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US Military Outpaces Its NATO Peers
Biggest threat to alliance may be gap between armed forces of Europe and US.
It was to have been a showpiece of cooperation and self-reliance: a French-designed spy satellite that would give the European allies their own eye-in-the-sky, reducing their need to pay for American intelligence.
But Germany's fiscal woes now appear to have grounded the nascent Franco-German project, Helios II, and with it one of the few European efforts to narrow the United States' massive lead in military might.
The US lead - in everything from basics like logistics and transport to cutting-edge sensor and information warfare technologies - is growing ever wider. As it does, so are concerns that American forces could leap so far ahead of their 15 NATO partners that they could have difficulties communicating, planning, and even fighting together in the coming decades.
Left unresolved, the capability gap could produce an alliance that is hamstrung by fiscal and strategic differences and even more dependent on US forces.
"There is a risk over time of a three-tiered alliance, with the US able to do everything, a few allies doing a range of these things, and some allies who are not going to be technologically in the same league," warns Robert Hunter, the US ambassador to NATO. "This is going to be one of the most important issues in preventing the hollowing out of the alliance."
Such concerns are being aggravated by NATO's decision in July to open its doors to the former Communist Eastern European states of Hungary, Poland, and the Czech Republic. Even as talks on their admission gather speed, doubts persist over whether they can rebuild armies equipped with outdated Soviet technologies into assets that can contribute to NATO's strength.
A noticeable gap
"There is a very big gap between [Eastern European] militaries and the US military. But at the same time, there is a very big gap between their militaries and the European allies in NATO," says a French military officer.
Expansion will also impose new burdens on NATO's current European members. Armies structured for almost 50 years to defend their homelands against a Soviet invasion will have to acquire the abilities to deploy rapidly to the alliance's easternmost borders and beyond.


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How a Sandwich Got 'Anchorman 2′ In Trouble With the MPAA (and Which US President Almost Had a Cameo)
Features By Jack Giroux on December 20, 2013 | Comments (1)As their world keeps evolving, Ron Burgundy (Will Ferrell) and his news team remain the same guys we met 10 years ago in Anchorman: The Legend of Ron Burgundy. They're stuck in their adolescent and ignorant mindsets, which Anchorman 2: The Legend Continues challenges. For a man like Burgundy, real drama is having to accept a black woman as his boss. Heavy stuff. The old Channel 4 news team may not have changed, but their sequel has. Co-writer/director Adam McKay and his characters were barely bound by structural rules, giving Anchorman 2 some wild directions to go in. To no surprise, McKay took full advantage of those opportunities, and 60% of the time it worked every time. I spoke with McKay, who explained his improv method for the film in depth, described his minor battles with the MPAA and revealed the cameos he wanted but couldn't get.
Could Ron Burgundy Oversaturation Jeopardize the Legend?
Features By Samantha Wilson on November 11, 2013 | Comments (4)Just in case you haven't heard, Anchorman 2: The Legend Continues is storming into theaters this December and bringing the Channel 4 News Team back into our lives. With the announcement of the sequel to 2004's beloved Anchorman came a slow but steady progession of trailers and fun marketing tactics that only amplified the excitement surrounding another round of Ron Burgundy. First came Will Ferrell visiting the set of Conan in character as Ron Burgundy in March to play a little jazz flute and announce the sequel. Clearly, it was delightful and people flipped their lids when they spotted that finely-crafted red suit hit the stage. In the months since March, the buzz grew with several trailers and the usual release of stills and one-sheets. But then came the constant in-character promotions and endorsements. Have we reached peak Burgundy saturation?
Ron Burgundy Releasing Leather-Bound Book to Keep in Your Apartment Smelling of Rich Mahogany
Movie News By Samantha Wilson on August 14, 2013 | Be the First To CommentOkay, it's probably paperback, but if the marketing team behind Anchorman: The Legend Continues is smart, they'll make this vision happen. As part of the viral (written?) campaign for the long-awaited sequel to 2004's Anchorman, Random House's Crown Archetype will be teaming up with the legendary broadcaster from the Action 4 News Team to release a memoir entitled Let Me Off at the Top!: My Classy Life and Other Musings. The memoir promises never-before told details about Ron Burgundy's (Will Ferrell) personal life, childhood, and meteoric rise to fame as one of the most successful and talented anchormen to ever sit behind a desk and bring you the damn news. And since it's Burgundy doing the writing, it's pretty much guaranteed that he won't skip any of the juicy details when talking about the ladies, either. It's a bit of a strange move to release a book to promote a films; it's not something you see much these days outside of kids' movies, but it's almost weird enough to work. I'm at least a little curious to see what Burgundy's childhood was like, or how he became a jazz flute master.
The News Team Assembles in These 'Anchorman: The Legend Continues' Stills
Movie News By Samantha Wilson on August 13, 2013 | Be the First To CommentRon Burgundy has clearly blown into his mighty conch and summoned his trusty news team to assemble in the 1980's, if these stills from Anchorman: The Legend Continues are to be believed. Will Ferrell is back as Burgundy, and it's unclear whether he and Veronica Corningstone (Christina Applegate) will ever be married on top of that mountain with garlands of fresh herbs, but they certainly look happy traipsing down the streets of New York City together. When you survive a bear attack together, you can survive anything as a couple. The whole team, including Brick (Steve Carell), Brian (Paul Rudd), and Champ (David Koechner) have left their local station in San Diego for a revolutionary 24-hour news channel in the Big Apple called…GNN. This is the 80's, so the overwhelming wall of news coverage that we're used to isn't a thing yet. And these are the brave men (and woman) who are being trusted to bring it to the world. From the second image, it's clear that Burgundy is still their faithful leader. Also, take a moment to just soak in their early 80's fashion. Good to know that Champ's cowboy hat survived the 70's. Take a look at the second still after the break.
'Anchorman 2′ Trailer: Ron Burgundy Solves Race Relations
Movie News By Scott Beggs on June 19, 2013 | Comments (1)The world is about to meet Ron Burgundy. Again. Anchorman 2 hits theaters this Christmas, and even though there's a second Anchorman movie already exists, this one still gets a "2" in its name. This time, Ron, Brick, Champ and Brian are re-teaming to polyester their way through the 1980s with the prospect of a 24-hour news channel dangling overhead. They've teased with images and one-liners and appearances on late night talk shows, but now the first trailer reveals that — just as he evolved for a world where women were empowered — Ron is learning a lot about race relations as his legend continues:
Brick Tamland Offers Child Hugging Advice in Latest 'Anchorman 2′ Teaser
Movie News By Christopher Campbell on May 18, 2013 | Comments (1)We've got another half year before our eyes, ears and funny bones get ahold of Anchorman: The Legend Continues. The highly anticipated sequel is not even finished filming — though it is close to wrapping up, with shooting moved from Atlanta to New York City this week. To further whet our appetites, and probably to give official supplement to all the set photos of cameo appearances being regularly leaked, Paramount has unveiled a new trailer for the movie. You still won't find any footage from The Legend Continues, however. Like the teasers we got a whole year ago, this is a simple promo featuring our four favorite newsmen saying "something fun about the movie." Well, except for Brick, of course, who doesn't understand what to do. Again. He gives us some advice on how to avoid being mistaken for a pedophile and wishes us a belated happy Easter. The holiday greeting is kind of fitting, though, we'll give him that. Narrator "Bill Lawson" introduces the latest teaser talking about returned figures such as Jesus and Jay-Z. Easter pertains to the former, obviously. See, Brick isn't dumb after all. But Ron Burgandy sure is mean. He calls us fat face. And he thinks we're going to come see his movie after such an insult? Okay, we will. We can't wait to hear him call us names and for Champ and Brian to intoxicate us with their alcohol breath and snake venom cologne, respectively.
Casting Couch: Kristen Wiig May Bone Brick in the 'Anchorman' Sequel, Casey Affleck is Behind the 'Boston Strangler,' and More
Casting Couch By Nathan Adams on December 6, 2012 | Be the First To CommentWhat is Casting Couch? It's the casting roundup that has news about Timothy Olyphant putting on cowboy boots again. Read on! Is Kristen Wiig going to be joining the cast of Anchorman: The Legend Continues? Maybe. The Wrap has a report that she's being looked at to play the love interest (presumably replacing lamp) of Steve Carell's dimwitted Brick Tamland in Paramount's upcoming sequel. Of course, this one is far from starting filming (the script isn't even done yet), and Kristen Wiig is being looked at for essentially every comedy that calls for a female part right now, so it's hard to say if everyone's schedules are going to synch up or not when all is said and done. Wiig getting thrown into the mix of the Anchorman crew does sound pretty dang promising though, doesn't it? We'll be watching this one for new developments very closely.
'Anchorman 2′ Teaser Poster Has a Foot Fetish
Movie News By Scott Beggs on May 16, 2012 | Comments (1)The teaser trailer for Anchorman 2 is in front of The Dictator, which means it should be swimming its way onto the internet any second now. Wait for it. Wait. For it. But while you're waiting, scope out this new poster for the forthcoming film which seems to have taken forever to greenlight and yet no time at all to film. It's nowhere near being done, but doesn't it feel that way? With Will Ferrell announcing the project on Conan, a trailer that's already ready to roll and now one sheet work, it almost seems like we should be seeing Ron Burgundy in theaters next week or something. Nevertheless, by great Odin's raven, here's the poster:
Neil Miller
Scott Beggs
Rob Hunter
Kate Erbland
Christopher Campbell

subset: commoncrawl


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What a weird week this is. There is something to complain about around every corner. I'm having a hell of a week myself but didn't want to steal SEOMoz.org's Rand Fishkin's Seven Short, Out-Of-Character Rants thunder, or add my own to his, because every other word out of my mouth is not in the dictionary.
I was so determined to not use the word "rant" or "complain" or "bitch" in my post title, that I grabbed my trusty Thesaurus to find a better word, only to discover that "bitch" is a word for "complain". Does that make it acceptable for my blog?
If I used it, would someone object? Heck yes.
So. Here is my list and please don't laugh.
1. It's almost springtime and once again, we got snow in March. We ran out of usable wood for the woodstove in my office two weeks ago. The previous owner never installed heat on this floor, so there's a beautiful wood stove that I use, and it creates a real cozy environment, when we have wood. Eric has been chopping some of the gihungus pieces into smaller ones for me, but we ran out of that on Sunday. Now we buy bags of wood at ridiculous prices from the local WaWa (convenience store) so I don't freeze to death. (Yes. We'll buy a truckload of wood for next winter.)
2. I can work upstairs with my laptop, where its warmer, but I can't test sites from there. I can, technically, but I have to dial into my test computer from upstairs to downstairs and it slows things down. And, when I'm out of the office, EVERYBODY thinks Mom is open for business.
3. Registerfly. See Rearranging Deck Chairs on the SS Registerfly. Everyone who has domains with Registerfly needs to know that they have literally frozen everything, so that nothing can be transferred out. I was only able to move 4 of mine that were with Registerfly, to Enom, where the rest of mine are located. I have many more at Registerfly that I am denied access to, other than possibly renewals. And why would I want to do that after the way they have handled business?
4. There is a lesson to be learned about putting up polls and surveys. They may be just linkbait nowadays and with the glory days of social media in full swing, credibility and polls just went out the window. First, Andy Beal's MarketingPilgrim hosted the Favorite SEO Godmother poll. It didn't take long for fans of certain women to start campaigns to get more votes. But, when Jeremy Shoemaker put in a word or two on behalf of Jennifer Slegg, it was all over after that. (Note: It looks like a lot of the comments are missing from that blog post, so you can no longer see the drama.)
Now, Lee Odden accidently neglected to add Cre8asiteforums to his favorite forums poll. That was big mistake. Never make loyal forum goers angry, as evidenced in Reader Poll: Best Forums for Search Marketing Tips. Some folks are now at Lee's poll protesting the proceedings. I feel badly for Lee, as he didn't intend to forget naming any particular forums. However, when putting up polls, etc., omissions do occur and it can be nasty!
Not Grumpy Stuff
I'd like to send kudos to Li Evans on her Women of Internet Marketing series. She's put a great deal of effort into it and it's become a regular every Wednesday read now.
Speaking of women, today is International Womens Day. "Annually on 8 March, thousands of events are held throughout the world to inspire women and celebrate their achievements." Thanks to Jim Hedger for his writeup on
International Women's Day – Women in Search Marketing
I will be reporting on sessions for SearchEngineRoundtable again, for Barry Schwartz (aka "Rustybrick"), Wednesday through Friday during the SES New York in April. I will be joined by a great team of people. It's hard work but also very fun. I'll be reporting on the usability sessions, of course, and others.
The new Social Media and Tagging forum at Cre8asiteforums has been a blast. Moderated by Chris Winfield (aka "skore") and Liana Evans (aka "storyspinner"), the conversations are all over the place and always educational. I wanted to open my mind more to Social Media and this new forum has been just the place to do that.
Speaking of Chris Winfield, he Dugg my post on why Marketing "hates" usability and the experience, so far, has been a lot more tolerable. Not only that, this time its one of my posts that gets talked about (ranted, bitched, complained, picked on, attacked) this time. I laughed my head off at the comment where usability has nothing to do with SEO because SEO is just about search engines.
Who in the hell uses search engines? Little green people from Mars?
The above belongs in the Grumpy section, doesn't it.


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Immune cells
NUS researchers make breakthrough discovery that could lead to future treatment for multiple sclerosis(24/11/14)
The latest findings may provide an avenue for therapeutic intervention of multiple sclerosis. A multi-disciplinary research team from the National University of Singapore (NUS) has made a breakthrough discovery of a new type of immune cells that may help in the development of a future treatment for multiple sclerosis (MS).
Led by Professor Xin-Yuan Fu, Senior Principal Investigator from CSI Singapore and Professor at the Department of Biochemistry at the NUS Yong Loo Lin School of Medicine, and Dr Wanqiang Sheng, post-doctoral fellow at CSI Singapore, the team found that a new type of immune T helper cells named TH-GM cells play a crucial role in the immune system and pathogenesis of neuronal inflammation. The findings shed light on a possible new avenue for therapeutic intervention, which can be used independently or in conjunction with other treatment options to improve outcomes in the treatment of MS.
Working with Dr Yong-Liang Zhang from the Department of Microbiology at the NUS Yong Loo Lin School of Medicine, Prof Fu and his team showed that STAT5, a member of the STAT family of proteins, programs TH-GM and initiates the immune response to an auto-antigen in responding to a signal from an interleukin, IL-7, causing neuro-inflammation, pathogenesis and damage in the central nervous system. Blocking IL-7 or STAT5 would provide a significant therapeutic benefit for this disease. The study was first published online on 21 November in the journal Cell Research by Nature Publishing Group.
MS is the most prevalent autoimmune disease of the central nervous system, affecting about 2.5 million people globally, with cases showing a higher prevalence in Northern Europe. Despite many years of research, the causes of MS are largely unclear and the disease remains incurable.
This study offers an important insight into the mechanisms behind MS. Dr Richard Flavell, Chair of the Department of Immunology at Yale University, USA, and a world leader in the immunology field, noted that the results from the study may now provide a mechanistic link between IL-7/STAT5-mediated signalling and T helper cell-mediated pathogenicity.
The STAT family of proteins and their signalling pathway (called JAK-STAT) were originally discovered by Prof Fu and his colleagues in 1992. Disturbance of this pathway was shown to be a major cause for many kinds of inflammatory diseases. Novel medicines interfering with JAK-STAT have since been approved in the United States, Europe, and Singapore for the treatment of numerous diseases, and annual sales of medicines involving JAK-STAT are expected to exceed US$1.6 billion in 2016. The newly discovered IL-7-STAT5 by Prof Fu and his team in neuro-inflammation significantly expands this line of medical research, development and therapeutic intervention in a number of major diseases.
Moving forward, Prof Fu and his team are researching the physiological function of TH-GM to further the development of therapy for various human autoimmune diseases.
Source: National University of Singapore (24/11/14)
Study unexpectedly blocks multiple sclerosis relapses in mice(12/11/14)
In multiple sclerosis, the immune system goes rogue, improperly attacking the body's own central nervous system. Mobility problems and cognitive impairments may arise as the nerve cells become damaged.
In a new study, researchers from the University of Pennsylvania and co-investigators have identified a key protein that is able to reduce the severity of a disease equivalent to MS in mice. This molecule, Del-1, is the same regulatory protein that has been found to prevent inflammation and bone loss in a mouse model of gum disease.
"We see that two completely different disease entities share a common pathogenic mechanism," said George Hajishengallis, a professor of microbiology in Penn's School of Dental Medicine and an author on the study. "And in this case that means that they can even share therapeutic targets, namely Del-1."
Because Del-1 has been found to be associated with susceptibility to not only multiple sclerosis, but also Alzheimer's, it's possible that a properly functioning version of this protein might help guard again that disease's effects as well.
Penn contributors to the study included Hajishengallis, Penn Dental Medicine postdoctoral researcher Kavita Hosur and Khalil Bdeir, a research associate professor at Penn's Perelman School of Medicine. They collaborated with senior author Triantafyllos Chavakis of Germany's Technical University Dresden and researchers from South Korea's University of Ulsan College of Medicine and other institutions. The work appears online in the journal Molecular Psychiatry.
In earlier studies, Hajishengallis, Chavakis and colleagues found that Del-1 acts as a gatekeeper that thwarts the movement and accumulation of immune cells like neutrophils, reducing inflammation. While neutrophils are needed to effectively respond to infection or injury, when too many of them accumulate in a tissue, the resulting inflammation can itself be damaging. Hajishengallis has found that gum tissue affected by periodontitis, a severe form of gum disease associated with inflammation and bone loss— had lower levels of Del-1 than healthy tissue.
While researching Del-1 in other tissues, such as gums and lungs, Hajishengallis and Chavakis found that Del-1 was also highly expressed in the brain. In addition, genome-wide screens indicate that the Del-1 gene may contribute to multiple sclerosis risk. For these reasons, the scientists hypothesized that Del-1 might prevent inflammation in the central nervous system just as it does in the gum tissue.
To test their theory, the researchers examined Del-1 expression in brain tissue from people who had died from MS. In MS patients with chronic active MS lesions, Del-1 was reduced compared to both healthy brain tissue and brain tissue from MS patients who were in remission at the time of their death. Similarly, Del-1 expression was reduced in the spinal cords of mice with the rodent equivalent of MS, experimental autoimmune encephalomyelitis (EAE).
Having confirmed this association between reduced Del-1 and MS and EAE, the scientists wanted to see if the reduction itself played a causal role in the disease.
Hajishengallis's and Chavakis's labs had previously utilized mice that lack Del-1 alone or Del-1 together with other molecules of the immune system. The researchers found that mutant mice lacking Del-1 had more severe attacks of the EAE than normal mice, with more damage to myelin, the fatty sheath that coats neurons and helps in the transmission of signals along the cell. Loss of this substance is the hallmark of MS and other neurodegenerative diseases.
Mice without Del-1 that had been induced to get EAE also had significantly higher numbers of inflammatory cells in their spinal cords at the disease's peak, a fact that further experiments revealed was due to increased levels of the signaling molecule IL-17.
Mice that were induced to get EAE that lacked both Del-1 and the receptor for IL-17 had a much milder form of the disease compared to mice that lacked only Del-1. These doubly depleted mice also had fewer neutrophils and inflammation in their spinal cords.
With a greater understanding of how Del-1 acts in EAE, the researchers were curious whether simply replacing Del-1 might act as a therapy for the disease. They waited until mice had had an EAE attack, akin to a flare-up of MS in human patients, and then administered Del-1. They were pleased to find that these mice did not experience further episodes of the disease.
"This treatment prevented further disease relapse," Chavakis said. "Thus, administration of soluble Del-1 may provide the platform for developing novel therapeutic approaches for neuroinflammatory and demyelinating diseases, especially multiple sclerosis."
The team is pursuing further work on Del-1 to see if they can identify a subunit of the protein that could have the same therapeutic effect.
"It's amazing that our work in periodontitis have found application in a central nervous system disease," Hajishengallis said. "This shows that periodontitis can be a paradigm for other medically important inflammatory diseases."
Source: Medical Xpress © Medical Xpress 2011-2014,Science X network (12/11/14)
Autoimmune disease progression appears to be reversed by naturally occurring molecule(08/10/14)
Type 1 diabetes, ulcerative colitis, and multiple sclerosis are among the more well-known autoimmune diseases. But according to the AARDA, there are more than 150 rare autoimmune diseases, which affect around 50 million Americans. Even with this large number, scientists are still in the dark regarding interventions that can help cure these diseases. But this might change with the discovery of a molecule called NAD+ that has the potential to reverse autoimmunity.
What is autoimmunity?
When an intruding pathogen, such as a virus or bacterium, enters our bodies, our innate immune system gets activated, immediately sending out its soldiers (antibodies and immune cells) to identify and eliminate the pathogen, thus protecting us. But sometimes something goes wrong with this innate immunity and it starts regarding the body's own tissues as foreign and repeatedly sends out soldier cells to attack them.
Autoimmune diseases can affect any part of the body, including the heart, brain, nerves, muscles, joints, lungs, kidneys, etc. There is still no established cause for autoimmunity, but genetic factors are considered to play a major role.
This new research conducted by Brigham and Women's Hospital (BWH) has identified NAD+ (Nicotinamide adenine dinucleotide), a naturally occurring molecule in living cells, plants, and food that has the potential to turn "destructive" cells that attack healthy tissues into "protective" cells. The molecule has also been found to reverse disease progression by restoring tissue damaged by the autoimmunity process.
"Our study is the first to show that NAD+ can tune the immune response and restore tissue integrity by activating stem cells," said Abdallah ElKhal, senior author, in a statement. "These findings are very novel and may serve for the development of novel therapeutics." The study is published online Oct. 7, in Nature Communications.
NAD+ plays an essential role in several metabolic processes. To test the action of NAD+ in pre-clinical trials, the scientists used experimental autoimmune encephalomyelitis, a pre-clinical model for human multiple sclerosis. They found that NAD+ could regulate the differentiation of immune cells called CD4+ T cells that have an established role in many aspects of autoimmune inflammation. Mice having NAD+ were administered with CD4+ T cells. They showed a significant delayed onset of disease, as well as a less severe form, therefore demonstrating the molecule's protective properties.
"This is a universal molecule that can potentially treat not only autoimmune diseases, but other acute or chronic conditions such as allergy, chronic obstructive pulmonary disease, sepsis, and immunodeficiency," said coauthor Stefan G. Tullius.
The scientists also successfully demonstrated the tissue-restoring capability of NAD+. This, they say, can benefit patients with advanced tissue damage caused by autoimmune diseases. The scientists are now exploring the other medical benefits of NAD+.
"Since this is a natural molecule found in all living cells, including our body, we hope that it will be well-tolerated by patients," said ElKhal. "Thus, we hope that its potential as a powerful therapeutic agent for the treatment of autoimmune diseases will facilitate its use in future clinical trials."
Source: Medical Daily © 2014 IBT Media Inc (08/10/14)
To boost or supress autoimmunity, that is the question(11/09/14)
Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: Boosting autoimmunity to fight-off chronic neuroinflammation.
Schwartz M, Baruch K.
Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS).
As neuroinflammatory processes within the CNS parenchyma are also common to other CNS pathologies, regardless of their etiology, including neurodegenerative disorders such as Alzheimer's disease (AD) and Amyotrophic lateral sclerosis (ALS), these pathologies have often been compared to MS, a disease that benefits from immunosuppressive therapy.
Yet, over the last decade, it became clear that autoimmunity has a bright side, and that it plays a pivotal role in CNS repair following damage. Specifically, autoimmune T cells were found to facilitate CNS healing processes, such as in the case of sterile mechanical injuries to the brain or the spinal cord, mental stress, or biochemical insults. Even more intriguingly, autoimmune T cells were found to be involved in supporting fundamental processes of brain functional integrity, such as in the maintenance of life-long brain plasticity, including spatial learning and memory, and neurogenesis.
Importantly, autoimmune T cells are part of a cellular network which, to operate efficiently and safely, requires tight regulation by other immune cell populations, such as regulatory T cells, which are indispensable for maintenance of immunological self-tolerance and homeostasis.
Here, we suggest that dysregulation of the balance between peripheral immune suppression, on one hand, and protective autoimmunity, on the other, is an underlying mechanism in the emergence and progression of the neuroinflammatory response associated with chronic neurodegenerative diseases and brain aging.
Mitigating chronic neuroinflammation under these conditions necessitates activation, rather than suppression, of the peripheral immune response directed against self.
Accordingly, we propose that fighting off acute and chronic neurodegenerative conditions requires breaking peripheral immune tolerance to CNS self-antigens, in order to boost protective autoimmunity. Nevertheless, the optimal approach to fine tune such immune response must be individually explored for each condition.
Source: J Autoimmun. 2014 Sep 5. pii: S0896-8411(14)00127-9. doi: 10.1016/j.jaut.2014.08.002 © 2014 Elsevier Ltd & Pubmed PMID: 25199710 (11/09/14)
Breakthrough hope for MS treatment(03/09/14)
Scientists say they have discovered how to "switch off" autoimmune diseases such as multiple sclerosis.
Researchers at the University of Bristol, who describe the work as an "important breakthrough", say it could improve the lives of millions around the world.
In their research, published today in Nature Communications, the team reveal how to stop cells from attacking healthy body tissue.
The team discovered how cells convert from being aggressive to protecting against disease, rather than the body's immune system destroying its own tissue by mistake.
It is hoped the insight will lead to the widespread use of antigen-specific immunotherapy as treatment for many autoimmune disorders.
Conditions which could be affected by the research include multiple sclerosis (MS), type 1 diabetes, Graves' disease and systemic lupus erythematosus.
MS alone affects around 100,000 people in the UK and 2.5 million people worldwide.
Professor David Wraith, of the university's School of Cellular and Molecular Medicine, led the "exciting" research - which was funded by the Wellcome Trust.
"Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment," Professor Wraith said.
"These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat."
In the study, scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body's own tissue, while converting them into cells capable of protecting against disease.
This type of conversion has previously been applied to allergies, in a treatment known as "allergic desensitisation", but its application to autoimmune disorders has only recently been appreciated.
The researchers have now revealed how the administration of fragments of the proteins that are normally the target for the attack leads to correction of the autoimmune response.
Their work also shows that effective treatment can be achieved by gradually increasing the dose of antigenic fragment injected.
In order to analyse how this type of immunotherapy works, the scientists looked inside the immune cells themselves to see which genes and proteins were turned off by the treatment.
They found changes in gene expression that help explain how effective treatment leads to conversion of aggressor into protector cells.
The outcome is to reinstate self-tolerance, where an individual's immune system ignores its own tissues while remaining fully armed to protect against infection.
Researchers say that by specifically targeting the cells at fault, the immunotherapeutic approach avoids the need for immune suppressive drugs.
These drugs are often associated with side effects such as infections, development of tumours and disruption of natural regulatory mechanisms.
The treatment approach is currently undergoing clinical development through biotechnology company Apitope, a spin-out from the University of Bristol.
"Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy" is published in Nature Communications today.
Source: The Courier.co.uk © 2014 DC Thomson & Co, Ltd. (03/09/14)
Researchers discover neuroprotective role of immune cell(22/07/14)
A type of immune cell widely believed to exacerbate chronic adult brain diseases, such as Alzheimer's disease and multiple sclerosis (MS), can actually protect the brain from traumatic brain injury (TBI) and may slow the progression of neurodegenerative diseases, according to Cleveland Clinic research published today in the online journal Nature Communications.
The research team, led by Bruce Trapp, PhD, Chair of the Department of Neurosciences at Cleveland Clinic's Lerner Research Institute, found that microglia can help synchronize brain firing, which protects the brain from TBI and may help alleviate chronic neurological diseases. They provided the most detailed study and visual evidence of the mechanisms involved in that protection.
"Our findings suggest the innate immune system helps protect the brain after injury or during chronic disease, and this role should be further studied," Dr. Trapp said. "We could potentially harness the protective role of microglia to improve prognosis for patients with TBI and delay the progression of Alzheimer's disease, MS, and stroke. The methods we developed will help us further understand mechanisms of neuroprotection."
Microglias are primary responders to the brain after injury or during illness. While researchers have long believed that activated microglia cause harmful inflammation that destroys healthy brain cells, some speculate a more protective role. Dr. Trapp's team used an advanced technique called 3D electron microscopy to visualize the activation of microglia and subsequent events in animal models.
They found that when chemically activated, microglia migrate to inhibitory synapses, connections between brain cells that slow the firing of impulses. They dislodge the synapse (called "synaptic stripping"), thereby increasing neuronal firing and leading to a cascade of events that enhance survival of brain cells.
Trapp is internationally known for his work on mechanisms of neurodegeneration and repair in multiple sclerosis. His past research has included investigation of the cause of neurological disability in MS patients, cellular mechanisms of brain repair in neurodegenerative diseases, and the molecular biology of myelination in the central and peripheral nervous systems.
Source: Medical Xpress © Medical Xpress 2011-2014 (22/07/14)
Tolerance-directed immunotherapy: Future of MS treatment?(30/05/14)
It may take some time and require overcoming certain hurdles, but the future of multiple sclerosis (MS) management may lie in delivering therapies that make immune cells tolerant of specific antigens.
These "tolerance-directed" immunotherapies could eventually provide a safe, cost-effective, and highly efficient alternative to current approaches to MS treatments that suppress the immune system and inevitably lead to patients becoming more susceptible to infections, cancer, and other disorders.
Stephan D. Miller, PhD, Judy Guggenheim Research Professor of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, elaborated on the development of these precisely targeted immunotherapies in his opening lecture at the 6th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research In Multiple Sclerosis (ACTRIMS).
He is also a cofounder and member of COUR Pharmaceutical Development Company Inc, a nanobiotechnology company focused on the development of novel immune therapies using nanotechnologies based on the Immune Modifying nanoParticle platform.
As Dr. Miller explained, targeted tolerance-directed immunotherapies intervene in the autoimmune response, affecting only the pathogenic autoreactive T cells that react to a specific antigen. Such therapies reset those particular cells to actually avoid an immune response, rather than suppressing a response.
In the future, such new therapies may allow clinicians to shut down the underlying disease process instead of just controlling MS symptoms, said Dr. Miller, who has more than 30 years of experience in the field of autoimmune research.
New Way to Treat MS?
"We hope that our tolerance-directed therapy offers a new way to treat newly diagnosed MS patients to halt their disease in a safe and efficient manner by treating the root causes of the disease without the need to take a lifetime of immunosuppressive drugs and in a way that will avoid potential side effects, such as infections and increased rate of cancer," Dr. Miller told Medscape Medical News.
He and his colleagues have already proven the tolerance-directed approach to be safe and effective in a mouse model and, with a group of German researchers, have shown it to be effective in humans. The results of that published study of 9 patients with MS found that the tolerance-directed immunotherapy reduced the patients' immune system reactivity by 50% to 75% (Sci Transl Med. 2013;5:188ra75).
The drawback in that study, though, was that it used a method that involved extracting white blood cells, processing them to deliver myelin antigens so that the body would develop tolerance for them, and then reinfusing these treated white blood cells into the patients.
Dr. Miller and his colleagues are planning another trial of tolerance-directed immunotherapy. However, rather than using the relatively complicated and pricey extraction-processing approach, they hope to be able to deliver the therapy via biodegradable polymer-based nanoparticles: poly (D,L-lactide-co-glycolide) or PLG. It's the same technology used in absorbable sutures that dissolve after tissue heals.
"We are currently in the planning stages of this phase 1 trial using myelin antigen containing PLG nanoparticles in newly diagnosed MS patients," confirmed Dr. Miller, adding that his team hopes to carry out the study in collaboration with neurologists at the Multiple Sclerosis Center at Rush University Medical Center in Chicago.
If all goes well, the study should begin within the next 6 months to a year, said Dr. Miller.
This novel treatment approach has broad implications not only for the treatment of MS but also for a variety of other immune-mediated diseases, including type 1 diabetes and rheumatoid arthritis, and other conditions for which physicians want to manipulate the immune system, such as asthma, food allergies, and islet transplantation in diabetes. Immunologic tolerance, said Dr. Miller, is the "holy grail" for autoimmune diseases.
Broad Implications
Asked to comment on this approach, Corey Ford, MD, director, MS Clinic, and professor, neurology, University of New Mexico, Albuquerque, who introduced Dr. Miller's lecture, told Medscape Medical News that the idea of "tolerizing" the immune system has been around for a long time and that this is the mechanism by which the drug glatiramer acetate (Copaxone, Teva Pharmaceuticals) may be working.
"We have thought for a long time that MS may be triggered by antigens of some sort — we don't know what they are; maybe they're viruses or other environmental triggers — and that desensitizing the immune system to those could play a role in treatment."
Dr. Ford used the example of a patient who is allergic to penicillin. "You can desensitize that person to penicillin by giving him very small doses and gradually increasing the amount so his immune system becomes tolerant," he said.
Dr. Miller's tolerance-directed immunotherapy would in essence be "a more targeted way to desensitize a person with an autoimmune disease to the antigens" that might be triggering their disease, said Dr. Ford.
Dr. Ford agreed that there's still a lot of research needed to determine which antigens and what sequence of antigens are important.
The "good news," he said, is that the nanoparticles "are safe, can be given to humans, and are approved." And the fact that the framework or platform the antigen attaches to is biodegradable removes the worry about toxicity, he added.
"If you can make educated guesses about the right ones to use, maybe you have a treatment for a disease like MS and for many other conditions. This is a strategy that's a framework; it's not just a single disease-targeted approach."
Dr. Miller is cofounder and member of COUR PharmaceuticalDevelopment Company Inc, a nanobiotechnology company focused on the development of novel immune therapies using nanotechnologies based on the Immune Modifying nanoParticle (IMP) platform. The IMP particles are derived from Food and Drug Administration–approved, biodegradable polymer poly(lactic-co-glycolic-acid) that, when modified and built using proprietary IMPtechnology, provide therapeutic relief in numerous inflammatory conditions.
6th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research In Multiple Sclerosis (ACTRIMS). Opening Lecture. Presented May 28, 2014.
Source: Medscape Multispeciality Copyright © 1994-2014 by WebMD LLC (30/05/14)
Genome study identifies three possible drug candidates for autoimmune diseases(02/05/14)
New pharmaceuticals to fight autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and psoriasis, may be identified more effectively by adding genome analysis to standard drug screening, according to a new study by a research team led by UC San Francisco and Harvard researchers, in collaboration with Tempero and GlaxoSmithKlein.
In a study reported online April 17, 2014 in the journal Immunity, the scientists combined drug screening with state-of-the-art techniques for analyzing the genome, leading to three small molecules that improved symptoms in a mouse form of multiple sclerosis.
The three potential drug candidates, selected from a large library of screened chemicals, each knocked down the response of Th17 cells, a type of immune cell that drives many autoimmune diseases by attacking normal cells in the body. More specifically, the drugs homed in on an essential molecule within the Th17 cells.
"We examined what makes Th17 cells – which play a crucial role in multiple autoimmune diseases – distinct from other closely related T cells within the immune system," said Alexander Marson, MD, PhD, a leading T cell expert and member of the UCSF Diabetes Center. "Then we investigated several small molecules that inhibit the development and function of these cells. When the Th17 cells were hit by these molecules we saw less severe multiple-sclerosis-like symptoms in the mice."
The research team, led by Marson and Vijay K. Kuchroo, PhD, an immunologist at Brigham and Women's Hospital in Boston and Harvard Medical School, combined powerful techniques to shed light on a class of protein molecules within cells known as transcription factors.
Drug designers have rarely targeted transcription factors. Each transcription factor binds to DNA at a unique set of locations along the 23 pairs of chromosomes, and thereby influences which genes are turned on and off to trigger the protein production that drives cell development and function.
Different transcription factors shape the development of different types of T cells within the immune system, Marson and others are discovering. In their new study, Marson found that the transcription factor called ROR gamma t has a unique role in guiding development of Th17 cells, while inhibiting the development of other immune cells.
Preventing Th17 cells from developing by inhibiting the function of ROR gamma t appears to be an effective strategy for fighting autoimmune diseases, Marson said. "There already are drugs in clinical trials for autoimmune diseases – including psoriasis and rheumatoid arthritis – that are antibodies for IL-17 or IL-17 receptors," Marson said, referring to signaling molecules secreted by Th17 cells that can help trigger an attack our own healthy tissue, and the receptors that receive those signals. "This is an entirely different and promising approach to fight autoimmune disease," he said.
"Our studies map a path to targeting transcription factors and provide both insight into how transcriptional regulators shape the identity and affect the development of Th17 cells, and also into how different drug molecules might affect these regulatory circuits in the cells," he said.
To reveal the distinct and sometimes subtle effects of the drug candidates, the researchers studied the entire genome to see where ROR gamma t attached to DNA, which genes were activated or turned off as a result, and how these effects were altered by the drug candidates.
"Not only did we look at which genes are turned on and off, but we also systematically looked at DNA-binding sites across this genome," Marson said. "This pushes the boundary of what's typically done."
In addition to attaching to DNA, ROR gamma t has a pocket that looks like it should bind a hormone, Marson said. But what this hormone might be, and its effects, are unknown. The different drug candidates that inhibited Th17 development had different effects on ROR gamma t and resultant DNA binding and gene activation, possibly because of distinct interactions with the hormone-binding pocket, Marson said.
Analyzing the large data sets generated through such experiments could help pharmaceutical companies wading into development of drugs that target transcription factors to test the waters, Marson said, enabling drug developers to better understand mechanisms of drug action and to more easily see gene activity that could trigger side effects. According to Marson, "This is a new, broadly applicable approach for systematically evaluating leading drug candidates for autoimmune diseases."
Source: MedicalXpress © Medical Xpress 2011-2014 (02/05/14)
OSU scientists discover possible treatment for MS and other autoimmune diseases(21/03/14)
Researchers tested the compound in mice that had a condition in which the immune system tries to eliminate foreign cells.
Oregon State University scientists have discovered a chemical compound that could be a safer alternative to treating autoimmune diseases, possibly bringing hope to people suffering from conditions caused by their immune system attacking their bodies.
Studies are still needed in humans, however. Autoimmune diseases can affect almost any part of the body and result in such diseases as colitis, multiple sclerosis and psoriasis.
"We mostly treat autoimmune diseases with high-dose corticosteroids or cytotoxic drugs to suppress the immune response, and the side effects can be very difficult to deal with," lead researcher Nancy Kerkvliet said in a statement. "But if this chemical works in clinical studies, it could result in a safer alternative to conventional drugs."
Kerkvliet and OSU professor Siva Kumar Kolluri tested thousands of chemical compounds and found that one of them, 10-CI-BBQ, binds to a protein inside T cells. The chemical and protein pass into the nucleus and change the cells into regulatory T cells, which shut down the immune response.
Researchers tested the compound in mice that had a condition in which the immune system tries to eliminate foreign cells. The disease can occur in humans when they receive stem cell or bone marrow transplants.
Daily injections completely suppressed the disease. The compound was rapidly metabolized and not toxic.
The research was published in the journal PLOS ONE.
Source © 2014 American City Business Journals. All rights reserved. (21/03/14)
New insights into immune response could lead to development of new treatments(19/03/14)
A team of biologists and engineers at the University of California, San Diego has discovered that white blood cells, which repair damaged tissue as part of the body's immune response, move to inflamed sites by walking in a stepwise manner. The cells periodically form and break adhesions mainly under two "feet," and generate the traction forces that propel them forward by the coordinated action of contractile proteins. Their discovery, published in the Journal of Cell Biology, is an important advance toward developing new pharmacological strategies to treat chronic inflammatory diseases such as arthritis, irritable bowel syndrome, Type 1 diabetes, and multiple sclerosis.
"The immune system requires the migration of white blood cells to the point of infection and inflammation to clear invaders and begin the process of digesting and repairing tissue. However, when the body fails to properly regulate the recruitment of these cells, the inflammation can become chronic resulting in irreversible tissue injury and loss of functionality," said Juan C. Lasheras, a professor in the departments of Mechanical and Aerospace Engineering and Bioengineering, and in the Institute for Engineering in Medicine. "Understanding the way in which these cells generate the necessary forces to move from the blood stream to the site of inflammation will guide the design of new strategies that could target specific mechanical processes to control their migration," Lasheras said.
Figuring out how white blood cells move required an interdisciplinary approach involving engineering and biological sciences. The lead author of the study is Effie Bastounis, a member of a team led by UC San Diego Jacobs School of Engineering professors Lasheras and Juan Carlos del Alamo, of the Department of Mechanical and Aerospace Engineering, and Richard A. Firtel, a professor of Cell and Developmental Biology in the Division of Biological Sciences. "This work was made possible through interdisciplinary approaches that applied mathematical tools to a basic question in cell biology about how cells move," stated Richard Firtel. "By first applying novel methodologies to study the amoeba Dictyostelium, an experimental system often used by cell biologists, we were able to discover the basic mechanisms that control amoeboid movement, which we then applied to understanding white blood cells."
The team used new analytical tools to measure, with a high degree of accuracy and resolution, the forces the cells exert to move forward. The novel methodology, which they have been refining during the last several years supported by grants from the National Institutes of Health (R01-GM084227 and R01-GM037830), is called Fourier Traction Force Microscopy. Before their study, scientists thought white blood cells did not move in a highly coordinated manner. Furthermore, their work discovered that cells move by not only extending themselves at their front and contracting their backs, but also by squeezing inwardly along their lateral sides pushing the front of the cell forward. These findings establish a new paradigm as to how cell move. The research team is currently extending their techniques, which they have used to study leukocytes and other types of amoeboid cells, to investigate the mechanics of cancer cell migration and invasion.
Source: MNT © 2004-2014 MediLexicon International Ltd (19/03/14)
Multiple Sclerosis might be predictable by blood tests(24/02/14)
Individuals who are suffering from Multiple Sclerosis might have a certain antibody inside their blood, perhaps permitting for early discovery with a blood test prior to any symptoms showing up. There is a potassium protein that contained the antibodies in question and they were found in over six of nearly 20 test subjects who did not have any MS symptoms during the time of testing. Yet each had ended up developing the disease by nine months after the test. Two other participants of the group ended up showing borderline existence of the antibodies.
The results of the entire group were measured against a control group of nearly 15 other people who were the same sex and age as the original group. These people did not have any of the unusual antibodies in their blood and none of them went on to develop MS. This test was held by a technical university located in Germany. The researchers plan on showing their findings at the American Academy of Neurology's yearly meeting, which is set to be held in April.
Such findings are very positive for the sufferers of MS, as information might help lead to early exposure and also to possible positive treatment. Eventually there may even be prevention of Multiple Sclerosis. The research study's leader, Dr. Viola Biberacher, stated that if such results could be repeated in bigger parts of the population, then the findings could possibly aid in finding MS earlier in patients. By discovering the disease before symptoms start to show up could mean that physicians and scientists might possibly be able to prepare and treat and maybe even stop some of the symptoms of MS.
These discoveries have also shown that antibodies that have developed in a protein known as KIR4.1, which has been discovered in several individuals with MS, came before the onset of the disease. This suggests a part of the auto antibody in the way of how MS might develop, Biberacher added.
Since the year 2008, Multiple Sclerosis diagnosis rates have risen almost 12 percent worldwide. There are over two and a half million people that are believed to be suffering from the incapacitating condition at this time. Presently there is not any sort of cure for MS either. It is an autoimmune disease which affects the insulating shields inside the cells of nerves throughout the spinal cord and brain.
It is believed that MS develops as the result of a genetic disposition, along with other exterior factors, such as having a deficiency of sun exposure. That seems to aid in the diseases advancement. Countries located in the northern part of the world, that have less sunlight seem to have a higher frequency of Multiple Sclerosis, with Canada having about 290 assessed cases for every 100,000 amount of their population. Sweden also has high rates of MS, with an estimated 190 cases for about every 100,000 individuals. But unlike these countries, doctors located in the United States are not obligated to report occurrences of the condition to the Centers for Disease Control. So the amount of official cases in America stays uncertain.
Biberacher is hopeful about treatments in the future. She stated that the next step of the process was to authorize findings in bigger groups and figure out just how many years there is before Multiple Sclerosis begins that the antibody response begins to start developing in the body. If the individuals who are suffering from Multiple Sclerosis do have such an antibody inside their blood, perhaps permitting for early discovery prior to any symptoms showing up will be available to them in the future.
Source: Guardian Liberty Voice (24/02/14)
New blood cells fight brain inflammation(17/02/14)
Hyperactivity of our immune system can cause a state of chronic inflammation. If chronic, the inflammation will affect our body and result in disease. In the devastating disease multiple sclerosis, hyperactivity of immune cells called T-cells induce chronic inflammation and degeneration of the brain. Researchers at BRIC, the University of Copenhagen, have identified a new type of regulatory blood cells that can combat such hyperactive T-cells in blood from patients with multiple sclerosis. By stimulating the regulatory blood cells, the researchers significantly decreased the level of brain inflammation and disease in a biological model.
The results are published in the journal Nature Medicine.
Molecule activate anti-inflammatory blood cells
The new blood cells belong to the group of our white blood cells called lymphocytes. The cells express a molecule called FoxA1 that the researchers found is responsible for the cells' development and suppressive functions.
"We knew that some unidentified blood cells were able to inhibit multiple sclerosis-like disease in mice and through gene analysis we found out, that these cells are a subset of our lymphocytes expressing the gene FoxA1. Importantly, when inserting FoxA1 into normal lymphocytes with gene therapy, we could change them to actively regulate inflammation and inhibit multiple sclerosis, explains associated professor Yawei Liu leading the experimental studies.
Activating own blood cells for treatment of disease
FoxA1 expressing lymphocytes were not known until now, and this is the first documentation of their importance in controlling multiple sclerosis. The number of people living with this devastating disease around the world has increased by 10 percent in the past five years to 2.5 million. It affects women twice more than men and no curing treatment exists. The research group headed by professor Shohreh Issazadeh-Navikas from BRIC examined blood of patients with multiple sclerosis, before and after two years of treatment with the drug interferon-beta. They found that patients who benefit from the treatment increase the number of this new blood cell type, which fight disease.
"From a therapeutic viewpoint, our findings are really interesting and we hope that they can help finding new treatment options for patients not benefiting from existing drugs, especially more chronic and progressive multiple sclerosis patients. In our model, we could activate lymphocytes by chemical stimulation and gene therapy, and we are curios whether this can be a new treatment strategy", says professor Shohreh Issazadeh-Navikas.
And this is exactly what the research group will focus on at next stage of their research. They have already started to test whether the new FoxA1-lymphocytes can prevent degradation of the nerve cell's myelin layer and brain degeneration in a model of progressive multiple sclerosis. Besides multiple sclerosis, knowledge on how to prevent chronic inflammation will also be valuable for other autoimmune diseases like type 1 diabetes, inflammatory bowel disease and rheumatoid arthritis, where inflammation is a major cause of the disease.
Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (17/02/14)
Are infections driving T-cells to increase Multiple Sclerosis progression?(06/02/14)
Scientists recently uncovered a key finding that CD4 T cells are not involved with Multiple Sclerosis progression after recent trials revealed that a depleting CD4-specific antibody failed to affect MS. The question is: did the depleting CD4 specific antibody fail to affect MS, or was the experimental design flawed? Essentially, immunologists claim that CD4 cells are at the center of the immunological research world simply because they are involved with other aspects of immune responses in order to be able to do what they do.
Zastepa et al., (Neurology Jan. 2014) have looked at whether altered naïve CD4 T-cell biology contributes to development of disease progression in secondary progressive multiple sclerosis (SPMS). The researchers were able to compare naïve CD4 T-cell gene expression profiles of 19 patients with SPMS vs 14 healthy controls using a whole-genome microarray approach. They looked at surface protein expression of critical genes by flow cytometry after T-cell receptor (TCR) activation of naïve CD4 T cells isolated from healthy controls and patients with SPMS.
The researchers separated patients with SPMS into two subgroups: SP-1, which had a short duration of relapsing-remitting MS, and SP-2, which had a long duration of relapsing-remitting MS. They discovered that SP-1 patients upregulated many immune genes, within the TCR and toll-like receptor (TLR) signaling pathways. SP-2 patients demonstrated down regulation of immune genes in comparison with healthy controls. They also found an SP-1-specific transcriptional signature of 3 genes which includes TLR4, TLR2 and chemokine receptor 1. These genes had a higher surface protein expression in SP-1 than SP-2. After researchers stimulated TCR for 2 days, only SP-1 showed a progressive linear increase in TLR2 and TLR4 protein expression.
The researchers suggest that changes in naïve CD4-T-cell biology, particularly that of TCR and TLR signaling pathways, identify MS patients with a rapid conversion to secondary progression. This is important because this identifies long-term disability in MS. In fact, certain proteins are in higher concentration on T cells from progressive MS patients that progress faster. What are these proteins doing you ask? That is not known as this time, however Toll-like receptors involved with microbe recognition and infections are important to the rate of progression. We know that blocking CD4 activity doesn't stop progression, but the question is whether it changes the slope (rate of change). We expect to find this answer from the SP1 and tysabri trials.
Source: BioNews Texas (06/02/14)
Scientist explores new avenue to fight Multiple Sclerosis(09/01/14)
A research scientist at Albany Medical College has identified a potential path to providing relief of symptoms of multiple sclerosis (MS), a disease with few treatments that affects 350,000 Americans.
Writing in the Journal of Clinical Investigation, Dorina Avram, Ph.D., professor in the Center for Immunology and Microbial Disease at Albany Medical College, said she was able to eliminate symptoms in mice which have an MS-like disease by removing a single molecule to alter the immune system's T-cells.
Dr. Avram said the work could highlight a new therapeutic strategy for MS, an autoimmune disorder that is more common in northern regions, including upstate New York.
"My team is thrilled that this work is showing such promise as a new approach toward treating this devastating disease that we see a lot of at Albany Med," said Dr. Avram. She said while her current research involves animal studies, she has been meeting with neurologists at Albany Medical Center to discuss research strategies.
"Dr. Avram's research is very exciting. Her results suggest that there may be new and very effective treatment options for people with MS," said Michael Gruenthal, M.D., Ph.D., chair of neurology at Albany Medical Center. "More laboratory research is needed before we can consider research studies in people with MS. When there's an opportunity to begin research in people with MS, we'll be ready."
In multiple sclerosis, the immune system mistakenly attacks normal cells and tissues in the central nervous system. The result is severe inflammation creating symptoms such as weakness, numbness, and loss of vision in one eye.
In the studies, Dr. Avram removed an immune system-controlling molecule called BCL11B from immune system T-cells, which weakened the immune reaction.
As part of a cascade of effects, removal of this molecule from the T-cells resulted in an increase in Interleukin 4 (IL-4), and consequently of retinoic acid, a metabolite of vitamin A critical for re-routing immune system cells from the central nervous system to the small intestine. Diminished T-cell infiltration into the central nervous system resulted in reduced severity and delayed onset of disease symptoms.
"We expected the T-cells to be less activated. What we did not expect was their diversion to the small intestine where they were rendered harmless," Dr. Avram said. In another study, Dr. Avram vaccinated diseased mice in a manner to boost IL-4 and found the same effect.
"If this method works in people, we don't expect it would provide a cure but rather an extended remission. Of course, we are still in the early phases of research but this is an important development that opens up new possibilities," said Dr. Avram.
Source: HealthCanal (09/01/14)


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Archive for 14 August 2012
An enterprising new Star Trek trailer from Namco [Video]
Namco has issued a short trailer for its forthcoming co-op focused Star Trek title, based on the 'rebooted' universe of JJ Abrams.
Hitman: Absolution has an intriguing 'Contracts' multiplayer mode
A new way of playing Hitman: Absolution was revealed today by I/O Interactive, and for the longest while I couldn't properly figure out how it worked.
Japan Studios' Puppeteer might just pull your strings [Video]
A game it might have been easy to overlook in Sony's somewhat packed Gamescom 2012 press event is Japan Studios' platformer, Puppeteer.
PlayStation Plus will get the God of War: Ascension beta first
Further proof that videogames should be banned from using the word "epic" until at least 2016 can be found in the new trailer for God of War: Ascension's multiplayer portion (below).
Dark Souls doesn't look any easier in its Prepare to Die incarnation [Video]
It's not at all long (next week, in fact) before Dark Souls: Prepare to Die Edition drags itself onto the PC.
Assault Beefeaters with a cricket bat in ZombiU [Video]
It's a rough time to be a member of the royal family in Ubisoft's ZombiU.
Deadly scuffles and Hank Williams in The Last of Us [Video]
Naughty Dog's impressive looking The Last of Us has a brand new trailer (albeit with some old footage) for Gamescom, backed by the cheerful tones of Hank Williams Sr.
'Teen Horror' Until Dawn announced for PlayStation Move
Supermassive's Until Dawn is a newly announced title for the PlayStation Move which examines the question "will young couples ever stop visiting scary, dark cabins in the woods?" The answer, of course, is no.
Call of Duty: Black Ops Declassified getting a special Vita bundle
What's a major press event at a videogames show without mention of a Call of Duty game, eh?
Tearaway and Killzone Mercenary announced for PS Vita
A pair of new PlayStation Vita titles have been revealed by Sony at is Gamescom press event today.
Assassin's Creed 3 gamescom trailer takes to the seas [Video]
Assassin's Creed 3 protagonist Connor is apparently just as happy at sea as he is on land, just so long as he puts on his Captain's outfit first.
Cloud storage limit on PlayStation Plus will soon be 1gig
Sony has plans to increase the cloud storage limit on PlayStation Plus from 150mb to a rather more impressive 1 gig, the company announced today at its Gamescom press event.
Sony reveals new 'Cross Buy' titles for PS3-Vita play
Sony's Gamescom 2012 press conference has introduced some new titles in the 'Cross Buy' program, a system where certain PlayStation 3 title purchases will give you access to a PS Vita copy as well for no extra cost.
Guildford, UK – Aug. 14, 2012 – Electronic Arts Inc. announced today that EA SPORTS™ has developed a new feature for FIFA 13 called EA SPORTS Football Club Match Day that will drive the deepest and most meaningful connection yet between a videogame and the real world of sport ever achieved.
Cyberpunk 'memory remixing' in Capcom's Remember Me [Video]
Do you recall Dontnod Entertainment's Adrift from Gamescom 2011? No, neither do I.
Need For Speed: Most Wanted's multiplayer is a Teenage Wasteland [Video]
The latest multiplayer trailer for Criterion's Need for Speed: Most Wanted employs the remixed talents of The Who, as well as a number of extremely fast virtual cars.
Dishonored's PC specs will not disgrace your rig
Amongst all the hustle and bustle of Gamescom, Bethesda has quietly revealed the minimum and recommended PC specs for Arkane's forthcoming assassination-fest, Dishonored.
Simcity coming to MAC in February 2013
COLOGNE, Germany – Aug. 14, 2012 – The king of city-builders is making its triumphant return to the Mac!


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Bing Ads Show Number of Twitter Followers
Bing's long-running partnership with Twitter has yielded a new feature – some ads running on Bing now display the number of Twitter followers that the advertiser has. The feature is similar to Google's annotations displaying advertisers' Google+ followers, but a Twitter follower count might be more likely to resonate with users. The feature appears to still be under tests, and is not displaying for all users, but it seems likely that this could become a permanent addition to the search engine. (more…)


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U.S. Navigation Usage and Satisfaction Study
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As navigation systems become more widely used, it is essential to understand owners' expectations of product quality, system design, and price. Examining these factors allows both manufacturers and suppliers to understand the performance that owners demand from their navigation system.
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The J.D. Power 2013 Navigation Usage and Satisfaction StudySM provides an in-depth analysis of owners' satisfaction with their factory-installed navigation system. The study also examines owners' usage habits, desired features, system quality, and pricing expectations at the model level, which allows competitive cross-industry comparisons.
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Study subscription provides access to the tools needed to improve existing products, benchmark against competitors, and develop new products by first understanding:
- Owner satisfaction with current navigation systems (including ease of use, routing, display screen, voice directions, system speed, voice recognition, and appearance)
- Frequency and types of usage behaviors
- Problems experienced
- Product support satisfaction
- Customers' perceived value of system
- Customer preferences for mapping software updates
- Navigation system preferences for future offerings
- Enhanced feature sections focus on satisfaction with real-time traffic; voice recognition; off-board navigation (with operator and without operator); and portable navigation devices


text: i am not sure where to post this as I have only been a member of 3FC for a couple wekks but my German Shepherd, Patience is at the Animal Hospital tonight. She is in surgery as I am writing this. We are not sure what is wrong yet but her stomach is bloated really big and nothing is moving. They need to do surgery to clean it out so it doesn't rupture. There is a possible twist but it could be something else since she has had intestinal problems for most her life. She is nine and is our baby. We love her so much. I will update more latter but want to get some prayers sent her way. She is a true gift from God and I hope that she can stay a little longer!


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English Standard Version (ESV) | New International Version (NIV) |
1 I will take my stand at my watchpost and station myself on the tower, and look out to see what he will say to me, and what I will answer concerning my complaint. | 1 I will stand at my watch and station myself on the ramparts; I will look to see what he will say to me, and what answer I am to give to this complaint. |
2 And the LORD answered me:"Write the vision; make it plain on tablets, so he may run who reads it. | 2 Then the LORD replied: "Write down the revelation and make it plain on tablets so that a herald may run with it. |
3 For still the vision awaits its appointed time; it hastens to the end--it will not lie. If it seems slow, wait for it; it will surely come; it will not delay. | 3 For the revelation awaits an appointed time; it speaks of the end and will not prove false. Though it linger, wait for it; it will certainly come and will not delay. |
4 "Behold, his soul is puffed up; it is not upright within him, but the righteous shall live by his faith. | 4 "See, he is puffed up; his desires are not upright-- but the righteous will live by his faith-- |
5 "Moreover, wine is a traitor, an arrogant man who is never at rest. His greed is as wide as Sheol; like death he has never enough. He gathers for himself all nations and collects as his own all peoples." | 5 indeed, wine betrays him; he is arrogant and never at rest. Because he is as greedy as the grave and like death is never satisfied, he gathers to himself all the nations and takes captive all the peoples. |
6 Shall not all these take up their taunt against him, with scoffing and riddles for him, and say, "Woe to him who heaps up what is not his own-- for how long?-- and loads himself with pledges!" | 6 "Will not all of them taunt him with ridicule and scorn, saying, " 'Woe to him who piles up stolen goods and makes himself wealthy by extortion! How long must this go on?' |
7 Will not your debtors suddenly arise, and those awake who will make you tremble? Then you will be spoil for them. | 7 Will not your debtors suddenly arise? Will they not wake up and make you tremble? Then you will become their victim. |
8 Because you have plundered many nations, all the remnant of the peoples shall plunder you, for the blood of man and violence to the earth, to cities and all who dwell in them. | 8 Because you have plundered many nations, the peoples who are left will plunder you. For you have shed man's blood; you have destroyed lands and cities and everyone in them. |
9 "Woe to him who gets evil gain for his house, to set his nest on high, to be safe from the reach of harm! | 9 "Woe to him who builds his realm by unjust gain to set his nest on high, to escape the clutches of ruin! |
10 You have devised shame for your house by cutting off many peoples; you have forfeited your life. | 10 You have plotted the ruin of many peoples, shaming your own house and forfeiting your life. |
11 For the stone will cry out from the wall, and the beam from the woodwork respond. | 11 The stones of the wall will cry out, and the beams of the woodwork will echo it. |
12 "Woe to him who builds a town with blood and founds a city on iniquity! | 12 "Woe to him who builds a city with bloodshed and establishes a town by crime! |
13 Behold, is it not from the LORD of hosts that peoples labor merely for fire, and nations weary themselves for nothing? | 13 Has not the LORD Almighty determined that the people's labor is only fuel for the fire, that the nations exhaust themselves for nothing? |
14 For the earth will be filled with the knowledge of the glory of the LORD as the waters cover the sea. | 14 For the earth will be filled with the knowledge of the glory of the LORD, as the waters cover the sea. |
15 "Woe to him who makes his neighbors drink-- you pour out your wrath and make them drunk, in order to gaze at their nakedness! | 15 "Woe to him who gives drink to his neighbors, pouring it from the wineskin till they are drunk, so that he can gaze on their naked bodies. |
16 You will have your fill of shame instead of glory. Drink, yourself, and show your uncircumcision! The cup in the LORD's right hand will come around to you, and utter shame will come upon your glory! | 16 You will be filled with shame instead of glory. Now it is your turn! Drink and be exposed ! The cup from the LORD's right hand is coming around to you, and disgrace will cover your glory. |
17 The violence done to Lebanon will overwhelm you, as will the destruction of the beasts that terrified them, for the blood of man and violence to the earth, to cities and all who dwell in them. | 17 The violence you have done to Lebanon will overwhelm you, and your destruction of animals will terrify you. For you have shed man's blood; you have destroyed lands and cities and everyone in them. |
18 "What profit is an idol when its maker has shaped it, a metal image, a teacher of lies? For its maker trusts in his own creation when he makes speechless idols! | 18 "Of what value is an idol, since a man has carved it? Or an image that teaches lies? For he who makes it trusts in his own creation; he makes idols that cannot speak. |
19 Woe to him who says to a wooden thing, Awake; to a silent stone, Arise! Can this teach? Behold, it is overlaid with gold and silver, and there is no breath at all in it. | 19 Woe to him who says to wood, 'Come to life!' Or to lifeless stone, 'Wake up!' Can it give guidance? It is covered with gold and silver; there is no breath in it. |
20 But the LORD is in his holy temple; let all the earth keep silence before him." | 20 But the LORD is in his holy temple; let all the earth be silent before him." |
The English Standard Version is published with the permission of Good News Publishers. (English Standard Version - The Holy Bible Online) | Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online) |


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Gear Review
A bit snug/skinny fit
I read the reviews and figured I'd be a-ok with these but they are a bit snug. If you like low-waisted pants and pants that sit lower on your back then these are for you. I like mine a bit baggier with room for a belt. I always wear a sz L in womens for the loose fit and these were too tight. As far as looks, they are VERY cool. I love Nomis designs since they aren't plain. They pay a lot of attention to detail and that sets their brand apart. Wishing they were looser :( but overall the style is more of the "skinny fit".
View More Details on Nomis Contour Shell Pant - Women's


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http://www.cryocath.com Toronto Stock Exchange Symbol: CYT
MONTREAL, Feb. 14 /PRNewswire-FirstCall/ - CryoCath(R) Technologies Inc., the global leader in cryotherapy products to treat cardiac arrhythmias, today provided an update on the enforcement of its patent portfolio.
Since its inception 13 years ago CryoCath has been, and continues to be the clear leader in innovation in the field of cryotherapy devices with cardiac applications and will continue to vigorously enforce its patent rights. CryoCath owns over 100 issued patents world-wide and has more than 100 patent applications pending. In the last five years, CryoCath has filed over 140 patent applications. Many of CryoCath's pending applications are expected to issue between 2008 and 2010, continuing to strengthen CryoCath's intellectual property position.
In October 2007, CryoCath filed a U.S. patent infringement suit against CryoCor, Inc. alleging infringement of six patents. Since that time, the United States Patent and Trademark Office (USPTO) has issued CryoCath two additional patents, U.S. Patent Nos. 7,303,554 and 7,318,821. CryoCath will amend its complaint to assert these patents in this patent infringement suit.
In early February 2008, CryoCath also filed a claim against CryoCor,
alleging infringement of a ninth CryoCath patent, U.S. Patent # 5,147,355
entitled "Cryoablation Catheter and Method for Performing Cryoablation"
issued to Friedman. Additionally CryoCath believes CryoCor and co-plaintiff
AMS Research Corporation assert AMS's patents in their January 2008 action
against CryoCath in a manner that illegally extends at least one patent
beyond its scope. Therefore, CryoCath filed counterclaims alleging patent
misuse, antitrust, and unfair competition. CryoCath believes CryoCor's case
is without merit, and that it does not infringe the two patents asserted in
the January 2008 action or the foreign count
SOURCE CryoCath Technologies Inc. Copyright©2008 PR Newswire. All rights reserved |


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Government innovation is not an oxymoron. The challenge and opportunity for making this transformation is for public service managers and staff alike to develop a common understanding and practice of what innovation looks like and thereby overcome the natural skepticism that asks "is innovation possible in a risk averse environment?". BridgePoint Effect has extensive expertise in making innovation achievable in government organizations. We can help you learn how make innovation structural, language-based, actionable and measurable and in the process we can help you reach new levels of performance.
Critical Thinking and Creative Problem Solving – 2 days March 10 – 11 2015 Critical Thinking & Creative Problem Solving – 1 day February 19 2015
For true success ask yourself these four questions: Why? Why not? Why not me? Why not now? – James Allen


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Rabble-rouser Josh Koscheck meets his match in fellow wrestler Mike Pierce, who came to the UFC 143 with a prop... watch video >>
Rampage Jackson takes on King Mo in the ultimate grudge match to end all grudge matches. Headlining the May 17th Pay Per View these two fighters are ready to prove who has the meddle. To learn more watch video >>
A grudge match simmering for three years finally explodes on October 9th when Nick Diaz seeks revenge against K.J. Noons. Watch their first bloody bout and prepare for Diaz vs. Noons watch video >>
Mark Munoz quickly breaks down who he thinks will win between Georges St. Pierre and Josh Koscheck. He talks to fight correspondent Marcos Villegas about what to look for in the fight! watch video >>
Megan Olivi takes on Urijah Faber in a heat UFC Trainer grudge match. watch video >>
Jon Fitch beats the clock with a vice-like rear naked choke of TUF vet Josh Burkman at UFC® Fight Night™ 4. watch video >>
See how Vitor Belfort - and the Brazilian crowd - greet Anthony Johnson as the former welterweight misses the mark by more than ten pounds. watch video >>
UFC on FOX Trailer - Nate Diaz vs Jim Miller, Josh Koscheck vs Johny Hendricks, Alan Belcher vs Rousimar Palhares, Lavar Johnson vs Pat Barry Date May 5, 2012 Venue IZOD Center City, East Rutherfo watch video >>
Anthony Johnson vs. David BranchTitan Fighting Championship 22Memorial Hall, Kansas City, Kansas, United StatesMay 25, 2012 watch video >>


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Comparing professional model shots against candid personal pics will always show a …
- Tags: AKB48, AV, Censorship, Fuji TV, Guro, Idol, Music, Prostitution, TV
Comment on AKB to SOD: Rina Nakanishi's Porno Decline Truly Mortifying by vanchrian:
Comparing professional model shots against candid personal pics will always show a stark contrast. Her lower eyelids have always been baggy, but it was previously hidden with the magic of makeup and shooping.
She looks fine, if a little overworked.
Recent comments by vanchrian:
- Macross Delta Unveiled:
Probably because: 1) The director is busy. 2) Guld is dead.
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How long before some otaku loses an eye because he failed to follow basic airsoft safety?
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She was the voice of Weekend in Witch Craft Works. And she did a pretty darn good job in the role. I could hardly tell it was her without looking up the voice list. Just goes to show the variety of roles she can perform now that she's free from the shackles of moeshit.
- FF14 "Failed Because Our Flowerpots Were Too Beautiful":
SO they're saying that, in hindsight, FF14′s original launch went poorly due to mismanagement, improper focus, and too much groupthink during development. That makes sense. Hope that the relaunch goes well for them.
- China Smog "Like Nuclear Winter":
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Ingredients: Whole organic linum usitatissimum (flax) seed.
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Just click "Add to Set & Save" when placing items in your cart.
Retail price: $7.92
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The crushed seeds or meal make a very useful poultice, either alone or with mustard.
Vitacost price: $4.29
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Sweet jesus, my bike shop has been crazy busy lately. After work I just want to eat half a herd animal and go to sleep. So this last story about my vacation in Florida and South Carolina is wretchedly delayed, but such is life. Last I left off, I had just confirmed my true ability at time trials, and I left my comrades-on-wheels to seek out Goal #4: the girl.
The secret is out: I've got a new custom track frame in the works. It's a project I started two years ago and is now just weeks away from completion. I designed the bike down to the millimeter and chose each and every bit of metal individually. This will be the third in a series of track frames that Sycip Designs has built for me, and I salute Jeremy Sycip for putting up with my whacked out requests over the years. Be sure to check in over the next couple weeks for updates.
Next time: the track bike with 3 down tubes
Ibex sent us arm and knee warmers and a jersey to try out. I took the New Zealand Merino wool clothes with me to Santa Barbara. It was thankfully warm in SBA and I didn't wear the warmers for very long, but did note during the ride that they were well-constructed and offer a unique blend of wool, nylon, and Lyrca. They're also made in the USA.
Temperature regulation is always tough in wet, cold climates (and Seattle has been the wettest and coldest this year!) and I think Ibex would meet the demand for training rides, commutes, and recreational rides. The material is probably too thick for hard riding, but I'll need to long-term test that factor on a colder, pouring, suffering ride to make sure.
Submitted by San Fran Cup
Check Pink Bike and Flowers post on racing hard to win a new pair of gloves, which is only slightly better than winning a tube, tire, or the all-time favorite, a seat post. Ah well, we don't do it for the money.
Related photos, including some road rash.


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This shoot is tagged with:
- short hair
- outdoors
- redux
- natural bush
- small breasts
- hairy
- pale skin
FREE PREVIEW VIDEO Nadja
Click the thumbnail above to watch a free sample preview from this shoot.
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IMAGESET | 27 Jun 2010Nadja


text: Earlier in my life around 28 i experienced a rapid onset of PCOS but was after a few years able to get my menstrual cycle back into regularity. I never lost the weight but and still suffer from facial hair. However as I get older (51) my PMT symptoms are getting longer and more horrendous. For at least 10 days before my period I feel anxious, on edge, hysterical and dangerously moody. This is a real liability in my professional life. Also serotonin deficiency insomnia, where I can go to sleep but wake up at 3 every night and are unable to go back to sleep. I started with natural progesterone cream about 2 months ago and take oxapazem to help with sleep. It started off by reducing the symptoms but now it seems worse, I feel on edge ALL THE TIME and have insomnia all the time and no relief after my periods. Far from stopping my periods they are as regular as always and if I forget to rub cream on bang my periods start up. This is really traumatic and I fear that I will become one of those women who go off their tree at menopause. I eat an excellent diet (mostly) and have tried every natural supplement suggested. Help!


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More Recipe Collections
Robin's Fav Easy Delicious Foods
(4 Recipes) Created by HOTMAMA2HCM
Recipes in this Collection
Incredible! 5.0/5
(2 ratings)
This is a very hearty, easy dinner. Submitted by MAMARUBADUE Carbs: 23.6g | Fat: 2.8g | Fiber: 3.3g | Protein: 20.7g | Calories: 201.8
This chili is packed with flavor and fiber. Make a big batch for a crowd or freeze it in single-serving containers for up to four months. Submitted by CHEF_MEG Carbs: 20.2g | Fat: 6.3g | Fiber: 4.6g | Protein: 25g | Calories: 234.5
Very Good 4.3/5
(8 ratings)
Cookbook creator says: I added a little lime juice, Worchestershire sauce, and a pinch of Lawrey's seasoned salt to the Dijon sauce to give it a little extra kick. Delicious!! Submitted by DSNYGIRL73 Carbs: 1.7g | Fat: 20.8g | Fiber: 0.4g | Protein: 29.2g | Calories: 325.7
This is a quick and easy chicken dish that looks and tastes like you went to a lot of work. Submitted by CARPROTH Carbs: 32.7g | Fat: 10.7g | Fiber: 10.2g | Protein: 35.7g | Calories: 365.5
Send this recipe collection to a friend - http://recipes.sparkpeople.com/cookbooks.asp?cookbook=297393


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"The harder you work, the luckier you get." by Gary Player
Below is the poem entitled high sChOOL which was written by poet Ashley Smith. Please feel free to comment on this poem. However, please remember, PoetrySoup is a place of encouragement and growth.
Read Poems by Ashley Smith
Best Ashley Smith Poems
He said, She said That's all you seem to hear When you walk down the hall It's the same thing every year Unecessary drama That's all high school's about You can try to avoid being trapped in it But you'll never find a way out Life was so simple Before our high school days Before we became caught up In the 'how to be popular' craze High school's so overrated Ive waited 13 years to say Im a senior so leave me out of it I'm just here til Graduation Day


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Who do you think looks best today? (5 photos)
The best street style from London Fashion Week: http://ow.ly/p48HS via @StyleCaster
WHAT SHE WORE Beckham took in Viva Forever in a crisp blouse and cropped trousers that she topped with a plum coat. A metallic box clutch and pointy-toe pumps completed the look.Read MoreLess


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Hebrew Names Version (HNV) | New International Version (NIV) |
31 After him was Shamgar the son of `Anat, who struck of the Pelishtim six hundred men with an ox-goad: and he also saved Yisra'el. | 31 After Ehud came Shamgar son of Anath, who struck down six hundred Philistines with an oxgoad. He too saved Israel. |
The Hebrew Names Version is in the public domain. (Hebrew Names Version - The Holy Bible Online) | Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online) |


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Blue Sea wins NMDA awards
Posted onBlue Sea Systems, the Washington-based manufacturer of marine electrical products, announced it won three awards at the recent National Marine Distributor Association conference, including Supplier of the Year.
NMDA distributor members vote to determine the award winners. Blue Sea also won Best All-Around Packaging and Supply Chain Standards Efficiency.
"We appreciate the vote of confidence from the members of the NMDA," Blue Sea senior vice president David Johnson said in a statement. "Our employees are committed to continually improving the design, quality, packaging and support of our product to distributors and their customers."
"We are proud of the efforts Blue Sea Systems has made to improve their scores and congratulate them on their award," NMDA executive director Nancy Cueroni said in a statement. "It is through the efforts of companies like Blue Sea Systems working with their distributor customers that enables retailers to continue growing their businesses."
Click here for the full release.
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I attended the launch of this vehicle six months ago, and I have to say that I still like its exterior styling, the latest evolution of Volvo's decidedly unboxlike design language. As to its interior, which a couple of my colleagues have expressed disappointment in, I'll only say that while it's true that the center stack is no longer cutting edge, the controls work well and are quite intuitive. The seats are as comfortable as Volvo seats always are, although I don't think they work quite as well visually when upholstered in black leather, as in this vehicle. The two-tone interior of the test vehicles I drove in October were, in my estimation, more attractive.
What doesn't work for me, as it doesn't for my colleagues, is the fact that the navigation system is operated solely by a remote control device. I remain confounded by the decision to forgo an in-dash controller--what an odd choice. I do like that the rear seats fold completely flat, making for a very spacious cargo hold, although I didn't have occasion to take advantage of all that space during my time with the XC60. Driving this crossover isn't exactly a scintillating experience, but then again, it's a crossover, not a sports car. Power delivery from the turbo in-line six is quite smooth, but fuel economy is pretty disappointing at just 18 mpg (combined EPA rating). Last but not least, the City Safety system (which brakes the car at speeds up to 19 mpg to avoid collisions) is quite impressive. I had a chance to test the system at the vehicle's launch, but it's not something anyone should try out on public roads. It's one of those features that you can't appreciate until it comes into use, which makes it hard to evaluate during a short test such as this. However, owners of the XC60 will surely be enamored of it should it ever be needed.
Amy Skogstrom, Managing Editor


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Gissy Dances in The City
This photo was shot on film. Taken by lawypop with a Lomo LC-A+ (available in our Online Shop) loaded with Expired Kodak Ektachrome 64 film in Singapore. These tags describe this photo: xpro, mx, double, cross_process, silhouette, girl, dance, night, city, and lc-a. Date: 2011-04. Time: Night. This photo can also be found in the album Dancing in the City.Please login to get more out of this site
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