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text:
This Merecedes A-Class is a very good car for the price. It is small (easy to park) but has a very good engine (1.9-litre). This is not only powerful but is also very economical and it delivers around 40 miles per gallon. Inside the car, you will notice that there is quite a lot of room for a car that seems too small to be in production. The A-class ranges from just £13,500 to nearly £19,000. The 1.9-litre A-Class has a 0-60 time of 8.8 seconds and is very quick and nippy on the road. All of these features came with my car: Adjustable steering rake Alarm Alloy Wheels Anti-lock brakes Central Locking Driver's airbag Electric mirrors Electric rear windows Electric sunroof Heated mirrors Immobiliser Leather seats Locking wheel nuts Passenger airbag Power steering Radio Remote central locking Seat height adjust. Seatbelt pretensioners Side airbags Side impact bars Split-fold rear seats Traction control The leather seats are an excellent addition to my car and I think they are extremely comfortable. Insurance costs are low as well and this car is only Insurance Group 8! Now everybody can own a Mercedes......The merc is a very good car, handles well, looks good, is easy to park, is easy to park, is very good to look at, is extremely cheap, for the less affleunt pocket (people who can't afford 'proper' Mercedes). It drives like a dream, and is great for all you stingy cheapskates out there!
I think the Mercedes-Benz A-class is a cracking wee car. However, I do think it is a bit onthe small side. So I'm relieved to tell you that they have just brought a new longer A-class out. This new longer A-class sticks to the clever packaging of the original but it now has seven inches extra. You may be thinking whats the big deal its only seven inches. However, this now gies the car so much more leg room in the back that it has more leg room than the S-class saloon. All you diesel buyers that the A170 CDI common rail engine has been uprated from 90 to 95 bhp, improving the acceleration yet keeping the high economy. Petrol engines have remaied as before. To cope with the old problems the car had when it kept toppiling over they have improved the electronic stability programme, ESP, has been linked up with the Brake assist system to optimize braking force in emergency situations. Safety has become a big aspect of the A-class as well as the engine which will fold and slide under the seats in the event of a front impact. As well as this driver and front passengers are also protected by front and side airbags and window airbags are an option. The air conditioning has also been improved, it now has a dew point sensor. What's that I hear you cry. Well its a thing you switch on when humidity reaches a certain level. Sorry thats all I know about that but you get the idea. Minor changes have have also beenmade to the exterior of the A-class. Contoured Bumpers, protective strips,and clear lamp covers . Inside they have used softer materials on the re-designed dashboard. All in all the A-class is a great little car from those great, big dealers Mercedes.

subset: commoncrawl


text: Follow the dual boot video and you will not only get a better install, you will gain a small amount of command line knowledge and more importantly you will see the part where you went wrong. Whats happened is you are trying to execute lilo from the disc which does not work. You need the chroot command to get into your hard disk you just installed. Again do the dual boot video on the wiki. It was made by backtracks core developer. Anyone who doesn't do it that way is not to smart in my opinion


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User of Windows & Apple Mac Vulnerable to Potential Threat
Sophos security experts issued a warning for businesses using Apple Macs and Windows to take recommended actions in view of Microsoft's revelation that critical vulnerabilities have been found in its software, as reported by InfoZine on May 14, 2008.
As usually Microsoft releases patches on "Patch Tuesday" every month, this month also it released several bulletins for six vulnerabilities found in its software. The patches released for bugs found in Microsoft Office (both Mac versions and Windows), Microsoft's security products Windows Live OneCare, Microsoft Windows, Microsoft Antigen, Microsoft Forefront Security and Microsoft Windows Defender.
The researchers revealed that these antispyware and antivirus prod...
» SPAMfighter News - 22-05-2008
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Journey to Mecca
|Journey to Mecca
Promotional movie poster for the film
|Directed by
|Bruce Neibaur
|Produced by
|Taran Davies
Dominic Cummingham-Reid
Jonathan Barker
|Written by
|Carl Knutson
Bruce Neibaur
Tahir Shah
|Chems-Eddine Zinoune
Hassam Ghancy
Nabil Elouahabi
Nadim Sawalha
|Narrated by
|Ben Kingsley
|Music by
|Michael Brook (original)
|Afshin Javadi
Ghasem Ebrahimian
Rafey Mahmood
|Distributed by
|SK Films
National Geographic
Release date
Running time
|45 minutes
|United States
|$13 million[1]
Journey to Mecca: In the Footsteps of Ibn Battuta[2] is an IMAX ("giant screen") dramatised documentary film charting the first real-life journey made by the Islamic scholar Ibn Battuta from his native Morocco to Mecca for the Hajj (Muslim pilgrimage), in 1325.
The 20-year-old Muslim religious law student Ibn Battuta (1304–1368),[3] whose full name was Abu Abdullah Muhammed Ibn Abdullah Al Lawati Al Tanji Ibn Battuta,[4] set out from Tangier, a city in northern Morocco, in 1325, on a pilgrimage to Mecca, some 3,000 miles (over 4,800 km) to the East. The journey took him 18 months to complete and along the way he met with misfortune and adversity, including attack by bandits, rescue by Bedouins,[5] fierce sand storms[4] and dehydration.[5]
Ibn Battuta spent a total of 29 years travelling and covered 75,000 miles[5] (117,000 kilometres)[4] before he finally returned home.[5] He travelled "further than any writer before him [...] covering most of the known world",[6] through Africa, Spain, India, China and the Maldives.[5]
On Ibn Battuta's return the Sultan of Morocco requested that he relate his experiences, and this was to become what the Saudi Gazette referred to as "one of the world's most famous travel books", the Rihla (Voyage).[4][5]
Film synopsis[edit]
With narration by Ben Kingsley, the film, which is "bookended" by scenes from the contemporary Muslim pilgrimage,[5] chronicles the first 18-month-long leg of Ibn Battuta's journey, to Mecca.[1][5] It was filmed in Morocco and Saudi Arabia in English and Arabic, with Berber in the background.[5]
On the way to Mecca, riding alone on horseback,[5] Ibn Battuta was held up by bandits, robbed and nearly killed, but when the leader of the bandits realized that he was a pilgrim, feeling ashamed, he offered to escort Ibn Battuta to Egypt (for a fee). It was a difficult journey by camel across the desert and they were faced with fierce sandstorms,[4][5] before taking to boats to navigate the Nile.[4] Reaching Egypt, he handed a letter given to him by a friend to a Sheikh, and based on a Hadith (an oral tradition) of the Prophet Muhammed, he was advised "to seek knowledge to China", hence his further extensive travels.[5]
Ibn Battuta had intended to continue his journey to Mecca by sea, via the port of 'Aydhab on the Red Sea,[7] but war and the dangers that posed made him travel by land through Damascus instead, joining a 10,000-strong caravan of fellow pilgrims along the way,[7] staying with them until they finally reach their destination, Mecca.[5]
Leading actor[edit]
According to The Jakarta Post, "The lead, Chems Eddine Zinoun, was born in 1980 in Casablanca [Morocco] and studied classical ballet and the piano. He died in a car accident on 11 Nov. 2008 in Casablanca, where he lived. His portrayal of Ibn Battuta shows a depth of feeling that will remain with audiences long after watching Journey [to Mecca]."[7]
Big Movie Zone described the film's genre as docudrama,[8] whilst a review at that site, remarking that it was the most unusual giant screen film the reviewer had yet seen, called it "a biopic guised as a documentary".[9]
According to a review on the National Post in Canada, the IMAX format is best suited to the vast landscapes which Ibn Battuta crossed and less so for the close-ups and market places. As for the Hajj itself, this has been described as "stunning footage". The reviewer writes that "Journey to Mecca succeeds best in capturing the wonder, pageantry and beauty that are the hallmarks of any religion's central celebration. Though it is arguably impossible to catch an image of the Almighty on film, this doc comes as close as any."[4]
Ann Coates, reviewing the film at Big Movie Zone, stated that with very little narration, unlike other giant screen productions, this helps the dramatic portrayal of Ibn Battuta and "his dangerous trek".[9] Ross Anthony, also reviewing at BMZ, is of the opinion that the early special effects are nice and moody, though the desert is barren and unappealing. However, "once in Mecca, the images shine." The reviewer finds the acting "very good for the format".[10]
Bruce Kirkland of Sun Media in Canada described Journey to Mecca as a "beautifully wrought film ... meticulously researched ... everyone, no matter their faith, should see it".[11] Trade Arabia in the UAE wrote: "A powerful, larger than life cinematic experience that has the power to educate both young and old. Its message of tolerance and respect will resonate strongly with audiences."[12] The Detroit Free Press in the USA said: "...dramatic desert landscapes ... unprecedented access to the Great Mosque ... breathtaking aerial views ... a cosmic experience";[12] and Nick Meyer wrote in The Arab American News that the film was a "... Breathtaking ... Beautiful, inspiring (story) with many visual delights ... Highly recommended."[12]
Martina Zainal of The Jakarta Post writes that "the photography is stunning and takes us to dizzying heights over grand scenes, and directors of photography Afshin Javadi, Ghasem Ebrahimian and Rafey Mahmood have helped show us a side of Islam that is rarely seen in today's news. It is a film worth seeing by Muslims and non-Muslims alike."[7]
The film has even received positive reviews in Jewish publications. For example, Anthony Frosh and Rachel Sacks-Davis not only praised the "breathtaking" cinematography in the Jewish journal Galus Australis, but also wrote "Whilst Ibn Battuta's 14th century Hajj was much closer in time to us than our biblical forefathers, his experience of travel was surely much closer to theirs. The isolation, danger and vulnerability that marked his journey surely also marked theirs. And the spiritual gifts that so explicitly mark the journeys of our forefathers are also implicit in Ibn Battuta's Journey to Mecca." Jews Witness the Hajj
The film was officially endorsed by Saudi Arabian Prince Turki bin Faisal Al Saud al-Faisal, the youngest son of the late King Faisal, former Director General of the kingdom's Al Mukhabarat Al A'amah (General Intelligence Presidency (G.I.P.)), former ambassador to the United Kingdom and Ireland, and former ambassador to the United States[13] who wrote, "Not only does the film represent an accurate and respectful portrayal of Islam, it provides a wonderful opportunity for Muslims to celebrate a revered hero in Ibn Battuta and to honor our faith."[1]
Journey to Mecca won Le Prix Du Public Most Popular Film at Le Géode Film Festival, Paris, 2009,[7][14] and a prize at the Tribeca Film Festival in New York City.[7]
See also[edit]
- Hajj
- Ibn Battuta
- Le Grand Voyage ( French film )
- ^ a b c McNeil Jr., Donald G. (2009-02-13). "The Long, Dusty Trek Toward Tolerance". New York Times. Retrieved 2009-08-27.
- ^ Staff. "Journey to Mecca". Cosmic Picture. Retrieved 2008-09-23.
- ^ Byrne, Joseph Patrick (2004). The Black Death (Greenwood Guides to Historic Events of the Medieval World). Greenwood Press. p. 131. ISBN 0-313-32492-1. Annotated edition (September 30, 2004). See google book search.
- ^ a b c d e f g Knight, Chris (2009-02-05). "Journey to Mecca: Spiritualizing your Imax experience". The National Post. Retrieved 2009-08-27.[dead link]
- ^ a b c d e f g h i j k l m Khan, Fouzia (2009). "Journey to Mecca". Saudi Gazette. Archived from the original on 2011-07-16. Retrieved 2009-08-27.
- ^ Wolfe, Michael (1998). One thousand roads to Mecca: Ten Centuries of Travelers Writing about the Muslim Pilgrimage. Grove Press. p. 51. ISBN 0-8021-3599-4.
- ^ a b c d e f Zainal, Martina (2009-06-30). "IMAX film 'Journey to Mecca' proves to be enlightening". Jakarta Post. Retrieved 2009-08-27.
- ^ Staff (2009). "Journey to Mecca: In the Footsteps of Ibn Battuta". Big Movie Zone. Retrieved 2009-10-03.
- ^ a b Coates, Ann (2009-03-23). "BMZ Review: Journey to Mecca: In the Footsteps of Ibn Battuta". Big Movie Zone. Retrieved 2009-08-27.
- ^ Ross, Anthony (2009-03-26). "BMZ Review: Journey to Mecca: In the Footsteps of Ibn Battuta". Big Movie Zone. Retrieved 2009-08-27.
- ^ Kirkland, Bruce (Sun Media) (2009). "Doc a 'Journey' of faith: Documentary Journey to Mecca chronicles the sacred Hajj". jam! showbiz at www.canoe.ca. Retrieved 2009-08-27.
- ^ a b c Staff (2009). "Journey to Mecca - a Giant Screen Film: Reviews". Giant Screen. Retrieved 2009-08-27.
- ^ Reuters (2006). "Embassy official: Saudi ambassador to U.S. resigns". cnn.com. Archived from the original on 2006-12-20. Retrieved 2006-12-12.
- ^ Staff (2009). "Journey to Mecca - a Giant Screen Film: Home". Giant Screen. Retrieved 2009-08-27.
External links[edit]
- 2009 films
- 2009 in Islam
- 2000s documentary films
- 2000s drama films
- American films
- Arabic-language films
- English-language films
- Docudramas
- Film scores by Michael Brook
- Films about Islam
- Films based on actual events
- Films based on non-fiction books
- Films set in the 14th century
- Films set in Damascus
- Films set in Egypt
- Films set in Saudi Arabia
- Films shot in Morocco
- Films shot in Saudi Arabia
- National Geographic Society films
- Travelogues


text:
News about wildlife often comes across as a litany of catastrophic decline. The startling truth, though, is that we generally succeed when we make the effort to fix a problem, or save a species.
Despite all the outrage and political posturing around the Endangered Species Act, for instance, 90 percent of the species it protects are recovering on schedule. You can see the results of that law, and other federal interventions, almost anywhere. Go to Manhattan's Central Park, for instance, and with a little effort you can now find red-tailed hawks, sharp-shinned hawks and a peregrine falcon doing its 200-mile-an-hour killer dive to pick off a pigeon for dinner. All of these species (except the pigeons) were far less common—and the peregrines were actually endangered—until the federal government passed protective legislation in the 1970s, including a ban on the pesticide DDT. The same laws saved our pelicans, ospreys, herons, cormorants and of course our national bird, the bald eagle.
Now Europe is struggling with the terrible specter of success at species protection. A report out last week by the Zoological Society of London and other conservation groups describes a broad recovery of iconic bird and mammal species across the continent. Gray wolves have recently begun to recolonize southern France (with familiar complaints from livestock farmers). European brown bears have recovered former range not just in Finland and Sweden but also in the Balkan nation of Slovenia. The wild boars for which Lancelot and others went questing in Arthurian legend have lately expanded their range deep into Italy and Germany. White storks, which entered our lore as bringers of babies and good luck, are recovering across southern Europe.
The report attributes this comeback story to laws addressing such mid-20th-century threats as massive overhunting, poaching, poisoning, habitat loss, pollution and the use of certain toxic chemicals, combined with active management techniques like habitat protection and reintroduction of species.
So what's so terrible about success? Critics worry that the focus on flagship species simply masks wider species loss. The report, and the recovery it documents, have neglected European insects, beetles and mollusks, according to Matt Shardlow of the invertebrate conservation group Buglife. For instance, about 15 percent of Europe's dragonflies are now listed as threatened or endangered. Scientists have also warned that more than half of Europe's amphibian species may face extinction over the next 40 years because of climate change, habitat loss and disease.
Writing in The Guardian, other critics worry about the kinds of wildlife protection being promoted. It may sound impressive that 21 percent of European land now has protected status, for instance. But only one percent of the continent is designated as wilderness. The critics doubt that Rewilding Europe, the organization that sponsored the study, aims to expand that wilderness area. Rewilding wants "to cover everywhere with herbivore excrement," warns Mark Fisher of the Wildland Research Institute. "In effect they want to create large-scale, open-air zoos, where herds of livestock and horses can be seen roaming around and eating the life out of the land.
"I can only imagine a sustainable wildlife comeback if there is enough space for animals to live without any (and I mean ANY) extractive use!," Zoltán Kun, of Pan Parks Foundation, added in an email. "No logging, no hunting, no grazing with domestic animals, no fishing, no mining and no biofuel or green energy production."
So what's the takeaway? It's easy for environmentalists to get bogged down in the bickering and pessimism that seem to be our second nature. Despair comes especially easily in the face of climate change. The Koch Brothers and other powerful interest groups spend heavily to instill that spirit of surrender and disparage environmental action of any kind.
But the powerful message in the Zoological Society of London report is that conservation works. "We're trying to find success stories," says Jonathan Baillie, director of conservation at the Society, "so we can learn from them, see what works and scale that up across the conservation movement globally."
We can save elephants in South Africa, tigers in India, rhinos in Sumatra, and amphibians everywhere. It's really just a matter of whether we can muster the will to commit the necessary resources. In the process we can save ourselves. Pausing now and then to reflect on fights we have won is one way to gather the strength we'll need for future battles.
Related stories on TakePart:
• Conservation Conundrum: Should Brazil Clone Endangered Species?
• Conservationists Weasel Endangered Ferrets Back Into the Wild
• Can We All Agree That Horses Should Not Be In Hamburgers?
• 6 of the Strangest Reasons Why Wildlife Is Killed
Original article from TakePart


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Worthing College Exam Portal - 2016/17
Welcome to the Worthing College Student Exam Portal for enrolled students, where you can access your exam results and UMS mark information.
If you require any other information please go to the
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Please enter your surname and PIN into the boxes below, then click 'Identify me.'
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Sunday, January 6, 2013
Test it for yourself
OK.... do not take my word for this. You can see it for yourself.... The politicians in DC patted themselves on the back and claimed to save the middle class from higher taxes. And the President is taking credit. But you can test this for yourself... Simply compare your next paycheck in 2013 to the last one in 2012 and compare all the rates and the amounts. Even check the Social Security rates. I think you will see who is telling the truth and who is playing you like a fool.
1 comment:
You have conflated the not raising of annual income tax rates and the expiration of the Payroll Tax Holiday. Did you give him credit for lowering all payroll taxes the last two year? I bet not. Besides the Payroll Holiday tax was not intended to continue ("Holiday") as it funds Social Security. smhReplyDelete
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Answers Home
» Adoption & Rescue
» Other Adoption & Rescue
Just rescued sweet 4 mo kitten & have spayed/vaccinated to make more adoptable (sadly can't keep.)Please advise:
I've asked everyone I know but noone wants a kitten. Vets will only take if I surrender & will be sent to pound/SPCA. This little girl is too sweet to be put to death (as are they all.) Other suggestions to help her find a home that will appreciate the dear one she is? As I said I paid for exam/shots/spay to help make her more adoptable. I humbly thank you.
Asked by
BooBoo & Romeo
on Oct 24th 2011
in Other Adoption & Rescue
- Cast your vote for which answer you think is best!
You should look for private "no kill" rescues in your area. You can check for them on www.Petfinder.com (on the left hand side there is a box that says "find animal welfare groups") and then contact them to see if they can help you find a home for the kitten. You can also create a profile for her here on Catster and mark her adoptable.
Allie answered on 10/25/11. Helpful? / 3
God bless you for caring about this baby. Allie's suggestions are GREAT ones! You can also speak with the shelters in your area and ask for their screening advice. There are very sick and cruel people out there who present themselves as wonderful adopters and you need to know how to spot them. If this kitten is black, try to hold onto it until the first week of November. Do not give her away for free. Since you have invested so much time and money into her, if it were me, I would ask at least $20 for her. You can also list her with these shelters with the understanding that you will "foster" her until a suitable adoptive family is found. Good luck and many purrs!
Izadore (Izzie) answered on 10/25/11. Helpful? / 2


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Presentation Date:
Wednesday, May 16, 2012
Peter Gallon, University Professor, Harvard University
Over the last fifty years, high-energy physics collaborations have grown from a handful of physicists in the 1940s, through dozens in the 1960s to hundreds in the 1980s, and now, in one of the most extraordinary association of scientists, to several thousand scientists on each of two experiments at CERN. At each stage of expansion, scientists have been painfully aware of how, fundamentally, credit and attribution were in flux. In this discussion, I analyze just what this struggle has yielded, and what the entity is that produces the results of these collaborations. When one of these CERN experiment like ATLAS announces a result, who, or what, is speaking?


text:
The Murdoch "Climate"
Blog ››› ››› ERIC BOEHLERT
Like a getaway bandit trying to lighten his load, Rupert Murdoch keeps making frantic sacrifices in hopes of containing the phone-hacking scandal that's now consuming his News Corp media empire.
Last week, Murdoch closed down his News of the World tabloid, and today News Corp announced it was giving up its bid to acquire BSkyB satellite television; a crowning acquisition that three weeks ago looked like a done deal.
From News Corp. today:
News Corporation ("News Corp") announces that it no longer intends to make an offer for the entire issued and to be issued share capital of British Sky Broadcasting Group PLC ("BSkyB") not already owned by it.
Chase Carey, Deputy Chairman, President and Chief Operating Officer, News Corporation, commented: "We believed that the proposed acquisition of BSkyB by News Corporation would benefit both companies but it has become clear that it is too difficult to progress in this climate.
"This climate," of course, is the wonderfully understated way of referencing the storm that's raging all around Murdoch. Last week I noted the News Corp. chief was in free fall and with no way to stop or even to slow down the run-away scandal story. This week, we need to come up with a new phase for free fall because Murdoch's descent has only accelerated and his options for halting it have decreased even further.
So no, the political "climate" is not good for Murdoch, and his hopes of owning BSkyB have now been dashed. But there's another "climate" in play and it's one that Murdoch for decades has had a great deal of control over, and that's the climate of fear and falsehoods and hysteria and smear campaigns that have routinely been carried out in Murdoch's name via his print, online and television outlets.
The there-are-no-rules "climate" that's now sinking Murdoch, his business, and his legacy is part of a signature media environment he fermented in which guidelines were optional and so was common decency.
And that "climate" isn't restricted to Britain. Just ask Kevin Jennings about how Murdoch's team operates, or Frances Fox Piven, or Supreme Court Justice nominee Sonia Sotomayor, or the Obama White House, or scores of other Fox News smear victims who have had to face off against Murdoch's minions.
I doubt they stress the notion of karma inside the News Corp. executive suites. And I doubt Murdoch's top media earners lose much sleep thinking about the kind of dreck they profit off of. But with the phone-hacking scandal now poised to do lasting damage to News Corp, the Murdoch "climate" has unleashed a very powerful storm.
- Network/Outlet
- News Corp.
- Person
- Rupert Murdoch
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Curlies of South Florida
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Join Date: Aug 2007
Posts: 236
Friday, May 23, 2008 at 01:38PM
I would have loved to join you, but it's not a good day for me. Some people drive crazy on that day, and I am still recovering from recent incident from a week ago.
3a brunette, medium texture and density.
CG since 5/16/2008.
Growing out an eeevil
haircut with 4 layers on the left side and 6 layers on the right side.
Currently using: Aubrey Organics' White Camelia, Glycogen Protein Balancing Conditioner and Island Naturals for co-wash. Alternating My Honey Child's : Caribbean Curling Creme, Honey Guava Balm, and Coconut Milk; and Moptop's Gel on top for styling.
Location: Boca Raton, FL


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Indulge your senses and taste the finest wines Italy has to offer!
Personalized tours of the best Italian wine regions
A Wine Tour in Italy is one of the best ways to discover the true essence of the country- the idyllic wine roads and castles of Tuscany and Piemonte, the haute cuisine of Lombardy, the romance and Villas of the Veneto, the delightful fishing villages on the Ligurian and Amalfi Coasts, etc. Cellar Tours offers private ultra-luxury wine vacations in the most beautiful regions of Italy, with an emphasis on wine tasting and dining.
We organize unbelievable Luxury Italian Honeymoon's, and extra special tours for anniversaries and special occasions. Here are a few of our most special sample Italian wine tours (all tours are available upon request, for you and your private group of 2 person minimum).
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New Elexio Media Center Release Improves Church Website Visitor Experience
As more churches become dependent on their church websites to deliver current information and media such as sermon podcasts, image collections, and relevant documents, Elexio has taken steps to enhance and improve the Media Center within its church website content management system (CMS), Amp Vibe, to empower churches with the best website tools available.
With website traffic now coming in from a variety of devices including smartphones and tablets, church websites need to have fluid web design that scales according to the device a person is using. The system has an improved intuitive design with more usability along with social media integration that will streamline church communication. Additional features also include customizable organization features and enhanced search capabilities.
This new version of the Elexio Media Center for our church website CMS provides the latest in design and necessary tools to equip today's church. Its use of fluid design adapts to your platform of choice, while enhanced search and media organization continues to show Elexio's innovative approach to church software," comments John Connell, marketing director for Elexio.
Elexio Amp Vibe church website CMS includes unlimited storage, bandwidth, blogs, calendars, password protected areas, audio and video blocks, slideshows, photo galleries, email, opt-in/opt-out email lists, RSS syndication, and much more.
Amp is a fully-integrated suite of church technology solutions. Just imagine having your website, database, mobile app, small group software, mass communication, donations, event registrations, check-in system and more all working together as one.
Amp Vibe Church Website Demo Video
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Elexio continues to provide the most intuitive and appealing solutions for church websites and church management software around the world. With an integrated set of products that focus on the local church's web presence, complete membership management, contributions, mobile, check-in, and much more, insight into your congregation and community are no longer a mystery. To learn more, please visit www.elexio.com or call toll free: 888.997.9947.


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Ya'll know how much I love garlic, right? It is truly one of my kitchen staples. What would dinner be with out garlic??!!
One of next loves is Parmesan cheese. And if you put them together…you have a match made in heaven. For.real.
My family loves wings but it isn't something I typically make at home. I decided to try and make a version of a baked garlic and Parmesan chicken wing we just love. And it was a success!
They are so easy and yummy. Seriously. My kids eat a ton of them.
Wings are also a great Trim Healthy Mama dish. A nice, solid S. We serve our wings with a side of homemade ranch and chopped up veggies.
To make your life easier in the kitchen, if you work with a lot of garlic, I love this (affiliate link) garlic twist. It makes mincing so nice and much easier to clean than my garlic press. (Which I also love)
I am not a fan of large kitchen messes, so to make this super easy to clean, I place foil in my baking dishes. The grease drips down on the foil and I can just throw it away. I use these (affiliate) racks to put the chicken on because they fit in my 9X13 pans.
If you have the same affection for garlic and parm as me, you should go try this recipe! (It's the most popular on the blog.)
Are you on Pinterest? I post lots of gluten free and Trim Healthy Mama recipes.
Do you enjoy wings? What is your favorite flavor?
- 5 pounds of chicken wings, thawed
- 1 stick of butter
- 6 cloves of minced garlic
- ¼ cup of parm cheese
- salt
- Heat oven to 450
- Line pans with aluminum foil and place a baking rack in pans.
- Place wings skin sized down and lightly salt
- Bake until for about 30 minutes
- Turn the oven up to 500 and flip the wings.
- Bake until the skin is crispy about 20 more minutes
- While the wings are cooking, melt the butter,add the garlic and let simmer for a few minutes.
- Add the parm cheese and stir in.
- When the wings are done, put in pan with butter mixture and coat well.
- Take and let sit a few minutes and serve.
This post is shared at Kelly the Kitchen Kop's Real Food Wednesdays and Recipes to Nourish for Savoring Saturdays.


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Chevy Cobalt Forum / Cobalt Reviews / Cobalt SS / Cobalt Parts (http://www.yourcobalt.com/forums/)
- Problems and Service (http://www.yourcobalt.com/forums/problems-service/)
- - Fuse for Hazards (http://www.yourcobalt.com/forums/problems-service/26550-fuse-hazards.html)
Fuse for Hazards
Driving home one night in the rain my friend decided to turn on the hazard lights... Once i noticed i quickly pushed the button to turn them off. But they didnt turn off. So i took apart the dash and just unplugged the switch. Is there any fuse I can take out that is connected to something i do not need? Because there is not a fuse for the hazards unless i completely missed it. I really don't want a circular hole in my dash without the hazard button. I figured it would be easier just to take a fuse out.
pull the fuse for turn signals. that should tell you. i would guess its that one.
Just get a new switch can't be that much and you already have the other one out so why not just replace it. I'm sure you can pull one out of a junk yard for just a few bucks.
id start by checking the switch. the problem is probably there if your turn signals work properly. like viper said, shouldnt be that expensive. maybe a pita to take out though. hopefully not a bcm problem. you could take it to a dealership and have them scan the bcm for codes first i guess.
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April 3, 2012
Art students, art leaders, administrators and anyone interested in the arts is welcome to attend "Artist Day," a free regional artist networking forum, on Wednesday, April 4, from 10 a.m. to 5 p.m. at the Graceful Arts Center in downtown Alva.
Those interested in attending should reserve a spot soon by contacting Ken Kelsey, director of the Alva Regional Hub of the Oklahoma Arts Council's Regional Arts Network and adjunct instructor in art and humanities at Northwestern Oklahoma State University, at firstname.lastname@example.com or (580) 603-0103.
Kelsey said that those attending the forum will learn the following:
• Learn how to "Photograph Your Work" with Kelsey Karper from OVAC;
• Hear about "Successful Art Making in Oklahoma" during a panel discussion featuring artists from OKLA – Oklahoma Lady Artists;
• Gain valuable information regarding grants, artist rosters, professional development opportunities, networking support and more with Molly O'Connor from the Oklahoma Arts Council and Karper.
The day's events will end with a reception Graceful Arts Gallery and Studios where those attending can connect with fellow artists, view Oklahoma artworks and enjoy substantial hors d'oeuvre.
Questions about the forum also may be directed to O'Connor at firstname.lastname@example.com or (405) 521-2025.
MISSION STATEMENT: Northwestern Oklahoma State University provides quality educational and cultural opportunities to learners with diverse needs by cultivating ethical leadership and service, critical thinking and fiscal responsibility.


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Even if you still have a VCR to play them, your tapes are probably beginning to degrade. You want to preserve those home movies, but how? Convert them to DVDs. Numerous commercial services will do this for about $20 per tape (check the yellow pages under Video), or you can convert the cassettes yourself — which isn't nearly as daunting as it sounds.
True do-it-yourselfers can transform old tapes using a video capture card in conjunction with Windows Movie Maker (included with Vista, free download for XP <www.microsoft.com/windowsxp/downloads/updates/moviemaker2.mspx>) or other video-editing software. You install the card, hook up your VCR or camcorder to it, use the software to import the movie, then convert the footage to a format you can burn to DVD. Mac users can follow the steps at <www.macworld.com/article/30972/2004/05/fromvhstodvd.html>.


text: NEW YORK, April 11, 2012 /PRNewswire/ -- BlackArrow, a worldwide provider of advanced advertising solutions for New Television platforms, today announced new capabilities of the BlackArrow Advanced Advertising System that enable service providers to work with programming networks to expand the sale, placement and measurement of dynamic advertising insertion across IP and traditional pay-TV platforms. The BlackArrow enhancements, Ad Router technology and a Business Suite of software tools, allow service providers to offer programmers an expanded menu of options to control and manage their ad inventory. The new products enable the use of third-party ad systems, or the BlackArrow Campaign Suite, for fulfillment of programmers' national ads across a service provider's multiple platforms. Moreover, the enhanced BlackArrow system enables pay-TV business models and affiliate agreements that already exist between service providers and programmers to be extended across new video delivery platforms. The Ad Router, a component of the BlackArrow Decision Suite, is designed to reside at the operator's data center and control and mediate all real-time advanced advertising workflows, including ad routing requests that are based on various platforms and inventory owners. The Ad Router allows operators to send national and local ad avails to different Ad Decision Services (ADS), enabling programmers and local sales organizations to use their existing campaign tools for real-time ad fulfillment. The Ad Router also can route ad requests from different platforms to different ADSs, streamlining cross-platform consistency for operators in business policies, reporting and measurement. The BlackArrow Business Suite enables programmers to manage metadata and avails, or placement opportunities, against their content. Programmers can specify how ad loads change through programming windows, such as the key C3 measurement timeframe, can gain visibility into asset availability at the operator plant, and can dynamically remove or replace "baked in" ads in on-demand content without having to re-pitch assets.


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Star-Banner readers share their opinions on Marion's heritage, marijuana and Obamacare among other issues.
Destroying heritage
With regard to Marion County's future, there are many good people here in Ocala and environs who are lately very concerned about a few ignorant and greedy developers and land speculators who have no interest in Ocala's unique geology, or its past and present glory in farming and the horse industries, or the growing future of equestrian sports in Marion County.
Marion County's very recent fever, among a few local developers, to convert rolling fields, family-owned farms and open spaces into suburban-like, multifamily environments, is in reality an ongoing push that has been activated by a few clever men who can only think in terms of their own future wealth.
Unfortunately, such a plan would also ensure that urban growth would become the priority, and beautiful open spaces and rolling hills full of young horses and all of the accompanying businesses that serve the horse industry will become a thing of the past.
Might this be the year that the county commissioners try to put the final nail into the coffin that contains the remnants of what used to be a thriving equestrian community? And why would they do that?
It's simple, really: because they think they can make more money for themselves if they do.
They need to be stopped.
Susan Woods
Voting on euphoria
Marijuana is a drug! According to the dictionary, it induces "euphoria." Think of all our young enjoying "euphoria."
Had I had known of the condition of "euphoria" when I was a young man, then I would have been into other vices or narcotics to enhance my life. Who knows how different it would have made me?
At least today I believe my life has been as good as intended, based on my upbringing, education, health, hard work and integrity.
So now, I am against any form of legalization of any drug or stimulant such as marijuana, now being brought up as a referendum for public vote.
Think of it, do we really need "euphoria"?
Hank Stevens
A game changer
I have worked in acute care hospitals for almost 24 years, of that in respiratory therapy for 18 years. I have been a respiratory therapist in acute care hospitals for 16 years.
I am writing in response to the opinion given by the director of trauma surgery at UF Health Shands ("With trauma center, more does not mean better," Jan. 26). I am not involved in the financial, administrative or any political aspects of my organization. I am a husband, father, son and proud resident of Marion County.
I am shocked that such an educated physician would make the statements that I read in the paper Sunday. I can testify that Ocala Regional Medical Center has profoundly changed since our inception as a provisional trauma center. To say that the care for our families and neighbors at local area hospitals is equal with the same results is simply inaccurate and untrue.
I have not just worked at ORMC. I have worked at Munroe Regional Medical Center, Seven Rivers and at Citrus Memorial. The changes at ORMC include new policies, procedures, staff, equipment and new specialty physicians.
I believe that care also includes the loved ones. To have a local facility treat patients with some of the brightest and most skilled physicians I have ever worked with in my 24 years is a blessing to the loved one who now does not have to commute 50 to 80 miles to be at the bedside.
The paradigm shift at my hospital is amazing. The care is not the same as it was two years ago.
I do not believe what the director of trauma surgery at Shands wrote is accurate.
I have witnessed a local community hospital change and rise exponentially above other local community hospitals simply because of the trauma status and the brilliant skilled physicians, policies, staff improvements, equipment, education and too many other variables to list.
Jason Barde
How it works
So, let me get this straight, under Obamacare, to insure the uninsured, we make the insured uninsured and then make them pay more to be insured again so the original uninsured can be insured for free?
Ronald Senick
Stick to what is
The writer of the Tuesday letter, "To Obama's critics," provides a classic illustration of why it is virtually impossible to have a meaningful debate with a Barack Obama supporter.
First, he dismisses the letters criticizing President Obama with unsubstantiated prejoratives such as "inaccurate," "hyperactive," and "ridiculous," deems them unworthy of a response and then changes the subject from present-day realities to his own utopian vision of a "very possible article" to be written 10 years in the future.
I have my own opinion of how historians will view the Obama regime, which is vastly different than his, but it is not very informative to debate hypothetical opinions about what the future may or may not hold.
Obama was elected on a promise of "hope and change." His supporters still cling to that empty promise, despite more than five years of harsh reality. They avoid like the plague engaging in any discussion whatsoever of the actual present day real-world consequences of Obama's policies by launching personal attacks against his critics, blaming others and changing the subject from "what is" to what they still hope "will be" at some future time.
Dan Ball
Global Gore
I just saw Al Gore on television giving a talk on global warming. Where the heck is this global warming? I'm freezing!
The only global warming I see is the hot air from Mr. Gore's mouth.
Sheila McCartney


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'The Baddy' is back: Paddy Pimblett to fight at CW88 in October
Liverpudlian star and former Cage Warriors featherweight champion inks new deal with Europe's top promotion
Browse News
CWFC Fight Night 3: Turner v Lahdesmaki
Graham Turner's rise through the featherweight division will encounter a difficult obstacle next month when he takes on Matteus Lahdesmaki at Cage Warriors Fight Night 3.
Watson: I'm still a force
Kyle Watson has told Juha-Pekka Vainikainen to expect the biggest challenge of his career when the pair clash in the main event at CWFC Fight Night 3 on February 11.
CWFC Fight Night 3: Alloway v Chimento
A welterweight bout has been confirmed for Cage Warriors Fight Night 3, with Ben Alloway set to take on Mauro Chimento in Beirut on February 11.
Juha-Pekka vows to deliver
Juha-Pekka Vainikainen insists he won't be daunted by the prospect of taking on a UFC veteran in next month's CWFC Fight Night 3 main event in Beirut.
CWFC 45: Mortimore v Bengtsson
Cage Warriors can confirm that Jay 'Mean Streak' Mortimore will face Eddy Bengtsson in a heavyweight bout at Cage Warriors 45 at the HMV Forum in London on February 18.
2012: Cage Warriors
With 17 shows in 13 different countries scheduled, here's a little taste of what fans can expect from Cage Warriors over the course of the next 12 months…
CWFC Fight Night 3 main event: Watson v Vainikainen
The main event for Cage Warriors Fight Night 3 in Beirut, Lebanon on February 11 will see two CWFC debutants going head-to-head.
WHOA! TV link up with CWFC
Cage Warriors have teamed up with WHOA! TV, the UK-based MMA lifestyle channel dedicated to news, views and interviews from around the globe.
Gabel enters the fray
Matt Gabel is the latest addition to the line-up for this year's Cage Warriors eight-man middleweight tournament.
Sky Stone and CWFC ink deal
Cage Warriors has continued its rapid expansion by joining forces with one of the world's largest production and entertainment companies.
2012 Schedule
A hectic schedule is on the agenda for Cage Warriors in 2012.
'Crazy Kid' is confident
Brad "The Crazy Kid" Wheeler has dismissed the notion that February's meeting with Norman Parke at Cage Warriors 45 will be the toughest fight of his career to date.
McGregor: I'm too slick
Conor McGregor says he's expecting "a good scrap" with Steve O'Keeffe in their February bout in London, but the Irishman insists he'll be too hot for his opponent to handle.
2012 tournament to crown CWFC Women's champion
A Cage Warriors 125lbs Women's champion will be crowned in 2012 with the organisation set to stage a four-fighter tournament.
Hectic start to 2012
Cage Warriors will continue to increase its global presence next year, kicking off our 2012 schedule by staging five shows in five different countries in the space of just two months.
O'Keeffe aims to impress
Steve O'Keeffe will tackle Conor McGregor in a highly-anticipated featherweight battle at Cage Warriors 45 in February, and the Londoner says the bout has left him feeling more excited than any other has in his professional career to date.
Roberts: I'm the underdog
"I think I'm definitely an outsider but I plan to change that. I'm going to thrive on this opportunity and I'll be ready to beat whoever's put in front of me."
Kyle keen to conquer
"I want to show people that my career is not over and that I'm still relevant in the lightweight picture. I plan on proving that by capturing the Cage Warriors lightweight title next year."
Norman Parke v Brad Wheeler
Brad Wheeler will face one of the toughest challenges of his professional career to date on February 18, 2012 when he takes on highly-rated Irishman Norman Parke in a lightweight clash at Cage Warriors 45 at London's HMV Forum.
Conor McGregor v Steve O'Keeffe
Having been announced as the latest addition to the CWFC 45 card last week, Cage Warriors can confirm that Steve O'Keeffe (5-1-0) will clash with Conor McGregor at the February 18 show at London's HMV Forum.
Search News
CW Merchandise
Recent Videos
Cage Warriors 72: Review
Event: Cage Warriors 72
Date: 13/09/2014
Venue: Newport Centre, Newport, Wales
Cage Warriors 71: Review
Event: Cage Warriors 71
Date: 22/08/2014
Venue: King Hussein Boxing Arena, Amman, Jordan


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Great thread, it'll definitely help me on my "build as cheap as I can" helmet. I have a set of Iwata airbrushes but am never against the use of spray cans.
I piked up almost every color listed here at home depot yesterday and spent about 25 bucks. I already had metallic silver and primer handy. Thanks so much for posting this. Now if I can get some really good headshots so I know what to mask off, I will be doing great!
there are thousands of reference shots in the gallery here. i can't imagine anyone needing more than that
guess I have to dig a little better. Most of what I saw were full costumes, not close ups
OHHHHH, there are OTHER albums!
Problem solved
bout to give this a try as my armor jetpack and gaunts are done and I have left over huntclub and moss green, claret whine, flat black primer silver and blue I think Im gonna spend some more time soaking in paint fumes this week...this might rival the jetpack in difficulty
We have em at work...
got the dome painted and all today...cheeks later
Been searching high and low for Rusto Sage Satin, and having no luck. Some research online seems to indicate that the color is being discontinued. Amazon has a few cans left for an outrageous price. I ordered one, but going forward, I was wondering if there is an equivalent color of a different brand. Thx!
it's always been pretty hard to find. i bought a case of it online a while back for around $50.
that's why i tend to do when i find a color i like... i'll get a dozen cans so that i have enough to go around if it becomes scarce
So far I've been able to find it in gloss at A.C. Moore, and that's it for brick & mortar stores. None at Lowes, Home Depot or Jo-Ann Fabrics (which has a surprisingly good spray paint selection...who knew?)
gloss or satin... either way you'll want to put a flat clearcoat on it.
Nice! I never really favoured the ROTJ myself as I love the 'eyebrow scratch' on the ESB but I really like what you've done with this. Thanks for the list as I'm not too bad with a rattlecan!
To be honest mate, i think the colours are damm near perfect!!
Brilliant job!
just amazing work.
Just bought all these cans from Home Depot and they still carry all the same colors with new updated cans. I had no problems finding the safe green either and was tempted to buy a few extra cans in case anyone needed some here.
Here are the new cans if anyone is interested in what they look like 4 years after this post started!
Last edited by Lostsaint; Dec 18, 2012 at 5:27 AM. Reason: Pic Added
There is a satin sage green...it may not be in the painters touch version which has a different cap ( the sprayer) but there is a satin version...normally found at walmart. Gloss will be glossy...not something you want on the Fett.
dullcote will kill the shine on gloss paint just fine
it's cool that things have come back around. for a while home depot was switching to krylon and this was all going to be useless. but now rustoleum is back!
one note though: you got hunter green, not hunt club green. different color entirely!
Nice catch, I will have to double check to see if they have it. The paint girl was asking me 20 questions a out why I was picking out so many cans. I think when she saw me grab th metallic first, she assumed I was going to be doing a paint huffing marathon or something.
Do you have a cap top picture so I can try an match to a similar color.
By the way, I picked up the dullcote and here is a pic for anyone interested...
Hunter green for the rear panels is correct...Hunt Club is for the armor...STG is getting old.


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The Victorian period was a magical time. Telephones, electrical lighting, cameras and even the first automobiles all came into the public's consciousness during this era of prosperity and technological advancement. Indeed, the speed and frequency with which inventions and discoveries appeared prompted people to wonder what other weird and fantastical things could be just around the corner. It was a time when it seemed anything was possible, and for some the lines between science, spiritualism and magic were blurred. This was a mind-set that magicians of all kinds took advantage of, including those skilled in mentalism – the art of demonstrating seemingly supernatural mental powers. It was to become the golden age of mentalism, and one in which some of the most creative and flamboyant characters ever to read minds or muscles would reach stratospheric heights of fame and fortune.
7) Stuart Cumberland
Born with the name Charles Garner, Stuart Cumberland enjoyed such success as a mentalist that a key part of contact mind reading is sometimes also known as Cumberlandism. The Englishman was a 'thought reader' who accomplished his theatrical feats by closely studying his subjects' 'facial expressions and muscular tensions.' It was by using this early knowledge of a phenomenon known as the ideomotor effect that Cumberland's muscle reading flourished.
With his act, he traveled throughout Europe and drew much acclaim for his talents. He was adept at discerning secret words (sometimes in languages he didn't even know) and locating hidden objects with what seemed like lightning speed, and he performed for Oscar Wilde, Andrew Carnegie and other great names of the era. He could even pinpoint physical pains and ailments known only to the sufferer. One quote describes him as able to "do all that Mr. Bishop [Washington Irving Bishop, a later entry in this list] ever professes to do without the fuss."
As a journalist and author, he also penned a newspaper and several books concerning mentalism and the techniques he used to help spot fraudulent mediums and phony psychics. More than one of his contemporaries came under attack (including Washington Irving Bishop) from Cumberland for claiming to possess a supernatural extra-sensory perception. He himself was one of the few mentalists who never claimed to have any kind of psychic powers whatsoever, attributing his extraordinary powers of insight entirely to muscle reading.
6) Samri S. Baldwin
Inspired by the Davenport Brothers' cabinet routine, Baldwin began his career as a stage magician, but it would be as a mentalist that he would achieve his greatest fame. Born Samuel Spencer Baldwin in Cincinnati, Ohio, he assumed the moniker "The White Mahatma" and formulated a double act with his first wife Clara (and later with his second, Kitty). He brought to the stage a trick well-known by the era's fraudulent mediums called the sealed envelope (or question and answer) act in which he would discern the answer to secret questions thought up by his audience members and sealed in envelopes. He might even have predated Harry Houdini's famous handcuff escape tricks on stage with an escape routine of his own.
He traveled the world with his routine and, despite insisting that his talents were very much of this earthly realm (he even authored the book Spirit Mediums Exposed in 1879), he was nonetheless regarded by many audiences as a genuine psychic. Alas, he is little remembered today.
5) Anna Eva Fay
The diminutive Anna Eva Fay was heralded as one of the 'greatest mind-reading phenomena' of her century. After beginning her career as a spiritualist medium, she later switched to mentalism and became a famous and much celebrated performer of the art. Unlike Cumberland she wholeheartedly claimed no less than a psychic ability to peer into her audience's minds and extract whatever information she so desired. This supernatural skill, she claimed, was gleaned from a time when she resided in Burmah, India and was trained by a 'high priest' there.
"The High Priestess of the Mysterious Mysteries", as she was billed, or "The Indescribable Phenomenon", mastered such tricks as the dancing spirit handkerchief, 'somnolency', the rapping hand, and even pulled off a levitation or two. Her shows drew large crowds that numbered in the several thousands and, like one of mentalism's first performers, J. Randall Brown (more below), she baffled the men of science who studied her. Even the venerated magician J. N. Maskelyne, with whom she fell out, admitted that she was "a fascinating little blonde."
One of Houdini's closest friends, Fay became an honorary member of that prestigious club The Magic Circle of London in an age when women were not even allowed to join. Fay revealed some of her secrets to Houdini upon her retirement.
4) J. Randall Brown
It was an American named J. Randall Brown who first brought mentalism to a nationwide audience by incorporating it into his stage shows as 'mind-reading'. Brown combined his childhood knowledge of the Victorian pastime called the Willing Game with his familiarity of séances to become an early pioneer of mentalism. He expanded upon the techniques used in the Willing Game with one of his favorite signature acts, in which the audience was enlisted to nominate one of their number to act as an imaginary murderer, another to be his victim, and to identify something to act as a murder weapon – all while Brown was out of the room. The Celebrated Brown, as he became known, would then return to the theater with a flourish, grasp the wrist of one of the audience and promptly discern all three nominations amid bemused gasps. Although it would seem that he was leading the audience member to the murderer, victim and weapon, it was in fact the other way around: Brown was 'reading' the minute muscular movements in the unwitting accomplice's wrist using the contact mind-reading techniques that Cumberland became so adept at.
But perhaps Brown's most amazing feat was the national excitement he managed to induce. He was tested under 'scientific conditions' by the eminent American neurologist, Dr. George M. Beard. Just as the recent advances with electricity had created amazing, almost magical results that reached tangibly into everyday people's lives, so the public's interest in Brown, Beard and mentalism became a brief fervor, as knowledge of the performer's talents generated a feeling that telepathy was a real and imminent skill. This excitement was captured and expounded by the media attention surrounding Beard's work, and Brown's fascinating abilities led him to even greater fame.
3) Washington Irving Bishop
No list of Victorian mentalists would be complete without the inclusion of Washington Irving Bishop. Bishop noticed the media attention and public enthrallment that J. Randall Brown enjoyed and craved the same for himself. A flamboyant and colorful figure with an oscillating career, Bishop learned Brown's secrets (some sources say he became his assistant for a time) and was soon making his own headlines. His career would eclipse even Brown's and would also culminate in a mysterious demise.
Perhaps Bishop's most celebrated spectacle took place in New York. On the morning of March 5th 1887 he gathered a large crowd of people outside Hoffman House, and from the throng a 'committee of gentleman upon whom no suspicion of confederacy can be claimed' was selected to aid Bishop in his endeavor. After entreating the watching crowd for an object, a lady volunteered her medallion pin, and the 'committee' was given 30 minutes to secrete the pin anywhere in the city within a one mile radius of the Hoffman. Bishop then allowed himself to have cotton wool bound over his eyes using a large handkerchief and a black sack placed over his head before being helped into a two-horse buggy. The returned committee of gentlemen, having executed their task, also climbed into the buggy, and two of them were attached to Bishop with a few feet of thin wire tied around their wrists.
Despite being blindfolded, Bishop was doing the driving. In what must have been a white-knuckle ride for the committee, the buggy and its passengers sped down 25th Street, Madison Avenue and 23rd and 4th Streets until Bishop finally pulled his horses up. The crowd had followed from the Hoffman with interest and now waited expectantly as Bishop was helped down to ground level. Still blindfolded and attached to the two gentlemen, Bishop walked shakily to the Gramercy Park Hotel and entered the lobby. Advancing through the reception he approached a bronze, sculpted figure and upon lifting the statuette, triumphantly produced the medallion pin, much to the crowd's wonder and delight. The blindfolded buggy drive was continued in more modern times by the British mentalist David Berglas using a car.
2) Alexander
While not quite reaching the height of his fame until shortly after the Victorian era, Alexander's exploits deserve an honorable mention. Born in 1880, Claude Alexander Conlin – "The Man Who Knows" – specialized in mentalism and 'telepathy'. Easily recognizable by his Oriental-style costume and feathered turban, he set attendance records across North America and became the highest-paid mentalist in the world, accruing a fortune of over $4 million.
He would ask audience members to write questions on pieces of paper before sealing them in envelopes. There seemed no possibility that Alexander could see the questions. Then, employing what he insisted were his considerable powers of telepathy, he would answer each of the secret questions in rapid succession. Although it has now been suggested that he used the 'one ahead' method (using sleight of hand to read the supposedly secret messages), nobody could figure out how he accomplished such feats of startling mentalism during his lifetime. It has even been suggested that his ample turban might have hidden an early use of wireless radio!
1) The Zancigs
A husband and wife double act called The Zancigs concocted a 'spectacularly successful' mentalist routine. Billed as "Two Minds with but a Single Thought", Agnes Zancig would sit blindfolded on stage, while her husband Julius would meander through their audience, plucking or receiving objects from the onlookers sat around him. Julius would hold aloft each item and simply ask Agnes to identify it, which she did – unfailingly. Personal effects, bus tickets, serial numbers, words, names – anything the audience could think of – would all be correctly named by the blindfolded Agnes Zancig. There were no accomplices in the audiences and no holes in Agnes's blindfold – she really couldn't see anything at all. But then she didn't have to, for The Zancigs were actually employing an extremely complicated code, undetectable to outsiders and still regarded to this day as 'the most dauntingly complex two-person communication system of its type ever devised.'
Together, the Zancigs had developed a vast list of simple, varying questions, each one paired with a letter of the alphabet, number or name. Once memorized, Julius merely had to match the question to the object and Agnes match the object to the question. So confident were they of their 'thought transmission' routine that they offered $100 to anybody whose name they could not detect. From their beginning as childhood sweethearts in Copenhagen, Agnes and Julius would take their act around the world and enjoy a unique success which lasted thirty years.


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HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.
Guinevere Q. Lee, Nina Orlova-Fink, Kevin Einkauf, Fatema Z. Chowdhury, Xiaoming Sun, Sean Harrington, Hsiao-Hsuan Kuo, Stephane Hua, Hsiao-Rong Chen, Zhengyu Ouyang, Kavidha Reddy, Krista Dong, Thumbi Ndung'u, Bruce D. Walker, Eric S. Rosenberg, Xu G. Yu, Mathias Lichterfeld
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB). In monocyte-derived macrophages, URMC-099 induction of autophagy led to retention of nanoparticles containing the antiretroviral protease inhibitor atazanavir. These nanoparticles were localized within macrophage autophagosomes, leading to a 4-fold enhancement of mitochondrial and cell vitality. In rodents, URMC-099 activation of autophagy led to 50-fold increases in the plasma drug concentration of the viral integrase inhibitor dolutegravir. These data paralleled URMC-099–mediated induction of autophagy and the previously reported antiretroviral responses in HIV-1–infected humanized mice. We conclude that pharmacologic induction of autophagy provides a means to extend the action of a long-acting, slow, effective release of antiretroviral therapy.
Divya Prakash Gnanadhas, Prasanta K. Dash, Brady Sillman, Aditya N. Bade, Zhiyi Lin, Diana L. Palandri, Nagsen Gautam, Yazen Alnouti, Harris A. Gelbard, JoEllyn McMillan, R. Lee Mosley, Benson Edagwa, Howard E. Gendelman, Santhi Gorantla
Current strategies for HIV-1 eradication require the reactivation of latent HIV-1 in resting CD4+ T cells (rCD4s). Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. In purified rCD4s from HIV-1–infected individuals on antiretroviral therapy, rapamycin treatment downregulated markers of toxicity, including proinflammatory cytokine release and cellular proliferation that were induced after potent T cell activation using αCD3/αCD28 antibodies. Using an ex vivo assay for HIV-1 mRNA, we demonstrated that despite this immunomodulatory effect, rapamycin did not affect HIV-1 gene expression induced by T cell activation in these rCD4s. In contrast, treating activated rCD4s with the immunosuppressant cyclosporin, a calcineurin inhibitor, robustly inhibited HIV-1 reactivation. Importantly, rapamycin treatment did not impair cytotoxic T lymphocyte (CTL) recognition and killing of infected cells. These findings raise the possibility of using rapamycin in conjunction with T cell–activating agents in HIV-1 cure strategies.
Alyssa R. Martin, Ross A. Pollack, Adam Capoferri, Richard F. Ambinder, Christine M. Durand, Robert F. Siliciano
Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.
Anjie Zhen, Valerie Rezek, Cindy Youn, Brianna Lam, Nelson Chang, Jonathan Rick, Mayra Carrillo, Heather Martin, Saro Kasparian, Philip Syed, Nicholas Rice, David G. Brooks, Scott G. Kitchen
Despite the efficient suppression of HIV-1 replication that can be achieved with combined antiretroviral therapy (cART), low levels of type I interferon (IFN-I) signaling persist in some individuals. This sustained signaling may impede immune recovery and foster viral persistence. Here we report studies using a monoclonal antibody to block IFN-α/β receptor (IFNAR) signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. We discovered that effective cART restored the number of human immune cells in HIV-1–infected hu-mice but did not rescue their immune hyperactivation and dysfunction. IFNAR blockade fully reversed HIV-1–induced immune hyperactivation and rescued anti–HIV-1 immune responses in T cells from HIV-1–infected hu-mice. Finally, we found that IFNAR blockade in the presence of cART reduced the size of HIV-1 reservoirs in lymphoid tissues and delayed HIV-1 rebound after cART cessation in the HIV-1–infected hu-mice. We conclude that low levels of IFN-I signaling contribute to HIV-1–associated immune dysfunction and foster HIV-1 persistence in cART-treated hosts. Our results suggest that blocking IFNAR may provide a potential strategy to enhance immune recovery and reduce HIV-1 reservoirs in individuals with sustained elevations in IFN-I signaling during suppressive cART.
Liang Cheng, Jianping Ma, Jingyun Li, Dan Li, Guangming Li, Feng Li, Qing Zhang, Haisheng Yu, Fumihiko Yasui, Chaobaihui Ye, Li-Chung Tsao, Zhiyuan Hu, Lishan Su, Liguo Zhang
A rare subset of HIV-1–infected individuals is able to maintain plasma viral load (VL) at low levels without antiretroviral treatment. Identifying the mechanisms underlying this atypical response to infection may lead to therapeutic advances for treating HIV-1. Here, we developed a proteomic analysis to compare peripheral blood cell proteomes in 20 HIV-1–infected individuals who maintained either high or low VL with the aim of identifying host factors that impact HIV-1 replication. We determined that the levels of multiple histone proteins were markedly decreased in cohorts of individuals with high VL. This reduction was correlated with lower levels of stem-loop binding protein (SLBP), which is known to control histone metabolism. Depletion of cellular SLBP increased promoter engagement with the chromatin structures of the host gene high mobility group protein A1 (
Ming Li, Lynne D. Tucker, John M. Asara, Collins K. Cheruiyot, Huafei Lu, Zhijin J. Wu, Michael C. Newstein, Mark S. Dooner, Jennifer Friedman, Michelle A. Lally, Bharat Ramratnam
In HIV-1–infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1–infected patients. Compared with healthy controls, untreated HIV-1–infected patients have an increased population of proliferating, granzyme B+, CD8+ T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1–infected patients correlated with circulating CD8+ T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which predicts disease progression in untreated HIV-1–infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linked to increased morbidity and mortality in treated patients.
Souheil-Antoine Younes, Michael L. Freeman, Joseph C. Mudd, Carey L. Shive, Arnold Reynaldi, Soumya Panigrahi, Jacob D. Estes, Claire Deleage, Carissa Lucero, Jodi Anderson, Timothy W. Schacker, Miles P. Davenport, Joseph M. McCune, Peter W. Hunt, Sulggi A. Lee, Sergio Serrano-Villar, Robert L. Debernardo, Jeffrey M. Jacobson, David H. Canaday, Rafick-Pierre Sekaly, Benigno Rodriguez, Scott F. Sieg, Michael M. Lederman
Current antiretroviral therapy (ART) is not sufficient to completely suppress disease progression in the CNS, as indicated by the rising incidence of HIV-1–associated neurocognitive disorders (HAND) among infected individuals on ART. It is not clear why some HIV-1–infected patients develop HAND, despite effective repression of viral replication in the circulation. SIV-infected nonhuman primate models are widely used to dissect the mechanisms of viral pathogenesis in the CNS. Here, we identified 4 amino acid substitutions in the cytoplasmic tail of viral envelope glycoprotein gp41 of the neurovirulent virus SIVsm804E that enhance replication in macrophages and associate with enhanced antagonism of the host restriction factor BM stromal cell antigen 2 (BST-2). Rhesus macaques were inoculated with a variant of the parental virus SIVsmE543-3 that had been engineered to contain the 4 amino acid substitutions present in gp41 of SIVsm804E. Compared with WT virus–infected controls, animals infected with mutant virus exhibited higher viral load in cerebrospinal fluid. Together, these results are consistent with a potential role for BST-2 in the CNS microenvironment and suggest that BST-2 antagonists may serve as a possible target for countermeasures against HAND.
Kenta Matsuda, Chia-Yen Chen, Sonya Whitted, Elena Chertova, David J. Roser, Fan Wu, Ronald J. Plishka, Ilnour Ourmanov, Alicia Buckler-White, Jeffrey D. Lifson, Klaus Strebel, Vanessa M. Hirsch
The rare patients who are able to spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants that underlie this response, we characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. HIV controllers from the ANRS CODEX cohort showed a highly skewed TCR repertoire that was characterized by a predominance of
Daniela Benati, Moran Galperin, Olivier Lambotte, Stéphanie Gras, Annick Lim, Madhura Mukhopadhyay, Alexandre Nouël, Kristy-Anne Campbell, Brigitte Lemercier, Mathieu Claireaux, Samia Hendou, Pierre Lechat, Pierre de Truchis, Faroudy Boufassa, Jamie Rossjohn, Jean-François Delfraissy, Fernando Arenzana-Seisdedos, Lisa A. Chakrabarti
Macrophages have long been considered to contribute to HIV infection of the CNS; however, a recent study has contradicted this early work and suggests that myeloid cells are not an in vivo source of virus production. Here, we addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. We were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. To determine whether tissue macrophages are productively infected, we used 3 different but complementary humanized mouse models. Two of these models (bone marrow/liver/thymus [BLT] mice and T cell–only mice [ToM]) have been previously described, and the third model was generated by reconstituting immunodeficient mice with human CD34+ hematopoietic stem cells that were devoid of human T cells (myeloid-only mice [MoM]) to specifically evaluate HIV replication in this population. Using MoM, we demonstrated that macrophages can sustain HIV replication in the absence of T cells; HIV-infected macrophages are distributed in various tissues including the brain; replication-competent virus can be rescued ex vivo from infected macrophages; and infected macrophages can establish de novo infection. Together, these results demonstrate that macrophages represent a genuine target for HIV infection in vivo that can sustain and transmit infection.
Jenna B. Honeycutt, Angela Wahl, Caroline Baker, Rae Ann Spagnuolo, John Foster, Oksana Zakharova, Stephen Wietgrefe, Carolina Caro-Vegas, Victoria Madden, Garrett Sharpe, Ashley T. Haase, Joseph J. Eron, J. Victor Garcia
The recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS.
Rikke Olesen, Michael D. Swanson, Martina Kovarova, Tomonori Nochi, Morgan Chateau, Jenna B. Honeycutt, Julie M. Long, Paul W. Denton, Michael G. Hudgens, Amy Richardson, Martin Tolstrup, Lars Østergaard, Angela Wahl, J. Victor Garcia
Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non–AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4+ T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21–treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.
Luca Micci, Emily S. Ryan, Rémi Fromentin, Steven E. Bosinger, Justin L. Harper, Tianyu He, Sara Paganini, Kirk A. Easley, Ann Chahroudi, Clarisse Benne, Sanjeev Gumber, Colleen S. McGary, Kenneth A. Rogers, Claire Deleage, Carissa Lucero, Siddappa N. Byrareddy, Cristian Apetrei, Jacob D. Estes, Jeffrey D. Lifson, Michael Piatak Jr., Nicolas Chomont, Francois Villinger, Guido Silvestri, Jason M. Brenchley, Mirko Paiardini
Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell–mediated clearance of HIV-1–infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity–mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected–patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.
Julia A.M. Sung, Joy Pickeral, Liqin Liu, Sherry A. Stanfield-Oakley, Chia-Ying Kao Lam, Carolina Garrido, Justin Pollara, Celia LaBranche, Mattia Bonsignori, M. Anthony Moody, Yinhua Yang, Robert Parks, Nancie Archin, Brigitte Allard, Jennifer Kirchherr, JoAnn D. Kuruc, Cynthia L. Gay, Myron S. Cohen, Christina Ochsenbauer, Kelly Soderberg, Hua-Xin Liao, David Montefiori, Paul Moore, Syd Johnson, Scott Koenig, Barton F. Haynes, Jeffrey L. Nordstrom, David M. Margolis, Guido Ferrari
Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting antibacterial immunity, maintaining epithelial barrier function, and supporting tissue repair. ILC3 alterations are associated with chronic inflammation and inflammatory disease; however, the characteristics and relevant regulatory mechanisms of this cell population in HIV-1 infection are poorly understood due in part to a lack of a robust model. Here, we determined that functional human ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1 infection in this model depletes ILC3s, as observed in chronic HIV-1–infected patients. In HIV-1–infected mice, effective antiretroviral therapy reversed the loss of ILC3s. HIV-1–dependent reduction of ILC3s required plasmacytoid dendritic cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade of these prevented HIV-1–induced ILC3 depletion in vivo and in vitro, respectively. Finally, we determined that HIV-1 infection induces CD95 expression on ILC3s via a pDC- and IFN-I–dependent mechanism that sensitizes ILC3s to undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated apoptosis.
Zheng Zhang, Liang Cheng, Juanjuan Zhao, Guangming Li, Liguo Zhang, Weiwei Chen, Weiming Nie, Natalia J. Reszka-Blanco, Fu-Sheng Wang, Lishan Su
Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1–transmitting mothers and 165 propensity score–matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1–infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3–specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.
Sallie R. Permar, Youyi Fong, Nathan Vandergrift, Genevieve G. Fouda, Peter Gilbert, Robert Parks, Frederick H. Jaeger, Justin Pollara, Amanda Martelli, Brooke E. Liebl, Krissey Lloyd, Nicole L. Yates, R. Glenn Overman, Xiaoying Shen, Kaylan Whitaker, Haiyan Chen, Jamie Pritchett, Erika Solomon, Emma Friberg, Dawn J. Marshall, John F. Whitesides, Thaddeus C. Gurley, Tarra Von Holle, David R. Martinez, Fangping Cai, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Raul Louzao, Samantha Wilkes, Saheli Datta, Marcella Sarzotti-Kelsoe, Hua-Xin Liao, Guido Ferrari, S. Munir Alam, David C. Montefiori, Thomas N. Denny, M. Anthony Moody, Georgia D. Tomaras, Feng Gao, Barton F. Haynes
Several HIV envelope-targeting (Env-targeting) antibodies with broad and potent neutralizing activity have been identified and shown to have unusual features. Of these, the PG9 antibody has a long heavy chain complementarity determining region 3 (HCDR3) and possesses unique structural elements that interact with protein and glycan features of the HIV Env glycoprotein. Here, we used the Rosetta software suite to design variants of the PG9 antibody HCDR3 loop with the goal of identifying variants with increased potency and breadth of neutralization for diverse HIV strains. One variant, designated PG9_N100FY, possessed increased potency and was able to neutralize a diverse set of PG9-resistant HIV strains, including those lacking the Env N160 glycan, which is critical for PG9 binding. An atomic resolution structure of the PG9_N100FY fragment antigen binding (Fab) confirmed that the mutated residue retains the paratope surface when compared with WT PG9. Differential scanning calorimetry experiments revealed that the mutation caused a modest increase in thermodynamic stability of the Fab, a feature predicted by the computational model. Our findings suggest that thermodynamic stabilization of the long HCDR3 in its active conformation is responsible for the increased potency of PG9_N100FY, and strategies aimed at stabilizing this region in other HIV antibodies could become an important approach to in silico optimization of antibodies.
Jordan R. Willis, Gopal Sapparapu, Sasha Murrell, Jean-Philippe Julien, Vidisha Singh, Hannah G. King, Yan Xia, Jennifer A. Pickens, Celia C. LaBranche, James C. Slaughter, David C. Montefiori, Ian A. Wilson, Jens Meiler, James E. Crowe Jr.
Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs.
Gregory M. Laird, C. Korin Bullen, Daniel I.S. Rosenbloom, Alyssa R. Martin, Alison L. Hill, Christine M. Durand, Janet D. Siliciano, Robert F. Siliciano
Pierre-Alexandre Bart, Yunda Huang, Shelly T. Karuna, Samuel Chappuis, Julien Gaillard, Nidhi Kochar, Xiaoying Shen, Mary A. Allen, Song Ding, John Hural, Hua-Xin Liao, Barton F. Haynes, Barney S. Graham, Peter B. Gilbert, M. Juliana McElrath, David C. Montefiori, Georgia D. Tomaras, Giuseppe Pantaleo, Nicole Frahm
Heme oxygenase-1 (HO-1) is an inducible, detoxifying enzyme that is critical for limiting oxidative stress, inflammation, and cellular injury within the CNS and other tissues. Here, we demonstrate a deficiency of HO-1 expression in the brains of HIV-infected individuals. This HO-1 deficiency correlated with cognitive dysfunction, HIV replication in the CNS, and neuroimmune activation. In vitro analysis of HO-1 expression in HIV-infected macrophages, a primary CNS HIV reservoir along with microglia, demonstrated a decrease in HO-1 as HIV replication increased. HO-1 deficiency correlated with increased culture supernatant glutamate and neurotoxicity, suggesting a link among HIV infection, macrophage HO-1 deficiency, and neurodegeneration. HO-1 siRNA knockdown and HO enzymatic inhibition in HIV-infected macrophages increased supernatant glutamate and neurotoxicity. In contrast, increasing HO-1 expression through siRNA derepression or with nonselective pharmacologic inducers, including the CNS-penetrating drug dimethyl fumarate (DMF), decreased supernatant glutamate and neurotoxicity. Furthermore, IFN-γ, which is increased in CNS HIV infection, reduced HO-1 expression in cultured human astrocytes and macrophages. These findings indicate that HO-1 is a protective host factor against HIV-mediated neurodegeneration and suggest that HO-1 deficiency contributes to this degeneration. Furthermore, these results suggest that HO-1 induction in the CNS of HIV-infected patients on antiretroviral therapy could potentially protect against neurodegeneration and associated cognitive dysfunction.
Alexander J. Gill, Colleen E. Kovacsics, Stephanie A. Cross, Patricia J. Vance, Lorraine L. Kolson, Kelly L. Jordan-Sciutto, Benjamin B. Gelman, Dennis L. Kolson
The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1–specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor–mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one
Shuying S. Li, Peter B. Gilbert, Georgia D. Tomaras, Gustavo Kijak, Guido Ferrari, Rasmi Thomas, Chul-Woo Pyo, Susan Zolla-Pazner, David Montefiori, Hua-Xin Liao, Gary Nabel, Abraham Pinter, David T. Evans, Raphael Gottardo, James Y. Dai, Holly Janes, Daryl Morris, Youyi Fong, Paul T. Edlefsen, Fusheng Li, Nicole Frahm, Michael D. Alpert, Heather Prentice, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Merlin L. Robb, Robert J. O'Connell, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, M. Juliana McElrath, Daniel E. Geraghty


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- Fits Glock 26, 27, 28, 33 pistols
- 3/4" thick suede lined Cordura pad. Secures with adjustable Velcro strap
- Attaches to left ankle for right handed draw (right hand models)
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- Rubberized paddle provides extra stability and increased comfort
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At least this time around, Motorola is quicker in releasing the Wi-Fi versions of the Motorola XYBOARD 8.2 and 10.1 – and in fact, pre-orders are now readily available for them. If you're seriously intent on picking either of these two Wi-Fi only tablets, you can actually head on over to Motorola's web site right now to place you pre-order for them.
In terms of pricing, the Motorola XYBOAD 8.2 will set you back $399.99, while the 10.1 model will go for an additional $100 more at $499.99. Fortunately, it seems as though Motorola did some homework this time around, because they priced the tablets at under the established golden price of $500, which is something we normally expect with most top-notch tablets.
Rather than being forgotten, we're certain that these two XYBOARDs are going to compete very well against the competition. And considering they'll be upgradeable to Ice Cream Sandwich down the road, there are absolutely no reasons why you shouldn't pick either of them. As it stands, if you place your pre-order right now, you can expect delivery sometime during the week of January 23rd.
source: Motorola via PocketNow