text:
cyber-rabbit by ZoonoidWatch
©2012-2015 Zoonoid
Another cyborg
its the psycho bunny guys from bioshock 1!!!! only cyborg-ized... evil yet cool
Great work! It looks so cool
this is so good
awesome stuff !
That's one adorable cyborg
The most kick ass bunny rabbit I have ever seen! If this was Bugs Bunny I'd want to see more! "Whats up doc!?" lol
I love the way you take all the most pertinent aspects of each animal -and build a character out of it. They are so masculine and bad-ass...
very nice i would love to see these characters in video games very badass games if you ask me.
very good details
this one is killer!! nice textures and render!!
Damn he's cool
reminds me of the clay fighter series
man, your new stuff is just a new level of art.. really impressive!!!!
incredible rendering and wonderfull textures... how many time do you spent on a drawing like this??? have you got some tips for this sorts of textures ?
solid!!, beautiful design!
Just... DAMN!
I discover your work, So I think it's just incredible, how do you create this textures?
Thank you on hi res image great details too.
Briareos' long-lost brother..hehe This is badass!
Can we see higher resolution please? This is really nice.
Wow! great details!!
It's been a while. Lookin good, Frank.
Battle bunny, love it! = )
Im in love with this concept man! Its so cool and proportional besides the muscular arms that u intentionally made that way....anyway im so jealous, great job
Awesome work. But I feel like, as a rabbit/hare type creature, its legs should be way more muscular/accentuated than its arms? Just seems slghtly top-heavy for an animal that is pretty much all leg.
Eh... What's up, Doc?
Stunning rendering and cool design!
how to do this 。。。。OMG
Freaky-cool design
это ахуенно... +100
just f***g very great awesom!
I'm ready for a "Jumping Flash" reboot
this is amazing
this is awesome and funny for several reasons.
Очень качественная работа! Здорово!
This amazing!!!!!!!!
Fantastic. I really like the eye sockets.
блин как ты так сделал?) круть
Ништяк!!! очень детально и чётко) молодец!!!
Awesome cyborg dude!
Looks freaking sleek, but powerful --!
Looks freaking sleek, but powerful --!
Чёрт побери, вот это материалы! о_о
I wish we could sit down and do some art lessons together. I would pay you over my professors any day. Keep knocking them out of the park! You're something to aspire to.


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AR2015's four-day program will feature more than 140 presenters from 80 organizations representing virtually all sectors of our movement. These presenters will appear in seven plenary sessions (bringing all attendees together), and more than 75 breakout sessions, configured along several concurrent tracks. In each time slot, you can choose the session that best fits your needs and interests:
Additionally, here are some other program highlights you won't want to miss:
View the detailed schedule here (with a few last-minute changes likely).
All sessions are recorded, and the recordings will be available for purchase.

subset: commoncrawl


text:
2000 Toyota Tundra • 191,000 miles
My truck is missing so I took it to Auto Zone and run a scan. It said that there was a misfire on number six cylinder. What do I need to do to correct this.
Phillip Hightower
January 6, 2013.
January 6, 2013.
Possible causes are compression, plug, wire/coil, vacuum leak or injector or wiring failure.
Plugs are the easiest to try.
Plugs are the easiest to try.
Jan 6, 2013.
Jan 6, 2013.
I have a 1996 Saturn SL1. The engine has a misfire and alternates between running fine for a few weeks and then running rough for a few weeks. When the car is running rough it has less ...
3 answers • 1996 Saturn SL1 • 183,173 miles
Can a compression test be done if engine will not turn? Car will not start. Mechanic wants to tow car to his workshop and have compression checked. All parts under bonnet have been ...
2 answers • 2000 Ford Ranger
In completing a dry compression test my results were as follows: 1 - 140 2 - 10???? 3 - 100 4 - 170 I repeated the test twice cranking the car for 5 seconds on each cylinder...
7 answers • 1996 Toyota Paseo • 165,000 miles
I just started the car and put it in drive and took off when i heard a puff noise and the car stalled. no it wont turn over. everything electrical works but it sound like no compression...
2 answers • 1998 Plymouth Breeze • 100,000 miles


text:
The Lap-Band Surgery is a minimally invasive laparoscopic medical method to get rid of chronic obesity. It involves surgically implanting a device inside the body. The device consists of a hollow silicone band, tubing, and an access port. This procedure takes from 20 to 30 minutes in the operating room and is considered one of the least invasive of the bariatric procedures performed in Mexico.
Lap Band Surgery is very effective:
A person who is willing to undergo the surgery must have a Body Mass Index (BMI) of at least 35, or a BMI of at least 30 with one or more unhealthy physical conditions, or at least 100 pounds over his / her estimated ideal weight.
During lap band surgery or gastric banding, a band is placed around the upper part of the stomach. This separation physically reduces the size of the stomach to hold very small quantity of food.
The restricted opening between the stomach pouch and the rest of the stomach controls the speed of food that passes from the pouch. This minimizes the amount of food that can be eaten at a time; and also takes more time to digest whatever food you have eaten.
This surgery also gives the option to increase or decrease the pouch size as per your need by inflating or deflating the hollow lap-band; thereby controlling the opening and the speed of food passage.
The passage can be made wider by deflating the lap band. This causes the food to pass more quickly. This adjustment is made possible by adding or removing the fluid inside the hollow lap band through a small button-like part called access port that is placed under the skin in a muscle in the chest wall. This access port is connected to the lap-band by tubing.
Obesity Solutions in Tijuana and Cancun Mexico are world leaders in Gastric Band (lap band) procedures and our surgical team are considered one of the top ten teams in the world for this procedure. Our Chief Surgeon Dr. Sergio Verboonen is not only one of the most qualified lap band surgeons he is also considered one of the most qualified.
Lap band surgery either in Cancun or Tijuana will help you lose weight and get rid of chronic obesity. The results are very encouraging. It has been reported that after three years of the surgery the average weight loss was 36% of a patient's excess weight. About 50% of the person lost at least one fourth of their excess weight and some results have shown the loss of over 75%.
This advance option has many benefits that include:
This surgery is very safe and has very minimal mortality risk compared to other obesity surgeries that are more invasive. It does not affect nutritional intake.
It allows for adjustments without another additional surgery. It is very helpful during pregnancy as it allows increase intake size needed for extra nutrition. It also facilitates adjustments suitable to each individual.
The best feature of Lap Band Surgery is that it is reversible. The Gastric Band can be removed any time and stomach generally restores its original shape.
This surgery is very suitable for the people looking for long term weight loss. It maintains over 50 percent of excess weight loss for the five years after surgery.


text:
Hukanui Primary School
Welcome to our website! Our school is located in the city of Hamilton in the North Island of New Zealand. Enjoy exploring our website and finding out about all the exciting learning happening at our school. Check out our honey bees under the Education for Sustainability menu!
" A leading learning environment maximising people's potential. "
HOT NEWS! - REMINDERS .... and direct links
NEW MATHS BLOG. Test yourself, can you solve today's problem?
Remember to check the events calendar on the menu to the left for all upcoming events this term.
Click on Facebook to view current photos.
More About Us:
We have around 700 fantastic children and 50 staff members who are passionate about learning and help make our school an exciting place in which to be. We set high achievement standards for learning in Literacy and Numeracy and teach to individual needs to help each child to achieve success in these areas. We also look to develop in children the skills and attributes that will help them be life long learners.
We identify and look to develop the gifts and talents in all our children through innovative programmes and a flexible curriculum that provides for personalised learning pathways. We value partnership with our parents and the wider community. We celebrate learning successes and regularly share our learning with our community and with wider audiences.To find out more about our learning priorities and programmes. Our Learning Priorities
We are a Green Gold Award winning Enviro school and welcome visitors who have an interest in the issue of sustainability. Click on the Sustainable Education menu button to find out about our history and our current student projects.
We also welcome international students to our school and provide for English tuition with qualified staff. International Students
We believe Hukanui School is a place where all members of our community can grow as learners. Our vision is that we are......
" A leading learning environment maximising people's potential. "
Enjoy our website
David Mossop


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UConn Stops Crimson Nine in NCAA Playoff
In baseball pitching is supposed to be 75 per cent of winning, and by the time the Harvard baseball team
Batmen Nip Cornell For EIBL Title
All season long Crimson coach Loyal Park and his players have been talking about the Harvard baseball team's ability to
Thomas Thinks Confidence and Unity Will Help Batmen Return to Omaha
Mike Thomas has been Harvard's third baseman for three years, and during that time the team has won 78 games
Batmen Prepare for EIBL Play-off
The Harvard baseball team beat Northeastern yesterday, 7-6, to win the BGL championship. The Crimson plays at Springfield today, but
Crimson Nine Could Win Championship Today
The Greater Boston League baseball title is on the line today when Harvard hosts Northeastern at Soldiers Field at 3
McGugan's Hot Batting, Fleet Feet Make Him a Likely Pro Draft Pick
In the top of the fifth in Sunday's game against Princeton, the score was tied, 3-3, Tim Bilodeau on first,
Crimson Ends EIBL Season Tied for First
The regular season of the Eastern League closed with a photo finish yesterday as Harvard and Cornell capped three-game winning
Batmen Need Four Straight to Take EIBL
Boston College scored seven runs in the fourth inning yesterday, and then coasted the rest of the way behind the
Batmen Play at B.C. Today; Crimson Near League Crown
The Harvard baseball team will play a GBL game at Boston College today at 4 p.m., before moving into the
The Papal Bull
Back then the Yankee tradition meant something, and we won the pennant by seventeen games that year. We had good
Diamondmen Beat Soggy Crusaders
For 7 1/2 innings yesterday the Harvard baseball team prevailed against hostile elements and the uninspired opposition of Holy Cross,
Crimson Nine Lose Lead With Split
Harvard's hitters produced more runs over the weekend than they had in the seven previous EIBL games this season, and
Batmen Face Crucial Series Against Cadets and Big Red
The Harvard baseball team embarks upon the most important weekend of its season today, and thanks to the rain which
Split With Penn Moves Batmen Into EIBL Lead
The Harvard baseball team took over first place in the EIBL on Saturday by splitting a doubleheader with Penn while
Crimson Nine Face Navy and Penn
Tied with Brown for the Eastern League lead with a 3-1 record, the Harvard baseball team has an opportunity to


text:
Caterpillar SARL LLC
|Caterpillar SARL LLC Patent applications
|Patent application number
|LOCKING MECHANISM FOR LIFT ARM ASSEMBLY - A locking mechanism adapted for use with a lift arm assembly. The lift arm assembly is connected to and operatively associated with a lift actuator for movement between raised and lowered positions. The lift actuator having a tubular body and an extendable rod. The locking mechanism includes a lockbar having a proximal end and a distal end opposite to the proximal end. The proximal end is configured to be pivotally connected to the lift arm assembly and movable between an inoperative position and an operative position to selectively prevent retraction of the rod within the tubular body of the lift actuator. The locking mechanism further includes a release lever pivotally connected at the distal end of the lockbar and is adapted to move between a rest position and a working position.


text: Posted 24 Feb 2014 · Report post Hey guys, I am on my second pack & second week of Ortho-Tri-Cyclen BC (brand name, not generic). Hm, well...the first month I seemed to do okay (not great, but not any worse or any better)--however, this could be b/c I was already on a different type of BC (Lutera) and it allowed for an easier transition, perhaps? Anyways, this second month...is either the same or worse. I have big cysts along my jawline, on my chin, some on my cheeks, and on the sides of my forehead. I know everyone says to give it a full 3 months, which I intend to do...I just wanted to hear if anyone had any personal stories regarding this BC. Did it take you a full 3 months to even notice anything good was happening? 6? I just want to know if I do see any positive effects from this pill, roughly when will it happen. Also, I'm pretty sure I have PCOS, and I am getting tested for it this week. If that's the case, I'm maybe going to ask for Spiro. Thanks guys! P.S. I'm also thinking about creating a log for my experience on this BC (maybe pictures included?), would anyone be interested in this? I've been searching and have found NO consistent logs with this BC. If no one answers yay or nay, I may just do it for my own progress anyways. In the same vein, does anyone know of any logs with pictures? Share this post Link to post Share on other sites


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Blowing Rock Vacation Packages
From Blowing Rock, the city of Charlotte is approximately 80 miles (129 kilometers) to the southeast.
Blowing Rock isn't the only spot in this popular region worth experiencing; visitors with plenty of time can also hit the road and discover the unique qualities of the nearby scenery, communities and cultural attractions. Enjoy the Appalachian State University and Daniel Boone Native Gardens in Boone, 6 miles (10 kilometers) distance from Blowing Rock. In addition, you could stop by the Lees-McRae College and Banner House Museum in Banner Elk. It is 11 miles (18 kilometers) from Blowing Rock.
While you are here in Blowing Rock, visit Hickory. Approximately 35 miles (56 kilometers) to the southeast, this regional city is where you can find Catawba Science Center, L. P. Frans Stadium and Hickory Museum of Arts. Hickory Metro Convention Center and Valley Hills Mall are just a few of the many other visitor attractions in Hickory.
If you believe a great holiday is pushing yourself to the limit in the great outdoors, then sign up for one of the hiking and zip-lining adventures the area around Blowing Rock has to offer. Why not have a go at some winter activities while you are here? Snowboarding is an idea. Another one is skiing.
Even the best vacation can't last forever, so when it's time return home, you'll find the nearest major airport in Tri-Cities, 45 miles (72 kilometers) to the northwest.


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A leading panel of library and publishing experts will provide an update on the library ebook lending market and discuss best ways for libraries to advance library access to digital content at the 2015 American Library Association's (ALA) Annual Conference in San Francisco. The interactive session, "Making Progress in Digital Content," takes place from 10:30 to11:30a.m. on Sunday, June 28, ... Read More »
Tag Archives: PLA
Chairman Wheeler E-rate game #OnPoint
E-rate is nothing if not opportunistic and opportunity struck while hundreds of librarians combed congressional offices during National Library Legislative Day to talk with representatives about funding the Library Services and Technology Act (LSTA) and to support programs for school libraries as well as Net Neutrality and privacy issues. I was able to sneak two away from the Leg Day ... Read More »
Marijke Visser honored with 2015 ALA Staff Achievement Award
The American Library Association (ALA) recently recognized a Washington Office staffer for her successful leadership advocating on behalf of libraries across the country in connection with the FCC's E-rate proceeding. ALA last week awarded Marijke Visser, associate director of the ALA Office for Information Technology Policy (OITP), the 2015 Staff Achievement Award for her work to push for the Federal ... Read More »
Strong coalition calls on libraries to plan now to secure E-rate funding
Libraries now have an extraordinary opportunity to upgrade their broadband following the Federal Communications Commission (FCC) vote to modernize the E-rate program and address the broadband capacity gap facing many public libraries. Today, a broad coalition of library associations, which includes the American Library Association (ALA), calls upon libraries to act to convert this policy win in Washington to real ... Read More »
If you missed it live: E-rate webinar available "Just in Time"
Heading into the home stretch of the 2015 E-rate application cycle, more than 100 librarians put their paperwork (or keyboards) aside to participate in yesterday's E-rate webinar hosted by the Public Library Association (PLA) and the American Library Association's (ALA) Office for Information Technology Policy (OITP). The webinar provided a detailed look at the filing process for the current (2015) ... Read More »


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Made in Chelsea star Ollie Locke: Women reject me because they think I'm gay rather than bisexual
Post your comment
Comments on this article are now closed.
Reader comments
Looking for PR ? Uninteresting –
After having dated for a while a man who not only claimed to be bisexual but also needing both genders as sex partners in his life at the same time (perhaps in order to maintain his label) I can see why. Not everyone wants to be part of a harem. Some people actually want to fall in love with someone they are attracted to.
Be the big man and just open those closet doors to see the light ;-)
He has. He' s bisexual. Get over it.
It's a real shame that bisexuality is still misunderstood. There should be a campaign to make more people aware that it is a REAL sexual orientation in its own right and that there ARE some people who remain bisexual all of their lives and AREN'T seeking to hide their homosexuality as in 'bi now, gay later'.
It's a real shame bisexuality is still so often misunderstood. There should be a campaign by Stonewall and others to try and make more people in society understand it. Of course, it is true that SOME people who are fully gay will say they are bisexual as they are not confident enough to say they are completely homosexual ie 'bi now, gay later' but there are plenty of bisexuals who DO have that genuine sexual orientation and will always have it.
The more openly bisexual men and women that there are who are out to the world the better it will be. Hopefully then more people will come to understand bisexuality.
I suspect the real reason he's rejected is because he's a complete nob.
He doesn't strike me as a nob, though definitely a knob.
Rehan, the spelling "nob" is a recognised variant of "knob".
Is it? How confusing. For some it means someone grand, as in 'noble'.
I've just checked my complete OED, Rehan. It states: "nob, n.4, variant of knob n."
Thanks Eddy – I see even my ancient 1993 complete OED says so too. But for the old-fashioned among us, nob will always mean something different from knob. And the individual in question is, IMO, by no means a nob.
Rehan: yes – it's now common usage, as in, "What a patronising, pedantic nob ….."
Heh. I can see it's common. :-P
A great many people foolishly seek TOTAL SECURITY in all things, including relationships. They reject anything or anyone that may not offer them TOTAL SAFETY. A lot of heterosexual women seek a 100% HETEROSEXUAL man. A stupid desire, of course, because all of us, including those women, exist on a sexual spectrum. None of us is 100% homosexual or 100% heterosexual.
I am "a gay man". I know however that I am not 100% inclined towards members of the same sex. In terms of my relationship I am, but if I were free I know that I have a minor attraction (a very minor attraction) to the opposite sex.
Women reject you because you're a pouting,preening Narcissus.A shame you can't clone yourself and get a date with yourself Ollie.Being bisexual has nothing to do with it
For this self-obsessed chap, all other people offer him is a mirror; he doesn't care whether the mirror is a boy or a girl. It's all variations of self-love.
These comments are un-moderated and do not necessarily represent the views of PinkNews. If you believe that a comment is inappropriate or libellous, please contact us.
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Star Wars Episode 7 - 2015
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November 5 2012, 07:15 AM
The Mirrorball Man
Vice Admiral
Location: Switzerland
Re: Star Wars Episode 7 - 2015
Slurms MacKenzi wrote:
The Mirrorball Man wrote:
I'm sure she is, but it doesn't matter. I'm smart and witty too, but I won't play the villain of a major summer blockbuster movie.
Then I'm not sure what you're getting at.
Just what I said: there's no way she's going to play the main villain or the protagonist.
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Kaspersky Lab informs that the 9th U.S. Circuit Court of Appeals has ruled in Kaspersky Lab's favor in claims brought by Zango.
Kaspersky Lab reveals award winners at its first European Partner Conference, as more than 100 top European channel partners and Kaspersky Lab executives travelled to Tenerife to discuss the conference's theme: "protecting your customers, protecting your margins."
Kaspersky Lab CEO and co-founder Eugene Kaspersky has received the State Prize of the Russian Federation for Science and Technology from Russian President Dmitry Medvedev in the Kremlin.
IT Security firm expands its capacity with environmentally friendly office in Abingdon


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I'm searching for months now a way to separate the discussion section (comments) from the article (in tab).
I know it exist plugin wich allows to separate an article in different tabs, but i did not find a plugin that does such with comments (and "post a comment") :
as theses websites do :
- Afisha.ru
- ThemeForest
- Deezer
This kind of thing :
Article (content) | Comments | Add Review
I have read this post but it does not seems to run a lot, and I'm ready to pay for a plugin or a theme wich allow this.
Does someone know if a theme wich allows this exist ? or a plugin ?
Thank you.


text:
Photo illustration of a young child in a time out.
- Filed Under
During a recent visit by a reporter, 4-year-old Keaton Caraway sneaked into his kitchen and grabbed a bag of Halloween candy and a pair of scissors.
When his mother, Shelly Caraway, took the candy and scissors away, the boy muttered under his breath.
"Shut up, bitch." ...


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Donald McNichol Sutherland, OC (born 17 July 1935) is a Canadian actor with a film career spanning nearly 50 years. Some of Sutherland's more notable movie roles included offbeat warriors in such war... More > movies as The Dirty Dozen, (1967), MASH (1970), and Kelly's Heroes (1970), as well as in such popular films as Klute, Invasion of the Body Snatchers (1978), JFK and Ordinary People (1980). Sutherland is now filming The Hunger Games. He is the father of actor Kiefer Sutherland. This book is your ultimate resource for Donald Sutherland. Here you will find the most up-to-date information, photos, and much more. In easy to read chapters, with extensive references and links to get you to know all there is to know about his Early life, Career and Personal life right away.< Less
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Product Information
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SAVANE Luster Wash Pleated No Iron Slacks
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Are you Nobuo Hanai?Claim your profile
Publications (105)403.9 Total impact
Article: New Sandwich-Type Enzyme-Linked Immunosorbent Assay for Human MxA Protein in a Whole Blood Using Monoclonal Antibodies Against GTP-Binding Domain for Recognition of Viral Infection[Show abstract] [Hide abstract]
ABSTRACT: To develop a clinically significant and practical enzyme-linked immunosorbent assay (ELISA) for the detection of MxA protein in human whole blood, a biological marker of viral infection. A sandwich ELISA suitable for the measurement of human MxA protein in whole blood was developed using mouse monoclonal antibodies (mAbs) raised against the GTP-binding domain of human MxA protein. Prior to the assay, the whole blood sample was treated with special buffer to extract the MxA protein, improve its stability, and avoid interference from hemoglobin. This ELISA meets all the requirements for use in routine clinical assays, especially in terms of sensitivity (detection limit: 1.3 ng/ml whole blood), accuracy (recovery: 93.0-100.0%), and rapidity (<1.5 h). The present ELISA had a sensitivity of 100% and a specificity of 100% for viral infection when compared to samples from healthy control and 87.1% and 90.9% when compared to samples from the bacterial infection group. We have developed a new ELISA for measuring MxA protein in human whole blood using mAbs specific for the GTP-binding domain of MxA. This ELISA has analytical performance enough for routine clinical assay and can be used in detecting the possibility of viral infection.Journal of Clinical Laboratory Analysis 05/2012; 26(3):174-83. DOI:10.1002/jcla.21507 · 1.04 Impact Factor
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ABSTRACT: Th e disappointing clinical effi cacy of anti-interleukin (IL)-5 monoclonal antibodies (mAbs) in asthma has been attributed to an incomplete depletion of eosinophils in lung tissue. These data have raised the possibility that more efficient strategies to deplete resident eosinophils may translate to greater clinical efficacy. MEDI-563, which has also been known as BIW- 8405, is a humanized anti-human IL-5 receptor α (IL-5Rα) antibody that not only inhibits the interaction of IL-5 with its high-affi nity receptor, but also depletes IL-5Rα-expressing cells through enhanced antibody-dependent cell-mediated cytotoxicity. IL-5Rα expression in humans is restricted to eosinophils and basophils and their progenitors in the bone marrow. Th erefore, quantitative depletion of eosinophils and basophils in bone marrow, blood and lung tissue by MEDI-563 might result in enhanced clinical effi cacy in diseases characterized by eosinophilic and/or basophilic inflammation.Progress in Respiratory Research 01/2010; 39. DOI:10.1159/000320807
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ABSTRACT: In the past decade, more than 20 therapeutic antibodies have been approved for clinical use and many others are now at the clinical and preclinical stage of development. Fragment crystallizable (Fc)-dependent antibody functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and a long half-life, have been suggested as important clinical mechanisms of therapeutic antibodies. These functions are primarily triggered through direct interaction of the Fc domain with its corresponding receptors: FcgammaRIIIa for ADCC, C1q for CDC, and neonatal Fc receptor for prolongation of the clearance rate. However, current antibody therapy still faces the critical issues of insufficient efficacy and the high cost of the therapeutic agents. A possible solution to these issues could be to engineer antibody molecules to enhance their antitumor activity, leading to improved therapeutic outcomes and reduced doses. Here, we review advanced Fc engineering approaches for the enhancement of effector functions, some of which are now ready for evaluation of their effectiveness in clinical trials.Cancer Science 06/2009; 100(9):1566-72. DOI:10.1111/j.1349-7006.2009.01222.x · 3.52 Impact Factor
Article: Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity[Show abstract] [Hide abstract]
ABSTRACT: Human interleukin-5 is the key cytokine involved in regulating the production and function of human eosinophils. IL-5 binds to its specific receptor composed of two heterogeneous alpha and beta polypeptide chains (hIL-5Ralpha and betac) that are expressed on the cell surface. The hIL-5Ralpha specifically binds IL-5 without involvement of the betac. It has been suggested that neutralizing antibodies to hIL-5Ralpha could serve as a therapeutic agent in eosinophil-associated diseases. We describe here the creation and biologic activities of a mouse monoclonal antibody against hIL-5Ralpha that blocks the following IL-5 dependent activities (a) binding of the IL-5 ligand to its receptor, (b) IL-5 dependent growth of hIL-5R expressing cells, and (c) IL-5-induced adhesion of human eosinophils. We also describe the process for humanization of the mouse Mab towards development of a therapeutic MAb. The humanized version of the monoclonal antibody also displayed potent neutralizing activity against IL-5 dependent activities.Human antibodies 02/2009; 18(1-2):17-27. DOI:10.3233/HAB-2009-0198
- Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 09/2008; 53(12 Suppl):1683-9.
Article: Immunological effects of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma[Show abstract] [Hide abstract]
ABSTRACT: We conducted an open label dose-escalation phase I trial of chimeric anti-GD3 mAb KM871 in patients with metastatic melanoma. Patients were entered into one of five dose levels (1, 5, 10, 20, and 40 mg/m2) and received three infusions of KM871 at 2-wk intervals. A metastatic melanoma site was biopsied at day 7-10. Pharmacokinetics, immune function, and mechanism of action of KM871 were analysed. A total of 17 patients were entered into the trial; 15 were evaluable. KM871 had a serum half-life (T1/2-beta) based on ELISA of 10.39 +/- 1.12 d (mean +/- SD). Trough levels >1.0 microg/mL KM871 at 2 wk postinfusion were seen with the 10 mg/m2 and higher dose levels. There were no significant changes in white blood cell subsets or serum complement levels during KM871 treatment. KM871 was stable in vivo and maintained binding affinity and complement-dependent cytotoxicity (CDC) function up to 2 wk postinfusion. No significant trends in CDC or antibody-dependent cellular-cytotoxicity (ADCC) activity in patients were observed during treatment. Analysis of tumour biopsies demonstrated a significant increase in CD4+ T cell infiltrates compared to control patient tumours (P = 0.010), and in patients with either stable disease (2 patients) or a clinical partial response (1 patient) at restaging, a significant increase in CD3 and CD4 infiltrates in tumour over nonresponding patients was observed. The favourable immune properties of KM871, combined with this preliminary clinical data, indicate that KM871 has potential for the treatment of metastatic melanoma.Cancer immunity: a journal of the Academy of Cancer Immunology 03/2005; 5:3.
Article: Defucosylated Chimeric Anti-CC Chemokine Receptor 4 IgG1 with Enhanced Antibody-Dependent Cellular Cytotoxicity Shows Potent Therapeutic Activity to T-Cell Leukemia and Lymphoma[Show abstract] [Hide abstract]
ABSTRACT: Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060. In addition, KM2760 also exhibited potent ADCC in the presence of lower concentrations of human PBMCs than KM3060. Because CCR4 is a selective marker of T-cell leukemia/lymphoma, the effectiveness of KM2760 for T-cell malignancy was evaluated in several mouse models. First, to compare the antitumor activity of KM2760 and KM3060, we constructed a human PBMC-engrafted mouse model to determine ADCC efficacy with human effector cells. In this model, KM2760 showed significantly higher antitumor efficacy than KM3060, indicating that KM2760 retains its high potency in vivo. Second, KM2760 suppressed tumor growth in both syngeneic and xenograft mouse models in which human PBMCs were not engrafted. Although murine effector cells exhibited marginal ADCC mediated by KM2760 and KM3060, KM2760 unexpectedly showed higher efficacy than KM3060 in a syngeneic mouse model, suggesting that KM2760 functions in murine effector system in vivo via an unknown mechanism that differs from that in human. These results indicate that defucosylated antibodies with enhanced ADCC as well as potent antitumor activity in vivo are promising candidates for the novel antibody-based therapy.Cancer Research 04/2004; 64(6):2127-33. DOI:10.1158/0008-5472.CAN-03-2068 · 9.33 Impact Factor
Article: Miklyaeva, EI, Dong, W, Bureau, A, Fattahie, R, Xu, Y, Su, M et al.. Late onset Tay-Sachs disease in mice with targeted disruption of the Hexa gene: behavioral changes and pathology of the central nervous system. Brain Res 1001: 37-50[Show abstract] [Hide abstract]
ABSTRACT: Tay-Sachs disease is an autosomal recessive neurodegenerative disease resulting from a block in the hydrolysis of GM2 ganglioside, an intermediate in ganglioside catabolism. The mouse model of Tay-Sachs disease (Hexa -/-) has been described as behaviorally indistinguishable from wild type until at least 1 year of age due to a sialidase-mediated bypass of the metabolic defect that reduces the rate of GM2 ganglioside accumulation. In this study, we have followed our mouse model to over 2 years of age and have documented a significant disease phenotype that is reminiscent of the late onset, chronic form of human Tay-Sachs disease. Onset occurs at 11-12 months of age and progresses slowly, in parallel with increasing storage of GM2 ganglioside. The disease is characterized by hind limb spasticity, weight loss, tremors, abnormal posture with lordosis, possible visual impairment, and, late in the disease, muscle weakness, clasping of the limbs, and myoclonic twitches of the head. Immunodetection of GM2 ganglioside showed that storage varies widely in different regions, but is most intense in pyriform cortex, hippocampus (CA3 field, subiculum), amygdala, hypothalamus (paraventricular supraoptic, ventromedial and arcuate nuclei, and mammilary body), and the somatosensory cortex (layer V) in 1- to 2-year-old mutant mice. We suggest that the Tay-Sachs mouse model is a phenotypically valid model of disease and may provide for a reliable indicator of the impact of therapeutic strategies, in particular geared to the late onset, chronic form of human Tay-Sachs disease.Brain Research 04/2004; 1001(1-2):37-50. DOI:10.1016/j.brainres.2003.11.067 · 2.84 Impact Factor
Article: Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells[Show abstract] [Hide abstract]
ABSTRACT: Eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 bind specifically and exclusively to CC chemokine receptor (CCR) 3, which is a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Bronchial epithelial cells represent an important source of chemokines, and thus we investigated in vitro and in vivo expression of eotaxin-2 and eotaxin-3 in bronchial epithelial cells in comparison with that of eotaxin-1. Immunohistochemistry showed increased expression of both eotaxin-2 and eotaxin-3 in addition to eotaxin-1 in asthmatics. Considerable amounts of eotaxins were secreted by bronchial epithelial lineage. As with eotaxin-1 production, generation of eotaxin-2 and eotaxin-3 by bronchial epithelial cells was up-regulated by IL-4 and IL-13, and attenuated by IFN-gamma and glucocorticoids. In addition to eotaxin-1 expression, but also eotaxin-2 and eotaxin-3 expression in the bronchial epithelium should be taken into consideration when developing the therapeutic strategies to treat eosinophilic airway diseases.Cellular Immunology 11/2003; 225(2):91-100. DOI:10.1016/j.cellimm.2003.10.001 · 1.92 Impact Factor
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ABSTRACT: We established a new monoclonal antibody (2C9) that reacted with prostate tissue. The immunohistochemical reactivity of this antibody is similar to anti-prostate-specific membrane antigen (PSMA). Herein, we report the antigenic determinant of 2C9 antibody. The reactivity of the antibody was characterized by immunohistochemical staining and the antigen target was characterized by amino acid sequencing after immuno-affinity purification from an LNCaP cell lysate and cloning of a cDNA using a mammalian expression cDNA cloning system. The amino acid and nucleotide sequences for the antigen molecule recognized with 2C9 monoclonal antibody demonstrated identity with PSMA. The target molecule of the 2C9 monoclonal antibody is PSMA, pointing to future diagnostic and therapeutic applications.International Journal of Urology 09/2003; 10(8):439-44. DOI:10.1046/j.1442-2042.2003.00655.x · 2.41 Impact Factor
Article: Improvement of biological activity and proteolytic stability of peptides by coupling with a cyclic peptide[Show abstract] [Hide abstract]
ABSTRACT: The cyclic moiety of an endothelin antagonist peptide RES-701-1, composed of 10 amino acids with an amide bond between alpha-NH(2) of Gly1 and beta-COOH of Asp9, was coupled to some biologically active peptides aiming to improve their activities and stabilities against proteolytic degradation. Coupling of the cyclic peptide to the N-terminal of RGD-peptides, maximally 4-fold improvement of in vitro activity compared to the original peptide has been achieved. Coupling of it to protein farnesyltransferase inhibiting peptides resulted to improve in vitro activity maximally 3-fold. These peptides coupled with the cyclic peptide also showed enhanced stability against some typical proteases. These results indicate that this cyclic peptide can stabilize the conformations of the peptides coupled to its C-terminus. Coupling of our cyclic peptide is anticipated to be a novel conformational stabilizing method for biologically active peptides, results to improve their activity and stability.Bioorganic & Medicinal Chemistry Letters 09/2003; 13(15):2583-6. DOI:10.1016/S0960-894X(03)00476-1 · 2.42 Impact Factor
Article: Immunohistochemical analysis of estrone sulfatase and aromatase in human breast cancer tissues[Show abstract] [Hide abstract]
ABSTRACT: We examined, by immunohistochemical analysis, the expression of aromatase and estrone sulfatase (E1-STS) which are the two major enzymes involved in in situ estrogen synthesis in breast cancer tissue. In the 83 cases examined, E1-STS, which hydrolyses estrone sulfate (E1S) to estrone (E1), was dominantly detected in tumor cells in 43 (59.0%) cases. Aromatase, which converts androgens to estrogens, was dominantly detected in stromal cells of the tumor. It was detected in 39 (47.0%) of the 83 cases. There was no significant correlation between the expression of these two enzymes and clinicopathological factors. We found a tendency for a correlation between aromatase expression and E1-STS expression in breast tumor (p=0.075). In terms of the possible use of these enzymes as prognostic indicators, patients who had aromatase in their tumor showed longer relapse-free survival than those lacking aromatase (p=0.045). Significant correlations between the expression of aromatase and the angiogenesis regulators, vascular endothelial growth factor and thymidine phosphorylase, were found (p=0.047 and p=0.046, respectively), though the presence of aromatase did not correlate with intratumoral microvessel density. This may indicate that aromatase is involved in vascular permeability and recruitment of endothelial cells rather than neovascularization. It may be useful to study the expression of aromatase and E1-STS using immunocytochemical analysis for understanding the tumor characteristics in breast cancer.Oncology Reports 07/2003; 10(4):791-6. DOI:10.3892/or.10.4.791 · 2.30 Impact Factor
Article: Ribonucleotide reductase immunoreactivity in adenocarcinoma cells and malignant or reactive mesothelial cells in serous effusions[Show abstract] [Hide abstract]
ABSTRACT: Ribonucleotide reductase (RNR) is a cytoplasmic enzyme that is essential for DNA synthesis. Its activity is strongly associated with cell proliferation. We assessed the value of immunostaining for RNR in distinguishing between reactive mesothelia (RM), malignant mesotheliomas (MM) and adenocarcinomas (AC) in serous effusions. Cytocentrifuged cell smears of serous effusions from 38 RM, 10 MM and 36 AC were immunostained with the monoclonal antibody KM1054 raised against the R2 subunit of RNR (RNR-R2) using the labeled streptavidin-biotin method. Quantitative RNR-R2 values were determined by counting the percentages of immunoreactive cells. RNR-R2 immunostaining was confined to the cytoplasm. The median RNR-R2 value was 1.4% (range, 0-7.9%) for RM, 11.2% (4.1-15.3%) for MM and 12.1% (2.0-40.6%) for AC. Significant differences in RNR-R2 values were found for both AC versus RM (P < .001) and MM versus RM (P = .009). There was no difference between AC and MM (P = .26). An RNR-R2 value > or = 7% was found in 30 of 36 AC, 8 of 10 MM and 2 of 38 RM. RNR-R2 immunostaining can be useful as an adjunct for differentiating AC or MM from RM in serous effusions.Acta cytologica 03/2003; 47(2):209-15. DOI:10.1159/000326506 · 1.56 Impact Factor
Article: The Absence of Fucose but Not the Presence of Galactose or Bisecting N-Acetylglucosamine of Human IgG1 Complex-type Oligosaccharides Shows the Critical Role of Enhancing Antibody-dependent Cellular Cytotoxicity[Show abstract] [Hide abstract]
ABSTRACT: An anti-human interleukin 5 receptor (hIL-5R) humanized immunoglobulin G1 (IgG1) and an anti-CD20 chimeric IgG1 produced by rat hybridoma YB2/0 cell lines showed more than 50-fold higher antibody-dependent cellular cytotoxicity (ADCC) using purified human peripheral blood mononuclear cells as effector than those produced by Chinese hamster ovary (CHO) cell lines. Monosaccharide composition and oligosaccharide profiling analysis showed that low fucose (Fuc) content of complex-type oligosaccharides was characteristic in YB2/0-produced IgG1s compared with high Fuc content of CHO-produced IgG1s. YB2/0-produced anti-hIL-5R IgG1 was subjected to Lens culinaris aggulutin affinity column and fractionated based on the contents of Fuc. The lower Fuc IgG1 had higher ADCC than the IgG1 before separation. In contrast, the content of bisecting GlcNAc of the IgG1 affected ADCC much less than that of Fuc. In addition, the correlation between Gal and ADCC was not observed. When the combined effect of Fuc and bisecting GlcNAc was examined in anti-CD20 IgG1, only a severalfold increase of ADCC was observed by the addition of GlcNAc to highly fucosylated IgG1. Quantitative PCR analysis indicated that YB2/0 cells had lower expression level of FUT8 mRNA, which codes alpha1,6-fucosyltransferase, than CHO cells. Overexpression of FUT8 mRNA in YB2/0 cells led to an increase of fucosylated oligosaccharides and decrease of ADCC of the IgG1. These results indicate that the lack of fucosylation of IgG1 has the most critical role in enhancement of ADCC, although several reports have suggested the importance of Gal or bisecting GlcNAc and provide important information to produce the effective therapeutic antibody.Journal of Biological Chemistry 02/2003; 278(5):3466-73. DOI:10.1074/jbc.M210665200 · 4.57 Impact Factor
Article: Cytokine enhancement of in vitro antibody-dependent cellular cytotoxicitymediated by chimeric anti-GD3 monoclonal antibody KM871[Show abstract] [Hide abstract]
ABSTRACT: The chimeric KM871 monoclonal antibody targets the GD3 disialoganglioside antigen and is under investigation for its immunotherapeutic potential in melanoma. Preclinical and phase I studies have demonstrated the biodistribution and specific tumour targeting of KM871 to metastatic melanoma in vivo, with a long half-life and lack of immunogenicity making it an attractive candidate for further clinical trials. In vitro studies have demonstrated KM871 induces high levels of cytotoxicity in both antibody-dependent cellular-cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays. In order to investigate the potential for cytokine upregulation of KM871-mediated ADCC, freshly isolated healthy donor PBMC effector cells were cultured in the presence or absence of the cytokines interleukin-2, interleukin-12 and granulocyte/macrophage-colony stimulating factor and the ADCC determined over a 10-day period. In the absence of these cytokines, ADCC activity of 1 micro g/ml KM871 on (51) Cr-labeled SK-MEL-28 target cells could not be detected after 72 hrs of culture of PBMC effector cells in media. In contrast, ADCC mediated by KM871 was significantly enhanced and maintained for the 10-day study period upon culturing PBMCs with media containing IL-2 and/or IL-12, but not with GM-CSF. FACS analysis of the effector cell population indicated CD3-/CD16+56+ NK cells were primarily responsible for the KM871-mediated ADCC activity and a direct correlation was observed between the percentage of NK cells and the level of cytotoxicity mediated by the PBMCs. Furthermore, ADCC was significantly reduced using NK-depleted PBMCs. These results suggest combining IL-2 or IL-12 with KM871 may enhance KM871 immune-mediated cell killing in patients with metastatic melanoma.Cancer immunity: a journal of the Academy of Cancer Immunology 11/2002; 2:13.
Article: Enhanced tumor cell selectivity of adriamycin-monoclonal antibody conjugate via a poly(ethylene glycol)-based cleavable linker. J Control Release[Show abstract] [Hide abstract]
ABSTRACT: A novel linker consisting of poly(ethylene glycol) (PEG) and dipeptide was used for conjugation of adriamycin with tumor-specific monoclonal antibody, NL-1, to confirm that the linker can be cleaved selectively with the tumor specific enzyme to express cytotoxicity of the anti-tumor agent. Initially, adriamycin-conjugated PEG linkers through different amino acid compositions, alanyl-valine (Ala-Val), alanyl-proline (Ala-Pro), and glycyl-proline (Gly-Pro) sequences, were prepared to confirm selective digestion with model enzymes. Adriamycin was released by particular model endoproteases, thermolysin and proline endopeptidase, from the linkers with different efficiency. When conjugates were prepared using these adriamycin-bound linkers, conjugates had no loss of binding affinity and specificity for common acute lymphoblastic leukemia antigen (CALLA) expressed on the Daudi cell surfaces as the target of NL-1 antibody. In addition, adriamycin release from the conjugates was also confirmed by incubating them with specific proteases. Tumor cell growth was inhibited dose-dependently for the conjugates carrying Ala-Val and Gly-Pro linkers, whereas significant inhibitory effect was abolished for the conjugate carrying Ala-Pro linker, indicating that cytotoxic effect can be controlled by specificity of antibody and composition of linker peptide. IC(50) for Ala-Val linked conjugate was approximately 3.5 microg/ml and that for Gly-Pro linked conjugate was 5.2 microg/ml. PEG-dipeptidyl linker demonstrated here will be an effective tool for the preparation of immunoconjugate, especially specific activation of anti-tumor agents at desired tumor tissues.Journal of Controlled Release 03/2002; 79(1-3):229-42. DOI:10.1016/S0168-3659(01)00554-5 · 7.71 Impact Factor
Chapter: Improvements of activity and stability against proteases of biologically active peptides by coupling of a cyclic peptide derived from an endothelin antagonist RES-701-112/2001: pages 764-766;
Article: Specific Targeting, Biodistribution, and Lack of Immunogenicity of Chimeric Anti-GD3 Monoclonal Antibody KM871 in Patients With Metastatic Melanoma: Results of a Phase I Trial[Show abstract] [Hide abstract]
ABSTRACT: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (111In) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.Journal of Clinical Oncology 11/2001; 19(19):3976-87. · 18.43 Impact Factor
Article: Construction of humanized anti-ganglioside monoclonal antibodies with potent immune effector functions. Cancer Immunol Immunother[Show abstract] [Hide abstract]
ABSTRACT: Gangliosides GD3, GD2 and GM2, which are the major gangliosides expressed on most human cancers of neuroectodermal and epithelial origin, have been focused on as effective targets for passive immunotherapy with monoclonal antibodies. We previously developed a chimeric anti-GD3 mAb, KM871, and a humanized anti-GM2 mAb, KM8969, which specifically bound to the respective antigen with high affinity and showed potent immune effector functions. Humanization of anti-ganglioside antibody is expected to enhance its use for human cancer therapy. In the present study, we generated a chimeric anti-GD2 mAb, KM1138, and further developed the humanized form of anti-GD2 and anti-GD3 mAbs by the complementarity-determining regions grafting method. The resultant humanized anti-GD2 mAb, KM8138, and anti-GD3 mAb, KM8871, showed binding affinity and specificity similar to those of their chimeric counterparts. In addition, both humanized mAbs had functional potency comparable to the chimeric mAbs in mediating the immune effector functions, consisting of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The production of these humanized anti-ganglioside mAbs, with potent effector functions and low immunogenicity, precedes the evaluation of the therapeutic value of anti-ganglioside mAbs in passive immunotherapy and the target validation for ganglioside-based vaccine therapy.Cancer Immunology and Immunotherapy 08/2001; 50(5):275-84. DOI:10.1007/PL00006689 · 3.94 Impact Factor
Article: Specific localization, gamma camera imaging, and intracellular trafficking of radiolabelled chimeric anti-G(D3) ganglioside monoclonal antibody KM871 in SK-MEL-28 melanoma xenografts.[Show abstract] [Hide abstract]
ABSTRACT: The chimeric monoclonal antibody KM871, directed against the G(D3) antigen, is under evaluation for its potential to target melanoma. To facilitate the in vivo evaluation of biodistribution properties and measurement of pharmacokinetics, KM871 was radiolabeled with (125)I via tyrosine residues and with (111)In via the bifunctional metal ion chelator C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid (CHX-A"-DTPA) to lysine residues. Using antigen-positive SK-MEL-28 melanoma cells, immunoreactivities of 42 and 40% cell binding were obtained, respectively, for the two radioconjugates. Binding was enhanced in the presence of added unlabeled antibody. A humanized A33 antibody was similarly labeled with the two isotopes and used as a control. To determine and compare in vivo biodistribution characteristics of KM871 radiolabeled with (111)In or (125)I, mixtures of the radioconjugates were injected i.v. into BALB/c nude mice bearing G(D3)-positive-SK-MEL-28 melanoma xenografts. Gamma camera images were acquired; groups of five mice were sacrificed at various time intervals, and tumors, blood, and tissues were analyzed. (111)In-labeled CHX-A"-DTPA-KM871 showed a maximum tumor uptake of 41.9 +/- 7.0% injected dose/g at 72 h with prolonged retention over a 15-day period. The tumor:blood ratio was 3:1 by 72 h, and higher ratios were observed at later time points. No abnormal accumulation of (111)In-labeled conjugate was found in normal tissues. In contrast, there was little accumulation of (125)I-labeled KM871 in the same tumors. The specificity of antibody localization was confirmed by the low tumor uptake values for radiolabeled control antibody. Gamma camera imaging demonstrated excellent uptake of (111)In-labeled CHX-A"-DTPA-KM871 in the xenografts. Chromatographic analyses of xenograft cytosolic extracts demonstrated tumor internalization and catabolism of radiolabeled KM871 with the formation of small molecular weight metabolites. Laser scanning confocal microscopy demonstrated that the majority of intracellular KM871 is localized to lysosomes. Despite the catabolism of the radioconjugate, a dose-dependent increase in KM871 tumor localization was shown through immunohistochemical examination of xenograft biopsies. This study demonstrates for the first time the in vivo localization of a radiolabeled anti-G(D3) monoclonal antibody to G(D3)-expressing xenografts using gamma camera scanning techniques and tumor cell internalization of KM871 tagged with a green fluorescent dye, Alexa Fluor 488, through confocal microscopy. KM871 has potential for targeting tumors in patients with melanoma.Cancer Research 07/2001; 61(11):4474-82. · 9.33 Impact Factor
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The best medicine for harpy halcro is to ignore him. Why not? When is the last time he has directly answered a question? He/she/it nevers states what his motive is except to be negative and disruptive. I suggest we all ignore him unless you like verbal dueling and recieving insults. He doesn't listen so why should we. GLTA longs , cheers!!
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Credit: © Brian To/FilmMagic.com
Bonnie Hunt (Apr 18th, 2009)
Curvy volume and rolled-under ends add fullness to Bonnie Hunt's soft, shoulder-length hairstyle.
Styling Tip
Apply a handful of volumizing mousse onto damp hair. Blow dry two-inch sections of hair with a round brush applying upward tension at the root for lift and then turn the brush several times to roll the length under. Dry your bangs straight down using a vent brush. Dab pomade on your fingertips and then slightly twist wispy pieces around your face. End with a spritz of finishing spray to lock in your style.Try on celebrity hairstyles in the Makeover Studio!


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Nubar has been raising cattle for the past 16 years. Taking care of animals requires continuous effort, but her husband helps her to raise the cattle. She also sells cheese, yogurt, butter and milk at the market. This is the only source of income for the family. From this business, her monthly profit is 150 AZN.
She plans to expand the business in order to bring more funds into the family.
She has applied for a loan of 2,000 AZN from Aqroinvest in order to buy more calves. She has plans on expanding the business to meet the high potential for milk in the market. This is her seventh credit. She has a good loan history.
Nubar appreciates your support.
Additional Information
More information about this loan
This loan is designed for clients residing in settlements for Internally Displaced Persons (IDPs) in Bilasuvar, Azerbaijan. An internally displaced person (IDP) is someone who has been forced to flee his or her home due to armed conflict, violence, human rights violations, or natural or manmade disasters, but who, unlike a refugee, has not crossed an international border (source: UN Office for the Coordination of Humanitarian Affairs). Many of these people have failed to qualify for loans through formal channels due to low income and lack of collateral. By funding this loan, you are creating opportunities and supporting economic development in extremely underserved communities.
About Aqroinvest:Aqroinvest Credit Union was founded in 2001 by a group of 32 farmers from Imishli. It has since grown to become the largest credit union in Azerbaijan, owned by its more than 5,400 borrowers and boasting a portfolio of nearly US$12 million.
AqroInvest is focused on providing loans to the following groups of people: rural farmers, people living in distant southern villages with little or no access to finance and internally displaced people and refugees, many of whom lost their homes and livelihoods during the violent conflicts in the 1990s.
In May 2011, Aqroinvest started a new project with Kiva proving higher education loans to students. The project gives students the support and financing they need to continue their education and helps pay for tuition fees at various universities in Azerbaijan. Aqroinvest is the first credit union in the country to offer students loans.
Loan tags help lenders find loans that match certain areas of interest. You can add up to 5 tags for this loan.
About Azerbaijan
68View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 19 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Sep 6, 2013
- Listed
- Sep 15, 2013
- Currency Exchange Loss:
- Covered
- Ended:
- Mar 17, 2015


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Escif: "Beautiful drawings can remain, but strange words must be buffed"Street Art // Tuesday, April 26, 2011
February 2011 cover artist, Escif, noticed something interesting in his hometown of Valencia, Spain recently in regards to two of his newest street pieces: his pieces had been buffed, not in full, but just his single word text was covered. . .
How Ron English Spent his April Fool's DayJuxtapoz // Monday, April 04, 2011
Ron English always has a bit of wit and political satire in his work that makes it capable of a bit of April Fool's Day joke. We know we are about 3 days late on this, but Ron went to the US-Mexico border somewhere and placed a few very politically astute pieces. Looks of the work after the jump . . .
JR's INSIDE/OUT in TunisiaStreet Art // Saturday, March 26, 2011
The amount of energy that JR has alone is inspirational. He just sees to be moving at a different pace at the moment, seizing the opportunity that the TED Award has afforded him and letting his unique interpretation of art and the world be seen as much as possible. We admire him for that. He has now taken his INSIDE/OUT Project to Tunisia. More after the jump . . .
The Art of Agapetus KristiandanaJuxtapoz // Tuesday, January 18, 2011
Obviously, we see a lot of art here, but these pieces seen last night by Indonesian painter and sculptor artist Agapetus Kristiandana caught our attention. The works, although humorous in appearance, are often highly political and metaphors of human conditions. More after the jump . . .


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Dr. Carin Cain specializes in dermatologic surgery, dermatology, procedural dermatology, mohs-micrographic surgery in Flagstaff, Arizona.
Dr. Carin Cain has been compared 43 times. Details of Dr. Cain's experience as an MD and her 2 hospital affiliations are available on your free doctor report.
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Dr. Carin Cain has been identified as specializing in Dermatologic Surgery, Dermatology, Procedural Dermatology and MOHS-Micrographic Surgery.
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December 30, 2007
Mike Farrell
Rivals.com Football Recruiting
For a while wide receiver Randall Dunn has said his leader is Virginia Tech and that still hasn't changed. He still plans on taking three official visits before Signing Day, but isn't ruling out the possibility of committing if his visit to Blacksburg goes well later in January.The 6-foot-3, 215-pound wide receiver from Virginia Beach (Va.) Ocean Lakes certainly looks the part of a contributor at the college level. Several things have him as perhaps a strong lean to Virginia Tech."The whole Hokie nation thing is a big reason," Dunn said. "I really enjoyed myself when I went up there. The fact that all four of their (top) receivers are leaving is something else. There's going to be an opening for some playing time."Dunn still plans on taking official visits to North Carolina (Jan. 11) and Virginia (Jan. 25). He was planning on rescheduling a trip to Penn State, but that's looking less likely that it did a couple of weeks ago."Me and Coach Kenney had talked about that the last time he called. It's a little bit up in the air at this point. They're a little bit (behind) the others."Dunn also said there was a chance he may commit to Virginia Tech if his official visit goes well."I've heard from everybody that I think is going to get involved at this point," he explained. "I'm leaving (his decision date) totally up in the air. It could take me until the Virginia trip or I could make it before." ...More... To continue reading this article you must be a member. Sign Up Now!
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This year for Haiku Code Drive, the student selection process has been completely overhauled. Unlike last year, where a public vote was held to select the students, our mentors have determined the combinations of <student>-<project>-<mentor>. Since our requirements for Google Summer of Code were greatly improved upon from last year, our mentors were able to confidently decide which of those combinations have the highest chance of succeeding.
The Services Kit will be a set of APIs that applications can use to communicate with various web services such as Facebook, Twitter, and Last.fm
There were several issues that limited this list. First, it is of utmost importance that Google Summer of Code remains the top priority. Based on that, the mentors have agreed that is not in the best interest of Haiku to encourage mentoring more than one student. Students such as Francesco Piccinno and JiSheng Zhang are participating in Google Summer of Code with other organizations and therefore are not eligible to participate in this year's Haiku Code Drive. Some students simply failed to reply to our requests to participate. Lastly, other students did not have someone capable of effectively mentoring them.
The format of Haiku Code Drive 2009, will in large be similar to last year. The timeline will closely follow Google Summer of Code's timeline. A stipend of $2,500 USD will be provided to successfully completed projects. Non-completed projects will be considered for half payment. The students will be encouraged to maintain a blog, provided to them on this website, with status updates. In general, they will be treated with the same respect and courtesy as our students who are participating through Google.
The finances for both students is already secured. As you may recall, some students from last year's Haiku Code Drive did not complete their projects. Due to this, $2,500 was left over and earmarked for future use. The other half of the money was paid to Haiku for our participation in Google Summer of Code 2008.
In celebration and recognition of the hard work put in by all of this year's Google Summer of Code applicants, several of Haiku's news sites have coordinated with each other to provide those students with an opportunity to be interviewed. These interviews will be covered by BeOSNews, BeGroovy, Haiku Gazette, Haikuware, and IsComputerOn, and will be spread out over the following two weeks.
Update: All of the received interviews have now been posted! I would like to congratulate and thank all of the participating newsites on this extensive collaboration effort. If any additional translations become available, feel free to Contact Me
Update: IsComputerOn has conducted another interview with Alexey Burshtein
Even though Johannes speaks English, his native language is German. As such Haiku Gazette was able to conduct the interview. The English translation will be provided to IsComputerOn.
Tom was interviewed in English by his mentor, Pier Luigi Fiorini.
We are pleased to announce that Google has allotted us with six students for this year's Summer of Code program! This is quite an achievement, seeing as how Google accepted only 1000 students, which is about 10% less than in 2008. As with the year before, the quality of the proposals submitted by students has increased significantly. This year, students who applied to Haiku were suggested to fix an issue in our bug tracker. This provided our mentors with a glimpse into the students' programming ability, as well as their ambition. Those contributions, several of which have already been committed to our SVN repository, proved to be a valuable resource when ranking the students. This allowed our mentors to strike a balance between projects that fill a need in Haiku and projects by students who have also shown themselves to be a worthy Google Summer of Code student. These students went above and beyond our requirements and expectations. They gave us hope that come October, November, and beyond, they will still be making contributions to our community. Since retaining students as community developers is one of the goals of Summer of Code, it weighed heavily in our decision. Without further ado, here is the list of students who will be sponsored by Google to contribute to Haiku in Google's Summer of Code 2009:
We encourage everyone to continue the hospitality that has always been a part of our community. This has become a well-earned reputation for the members of Haiku's community.
We would like to take this time to express our gratitude for all students who have submitted project proposals. Many of you have displayed that your abilities rival those who were accepted. It is an unfortunate situation that we were not allocated more student slots by Google. We are looking at ways to express our appreciation of your efforts so far. In addition we are investigating the possibility of sponsoring another Haiku Code Drive. At this point, no decision has been made and we are welcoming comments on regarding this matter. If you would like feedback regarding your proposal and suggestions for next year, feel free to contact (Matt Madia).
Thank you to all who have and continue to take the time to make Haiku's participation in Google Summer of Code a successful adventure. This includes Google for sponsoring Summer of Code, the Melange developers and contributors, and of course Haiku's Mentors.
Haiku's application for Google Summer of Code 2009™ has been accepted!
This year, the role of Haiku's Google Summer of Code primary administrator has been taken up by Matt Madia, with Stephan Aßmus acting as the backup administrator. Over the past few days, Google program administrators evaluated a total of 395 Mentoring organization applications and published their list of those accepted on Wednesday, March 18th 19:00 UTC. As you may imagine, time had seemingly slowed to a crawl in anticipation of the results!
As usual, we have created a list of suggested ideas. We encourage interested students to begin considering possible projects and more importantly to engage yourself in our community!
Here's some anecdotal data involving Google Summer of Code from the past and this year. The number of mentoring organizations has grown from 40 in 2005, to 100, to 130, and up to 175 in 2008. There were roughly 500
mentoring applications in 2008, however a good portion of those were "spammy" and does not represent an accurate count of actual applications. Google's application process this year has greatly reduced the number of "spammy" applications. The number of participating students in 2005 was 400 and has grown over the years to 1125 as of last year. For this year, Google will be establishing a cap of around 1000 students for 2009.
If you happen to be visiting the Chemnitzer Linux-Tage conference on March 14-15, 2009, make sure to stop by the Haiku booth and say "Hi!". Attending this year on behalf of Haiku will be Stephan Aßmus, Axel Dörfler, Denise Wein and Daniel Wünsch.
The Haiku booth is next to the one of the Fedora Linux project, together with many other open source operating systems like FreeBSD, Ubuntu, openSUSE, NetBSD, OpenBSD, etc.
The Chemnitzer Linux-Tage are an event around the topic Linux and open source for everyone. The entrance ticket costs 5 EUR for both days (3 EUR for students). The event will be held at the following location:
Universität Chemnitz
Reichenhainer Straße 90
Chemnitz, 09126
This Saturday, the 28th of February, the software that powers the website, Drupal and 47 (!) modules, have been upgraded to the Drupal 5 platform. This upgrade creates the foundation to continue to improve the functionality and information on our website, as the demands change, also in the face of the upcoming Alpha 1 release.
While the upgrade team has concluded that most of the data migrated smoothly, there are some rough edges. Most notably, the data of the conferences did not migrate properly, and as such, we are now in the process of reconstructing the conference module. Please read on for a more detailed list of issues. Naturally we expect some more minor issues popping up. If you find any one of them, please check out the list below, and if the issue is not there, drop a comment!
The known issues are the following:
Drop a comment if there is more. We did not thoroughly test the functionality with the different permission groups. Is anything not working, while it used to work? Drop a line!
As many Haiku community members know, one major hurdle that has been making it difficult to port new software to Haiku has been the lack of an up-to-date GCC4 compiler. While a GCC 4.1.2 cross-compiler has been available now for some time, cross-compiling software for a GCC4-built Haiku can be painful and frustrating. What Haiku really needed was a native GCC4 toolchain to run on a GCC4-built Haiku install.
That time is now! A native Haiku GCC4.3.3 is now a reality.
Michael Lotz set out to tackle this task and the fruits of his labor have finally been committed to the Haiku repository for all to benefit from.
To demonstrate what process was necessary to perform this task, he has written a detailed blog post recounting his experience. It's a long read, and certainly lists some confusing concepts. If you were at all curious what it would take, going from a GCC2-built Haiku to a GCC4-built Haiku with its own native compiler, the steps are all there.
During the process, Michael was even "fortunate" to find and submit a patch for a bug in libiberty. You will read about the strange behavior that led to the discovery in his blog post.
If you're paying attention while reading his blog, you'll note that Michael is "dogfooding" during his Haiku development. Not only does he use Haiku for development purposes, but it's also the only operating system he uses currently. This suggests a couple of important points: a) Haiku is stable enough to use daily and develop in and b) Haiku developers are serious about Haiku, intending to use it as their daily OS. I know of several developers who use Haiku daily for various tasks, including development. This demonstrates a dedication to the quality they are pursuing, and increases the likelihood that even little annoying things about Haiku are going to get fixed eventually.
So, what should we expect from Haiku now that it has a native GCC4 toolchain?
I'm not sure - and that's the exciting part actually! This opens the door for easier porting of modern software, and more easily moves Haiku out of the "dark" GCC2 cloud that BeOS had lived under.
Several existing Haiku porting projects already require GCC4 to proceed and/or update to latest versions: Firefox 3, Webkit, VLC, and more.
Haiku already supports a "hybrid" environment where it is built with GCC2 for backward compatibility but also providing GCC4 libraries for future software support - or even more interesting: a GCC4-built Haiku with GCC2 libraries for backward compatibility. I think we'll see the latter becoming more common now with the availability of a native GCC4.
There are still some minor loose ends to tie up - such as providing the remaining development tools for a GCC4 Haiku (the GCC2-built ones will work, but they are not yet automatically installed with the "Development" optional package). Additionally, those who wish to build a GCC4 Haiku from within an existing GCC2-built Haiku might find it a little bit challenging. If you'd like to experiment, you may want to compile your own GCC4 Haiku from Linux, BSD, etc., or even wait for the availability of pre-built GCC4 images to appear.
These are very interesting developments, I hope you're as excited as I am at what the future holds :)
On behalf of Haiku, we'd like to wish everyone Happy Holidays!
While the news may seem a little slow lately (people are likely busy during the holiday season), there has indeed been a few things happening of note.
One exciting announcement was from Christof Lutteroth letting us know that some final-year projects from the University of Auckland were prototyped using Haiku. While these prototypes and the code behind them are not yet publicly available, they have generously offered to donate this code to Haiku in the future.
In other developments, we have seen some improvements to Haiku's network drivers, including a couple drivers ported from FreeBSD by Ithamar Adema to improve the wired LAN support for EeePCs. Ithamar has also reported that he would like to work on porting FreeBSD's wireless stack where Fredrik Holmqvist left off.
It also seems that Oliver Ruiz Dorantes has recently completed Phase 1 of his Bluetooth stack and thus completed the associated Haikuware bounty.
There have been many other improvements to Haiku recently and you can always see what's going on in the Haiku Trac Timeline if you need a "quick fix". :)
At the end of the month, the main user mailing list firstname.lastname@example.com will finally be renamed to firstname.lastname@example.com, removing the most apparent reference to our previous name, OpenBeOS, that our project had until summer of 2004. The old archive will remain accessible, and all subscribers will be moved to the new list automatically. We'll even send you a reminder when it's done, so that you'll remember to send future mails to firstname.lastname@example.com instead.
Thanks to FreeLists.org for making this possible, they have provided an awesome service for us over the past 7 years!
Stephan Aßmus asked me if I'd like to translate my article on BeGeistert 019
http://haiku-gazette.blogspot.com/2008/10/das-war-begeistert-019.html to English. How could I refuse? :) Here it is:
BeGeistert 019 was held last weekend in Düsseldorf and was, as far as I can tell, a great success. I've been to BeGeistert twice in the past (I think 2002 and 2003) and in my opinion the spirit of BeGeistert hasn't changed since then. Maybe there used to be some more non-coders among the guests and the focus was more on applications; that was of course because Haiku was still in its OpenBeOS nappies at that time...
©2001-2015 Haiku, Inc. Haiku® and the HAIKU logo® are registered trademarks of Haiku, Inc.
Latest News | Haiku Blog-O-Sphere | Development Aggregator


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girl in the room
I write about politics, pop culture, and fashion. I am from Los Angeles, the center of the universe. I don't write about knitting and how it saved my soul. Or about babies. Unless I take up knitting or have babies.
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This profile was last updated on 11/5/14 and contains information from public web pages and contributions from the ZoomInfo community.
Dr. Ross TuckerWrong Dr. Ross Tucker?
Specialist Scientist
Local Address: Cape Town , South Africa
Company Description: The Sports Science Institute of South Africa offers a range of services to both local and international teams in training camps as well as on an ongoing basis.
Pro2015_Iteration9_NoTests.148[03] SEIDXWK-49


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This is a public group for hopefuls to post their sets and talk about becoming a SuicideGirl with SGs, members, and other hopefuls. PLEASE read the "Welcome! Please Read Me!!" thread before posting! *Please wait until your set is visible to members to post a thread about it in this ...
Welcome to the SG Army group! Check in here for the latest news and info.
the zodiac astrology and divination
Where people can talk about their zodiac signs and the study of Astrology.


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The World's Largest Coalition of Nontheists and Nontheist Communities!
Mike Bickle of the International House of Prayer explains that he has been personally attacked by demonic spirits at least ten times in his life.
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Wedges - Brown
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Leather wedge front WHYRED. Wedges made of wood and featuring a rounded toe. Zip on the outside of the ankle. Decorative stitching over the foot to the front.
Heel height 9.5 cm. Platform Height 3 cm. Ankle height 9 cm. Circumference of the ankle about 24 cm.
Made of leather. Inside of leather. Rubber outsole.
Whyred produces clothes, shoes and accessories for individuals who are inspired by a life characterized by independence. Whyred embodies a mature, "No fuzz attitude" and offers its customers unique garments year after year. Whyred designs are a combination of clean lines and cool features. The unique creations have been influenced by music and art. Find a unique Whyred des...ign here at Nelly.com UK. Read more
Free delivery when you spend over £75. Standard shipping £3.95. Delivery time: 3-6 days. We deliver with UPS.
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