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24 – 28/10/2016:
Field Trip to Coca-Cola Factory – Grade 8-9
Happy Halloween – All Campuses
31/10 – 4/11:
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Mr. Tran Huu Thuan
Dao Nguyen Bao Ngoc
" My favorite subject is literature. Every time I write my compositions, I have a feeling that the whole world were under my pen, and it had been waiting to be written down. Our class is always excited about how our teachers inspire us with the suggested images or ways to use figurative language such as simile or personalization....
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Welcome to the GrenoblIX IXP
GrenoblIX is the Internet traffic eXchange Point of Grenoble operated by Rezopole, a non-profit organization.
GrenoblIX members can improve the quality of their Internet traffic and can benefit from lower bandwidth prices. Therefore the IXP helps develop very high speed Internet in Lyon.
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GrenoblIX news
The Rezopole technical team now shares its network tools software developments on a github repository. Two projects are already published: lint_conf and capstat.
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Rezopole was present at the L'Instant Numérique showroom in Roanne on September 15th 2016. For this occasion Le journal de l'éco interviewed Samuel Triolet, CEO, to explain the Rezopole role in the Auvergne - Rhône-Alpes region.
Plus d'ingénieures diplômées, mais les inégalités persistent
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The observatory of the French Internet resilience publishes its 2015 report
Pour la cinquième année consécutive, l'Agence nationale de la sécurité des systèmes d'information (ANSSI) avec la participation de l'Afnic, analyse la résilience de l'Internet français en étudiant deux protocoles, BGP et DNS.
IXP: Critical interconnection point in 2019?
According to Cisco, the annual IP datacenter traffic will globally reach 10.4 Zb in 2019, including 8.6 Zb generated by the only Cloud services.
When the State told you that Internet had no future...
Philippe Silberzahn, professor at EMLYON Business School and researcher associated with the Ecole Polytechnique, published an article on the errors of Thery report 1994 "Information highways". In this article Silberzahn reveals the errors of this report focusing on the future of information highways and the Internet role.


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Derek Stepan takes the praise for what it's worth right now. It's nice knowing Rangers coach John Tortorella considers him the team's most consistent skater and top center. But Stepan, 22, knows it means little as the sixth-seeded Rangers prepare for Game 1 of their Eastern Conference quarterfinal against the third-seeded Capitals on Thursday night at Washington.
Derek Stepan Elevating His Play
From NorthJersey.com
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Rupert Murdoch in "Unprecedented Firestorm" as U.K. Panel Finds Him Unfit to Run Global Media Empire
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81–205). Erlbaum. Automation and human performance, mouloua.
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After the Oklahoma City Thunder finished off the San Antonio Spurs on Wednesday night, only three teams remain in the NBA playoffs.
A couple of weeks ago, I wrote a column on the eight players who had the best chance of taking home the NBA Finals MVP in June. Here are my updated rankings.
I bet you can guess who's No. 1 on this list.


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HOUSTON ‐ Who would've thunk it? The Dallas Cowboys are the NFC East's current model of stability.
Their general manager has been their general manager for 27 years. And, quite frankly, because Jerry Jones doubles as the owner, he's going to be the general manager until he dies or is no longer physically capable of handing the responsibility. That's the perk of being the man that signs the checks.
In addition to the "general manager," the Cowboys also have the NFC East's longest-tenured coach. Jason Garrett has been at the helm for five years. Meanwhile, Jay Gruden just finished his second season in Washington and the Giants and Eagles are looking for coaches.
This consistency still doesn't seem to be giving Jones much comfort following a 4-12 season ruined by injuries to quarterback Tony Romo and wide receiver Dez Bryant.
"I'm looking up, on my back and all I see is ass," Jones said Tuesday night at The Westin Houston, Memorial City Hotel following relocation meetings where Jones championed a plan that sent the St. Louis Rams to Los Angeles with the San Diego Chargers likely on deck. "I want a different perspective."
The NFC East was turned upside down in 2015. The Redskins (9-7) went from worst to first. The Cowboys (4-12) made the unenviable move in the other direction while the Eagles (7-9) and Giants (6-10) remained stuck in the middle.
Still, it wasn't as if Washington ran away with the division in convincing fashion. It had to win five of its last six to become the only NFC East team above .500 this season. The Redskins were then eliminated in the wild card round of the postseason, losing convincingly at home to the Green Bay Packers.
The NFC East could have a vastly different look and feel next season, and it wouldn't be much of a surprise if the standings flipped again. It seems to happen almost every year. There hasn't been a repeat winner of the division since the Eagles in 2001-04.
Jones sees potential for next season to be the Cowboys' year. He's intent on stressing that to just about everyone in the organization this offseason.
"I do see opportunity though," Jones said, despite his team's record in 2015. "But I want a different view and that will ring and intertwine through every meeting, every personal visit I have with everybody involved with the Cowboys. I want to see a different look."
It could work in their favor that the Giants and Eagles will have new looks and feels. They're both in the midst of a coaching search. And with new coaches often comes an adjustment period.
This could further open the door for the Cowboys who, if healthy, many believe still have the best roster in the division. And Jones is hopeful is good enough to prevent them from being stuck under a pile of backsides for another offseason.
TALK IS CHEAP, Ep. 38: Who should replace Tom Coughlin as Giants coach?Subscribe to the podcast on iTunes or Stitcher.
Jordan Raanan may be reached at email@example.com. Follow him on Twitter @JordanRaanan. Find NJ.com Giants on Facebook.


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|4th December 2009, 09:05 PM
New Member
Join Date: Aug 2006
Posts: 13
New Quiver
Posted this on the team forum but seem to be getting a slow response. Welcome any advice from people who have experience with any of the boards I am talking about .
Looking for some advice on updating my quiver. I currently have a Trance 94 04 and an Acid 74 05. Weight 66kg. Sailing mostly rivers and Great Lakes Canada with yearly trips to the ocean at Cape Hatteras. Current sail quiver 6.0, 5.3, 4.7, 4.2 and 3.7. Advanced B&J sailor learning to sail the ocean, looking to learn learn freestyle and tired of back and forth sailing.
Other board is 12-6 SUP which I paddle as much as possible ocean and flatwater and lightwind sail and wave sail. If I had to keep one board this would be it because it does everything. The SUP covers me from 0 - 15 knots. Sailed it in much higher wind and loved it then as well. Something about strapless!
Thinking of replacing the Trance first with a K94 with the hope that I can learn some freestyle and still use it for B&J and onshore wave sailing in the Great Lakes. Although I wonder if a Flare might do the same thing with an obvious bias for more flatwater but with slightly better early planing?
Looking to replace the Acid 74 with maybe 2 boards although I would love to some advice on a 1 or 2 board replacement. The current 20 ltr drop is doable and I use the Acid for 3.7 - 4.7. The problem is that it is very gusty inland and the Acid seems to have an on/off switch.
Thinking I would like to try the Quads but can't figure which one or ones would replace the Acid. From what I have read the Q71 would seem to be the ideal 1 board replacement but what if I wanted to go to a 2 board replacement and expand my sail quiver to carry a 3.3?
Q66 and Q76?
Finally majority of wave sailing is the Great Lakes which is pretty well dead on shore.
Any advice would be greatly appreciated.
|8th December 2009, 08:39 AM
Posts: n/a
bro, your request is too long winded... I fell asleep after like 3 lines. You may as well ask "can anyone tell me how to achieve peace on earth without scratching my car or eating wheat based products?"
However, you sound like a sweet rider man, wish i was that good...
|8th December 2009, 05:59 PM
New Member
Join Date: Aug 2006
Posts: 13
Well Bro, since we are brothers you are right the posting was a little long winded and thanks for the feedback. I decided to put in all the info that would help people give me the best feedback possible i.e. weight, freshwater, ocean, sailing ability, sail range, sailing goals, current equipment all the sorts of questions that would come up had I posted.... "Need a Two Board Quiver Man?" However based upon the poor response to my original question lets try your approach and we will see if I end up answering all the same questions i.e weight. ability blah blah blah. I will try and keep it to less than 3 lines.
|20th December 2009, 04:24 AM
New Member
New Quiver
Im just interested, how are you going to celebrate New Year? Where and how are you going to celebrate it?
About me - Im going to celebrate it in the restaurant with my husband, just from 31 of December, and after that well go to the booked hotel lux room.. What about you?
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All Blog Posts Tagged 'Beast' - TwiFans-Twilight Saga books and Movie Fansite 2016-10-27T18:51:55Z http://twifans.com/profiles/blog/feed?tag=Beast&xn_auth=no Stephenie Meyer talks with The Daily Beast about her favorite movie romances tag:twifans.com,2013-03-29:2644331:BlogPost:10763363 2013-03-29T17:37:19.000Z sarah cullen http://twifans.com/profile/saracullen388

Today, Stephenie Meyer's sixth book-to-film adaptation (and her first non-Twilightfare) hits theaters. The Host, a science-fiction romance set in a post-apocalyptic reality marks Meyer's first novel catering to an adult audience, and revolves around a world where human bodies become the host for alien residents.…

Today, Stephenie Meyer's sixth book-to-film adaptation (and her first non-Twilightfare) hits theaters. The Host, a science-fiction romance set in a post-apocalyptic reality marks Meyer's first novel catering to an adult audience, and revolves around a world where human bodies become the host for alien residents.

The Daily Beast asked the bestselling author—whose novels have sold more than 220 million copies worldwide—her favorite movie romances of all time, which she narrowed down to 10 filmic couplings.

Here are Meyer's picks:-

Penelope (2006)

"James McAvoy—as if you need any more descriptor other than just… James McAvoy. If you haven't seen it, see it. It's such a lovely fairytale because it feels like a children's story in some ways. It seems almost illustrated. The visuals are so fairytale-like, heightened and surreal. It's a lovely, sweet little romance. Sometimes, it bothers me when the problems that come between people are easily surmountable. That's why I write complicated love stories, where there's an actual problem—as in you have an alien in your head—it's not your normal, everyday, "Well, we just don't get along" story. So in Penelope, there was a true misunderstanding, and there was a reason for it and the logic lined up. It was so sweet and adorable and… James McAvoy."

(500) Days of Summer (2009)

"Romantic comedies in some ways have stalled out a little bit, where we are seeing the same thing. And it's rare when you can break through and [they] feel fresh and exciting again. Sometimes the stereotypes get so insulting. They're there, and we know what they are. (500) Days of Summer is this completely novel way of doing things. Having become more involved with filmmakers, the creation and the way the story is told is probably more fascinating to me than it would have been before. [The director] breaks all these rules and I remember sitting there with my mouth open in the theater when they did the "Expectations vs. Reality" split screen. I was like, "This is genius!" because that is how we see things and how we experience them and no one has ever visualized it like this before. And, of course, Joseph Gordon Levitt. I love Zooey Deschanel too, and they made an adorable couple. It felt very real because it wasn't all candy canes and bubblegum, it was: "Sometimes they don't like you as much as you like them."

Notting Hill (1999)

"I've always been a sucker for Notting Hill, I don't know why, and I don't know why I can't change the channel when that movie comes on. It's so cute. It was one of my last favorite romantic comedies for a long time."

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Space Shuttle NASA Mission Report: STS-1, April 1981 - Young and Crippen Pilot Columbia on the First Space Shuttle Mission - Complete Technical Details of All Aspects of the Historic Flight
by Progressive Management
- #159 in Nonfiction, Science & Nature, Science, Other Sciences, History
- #78 in Nonfiction, Science & Nature, Science, Physics, Astronomy
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This is the official final mission report issued by the NASA Johnson Space Center for the flight of STS-1, the first Space Shuttle mission launched in April 1981 with John Young and Robert Crippen. In addition to technical details, this report includes the report of Young and Crippen on the mission. Over 60 orbiter anomalies are discussed.
Contents include: Propulsion Systems * Orbiter Main Propulsion System * Orbital Maneuvering System * Reaction Control System * Power Systems * Auxiliary Power Unit * Hydraulic Subsystem * Power Reactant Storage And Distribution * Power Generation Subsystem * Electrical Power Distribution And Control * Avionics Systems * Integrated Guidance, Navigation, And Control * Data Processing System And Software * Backup Flight System * Displays And Controls * Communications And Tracking * Instrumentation * Systems Management * Redundancy Management * Environmental Control And Life Support System * Active Thermal Control System * Air Revitalization System * Air Revitalization Pressure Control System * Airlock Support System * Water And Waste Management System * Crew Station And Equipment * Cabin Arrangement * Cabin Environment * Noise Level Survey * Stowage * Flight Crew Equipment * Flight Test Requirements * Structures * Flutter/Buffet * Loads And Stress Evaluation * Midbody Deflection/Door Closing Test * Entry Flight Loads * Aerodynamic Pressure Distribution * Window Cavity Conditioning Systems * Mechanical Systems * Purge And Vent Subsystem * Orbiter/External Tank Separation And Umbilical Devices * Payload Bay Doors And Radiators * Star Tracker Doors * Air Data Probe * Landing Deceleration Subsystem * Aerothermal Seals * Crew Escape System * Pyrotechnics * Thermal * Thermal Control * Thermal Protection * Aerothermodynamics * Aerodynamics * Ascent * Entry * Aerodynamic Coefficient Identification Package * Environments Analysis * Acoustics Evaluation * Vibration Evaluation * Thermal Analysis * Contamination * Payload Bay Environment Analysis * Lift-Off Accelerations * Landing Accelerations * Quasi-Static Accelerations * Acoustic * Vibration * Thermal * Crew Report * Training * Sts-1 Prelaunch And Ascent * Prelaunch Activity To Crew Ingress * The First Launch Attempt - April 10 * Prelaunch Activity - April 12 * Ascent Phase * General On-Orbit Operations * Crew Timelines * Zero Gravity Operations In Columbia * Vehicle Surface Observations * On-Orbit Guidance, Navigation And Control System Performance * Attitude And Translation Maneuvers * Data Processing System (DPS) Operations * Flight Control System (FCS) Checkout * Star Tracker, Inertial Measurement Unit, And Optical Alignment Sight Operations * Systems Operations * Electrical Power System * Water Dumps * Communications Operations * Auxiliary Power Unit (APU)/Hydraulic System Operations * Mechanical Systems Operation * Fire/Smoke Detection System Checks * Environmental And Thermal Control "Systems Performance Operations * Radiator Operations * Cabin/Avionics Bay Water Loop Operations * Pressure Control System Reconfiguration Operations * Crew/Orbiter Compatibility Tests * Television Camera Operation * Crew-Operated Camera * Food Operations * Window Operations * Cabin Noise * Inflight Maintenance * Pressure Suit Doffing And Donning Operations * Gas Sampling And Solid Solvent Sampling * Waste Management System Operations * Stowage * Entry Phase * Deorbit Maneuver * Post-Firing Maneuver to the Entry Attitude * Entry Interface Minus 5 Minutes * Entry * Post Landing Operations * Biomedical Evaluation * Trajectory * Mission Control And Flight Control Evaluation * Orbiter Anomaly Summary
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The Politically Incorrect Guide to American History
|Thomas E. Woods
|United States
|The Politically Incorrect Guide
|Regnery Publishing
Publication date
|December 2004
|Media type
|Hardback & Paperback
The Politically Incorrect Guide to American History is a "non-fiction" book covering various issues in U.S. history by Thomas E. Woods, published in December 2004. This book was the first in the Politically Incorrect Guide series published by Regnery Publishing, who view the series as covering topics without consideration for political correctness.[1] The book, "a pro-Confederate, revisionist tract",[2] was a top seller on Amazon.com, reaching No. 2, and was present on The New York Times best-seller list for many weeks.[3]
Background and contents[edit]
The book challenges modern notions of American history; the author argues, among other viewpoints, that America's founding fathers were conservatives, the War on Poverty made poverty worse and that hundreds of American liberals had ties to the Soviet Union during the McCarthy Era. It also contests the cost-effectiveness of government projects, especially the Transcontinental Railroad.[citation needed]
Reviews and further discussions[edit]
Council on Foreign Relations senior fellow Max Boot published a critique of the book in The Weekly Standard on February 2005. Boot labeled Woods' views as a 'Bizarro world.' Boot also criticized Woods for what he saw as ignoring African-Americans' struggle for civil rights and ignoring the fact that Clinton's intervention in the Balkans stopped a potential genocide.[4]
Woods has hosted an eight-lecture seminar covering the material in his book to the Auburn University's Academy for Lifelong Learners, a project hosted by the Ludwig von Mises Institute.[5]
Paul Craig Roberts, former assistant secretary of the U.S. Treasury, praised the "highly readable" book. He referred to it as an "important work that refutes the misinterpretations of American history that have misinformed generations about their country, its origins, purposes, successes, and failures." Ron Paul, a Republican member of the U.S. House of Representatives, stated about the book, "Knowing our past is essential if we are to preserve our freedoms. Professor Woods's work heroically rescues real history from the politically correct memory hole. Every American should read this book."[6]
- ^ "Anti-PC series takes on history, Islam, feminism - Striving to be 'incorrect'". The Washington Times. July 20, 2006.
- ^ Livingstone, David (2015). Transhumanism: The History of a Dangerous Idea. CreateSpace Independent Publishing Platform. p. 321.
- ^ New York Times "Bestseller List" (Paperback non-fiction), 9 January 2005 [1]
- ^ "Incorrect History". By Max Boot. The Weekly Standard. Published February 15, 2005. Accessed August 22, 2009.
- ^ "The Politically Incorrect Guide to American History: Lecture Series". Mises Institute.
- ^ http://www.radioliberty.com/bpigah.html


text:
Dark Ranger Marrah wants you to steal 5 Vrykul Weapons from Utgarde Keep and bring them to her inside Utgarde Keep.
If you'd have seen how easily they cut through my companions, you'd understand my sense of urgency.
Scour the place. Gather all of their arms that you can carry.
You will receive:
4 70
|Vrykul Weapon (5)
DescriptionWe must discover the secret to these savages' weapons!
If you'd have seen how easily they cut through my companions, you'd understand my sense of urgency.
Scour the place. Gather all of their arms that you can carry.
What have you got there, <class>?
Marrah has informed us of the superiority of the Vrykul's weaponry. We'll have a look at these and see if there's anything to learn.
Take this for your trouble, <class>.
Take this for your trouble, <class>.
You will be able to choose one of these rewards:
|Necklace of Calm Skies
|Hundred Tooth Necklace
|Amulet of Constrained Power
|Tiled-Stone Pendant
GainsUpon completion of this quest you will gain:
- 10,950 experience
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Councils to get the message about challenges of open source
A conference to discuss the challenges facing local authorities in choosing software platforms for delivering e-government programmes will be held on 6 February. The conference is being staged by London Connects and the Open Source Academy (OSA).
This Article Covers
Business applications
A conference to discuss the challenges facing local authorities in choosing software platforms for delivering e-government programmes will be held on 6 February. The conference is being staged by London Connects and the Open Source Academy (OSA).
How businesses can win talent war with mobile apps, HR data analytics and cloud technology
Latest articles on HR best practices: mobile apps disrupting the annual staff appraisals; reasons for and against open-source software; and Rolls-Royce case study.
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The OSA, which is funded through the Office of the Deputy Prime Mininster's e-Innovations programme, is tasked with providing answers to local authorities on the use of open source software (OSS) and its integration with the proprietary systems that dominate the sector.
The ODPM wants to see greater competition in the software market and aims to encourage local authorities to make more use of OSS as it believes it is potentially cheaper and more secure.
The conference will mark the launch of a certification scheme to enable councils more easily to understand the implications that proprietary software lock-ins can have on future procurement decisions.
Called Certified Open, the scheme will gauge the "openness" of software and its potential for integration and use with other software systems, which will assist local authority officers when making decisions about software procurement.
The conference will also announce the results of all the projects being run under Open Source Academy auspices, including the implementation of the open source Star Office collaboration suite at Bristol City Council, and the roll-out of OSS at Birmingham City Council.
For further information about the conference and the OSA go to:
Enjoy the benefits of CW+ membership, learn more and join.
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Gulf Air tinkers with Oracle suite and explores hybrid cloud models
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text:
We spent a lot of time researching different mystery shopping providers. There are a lot of them out there and there are many things to consider when trying to compare apples with apples.
What really stood out with Above Benchmark was the flexibility and attention to our specific needs. Jen Wells has remarkable insight and aptitude in all areas of the retail industry. Together we developed a mystery shopping program that was directly aligned with our training program and our unique pathway to a sale.
That was my perspective prior to our first survey being published. When the reporting results came out I was totally blown away. We now have a system in place that totally isolates any weaknesses in our sales process that we can address with pinpoint accuracy.
Above Benchmark have totally under promised, over delivered and exceeded our expectations. The amount of groundwork and personal attention they have given us, in my opinion totally outweighs the monthly fee that we pay for the service.


text:
Darnell Cruickshank
Oxford Property Group
Oxford Property Group
A long-time resident of New York, Darnell has worked in Real Estate since April 2012. He is a dedicated real estate professional who believes that trust and integrity Specializing in Luxury Condos and High end Rentals, with encyclopedic knowledge of the entire island of Manhattan. Prior to joining Real Estate Darnell has been employed in many different fields. Some of his Hobbies include reading, studying History, Art, and ancient civilizations. Feel free to contact Darnell anytime for unparalleled service.


text:
Mofos fetish VIDEOS (100)
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After putting on a little striptease in a cage, Aspen Ora takes the show inside, where she pops her cute booty up into the air, packs her tight pussy to the hilt with her boyfriend's dick, and takes a pounding that makes her cum over and over!
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94 %
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Renee Roulette just has to have the colorful clothes to match her new Miami lifestyle, but those cute outfits don't come cheap. This petite teen won't let anything stand between her and fashion, so she gets right down to it and pays with her pussy!
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Coming from the mean streets of Miami, Michel Martinez can sure talk tough, but can this extra-small Latina take on a massive dick? Monica is going to muster up all that tiny teen energy to throw her little pussy back on dude's huge cock!
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When this clumsy bro locked himself in the giant cage he keeps in the backyard, his GF Shay Evans started teasing him with her big fake tits. Shay only let him out when she knew he was desperate to bring her inside and pound her latina pussy!
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text:
realmagick.com The shrine of knowledge.
Original articles from our library related to the Bastard Games. See Table of Contents for further available material (downloadable resources) on Bastard Games.
- Lughnasadh
- Lughnasadh (pronounced Loo-nas-ah), August 1st, is the first harvest festival in the Celtic and Neo-Pagan Year. Like all Celtic Fire Festivals, it begins on the eve of the actual day. Although it later became known as Christian Lammas, it still survives in...
Holidays >> Lammas
- Tarot Cards Overview
- Tarot is made up of four suites of regular playing cards, each having 14 pieces of cards. What distinguishes a deck of tarot cards from conventional playing cards is a single card called the Fool.
Divination >> Tarot Cards
- The Tarot Queens and the Kama Sutra
- '"Being the source of virtue, woman is the best means of reaching heaven. Man's efforts to be virtuous are impossible outside of conjugal virtue... There is no doubt that women are a source of happiness."' Vatsyayana An ancient principle of Indian...
Tarot Cards >> The Minor Arcana
- King James Bible: Deuteronomy, Chapter 23
- Chapter 23 23:1 He that is wounded in the stones, or hath his privy member cut off, shall not enter into the congregation of the LORD. 23:2 A bastard shall not enter into the congregation of the LORD; even to his tenth generation shall he not enter into the...
Old Testament >> Deuteronomy
- Lavender: Solace and Majestic
- Lavender, the Herb of Air, My friend when I am in despair. I ask Earth's blessing to bestow, As I tend and watch you grow. Strong roots and dainty stems, Bring joy to life when pleasure dims. Wee green bud with purple top, All your uses never stop. From...
Herbalism >> Herbs dictionary L
- The Character of Magick
- I have a friend, her husband is morbidly obese through indulgent overeating. Whole roasts at night! She feels betrayed. My husband is unconscious in the hospital bed, as I sit here I feel incredibly alone and abandoned. I miss him, yet he is right there. A...
Paganism & Wicca >> Daily Life
Bastard Games is described in multiple online sources, as addition to our editors' articles, see section below for printable documents, Bastard Games books and related discussion.
Suggested News Resources
- Guillermo Del Toro: Games are 'only limited by the bastards with money'
- Del Toro made the comments as he and Metal Gear Solid game creator Hideo Kojima were interviewed by game broadcaster Geoff Keighley, president of Gameslice, at the DICE Summit game event in Las Vegas today. DICE is one of the biggest gatherings ...
- C's winning formula simple
- ("Look, you stupid bastard, you've got no arms left." . .
- The Many Lives of Elizabeth Marsh
- In that year Henry campaigned in France and took Tournai; when he handed Brandon the city keys, Italian observers deduced he was giving his prize to a bastard brother. To boost his status among Henry's commanders, he was .....
- 5 things we learned from new Game of Thrones season 6 red band trailer
- We see Red Witch Melisandre (Carice van Houten) standing over his corpse and Ser Davos Seaworth (Liam Cunningham) attending a burning pyre – the body presumed to be that of the Stark bastard. That said, a screen-grab reveals a Harington lookalike ...
- Martin Garrix Will, Once Again, Have a Much Cooler Miami Music Week Than You
- Because he's a likable bastard — like it or not — and very humble, Garrix is quick to praise his team and likes to deflect attention away from himself. Despite the occasional mountain adventure, he prefers to keep things low-key.
Great care has been taken to prepare the information on this page. Elements of the content come from factual and lexical knowledge databases, realmagick.com library and third-party sources. We appreciate your suggestions and comments on further improvements of the site.
Bastard Games Topics
Related searchespotchefstroom potchefstroom museum
irish art the irish impressionists
death and dying
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text:
Most Cited Clinical Immunology Articles
The most cited articles published since 2011, extracted from Scopus.
Clinical and immunological manifestations of patients with atypical severe combined immunodeficiencyKerstin Felgentreff | Ruy Perez-Becker | Carsten Speckmann | Klaus Schwarz | Krzysztof Kalwak | Gasper Markelj | Tadej Avcin | Waseem Qasim | E. G. Davies | Tim Niehues | Stephan Ehl
Volume 141, Issue 1, October 2011, Pages 73-82
Hypomorphic mutations in genes associated with severe combined immunodeficiency (SCID) or Omenn syndrome can also cause milder immunodeficiencies. We report 10 new patients with such "atypical" SCID and summarize 63 patients from the literature. The patient groups with T lowB low (n=28), T lowB + (n=16) and ADA (n=29) SCID variants had similar infection profiles but differed in the frequency of immune dysregulation, which was observed predominantly in patients with recombination defects. Most immunological parameters were remarkably similar in the three groups. Of note, 19/68 patients with "atypical" SCID had normal T cell counts, 48/68 had normal IgG and 23/46 had at least one normal specific antibody titer. Elevated IgE was a characteristic feature of ADA deficiency. This overview characterizes "atypical" SCID as a distinct disease with immune dysregulation in addition to infection susceptibility. Lymphopenia, reduced naïve T cells and elevated IgE are suggestive, but not consistent features of the disease. © 2011 Elsevier Inc.
Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseasesFranziska Di Pauli | Simone Mader | Kevin Rostasy | Kathrin Schanda | Barbara Bajer-Kornek | Rainer Ehling | Florian Deisenhammer | Markus Reindl | Thomas Berger
Volume 138, Issue 3, March 2011, Pages 247-254
Recent studies demonstrated the presence of autoantibodies to native myelin oligodendrocyte glycoprotein (MOG) in juvenile patients with acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). However, so far no longitudinal studies on anti-MOG antibodies have been performed. Therefore, we determined serum and CSF antibodies against native human MOG in 266 pediatric and adult subjects with ADEM, clinically isolated syndrome (CIS), MS, other neurological diseases (OND) and healthy controls (HC) and longitudinal samples of 25 patients with ADEM, CIS, MS and OND using an immunofluorescence assay. We detected serum high-titer MOG IgG in 15/34 (44%) patients with ADEM, but only rarely in CIS (3/38, 8%), MS (2/89, 2%), OND (1/58, 2%) and HC (0/47). Longitudinal analysis of serum anti-MOG IgG showed different temporal dynamics of serum antibody responses in ADEM, CIS and MS and indicated an association of a favorable clinical outcome in ADEM with a decrease in antibody titers over time. © 2010 Elsevier Inc.
Mannan-binding lectin deficiency - Good news, bad news, doesn't matter?Sabine Heitzeneder | Markus Seidel | Elisabeth Förster-Waldl | Andreas Heitger
Volume 143, Issue 1, April 2012, Pages 22-38
Mannan-binding lectin (MBL) deficiency has been classified as a commonly occurring immune disorder, affecting approximately 30% of the human population. MBL, being part of the innate immune system, supports the recognition of infectious pathogens by binding to carbohydrate moieties expressed on microorganisms and activates the lectin pathway of the complement system. MBL2 gene polymorphisms are associated with quantitative and qualitative MBL abnormalities in the serum. The clinical impact of MBL deficiency and its association to a wide variety of diseases has been extensively studied. The picture is puzzling as the studies suggest a detrimental or beneficial or no impact of low or high MBL serum levels on disease susceptibility. In this review we attempt to extract what is relevant from the literature and address controversial issues. We finally suggest that a comprehensive understanding of the role of MBL in human diseases requires considering its context-dependency. © 2011 Elsevier Inc.
IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction - A comparative study of human clinical-applicable DCMartine A. Boks | Judith R. Kager-Groenland | Michiel S P Haasjes | Jaap Jan Zwaginga | S. Marieke van Ham | Anja ten Brinke
Volume 142, Issue 3, March 2012, Pages 332-342
Tolerogenic dendritic cells (tDC) are a promising tool for specific cellular therapy to induce immunological tolerance in transplantation and autoimmunity. To date, most described tDC methods have not been converted into clinically applicable protocols and systematic comparison of required functional characteristics, i.e. migration and functional regulatory T cell (Treg) induction, is lacking. We compare clinical-grade tDC generated with vitamin D 3, IL-10, dexamethasone, TGFβ or rapamycin. For good migratory capacity and a stable phenotype, additional maturation of tDC was required. Maturation with a cocktail of TNFα, IL-1β and PGE 2 induced optimal migration. Importantly, all tDC showed a stable phenotype under pro-inflammatory conditions. Especially IL-10 DC showed most powerful tolerogenic characteristics with high IL-10 production and low T cell activation. Moreover, in a functional suppression assay only IL-10 DC induced Treg that strongly suppressed T cell reactivity. Thus, clinical-grade IL-10 DC show functional characteristics that make them best suited for tolerance-inducing therapies. © 2011 Elsevier Inc.
On the armament and appearances of human myeloid-derived suppressor cellsIsabel Poschke | Rolf Kiessling
Volume 144, Issue 3, September 2012, Pages 250-268
Myeloid-derived suppressor cells (MDSC) have frequently been observed in patients with cancer. This heterogeneous population of myeloid cells can exert potent suppression of lymphocyte function and thereby poses a significant hurdle to natural or therapeutically induced anti-tumor immunity. On the other hand, the natural function of MDSC is not yet well understood and their role in infection, inflammation and autoimmune disease is still puzzling.Understanding MDSC biology will provide the tools necessary for therapeutic targeting of this population, but also permit exploitation of their strong tolerogenic function in the treatment of inflammatory conditions and the prevention of graft rejection. © 2012 Elsevier Inc.
Immune mechanisms of new therapeutic strategies in MS - TeriflunomideMalte C. Claussen | Thomas Korn
Volume 142, Issue 1, January 2012, Pages 49-56
At present, a series of oral disease-modifying agents is being introduced for the treatment of multiple sclerosis. With the exception of laquinimod, the "new" oral compounds have already been approved for other indications such as organ transplantation (FTY720), psoriasis (dimethylfumarate), hairy cell leukemia (cladribine), and rheumatoid arthritis (leflunomide). Leflunomide is the prodrug of teriflunomide which is the latest compound that has successfully been tested in a large phase III clinical trial in relapsing MS. Due to its favorable safety profile and its efficacy in rheumatoid arthritis where the aberrant immune response is in various aspects similar to the autoimmune reaction in MS patients, teriflunomide is a promising treatment option for MS patients. Here, we review the most important cell biological and immunological modes of action of teriflunomide, report on the available data on its pharmacokinetics in humans, and summarize the recent clinical trials of teriflunomide in relapsing MS. © 2010 Elsevier Inc.
Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injuryS. R. Hofmann | A. Rösen-Wolff | G. C. Tsokos | C. M. Hedrich
Volume 143, Issue 2, May 2012, Pages 116-127
The IL-10 cytokine family has nine members, four of which are located in the IL10 cluster on chromosome 1q32. These cytokines are the immune regulatory cytokine IL-10 itself, and the IL-20 subfamily members IL-19, IL-20, and IL-24. IL-10 instructs innate and adaptive immune responses and limits pro-inflammatory responses in order to prevent tissue damage. The IL-20 subfamily members are involved in host defense mechanisms, particularly from epithelial cells and seem essential for tissue integrity. Dysregulation of IL-10 family cytokines results in inflammation and autoimmune disease. Here, we discuss cellular source, gene regulation, and receptor complexes of cytokines in the IL10 cluster and their contribution to autoimmune disease and tissue damage. © 2012 Elsevier Inc.
Immunopathogenesis of osteoarthritisAbdul Haseeb | Tariq M. Haqqi
Volume 146, Issue 3, March 2013, Pages 185-196
Even though osteoarthritis (OA) is mainly considered as a degradative condition of the articular cartilage, there is increasing body of data demonstrating the involvement of all branches of the immune system. Genetic, metabolic or mechanical factors cause an initial injury to the cartilage resulting in release of several cartilage specific auto-antigens, which trigger the activation of immune response. Immune cells including T cells, B cells and macrophages infiltrate the joint tissues, cytokines and chemokines are released from different kinds of cells present in the joint, complement system is activated, and cartilage degrading factors such as matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2) are released, resulting in further damage to the articular cartilage. There is considerable success in the treatment of rheumatoid arthritis using anti-cytokine therapies. In OA, however, these therapies did not show much effect, highlighting more complex nature of pathogenesis of OA. This needs the development of more novel approaches to treat OA, which may include therapies that act on multiple targets. Plant natural products have this kind of property and may be considered for future drug development efforts. Here we reviewed the studies implicating different components of the immune system in the pathogenesis of OA. © 2013 Elsevier Inc.
Characterization of Zaire ebolavirus glycoprotein-specific monoclonal antibodiesXiangguo Qiu | Judie B. Alimonti | P. Leno Melito | Lisa Fernando | Ute Ströher | Steven M. Jones
Volume 141, Issue 2, November 2011, Pages 218-227
Zaire ebolavirus (ZEBOV) can be transmitted by human-to-human contact and causes acute haemorrhagic fever with case fatality rates up to 90%. There are no effective therapeutic or prophylactic treatments available. The sole transmembrane glycoprotein (GP) is the key target for developing neutralizing antibodies. In this study, recombinant VSVδG/ZEBOVGP was used to generate monoclonal antibodies (MAbs) against the ZEBOV GP. A total of 8 MAbs were produced using traditional hybridoma cell fusion technology, and then characterized by ELISA using ZEBOV VLPs, Western blotting, an immunofluorescence assay, and immunoprecipitation. All 8 MAbs worked in IFA and IP, suggesting that they are all conformational MAbs, however six of them recognized linearized epitopes by WB. ELISA results demonstrated that one MAb bound to a secreted GP (sGP 1-295aa); three bind to a part of the mucin domain (333-458aa); three MAbs recognized epitopes on the C-terminal domain of GP1 (296-501aa); and one bound to full length GP (VLPs/GP1,2 δTm). Using a mouse model these MAbs were evaluated for their therapeutic capacity during a lethal infection. All 8 MAb improved survival rates by 33%-100% against a high dose lethal challenge with mouse-adapted ZEBOV. This work has important implications for further development of vaccines and immunotherapies for ZEBOV infection. © 2011.
Immunopathogenesis of multiple sclerosisManuel Comabella | Samia J. Khoury
Volume 142, Issue 1, January 2012, Pages 2-8
Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by autoimmune inflammation, demyelination, and axonal damage. MS etiology remains unknown, but disease phenotype is most likely the result of an interaction between complex genetic factors and environmental influences. The better understanding of the mechanisms involved in the immunopathogenesis of MS has led to the development of promising new therapeutic strategies for the disease. This review will discuss the key pathogenic steps implicated in the disease and the role of the main cellular populations that drive the immune responses in MS. © 2011 Elsevier Inc.
Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapyKazuki Yamasaki | Shigetoshi Horiguchi | Motoyoshi Kurosaki | Naoki Kunii | Kaoru Nagato | Hideki Hanaoka | Naomi Shimizu | Naoyuki Ueno | Seiji Yamamoto | Masaru Taniguchi | Shinichiro Motohashi | Toshinori Nakayama | Yoshitaka Okamoto
Volume 138, Issue 3, March 2011, Pages 255-265
Vα24 natural killer T (NKT) cells have potent anti-tumor activity. We performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using . ex vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses. The subjects were 10 patients with locally recurrent and operable HNSCC. One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated. Five cases achieved objective tumor regression. The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression. The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects. © 2010 Elsevier Inc.
Treatment of multiple sclerosis with Anti-CD20 antibodiesBarbara Barun | Amit Bar-Or
Volume 142, Issue 1, January 2012, Pages 31-37
The recently successful targeting of B cells in patients with multiple sclerosis (MS) using monoclonal antibodies (mAbs) targeting CD20 has established that it is no longer a question of whether B cells contribute, but how they contribute, to MS disease activity. Here, the focus will be to review results that have emerged over the last few years from clinical trials of different anti-CD20 mAbs in patients with MS. We will also consider the biological basis underlying the apparent therapeutic efficacy of B cell depletion in MS. To this end, we will draw on several instructive observations made in MS patients who were treated with the anti-CD20 mAb rituximab. While the initial application of rituximab to patients with MS was based on the concept that B cell depletion may translate into decreases in potentially pathogenic CNS-autoreactive antibodies, insights from these studies have underscored the importance of non-antibody mediated functions of B cells. © 2011 Elsevier Inc.
Fumaric acid and its esters: An emerging treatment for multiple sclerosis with antioxidative mechanism of actionR. Gold | R. A. Linker | M. Stangel
Volume 142, Issue 1, January 2012, Pages 44-48
Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+ and CD8+ T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethylfumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal experiments in the mouse model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis, revealed a clear preservation of myelin and axonal density in the plaque. Molecular studies showed that this is based on the antioxidative mechanism of action via induction of the transcription factor Nrf-2. A phase II clinical trial in relapsing-remitting multiple sclerosis (RRMS) patients with dimethylfumarate showed a significant reduction in the number of gadolinium enhancing lesions after 24. weeks. © 2011 Elsevier Inc.
Programmed death-1 pathway in cancer and autoimmunityAriel Pedoeem | Inbar Azoulay-Alfaguter | Marianne Strazza | Gregg J. Silverman | Adam Mor
Volume 153, Issue 1, January 2014, Pages 145-152
Programmed death-1 (PD-1) is a co-receptor that is expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system. A major functional role of the PD-1 signaling pathway is the inhibition of self-reactive T cells, which serve to protect against autoimmune diseases. Elimination of the PD-1 pathway can therefore result in the breakdown of immune tolerance that can ultimately lead to the development of pathogenic autoimmunity. Conversely, tumor cells can at times co-opt the PD-1 pathway to escape from immunosurveillance mechanisms. Therefore, blockade of the PD-1 pathway has become an attractive target in cancer therapy. Recent clinical trials have shown that anti-PD-1 agents have profound effects on solid tumor regression. Current approaches include six agents that are either PD-1 and PD-L1 targeted neutralizing antibodies or fusion proteins. More than forty clinical trials are underway to better define the role of PD-1 blockade in variety of tumor types. In this review we will highlight the basic biology of the PD-1 system and discuss its potential roles in both autoimmunity and cancer. We propose that future research on PD-1 may lead to the translation of fundamental regulatory pathways into the development of practical new approaches for the treatment of autoimmune diseases and cancer. © 2014 Elsevier Inc.
Disturbed Th1, Th2, Th17 and TSebastian Dolff | Marc Bijl | Minke G. Huitema | Pieter C. Limburg | Cees G M Kallenberg | Wayel H. Abdulahad
reg balance in patients with systemic lupus erythematosus
Volume 141, Issue 2, November 2011, Pages 197-204
Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by disturbed T-cell homeostasis. Dysbalance of T-helper-cell (Th) subsets (Th1/Th2/Th17) and regulatory T-cells (T regs) is suggested to contribute to the pathogenesis of SLE. Recent reports suggest functional deviation of T regs in terms of producing IL-17A, a process that may be aberrant in SLE. Therefore, we analyzed these T-cell subsets in SLE to test the hypothesis that aberrant T-cell subset skewing is present in SLE-patients. We investigated simultaneously the intracellular cytokines IFN-γ, IL-4 and IL-17A in CD4 +T-cells as well as in T regs. Skewing of T-cell subsets towards Th17 cells was observed in SLE-patients. Although the proportion of T regs was similar between SLE-patients and healthy controls, the ability of T regs to express IFN-γ and IL17A was impaired in SLE-patients. Even in quiescent SLE-patients T-cell homeostasis is aberrant in terms of skewing towards IL-17 producing T-cells. © 2011 Elsevier Inc.
Efficacy and safety of Hizentra® in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapyS. Jolles | E. Bernatowska | J. de Gracia | M. Borte | V. Cristea | H. H. Peter | B. H. Belohradsky | V. Wahn | J. Neufang-Hüber | O. Zenker | B. Grimbacher
Volume 141, Issue 1, October 2011, Pages 90-102
A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra®, a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra® at doses equivalent to their previous treatment. IgG levels achieved with Hizentra® were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra®-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27h. Hizentra® maintained or improved serum IgG levels without dose increases and effectively protected patients against infections. © 2011 Elsevier Inc.
Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficienciesMelvin Berger | Mikhail Rojavin | Peter Kiessling | Othmar Zenker
Volume 139, Issue 2, May 2011, Pages 133-141
Bioavailability and pharmacokinetics of subcutaneous IgG (SCIG) and intravenous IgG (IVIG) differ. It is not clear if and/or how the dose should be adjusted when switching from IVIG to SCIG. Area under the curve (AUC) of serum IgG versus time and trough level ratios (TLRs) on SCIG/IVIG were evaluated as guides for adjusting the dose. The mean dose adjustments required for non-inferior AUCs with 2 different SCIG preparations were 137% (± 12%) and 153% (± 16%). However, there were wide variations between adjustments required by different subjects, and in the resulting TLRs. In contrast, combined data from multiple studies allow estimation of the ratio of IgG levels with different dose adjustments, and of the steady state serum levels with different SCIG doses. When switching a patient from IVIG to SCIG, individualizing the dosage based on measured serum IgG levels and the clinical response is preferable to using mean pharmacokinetic parameters. © 2011 Elsevier Inc.
Galectin-1 research in T cell immunity: Past, present and futureFiliberto Cedeno-Laurent | Charles J. Dimitroff
Volume 142, Issue 2, February 2012, Pages 107-116
Galectin-1 (Gal-1) is one of 15 evolutionarily conserved ß-galactoside-binding proteins that display biologically-diverse activities in pathogenesis of inflammation and cancer. Gal-1 is variably expressed on immune cells and endothelial cells, though is commonly found and secreted at high levels in cancer cells. It induces apoptosis in effector T cells through homodimeric binding of N-acetyllactosamines on membrane glycoproteins (Gal-1 ligands). There is also compelling evidence in models of cancer and autoimmunity that recombinant Gal-1 (rGal-1) can potentiate immunoregulatory function of T cells. Here, we review Gal-1's structural and functional features, while analyzing potential drawbacks and technical difficulties inherent to rGal-1's nature. We also describe new Gal-1 preparations that exhibit dimeric stability and functional activity on T cells, providing renewed excitement for studying Gal-1 efficacy and/or use as anti-inflammatory therapeutics. We lastly summarize strategies targeting the Gal-1-Gal-1 ligand axis to circumvent Gal-1-driven immune escape in cancer and boost anti-tumor immunity. © 2011 Elsevier Inc.
Anti-interferon alpha treatment in SLEKyriakos A. Kirou | Elena Gkrouzman
Volume 148, Issue 3, September 2013, Pages 303-312
Several studies in the last decade have highlighted the role of the type I interferon (IFN-I) pathway, and particularly interferon alpha (IFNα) in SLE pathogenesis. As a result, a multitude of potential treatments targeting IFNα have emerged in the last few years, a few of which have already completed phase II clinical trials. Some of the treatment strategies have focused on blocking IFNα or its receptor and others the plasmacytoid dendritic cell (pDC), which is the principal IFNα producing cell. In this review, we will discuss the evidence supporting a pathogenic role of IFNα and pDC in SLE, provide an update on the current status of these therapeutic strategies, and discuss the potential advantages and disadvantages of each therapeutic approach. © 2013 Elsevier Inc.
A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitorKonrad Bork | Karin Wulff | Peter Meinke | Nicola Wagner | Jochen Hardt | Günther Witzke
Volume 141, Issue 1, October 2011, Pages 31-35
In hereditary angioedema with normal C1-inhibitor two different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported in some families. In this study a novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018. +. 24del72*), was identified in a family of Turkish origin, in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father. This deletion caused a loss of 48. bp of exon 9 (coding amino acids 324* to 340*) in addition to 24. bp of intron 9, including the authentic donor splice site of exon 9. The large deletion of 72. bp was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg* reported previously. Our findings confirm the association between F12 gene mutations modifying the proline-rich region of the FXII protein and hereditary angioedema with normal C1-inhibitor. © 2011 Elsevier Inc.
Dynamic role of epithelium-derived cytokines in asthmaKathleen R. Bartemes | Hirohito Kita
Volume 143, Issue 3, June 2012, Pages 222-235
Asthma is an inflammatory disorder of the airways, characterized by infiltration of mast cells, eosinophils, and Th2-type CD4+ T cells in the airway wall. Airway epithelium constitutes the first line of interaction with our atmospheric environment. The protective barrier function of the airway epithelium is likely impaired in asthma. Furthermore, recent studies suggest critical immunogenic and immunomodulatory functions of airway epithelium. In particular, a triad of cytokines, including IL-25, IL-33 and TSLP, is produced and released by airway epithelial cells in response to various environmental and microbial stimuli or by cellular damage. These cytokines induce and promote Th2-type airway inflammation and cause remodeling and pathological changes in the airway walls, suggesting their pivotal roles in the pathophysiology of asthma. Thus, the airway epithelium can no longer be regarded as a mere structural barrier, but must be considered an active player in the pathogenesis of asthma and other allergic disorders. © 2012 Elsevier Inc.
Altered microRNA expression in B lymphocytes in multiple sclerosis. Towards a better understanding of treatment effects.Claudia Sievers | Maria Meira | Francine Hoffmann | Paulo Fontoura | Ludwig Kappos | Raija L P Lindberg
Volume 144, Issue 1, July 2012, Pages 70-79
MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. We compared the expression of 1059 miRNAs in B lymphocytes from untreated and natalizumab treated relapsing-remitting multiple sclerosis (RRMS) patients and healthy volunteers (HV). Forty nine miRNAs were down-regulated in untreated MS patients compared with HV. A distinct pattern of 10 differentially expressed miRNAs was found in natalizumab treated patients compared with untreated patients. Two clusters, i.e. miR-106b-25 and miR-17-92, were particularly deregulated. MiRNA-mRNA interaction analysis revealed B cell receptor, phosphatidyl-inositol-3-kinase (PI3K) and phosphatase and tensin homology (PTEN) signaling being the key affected pathways. We discovered deregulated viral miRNAs in untreated patients as compared with HV and natalizumab treated patients, a novel finding that may be related to latency and activation of viruses in MS. Our findings provide first insights into miRNA dependent regulation of B cell function in MS and the impact of a therapy not primarily targeting B cells on this regulation. © 2012 Elsevier Inc.
Monogenic autoinflammatory diseases: Concept and clinical manifestationsAdriana Almeida de Jesus | Raphaela Goldbach-Mansky
Volume 147, Issue 3, January 2013, Pages 155-174
The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency. Published by Elsevier Inc.
Therapy of type 1 diabetes with CD4+CD25highCD127-regulatory T cells prolongs survival of pancreatic islets - Results of one year follow-upNatalia Marek-Trzonkowska | Małgorzata Myśliwiec | Anita Dobyszuk | Marcelina Grabowska | Ilona Derkowska | Jolanta Juścińska | Radosław Owczuk | Agnieszka Szadkowska | Piotr Witkowski | Wojciech Młynarski | Przemysława Jarosz-Chobot | Artur Bossowski | Janusz Siebert | Piotr Trzonkowski
Volume 153, Issue 1, January 2014, Pages 23-30
It is hypothesized that CD4+CD25+FoxP3+ regulatory T cells (Tregs) can prevent destruction of pancreatic islets protecting from type 1 diabetes (DM1).Here we present results of one year follow-up of 12 DM1 children treated with autologous expanded ex vivo Tregs. Patients received either a single or double Tregs infusion up to the total dose of 30×106/kg. No severe adverse effects were observed. The treatment did not impair post-immunization antibody responses. Tregs infusion was followed by increase in Tregs number in peripheral blood. Most of the patients responded to the therapy with increase in C-peptide levels (8/12 and 4/6 after the first and the second dose, respectively). Tregs administration resulted also in lower requirement for exogenous insulin (8/12 treated patients versus 2/10 untreated controls in remission) with two children completely insulin independent at one year. Repetitive administration of Tregs is safe and can prolong survival of β-cells in DM1 (registration: ISRCTN06128462). © 2014 Elsevier Inc.
Clinical experience with α-galactosylceramide (KRN7000) in patients with advanced cancer and chronic hepatitis B/C infectionFamke L. Schneiders | Rik J. Scheper | B. Mary E von Blomberg | Andrea M. Woltman | Harry L A Janssen | Alfons J M van den Eertwegh | Henk M W Verheul | Tanja D. de Gruijl | Hans J. van der Vliet
Volume 140, Issue 2, August 2011, Pages 130-141
For over a century, research has sought ways to boost the immune system in order to eradicate tumors and viruses that exist after escaping immunosurveillance. For the treatment of cancer and hepatitis immunotherapeutic strategies have overall had limited clinical success. An urgent need exists therefore to introduce more effective therapeutic approaches. Invariant (i)NKT cells constitute a conserved T lymphocyte lineage with dominant immunoregulatory, antitumor and antiviral effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide in the context of CD1d resulting in their activation. Activated iNKT can promote the development of a long-lasting Th1 biased proinflammatory immune response as demonstrated in multiple tumor-metastasis and viral infection models. Here, we will provide a brief overview of the preclinical data of α-galactosylceramide that formed the basis for subsequent clinical trials in patients with advanced cancer and chronic hepatitis B/C, and elaborate on our own clinical experience with α-galactosylceramide in these patient groups. © 2010 Elsevier Inc.