is trained on exactly the same datasets. Methods we tested included SVMs, RFs, neural nets (NNs) and partial least squares regression (PLSR). In pilot studies we found that NN and PLSR did not perform well compared with RF and SVM and NN was computationally expensive to run, so comprehensive tests were only performed to compare the KNN, SVM and RF methods.
The KNNs algorithm is a very simple method based on the principle that similar inputs generally yield similar outputs. The Hamming distance between every pair of aligned proteins was calculated. For every query protein, the closest proteins in the training set served as the reference proteins. The average of reference proteins' PFMs were then used as the prediction for the query protein. If the k parameter is set to 1, only the closest protein is included in the reference set. If it is set to 2, then the second closest protein is also included, etc. In the case of a tie all of the corresponding PFMs were averaged together. We used the knnflex R package for the KNN analysis. Surprisingly, in preliminary studies involving the HD dataset, we found that tuning the k parameter did not increase performance, so we fixed the k=1 for all subsequent analysis.
RF is an ensemble method that makes use of a collection of weak decision trees (Breiman, 2001). There are only two main user specified parameters, the total number of trees in the ensemble (ntree) and the number of randomly selected features to use to determine the best split at every node in each tree (mtry), so the method is simple to tune. In practice, it works well even without tuning, although we did tune the mtry parameter for every RF model. We iteratively tried increasing values of mtry, from 2 to 50. For all of these iterations, we set ntree to 50 for increased speed. Next, the mtry versus mean squared error (MSE) curve was smoothed and the mtry parameter that yielded the best MSE value was determined. Then, we used the optimal mtry parameter, and we set ntree to 500, which is the default value. We used the R randomForest package (Liaw and Wiener, 2002) to generate and make predictions with RFs.
SVMs are a popular machine learning binary classifier that has been adapted to perform regression. SVMs use a kernel function to map a set of training vectors into a higher dimensional space. They find the linear separating hyperplane that maximizes the margin of separation in this higher dimensional space. A non-negative cost parameter, C, is set by the user and determines the weight of the error term in the minimization (Chang and Lin, 2011). The e1071 R package was used to train and tune the SVM models. This package is based on the libsvm program (Chang and Lin, 2011). The dependent variables were each centered and scaled as recommended. Of the available kernel functions, the authors of libsvm recommend the radial basis function as the simplest to tune and the most generally applicable. The radial basis function includes a gamma parameter, which we tuned along with the cost parameter using the grid search function implemented in the e1071 package. We searched over the range 2−15 ≤γ≤23 and 2−5 ≤C≤23 using a step size of 22. In preliminary studies involving the HD dataset, we tried using all of the different kernel functions available in libsvm. However, we found that the radial basis function performed better than, or as well as, the other kernel functions and it was much less expensive to tune in most cases.
We aligned the HD amino acid sequences and DNA binding specificities (described as PFMs) for a set of 263 HD proteins (Table 1). MIp analysis of these proteins successfully ranked the most important key residues with only one false positive in the case of the HD dataset (Fig. 3, Table 2). Position 19 had a high MIp score but to our knowledge it has never been observed to make base-specific interactions as it is found on the opposite side of the domain from the DNA-recognition surface (Fraenkel et al., 1998). The other top six positions identified by our MIp-based feature selection analysis are key residues known to interact with the bases directly in at least one structure (Fraenkel et al., 1998; Passner et al., 1999; Wolberger et al., 1991) or influence specificity by substitution between HDs (Damante et al., 1996). While other groups have used overlapping, but somewhat different, sets of key residues (Alleyne et al., 2009), we find that including additional features beyond the set selected using MIp actually decreased performance for the SVM and KNN models, and only increased performance slightly for RF (see below).
Assessments of each method were based on 10-fold cross validation. The entire set of 263 HD proteins and their motifs were randomly divided into 10 subsets and in each of 10 training runs, 9 subsets were used for training the model and the remaining 1 was used to assess the accuracy of the model. Accuracy was measured as the MSE for each parameter of the predicted PFM compared with the observed PFM for each protein in the test set.
Figure 4 shows the performance for the KNN, SVM and RF methods as increasing numbers of features (protein positions) are included. All methods increase in performance (decrease in MSE) for the first seven features, after which they plateau or even increase MSE. Table 2 lists the positions added as features, the order of which was determined by the MIp ranking. Those features that improved the MSE appreciably for all methods are highlighted in yellow. For the KNN and SVM methods, performance tended to decrease when eight or more features were employed. The performance of the RF model did increase slightly in general as more features were added. Apparently the RF method does a slightly better job of internal feature selection here than even the SVM method. Based on the literature (Damante et al., 1996; Ekker et al., 1994; Kissinger et al., 1990; Noyes et al., 2008), six of these seven residues are thought to be important residues in sequence specific DNA recognition in at least some contexts.
Our previously published KNN-based method, flyhd (Noyes et al., 2008), was used to make predictions for all 154 mouse proteins considered in this study. Flyhd made predictions for 130 of these. A RF-based model was trained using the same training data employed by flyhd, which consists of, on average, 22 binding sites selected by B1H per fly HD protein. The MSE for predicting the mouse PFMs with flyhd was 0.0159, whereas the MSE for the RF model was 0.0113, 29% lower. Training an RF model using the latest SOLEXA motifs available from flyFactorSurvey lowered the MSE by an additional 8.6% to 0.0099.
The goal of this study was to find improved recognition models for the HD family of TFs. Although they are a very abundant TF family in nearly all eukaryotic organisms, previous models have focused on simple nearest neighbor type predictions of specificity based on large archives of reference recognition motifs (Alleyne et al., 2009; Noyes et al., 2008). These previous models have not been informed by the combination of feature selection derived from mutual information and modeling against reliably aligned recognition motifs, which could limit their predictive power. We had previously published a nearest neighbor approach (Noyes et al., 2008) for predicting PWMs for new HDs, but we found that an RF-based model trained with the same fly B1H Sanger data had better performance on a mouse test set. Alleyne et al. (2009) also used a nearest neighbor approach but they only attempted to predict 8mer enrichment scores for novel HD proteins. They compared various machine learning methods but found nothing that was better than nearest neighbors, but their efforts may have been hampered by an inability to align the motifs they used for training and therefore having to rely on 8mer enrichments. Our results demonstrate that with ample high quality and quantitative training data sophisticated machine learning methods are capable of determining very good recognition models for HD proteins. We believe that these models should be broadly applicable to other families of TFs with the caveat that large deviations in domain docking within subgroups could complicate family analysis (Pabo and Nekludova, 2000; Siggers and Honig, 2007). In support of this view, we have preliminary data demonstrating that this type of approach can provide improved models for DNA recognition by zinc finger proteins even though they have been extensively studied (Benos et al., 2001; Liu and Stormo, 2008; Persikov and Singh, 2011).
In the 10-fold cross validation analysis, the average MSE for this RF model was 0.0085 (Fig. 4). Figure 5 compares the observed and predicted motif logos for 12 different HD DBDs that are in the range of the average MSE (0.0080–0.0091) to illustrate the expected accuracy of the predictions. We have produced a web-based prediction tool, PreMoTF (Predicted Motifs for Transcription Factors) (http://stormo.wustl.edu/PreMoTF), for predicting PFMs based on protein sequence. It currently contains prediction tools for HD proteins and additional protein families will be added as they are developed.
We gratefully acknowledge Yue Zhao for providing the HD BEEML-PBM PWM models and for helpful advice and discussions. We also thank the other members of the Stormo, Wolfe and Brodsky labs for insightful comments and discussions.
Funding: This work supported by National Institutes of Health grants HG00249 (GDS) and HG004744 (SAW and MHB).
Conflict of Interest: none declared.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's Canada Institute for Scientific and Technical Information in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Yeoman outbound towards Clevedon
Yeoman Bank coming towards Portishead Point
YEOMAN BANK docked at Leith docks edinburgh
Yeoman Bank passing Portishead Point
Yeoman Bank passing Portishead Point.
Yeoman Bank passing Portishead Point
Just about to drop her anchors in the Carrick Roads after her spell in the dry dock
Seen here being manoeuvred out of Dry Dock, Falmouth
in A&P Falmouth's dry cock number 2
in Falmouth dry dock 2
in A&P dry dock Falmouth
Welcome Point, Wedel/Schulau
Passing Portishead inbound for Royal Portbury Dock with Gypsum from Garrucha
19th April 2014. At anchor in the Bay of Gibraltar.
Cargo Vessel YEOMAN BANK, in heavy rain, passing Dunoon, Argyle - inward bound for King George V Dock, Glasgow.
Heading up the river Clyde to Glasgow
Passing Portishead inbound for Royal Portbury Dock with gypsum from Garrucha
06 October 2013. Gibraltar
Passing Battery Point, Portishead having departed Royal Portbury Dock for Glensanda
Assisted by tugs 'Ayton Cross' (bow) and 'Svitzer Milford' (stern attached)at around 2038hrs


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NY building shows how mod design stacks up as cool - 0 Comments
NEW YORK — In a city piled high with ambitious architecture, a seven-floor structure off the beaten path boasts a distinction of its own: It's billed as the first multistory, modular-built apartment building to open in the nation's apartment capital.
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News in "Digital Media & Learning"
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