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The Top 7 Things of All Time
Many of you may have noticed that we write a lot of list-based articles here at Cracked. We have our reasons for this: They allow our busy, important readers to read them in small chunks, they're ridiculously clickable, and we just really like numbering things. But despite being so plainly intelligent and justifiable, this list-based tendency of ours has, on occasion, in the minds of some, been a cause for mockery. "Cracked can't publish anything that isn't a list," these weak-minded people say. "Did you see Cracked's newest article? 'The 6 Most Surprising Things You Didn't Know About Baffling?' they'll add, thinking they're so fucking clever. "Or was it 'The 7 Most Things?' HAHAHHAHHAHHAHA- HHAHAHAHA."
We hate these people.
But what the fuck. It's the holidays, and the only people reading Cracked right now are the diehards and search-engine aggregation spiders. So here it is, folks. "The 7 Most Things." Happy freaking holidays.
#7. Volkswagen Thing
More properly known as the Volkswagen 181, the Volkswagen Thing was what happened when a Beetle was made to fuck a dumpster, with sexy results.
Sven Storbeck
Less a car, more a poem wrought from corrugated tin.
Originally meant to be a military vehicle, the Thing was eventually sold to civilians, because someone thought that would be pretty funny. Featuring interchangeable doors, a windshield that looked a bit like a door, and an engine that could accelerate it up to highway speeds in about half an hour, the Thing also had the distinction of being about 50 percent more expensive than the Beetle, and infinite more percent than common sense dictated.
Graphics: 2/5 (Big deduction for the low-poly models.)
Sound: Braaaaaaaaaaap, ka-chunk, chunk, grrrrnnngng, "Shift, goddamnit," chunk, "Got it, you bastard." Braaaaaaaaaaaaaaaaaaap.
Fun Factor: 2/5 (It is the fastest thing on this list, but only just barely.)
#6. Thing (Philosophical Concept)
It turns out that a "thing" isn't a simple concept. Philosophers have spent tremendous amounts of time considering the problem and come up with a whole variety of definitions for what makes a thing a thing, and various tests to quantify a given thing's thinginess. Go ahead and click on that link if you're feeling up to a challenge, but I'll just summarize it here, probably a bit unfairly: They don't have any fucking idea.
Just to illustrate this problem a bit, let's take a specific example and consider an actual thing.
Here's a good one.
Most philosophers will look at this and agree to at least classify this as a concrete thing, although depending on whose thing it is, they may make some jokes about it being more semi-concrete. But they can agree on little else about it. Is it a thing in and of itself, or is it only a thing because of its properties that we can perceive (texture, girth, purpleness)? And can those same classifications be used to describe non-concrete things? Things like ideas?
"Yeah, no, just thinking about this thing is making me feel a little more concrete."
Graphics: 4/5 (Lost points for pixelated censoring.)
Sound: Sproing!
Fun Factor: SPROING!
#5. Thing (Scandinavian Assembly)
"Thing," or "ting," is an old Scandinavian word for a governing assembly. Varying in size from small community meetings all the way up to massive multi-tribe gatherings, these were the places where heavily bearded citizens could meet and discuss the issues of the day.
Wikimedia Commons
The name lives on in the formal names for many national parliaments in the region, including the Danish Folketing ("Thing of the People"), Norway's Storting ("Great Thing"), and the Icelandic Althing ("General Thing").
(Now, I know it's pretty cheap to make fun of foreign words that sound goofy to English ears, so I won't do that here. But learning that Iceland's Parliament is called the "General Thing" is one of the things that make me love writing for Cracked.)
Wikimedia Commons
God do I hope their parliamentary sub-committees are called "Specific Things."
Graphics: 2/5
Sound: "Bullshit, bullshit, bullshit, bullshit, bullshit."
Fun Factor: 4/5 (It's a parliament, so it can't be that much fun, but I'm giving it massive bonus points for the "General Thing" thing.)
#4. The Thing (Soviet Listening Device)
This particular Thing was a Soviet listening device, also sometimes called the Great Seal Bug. Concealed within an ornately carved version of the Great Seal of the United States, a gift to the American ambassador from a group of treacherous Soviet schoolchildren, it recorded conversations within the ambassador's residence in Moscow for almost seven years before its discovery.
"We figured it out when it started giggling."
The Thing was more than just a normal bug, though, and would have to be to get such a cool nickname. Invented by Leon Theremin (yes, the one who invented the theremin), it's an incredibly clever device, its breathtaking simplicity leaving it almost undetectable. Which it'd have to be, considering the anti-eavesdropping precautions the Americans would have taken (beyond playing music really loud while talking).
Also, they always coughed when saying "bullshit."
Notably, they'd have regularly swept the room with bug-sweeping equipment capable of detecting electronic devices or radio signals. But the Thing was barely an electronic device, with almost no circuitry or batteries, and it almost never broadcast a radio signal. Powered by an external radio source, it would use its own ultra-simple microphone to modulate that radio source and reflect it; the rest of the time, it was completely inert and undetectable. This is basically the same idea used in RFID chips invented five decades later, and pretty conclusive proof that Theremin was a time traveler.
Graphics: 4/5 (For the bitchin' carved eagle, if nothing else.)
Sound: "God do I hate Russia. Thank goodness they can't hear me right now. So many goddamned cabbage dishes."
Fun Factor: 4/5 (Time traveling and treacherous children? This Thing is rad. The Cold War was full of cool stuff like this. Shame about that constant threat of annihilation.)


text:
Watering Can, 7 Liter
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Colorful All-Purpose Watering Can
- Well-balanced watering can is easy to carry
- Long neck for greater reach and fewer spills
- Removable rose applies a gentle shower
- Choice of Blue or Violet
Made in USA from high grade, injection-molded plastic that won't rust, leak or corrode, this watering can comes with a plastic rose for applying a gentle shower to delicate plants. Well-balanced and easy to carry, with an arc-shaped grip for comfortable hand placement when carrying and pouring. The long spout extends your reach and reduces spilling when watering can is full. Holds 7 liters (approx. 1-3/4 gallons).
Product Details
- Injection-molded plastic
- 23" L x 7" W x 13-1/2" H
- Spout is 15-1/4" L
- Rose is approx. 4" in diameter
- Fill opening is approx. 5" in diameter
- Holds 7 liters or approx. 1-3/4 gallons
- Made in USA
There are no special shipping restrictions or charges associated with this item. For detailed information about our delivery methods and charges, click here.
We're proud of the fact that this item is shipped to you directly from our warehouse in Vermont, by one of our 250 employee-owners. In-stock items are packed with care and shipped within the next business day to ensure prompt delivery to your home and garden!

subset: commoncrawl


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June 23, 2010
Park days are in full swing.
18 comments:
adorable! park days are the best!ReplyDelete
She is too beautiful!ReplyDelete
I adore this picture of Ivy! So precious!ReplyDelete
every time I see a picture of Ivy I can't help but think "she looks so much like the girls" must be the age and those beautiful chubby cheeks! :)
What a cut smile! Ivy you are a cutie!!!! And you are gorgeous like your Mama!!!ReplyDelete
Oh, the darling-ness. I can't stand it.ReplyDelete
What a beautiful picture!ReplyDelete
That face! I can hardly bare the adorable-ness....ReplyDelete
and she looks like she is loving it! great shot Steph!ReplyDelete
I can't wait until we are done working on the house so we can enjoy the park too, save some fun for us,ReplyDelete
That photo is EXCELLENT! You really have a knack for photography!ReplyDelete
Love the happiness in her face.ReplyDelete
Gorgeous picture!ReplyDelete
Absolutely PRECIOUS girl that Ivy!!! And a great picture composition by you - what a shot!!ReplyDelete
Such a sweet shot!ReplyDelete
Park days are happening here, too. And I love it. :)
LOVE. THIS. PICTURE.ReplyDelete
We love park days too!! Such a pretty shot of your little girl. Enjoy those swings this summer.ReplyDelete
oh my word, this is PERFECT!!! what a beautiful smile. LOVES.ReplyDelete
Pure happiness. :)ReplyDelete
Our park days happen in the fall, winter, and spring. It's much too hot in the summer.


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On a recent airport shuttle to DIA, I met a woman from Miami who spoke enthusiastically about her next vacation. It was going to be in her backyard. No, she did not live on the beach. No, she did not recently locate to the Florida vacation destination. In fact, she was born in Miami, she said.
Here's what made it a vacation: she was going to indulge herself in five good books and five favorite restaurants, including those she might never experience because they were the splurge "only tourists could afford." Some of these were ethnic "treats" similar to what she might visit were she in South America or Asia.
I asked her why she had made this decision, half anticipating that she'd blame the economy for a forced staycation.
"I think we're blind to the beauty in our own backyards and selectively deaf when we hear about good local food," she said. She went on to explain that her bucket list included making a deliberate effort to enjoy things, "especially food" served "within two hours" of home.
I thought about her statement and began making silent excuses for not visiting Mesa Verde more often. It takes a house guest to get me there.
I ride the train about once a year, but that's because all trains fascinate me, even commuter trains in busy, industrial corridors. I'll create any excuse to ride the Durango & Silverton Narrow Gauge.
However, there are too many local restaurants I have not tried because I will not take the time to plan a special night out. Of course, as a food writer, I have my favorite places. But if the truth were to be told, most of my meals away from home are on the fly. I'm either running between appointments or I want to collapse with an uninterrupted conversation with my husband. When either situation occurs, we put on a pair of old, worn slippers – like cows wandering back to the comfort and familiarity of the barn.
We've already selected what we want, I rationalize. But what of the exciting, young chef eager to introduce foods of another shade or stripe?
I hear it said by recent transplants to Durango: "There are so many good restaurants here."
Yet I'm probably one of the majority who look for consistency and no disappointments when I sit down to a restaurant meal in Durango.
I have a cousin who is just as much of a foodie as I am. She is a caregiver who is mostly home-bound, so uses these hours to make food preparation a form of entertainment. She studies food and occasionally splurges on great meals, so she can duplicate what she enjoys. She posts her successes on Facebook. Indeed, 75 percent of our online chatter goes back to food.
I've decided she's a greater chance-taker than I am.
I credit my book club for forcing me to open drawers I might never open. I'm the first to bitch when I've purchased a poorly-written book. Yet, on balance, there are just as many authors I might never have discovered, had I not been "required" to read a book that was not my first choice.
Too bad there are not restaurant "libraries."
In the meantime, I'm going to try to be less critical if the Hollandaise lacks enough lemon. In fact, I'm going to pass on the Hollandaise and see if there's a better sauce for asparagus, artichokes and spinach.
Before the snow flies, I'm going to order something from a menu that goes counter to what I "know" about food.


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Lead Chains
A range of lead chains are available to suit all equestrian disciplines including leading difficult horses including stallions and racehorses or for the show ring. Some chains come with a quality leather lead which is available in black or brown. Lead c
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text:
(based on 32 reviews)
Ratings Distribution
5 Stars
4 Stars
3 Stars
2 Stars
1 Stars
of respondents would recommend this to a friend.
Most Liked Positive Review
Awesome Bag
My wife purchased this bag for my birthday, about 7 years ago. I train to Chicago several days a week, fly a couple of times a month, and also drive to several meetings...Read complete review
My wife purchased this bag for my birthday, about 7 years ago. I train to Chicago several days a week, fly a couple of times a month, and also drive to several meetings each months. In short, I use this bag daily in a variety of ways. I have had bags by Hartmann, Tumi, Boyt - all good but with some flaws. This bag has none, It looks great, opens easily when standing or flipped on side, is functional, tough, and still looks virtually new - despite being loaded to capacity frequently. One of the best business accessory purchases I have ever made - and that is saying a lot.
Most Liked Negative Review
Stylish but not durable
Let me first say that from a style standpoint this brief bag gives the appearance of professionalism and class. That being said, it took me two years of owning/using this bag to realize...Read complete review
Let me first say that from a style standpoint this brief bag gives the appearance of professionalism and class. That being said, it took me two years of owning/using this bag to realize the quality was not commensurate with the price. In particular, the outside of zipper enclosure (a canvas type material) began separating from the bag during the second year. Shortly thereafter the zipper began to work only in one direction. Not once did I overload or mistreat the bag so this is not a case of improper use. Although I enjoyed it while it lasted, this product does not have the level of quality necessary to justify the price.
Reviewed by 32 customers
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Briefbag that is far from brief
By Bridgebuilder
from Long Island, NY
Comments about Levenger Tusting Briefbag:
This briefbag is elegant yet a work horse. Classy & Casual. A conversation piece and envy of the office. Just got it and can't wait for it to show its age. Built to last.
Bottom Line Yes, I would recommend this to a friend
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Sturdy, well-made briefcase.
By One-L
from Detroit, MI
Very satisfied with this quality briefcase. Tusting recommends occasionally treating the leather with its Hide cream, which is only available via shipment from UK. I twice contacted Levenger and was referred to two separate web-sites which don't carry the Tusting Hide Cream. It would be helpful if Levenger carried this product or could refer to a supplier in the US or could provide an accessible alternative. Not satisfied by the serve after the sale.
A Wonderful Bag
By BradL
from Seattle, WA
I had been looking at this bag for a while, and so far my only regret is that I waited this long. Daily I carry my computer, files and misc items. This bad has space for all of it and room left over. The only complaints I have are minor. There are only 2 pen loops, so I have used the edge of one of the pockets and that has worked well. Also, the zippers hit on the snap if you walk with it fully unzipped. Both of these are easily overcome. I range from casual to formal and these bad suites the full spectrum without being pretentious.
Great Brief Bag
By BillJest
from Providence, RI
I purchased this brief bag because of its size and the separate laptop case that comes with it. The appearance is fantastic and has the look of a much more expensive bag. It is very roomy and has pockets and holders for all of my accessories for my laptop. I have purchased other Tusting products through Levenger and have been very happy with their quality. I also want to comment on Levenger's customer service. When I first received the brief bag the second time I used it I notices a stitch was missing from one on the bottom corners of the bag. I returned the bag to Levenger and promptly received a replacement (brand new bag) that I am very happy with and I am sure will be happy with for years to come. Great products and excellent customer service is what makes Levenger a company I am happy to recommend to others.
Beautiful and luxurious
By jjones940
from Fort Worth, TX
I have looked at these bags in the catalog for years and wanted one for a long time. My wife recently found out and bought me one for my birthday. WOW! What a great surprise.This bag looks and feels incredible. The attention to detail is evident. The leather is tough but soft to the touch. This is one of those items that help define a person and as I walk into meet with customers I know they see it and respond to it. However, that isn't what makes it great. Even though it was a present, it gives me a feeling of accomplishment to know that I have worked to be in a position to use a bag like this.The irony of the review is that my only knock is on function because I have carried a laptop backpack for years and all the pockets in the backpack are missed. I have purchased some storage components to use in the bag and would suggest Levenger consider including an inexpensive cube or two with the bag.Other than that little learning curve for me, I am ecstatic to own this bag.
Bottom Line No, I would not recommend this to a friend
(2 of 2 customers found this review helpful)
By Scotto
from St. Charlesl, IL
(1 of 1 customers found this review helpful)
By Maximus
from New Orleans, LA
I bought this case several years ago and it quickly became the workhorse in my collection. I have over a dozen briefcases and like to rotate them frequently, but the Tusting/Cambridge Briefbag is the one I use most often. I rarely use the laptop sleeve, but that only gives me more room for other essentials.Once a month I use a leather cleaner/conditioner to repair the scuffs and scraps I subject the bag to and it comes up looking nearly new.
Great product and service
By Bobg
from Providence, ri
My wife purchased this bag for me 9 years ago and i greatly enjoy using it daily. This year the zip broke and I contacted customer service. Days later a new bag arrived at my home and the process was hassle free. I already shared my experience with several co-workers and friends and they are planning to make their next quality purchase from levenger.
Excellent Briefcase
By Dougster
from Orange Co, CA
I had balked at purchasing this due to the price, but bought in when they ran a sale. I am very pleased. I was looking for a case that would stand open next to my chair or at my feat on a train. I can slip folders into it or file papers temporarily in the outside pockets on both sides. the interior pockets are well arranged and useful. Two places for business cards and a slot for a phone or calculator, plus a large zippered pocket to hold things I might loose. In 6 months it has a few scuffs, but still looks great. The interior color, kind of a mustard, put me off at first, but it does allow one to find things in dim light. I don't usually use the laptop sleeve. I replaced it with a Levenger Ambi Leather folio, that I use to store my iPad. I grab the folio for meetings and when I don't want to carry the whole briefcase.
A Bag of Substance
By mjr59
from Philadelphia, PA
This bag is very substantial, quite handsome, and exudes quality. I expect to own it a very long time.I do wish there were a few more internal pouches for pens and other miscellany (but it hardly bothers me and forces me to be a bit more organized). One note for you taller gents is to order the extended strap because the default one is a bit too short for me (I'm 6'1"); it would be nice if you could select between the two straps at the time of purchase.As with the majority of darker colored articles, especially dyed leather goods, markings may rub-off on lighter colored clothing (one of my initial hesitations to ordering the bag). I minimized this risk by rubbing the bag down with a clean shoe-polishing cloth (the cloth turned brownish).There was zero buyers' remorse when I received the bag and I'd repurchase it (if I had a time machine) in a heartbeat.
© Copyright Levenger Company
2016. All Rights Reserved.


text:
(Sports Network) - The Dallas Cowboys and quarterback Tony Romo have
reportedly reached an agreement on a blockbuster six-year extension.
According to NFL.com, the deal is worth $108 million with $55 million
guaranteed and a $25 million signing bonus. If so, Romo would receive more
guaranteed money than the six-year, $120.6 million contract that Joe Flacco
recently signed with the Baltimore Ravens.
Flacco, a Super Bowl champion, got $52 million in guarantees.
In addition, the deal would make Romo the highest paid player in franchise
Romo, who has just one postseason win in nine seasons, would have become an
unrestricted free agent after the 2013 season.
More to follow...
The Sports Network


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Nordic ski racing in the Sierra Nevada can be a fickle sport. At times, it seems as though participation might be down among the citizen racing crowd, as evidenced by the small turnout for a few races earlier this season.
But at Monday's Sierra Skogsloppet at Tahoe Donner Cross Country, to paraphrase Mark Twain, the rumors of Nordic racing's demise are greatly exaggerated.
A whopping 184 registrants showed up on a crystal clear, beautiful morning on the tracks at TDXC, and participants were treated to a rollicking good time over a new course for this annual event.
The 15-kilometer Skogsloppet (a "race through the forest" in Swedish) is a benefit for the Truckee Nordic ski teams from Truckee High School and Alder Creek Middle School, with Tahoe Donner generously donating all the proceeds from the race.
With new management and a heightened commitment to the cross-country ski area, Tahoe Donner was eager to show off the perfectly groomed trails on the twisty, hilly race course throughout the Home Range of the Nordic Center. And with TDXC hosting most of the prestigious Super Tour Spring Series and USSA National Distance Championships this April, XC manager Sally Jones was eager to show off some of the course features planned for those events.
In the men's division, it didn't take long for a quintet of fast, young racers to gap the rest of the field. Four members of Far West Nordic's Farm Team of senior racers and one guest racer from Australia led the way, sticking close together for the first lap of the two-lap course and jumping out to a 40-second lead within the first 3 kilometers.
By the 10-kilometer mark, it was Tahoe Donner's own Spencer Eusden and former UNR racer Wyatt Fereday who pulled away from the other leaders to take a 20-second lead. They built upon their lead until the final sprint, where Eusden narrowly took the win with a time of 38 minutes and 27 seconds. Another racer benefiting from a "home-court advantage," Gustavo Johnson, managed to outlast the rest of the field for third place (39:00).
In the women's field, yet another Far West Farm Teamer, Holly Whitney, easily cruised to a solo victory with a time of 45 minutes and 24 seconds, almost 40 seconds in front of her nearest competitor. Whitney, the Truckee High assistant coach and also an employee at TDXC, opened up a 15-second lead early in the race, and eventually managed a 40-second win with a time of 45 minutes and 24 seconds. Cathy Howard of Truckee was second (46:03), and Beth Thomas of Truckee easily took third place honors with a time of 46:50.
In the 7.5-kilometer junior and novice division, it was a couple of visiting Australian juniors who took the top two spots. Hugh Pollard won with a time of 23:01, Rowan Kaye was second (23:37) and Alder Creek's Zach Williams was third (24:30).
The women's race was won by San Jose skier Raylene Chew with a time of 23:01, followed by two more Australian girls, Jillian Colbourn (23:17) and Katarina Paul (23:29).
And finally, the 2-kilometer youth race was won by Mason Payne for the boys (8:17) and Alexandra Tinsley for the girls (7:51).
The race season is in full tilt this month, with Far West Nordic's Tahoe Rim Race and Tour up next on Sunday, a 26-kilometer, point-to-point event from Tahoe Cross Country up and over the mountain to Northstar Cross Country.
Go to www.farwestnordic.org for full results. Find an extensive gallery of photos from all three races last weekend at www.macbethgraphics.com.


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Friday, October 11, 2013
Students at Cane Bay High School met for a group prayer at the school flagpole on Sept. 25 as part of See You at the Pole.
See You at the Pole was started by a youth group in Burleson, Texas in 1990 and has since become an international event during the Global Week of Student Prayer.
CBHS Spanish teacher and FCA sponsor Ricky Reyes said there were 70-80 students and faculty who took part in the event.
"They prayed for their school, country, leaders and our military," he said. "The students were excited to have the event and we were excited to have students who wanted to pray for their school and for their country."
Principal Lee Westberry took a photograph of the event and sent it to a student that she became close with when she was an assistant principal at Stratford High School. Jason Horton, 31, is in the 112th Special Operations Signal Battalion (Airborne) stationed in Afghanistan. A graduate of Stratford in 2000, Horton has kept in-touch with Westberry and refers to him as her son or baby when pointing him out in pictures. Horton said the picture resonated with the troops.
"They were shocked when I showed it to them. It was warming and (the troops) faces were very happy and we wanted to give back how we could."
The battalion sent back a picture of their own to the school to show their gratitude for the thoughts and prayers.
"When I saw it, it brought me a lot of joy," said Reyes. "Thinking about our military and the many people who have lost loved ones, it's something to pray for and to know that it touched somebody overseas meant a great deal to me and all the others who saw it."
Horton said that receiving the picture was important to him and that it was a special reminder of the pulse coming from home.
"It was very, very heartfelt," Horton said. "It is nice to see that people still have patriotism and that people are still supporting us."
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text:
Lake Worth, Fla. – The Stetson men's golf team played with the kind of poise on Saturday that head coach Larry Watson has been looking for all spring.
The Hatters turned in their lowest round of the spring on the second day of the Slomin Autism Invitational, improving by 28 shots over their first round score. All five Stetson players played to within one shot of par, finishing with a two-over par score of 286.
That total included the low nine-hole score of the tournament has Stetson made the turn on Saturday at five-under par as a team.
"I am really proud of the way the guys came back and played today," Watson said. "This is what we have been working toward all year. I have seen these guys play like this in practice all year, but it has been tough to translate that play into competition."
The Hatters were led by freshman Zach Stark, who made the turn on Saturday at three under par 32. He was still at three under until a double bogey on the seventh hole. He finished with a one-under par 70.
Classmate Dirk Kuehler continues to lead the Hatters in the individual standings. His one-over par 72 on Saturday has him tied for 26th entering Sunday's final round.
In addition to Kuehler, junior Matt Taylor, sophomore Dustin Dingus and freshman Brian Kehoe all posted scores on Saturday of one-over par 72.
Senior Tyler White, who is playing as an individual, finished Saturday's round with a 79, matching his score from Friday.
With the 28-shot improvement on Saturday, the Hatters (600) moved past Murray State (607) into 10th place in the tournament. Stetson is within two shots of Bethune-Cookman (598) for ninth entering the final round.
UCF took over the tournament lead from Georgia Southern by posting an 11-under par team score of 273. The Knights' Ricardo Gouveia and Greg Eason both posted six-under par scores of 65 in the second round and stand first and second overall.
UCF has a two-day score of 558 and leads Georgia Southern by five shots entering Sunday's final round. Middle Tennessee State (575) is third, followed by DePaul (578) and Jacksonville State (583).
Live scoring for Sunday's final round of competition will be available on Golfstat.com.


text:
Josh Brolin and Diane Lane's eight-year marriage is ending in divorce, but the road wasn't always rocky for the occasionally tumultuous pair.
"We're very similar in that celebrity is not a necessity," Brolin, 45, told PEOPLE in 2003, after meeting his soon-to-be-bride, 48, the previous year through stepmom Barbra Streisand. "Everything is easy."
The simplicity seemingly continued for Brolin and his beauty, who wed the following year in a ceremony at the actor's central California ranch.
Though there was a bit of a rocky start to their marriage, the pair got on track in 2005. As Lane told PEOPLE at the time, "I feel much better having a strong man with me who makes me feel embraced and secure. It's wonderful."
With her first marriage to actor Christopher Lambert behind her, Lane went on to say, "I wasn't going to go relationship shopping with my young daughter. I didn't want her to get attached to something that wasn't going to last."
In 2008, Lane praised Brolin, telling Redbook: "It's just invigorating to be around him. Josh completes me because I'm so attracted to his otherness."
On Thursday, reps confirmed the pair split, with a source telling PEOPLE, "They've been separated for several months. This was a hard decision for both of them to make. They were together for 11 years, the relationship just ran its course."
News of the breakup came almost two months after Brolin was held for public intoxication just before midnight on New Year's Eve 2013. Released without charge, the actor was spotted without his wedding ring the following day, donning sunglasses, in Venice, Calif., where he seemed unfazed by the trouble as he ate with a male friend at Sauce on Hampton.
Josh Brolin & Diane Lane: Inside Their Up-and-Down Marriage
Steve Granitz/Wireimage


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No Trade Clauses on both would make that rather difficult. Maybe for comedy purposes, they'll use Eaves in the shootout if he's still around.
Hear you there. If the NHL keeps 'em, they need to adjust the points system: 2 pts for a reg/OT win, 1 for shootout, & 0 for a loss.
What about 3-2-1-0


text:
Glocal is a co-curricular group in the Laurier Faculty of Education. The purpose of Glocal is to raise Teacher Education Candidate awareness and to develop education-related activities regarding global, outdoor, and environmental education.
We want to help educators blend global and local realities (hence, glocal) in the classroom, seeing the world out there as sharing many of the same characteristics and traditions as here (t/here). Our primary motivation is to respond to the question: How can we help teachers and students develop glocal thinking and acting?
Certificate Program:
Upon completion, this unique program provides you with a certificate attesting to your interest, skills, and ability in glocal/environmental education. The Glocal Certificate Program is completed over four blocks of time, two in the fall and two in the winter.
Other activities Glocal has coordinated:
- Milk bags into sleeping mats for an orphanage in Ghana
- Curriculum development on chocolate and fair trade
- Change for a change fundraiser for Haiti earthquake victims
- School supplies for Haiti
- Unity Games @ Franklin Public School and WLU
- Aboriginal learning styles workshop at the WLU Aboriginal Student Centre
- Ride for Refuge bike-a-thon
- Chapati fund-raiser for migrant workers
- Micro-credit support for artisans in Peru
Check out our website for pictures and more information: www.laurierglocal.com
or contact Dr. Steve Sider (firstname.lastname@example.com)


text:
This is one of those increasing number of weekends that I wish I had a whole section of the newspaper to give every event its due. So let's not delay and jump right in to what's happening.
If you didn't sign up for the only weekday race in the streets of downtown Charleston (not Hampton Park) a month ago, you're out of luck.
Still, it's worth noting because of its popularity, especially with younger adults, and because it will block off portions of Washington, Concord and East Bay streets and a short section of Murray Boulevard in front of White Point Garden starting at around 6:30 p.m. Thursday.
Mud, Round 2
The second of three obstacle races featuring mud, and the longest-running local one, on consecutive weeks will be Saturday at The Citadel.
The 17th annual Bulldog Challenge is a grueling six-mile race that has grown from a primarily military event to one that attracts more than 700 people from all walks of life, military and civilian. This year's race, scheduled about a month later than in years past, is expected to surpass that number.
Teams of four will work their way through challenges with names like "House of Pain" and "Guadalcanal." Before reaching the finish line, teams will slog through the Lowcountry's famous pluff mud carrying 25-pound sand bags.
That's in addition to running steps at Johnson Hagood Stadium, hauling water jugs, wrestling giant truck tires, climbing ropes on the Marine Corps Obstacle Course and more.
To keep everyone on task and on course, Citadel Marines and Naval Reserve Officers Training Corps cadets will yell (and encourage) participants along the way.
The Bulldog Challenge raises about $29,000 a year to support scholarships selected by The Citadel Semper Fidelis Society, sponsor of the competition. This year, proceeds will go to the Semper Fi Society Scholarship Fund, which provides financial aid to a participating member of the society enrolled in NROTC and working toward a commission in the Marine Corps.
Late registration wraps up today.
Pinewood Back Nine
Saturday's only 5K is the Pinewood Back Nine, which also includes a one-mile fun run, to be held at 7:45 a.m. Saturday at Legend Oaks Golf Club in Summerville. Proceeds benefit Chase for a Cure.
Like the Bulldog Challenge, if you haven't signed up for the TryCharleston half ironman and sprint distance triathlons Saturday in Mount Pleasant, you need to hurry as registration ends today.
For those not participating, be aware that triathletes will be biking on segments of U.S. Highway 17 and S.C. Highway 41 in the northern part of Mount Pleasant on Saturday morning.
The event is staged from the KOA campground in Mount Pleasant.
Bike racing
Triathletes won't be the only ones riding bikes on Lowcountry pavement this weekend.
In what is the biggest weekend in competitive cycling, the Low Country Racing Team will host the I'On Smackdown Race on Saturday and the S.C. State Criterium Championships at West Ashley High School on Sunday. Both events feature division races, ranging from pros to amateurs.
Spectators are welcome to watch.
(Nearly) free sailing
Ever wondered what sailing might be like? Want a chance to find out? Then check out Sail Charleston, a free, one-day exhibition of sailing for nonsailors.
On Saturday, Sail Charleston, an adjunct event of the Sperry Top-Sider Charleston Race Week, which is organized by volunteers from the Charleston Ocean Racing Association, will hold the event at the Charleston Maritime Center.
From 10:30 a.m. to 3 p.m., those interested will be able to meet and talk with representatives from local yacht clubs, sailing associations and sailing-oriented businesses, as well as check out a variety of boats from single-person dinghies to world cruising yachts.
Those wanting to get out on the water can pay $10 for a short tour of the harbor and check out the exciting racing action of Charleston Race Week.
The organizations and businesses that will be on hand include Charleston Community Sailing (junior and adult sailing programs), the College of Charleston Sailing Association, Sayre Sailing, St. Barths Yachts and Charleston Yacht Club.
Banff Film Festival
Indoor events rarely make this column, but the Banff Mountain Film Festival World Tour, to be held 7 p.m. Saturday at the College of Charleston's Physicians Auditorium, is one exception.
Brought to Charleston by Half-Moon Outfitters, the film festival presents the best of 350 award-winning films on the outdoors for one night of indoor adventure, action and environmental awareness.
Tickets are $10. The event benefits Charleston Waterkeeper, "a data-driven, nonprofit organization" focused on water quality issues in the basin of the Ashley and Cooper rivers, and the College of Charleston School of Sciences and Mathematics.
SUP ocean races
The folks at Half-Moon are busy this weekend.
Following Banff, the Half-Moon Open Ocean Challenge, formerly Bodhi's Revenge, will be presented by Half-Moon and the Charleston County Park and Recreation Commission on Sunday on Folly Beach.
Hot on the heels of the Golden Nugget SUP Race, the Half-Moon Open Ocean Challenge is the area's only stand-up paddleboard surf slalom and Battle of the Paddle-style event.
This event will appeal to intermediate and advanced paddlers as well as spectators.
An unusual surf-style race, the Half-Moon Open Ocean Challenge will feature a slalom surf course with buoy turns in the impact zone. The 2-mile short course will feature one loop with a beach sprint, while the long course will run the route twice with two beach sprints.
The races also benefits Charleston Waterkeeper.
And more
All of this, plus Earth Day events and the East Coast Paddlesports and Outdoor Festival.
Whew, and we thought Cooper River Bridge Run weekend was big.
Reach David Quick at email@example.com.
Todd Tyler and Kip Downer, part of team Recon 365, do 10 fire team pushups during the 14th annual Bulldog Challenge.×
Competitors in The Citadel's Bulldog Challenge have to make it up and over obstacles, including bars, pipes and rope ladders.×
Senior Citadel Cadet Drew Ferris climbs the ropes during the Bulldog Challenge.×
Citadel cadet Randy Stamper twists his body around a couple of bars during an exercise on an obstacle course at a past Bulldog Challenge.×
University of South Carolina student Erin Sterbling holds on to teammate Amy Zion as they near the finish line during the half-mile fireman's carry as their Citadel competitor Terrence Jackson carries his teammate Anthony Reynolds during a past Bulldog Challenge.×
Jeffrey Steele, Terry Fellows, Matthew Rogers and Drew Schildwacher of The Citadel demonstrate the stadium run, which will involve running up and down stairs with sandbags.×


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quote: you can plant more corn in the short and long run. let me see you "plant" more crude in the long run.
quote: Number of days until all the ethanol is gone and the US has completely exhausted its domestic corn supply = 15.5
quote: Furthermore, your solution of 15.5 is the number of days corn supply TO MAKE a barrel of corn oil ...
quote: As soon as you find the resources (manpower, land, and others) to support a twenty-five-fold increase in corn production, by all means - let me know.
quote: (Remember, we need to feed ourselves too.)


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on January 27, 2013 - 1:06 PM
Cars crossed the Peace Bridge 1.1 million fewer times last year compared to 2003.
Of that, 45,000 fewer trucks crossed the Niagara River span between Buffalo and Fort Erie, Ont.
So why do Peace Bridge officials want to spend tens of millions of dollars to widen the bridge approach to the U.S. plaza and build a ramp and underpass to the Niagara Thruway?
They want reduce truck backups and improve traffic flow – neither of which can happen by reduced traffic levels alone.
"Those are good projects that will make a difference but do not involve expanding the plaza," said Ron Rienas, general manager at the Buffalo and Fort Erie Public Bridge Authority, commonly known as the Peace Bridge Authority.
The bridge authority also counts on a pilot project that will allow American personnel to inspect U.S.-bound trucks in Fort Erie as a way to improve traffic flow across the Peace Bridge.
With the inspecting and processing of trucks done on the Canadian side of the border, but with enforcement done in the United States, the project should free up more space passenger cars on the plaza.
Though the project focuses on trucks, "the benefits accrue to the cars," Rienas said.
All the projects are designed to improve the traffic flow out of the plaza.
The amount of processing time and document review has increased at the primary inspection booths compared with 2001. It takes far longer, which is why there is more congestion even though there is less traffic.
As for trucks, all it takes is a handful designated for further inspection – without adequate parking space to accommodate the rigs – to keep all of the other trucks stuck in line behind them, even those cleared during their first inspection.
The Peace Bridge was one of two places picked for the pilot project.
U.S. Sen. Charles E. Schumer, D-N.Y., announced the pilot agreement in October after yearlong negotiations involving the U.S. Department of Homeland Security and its Canadian counterpart.
The Western New York congressional delegation has supported the concept. However, several environmental and community groups, as well as residential neighbors, object to measures they say would bring more trucks through the West Side neighborhood and aggravate health and air pollution concerns.
The pilot concept will be tested first at a border crossing in Blaine, Wash., before coming to the Peace Bridge.
Government and bridge officials will study data collected over six months in Blaine before beginning the 18-month project here.
Now, nine of every 10 trucks that cross the Peace Bridge are released after their initial inspections, with just one of 10 directed to undergo secondary inspection.
It is that one out of every 10 trucks that blocks traffic in the cramped U.S. plaza. By moving inspection duties over to Fort Erie, where there is more acreage available, more space is freed up on the U.S. for trucks to park for their secondary inspections, out of the way of the trucks cleared to depart the plaza.
Officials here want to see if the new inspection set-up in Washington changes how many trucks are referred for further inspections there.
Peace Bridge officials want to be prepared if they detect a change in the percentage of trucks cleared after initial inspections at the Washington crossing, Rienas said.
The pilot project may begin at the Peace Bridge in late summer or early fall, he said.
A previous "shared border management" effort failed in 2007, in part, because the two countries could not agree on how U.S. and Canadian customs officers should respond to any vehicle turned back from entering the United States. The Department of Homeland Security insisted that any such vehicle be apprehended by U.S. officials working in Fort Erie, with the driver and passengers fingerprinted. Canadian officials said that would violate the Canadian Constitution, which provides that no one may be arrested without probable cause.
Under the pilot project, the truck drivers would be questioned by U.S. officials in Fort Erie, but the drivers would cross the Peace Bridge before being told if they were cleared.
A 'go/no go" message would be sent to inspectors in enforcement booths on the Buffalo plaza, who would then tell the drivers if they were subject to more inspections or enforcement actions.
There's space in Fort Erie for 12 lanes with inspection booths for the U.S.-bound trucks, Rienas said.
Two enforcement booths for the trucks would be installed on the U.S. plaza.
Another project, the $10 million-plus widening project, would provide an additional 215,000 square feet of approach space for U.S.-bound vehicles.
The 500-feet wide by 60-feet long concrete deck would allow better access to a NEXUS lane for travelers in that program.
It would get trucks off the bridge quicker, Rienas said.
Construction is expected to begin this fall, with a construction schedule of one to two years.
The exit-ramp and underpass project is scheduled to begin this spring, with construction expected to last a year.
Now, vehicles leaving the U.S. plaza cross paths depending on which exit they want, one for the northbound Niagara Thruway and the other for the southbound Niagara Thruway.
The authority plans to create a single plaza exit point and eliminate the criss-crossing traffic patterns.
The new ramp – to be built over the current entrance way into the plaza for vehicles coming from the northbound Niagara Thruway – would allow exiting cars wanting to head north on the Niagara Thruway to access the entry to that expressway after driving around the perimeter of Front Park.
email: firstname.lastname@example.com


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3 Reasons It's So Hard to Make Superman Interesting
There Are People Superman Can't Save (and That's a Good Thing)
Batman has Gotham, the Flash has Central and Keystone City, and Martian Manhunter has Middleton. While Superman may live in Metropolis, he is America's hero. He has a lot more ground to cover, and also divides his time hanging out on other continents (wintering in the Fortress of Solitude, etc.). Now, a man who can travel faster than a speeding bullet still can't be everywhere at once, which suggests that somewhere there are people dying in warehouse explosions and mass murders and roofing accidents every single day because he's busy flirting with Lois Lane or fighting Lex Luthor. For every person he saves, there are hundreds more, some of them children, taking their last breath while staring hopefully at empty skies.
Superman can't help but set a precedent he can never live up to. From the first time he stopped a bridge from collapsing or diverted a tornado from a town, he instilled a false hope among Americans. That means that every day, even if he never bothered to put on glasses and go to work again at The Daily Planet, Superman is still letting down hundreds if not thousands of people.
Somewhere, someone left an infant in the car with the windows rolled up. Superman has to decide which life is more valuable.
Add on top of that everyone who is dying of societal problems that are beyond his capacity to fix, and suddenly a really interesting portrait of Superman starts to emerge. Nearly every writer who has ever tackled a Superman story arc has tried to test the limits of his powers by pitting him against an alien being who's even stronger and more super, but they are completely ignoring the potential all around them for an engaging narrative about Superman struggling and failing to help everyone all at once from broad, systemic issues.
He stands for truth, justice, and the American way, but justice and the American way don't always see eye to eye. There's no way Superman can stop homelessness, disease, teen suicide, or domestic abuse. How could he? One of his powers isn't lobbying local politicians. That's why the most interesting Superman arc isn't about Lex Luthor building a secret island or bad guys coming from another galaxy to wipe out civilization. It's about a country of people who live at the edge of Superman's capacity to help, but because of that part in his super brain that wants to protect humanity at all costs, he nearly destroys himself trying. It wouldn't be about Superman, it would be about the people struggling and dying in a world where he exists, but he still can't save everyone. Give me that movie and I would watch it over and over just to see the greatest version of a human driven to the breaking point like an engine with no oil. Superman could be our test-drive hero. I would watch the hell out of that.
You can follow Soren on Twitter or Tumblr. You are also welcome to join his Classics Club that meets on Thursday afternoons in the quad.


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As Immunotherapy Revolutionizes the Cancer Treatment...
Developers of DTC Genetic Testing Are...
LC-MS Gains Favor Due To the...
Wall Street Decline Takes Its Toll...
Technical advances in the use of protein-expression systems have enabled scaled production of membrane proteins and other difficult to express proteins. These advances have also helped preserve the structure and function of the expressed proteins.
Shuguang Zhang, Ph.D., associate director of the Center for Biomedical Engineering at MIT, has found that the use of short peptide surfactants in commercial E. coli cell-free systems facilitates the rapid production of membrane proteins.
GPCRs, the most difficult integral membrane proteins to produce, can be produced in milligram quantities when the right surfactant is added to the cell-free system. The soluble GPCRs that Dr. Zhang's team has produced show a-helical secondary structures, which suggest proper folding; ligand binding studies have confirmed the maintenance of biological function.
"I am convinced that the use of short, simple peptide surfactants is absolutely the key for successful production of membrane proteins in cell-free systems," he says. "Further, the use of cell-free systems allows for industrial-scale standardization of protein production. We have demonstrated its utility on GPCRs. If we can just reduce the cost 10–20 fold in the next decade, I have no doubt you'll see an increase in its use for protein production."
The benefit of using cell-free systems is the ease of use and the ability to add components to promote protein production and stability. These cell-free systems can be maintained for a long time, though they are not amenable to repeat production.
As for the addition of peptide surfactants, it is essential to screen different surfactants to ensure matching with each individual membrane protein for optimal production. The peptide surfactants that have been used are designed with a hydrophilic head (1–2 residues) and a hydrophobic tail (3–6 residues). They are usually 2–3 nm in length, their ionic character and strength can be controlled by selection of the intervening residues.
The surfactants have a tendency to self-assemble to form membrane-like environments that provide stability for the membrane proteins, even though the mechanism remains unclear.
Joining Dr. Zhang as a presenter at the upcoming "PEGS" conference in Boston will be Mark Welch, Ph.D., director of gene design at DNA2.0.
DNA2.0's custom gene design and synthesis service enables customers to obtain optimal protein expression for their gene of interest, according to Dr. Welch. The company is guided by informatics and experimental studies of the effect of gene usage on heterologous protein expression from different expression and production hosts (bacterial, yeast, and mammalian cells). From this analysis, the company has developed robust algorithms that predict optimal gene sequences that will provide abundant protein yields.
At present, DNA2.0 has turned its attention to the application of these tools for optimal production of pharmaceutical target proteins in mammalian hosts. "We have developed solid algorithms for production of a variety of proteins in bacteria and yeast systems," Dr. Welch explained. "We are now focused on building that same level of knowledge in mammalian cell systems."
Working with an academic partner, DNA2.0 is also exploring the optimization of protein expression of difficult to express membrane proteins as well as the effects of gene sequence on expression level and localization in differentiated mammalian tissues.
Dr. Welch will also talk about Infologs™, non-natural gene variants that are designed through informatics to capture maximal structure/function correlations in the biological space of interest. DNA2.0's research demonstrates how the technique leads to uniform sampling, systemic variance, and unrestricted information-rich results.
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The IMF Brian D. Novis Reseach Grant Award presentations took place on Saturday, December 7th, 2002 in Philadelphia, PA during the 44th annual meeting and exposition of the American Society of Hematology. In attendance were many members of the IMF Scientific Advisory Board, IMF Directors, staffers, and supporters whose efforts helped make the grants possible.
IMF President Susie Novis opened the reception with a warm welcome, and provided background information on the IMF research program that dates back to 1995. Dr. Robert A. Kyle, Chairman of the IMF Scientific Advisory Board, and Dr. Brian G.M. Durie, Chairman of the Board, were on hand to present the awards. Individual donors were introduced to the researchers whose projects they are funding. The grant recipients spoke of the objectives of their research projects.
This issue of Myeloma Today features research abstracts of several Junior Grant recipients. Others will be profiled in the upcoming issue of the newsletter.
Dr. Kewal Asosingh
Tumor-host interactions during MM disease progression; functional roles of CD45 subsets
Vrije Universiteit Brussel (VUB)
Brussels, Belgium
For the development of new, more effective strategies in the treatment of cancer, understanding of the biological heterogeneity in the tumor population is an important goal. Only specific subsets within the parental tumor have the necessary receptors for motility, invasiveness, and tumor spread. In different tumor stages remodeling of the extracellular matrix occurs, by exchange of proteinases and cytokines between stromal cells and cancer cells. This modified microenvironment stimulates invasion and promotes survival and proliferation of the cancer cells. Only specific cancer cell populations are able to induce the production of survival/growth factors and proteolytic enzymes by local stromal cells and have the capacity to induce angiogenesis, which is pivotal for progressive tumor growth. In multiple myeloma (MM) research, understanding of the heterogeneity, in general, and understanding of the specific roles of CD45 subsets, in particular, is still in its infancy. CD45 is a transmembrane tyrosin phosphatase. While immature plasma cells are CD45 positive, fully matured plasma cells lose all CD45 expression. Myeloma patients have a heterogeneous CD45 expression pattern and very recently CD45 appeared to be a predictor of therapeutical response. In our previous work the in vivo bone marrow homing, differentiation and proliferation of CD45 subsets in the 5T experimental mouse model (11, 12) were investigated. In the current project the roles of CD45+ and CD45- 5TMM cells during myeloma disease progression will be analyzed. Experiments with mice injected with the heterogeneous 5T2MM cell population indicated major alteration in the CD45 subset composition during disease progression. In the early stage of the disease (few weeks after intravenous injection) the majority of the MM cells had an immature, invasive and apoptosis resistant phenotype (CD45+CD138-IL6-Ra+). In contrast, end stage MM cells had a mature, less-invasive and apoptosis sensitive phenotype (CD45-CD138+IL6-Ra-). In between there was a gradual progression in the subset composition towards the endstage phenotype. The early-, intermediate- and endstage myeloma cells will be investigated for functional differences. Invasion, apoptosis and proliferation will be analyzed. Bone marrow samples collected at different time points (with one-week time interval) will be examined for the presence of angiogenesis and osteolysis by microvessel density quantification and micro CT, respectively. Correlations with the presence of CD45 subsets will be analyzed. The observed alterations in the subset composition suggest alterations in tumor-host interactions during the disease progression. Alterations in gene expression profile of BM stromal cells and MM cells during disease progression will be identified by differential gene expression analysis (cDNA micro array) at different time points (early tumor stage, middle and endstage). In particular, differential expression of genes involved in apoptosis, invasion, proliferation, angiogenesis and osteolytic bone disease and in the signaling cascades of these processes will be analyzed. The differential expression will be confirmed by Real Time-PCR and at protein level by flow cytometry, Western blot or immunohistochemistry. The overexpressed/ down-regulated proteins will be tested for their functional involvement.
Dr. Chao-Lan Yu
Suppressor of Cytokine Signaling (SOCS): Its Regulation and Potential Implication as a Therapeutic Agent in Multiple Myeloma
Vanderbilt University School of Medicine
Nashville, Tennessee
Interleukin-6 (IL-6) is the major growth and survival factor in human multiple myeloma (MM) cells. Through the signaling receptor subunit gp130, IL-6 activates the receptor-associated JAK family protein tyrosine kinases and, subsequently, the downstream signal transducer and activator of transcription 3 (STAT3). STAT proteins are latent cytoplasmic transcription factors that regulate the expression of specific cellular genes. Consistent with the critical role of STAT3 in IL-6 signaling, constitutive STAT3 activation has been reported both in human myeloma cell lines and in bone marrow cells from MM patients. Aberrant STAT3 activation may contribute to the malignant progression of MM by the induction of antiapoptotic proteins Bcl-2 and Bcl-xL. Furthermore, STAT3 activation is also linked to cell cycle progression by the induction of cyclinD1. However, the molecular mechanisms of constitutive STAT3 activation in MM cells still remain largely unclear.
STAT3 can be down-regulated through negative feedback control following cytokine-induced activation. The suppressor of cytokine signaling (SOCS) family members are key players in this process. SOCS proteins are induced by cytokines to prevent further activation of the JAK-STAT pathway. Among eight SOCS family members, both SOCS-1 and SOCS-3 have been shown to be induced by IL-6 and to inhibit subsequent IL-6 signaling. SOCS-1 and SOCS-3 inhibit JAK kinase activity either by direct association with JAK kinases or by simultaneous interactions with JAK and the receptor. We have preliminary data indicating that the absence of SOCS gene expression correlates with constitutive STAT activation in leukemic T cells. Therefore, we would like to hypothesize that defect of negative feedback control through SOCS-1 and SOCS-3 proteins may contribute to constitutive STAT3 activation and resistance to apoptosis in MM cells. This hypothesis will be tested in a well-characterized human myeloma cell line, U266, through the following specific aims:
1. To determine if the negative feedback control involving SOCS-1 and SOCS-3 proteins is intact in MM cells. The observation that exogenous IL-6 could induce further STAT3 activation in U266 myeloma cells suggested that JAK kinases are not effectively inhibited by SOCS-1 and SOCS-3. It is possible that, in U266 myeloma cells, IL-6 autocrine loop cannot induce SOCS-1 and SOCS-3 expression to a level high enough to inhibit JAK kinases. We will first compare the expression levels of SOCS-1 and SOCS-3 in U266 myeloma cells with varying degrees of STAT3 activity. This can be achieved by treating U266 cells with a high dose of exogenous IL-6 or AG490, a JAK-specific inhibitor. A constant low or undetectable SOCS expression regardless of endogenous STAT3 activity will suggest an intrinsic defect in SOCS expression in U266 myeloma cells. On the other hand, if SOCS expression correlates with STAT3 activity in U266 myeloma cells, we will determine its ability to associate with and inhibit JAK kinases. Our expectation is that functional expression of SOCS-1 and/or SOCS-3 will be defective in U266 myeloma cells.
2. To evaluate the effects of ectopic expression of SOCS-1 and SOCS-3 on survival and growth of MM cells. We will transiently transfect U266 cells with an enhanced green fluorescent protein (EGFP) expression construct encoding SOCS-1, SOCS-3, or the empty vector. EGFP-expressing cells will be isolated by FACS sorting and then subjected to biochemical assays to confirm the expression of SOCS proteins and inhibition of STAT3 activity. Northern blot analysis will follow determine if SOCS proteins reduce the expression of bcl-2 and bcl-xL, two known antiapoptotic genes. To determine if SOCS proteins promote Fas-mediated apoptosis, transfected U266 cells will be stimulated with Fas ligand or Fas agonistic antibody CH-11, and then examined by Annexin V-PE staining and FACS analysis. We predict that exogenous expression of SOCS-1 and/or SOCS-3 in U266 myeloma cells will result in lower STAT3 activity, reduced levels of bcl-2 and bcl-xL transcripts, and increase in Fas-mediated apoptosis. In addition, we will perform cell cycle analysis and examine cyclinD1 expression on transfected U266 myeloma cells. We hypothesize that forced SOCS-1 and/or SOCS-3 expression may also induce cell cycle arrest by inhibiting cyclinD1 expression.
SOCS proteins have been shown to inhibit proliferation signals induced by a number of oncoproteins. Consistent with the role of SOCS as tumor suppressor, higher incidence of malignancies have been reported both in humans and in mice with defective SOCS expression. Furthermore, SOCS proteins have also been shown to be more effective than dominant-negative STAT proteins in the treatment of certain immune disorders. Results from this proposed research project, therefore, should provide additional insights into the molecular mechanisms that contribute to the pathogenesis of MM and may suggest novel strategies for potential treatment of MM.
Dr. Lee Ann Garrett-Sinha
Identification of the Role of Ets-1 in Regulating Plasma Cell Numbers
University of Buffalo
State University of New York
Buffalo, New York
Plasma cells normally function to produce antigen-specific antibodies and thus help control infections. As such they are a critical part of the immune system. Indeed, people who lack plasma cells due to the genetic disease, X-linked agammaglobulinemia (XLA) are subject to severe recurrent bacterial infections. On the other hand, unregulated plasma cell growth can lead to the development of certain tumors (plasmacytomas and multiple myelomas). Thus, it is critically important for an organism to strictly control the production and the loss of plasma cells to ensure that sufficient cells are available to fight infection, but that excess cells are eliminated.
The processes of cellular differentiation, proliferation, and apoptosis require specific proteins that promote each cell's fate. Transcription factors regulate the expression of the various proteins necessary for each of these different cellular outcomes. Ample evidence implicates members of the Ets family of transcription factors in the regulation of B cell development, expansion, maturation, and death. Ets proteins regulate the expression of membrane receptors that promote cellular differentiation and proliferation such as the interleukin (IL)-7 receptor, the granulocyte/macrophage colony stimulating factor (GM-CSF) and the B cell receptor (BCR) (11,13-18). Ets proteins also regulate the expression of anti-apoptotic proteins such as Bcl-XL and c-rel as well as pro-apoptotic proteins such as Fas and caspase-3. Therefore, Ets proteins regulate diverse pathways that can lead to cell survival, cell proliferation, or cell death.
Interestingly, up-regulation of Ets-1 protein is detected in a sub-set of tumors. In addition to the receptor genes, pro- and anti-apoptotic genes discussed above, Ets-1 is also known to regulate the expression of certain metalloproteinase genes. Expression of proteinases is required for tumor cells to degrade surrounding extracellular matrix, invade nearby tissues, and metastasize to distant sites. Over-expression of Ets-1 in tumors generally correlates with their increased invasiveness and metastatic potential and with a poorer prognosis for the patient. In addition, expression of Ets-1 in vascular endothelial cells is important during the process of angiogenesis. Since tumor growth requires new blood vessels, the role of Ets-1 in angiogenesis has important implications for cancer growth.
Gene-targeted mice lacking Ets-1 exhibit a ten-fold increase in the numbers of plasma cells in the spleen. The deregulated production of plasma cells found in these animals is reminiscent of unregulated plasma cell growth found in plasmacytomas and multiple myelomas. Thus, Ets-1-/- animals provide an animal model to study factors affecting the equilibrium between plasma cell formation and deletion. The investigations we propose in this application will address how Ets-1 regulates the differentiation of plasma cells, their proliferation and/or their survival. We believe that our studies will have direct bearing on understanding, and perhaps treating, diseases caused by uncontrolled plasma cell growth.


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'Dark Wallet' for Managing Bitcoin Arrives This Week
The anti-government bitcoin wallet launches Thursday.
Last year, the Journal told readers about Cody Wilson's efforts to take the virtual currency off the grid through a project called Dark Wallet, the 26-year-old's latest effort to use technology to sidestep the government. Mr. Wilson is most famous for creating the first working gun made by a 3-D printer.
After months of programming, Wilson and his partner, British anarchist Amir Taaki, also 26, are releasing an early version of the software for free download. It will work as an add-on for Google's Chrome browser.
For all the talk of bitcoin being untraceable, it's actually pretty easy for cops to figure out who is spending what unless suspects take very technical precautions. Wilson seeks to change that by making it easier for non-techies to have an anonymous currency online.
Mr. Wilson wants people to buy whatever they want on the Internet, whether it be drugs, guns or an artistically questionable CD. He's gained fans in libertarian circles — including PayPal founder Peter Thiel.
Among other things, Dark Wallet is designed to encrypt bitcoins as they're spent, making it difficult to see who is buying what. Think of it as throwing a ball into a spinning lottery tumbler and picking out a different ball.
If more people use Dark Wallet, the theory goes, more people put balls in the lottery tumbler and make it harder to determine which belongs to whom.
"Is it at the level where grandma can be mixing bitcoins and becoming the next drug kingpin? No," Mr. Wilson said in an interview Tuesday. "I think it's ripe for the initiated to begin experimenting."
In an email Monday, Stephen Hudak, spokesman for the U.S. government's Financial Crimes Enforcement Network, declined to comment specifically on Dark Wallet. He did, however, say, "We are well aware of the many emerging technological efforts designed to subvert financial transparency. It's certainly our business to be interested and vigilant with respect to any activities that may assist money laundering and other financial crimes."
Wilson meantime faces more mundane issues.
He is still working to achieve tax-exempt status for Defense Distributed, the self-described nonprofit he launched in 2012. The Internal Revenue Service, which declines to discuss pending applications, hasn't ruled on the matter.
He also needs to raise money at a time when bitcoin's value is wildly unstable. Wilson and Taaki had raised about $100,000 for Dark Wallet in online donations, much of it in bitcoin.
But by the time they converted bitcoins to dollars earlier this year — after bitcoin's value tumbled — Wilson estimated they had about $65,000 to $75,000.


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Known as one of the most famous sites in the world, Stonehenge in England is the remains of a ring of standing stones set within the Earth. Take a look at how many Americans reimagined this prehistoric monument.
Stonehenge recreated across America
Cars, refrigerators used to make siteUPDATED 10:59 PM CDT Aug 23, 2013
CommentsThe views expressed are not those of this site, this station or its affiliated companies. By posting your comments you agree to accept our terms of use.blog comments powered by Disqus


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Expanding Use of NGS Has Largely...
Wall Street Decline Takes Its Toll...
Developers of DTC Genetic Testing Are...
As Immunotherapy Revolutionizes the Cancer Treatment...
Kadcyla® (T-DM1 or ado-trastuzumab emtansine), a new treatment for patients with HER2-positive, metastatic breast cancer to be marketed by Roche's Genentech subsidiary, won FDA approval this morning.
Kadcyla is a trastuzumab-DM1 antibody-drug conjugate intended for patients previously treated with Herceptin® (trastuzumab), another anti-HER2 therapy, and taxanes, a class of chemotherapy drugs commonly used for the treatment of breast cancer. The newly-approved drug is a combination of Herceptin and DM1, which Kadcyla delivers to the cancer site, shrinking the size of the tumor, slowing disease progression, and prolonging overall survival.
The fourth FDA-approved drug that targets the HER2 protein, Kadcyla was developed by ImmunoGen, and joins three other HER2-positive breast cancer treatments approved in the past decade and a half: trastuzumab (1998), lapatinib (2007), and pertuzumab (2012). Like Kadcyla, trastuzumab and pertuzumab are made by Roche's Genentech subsidiary.
However, ImmunoGen will yet benefit from Kadcyla's approval. While the company was rebuffed by FDA nearly three years ago when it sought fast-track review for the drug, ImmunoGen will receive a $10.5 million milestone payment from Roche, as well as royalties on commercial sales of Kadcyla.
In 2000, nine years before its acquisition by Roche, Genentech licensed from ImmunoGen exclusive rights to use the company's maytansinoid TAP technology to develop anticancer products targeting HER2. Six years later, Genentech advanced T-DM1/Kadcyla into clinical testing.
Kadcyla won FDA approval through the agency's priority review program, which allows a speedier six-month review of drugs judged as having potential to provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.
FDA based its decision on safety and effectiveness results from a clinical trial of 991 patients randomly assigned to receive T-DM1 or GlaxoSmithKline's lapatinib plus another chemotherapy drug, capecitabine. Patients treated with T-DM1 had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine. The median overall survival was 30.9 months in the T-DM1 group and 25.1 months in the lapatinib plus capecitabine group.
During the trial, patients received treatment until either the cancer progressed or the side effects became intolerable. The study was designed to measure progression-free survival (the length of time patients lived without the cancer progressing) and overall survival (the length of time patients lived before death).
However, T-DM1 is being approved with a Boxed Warning alerting patients and health care professionals of the drug's potential side effects, which include liver toxicity, heart toxicity, and death. The drug can also cause severe life-threatening birth defects, and pregnancy status should be verified prior to starting treatment, the warning cautions.
In patients treated with T-DM1, the most common side effects were nausea, fatigue, pain in the muscles or joints, low levels of platelets in the blood (thrombocytopenia), increased levels of liver enzymes, headache, and constipation.
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Six musical themes, which perfectly will approach for various video-projects. This Music Pack is created for the purpose of economy of money of the buyer.
1. Time Machine 1:01
This musical theme has a retro sound and sets an image of a time machine, which moves us to the past.
2. East HipHop 1:08
This is hip-hop instrumental in the east coast style. There is image of New-York's streets.
3. Mission Completed 1:26
Slightly cheerful, but serious musical theme.
4. Flying Human 1:06
This musical theme will suit something mysterious, maybe for something from science-fiction.
5. Guy 1:11
This quirky, urban hip-hop theme creates an image of a bad guy with malicious intentions, maybe with criminal character.
6. Gentleman 1:01
Very useful rap beat for the description of a serious person who won't back down. Hard drums and powerful bass are used.


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STATE COLLEGE - To a man, every Penn State player wanted the win more for Bill O'Brien than for himself.
"He's been through a ton so far here," quarterback Matt McGloin said.
The Nittany Lion players have been through more than their share of adversity, too, and Saturday's 34-7 win over Navy took, as center Matt Stankiewitch said, "a lot of weight off our shoulders."
"A lot of people hit the panic button after the 0-2 start," McGloin said of those outside the program.
Even the players, whether most would admit it or not, started having doubts after two tough losses.
"Everything's shaken -- your character, your confidence," Stankiewitch said of losing.
So they looked to their head coach to keep their spirits up. To keep them inspired. To keep them focused.
O'Brien has been the rock that has kept everything together since taking over in January, and the players desperately wanted to reward him with the first victory of his head coaching career.
"In many ways, it was a long time coming," O'Brien said.
Officially, Saturday's win was the first for Penn State in 15 years, since it beat Wisconsin, 35-10, on Nov. 22, 1997. The quarterback that day was none other than Mike McQueary, who turned out to be a central figure in the Jerry Sandusky scandal that resulted in all wins from 1998 through 2011 being stripped from the program.
O'Brien can't worry about all of the past. As he has said before, he's got enough problems of his own right now, and an 0-3 start could have been devastating.
"The one thing that winning does is it cures a lot of things," O'Brien said. "Winning also breeds confidence."
It didn't take long for Penn State (1-2) to establish control against Navy (0-2), scoring on its first two possessions for a 14-0 lead less than nine minutes in. A crowd of 98,792 celebrated Military Appreciation Day at Beaver Stadium and watched the spirited Midshipmen give everything they had, but it wasn't nearly enough on either side of the ball.
The outcome was never in doubt in the second half, and when the fourth quarter rolled around, McGloin first got the idea in his head to douse O'Brien with the traditional Gatorade bath (water in this case).
"I had to convince Stank to do it," McGloin said.
The players wanted to keep it secret from O'Brien, but Stankiewitch was concerned McGloin would spoil it because he kept telling everyone on the sideline. As it turned out, the offense was on the field near the end of the game, so the honors fell to defensive tackle Jordan Hill and linebacker Gerald Hodges to pick up the Gatorade jug.
"I heard the crowd, so I figured something was up," said O'Brien, who saw the bath coming and was able to step forward and save himself from the entire dousing.
The coach later said he wished the players hadn't done it but acknowledged, "They probably enjoyed it and will get a laugh about it tonight when they are sitting around commiserating about the game."
O'Brien's new tradition of having the players sing the alma mater took place after the game -- he forgot to have them do so following the opener against Ohio -- and the coach noted, "It felt really good doing it after a win."
O'Brien made a key decision right off the bat to help his team prevail. Penn State won the coin toss, and while he likes to defer to the second half, this time O'Brien took the ball -- realizing possessions are important against a methodical offensive team like Navy and that getting an early lead could help.
Sophomore receiver Allen Robinson enjoyed a huge day for the Lions, and it started with him making a 45-yard catch down to the Navy 4 on the opening series. That set up a touchdown, and on the next series, Robinson pulled in a 45-yard TD pass from McGloin for a 14-0 lead with 6:40 left in the first quarter.
Robinson caught two more TDs -- a 2-yarder in the second quarter and a tipped pass from 25 yards out in the third -- and finished with 136 yards on five catches.
"It definitely felt great to get our first win," Robinson said. "I wish it came a little earlier in the season, but that's what we worked hard for."
Robinson has turned into a major weapon for the PSU offense as he already has 24 catches through three games. O'Brien said the receiver often gets single coverage because of the offensive scheme, and when that happens, Robinson usually finds a way to get open.
"His routes are so crisp and so good, that's why gets open a ton," said McGloin, who finished 13-of-21 for 231 yards and four touchdowns.
With win No. 1 out of the way, and that weight off their shoulders, the Lions will try to make it two in a row next week against Temple. The Owls went 0-28 all-time against PSU during Joe Paterno's tenure.
A win next week, and all of a sudden the Lions would have a little streak going and a good bit of confidence heading into Big Ten play.
"I'm very confident we can get on a winning streak," Hill said. "We're a good football team."


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Top Definition
the combination of thank and you. it is usually used by ppl who want to sound cute or funny. mostly used by girls in a high pitched voice, but can also be used by guys.
Fransheska: Here's your stuff, Stefanie.
Stefanie: Tankuz! =D
Stefanie: Tankuz! =D
dafuzziesによって 2009年01月24日(土)
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Top Definition
The stupid miscellaneous noise that Dilberts make when they learn that they are going to dissect a pig in biology. Dili is a stupid fag wag.
Pan: Hey Dili, we're gonna dissect a pig this year!
Liz: ERM! I LIKE HARRY POTTER!! IM A LURD!
Liz: ERM! I LIKE HARRY POTTER!! IM A LURD!
dodane przez LizHater styczeń 18, 2005
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eeew means disgusting or not-good, but can sometimes mean good or awesome in certain places.
1. eeew, thats just plain gross.
2. eeew, that was fun!
2. eeew, that was fun!
dodane przez Sean B. październik 12, 2003


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Al McMordie CASHED his NCAA Football Game of the Month last week on the Louisville Cardinals over Florida State, and his NFL version goes this Sunday. It's backed by two situations that are 22-2 ATS combined. Don't miss this AWESOME 10* PLAY. Al's 50-29 his last 79 NFL, so pick up Big Al's #1 NFL Game of the Month for September and get the $$$$
At 4:05 pm, our complimentary selection is on the Seattle Seahawks minus the points over the San Francisco 49ers. Both of these teams come into this game with 1-1 records. The 49ers upset the Rams in their opener, 28-0, but were blown out by the defending NFC Champion Panthers, 46-27, last week. Meanwhile, Seattle's a fortunate 1-1, as it barely got by a mediocre Miami team in Week 1, 12-0, as a double-digit favorite, and then lost to another mediocre team last week, when the Rams upset them, 9-3, as a 5.5-point dog. Thus, Seattle is 0-2 against the spread to start the season, but this lack of pointspread success is one of the reasons why I like them this week. Since 1980, unrested teams that failed to cover the spread as a favorite in Weeks 1 and 2 are 66% ATS in Week 3. And the Seahawks are 72-26 straight-up and 61-33-4 ATS at home since 2005, including 11-3 ATS off an upset loss. Finally, Seattle's a dominant 53-25 ATS after scoring less than 20 points in back to back games, including 11-0 ATS their last 11. Take the Seahawks. Good luck as always…Al McMordie. And don't miss any of my huge winners, including our Baseball (currently on a 26-8 MLB Run), and our NFL Game of the Month (50-29 Last 79 NFL). Or, better yet, join for a week or month today to get all of our award-winning plays (on a 463-334, + $55,163 Run)!


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Top Definition
It's a girls name. Usually the girls who have this name are gifted with big boobs and a sweet disposition. Their favorite thing to do is lay in the sun with out a care in the world.
Oh there is Tsile laying in the sun... her boobs give her shade.
dari WhentheAngelsCry Minggu, 09 Mei 2010
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David Zalubowski/Associated Press file photo
David Zalubowski/Associated Press file photo
John Fox and Mike Smith each emphasized power running games in their three years together in the NFC South.
They were perceived as conservative, strong-willed and unbending in their run-first convictions.
The stereotypes are changing as suddenly no one seemed to know what offensive philosophy to expect from either coach entering the 2012 season.
How would Fox, the former longtime Carolina Panthers coach beginning his second season in Denver, adjust to the dramatic addition of Peyton Manning?
Would Smith, entering his fifth season in Atlanta, allow new offensive coordinator Dirk Koetter to pump up the passing game with Matt Ryan?
Week 1 victories offered encouraging and exciting opening acts for each offense, setting the stage for the Broncos� visit to Atlanta on Monday night.
Manning completed 19 of 26 passes for 253 yards with two touchdowns in last week�s 31-19 win over Pittsburgh. It was an important step in Manning�s comeback after a 20-month layoff for neck surgery. Then again, could anything less be expected from the four-time MVP?
Smith said Manning�s re-emergence leaves Atlanta�s defense with little margin for error.
�I think the most important thing is we have to play sound technique and make sure we�re in the right place because if you�re out of place by half a yard, you�re going to pay for it,� Smith said. �He has a very good understanding of how you�re trying to defend him. You give him pre-snap reads, he�s going to know where to go with the football.�
The Falcons, meanwhile, showed that their increased emphasis on Ryan�s passing game was no preseason mirage. Ryan completed 23 of 31 passes for 299 yards and three touchdowns in last week�s 40-24 win at Kansas City.
The Falcons� emphasis may have changed from Michael Turner�s running to Ryan�s passing, but Fox said he sees similarities to the Atlanta offenses he prepared game plans for twice a year from 2008-10.
�They utilized the no-huddle even when I was back there, but that is what makes them such a good offense,� Fox said. �They have the ability to get big and pound you and get small and stretch it that way. That�s what good offenses are capable of, and they�re definitely one of them.�
The 30-year-old Turner only had 11 carries for 32 yards against the Chiefs. Ryan had Atlanta�s only touchdown rushing. Turner, Jacquizz Rodgers and Jason Snelling combined for only 20 carries.
Ryan said last week�s run-pass ratio did not set a mold for the season.
�I think it�s one of those cases where Kansas City is stout against the run,� Ryan said. �They�ve got some defensive tackles who are really good in their 3-4 scheme. We feel like it was to our advantage to throw last week.
�It�s one of those things I think we can do whatever we need to do. I think we�re talented that way, so if we�ve got to run it 50 times, we�ll run it 50 times. It�s just the way certain games shake out.�
As the Falcons embrace the no-huddle offense, second-year wide receiver Julio Jones is emerging as a top threat worthy of equal billing with Roddy White and tight end Tony Gonzalez. Jones had six catches for 108 yards and two touchdowns last week.
Broncos cornerback Champ Bailey said Jones (6-3, 220) reminds him of a young Terrell Owens. Bailey said Jones can be even better than Owens.
�I was telling somebody he looks like a young T.O. when T.O. was big, strong and fast and youthful out there,� Bailey said. �He looks a lot like him, but I think his hands are better. He�s more polished at a younger age. I just think his upside is greater than what T.O.�s was.�
Thanks to the opener, the Falcons� offense received a confidence boost after the 2011 season ended with a 24-2 loss to the New York Giants in the NFC wild-card game.
�For sure. You see how explosive we can be offensively,� center Todd McClure said.
White took a cautious approach when asked for his review of the win.
�Not to take anything away from the Kansas City Chiefs, but we�re going to play a lot of teams who are better on defense than those guys are,� White said. �It�s going to be a whole lot different this week.�
The Falcons are adjusting to the loss of starting cornerback Brent Grimes to a torn Achilles tendon. Smith said Dunta Robinson, who had been the nickel back, will start at right cornerback. Christopher Owens moves into the nickel spot. Asante Samuel is the left cornerback.
Joe Mahoney/Associated Press file photo


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Wall Street Decline Takes Its Toll...
Process Development Jobs Still the Most...
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As Immunotherapy Revolutionizes the Cancer Treatment...
High-content screening (HCS) is a powerful technology that addresses a variety of questions within biological research. Established for pharmaceutical small molecule screening, it is regularly applied in target discovery and validation. Capable of observing phenotypic changes, HCS requires a technically complex infrastructure of hardware and software components. This complexity is compounded by the management of HCS images and image-analysis results, which can be resource- and time-consumptive.
Genedata Screener® for HCS overcomes these challenges (Figure). Its integrated image-management capabilities handle all data-management issues even for heterogeneous, multi-instrument environments. And, its data-analysis functionality gives scientists access to a broad range of screening applications, completely independent from the high-content infrastructure.
The following outlines key HCS lab activities and challenges, and how Genedata Screener for HCS addresses them.
1. HCS Instruments and Image-Analysis Software
The breadth of HCS biological research is reflected by the variety of HCS instruments in laboratories. While each instrument comes with its own image-analysis application, additional commercial or open-source applications are also available; screening scientists must select the right combination of instrument and image-analysis software most appropriate for their research. While scientifically optimized, this workflow is not easily supported as integrating different software components is a manual process.
Genedata Screener for HCS tackles this workflow issue by automatically importing images from any instrument, preserving the original files. The results from image analysis are imported automatically as well and are annotated and linked to the images from which they were derived.
2. Cell-Level Data Analysis
HCS image analysis works on individual biological objects such as cells or nuclei: During segmentation, individual biological objects are identified; subsequent quantification provides a set of numbers describing them. Individual cell-based data must be aggregated to deliver a result per well as all cells in a well are treated the same and any difference is due to different phenotypes or biological variability.
For example, in a receptor internalization assay, the amount of receptor moving from the cell membrane to the nucleus may be of interest. During image analysis, information such as size and intensity, and nucleus size and intensity are obtained for each cell. To obtain a result the cellular information is averaged across all cells in a well. Whether a cell is included in the average is defined as part of the image-analysis process, before the actual data for the complete experiment is available. If you want to change selection criteria afterward, the image analysis must be repeated.
Genedata Screener for HCS stores cell-level data in parallel with well-level data enabling scientists to define and edit—on-the-fly—cell populations. It also allows scientists to generate new well results by selecting different cell aggregations from a wide range—from simple average-up to advanced methods such as Kolmogorov–Smirnov.
3. Plate Data Processing: Quality Control and Result Generation
In HCS experiments, the plate is the processing unit of interest. Each plate contains samples plus controls to gauge the signal range and for normalization. Scientists should perform plate QC to identify and invalidate suspicious wells based on one or more QC features; and to calculate quality metrics such as Z´ or Signal over Background. Calculation of new signals based on a linear composition of other measured features may also be needed. All necessary data processing and review is provided by Genedata Screener; basic operations are done in seconds, allowing scientists to focus on experiment QC.
Result calculation follows plate processing; for different experiments different results have to be calculated: In genetic screens, the validity of a connection between a known target and a phenotype is verified. In small compound screens, the potency of known substances is compared across different cell lines to understand the relevance of the biological system for the target–phenotype relationship. Compound combination experiments may be conducted to understand the mechanistic relation between the phenotypic effects of two compounds affecting the same target. Genedata Screener provides a single platform for these and all other types of screening experiments.
4. Image Access
Image access is vital in all HCS. A promising well requires visual inspection to ensure phenotypic changes are as expected and to exclude artifacts. Poor-quality wells are inspected to understand issues and to improve operational quality for subsequent experiments. In a small screen of about 1,200 compounds, there are 10,000s of images, making it impossible to review all of them. With Genedata Screener image management, scientists can display images for wells and compounds of interest with a single mouse click without leaving the software.
5. Results Storage, Access, and Browsing
With Genedata Screener, you can trigger the automatic transmission of all results for a selected experiment to a corporate data warehouse. Most data warehouses, however, cannot accept data from HCS (multiple results per well), cannot store HCS images (needed to validate the numerical results), and cannot handle multiple substances per well (as in compound combination experiments). Genedata Screener overcomes this issue with a result database.
This result database stores all relevant data in functional tables (e.g., a table for all compound potency results, one for all compound combination results, and one for all gene activities). These tables contain links to underlying data-analysis sessions in Genedata Screener, allowing scientists to interpret a given result in the context of the original data-analysis session. Furthermore, the result database stores the references to the wells of interest, for which relevant images can be retrieved by the stand-alone image viewer. Stored data can be browsed with a variety of downstream tools such as Spotfire, Excel, or web interfaces.
6. Image Life-Cycle Support
Image handling, a concern in all HCS experiments, is particularly important in target validation. Storing all images in full-resolution for long-term instantaneous access presents a serious investment in central hard-disk capacity. Genedata Screener image management supports archiving—for all image formats—while maintaining full access to the images in context of the downstream analysis or for result storage.
At image import time, one or multiple thumbnails are automatically generated for every image and separately stored from original image files. If the latter have been archived and sequentially deleted from the fast disks to free resources, thumbnails are still available and will allow scientists to operate the data-processing pipeline connected to image management without any noticeable difference. In the event that scientists want to re-access the original images, they can restore these at any time.
The aforementioned key HCS lab activities illustrate how Genedata Screener effectively eliminates multiple software packages and provides a systematic and standardized methodology for innovative HCS data management and analysis. Using Genedata Screener, lab scientists report the time it takes to conduct an experiment can be reduced from eight weeks to one week, with HCS data-handling times reduced by more than 85%. These time efficiencies and productivity gains are especially important for target discovery and validation groups, which run a diverse portfolio of complex HCS-based experiments. Genedata Screener for HCS streamlines data management and analysis for these groups, giving scientists instant access to images and empowering them to focus on the wet work.
Oliver Leven, Ph.D. ([email protected]), is head of Genedata Screener Professional Services/Genedata.
Oliver Leven, Ph.D. ([email protected]), is head of Genedata Screener Professional Services/Genedata.
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While Zika continues to garner a lot of news coverage, a Mayo Clinic survey reveals that Americans believe the country's most significant healthcare challenge is cancer. Compared to other diseases, does the possibility of developing cancer worry you the most?
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Top Definition
a FOB (fresh off the boat) who does not drink, smoke, have sex, gamble, or partake in any other "sins."; would rather talk on AIM rather than have fun; would rather play water pong, and not drink the water, and then spread the word that he played pong; has a maniacal chin strap that seems to display signs of fighting for gay rights; always wears a visor regardless of weather; thinks he can do bhangra;
yo stop being such a nikul, lets have fun for once.
Struti 가 작성 2007년 06월 10일 (일)
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