text:
Browsing University Libraries by Title
Now showing items 41-60 of 279
Content Selection, Preparation, and Management (Educopia Institute, 2010)Here is a set of best practices for policies regarding the selection, preparation, and management of digital content for preservation purposes. Though the authors draw upon PLNs (Private LOCKSS Networks) in their featured ...
Copyright in Research and Scholarship for Engineering Education Graduate Seminar (2015-05-01)Copyright in Research and Scholarship for the Engineering Education Graduate Seminar, May 1, 2015.
Copyright in Scholarship (2012-11-05)You can legitimately use someone else's work in your own when you know about copyright and you understand your rights as well as your responsibilities.
Copyright in Scholarship & Instruction and an Open Access Primer (Digital Library and Archives, 2012-02-06)Increase your understanding of US copyright law, particularly US Code Title 17, Sect. 106-108, and your appreciation of rights and responsibilities with regard to intellectual property issues that faculty and students ...
Creating Trust Relationships for Distributed Digital Preservation Federations (iPRES 2008: The Fifth International Conference on Preservation of Digital Objects, 2008)The authors outline a model for digital preservation federation based upon several existing models including the U.S. Federal Reserve Bank regional governance model and its similarities to successful large-scale redundant ...
Creative Convergence: Conducting a Systematic Review Project Through Cross-Institutional, Distance Collaboration (2014-10-30)Objective: To reflect on a cross-institutional systematic review project: What are effective collaboration methods for geographically dispersed research teams? Methods: Conduct a scoping literature review on effective ...
Deconstructing the collaborative impact: Article and author characteristics that influence citation count (2013-08-16)It is well known that collaborative papers tend to receive more citations than solo-authored papers. Here we try to identify the subtle factors of this collaborative effect by analyzing metadata and citation counts for ...
Determination Of Unit Costs For Library Services (ACRL Publications, 1979-05-01)As with other public service activities, inflationary trends and public opinion provide a clear mandate for attempts to control the increasing costs of providing library services. Cost control necessarily requires knowledge ...
Developing a Financially Sustainable Business Model for Library Resources and Technical Services (LRTS), the Official Journal of ALCTS (2013-06-19)The Board of Directors of the Association of Library Collections and Technical Services (ALCTS) tasked a sub-group of the American Library Association Emerging Leaders 2013 cohort with investigating different pricing and ...
Development and evaluation of the Healthy Eating Index-2005 (United States. Department of Agriculture. Center for Nutrition Policy and Promotion, 2007-11)The Healthy Eating Index (HEI) was developed to measure compliance with dietary guidelines, and is used by the USDA to monitor change in the Nation's diet. The HEI-2005 was specifically developed to measure compliance ...
Diet quality of Americans in 1994-96 and 2001-02 as measured by the Healthy Eating Index-2005 (United States. Department of Agriculture. Center for Nutrition Policy and Promotion., 2008-08)This publication describes the diet quality of Americans 1994-96 and 2001-02, as measured by the Healthy Eating Index-2005.
Dietary Guidelines 2010: selected messages for consumers (United States. Department of Agriculture; United States. Department of Health and Human Services, 2011-06)This one-page document breaks down the 2010 Dietary Guidelines for Americans into three categories: balancing calories, foods to increase, and foods to reduce. Two simple recommendations are made in each category.
Dietary Guidelines for Americans 2010 (United States. Department of Agriculture; United States. Department of Health and Human Services, 2010-12)This publication represents the 7th edition of the Dietary Guidelines. The Dietary Guidelines are usually released every five years or so. The Guidelines provide science-based nutrition guidelines for all Americans aged ...
Digital Collection Development Policy: From Documenting Content to Documenting Process (University of North Texas Libraries, 2010)This poster discusses collection policies. Drawing from the experience of developing digital collections and a digital library infrastructure, the University of North Texas Libraries is developing a new collection policy ...
Digital Libraries for Biodiversity and Natural History Collections (American Society for Information Science and Technology, 2010-10)This panel aims to discuss the importance of creating digital libraries for biodiversity and natural history collections, the state of the art in terms of standards, best practices and the challenges that natural history ...
digital library and archives (Digital Library and Archives at Virginia Tech's University Libraries, 2000)
Digital Library and Archives 2006/07 (Digital Library and Archives at Virginia Tech's University Libraries, 2007)
Digital Library and Archives annual report 2002/2003 (Digital Library and Archives at Virginia Tech's University Libraries, 2003)


text:
SALT LAKE CITY — About 12 percent of Utah's population is Hispanic. But Latinos cast a mere 2 percent of Utah's votes in the 2008 presidential election, according to census estimates.
That suggests the politicians who support Rep. Stephen Sandstrom's tough illegal immigration enforcement bill — which Hispanics fear could make life tough for anyone with a Hispanic accent — have relatively little to fear politically in this year's elections from upset Latinos.
"It would give sponsors more pause if a higher percentage of Latinos voted, but I don't know that it would prevent the bill," said Rep. Rebecca Chavez-Houck, D-Salt Lake.
Sen. Luz Robles, D-Salt Lake, added, "Every legislator has a constituency. They would think twice about this (the Sandstrom bill) if more Latinos voted." But, she adds, "It's an interesting question because Hispanics are well-represented in Arizona, and that didn't stop its immigration bill."
Kirk Jowers, director of the University of Utah's Hinckley Institute of Politics, said because of their skyrocketing population in Utah in recent years, "Hispanics should be a growing political force. But until they are voting on par with other groups, it allows for their opinions and positions to be discounted."
Sandstrom, R-Orem, is pushing a bill patterned after one in Arizona to require police to question the immigration status of people stopped for other crimes if they have "reasonable suspicion" they are in the country illegally. Critics say that may subject anyone with a Hispanic accent to harassment, and force them (but not others) to carry proof of citizenship at all times.
A Deseret News-KSL poll by Dan Jones & Associates in April showed that 65 percent of Utahns favored the bill — but it did not ask questions to measure support by ethnicity. Several national polls, however, have shown that up to 70 percent of Hispanics oppose such laws.
Surveys on voting by the Census Bureau after the 2008 election estimated that 59.7 percent of all residents of Utah age 18 or older voted that year. Among whites, 60.3 percent voted. But among Latino residents, only 26.3 percent voted — a voting rate less than half of that of whites.
That low turnout coupled with the fact that only about 12 percent of the state's population is Hispanic meant that only 2 percent of Utah votes in 2008 were cast by Latinos, according to Census estimates.
Hispanic leaders have long known about the low voting rates, struggled to figure out reasons behind it, and worked to improve voter turnout.
For example, in the lobby of Centro Civico Mexicano in downtown Salt Lake City, voter registration forms and posters about the need to vote are always available. But Centro President Frank Cordova says many factors hinder Hispanics from voting, even when they do register.
"We might register them in June or July. But many of our people are renters, and if they find a cheaper place to live, they move. They don't understand they have to re-register when the move out of their precincts," said Cordova.
Chavez-Houck passed a bill this year — recommended by the Governor's Commission on Strengthening Democracy — to help address part of that problem. It allows the lieutenant governor to automatically re-register voters who report new addresses for driver's licenses. But it still doesn't help people who move shortly before elections, or who have not updated driver's licenses.
Cordova says another problem is that many Hispanics work several jobs, often making it difficult to vote on Election Day. Jowers said that excuse should be disappearing because of recent changes that allow early voting and absentee-voting-by-mail.
Cordova also said a big reason many Hispanics do not vote "is a lack of understanding and education. Many people say their vote doesn't count. They don't think it makes a difference."
- 2 homes, 3 other buildings damaged in...
- Author, activist speaks at Theodore Roosevelt...
- Man accused of killing UTA worker dies in prison
- Women underrepresented across Utah's...
- Mike Lee, US Senate to hold monument meeting...
- 7 tips for summer travel while pregnant
- Man wanted for questioning in Tooele fire...
- Utah officials find no pesticide violation...
- Utah delegates finally stand and cheer... 94
- The day after: Lee defends Cruz at GOP... 32
- Should mountain biking be allowed in... 28
- Utah Democrats headed to 'historic'... 28
- Can police-community relations be... 14
- Rep. Mia Love buying $1M in TV ads for... 14
- Giant algal bloom likely to fuel Utah... 10
- Appellate court upholds water rights... 8

subset: commoncrawl


text:
Pakistan to appeal ruling allowing Musharraf to leave country: Lawyer
Islamabad: Pakistan`s government on Saturday filed an appeal with the country`s Supreme Court seeking to overturn a decision allowing ex-military ruler Pervez Musharraf to leave the country, his lawyer said.
"The federal government has filed an appeal in the Supreme Court," Ahmad Raza Kasuri, a member of Musharraf`s legal team, told AFP.
The move comes after a court in Karachi on Thursday ordered the lifting of a travel ban imposed on the 70-year-old, a ruling his supporters hoped would draw a line under a raft of legal troubles.
Musharraf has been battling several court cases -- including treason charges for imposing emergency rule in 2007 -- since he returned to Pakistan last year to contest elections, stoking tensions between civilian authorities and the powerful military.
Akram Sheikh, a senior lawyer who is the chief prosecutor in the treason case, confirmed an appeal had come from the attorney general`s office.
"I hope it will be fixed for (hearing on) Monday," he added.
Observers say the former general`s exit from Pakistan could help ease tensions between the army and civilian authorities at a time when the country is fighting a resurgent Taliban following a brazen attack on Karachi`s airport last week.
More from India
More from World
More from Sports
More from Entertaiment
- No trace of IAF's AN-32 aircraft and survivors
- Rio Olympics 2016: NADA to take decision on Narsingh Yadav's fate today
- Intruder who 'spiked' wrestler Narsingh Yadav's food identified: Sources
- China increases soldiers at Ladakh's Pangong Lake
- Madhya Pradesh: Two women assaulted at railway station for carrying beef
- Pacer Kagiso Rabada scoops six South African awards
- French Open champ Garbine Muguruza withdraws from Montreal
- Olympics 2016: More Russians banned in mounting Rio toll
- Throwback! Diana Penty's Italian vacation pics will inspire you to visit the country
- Singer Shweta Pandit gets married to Italian beau Ivano Fucci


text:
Munkebjerg Bed & Breakfast, Vejle (and vicinity)
- Free WiFi and free parking
Main amenities
- 10 smoke-free guestrooms
- Breakfast available
- Terrace
- Garden
- Multilingual staff
- Barbecue grills
- Limited hour front desk
- Tour/ticket assistance
- Playground
Feel at home
- Free cribs/infant beds
- Playground on site
- Rollaway/extra beds available
- Television
- Garden
- Terrace
What's around
- Vejle Golf Club (2.8 mi / 4.6 km)
- Vejle Windmill (5.9 mi / 9.5 km)
- Vejle Art Museum (6.1 mi / 9.8 km)
- Vejle Music Theatre (6.2 mi / 9.9 km)
- Vejle Town Hall (6.3 mi / 10.1 km)
Munkebjerg Bed & Breakfast, Vejle (and vicinity)
Hotel Info: 866-539-8117from $42
- Apartment, 2 Bedrooms
- Apartment, 2 Bedrooms
- Apartment, 2 Bedrooms (Large)
- Studio (Apartment)
- Double Room, Shared Bathroom
- Apartment, 4 Bedrooms
- Family Studio (Apartment)
- Single Room, Shared Bathroom
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 10 rooms
- This hotel is arranged over 2 floors
- Check-in time ends at 11 PM
There is no after-hours reception at this property. Guests arriving late won't be able to check in until the next morning.
Required at check in
- Cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 18
Travelling with others
- One child (2 years old and younger) stays free when occupying the parent or guardian's room, using existing bedding
- No pets or service animals allowed
Extra people
- Roll-away beds available, charges may apply*
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
Other information
- Smoke-free property
Nearby Three Star Vejle (and vicinity) hotels
In the hotel
- Continental breakfast daily (surcharge)
- Barbeque grills
- Playground on site
- Golfing nearby
- Hiking/biking trails nearby
- Front desk (limited hours)
- Tours/ticket assistance
- Multilingual staff
- Number of buildings/towers - 4
- Garden
- Terrace
In the room
- Coffee/tea maker
- Pillowtop mattress
- Shower only
- Free WiFi
Top Vejle (and vicinity) hotels
Recently reviewed hotels in Vejle (and vicinity)
- Zleep Hotel KoldingFrom
"Stayed for 1 night. The room was spacious and comfortable, the staff was friendly and helpful "Jun 17, 2016
- Hotel BredehusFrom
"We stayed at the hotel because we went to Queen concert at Jelling Festival."May 30, 2016
- Comwell KoldingFrom
"Stayed one night. Hotel was very nice, clean, quite adequate. Would recommend to others."May 16, 2016
- Hotel GudenåFrom
"This is a great little family-run hotel near the charming village if Tørring where we spent a few days visiting friends in the area. The room was spotlessly clean, the bed quite…"May 13, 2016
Nearby hotels
Munkebjerg Bed & Breakfast, Vejle (and vicinity)'s small print
Also known as
- Munkebjerg Bed & Breakfast
- Munkebjerg Bed & Breakfast Borkop
- Munkebjerg Borkop
This property does not have elevators.
Optional extras
Onsite credit card charges are subject to an extra charge
Rollaway beds are available for an additional charge
Continental breakfast is offered for an extra charge of DKK 50 for adults and DKK 25 for children (approximately)
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Recent reviews
Outstanding 4.6 /5 from 149 reviews
Comfortable and clean. A bit remote but good value. Would have liked private bath but understand sharing arrangement.
I was initially concerned about having to share a bathroom, but the place is so well organized it was not an issue. The b
Nice, friendly. Free coffee, tea and other basic items, cooking facility. It is a farm with animals. Daughter loved the kittens. Overall a pleasant experience. Unpaved access road with some pot holes. Fee for paying by card. Bad rate for paying with Euro. Would I recommend it? sure it is a nice stay and value for the money.
The owner was very friendly and she was very fluent in german and english.Beautiful barnhouse with almost everything that you need. Was given full freedom to use the property.
Lovely quiet countryside setting. Well laid out B&B with total seperation between the owners and the guests. A smart bedroom with a good kitchen/diner and a lovely bathroom. Ample parking, free wifi which is a little tempermental at times but fine most of the time, very pleasant host, easy to find if you read the instructions on the email
Is the description of this hotel not correct? Tell us


text:
50% Off a Therapeutic Massage
Up to 45% Off Deep-Tissue Massage
Up to 48% Off Custom Massages
51% Off 60-Minute Massage
Up to 56% Off Deep Tissue Massage
Up to 56% Off Deep-Tissue Massages
Up to 67% Off Neurosomatic Massages
Up to 48% Off Massage
Up to 56% Off 60-min Swedish or Sports Massage at Livefit Spa
Up to 54% Off Swedish or Deep-Tissue Massages
Up to 57% Off Individual or Couples Massage
64% Off Reflexology Session
Up to 54% Off Aromatherapy Massage
50% Off Neck Massages
61% Off Massage at MassageLuXe
49% Off Full-Body Massage
Up to 55% Off Massage or Body Wrap
51% Off Massage at Massage & Wellness Spa
50% Off Couples Massages at The Massage Center
To help you plan your pampering for the remainder of the summer, we talked the experts behind some of the country's most luxurious spas.
47% Off at Spa ZenAura
Learn why Swedish massage isn't so Swedish after all and why it's possibly the most popular technique in the Western world.
Your trip to the spa should be invigorating, not boring. Stay away from the usual by booking one of these 8 uncommon yet relaxing treatments.
Discover new restaurants, spas, things to do & more great deals added daily!
You can change your email preferences at any time
By clicking Continue, I agree to the Terms of Service and Privacy Statement
No Thanks
*Valid on 1 unit (min. price $25) per transaction; max 1 use per customer. Exclusions apply.
Full details: gr.pn/promofaq


text:
Associate Professor of Gender Studies
Christian Gundermann understands theory as a daily practice like breathing and eating. He teaches students in different contexts as diverse as the interpretation of films, the history of the queer movement, the questioning of the human/animal boundary, the historical study of horsemanship, the practice of body modifications, the connections between feminism and the sciences, the nexuses of power, knowledge, pleasure, and suffering etc. that there is no practice without theory, and that every theory is always already a practice.
311 Shattuck Hall
Senior Lecturer in Gender Studies
Martha Ackmann's research interests include women athletes, women in aviation and space, women in national politics, U.S. women's movements, Emily Dickinson; narrative non-fiction; journalism; media; women's public voices
313 Shattuck Hall
Associate Professor of Psychology and Education; Associate Professor of Gender Studies
311 Reese Psych-Education Building
Jacquelyne Luce
Visiting Lecturer in Gender Studies
315 Shattuck Hall
Professor and Chair of German Studies, Professor of Gender Studies, Professor of Critical Social Thought
Karen Remmler's interdisciplinary research and teaching in English and German focuses on the politics and culture of memory in the aftermath of atrocity and war in European and Asian contexts; German literature, film, and sites of memory within transnational contexts; 19th century critical social thought through the lens of contemporary social critics; and the interrelationship between national processes of transitional justice and the work of memory in films by the descendants of genocide survivors and perpetrators in non-western contexts.
305 Shattuck Hall
Chair of History, Professor of History
U.S. Historian Mary Renda continually pushes the boundaries of her discipline through her focus on the role of women and gender, the multicultural nature of U.S. history, and the international contexts in which that history has taken shape. In addition to her course offerings in U.S. women's history, U.S. imperialism, and other areas of United States history, Renda teaches interdisciplinary women's studies courses. It's not a vacation from her area of specialty, however. "When I teach women's studies," says Renda, "it brings into sharper relief the importance of history."
307 Skinner Hall
Erika Rundle
Associate Professor in Theatre Arts and Gender Studies, Dramaturg
Erika Rundle's research interests include theatre history; dramatic theory; performance studies; critical animal studies; Darwinian literary criticism; translation
305 Shattuck Hall
Professor of Sociology, Director of Nexus, on leave Fall 2016
Eleanor Townsley is interested in the role of intellectuals in social life. She teaches a range of courses in social theory, media, gender, and social science research methods. Her recent work considers the rise of media meta-commentary in democratic deliberation, the social reorganization of expertise and the changing social roles of academics as public intellectuals. Townsley served as an associate dean of faculty from 2012-2016 and is the faculty director of the Nexus Curriculum to Career program.
122 Porter Hall
Elias Vitulli
Visiting Lecturer in Gender Studies
310 Shattuck Hall
Angela Willey
Five College Assistant Professor of Feminist Science Studies
Angela Willey's areas of research include feminist science studies; history of race, gender, and sexuality in science; cultural studies; sexuality; and monogamy.
310 Shattuck Hall
By appointment only
Bridget Barrett
Academic Department Coordinator
Art Building 201


text:
Gov. Mark Dayton has declared a "peacetime state of emergency" in response to a propane shortage gripping Minnesota during the brutal cold.
The order authorizes the National Guard to active duty if required. The Guard is authorized to respond to needs of communities, which could include shelter in armories for people who've run out of propane, said Bruce Gordon, spokesman for the state Department of Public Safety.
With propane supplies being squeezed, the fuel's price has risen from $1.55 per gallon wholesale last fall to nearly $5 — and most of that increase has come just recently.
Dayton said Monday in a news release that he plans to meet with propane industry officials Tuesday and that his office has joined the state's congressional delegation in petitioning President Obama for emergency assistance and a halt to U.S. propane exports. Also, Dayton said he's asking the federal government and Texas to waive shipping restrictions and increase propane transports.
Mike Hughlett
StarTribune.com welcomes and encourages readers to comment and engage in substantive, mutually respectful exchanges over news topics. Commenters must follow our Terms of Use.
- Keep it civil and stay on topic.
- No profanity, vulgarity, racial slurs or personal attacks.
- Comments with web links are not permitted.
- Comments that violate the above will be removed. Repeat violators may lose their commenting privileges on StarTribune.com.
Comments will be reviewed before being published.
- Obama boosts Clinton: Carry her like you carried me
- In Jordan, an old-country feel contrasts a desire to grow
- Trump, Putin and the 2016 campaign: 'A lot of people say' something's fishy
- Twins' Sano has whiffed at a record rate
- Donald Trump urges Russia to hack Hillary Clinton's emails
- Pope says the world's at war, urges Europe to greet refugees


text:
Written on: 20/03/2008
Good Points
There are none.
Bad Points
Just continental rubbish now.
General Comments
I used to love these chocs but now they have been replaced by continental style truffle centres, yuk, why trade this muck under same name, its misleading customers, just a waste of money now.
As rated by our community of reviewers
" Horrible Black sweets " Read More
" Like Eating Raw Sugar " Read More
Written by Daisy1946
" Change is not always for the better " Read More
" Auful. Where has the Turkish delight gone!!!!!!!! " Read More
" Not what is says on the bag " Read More


text:
Karen and Shana Smith
Posted in the Bowling Green Forum
United States
#1 Mar 21, 2012
Does anyone know Karen Smith who use to do hair? She had a daughter Shana, smith was her maiden name. I remember Shana from 11th street when i was in school there and was wondering about them, she was a good beautician.
#2 Mar 28, 2012
yeah I know them. Karen is a sweet lady. Her daughter is CRAZY, and i dont mean funny! She is actually crazy!!! That girl needs to be comitted! She is a mental case!
#3 Oct 9, 2012
Who the hell are you to say some stuff about Shanna? You can't even put your name on here. Don't talk smack unless you can back it up.
#4 Oct 9, 2012
Karen does not do hair anymore. Shanna has never talked about knowing a Melissa. Who are you and why are you asking about these two?
United States
#5 Dec 13, 2012
I do know Shana from way way back, we had a nasty encounter and I would like to see her again, she was a biatch and wanted to come to my home. Met her mom at the salon and she was a great person, did my hair once. I want to see Shana. I live in Mississippi now, but am back and forth.
#6 Dec 17, 2012
Next time spell my name right. You must not have been that important because I do not remember who you are but when you feel froggy hop your a$$ back to KY and get you some. And my mom hasn't done hair in over 16 years.
#7 Dec 17, 2012
Better yet my email is [email protected] so whenever you ready you just let me know. I don't do the arguing behind the computer screen thats for scared biatches.
#9 Dec 17, 2012
Shanna it has been a long time, are u still fat as ever. I remember when you screwed with me a long long time ago, You were trouble down at 11th and remember seeing you out at honkers or judys or sinewhere a few years later, remember when you told me off and then wanted to come to my folks home.
Long story short, been suffering from a tumor that might take me away and I'm trying to look up old acquaintances, really was wanting to see you and see if you were still tough. Will be back in town the the week between Christmas and new years.
#10 Dec 18, 2012
Once again, I left my email address for whoever to contact me through. Still do not know who you are...... maybe a last name might help. Feel free to email me your number and we can set up a time and place for this big epic get together. Til then, Happy Holidays...... oh and I do wish you would come up with something better than I am crazy.....
United States
#11 Dec 19, 2012
Ok, merry Christmas, I didn't write the post about being crazy above the last one, hope everything works out for you and your family, your mother was a very good person, when I met her at the salon. Tell her hi.
#12 Jul 25, 2013
Shanna's crazy a$$ was arrested in June! Look on Simpson county jail website.....LMAO pure TRASH that's all she will ever be! I told ya'll the bi#*h was nuts
United States
#13 Sep 28, 2013
I remember Shana from the old school days, where is she now? She was a tough girl. What is she in trouble for now?
#14 Nov 19, 2013
This is Shana, who's mom karen does hair...
#15 Nov 19, 2013
. Could I possibly be the Shana you are possibly referring to?
#17 Oct 12, 2015
she's still CRAZY!!! She gave birth to 2 kids but they were both taken from her because she's a sorry piece of sh!t who wasn't even fit to raise a fish let alone an innocent child! As far as a man, she's not into men these days.
#18 Feb 23, 2016
So I was looking for a Shanna and this popped up. I was reading through and I came to the conclusion that this isn't the Shanna I was looking for. However, what kind of f*cked up people are you? Talking about this woman on the internet... I don't care if you have proof of anything you are saying. This makes each of you look ignorant, pompous, and frankly pathetic!
#19 Feb 27, 2016
Yet you are on this sight commenting as well! Shanna was, is, and always has been a PATHETIC piece of garbage and anything that has been said on here by me or anyone else has been 100% the truth! She is a NUTCASE and should've been committed years ago. Why else do you think she doesn't have her children? Because she is not fit to raise a cockroach let alone a child. Now if me speaking the truth makes me look ignorant oh well, but tell me...how do you think it makes you look? After all you are commenting on something that you obviously took the time to read all about so I guess your just as ignorant and pompous as the rest of us! LMAO
Tell me when this thread is updated:Subscribe Now Add to my Tracker
Add your comments below
Bowling Green Discussions
|Last By
|Really missing you
|5 min
|Who shot Ricky Ray Miller????
|15 min
|RACE Aquatics-need help fast. (Mar '15)
|20 min
|Best Chinese in bg?
|30 min
|Angie cherry
|51 min
|Cry Me A River
|1 hr
|Drug test
|1 hr
|Michael Hardy found guilty
|2 hr
Find what you want!
Search Bowling Green Forum Now
Copyright © 2016 Topix LLC


text:
Developing Story
View All
View All
Content Type
View All
Research Activities
General Information
Politics and Elections
REUTERS/Kevin Lamarque - U.S. President Barack Obama delivers his State of the Union address to a joint session of Congress on Capitol Hill in Washington January 24, 2012.
Blog Post
The thing both conservatives and liberals want but aren't talking about
July 22, 2016, Shadi Hamid
What does it mean to say that the Republican Party is on the "right"? Shadi Hamid distinguishes between conservative values and those of the latest iteration of the Republican Party, while exploring the shared values of both liberals and conservatives.
Refine by:
Politics and Elections
U.S. Politics
Polling and Public Opinion
July 11, 2016, Shibley Telhami
March 31, 2016, Jason Delisle
March 8, 2016, Raymond J. La Raja and Jonathan Rauch
Paper | Stanford Pathways Magazine
February 29, 2016, Harry J. Holzer
February 11, 2016, Matthew M. Chingos
Everything You Need to Know about How America Nominates Its Presidential Candidates
2015, Elaine Kamarck
Article | The New York Times
September 30, 2015, Sarah A. Binder
Article | The Washington Post
September 25, 2015, Sarah A. Binder
Policy Brief
July 2015, Kevin Casas-Zamora and Daniel Zovatto
View in:
How Hacks, Machines, Big Money, and Back-Room Deals Can Strengthen American Democracy
2015, Jonathan Rauch
View All Research on Political Campaigns ›Show 10 More
Read the latest commentary and analysis from Brookings experts on the 2016 presidential election
You have not selected any newsletters.
Mar 08
Brookings Institution
Feb 26
Get Updates
William A. Galston
Senior Fellow, Governance Studies
The Ezra K. Zilkha Chair in Governance Studies
Thomas E. Mann
Darrell M. West
Vice President and Director, Governance Studies
Founding Director, Center for Technology Innovation
View All Experts on Political Campaigns »
The Brookings Institution is a nonprofit organization devoted to independent research and policy solutions. Its mission is to conduct high-quality, independent research and, based on that research, to provide innovative, practical recommendations for policymakers and the public. The conclusions and recommendations of any Brookings publication are solely those of its author(s), and do not reflect the views of the Institution, its management, or its other scholars.
More ›
1775 Massachusetts Ave, NW,
Washington, DC 20036
© 2016 The Brookings Institution


text:
|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Döring Markus <Markus.Doer...@tcc-products.de>
|Tomcat, MyFaces and JSP 2.1
|Tue, 26 Sep 2006 10:08:21 GMT
Hello, I'm currently developing an web-application with JSP 2.0, MyFaces 1.1.4, Trinidad M1 All this is running on JBoss 4.0.3 SP1 and Tomcat 5.5 I have to include some functions included in JSP 2.1 and searched the web for it, but didn't find much information. Is it possible to use MyFaces and JSP 2.1 together? Is there any tutorial how to setup tomcat with JSP 2.1? Only found the GlassFish implementation yet, are there other JSP 2.1 implementations available? If not can I use only the JSP 2.1 implementation of GlassFish without changing the other parts of the JEE implementation? Any help is welcome. Greetings Markus --------------------------------------------------------------------- To start a new topic, e-mail: email@example.com To unsubscribe, e-mail: firstname.lastname@example.com For additional commands, e-mail: email@example.com
|View raw message


text:
"The labor strife at the Metropolitan Opera took on a new urgency Wednesday, when the company's general manager, Peter Gelb, sent its orchestra, chorus, stagehands and other workers letters warning them to prepare for a lockout if no contract deal is reached by next week." [New York Times]
Daniel Wakin reports that "WQXR pulled a blog posting critical of the Metropolitan Opera's new Ring cycle last month after the Met's general manager, Peter Gelb, personally complained to the radio station's top executive…. The Met has a small sponsorship arrangement with WQXR, which for decades has broadcast live Met performances on Saturdays." Read more »
The celebration of 50 years of the Mostly Mozart Festival at Lincoln Center includes "The Illuminated Heart," a theatrical fantasy of Mozart operas and ensembles featuring Christine Goerke, Ana María Martínez, Matthew Polenzani and Peter Mattei; plus staged concerts of Così fan tutte and Idomeneo. Tickets and more information are at MostlyMozart.org. Read more »
Tamara Mumford (Flosshilde in Das Rheingold) explains the concept of the Met's new production of the Ring. Read more »


text:
do any thing crash when u use the snow leopard
1 Answer from the Community
Snow Leopard has been extremely stable for me. I have only experienced minor issues, mostly with very old software.
Visit the websites for your most important software and search for System Requirements to see if the software is compatible with 10.6.
- Answered by James B from Hillsborough
- Flag as inappropriate Answer 1
Related Questions
How sturdy is this thing?
- Asked by Gregory H from Sodus
- May 19, 2015
- Flag as inappropriate (How sturdy is this thing?)
- Asked about: iPhone Lightning Dock - White
Answer now (How sturdy is this thing?)
No answers yet
Do u turn on or off when charging
- Asked by Jamie F
- Feb 3, 2016
- Flag as inappropriate (Do u turn on or off when charging)
- Asked about: Powerbeats2 Wireless Earphones - Bl…
Answer now (Do u turn on or off when charging)
No answers yet
What does this thing do?
- Asked by Richard G from Philadelphia
- Apr 9, 2015
- Flag as inappropriate (What does this thing do?)
- Asked about: Apple 29W USB-C Power Adapter
Answer now (What does this thing do?)
No answers yet


text:
Resorts in San Antonio
Search for resorts in San Antonio
Last minute San Antonio deals
- Wyndham Garden San Antonio near La Canterafrom $129
- Hotel Contessa - Luxury Suites on the Riverwalkfrom $189$151
- Eva's Escape at the Gardenia Innfrom $154
- Crockett Hotelfrom $129$103
- Mokara Hotel & Spa San Antoniofrom $299$254
Trending now in San Antonio
- Most bookedHyatt Regency Hill Country Resort & Spa
321 people looked at this hotel in the last hour
Most recent review
"The staff outstanding the activities awesome the lazy river and the surf wave is great even for the big kids and professionals on a team building trip! Antlers Restaurant the tops! Great service from Manger Brittany at Check in and Katie both true pros even called to check on if everything..."
A Traveller, May 2016, US
198 people looked at this hotel in the last hour
Most recent review
"Great service will recommend to anyone needing a getaway!"
A Traveller, May 2016, US
153 people looked at this hotel in the last hour
Most recent review
"Great but Need to keep pool area and beds clean. Some were really grubby"
A Traveller, Apr 2016, GB
94 people looked at this hotel in the last hour
Most recent review
"This is by far one of the nicest hotels I've stayed at. I will definitely return again as a personal weekend getaway rather than business"
A Traveller, May 2016, US
41 people looked at this hotel in the last hour
Most recent review
"Fantastic! Staff was great! The hotel and grounds were beautiful. Kids loved the pool and the lazy river. Great for families!"
A Traveller, May 2016, US
34 people looked at this hotel in the last hour
Map of resorts in San Antonio
- River Walk
- Six Flags Fiesta Texas
- Henry B. Gonzalez Convention Center
- AT&T Center
- Alamo
- Dolphin Cove-Seaworld
- Shops of La Cantera
- Market Square
- Fort Sam Houston
- San Antonio Zoo and Aquarium
- University of Texas-San Antonio
- Alamodome
- Rivercenter Mall
- South Texas Medical Center
- North Star Mall
- Freeman Coliseum
- Natural Bridge Caverns
- Aztec on the River (Aztec Theater)
- St. Mary's University
- San Antonio Majestic Theater
San Antonio Resorts
Browse Hotels.com's picks for the best San Antonio resorts with first class service and luxury from all over the world. The beautiful San Antonio has the best resorts offering luxury, elegance for total relaxation by the ocean. On this page you can find and book San Antonio resorts with the best deals and discounts, and if you still can't find a deal that fits your travel budget, you can search further and find the season featuring resort deals near San Antonio.
Hotels.com always has the best prices on San Antonio resorts located near the most paradisiac locations and exciting attractions. Whether you are going to the beach on vacation or for a wedding or other celebration, make sure you easily book your San Antonio resort online, receive your itinerary and confirmation message in your email and prepare to enjoy a your stay in San Antonio.
Check our latest Hotels.com genuine guest reviews on San Antonio hotel resorts and compare to Expedia.com and Trip Advisor reviews so you can choose a hotel that will give you the most pleasant stay experience with no undesirable surprises.
Remember when you book a San Antonio resorts with Hotels.com you win a hotel or resort night stay with the Welcome Rewards Program – For every 10 nights you stay in any resort, you can earn 1 free night*. So even a quickly weekend getaway in San Antonio can get you a free night. Book your San Antonio resort now with Hotels.com.
San Antonio travel guides
San Antonio Shopping Guide - where and what to shop and buy
San Antonio is a Texan retail mecca, and like everything in Texas, it goes big. The dazzling array o...
Top 10 Cultural things to do in San Antonio
Mariachi bands, Spanish colonial art and German music create a unique San Antonio culture. Book a Sa...
Winter vacations in San Antonio
Winter vacations in San Antonio mean unique Christmas festivals and evenings along the River Walk th...


text:
MiLB.com News
- Astros bringing up Bregman from Triple-A
- Rockies reportedly calling up red-hot Dahl
- Lopez shuts out Red Wings in return to Chiefs
- Scorching Dubon collects four hits for Sea Dogs
- No. 1 Arizona prospect Shipley ready for 'Show'
- DeJong, Springfield garner second triple play
- Long fans career-high 11 in shutout for Keys
- Esurance #CallUpWorthy Central
MiLB.com Video
More Video »
MiLB.com Photos
View MiLB.com photos »
Awards and Honors
- Full Name:
- Born:
- Age:
- Birthplace:
- Bats:
- Throws:
- Height: ' "
- Weight:
- Draft: (, )
Selected by the San Diego Padres in the first round (25th overall) of the 2011 First-Year Player Draft out of Bishop O'Dowd High School in Oakland, Calif. ... Was named the Padres' No. 11 prospect by MLB.com entering the 2012 season. ... Is the younger brother of Athletics right-hander Tyson Ross.


text:
Both the authors have contributed equally to this work and their order should be considered arbitrary.
Comprehensive Review
Advances in Direct T-Cell Alloreactivity: Function, Avidity, Biophysics and Structure
Version of Record online: 7 DEC 2011
DOI: 10.1111/j.1600-6143.2011.03863.x
©Copyright 2011 American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 12, Issue 1, pages 15–26, January 2012
Additional Information
How to Cite
Smith, C., Miles, J. J. and Khanna, R. (2012), Advances in Direct T-Cell Alloreactivity: Function, Avidity, Biophysics and Structure. American Journal of Transplantation, 12: 15–26. doi: 10.1111/j.1600-6143.2011.03863.x
Publication History
- Issue online: 13 JAN 2012
- Version of Record online: 7 DEC 2011
- Received 10 August 2011, revised 10 October 2011 and accepted for publication 11 October 2011
- Abstract
- Article
- References
- Cited By
- Alloreactivity;
- alloreactive T cells;
- allorecognition;
- bone marrow;
- HLA antigens;
- memory T cells;
- transplant;
- transplant immunobiology;
- viral immunity;
- viral infection
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
Although T-cell-based adaptive immunity plays a crucial role in protection against infectious pathogens and uncontrolled outgrowth of malignant cells, a large portion of these T cells are also capable of responding to allogeneic HLA molecules, violating the paradigm of self-major histocompatibility complex (MHC) restriction. Recent studies have provided insights into the mechanisms by which these T cells recognize allogeneic targets. The role of antiviral T cells in direct alloreactivity through peptide-dependent molecular mimicry and alternate peptide-MHC docking modes has emerged as major models for the human alloresponse. Here, we review in depth recent advances in this field and discuss how molecular interactions between T cells and HLA molecules drive the activation of these effector cells and its potential implications for alloreactivity in human transplantation.
- NFAT, nuclear factor of activated T cells; SLP-76, SH2 domain containing leukocyte protein-76; TCR, T-cell receptor; ZAP-70, zeta chain associated protein kinase-70.
T Cells in Adaptive Immunity
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
The ability of the adaptive immune system to distinguish self from nonself and establish immunological memory provides crucial defense against invading pathogens (1–3). Immunological memory allows the host to mount a more vigorous response against reinfection or challenge with related antigens. T lymphocytes play several roles in adaptive immunity which includes direct killing of virus-infected and malignant cells and also contribute to the generation and maturation of humoral immune responses. T cells recognize peptide epitopes bound to major histocompatibility complex (MHC) class I (MHC-I) or class II (MHC-II) molecules. These peptide epitopes are generated by the components of the antigen processing machinery which are specifically dedicated to generate epitopes for MHC-I and MHC-II molecules that are recognized by CD8+ and CD4+ T cells, respectively (4).
T cells express heterodimeric T-cell receptors (TCR), which are composed of either the αβ or the γδ chains. These chains are encoded by multiple variable (V), diversity (D; for β and δ chains) and joining (J) segments. Similar to immunoglobulin gene rearrangement, TCR diversity results from V(D)J recombination which allows T cells to recognize a diverse array of MHC-peptide complexes. Each T cell undergoes highly stringent thymic processes of positive and negative selection (2). This selection process is determined by the strength of interaction between TCR and self-peptide (p) MHC complexes and the cells that fail to interact strongly enough with self-pMHC complexes are eliminated by apoptosis (referred to as death by neglect). During the positive selection process, T cells which interact with MHC-I complexes mature to become CD8+ T cells, whereas cells selected through interaction with MHC class II molecules emerge as CD4+ T cells. T cells, which display high levels of avidity with self-pMHC complexes are eliminated to ensure that potentially self-reactive T cells do not survive into the periphery.
After exposure to an antigen, naïve T cells (both CD4+ and CD8+) undergo rapid clonal expansion and a small proportion of these cells survive the expansion phase and persist as memory T cells (1). Depending on the cytokine and costimulatory environment during antigen exposure, T cells acquire unique phenotypic and functional characteristics which include the expression of chemokine receptors that allow them to migrate to sites of inflammation or infection (5,6). In addition, these cells also acquire the ability to express effector cytokines such as IFN-γ, TNFα and/or IL-2 and direct cell contact-dependent cytolytic function (especially CD8+ T cells; Refs. 7,8). CD4+ T cells play a crucial role in the maturation of the CD8+ T-cell memory response by multiple mechanisms, including through the maturation of dendritic cells and the production of IL-2 (9–11). Memory CD8+ T cells are broadly divided into central and effector memory cells, which reside in lymphoid and nonlymphoid organs, respectively (12). Whereas the central memory cells do not have immediate lytic function, effector cells generally express immediate lytic function on restimulation (13). Extensive studies in humans and murine models have shown that in addition to helping in the maturation and maintenance of CD8+ T-cell memory responses (9–11), CD4+ T cells also play a crucial role in B-cell-mediated immune regulation, including both high-affinity antibody production and class switching (14–16), and also directly mediate clearance of virus-infected cells. Historically, CD4+ T cells were divided into two major subsets, Th1 and Th2 which could be distinguished by the secretion of specific cytokines (17). More recent studies have defined additional subsets including Th17, Th22, regulatory T cells and follicular helper T cells (Tfh), each distinguished by unique cytokine profiles and transcription factor expression (reviewed in Ref. 18). These T-cell subsets express distinct immunological functions to effectively mediate the response toward the antigen/pathogen to which they have been previously primed.
Structural Insights Into TCR and pMHC Interactions
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
During T-cell recognition of target cells, the highly flexible complementarity determining regions (CDRs) of TCR contact the surface of the MHC antigen-binding cleft as well as the peptide cradled by this molecule (Figure 1; Ref. 19). MHC-I and MHC-II molecules present the peptide epitopes in an extended conformation, within the peptide-binding groove which is formed by two flanking α-helices and a floor composed of antiparallel β-strands. Although the peptide-binding groove of MHC-I molecules is closed at either end, this groove is open in MHC-II molecules, which allows longer peptides to hang outside the groove. The first two turns of the MHC-I α1-helix are replaced in MHC-II by a β-strand. Over the last decade and a half, a consensus has emerged on the docking mode of TCR with the pMHC complex. These studies have shown that the TCR heterodimer is generally oriented, diagonally relative to the MHC-peptide-binding groove. The Vα domain of the TCR contacts the N-terminus of the peptide and is also in close proximity to the MHC α2 helix, whereas the Vβ domain more often contacts the C-terminal section of the peptide epitope and MHC α1 helix. The TCR contacts with the peptide epitope are primarily made through the CDR3 loops, which form the most diverse region of the TCR, although significant CDR1 loop contact has been observed. Generally, the germline-encoded CDR1 and CDR2 loops of the TCR drive the MHC specificity of T-cell recognition. It is important to note that there are many other examples of TCR-pMHC structures which do not display these conserved interactions, indicating that additional forces may guide the interaction of the pMHC complex with the TCR. Furthermore, not every interaction of pMHC complex with cognate TCR results in T-cell activation. Indeed, previous studies have shown that altered peptide ligands can either completely or partially inhibit T-cell activation, however, structural analysis have failed to provide a detailed insight into the mechanism of altered peptide ligand action. The structural analysis of pMHC and TCR interaction defines the point of the docking process from where the TCR signaling initiates.
T-Cell Activation
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
TCR and pMHC affinity/avidity
T-cell activation involves a series of signaling events that commence after engagement of the TCR with the pMHC complex. Paramount in the context of successful T-cell activation are a number of factors that dictate a successful signaling cascade including the affinity of the TCR for the pMHC complex, the number of pMHC complexes on the surface of the antigen-presenting cells (APCs), the influence of costimulatory signals delivered after ligation of coreceptors on the surface of both the T cell and APC and finally a complex set of signaling molecules which dictate T-cell activation.
The affinity of a TCR for a given pMHC complex can be defined by the rate at which the TCR associates and then dissociates with the pMHC complex (20). Although it is well established that TCR typically have low affinity for pMHC complexes, studies of a broad range of human and mouse TCR-binding affinities suggests that the generation of a strong agonistic signal can be influenced by the rate of association and is dependent upon a dissociation rate that is significantly long enough to allow complete intracellular signaling to occur. Both human and murine studies using peptide epitopes mutated at a single amino acid residue complexed to MHC have shown that reducing the TCR on-rate can result in a weak agonistic or even an antagonistic response (21,22). Conversely, TCR with rapid dissociation rates can also function as weak agonists or antagonists (23–25). Despite these observations, other studies have demonstrated that TCR with rapid dissociation rates can still function as agonists (26). Consequently, the binding parameters, which dictate the likely generation of agonistic signals, have not yet been fully defined. It is also evident that T-cell activation is not simply a consequence of pMHC and TCR affinity but can be influenced by other factors (e.g. expression of costimulatory molecules and levels of surface TCR expression) intrinsic to the T cell itself which may alter the avidity of the T cell.
As opposed to measurements of TCR affinity that define the rate of association and dissociation between the TCR and pMHC, measurements of T-cell avidity are based upon the more complex interaction of TCRs on the surface of T cells and pMHC complexes. Strategies to define T-cell avidity have generally been based upon the stability of binding of pMHC tetramers or through sensitivity to cognate peptide. T-cell avidity can be influenced by a number of factors other than the affinity of the pMHC/TCR interaction, including coreceptor binding and T-cell differentiation status.
The role of costimulation in T-cell activation
Costimulatory molecules have been shown to influence the activation of T cells after TCR engagement and can function, either after ligation directly with the MHC or after ligation with coreceptors on the surface of the APC. The primary coreceptor on T cells is CD3 which is found on all T cells, and contains immunoreceptor tyrosine-based activation motifs which are phosphorylated after TCR-pMHC ligation and are absolutely critical for recruitment of ZAP70 and the signaling cascade which follows (reviewed in Ref. 27). T cells also express either CD4 or CD8 which bind MHC-II and MHC-I, "respectively," and function differently with regard to their impact on TCR-binding kinetics and T-cell activation. CD4 seems to have minimal effect on the binding kinetics of TCR (28), although there has been some suggestion that CD4 reduces the number of pMHC complexes required for T-cell signaling to occur (29). CD4 may function to enhance signaling by increasing TCR cross-linking and promoting the formation of heterodimeric complexes of MHC with agonist or endogenous self-ligands (30,31). CD8 has been shown to have some influence on the binding kinetics of TCR for MHC-I molecules. Although high-avidity T cells can signal after TCR engagement in the absence of CD8 (32,33), lower avidity T cells are critically dependent upon CD8 for signaling (32). Studies using MHC molecules engineered to reduce the affinity of CD8 demonstrated that CD8 cobinding stabilizes the interaction of the pMHC-TCR complex, reducing the threshold for T-cell activation in low-avidity T cells (34) and functional studies have shown that CD8 can "tune" the number of pMHC ligands, which a TCR can recognize (35). Nevertheless, recent observations demonstrating allogeneic recognition of pMHC-II complexes by CD8+ T cells further emphasize that T-cell activation is not critically dependent upon costimulation by CD4 or CD8 (36).
In addition to the coreceptors which bind MHC, T cells also express a range of receptors which bind other ligands on the surface of the APC and can enhance T-cell activation. Members of the CD28 receptor family signal after interaction with the family of B7 molecules on the surface of APCs, which can promote either stimulatory of inhibitory signals to T cells (reviewed in Refs. 37,38). During an inflammatory response, licensing of APCs, in particularly dendritic cells, either by helper T cells or by inflammatory stimuli such as IFN-γ, induces the upregulation of a number of costimulatory ligands, including the B7 family members, CD80 and CD86. During TCR engagement with surface pMHC complexes, CD28, which is constitutively expressed on naïve CD8+ T cells, interacts with CD80 or CD86 on the surface the APC and promotes the expression of IL-2 by NF-κB signaling (39). Although TCR signaling and the priming of the cytotoxic T lymphocyte (CTL) response against viral antigens can occur in the absence of CD28 (40,41), costimulation by CD28 has been shown to lower the activation threshold required for TCR signaling (42), and is important in the recall of memory responses against some pathogens (43,44). Despite this, it is well established that some memory CTL populations in humans, particularly those directed against human cytomegalovirus (HCMV), express low levels of CD28 (6,45) and are therefore either less dependent upon costimulation for TCR signaling or are dependent upon other costimulatory molecules to enhance TCR signaling. Other immunoreceptors, including ICOS and 4–1BB (CD137) that are up regulated after activation can function to replace the costimulatory signals delivered by CD28 (46,47), and potentially lower the threshold required for T-cell activation (48).
T-cell signaling in naïve and memory T-cell populations
In addition to the role affinity and costimulation play in defining the outcome of pMHC:TCR interactions, alterations in T-cell signaling pathways can also influence T-cell activation. This is particularly evident in memory T-cell populations, which respond more rapidly after activation (12,49,50), may be tissue resident (51), can be activated by a diverse range of APCs (52–54) and have a reduced antigen threshold required to induce TCR signaling (50,55,56). As outlined above, TCR engagement leads to the phosphorylation of CD3 molecules, followed by the recruitment and activation of zeta-chain-associated protein kinase 70 (ZAP-70). This is followed by the phosphorylation of key adaptor molecules, SH-2 domain containing leukocyte protein-76 (SLP-76) and linker for activation of T cells (LAT), inducing a signaling cascade that eventually leads to the translocation of nuclear factor of activated T cells (NFAT), the activation of NF-κB and the expression of genes associated with T-cell activation, including IL-2 (reviewed in Ref. 57). Memory CD4+ T cells display increased expression of ZAP-70 and other associated downstream signaling, which is likely responsible for the rapid expression of effector functions (58). These observations suggest the presence of a distinct signaling pathway in memory T cells, not found in naïve T cells, which is likely responsible for the rapid expression of effector functions. Although memory T cells do require costimulation by CD28 to generate IL-2 for optimal proliferation in vivo, CD28 is not required for the rapid production of IFN-γ (59). It is therefore evident that memory T cells may have two distinct TCR signaling pathways, both dependent upon ZAP70 signaling, a CD28 independent pathway that leads to the rapid induction of effector functions and a CD28 dependent pathway that leads to later cytokine production and the induction of cell proliferation.
Although not completely evident from the current literature, it is possible to speculate that this CD28 independent memory specific activation pathway may have a lower activation threshold that allows the rapid generation of effector functions in the absence of cosimulation and potentially in the presence of lower levels of pMHC. This pathway may be particularly applicable in the context of memory CMV-specific T cells in humans which dominate the human T-cell repertoire (60,61), display a highly differentiated phenotype, including low levels of CD28 expression (6,61) and display immediate effector function after TCR engagement (62,63). These differential requirements for activation of effector memory T-cell populations, including less costimulatory requirements and a lower activation threshold could potentially facilitate a dominant role for these T cells in triggering alloreactivity after transplantation.
Direct Allorecognition by T Cells
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
The affinity of T-cell alloreactivity
Allorecognition occurs through three distinct mechanisms, that is, direct, indirect and semidirect. These pathways involve recognition of (1) intact allogeneic pMHC molecules on the surface of donor cells, (2) donor MHC molecules presented as peptide epitopes by the host APCs or (3) intact allogeneic pMHC complexes transferred through cell-to-cell contact (64). This review primarily focuses on the direct alloreactivity. Mapping of alloepitopes or "allotopes" recognized by these T cells has allowed the precise measurement of alloreactive TCR binding using surface plasmon resonance (SPR). These studies have revealed that an allospecific TCR can bind its MHC ligand with highly robust affinities of 1–49 μM (KD; Refs. 65–67). These affinities are comparable to those seen for TCRs specific for viral epitopes (1–20 μM) and cancer antigens (20–200 μM) and are greater than those seen for autoimmune antigens (>250 μM; Refs. 19,68,69). Previous studies have also shown that in some cases the affinity of TCR for an allogeneic ligand can be greater than its syngeneic target. This is best exemplified by studies on the Epstein–Barr virus-specific LC13 TCR, which recognizes its syngeneic HLA-B*0801 bound to an EBV epitope (FLRGRAYGL; referred to as FLR) with affinity of 10 μM (70), whereas the allogeneic HLA B*4402 molecule bound to EEYLQAFTY peptide (referred to as EEY) is recognized with an affinity of 1 μM (65). These observations have also been confirmed with SPR analysis of the murine 2C TCR which binds its syngeneic H-2Kb with an affinity of 83 μM and allogeneic H-2Ld complex with an affinity of 2 μM (67). Recent studies have shown that alloreactive TCRs are even capable of transcending MHC-I and MHC-II boundaries with minimal loss in affinity. The mouse YAe62 TCR binds its syngeneic MHC-II complex (IAb) with an affinity of 9 μM and allogeneic MHC-I complex (Kb) with an affinity of 15 μM (66). Taken together, these studies demonstrate that the interaction between TCR and allo-pMHC complex can display strong affinity, which may be even higher than that seen for the syngeneic pMHC complex.
Structural overview of T-cell alloreactivity
Before the resolution of the stoichiometric structural landscape of TCR-allo-pMHC complexes, it was hypothesized that the docking of TCR with allo-MHC molecules may be heavily focused on the MHC molecule rather than the peptide epitope bound to this molecule. However, growing evidence based on structural analysis of allogeneic TCR:pMHC complexes has shown that the "peptide independent" hypothesis is incorrect. Allogeneic TCR dock with normal binding geometries, heavily engage the peptide epitope, and interact in a manner that is generally indistinguishable from syngeneic docking. Structural analysis of the murine 2C TCR revealed that this receptor docks with both syngeneic pMHC-I (Kb) and allogeneic pMHC-I (Ld) complexes centrally with a crossing angle of 15° and 30°, respectively (67). The buried surface area (or area contact footprint) of the syngeneic and allogeneic complexes was 1975 Å2 and 1700 Å2, respectively which are well within the range 1100–2400 Å2 observed for other syngeneic TCR-pMHC complexes. In the syngeneic complex, MHC contact was roughly split between the TCR α- and β-chain, whereas the allogeneic complex, showed dominant interaction between pMHC and TCR β-chain. One of the important conclusions drawn from these studies was that the allorecognition of unrelated pMHC complexes could occur in the absence of molecular mimicry. However, recent studies using a human TCR (LC13) have shown that allorecognition can be driven by molecular mimicry (65). These studies showed that although the two peptide epitopes (FLR and EEY) recognized by the LC13 TCR display little sequence homology they seem remarkably 3D superimposable when comparing the syngeneic and allogeneic complexes (Figure 2). Across both syngeneic and allogeneic HLA molecules, the LC13 TCR was perched with the same superimposable 60° crossing angle and engaged the same C-terminal region of both peptides, verifying peptide-dependent molecular mimicry. Thus, both molecular mimicry and disparate docking modalities have been recognized as mechanisms of direct alloreactivity (Figure 2). More recently, these studies have been extended to another murine TCR YAe62, which displays a highly unusual cross-recognition of both pMHC-I and pMHC-II (66). These studies revealed that the YAe62 TCR adopts a similar orientation on the syngeneic pMHC-II (IAb) and allogeneic pMHC-I (Kb) molecules, but slightly adjusts its CDR3 loops to accommodate the different peptides in each MHC groove (Figure 2). Interestingly, the TCR also "flexes" the region between the V and J genes when swapping between MHC-I and MHC-II ligands. It will be important to expand these analyses to other TCR-pMHC complexes to determine which mode of interaction, that is, disparate docking versus molecular mimicry, can best describe the phenomenon of T-cell alloreactivity.
Quantifying and mapping of T-cell alloreactivity
In vitro studies based on mixed lymphocyte reactions have shown that 1–10% of T cells in then peripheral blood display strong alloreactive responses (71,72). The degree of alloreactivity is influenced by a number of variables, including the number of mismatched MHC alleles (73) and taboo allele combinations, which together significantly enhance or decrease graft survival (74). Interestingly, taboo combinations include specific HLA-A/B and HLA-DR pairings, indicating that there is cross-talk across MHC-I and MHC-II alleles (74). Recent studies have shown that MHC class I-restricted CMV-specific T cells display strong cross-recognition of allogeneic MHC class II molecules bound to an as yet undefined allotope (36). This cross-MHC class I and class II recognition can also work in reverse with T cells specific for syngeneic MHC-II (IAb) molecules and allogeneic MHC-I (Kb) alleles (66). These observations provide a new paradigm shift for T-cell recognition of allogeneic targets and potentially have new implications for clinical transplantation. For instance, the ability of CD8+ and CD4+ T cells to cross-recognize MHC-I and MHC-II alleles suggests that matching for both HLA class-I and class-II alleles may be equally important during allograft selection. This proposition contrasts with some historical studies, which suggest matching HLA-DR alleles imparts greater effect on graft and recipient survival than matching HLA-A, -B or -C alleles (75–77). Although an earlier study indicated, matching HLA class-I alleles can be as equally important as matching HLA-DR (78). These findings are supported by previous studies which have shown that HLA-B allele-restricted T-cell responses often dominate during host defense (79). Other factors influencing alloreactivity include gender, with females exhibiting generally higher frequencies of T-cell alloreactivity and allogeneic immunodominance, where clear alloreactivity hierarchies can be seen across different HLA alleles-–more frequent responses toward HLA-B alleles than HLA-A, for example (80).
An additional variable to consider in alloreactivity is the past and current viral status of the host. The memory T-cell response to human viruses, especially to the human herpesviruses, can be strikingly high in frequency. In healthy individuals, EBV and CMV-specific tetramer frequencies can range from 10% to 40% of the total CD8+ T-cell repertoire (81). In general, as the magnitude of the memory response increases, clonality decreases and these virus specific T-cell populations tend to exhibit highly focused TCR repertoires (82–86). There is now increasing evidence to indicate that these extremely large, virus-specific T-cell populations have significant allospecific footprints. Indeed, CD8+ T cells specific for EBV and CMV frequently demonstrate cross-recognition of MHC-I alloantigens (84,87–89). Similarly, CD4+ T-cell clones specific for EBV and CMV antigens also display strong alloantigen-specific cross-recognition (90,91). In a recent study, Amir et al. reported a comprehensive analysis of alloreactivity by virus-specific memory T cell by scanning a large panel of T-cell clones against 37 unrelated MHC mismatched lines, which collectively expressed roughly 100 HLA class-I and class-II alleles (92). These analyses revealed that 45% of virus-specific T cells were alloreactive and recognized one or more HLA alleles. A summary of these analyses and other previously published alloreactivities display by virus-specific T cells is presented in Figure 3. It will be of great interest to gauge the alloreactivity rate of a TCR across the bulk of the ∼6800 HLA alleles found in the Homo sapiens lineage.
To explain the high frequency of alloreactive T cells, two divergent theories have been proposed. The "multiple binary complex" theory predicts that T cells engage a large number of different allo-pMHC complexes with the TCR predominantly recognizing processed antigen (93). Conversely, the "high-determinant density" theory predicts that TCR predominantly recognize the foreign MHC rather than processed antigen (94). Structural analyses of TCR-allo-pMHC complexes support the multiple binary complex theory as the processed peptide is heavily involved in TCR recognition (65,66), while MHC interaction is similar to the syngeneic complex. Indeed alloreactive TCRs with multiple peptide specificities have been identified (95). In addition, gene silencing of a self-protein encoding, a known allotope only partially reduced the allorecognition suggesting additional allotopes may be involved in allorecognition (65). However, the precise mechanisms underlying high-alloreactive T-cell precursor frequencies, including the role of large memory monoclonal T-cell expansions remain to be fully defined.
Another important factor to consider in alloreactivity is the indirect pathway, defined by allogeneic protein fragments, often of MHC origin, presented in the context of self-MHC. MHC-derived peptides constitute more than 30% of the MHC-bound repertoire on the cell surface (96,97) and may represent key targets for T-cell alloreactvity. A good example of MHC fragments being presented by other MHC molecules is the murine Y-Ae model (98). The Y-Ae-specific antibody detects a highly conserved peptide fragment from the H2-Eα chain presented by H2-Ab (99). Interestingly, this pMHC complex can be detected in mice expressing H2-Ab and H2-E but not in mice expressing H2-Ab alone or in mice expressing H2-E with other H-2A alleles. It is also known that T cells specific for a MHC fragment can be relevant in experimental pathology (100) and in a clinical setting (101,102).
Given both the high intrinsic potential of alloreactivity and the immensity of the T-cell repertoire, it could be argued that T-cell alloreactivity may be difficult to delineate and more difficult to predict. However, extensive analysis of human T-cell repertoires has revealed that there are inherent biases in T-cell repertoire formation and common CDR3 sequences can be detected in different individuals. These "public" TCR sequences can be consistently found against both infectious pathogens and self-antigens and encompass an element of predictability in an otherwise complex TCR selection process (reviewed in Ref. 69). Restricted TCR repertoire profiles have also been observed during transplantation including clonal persistence at the graft site (103) and biased repertoire formation coinciding with clinical events (104). Predictable TCR bias has been observed in experimental alloreactive transplant models in the rat (105) and swine (106). Interestingly, in rats, prolonged allograft survival could be achieved by vaccinating animals with the pathologic TCR Vβ family gene (107) suggesting induction of tolerance. In a xenograft model, bona fide public T cells were identified in both the lymph nodes at the site of graft rejection (108). Across genetically heterogeneous human beings, the reality is that the alloreactive TCR repertoire is considerably more multifaceted, however Vβ gene bias and oligoclonal expansions have been observed in acute lesions of kidney allograft patients (109) and curiously in operationally-tolerant kidney allograft patients (110). A large study in a cohort of renal transplant patients found that alterations in T-cell repertoire correlated directly with Banff score (111), an observation in agreement with a similar study showing that the magnitude of T-cell repertoire distortion correlated with graft failure (112). Thus, mapping the alloreactivity footprints of a high frequency, herpesvirus-specific, public T-cell clonotype may produce a valuable alloreactivity "roadmap" for clinicians when deciding on appropriate host and graft matches. Overall, drafting alloreactive roadmaps across sets of commonly found public clonotypes may improve consequences for graft survival after transplantation and may delineate the mechanism underlying the "taboo concept". Such disease-predictive T-cell strategies could be complimented with other predictive tools such as HLA-Matchmaker, a quantitative algorithm used to determine the degree of a HLA mismatch and likelihood of alloantibody responses (reviewed in Ref. 113).
Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
As outlined above, recent observations have demonstrated the high prevalence at which virus-specific T cells are capable of recognizing allo-MHC-I and/or MHC-II molecules (87,92). However, the precise role of these cross-reactive T cells in organ rejection remains to be elucidated. Recent studies by Macedo et al. have shown that T cells from both the naïve and memory T-cell compartments display similar levels of alloreactivity, suggesting that both these populations have the potential to initiate rejection (114). Furthermore, previous studies have shown that memory T-cell populations can rapidly infiltrate allografts (115) and can be found in human allografts (116–118). Experimental animal models have demonstrated that alloreactive T cells can be generated after viral infection (119,120) and can mediate transplant rejection (121). These studies indicated that strategies used to induce tolerance, such as the blockade of T-cell costimulation, were ineffectual in animals exposed to multiple rounds of infections (121). Similar observations using costimulation blockade in humans are also suggestive of a role for memory T cells in mediating acute transplant rejection. Clinical studies have commenced in humans investigating the use of costimulation blockade as an alternative approach to current immunosuppressive regimes (122,123). These studies indicated that while blockade of CD28 using belatacept was associated with reduced toxicity compared to cyclosporine it was also associated with an increased risk of acute graft rejection (122).
The clear association between CMV reactivation and an increased risk of allograft rejection in solid organ transplantation is also suggestive of a potential direct role for viral reactivation in initiating transplant rejection (124–126). Studies have begun to investigate the role of alloreactive virus-specific T cells in mediating transplant rejection. Although preliminary observations have thus far, found no direct evidence (127), it will be important to carefully design these studies as the probability of detecting cross-reactive virus-specific T cells would be much higher during the acute phase of viral reactivation. Furthermore, it is apparent that in vitro evidence for alloreactivity by virus-specific T cells will not necessarily translate to an in vivo setting, and that antigen context will play a significant role in determining if an alloresponse is generated. This was exemplified in a recent study demonstrating tissue specific alloreactivity (128). Although HLA-B*0801-restricted EBV-specific T cells efficiently recognized HLA-B*4402-restricted allotope EEY on human B cells, these effector cells were unable to recognize proximal tubular endothelial cells from kidney transplant biopsy specimens or human umbilical vein endothelia cells from B*4402 positive donors. Thus, tissue antigen specificity adds another level of complexity for detecting the role of cross-reactive virus-specific T cells play in transplant rejection. Comprehensive mapping of virus-specific alloreactive T cells, defining the public nature of TCR usage in the alloreactive populations and the prevalence of the alloantigen in different tissues, and finally validating a role of these alloreactivities in vivo, will be necessary to provide definitive evidence of a role for virus-specific T cells in transplant rejection and graft-versus-host disease.
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
J.J.M. is a National Health and Medical Research Council (NHMRC) Biomedical Fellow supported by a Wales Office of Research and Development (WORD) Research Funding Scheme. RK is supported by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. This work is supported by The Roche Organ Transplantation Research Foundation (ROTRF).
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation
- Top of page
- Abstract
- T Cells in Adaptive Immunity
- Structural Insights Into TCR and pMHC Interactions
- T-Cell Activation
- Direct Allorecognition by T Cells
- Role of Virus-Specific T Cells in Transplant Rejection and Graft-Versus-Host Disease
- Acknowledgments
- Disclosure
- References
- 1CD8+ T-cell memory to viruses. Curr Opin Immunol 1994; 6: 545–552., , .
- 2Thymic selection: Two pathways to life and two to death. Immunity 1994; 1: 3–6..
- 3Role of self-peptides in positively selecting the T-cell repertoire. Nature 1990; 344: 65–67., .
- 4The known unknowns of antigen processing and presentation. Nat Rev Immunol 2008; 8: 607–618., , .
- 5Chemokine receptor expression identifies Pre-T helper (Th)1, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells. J Exp Med 2004; 200: 725–735., , , , , .
- 6Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 2002; 8: 379–385., , , et al.
- 7Central memory and effector memory T cell subsets: Function, generation, and maintenance. Annu Rev Immunol 2004; 22:745–763., , .
- 8Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells. J Exp Med 2001; 194: 1711–1719., , .
- 9Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998; 393: 478–480., , , , , .
- 10Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help. J Exp Med 1997; 186: 65–70., , , , .
- 11Cognate CD4(+) T cell licensing of dendritic cells in CD8(+) T cell immunity. Nat Immunol 2004; 5: 1143–1148., , , et al.
- 12Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401: 708–712., , , , .
- 13Immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of CD8+ T cells. J Exp Med 2004; 199: 925–936., , , .
- 14Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med 1991; 173: 747–750., , , , , .
- 15Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 2009; 10: 385–393., , .
- 16CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 2000; 192: 1553–1562., , , , , .
- 17Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348–2357., , , , .
- 18Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010; 28:445–489., , .
- 19How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol 2006; 241: 419–466., , .
- 20T-cell receptor binding affinities and kinetics: Impact on T-cell activity and specificity. Immunology 2009; 126: 165–176., , .
- 21Antagonism of antiviral and allogeneic activity of a human public CTL clonotype by a single altered peptide ligand: implications for allograft rejection. J Immunol 2005; 174: 5593–5601., , , et al.
- 22The impact of duration versus extent of TCR occupancy on T cell activation: A revision of the kinetic proofreading model. Immunity 2001; 15: 59–70., , , et al.
- 23Alphabeta T cell receptor interactions with syngeneic and allogeneic ligands: Affinity measurements and crystallization. Proc Natl Acad Sci USA 1997; 94: 13838–13843., , , et al.
- 24Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex. Immunity 2000; 13: 529–538., , , et al.
- 25A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity 1996; 5: 53–61., , , et al.
- 26CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate. J Immunol 2007; 179: 2952–2960., , , .
- 27T cell activation. Annu Rev Immunol 2009; 27:591–619., , .
- 28Differential clustering of CD4 and CD3zeta during T cell recognition. Science 2000; 289: 1349–1352., , , .
- 29Direct observation of ligand recognition by T cells. Nature 2002; 419: 845–849., , , .
- 30Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity. Nature 2005; 434: 238–243., , , , , .
- 31Costimulation and endogenous MHC ligands contribute to T cell recognition. Nat Immunol 2002; 3: 42–47., , , , , .
- 32Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation. Immunity 2003; 18: 255–264., .
- 33Interplay between TCR affinity and necessity of coreceptor ligation: High-affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement. J Immunol 2003; 171: 4493–4503., , , et al.
- 34Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell receptor-antigen complexes at the cell surface. J Biol Chem 2005; 280: 27491–27501., , , et al.
- 35CD8 controls T cell cross-reactivity. J Immunol 2010; 185: 4625– 4632., , , et al.
- 36Cross-recognition of HLA DR4 alloantigen by virus-specific CD8+ T cells: A new paradigm for self-/nonself-recognition. Blood 2009; 114: 2244–2253., , , , .
- 37Mechanisms of costimulation. Immunol Rev 2009; 229: 5–11..
- 38The B7-CD28 superfamily. Nat Rev Immunol 2002; 2: 116–126., .
- 39The interleukin 2 CD28-responsive complex contains at least three members of the NF kappa B family: c-Rel, p50, and p65. Proc Natl Acad Sci U S A 1993; 90: 1696–1700., , , , .
- 40Differential T cell costimulatory requirements in CD28-deficient mice. Science 1993; 261: 609–612., , , et al.
- 41Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory. J Immunol 2001; 167: 5565–5573., , , et al.
- 42T cell activation determined by T cell receptor number and tunable thresholds. Science 1996; 273: 104–106., .
- 43Memory CD8+ T cells require CD28 costimulation. J Immunol 2007; 179: 6494–6503., , , et al.
- 44Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the recall response. J Immunol 2008; 180: 1148–1157., , .
- 45Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J Immunol 1999; 162: 7569–7577., , , , .
- 46A switch in costimulation from CD28 to 4–1BB during primary versus secondary CD8 T cell response to influenza in vivo. J Immunol 2004; 172: 981–988., , , , , .
- 47Role of 4–1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells. Blood 2002; 100: 3253–3260., , .
- 48Costimulatory ligand 4–1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses. Proc Natl Acad Sci U S A 2004; 101: 1291–1296., , , , .
- 49Activated and memory CD8+ T cells can be distinguished by their cytokine profiles and phenotypic markers. J Immunol 2000; 164: 208–216., .
- 50Functional responses and costimulator dependence of memory CD4+ T cells. J Immunol 2000; 164: 265–272., , .
- 51Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001; 291: 2413–2417., , , .
- 52Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J Immunol 1994; 152: 2675–2685., , .
- 53Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 2008; 319: 198–202., , , , .
- 54Dendritic cells maximize the memory CD8 T cell response to infection. Immunity 2005; 22: 561–570., , , .
- 55The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells. Eur J Immunol 1997; 27: 3310–3317., , .
- 56Qualitative changes accompany memory T cell generation: Faster, more effective responses at lower doses of antigen. J Immunol 2000; 164: 2338–2346., , .
- 57Biochemical signaling pathways for memory T cell recall. Semin Immunol 2009; 21: 84–91..
- 58A biochemical signature for rapid recall of memory CD4 T cells. J Immunol 2007; 179: 3689–3698., , , .
- 59Control of memory CD4 T cell recall by the CD28/B7 costimulatory pathway. J Immunol 2006; 177: 7698–7706., , , et al.
- 60CD8highCD57+ T lymphocytes in normal, healthy individuals are oligoclonal and respond to human cytomegalovirus. J Immunol 1995; 155: 5046–5056., , , , , .
- 61Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 2002; 169: 1984–1992., , , et al.
- 62Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med 2006; 203: 2865–2877., , , et al.
- 63Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells. J Immunol 2002; 169: 5838–5843., , , , , .
- 64Allorecognition and the alloresponse: Clinical implications. Tissue Antigens 2007; 69: 545–556., , .
- 65T cell allorecognition via molecular mimicry. Immunity 2009; 31: 897–908., , , et al.
- 66A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers. Immunity 2011; 35: 23–33., , , et al.
- 67How a single T cell receptor recognizes both self and foreign MHC. Cell 2007; 129: 135–146., , , et al.
- 68Human TCR-binding affinity is governed by MHC class restriction. J Immunol 2007; 178: 5727–5734., , , et al.
- 69Bias in the alphabeta T-cell repertoire: Implications for disease pathogenesis and vaccination. Immunol Cell Biol 2011; 89: 375–387., , .
- 70A structural basis for the selection of dominant alphabeta T cell receptors in antiviral immunity. Immunity 2003; 18: 53–64., , , et al.
- 71The molecular basis of allorecognition. Annu Rev Immunol 1993; 11:385–402., .
- 72Quantifying the frequency of alloreactive T cells in vivo: new answers to an old question. J Immunol 2001; 166: 973–981., , , , , .
- 73
- 74Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept. Lancet 1996; 348: 850–853., , , et al.
- 75Ten-year survival of second kidney transplants: Impact of immunologic factors and renal function at 12 months. Kidney Int 2003; 64: 674– 680., , , et al.
- 76Simpler and equitable allocation of kidneys from postmortem donors primarily based on full HLA-DR compatibility. Transplantation 2007; 83: 1207–1213., , , et al.
- 77Substantial benefits of tissue matching in renal transplantation. Transplantation 1987; 43: 669–674., , , .
- 78Correlation of HLA matching with kidney graft survival in patients with or without cyclosporine treatment. Transplantation 1985; 40: 240–243..
- 79Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 2004; 432: 769–775., , , et al.
- 80Immunodominance hierarchies and gender bias in direct T(CD8)-cell alloreactivity. Am J Transplant 2008; 8: 121–132., , , , , .
- 81Epitope-specific evolution of human CD8(+) T cell responses from primary to persistent phases of Epstein-Barr virus infection. J Exp Med 2002; 195: 893–905., , , , .
- 82Dominant selection of an invariant T-cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med 1994; 180:2335–2340., , , et al.
- 83Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection. Blood 2008; 111: 4283–4292., , , et al.
- 84T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen. J Exp Med 1995; 182: 1703–1715., , , , , .
- 85CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals. Blood 2008; 111: 2053–2061., , , , .
- 86Narrowing of T-cell receptor beta variable repertoire during symptomatic herpesvirus infection in transplant patients. Immunol Cell Biol 2010; 88: 125–135., , , et al.
- 87Cross-reactivity of herpesvirus-specific CD8 T cell lines toward allogeneic class I MHC molecules. PLoS One 2011; 5: e12120., , , et al.
- 88An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: Implications for graft-versus-host disease. J Exp Med 1994; 179: 1155–1161., , , .
- 89Cross-reactive memory T cells for Epstein-Barr virus augment the alloresponse to common human leukocyte antigens: Degenerate recognition of major histocompatibility complex-bound peptide by T cells and its role in alloreactivity. Eur J Immunol 1997; 27: 1726–1736., , , et al.
- 90EBV-specific CD4+ T cell clones exhibit vigorous allogeneic responses. J Immunol 2006; 177: 1427–1433., , , et al.
- 91Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: Implications for graft-versus-host disease. Blood 2005; 105: 1362–1364., .
- 92Allo-HLA reactivity of virus-specific memory T cells is common. Blood 2010; 115: 3146–3157., , , et al.
- 93Hypothesis: Why do so many lymphocytes respond to major histocompatibility antigens? Cell Immunol 1977; 29: 1–5., .
- 94High determinant density may explain the phenomenon of alloreactivity. Immunol Today 1984; 5:128–130..
- 95Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes. Nat Immunol 2007; 8: 388–397., , , et al.
- 96Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med 1993; 178: 27–47., , , , , .
- 97Sequence analysis of peptides bound to MHC class II molecules. Nature 1991; 353: 622–627., , , , .
- 98On the complexity of self. Nature 1991; 353: 660–662., , , , .
- 99Monoclonal antibody detection of a major self peptide. MHC class II complex. J Immunol 1992; 148: 3483–3491., , , et al.
- 100Restricted MHC-peptide repertoire predisposes to autoimmunity. J Exp Med 2005; 202: 73–84., , , et al.
- 101Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts. J Clin Invest 1998; 101: 398–405., , , et al.
- 102Analysis of indirect pathway CD4+ T cells in a patient with metastable tolerance to a kidney allograft: Possible relevance to superior graft survival of HLA class II closely matched renal allografts. Transpl Immunol 2009; 20: 203–208., , , .
- 103Coronary arteries from human cardiac allografts with chronic rejection contain oligoclonal T cells: Persistence of identical clonally expanded TCR transcripts from the early post-transplantation period (endomyocardial biopsies) to chronic rejection (coronary arteries). J Immunol 2000; 165: 3469–3483., , , , .
- 104Modulation of the T cell receptor beta chain repertoire after heart transplantation. Transpl Immunol 2000; 8: 83–94., , , , , .
- 105Selection of T cell clones with restricted TCR-CDR3 lengths during in vitro and in vivo alloresponses. Int Immunol 1998; 10: 71–83., , , , , .
- 106A particular TCR beta variable region used by T cells infiltrating kidney transplants. J Immunol 2001; 166: 2589–2596., , .
- 107Anti-TCR Vbeta-specific DNA vaccination prolongs heart allograft survival in adult rats. Eur J Immunol 2000; 30: 2460–2464., , , et al.
- 108Compartmentalization of TCR repertoire alteration during rejection of an intrabrain xenograft. Exp Neurol 2005; 192: 373–383., , , et al.
- 109Highly altered V beta repertoire of T cells infiltrating long-term rejected kidney allografts. J Immunol 2000; 164: 1553–1563., , , et al.
- 110Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation. Am J Transplant 2005; 5: 330–340., , , et al.
- 111Analysis of the peripheral T-cell repertoire in kidney transplant patients. Eur J Immunol 2010; 40: 3280–3290., , , et al.
- 112Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys. Transplantation 2003; 75: 398–407., , , et al.
- 113Clinical usefulness of HLA matchmaker in HLA epitope matching for organ transplantation. Curr Opin Immunol 2008; 20: 594–601..
- 114Contribution of naive and memory T-cell populations to the human alloimmune response. Am J Transplant 2009; 9: 2057–2066., , , et al.
- 115Donor-reactive CD8 memory T cells infiltrate cardiac allografts within 24-h posttransplant in naive recipients. Am J Transplant 2008; 8: 1652–1661., , , , .
- 116The development of primed/memory CD8+ lymphocytes in vitro and in rejecting kidneys after transplantation. Clin Exp Immunol 1990; 81: 225–231., , , , , .
- 117Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Am J Pathol 1990; 137: 871–882., , , et al.
- 118Predominant infiltration of rejecting human renal allografts with T cells expressing CD8 and CD45RO. Transplantation 1995; 59: 724–728., , .
- 119Characterization of dual-reactive H-2Kb-restricted anti-vesicular stomatitus virus and alloreactive cytotoxic T cells. J Immunol 1987; 138: 3654–3660., , .
- 120Induction of alloreactive cytotoxic T cells by acute virus infection of mice. J Immunol 1986; 136: 1186–1193., .
- 121Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest 2003; 111: 1887–1895., , , et al.
- 122A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 2010; 10: 535–546., , , et al.
- 123Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005; 353: 770–781., , , et al.
- 124Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA 1989; 261: 3561–3566., , , , , .
- 125Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis 2001; 184: 1461–1464., , , et al.
- 126CMV infection, class II antigen expression, and human kidney allograft rejection. Transplantation 1986; 42: 364–367., , , .
- 127Quantitative and functional diversity of cross-reactive EBV-specific CD8+ T cells in a longitudinal study cohort of lung transplant recipients. Transplantation 2010; 90: 1439–1449., , , .
- 128Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T cells. Transplantation 2011; 91: 494–500., , , et al.


text:
Crazy Substitute Teachers
Enjoy, NG4.04 / 5.00 1,847 Views
Vacuum Salesman
This dude and his Megazord vacuum cleaner4.00 / 5.00 2,524 Views
Markiplier Animated | Mark Of The Survey Corps
This took far too long to make...3.89 / 5.00 4,764 Views
wont be continued
It was a good idea but it was really fucking boring.
I'm blamin this.
See above review for further information.
Good work
Would have been much better if you had spent more time on the backgrounds and understood perspective. I couldn't follow the story, probably because I was being spoken to on MSN, but your fla's of characters are very high class drawings and I know that you can improve a great deal. Good luck on your next one.
Fucking Brilliant
Nice job, Brit. You made a fantastic CC movie.
You win.
T'was great!
It was great!The story was good,the graphics awesome and overall great!BDW:after 2 days my trial will be over so i can post on the forum.Hope it dousnt bother you im a n00b but dont worry:i never make retard posts nor do i say B every 5 seconds :P


text:
Upcoming NW Fight Events
(Events and Venues subject to change)
Saturday, July 30th
2016 Sub League Championships
Portland CC Rock Creek Campus - Portland, Oregon
Tuesday, August 2nd
War at the Wolf
Friday, August 5th
Boxing at the University Club - Amateur Boxing
Saturday, August 6th
Summer Showdown 3
King of the Cage "Provoked"
Chinook Winds Casino - Lincoln City, Oregon
AX Fighting #55
Edmonds Community College - Lynnwood, Washington
Friday, August 12th
Front Street Fights 9
Thunder and Lightning
Saturday, August 13th
Total Combat - Amateur Boxing
North Medford High School - Medford, Oregon
Thursday, August 18th
King of the Cage "No Remorse"
Coeur d'Alene Casino - Worley, Idaho
Saturday, August 20th
Rumble on the Ridge 35
Snoqualmie Casino - Snoqualmie, Washington
Saturday, August 27th
Midtown Throwdown 9
UFC on FOX 21
Rogers Arena - Vancouver, British Columbia
Warehouse Wars - Full Contact Kickboxing Smoker
AKA MMA & Fitness - Arlington, Washington
Lethal Limbs Fight Night
Lethal Limbs Academy - Olympia, Washington
Saturday, September 3rd
Reign FC
Clearwater Casino - Suquamish, Washington
Saturday, September 10th
Battle at the Boat 107
Emerald Queen Casino - Tacoma, Washington
Hard Rock Casino - Coquitlam, British Columbia
2015 NAGA Seattle Grappling Championshp
Everett Community College - Everett, Washington
Saturday, September 24th
COGA MMA "Breaking Point 2"
Brawl at Harmony Hall 2 - Professional Boxing
Saturday, October 1st
Rumble on the Ridge 36
Snoqualmie Casino - Snoqualmie, Washington
King of the Cage
Chinook Winds Casino - Lincoln City, Oregon
Rumble at the Roseland 89
Roseland Theater - Portland, Oregon
UFC Fight Night
MODA Center - Portland, Oregon
Saturday, October 8th
Proving Grounds IX BJJ/Nogi Submission Only Tournament
Prime Fighting 8
Clark County Event Center - Ridgefield, Washington
Submission Grappling Federation "West Coast Clash"
Salem Armory - Salem, Oregon
Saturday, October 15th
The Redemption 8
Saturday, October 22nd
CageSport presents SFL
Fall Brawl - Amateur Boxing
Yakima Eagles - Yakima, Washington
Saturday, November 12th
The Revolution XXXII - Adults
Pacific Lutheran University - Tacoma, Washington
Sunday, November 13th
The Revolution XXXII - Kids
Pacific Lutheran University - Tacoma, Washington
Thursday, November 17th
King of the Cage
Coeur d'Alene Casino - Worley, Idaho
Saturday, November 19th
Battle at the Boat 108
Emerald Queen Casino - Tacoma, Washington
King of the Cage
Fort Hall Casino - Fort Hall, Idaho
All Photos, Design, and Content © 2006-2016 NW Fightscene™, unless otherwise noted.
Any usage of content on this site is strictly prohibited without the express written consent of NW FightScene™.
Report any errors to firstname.lastname@example.com