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5 Movie Monsters Ripped from the Pages of History Books
It seems like the subtext in most horror movies is that the true monster ... is us. Normally, that's a heavy-handed metaphor for man's inhumanity to man, but sometimes that whole "man is the real monster" bit is a tad more literal. Take, for example, these five poor wretches ...
#5. The Demon King
The Byzantine empire was the Matrix: Revolutions of Roman empires: It made a ton of money and stopped some big invasions but wasn't much to talk about. (Also, Keanu Reeves was there.)
Michael IV ruled from 1034 to 1041. He was a peasant who fell in love with the empress (aw, that's sweet), even though she was married (aw, that's ... really not smart). Since Empress Zoe was the previous emperor's daughter, her husband, Romanos III, feared losing both his wife and his throne. The emperor asked Michael to swear on holy relics that there were no shenanigans going on, which he did. Silly Romanos! A peasant with the stones to ball the friggin' emperor's wife probably isn't afraid to break a sanctified pinkie swear.
Sure enough, in April of 1034, Romanos III was found dead in the tub. Cause unknown, but, y'know, not that unknown. Especially since Michael and Zoe were married the same day.
History's first twee murderers.
The new emperor, Michael, bribed the patriarch into properly crowning him, adding to his lousy reputation as a counterfeiter, adulterer, and regicidal boy toy. That's when Michael began bleating like a sheep, moving in erratic jerks, and hurting himself ... all things you might recognize from that exorcism movie that gets remade with a new title every year.
Screen Gems, Lionsgate, Warner Bros., Paramount
What was it called again? The Demon Be-gonner Guy?
Despite his efforts to conceal it, a lot of folks concluded that Michael was suffering from demonic possession as punishment for his sins. Although some historians considered him an "honest" and "brave" general who fought for the common folk against the nobility, Ioannes Scylitzes was not a fan, and further suggested that the empress's love for Michael was demonically influenced. By our count, he was at least three Game of Thrones characters.
The Boring Reality
It's often said that for every beautiful woman there's a guy who's bored of screwing her after he's murdered her husband and stolen her kingdom. Michael was that guy. Ignoring his adoring cougar wife, he struggled to rule amid epileptic fits. And just like all those crappy exorcism movies, epilepsy explains pretty much everything about this story.
#4. The Werewolf's Last Confession
Peter Stumpp had many aliases, which is weird, considering that he was pretty conspicuous (he was missing his left hand). Oh, and also because all of his crimes were committed in wolf form. How many canines do you know with alternate identities?
Now, witch and werewolf trials were pretty common in Germany in 1589, due to it being Germany in 1589. The only things to do at the time were farm, worship the devil, and make either sausage or war. Clearly, Stumpp was a big fan of those first three. But it was the brutal manner of his execution that put this story on the front page of the Syphilitic Holsteiner Gazette.
When caught and pressed, Stumpp admitted to eating livestock and at least 14 kids (including his own son), two pregnant women, and sundry German maidens.
Jupiterimages/liquidlibrary/Getty Images
Not a fun guy at parties.
Stumpp credited his master-level display of lupine dickitry to a magic belt given to him by Satan. But in a Faustian twist, the pumps that came with it didn't match! Curse your treachery, Beelzebub!
Stumpp perpetrated his crimes on countless victims for 25 years by exploiting the "killer in the woods" cliche. He practically invented Jason Voorhees' patented shtick, including the bit about waiting for the rest of the stupid teenagers to split up and go looking for their missing friend. But one day some hunters got the belt off of Stumpp, and then it was time for old-timey German country justice, as seen in this creepy paper animation:
The captured Stumpp was tortured with a breaking wheel, stripped of his flesh with hot metal pincers, and then had all of his limbs broken. Which, for the record, is about as dead as you can get, short of being ground into a fine powder, mixed into a power shake, and digested by fitness freaks with high metabolisms.
The Boring Reality
What if I told you that people don't actually turn into werewolves?
Stumpp was a Protestant in a part of Germany that had recently been returned to Catholic control. Torturing a fellow Christian, even a heretic, could be a dodgy proposition to explain before the Lord, but a Satan worshiper guilty of the worst crimes -- ah! That's doing God's work. Basically, the new ruler of the region made a bloody example of him.
But Stumpp confessed to prosecutors, right? More like persecutors -- people give false confessions all the time, especially while you're torturing them. And even if you don't confess, what's to stop them from saying you did? If you're still not convinced that Stumpp's conviction wasn't on the level, his mistress and daughter (who were known to be of good character, save for that whole Protestant thing) were also tortured, flayed, strangled, and burned.
It would be 400 years before Germany finally settled down and took up much more acceptable hobbies, like fascism and coprophilia.
#3. The Rebel Vampire
In the early 1700s, Serbian peasant Arnold Paole fought against the Ottomans as a hajduk -- a term that meant either "highway bandit" or "freedom fighter."
In Serbia is same thing.
Returning home from the war in Turkish Serbia, Paole had a great life waiting for him: a new patch of farmland ready for plowing, an eager new wife ready for plowing, and a hero's welcome from his town, which hopefully also involved plentiful plowing.
But something wasn't right with young Paole. He had ... changed. Neighbors noted his now gloomy demeanor. Of course, this being a rational period in history like rural 18th century Eastern Europe, everybody chalked it up to PTSD and worried no more. So imagine how unsettled they were to hear Paole's explanation: He had been attacked by a vampire.
According to Paole, he managed to slay the vampire, but sustained a nasty wound in the process. He made the mistake of trying to inoculate himself from vampirism by rubbing his foe's blood in his wound and eating soil from its grave. Come on, man, everybody knows you're supposed to eat the blood and rub the soil. What is this, your first vampire rodeo?
Astonishingly, villagers did not run to get their pitchforks, and Paole lived out the rest of his days in gloomy peace -- which in this case was literally just days. He fell from a hay wagon in the stupidest death any vampire ever suffered. What's a wagon's top speed? 5 mph? Geez, even toddlers and hemophiliacs laugh off a wagon fall, Your Dark Majesty. So the villagers buried Crazy Arnie, made a few wagon-based puns at his expense, and went back to plowing fields and each other.
And that's when the corpses started piling up.
About three weeks after his death, four people reported Paole stalking them ... and then died soon after. You know what happens next: shovel, stake, saw, scorch. The report says the mouth of Arnold's corpse was full of blood, he hadn't decomposed at all, and even creepier, he allegedly groaned when stabbed. Five hasty piles of ash later, everyone could rest easy.
Brand X Pictures/Brand X Pictures/Getty Images
Except for Paole's mother, who was not invited to bridge club that week.
The Boring Reality
Those attributes are as common in corpses as poor life choices at a Gathering of the Juggalos. Mostly they're due to gasses that escape during decomposition. Which, come to think of it, also describes a gathering of the Juggalos. Best to stab them through the heart just to be safe. Hey, it worked for the Serbs.


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The Sizzling Hot Ramadan Giveaway
In celebration of the holy month of Ramadan, all of us here at La Moda are proud to announce the Sizzling Hot Giveaway, a special month-long event that is all about the spirit of generosity and charity. As a way of saying thank you, we are giving away a bunch of awesome prizes to a few lucky readers.
We have partnered with the hottest brands in town to help make your Eid holidays just a little bit brighter and more exciting. Chic Parisian makeup brand Bourjois is giving away twin goodie bags filled with products from foundation to eye shadow worth AED 500 each. Colourfully trendy Rimmel London is giving you a chance to win a a goodie bag of cosmetics so huge it can last for an entire year.
And MODAHOUSE, the UAE's online shopping destination, is offering vouchers that can buy one very lucky reader a new pair of Louboutins, Miu Mius or Manolos. The choices of brand, style, and size are solely up to the competition winner. So if you're not into makeup, this prize is definitely something to look out for.
"How do I win any of these wonderful prizes?" you ask. Well, we're certainly not going to ask you to jump through hoops or do the tango barefoot on a bed of red-hot coal. For each competition, you just need to answer a very simple question, fill out the form, share the story on Facebook or Twitter, and you're totally in the draw. At the end of Ramadan, which will be in early September, we will announce the winner. That doesn't sound so hard, does it?
Okay, no more explaining. Time to win! Choose the competition you would like to participate in from the list below to get started. You can join all three for more chances of winning something at the end of the day. Good luck!
- Win vouchers to buy yourself a pair of Louboutins with MODAHOUSE
- Win a makeup goodie bag worth AED 1,000 from Rimmel London
- Win a makeup goodie bag worth AED500 from Bourjois Paris
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subset: commoncrawl


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Brasilaccesspoint (ponto de acesso Brasileiro ) Foi criado para que os(as) cosplayers Brasileiros(as) possam , achar com mais facilidade pessoas do mesmo país, quando um Brasileiro seguir a pagina e for cosplayer e ainda não foi seguido ele será acrescentado a lista, ps: tem algumas pessoas que não são cosplayers na lista pois não tive tempo de verificar todos os perfis Muito Obrigado!!!! °w° facebookpage:https://www.facebook.com/WC-Brasil-Access-Point-1650532271863446/?ref=hl
follow my page! facebook page https://www.facebook.com/guilcosplaydattebayo/
deviantART: http://miss--valentine.deviantart.com/ Facebook: https://www.facebook.com/MissValentineCosplay
Hi Everyone! Im From Malaysia and Im New To Cosplaying... Teach Me Senpai!www
FACEBOOK: https://www.facebook.com/clairemarielle WATTPAD: http://www.wattpad.com/user/YaoiFujoshi
I´m Paraguayan Cosplayer and Propmaker.. Page on Facebook: https://www.facebook.com/ferchu.ozito Instagram: http://instagram.com/ozitofer twitter: doraeferchu991 World Cosplay: http://worldcosplay.net/member/ozito_cosplay
Hellooo! ヾ(。◕ฺ∀◕ฺ)ノ My name is Camila, but you can call me "Kami". I'm a cosplayer since 2012! Thanks for visiting my profile, you can also find me at: ❀ DeviantArt: http://kamiimak.deviantart.com/ ❀ Cure: http://en.curecos.com/profile/?ch=370717 ❀ Facebook Fanpage: https://www.facebook.com/KaMisakiq
My name is Giovanna. I'm have 12 years... I'm Cosplayer since I was 9 years. I am very low in height. But I have a big heart, captive everyone around me. I hope you like my cosplays. <3. <3
Hi, my name is Yuu and I am a Brazilian cosplayer I'm a cosplayer since July 2011, so I still do not have much experience, "But I want to continue improving my cosplays so they can look more like the characters Tumblr: http://yuu-hiko.tumblr.com/ Facebook: https://www.facebook.com/patricia.p.pinheiro.5 Intagram: http://instagram.com/yuuhiiko twitter: https://twitter.com/Yuu_Hiko
My name is Samantha but you can call me SammyKoi. I like my life as cosplayer. I hope you all enjoy what you'll see here. ♥ facebook: facebook.com/sammykoicosplayer ♥ Ask: ask.fm / MapleVodka ♥Deviantart: sammykoi.deviantart.com
Hey guys! Just a cosplayer from Brazil, I like anime, mangas, tv-series, ball jointed dolls and cosplay of course ^^ Friends are very wellcome! :) All my best to you all!
I'm a Brazilian cosplayer since 2009, hope you enjoy my work =^.^= DeviantART: http://riseofthetraider.deviantart.com/
Hey! My name is Dayane, I'm 15 ^^ I love cosplaying because I can bring a character that i love to life.


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In fact, #BreakingBad was a trending topic on Twitter for several days following Sunday night's mind-blowing (get it?) episode. Even Dean Norris (Hank) had something to say – via a FunnyOrDie video (Spoiler, obviously).
And while people were live-Tweeting their reactions to the shocking show, BatDad was dispensing valuable advice, the '80s came back, and more random stuff happened online. Check it out:
Dean Norris Reacts to Breaking Bad
He proves that nothing can keep Hank down. Except a dome.
BatDad Offers Fatherly Wisdom – in a Batman Mask – on Vine
Spoken in Christian Bale's signature gravelly Batvoice, cautions his kids on the dangers of artificial sweeteners and putting Katie Holmes in your movie.
Here's a compilation of his clever Vines:
New Volkswagon Commercial Channels Iconic A-Ha Video "Take on Me"
Now you can relieve the '80s – without the mullets.
Adam Richman Loses 60 lbs. After Quitting Man V. Food
Next challenge? Trying to win over Winnie Cooper, because he now looks exactly like Fred Savage.
i0s7 Came Out for iPhone – and Everyone Hates It
Even Miley Cyrus stopped taking selfies to complain about the software.
I hate the iPhone update.— Miley Ray Cyrus (@MileyCyrus) September 20, 2013


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Georges-Henri Lemaître
Georges-Henri Lemaître (1894–1966) first proposed (in 1927) the creation of the universe through a "Big Bang." A Belgian, Roman Catholic priest, and veteran of World War I, he was considered by the secular physics community an accomplished physicist and astronomer. Despite Edwin Hubble being said to have found evidence to support Lemaître's theory two years later, the theory is still behind creationism in the competition to describe the origin of the universe.
Lemaître's view was revolutionary for his time and decades ahead of the rest of the secular physics world. Indeed, supposed "confirmation" of some of Lemaître's ideas were still being realized, over the objection of leading physicists, towards the end of the 20th century.[1]
Most physicists, including Einstein, disagreed with Lemaître at first,[2] as they thought the universe existed forever in a steady state. But they subsequently changed their opinion, agreeing with Lemaître as evidence supposedly mounted to support his theory and the scientific community ironically shifted away from the better-supported creationist explanation.
- ↑ Catholic Education Resource Center: 'A Day Without Yesterday': Georges Lemaitre & the Big Bang
- ↑ Astronomy Notes: Observations and Some Implications


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First Year Academic Advising Program - New Students
You are about to embark on a wonderful, exciting and mysterious adventure! The START Center is here to help reduce some of the mystery of this adventure. We are here to assist you in creating a path for this journey and academic advising is critical to your success along this path. It is important during your entire journey but it is VITAL as you begin.
The videos and links in the 'Steps for Registration' will prepare you for your first advising appointment. Work through all the videos and links and as you do so, jot down any ideas, questions or concerns you have so they can be addressed during your advising appointment. Also please look through the First Year Program guide that you received in the mail and pick two or three Learning Communities that look interesting. The final video will explain how to schedule your first advising appointment.
STEPS FOR REGISTRATION with standard videos
To get started click on the above title. It will link you to the six (6) videos you need to watch and the First Year Academic Advising Tutorial for you to complete in order to schedule your advising appointment.
STEPS FOR REGISTRATION with captioned videos
To get started click on the above title. It will link you to the six (6) videos with closed captioning you need to watch and the First Year Academic Advising Tutorial for you to complete in order to schedule your advising appointment.
First Year Program
Westminster College recognizes the importance of a coordinated, dynamic, and successful first year for our students. In addition to our First Year Orientation program, we also offer Learning Communities for each student and a First Year Mentoring Program. Click HERE to view the online First Year Program Guide. Click on the above title to go to the First Year Programs home page.
First Year Student Orientation
First Year Student Orientation is more than an orientation. It is an opportunity to join your future classmates in fun activities and informative discussions about what to expect at Westminster College. Click on the above title to go to the First Year Student Orientation home page.
New Student Important Contacts
Click on the above title to go to a list of departments and centers that new students need to know about. The list includes a brief description of services and links to the department's web page and the location on the map.
Outdoor Orientation Program
Start your Westminster experience with the Outdoor Recreation Program by exploring the Intermountain West's amazing wilderness with fellow students! The Outdoor Orientation occurs before and is a complement to the First-Year Student Orientation. Click on the above title to go to Outdoor Recreation's home page and learn more about the trips.
Eportfolios showcase your student experience, allowing you to include evidence of learning not just from coursework, but from your daily life. Click on the above title to get more information.


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Purchasing staff provide training on online requisition, travel, and other topics by request. Please contact the Purchasing Office to schedule training for your department.
Office Hours:
Monday - Friday
8:00 a.m. - 5:00 p.m.
The University of Texas at Brownsville website uses Javascript.
To access this page as it is meant to function please use a Javascript
enabled browser.


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HEDGESVILLE - More than 2,000 community members are anticipated to join together in celebrating more than 175 years of history and heritage at the 17th annual Hedgesville Heritage Day Festival.
The festival has been an occasion of town pride since 1996, a revival of the festival the town used to host in the 1950s and '60s.
From 10 a.m. to 4 p.m. Saturday, Hedgesville will be rich in activities and people celebrating community and tradition. The festival will feature activities for everyone, from a moon bounce to live bluegrass music by the Back Creek Valley Boys.
Article Photos
The featured presenter for the event will be local author Rodger Engle, who recently published his first book, "Stories of a Small Town," which recounts his experiences as a child in Hedgesville between 1948 and 1964.
"Rodger being a native of Hedgesville and writing about his hometown, that is Heritage Day," Hedgesville Mayor Mary Sue Catlett said.
Engle will be signing copies of his book as well as reading excerpts from "Stories of a Small Town" throughout the festival. Engle pledged to donate a portion of the day's proceeds to help fund the construction of the Hedgesville Library.
"It's an honor to be asked to be a part of this. Growing up here, it was just a wonderful place to be and a wonderful time to be in that place. ... I can't imagine as a child having a better place to grow up," Engle said.
Local Civil War authors Jim Droegemeyer and Steve French will also present "Hedgesville and the Civil War" at the Naylor Library, with French speaking at 11 a.m. and Droegemeyer presenting at noon.
Festival-goers will be able to shop among 24 artisans featuring hand-crafted works, find new reads at the Friends of the Hedgesville Library book sale and visit the Love Your Neighbor "non-sale" giveaway at the Hedgesville Presbyterian church.
Additional attractions include scheduled magic shows by Michael T., multiple guided historic tours of different locations throughout the town and sampling fall favorite foods and baked goods from vendors.
Participants also will have the opportunity to give back to the community by bringing a nonperishable item to donate to the Berkeley County Back Pack Program that helps feed more than 180 students just from Hedgesville schools.
"(The festival) brings the community together. Everybody is in a good mood, the weather is always nice, the churches are friendly and helpful, everyone helps each other and there's something for everyone to do," Hedgesville Town Secretary Amy Corvin said.
taff writer Samantha Cronk can be reached at 304-263-8931, ext. 132, or firstname.lastname@example.com.


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Skip to main content
Cornell University
Asian Studies Department
more options
Korean Language At Cornell
Language Information
Other Resources
Food, Bibimpap
Language Contact Person:
Meejeong Song
Phone: 255-8498
Office: 123 Rockefeller
Complete List of Staff
Office Hour: Tuesdays 1:30-2:20 or by appointment
The Korean language is spoken by more than 70 million people living on the Korean peninsula and its outlying islands (the Republic of Korea in the south and the Democratic People's Republic of Korea in the north) and it is ranked the 13th largest language group in the world. Hangul (한글), the Korean alphabet, was invented in 1443 by King Sejong and his royal scholars, and began to be recorded using a completely phonemic writing system. Hangul consists of 10 basic vowels and 14 consonants and the individual consonant and vowel letters are combined into syllable blocks to spell Korean words and sentences.
The Korean Language At Cornell
The Department of Asian Studies offers courses in Korean in four levels: Elementary, Intermediate, High-Intermediate and Advanced Korean. The Elementary and the Intermediate level courses are in two tracks:Heritage (KOREA1109-1110-2209-2210)and Non-Heritage (KOREA1101-1102-2201-2202). The KOREA 1101-1102 sequence is for true beginners who have had no or very little prior knowledge of Korean, and the KOREA 1109-1110 sequence (Elementary Reading and Writing) is for heritage students to improve their reading and writing skills.
Cornell Area Program Affiliation:
East Asia Program
On-line Korean Placement Test and Written Exemption Test
Placement Test: All students who wish to take a course are required to take a placement test to determine the right course for them, except KOREA 1101. The placement test can be taken anywhere any time of the year on-line at http://collt.lrc.cornell.edu/. Students can take the test once per semester only. Results from this test cannot be used to pass any college language requirement or to be exempted from that requirement. For exemption in Korean, you must take the Korean exemption test.
Exemption Test: Students who wish to be exempted from the language requirement may take the written exemption test. Those students should be familiar with advanced vocabulary on newspaper and be able to write one's opinion on current issues in Korea. The exemption test is scheduled twice per semester. Find the information of exact date and location at http://lrc.cornell.edu/asian/programs/placement and go to the location on the scheduled test date. No need to sign up for the test.
Last edited by ms296 on Thu Jan 10 2013 at 09:19 AM.


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UNIVERSITY PARK - Most expected Central Florida to provide the stiffest test Penn State had seen so far this season and maybe even come in here and win.
Almost no one, though, could have envisioned the Nittany Lions' defense being bludgeoned to the extent that it was in a 34-31 loss Saturday night at Beaver Stadium.
En route to allowing 507 yards of total offense, Penn State struggled equally in failing to stop the run (219 yards, 5.8 per rush) and pass (20-for-27-288).
"We felt we would be able to handle both better," defensive coordinator John Butler said.
Butler credited Central Florida - "our tackling was an issue, and their skill was an issue," he said - and its coaches.
"We knew what we needed to stop, but we didn't," he said. "They did a better job collectively of executing their game plan."
Bill O'Brien was also effusive in his praise for UCF and preferred not to heap blame on his defense.
Like Butler, he acknowledged, "we didn't tackle very well," but he was quick to mention that the offense, special teams and coaching could have been better, too.
And, like all coaches in the emotional moments following an unexpected loss, he said he'll have a more definite opinion after watching the films.
What he'll see, though, will be startling.
After the Lions opened the season with two strong defensive performances, they were housed by a team that ran through and passed over them.
When the Lions sent blitzes at Central Florida quarterback Blake Bortles, his quick feet eluded them, and Penn State did not manage a single sack. And when the Nits sat back in coverage, giving too much ground like they did early, Bortles picked them apart - particularly exposing their young cornerbacks.
Butler made some changes in the second half, shifting Adrian Amos back to cornerback and inserting Ryan Keiser at safety.
"We tried everything - we emptied the game plan," Butler said. "We tried man, zone, half-man, half-zone."
Down 31-24, the defense did rally and appeared to force a change of possession until a late flag following a third-and-9 incompletion with 12 minutes to play came flying in from Centre Hall.
"Those are big," Butler said, adding it's a "buzz-kill" of a raucous crowd that certainly saw an entertaining game, albeit not the desired outcome.
Butler didn't argue the call, at least in the Beaver Stadium media room, instead calling it "a bang-bang play."
Maybe it was an official's error, but the Lions' defense had already been torched so complaining about that penalty - especially since that seemed to be about the only really big call Penn State didn't get - would have been sour grapes.
The Lions' lack of defensive depth was a major concern entering the season. Linebackers Mike Hull and Ben Kline returned for spot duty Saturday, but the entire back seven appeared to suffer from not having much contact in practice because the coaching staff needs to limit the injuries.
It's a domino effect that, on this night, fell apart like a Jenga game.
Nonetheless, O'Brien and Butler were confident the Lions would bounce back emotionally. After all, it's not like a bowl bid was lost.
"Our players," Butler said, "have been through a lot worse than losing to Central Florida."
Isn't that the truth?
Rudel can be reached at 946-7527 or firstname.lastname@example.com. You can also follow him on Twitter@neilrudel.


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CHESTER - For the first three and a half years of his professional boxing career, Youngstown's Jake "The Bull" Giuriceo had always had his hand raised when the final bell rang.
Giuriceo made his pro debut in Feb. of 2009 and remained undefeated through his first 17 bouts. All that changed on July 21 when "The Bull" lost a majority decision to veteran Michael Clark.
Clark (42-7-1, 18 KOs), who came into the contest with more knockouts than his opponent had fights, used his experience to hand Giuriceo (16-1-1, 3 KOs) the first defeat of his career to win the Ohio State light welterweight title at Promo West Pavilion in Columbus.
Article Photos
Jake Giuriceo
Now, Giuriceo will have his chance at getting back in the win column on Dec. 1 against Peter Oluoch in one of the co-features in a night full of boxing action at The Harv at Mountaineer Casino, Racetrack & Resort.
While the loss to Clark was clearly a set back for Giuriceo, the young boxer said it could have been a blessing in disguise.
"I learned a lot from that loss," he said. "Mainly in the training aspect. Training at home just wasn't getting the job done."
For his bout against Clark - and a win over Juan Santiago at Mountaineer in April - Giuriceo had been training locally where he also got married in May. But, for his most recent fights prior to that he had been working with trainer Frankie Duarte in California.
"I needed to get back out here (California) because I was learning boxing better," Giuriceo said. "I can get better sparring here. There's a lot bigger name guys out here. I'm able to work with a lot of up-and-coming fighters. I'm just able to learn the game better here."
While training on the West Coast has given Giuriceo renewed energy, he said he is happy to be having his fight back at Mountaineer.
"I really enjoyed fighting there last time," he said. "I'm excited they wanted me back and I thank God for that. I'd fight there every time they do a show if they let me."
Giuriceo's opponent, Oluoch, is a 34-year-old native of Kenya who has a record of 11-6-2 with six knockouts. Oluoch's last fight was a unanimous decision loss to Jose Hernandez (13-6-1) in March in what was his first fight in the United States.
In June of 2011, Oluoch fought for the WBO African welterweight title, losing to Bethel Ushona (27-2-1).
"Honestly, I don't know very much about him," Giuriceo said of Oluoch. "I'm going to see if my manager can get some film on him. But, I know he'll come to fight and be trying to win. I think a lot of those guys with records around .500 are actually tougher than some of the undefeated fighters. I'm training like this is a world title fight."
The Giuriceo-Oluoch bout is one of many on the card with local interest.
At the top of the card, promoted by Roy Jones Jr., is Paul Spadafora against Solomon Gerome (22-3-1, 11 KOs). Spadafora (46-0-1, 19 KOs), won his last fight on Aug. 18 at Mountaineer against Humberto Toledo (41-8-2, 25 KOs) and is looking to climb back onto the world title stage at age 37. Spadafora, a McKees Rocks native who formerly held the IBF lightweight world championship, served a 13-month prison sentence in 2005 for attempted murder and completed a lengthy stay in rehab earlier this year.
The other co-feature will pit Monty Meza-Clay (33-3, 21 KOs) against Emmanuel Lacero (26-12-1, 14 KOs) in a rematch of a majority decision win for Clay in their bout on July 14 at Rivers Casino in Pittsburgh.
Meza-Clay, a native of Rankin, Pa., has won five straight fights and could be in the mix for a title shot with a victory. Lacero, who started his career at 21-0-1 and has since dropped 12 of his last 17 bouts, has fought the likes of Manny Pacquiao, Daniel Ponce de Leon, Rocky Juarez, Diego Magdaleno and Patrick Hyland.
On the undercard, Pittsburgh's Billy Hutchinson (4-1-2) will take on Jose Caraballo (5-4); Pittsburgh's Morgan Fitch (7-0) will battle Cameron Allen (4-11); East Liverpool graduate Joey Holt will make his pro boxing debut against Alan Moore (3-17); and former Steubenville Big Red football standout Angelo Magnone will fight in an amateur contest to begin the night.


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Jacques Arbeau, who often used the pseudonym Jacarbo, worked as a librarian when he made his first illustrations for text stories and novels in the Del Duca magazine L'Intrépide in 1949. In 1952 he created his first comic, 'Dop le Chien', in Reflets, followed by 'En Avant la Flibuste' for Junior in 1954. Between 1954 and 1972, Arbeau worked for various magazines, like Âmes Vaillantes, Record, Fripounet, Marius, Ima, Moi en Monsieur and Tintin, creating various short stories and game pages. He also worked on several horizontal and vertical strips for newspapers.
He developed a semi-realistic style for his serial 'Le Roman de la Table Ronde', that was published in 630 strips in several regional papers through Intermonde Presse. He made numerous comic adaptations of novels for Paris-Jour ('Accusé, levez-vous!', 'Colomba', 'L'Horloger du Diable'), as well as educational strips for Presse-Service Magazine. He also worked for the agency Mondial Presse ('L'Horloger du Diable') and the newspaper Franc-Tireur ('Truand et Gentilhomme', with Yves Dermèze in 1956).
In 1959, he took over the series 'Brik' from its creators J.K. Melwyn-Nash and Cézard for Éditions Aventures et Voyages. He created 'Perle' in Anouk with Roger Lécureux in 1967 and 'Mirabelle et Sauriné' in Lorraine Magazine from 1969. In 1974, he took over another famous series - 'L'Espiègle Lili' - following the death of Gérard Alexandre. He made new, and more modern, stories for Lili-Aggie Magazine, and in several books published by the Société Parisienne d'Édition in cooperation with Paulette Blonay until 1986.
By 1982 Arbeau also drew 'Les Pieds Nickelés' from scripts by Serge Saint-Michel. Furthermore, he made illustrations for editorial sections in Système D from 1981, and provided art for comics biographies of Anne Le Roy, Élisabeth de Surville and Émilie de Villeneuve for Fleurus. He also worked for Sadifa ('La Force d'Évangile') and Imagi ('Des Pépins dans le Pruneau', 'La Disparue de Montgeron', both with Serge Saint-Michel). Among his final comics work were two books of 'Aventures d'Agenius' with Jacques Dubourg, dealing with the history of the Lot-et-Garonne area. He retired in the late 1980s.


text:
Top Definition
When a person expresses love, interest, or affection for someone or something and the person they are speaking to only says "Ditto", like Patrick Swayze in the movie Ghost.
Ron told his girlfriend he loved her, only to be ghosted by her response of "Ditto".
viết bởi B. Peppers 18 Tháng mười, 2007
Trending Now
Can you define these popular missing words?
1. To leave a social event without saying good bye.
2. To say you'll be right back or step outside and not come back to the party.
3. To hang out and after not too long of a duration, the person is no where to be found.
2. To say you'll be right back or step outside and not come back to the party.
3. To hang out and after not too long of a duration, the person is no where to be found.
Brian's hanging out with his co-workers at the bar and says he's going to step outside to grab a smoke. After sometime, his co-workers realize he never came back.
Co-workers reaction - That fool freakin' ghosted us again.
Co-workers reaction - That fool freakin' ghosted us again.
viết bởi J'abu 22 Tháng tư, 2010
When you walk by somebody pretending they don't exist. Or when somebody says something to you and you pretend you didn't hear it from close range.
Delaris: "Welcome home Dick!:)" *Dick walks right by her*
Dick has ghosted Delaris in both ways.
Dick has ghosted Delaris in both ways.
viết bởi the6man 29 Tháng ba, 2015
To be ignored, or not having anyone respond to your opinion and disregarding your remark, leaving you feeling insignificant. Mainly a term that is used on Facebook for trollers who wish to humiliate users when no one comments or likes their statuses.
A: "Oh my god, the weather is gorgeous today! Good morning everyone :)"
*no one comments*
B: Ghosted.
*no one comments*
B: Ghosted.
viết bởi Sarah&Renee 15 Tháng tám, 2011
to be moved from one prison to another without being told in advance.
you get unlocked for breakfast and the screw tells you pack your stuff you're being ghosted
viết bởi mos1975 28 Tháng sáu, 2011
When craigslist fools you.
When you think your ad was posted to craigslist and you go to look for it and realize it has been ghosted.
viết bởi monsterman123 09 Tháng mười, 2010
Inhaling a hit off of a marijuana cigarette and then swallowing it.
Bro did you hit that?
Ghosted it
Oh your fucked bro
Ghosted it
Oh your fucked bro
viết bởi trycoke25 26 Tháng năm, 2010


text:
Miranda Lambert, Luke Bryan and Eric Church each picked up four nominations Monday, PEOPLE can reveal exclusively. They are followed by country veterans Jason Aldean, Kenny Chesney and Rascal Flatts, as well as first-time nominees Florida Georgia Line, with three nominations each.
Carrie Underwood, who led last year's nominations with five (and won video of the year), has two nods this year. She is joined by Taylor Swift, Brad Paisley, Tim McGraw, Hunter Hayes, Jana Kramer, Kacey Musgraves, Little Big Town and the rock group Journey.
Lambert's "Mama's Broken Heart" is up for video of the year and female video of the year. The singer, 29, is also competing for group video of the year and CMT performance of the year.
Bryan and Church, both 36, will square off in the same four categories: video of the year, male video of the year, collaborative video of the year and CMT performance of the year.
Bryan's "Kiss Tomorrow Goodbye" is nominated in those first two categories, while Church, somewhat unusually, has two different videos competing for those awards – "Springsteen" is up for video of the year, while "Creepin'" is up for male video of the year.
See all of this year's nominees on the CMT website.
It will be a busy night for Aldean, who, along with his three nominations, is co-hosting the show with Kristen Bell.
The 12th anniversary show, taking place at the Bridgestone Arena in Nashville, will be broadcast June 5 at 8 p.m. ET/PT on CMT and CMT.com.


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|Welcome to the MANGA Forum.
|You will have to register before you can post: log in or sign up at the top of the page to proceed. To start viewing messages, select the forum that you want to visit from the selection below.
So is this like the other things that you can talk to ppl on and talk about things tooor what.
we all pretty muchtalk about anything and everything on here. "Those who live in darkness wander aimlessly."
so how do i get my rank up like yours
You get three points per post annd the more comments the higher the rank "Those who live in darkness wander aimlessly."
shez rite
i see then i guess i must start talking to people
HI, bye!
the one that said hi bye hi to you too
Hey im ayla, nice to meet u


text:
Wind advisory extended for Erie region (VIDEO)
The National Weather Service in Cleveland has extended a wind advisory for Erie and Crawford counties until 4 p.m. as area emergency crews continue to respond to reports of tree limbs and wires down.
Area emergency dispatchers and police agencies report no serious issues this morning from strong winds that blew into the region on Sunday, but said they have received numerous reports of trees, branches and wires down.
The most recent came shortly before 7 a.m., when firefighters in Waterford were sent to the 11500 block of Trask Road.
Penelec reports scattered small power outages throughout Erie and Crawford counties, according to information on the company's website.
The peak wind reported at the Erie International Airport on Sunday was 52 miles per hour, while a peak wind of 46 miles per hour was measured this morning, according to the weather service.
Forecasters said the highest wind gusts are expected this morning, with wind speeds gradually diminishing this afternoon.
Sign up for weather text alerts and a daily forecast message at GoErie.com/alerts. Go to GoErie.com/weather for forecasts and real-time radar.


text:
SALEM-When it comes to cars, everyone, it seems, has his or her own preference. Some prefer a certain make, while others like cars from specific periods in time.
For Kevin Shar of Canfield, rarity is what counts. On Saturday at the Steel Valley Super Nationals, Shar took two Pontiacs down the dragstrip at Quaker City Motorsports Park.
Both cars-a 1996 Comp T/A and a 2001 NHRA edition T/A-are among the few of those types found anywhere in the world. There were only 45 '96 Comp T/A's produced and only 145 2001 NHRA T/A's.
"I bought both cars because of how rare they are more than any other reason," Shar said. "I also like the fact that they are both clean cars, but their rarity was what attracted me more than anything else."
Shar grew up in Leetonia and has been coming to Quaker City since he was a kid in the 1970s. His interest in rare cars took off when he watched a car show on TV that featured the 1991 Pontiac Firehawk.
"After I saw the show I wanted to buy a car like that," Shar said. "As rare as the Firehawk is, the Comp T/A's are a level more rare."
Both of Shar's purchases involved a considerable amount of luck. In September of 1996 he went to Stadium GM in Salem intending to buy a pickup truck. While looking around he noticed a single '96 Comp T/A sitting right in the lot. He recognized the car immediately and placed a deposit. Stadium Used Car Manager Dan Chaffee-who sold the Pontiac to Shar-explained how the store ended up with such a rare automobile.
"There were rewards set up for local dealerships who sold the most Pontiacs," Chaffee said. "We did well that year and were awarded that car. I believe it was only in the lot for one day before Kevin snapped it up. I like that he's been able to keep it looking brand new ever since."
Several years later Shar landed the 2001 NHRA Trans Am, and once again fate was on his side. He was strolling through a parking lot when he saw the car sitting unoccupied in an open space. He waited for the owners to arrive back, asked them if they were interested in selling and, as it turned out, they were.
"It was a couple that had just moved up here from Florida," Shar said. "They were worried about how the car would handle during the winter and they were looking to sell."
Shar also remembered that the owners knew exactly what they had and did not want to give their car to just anybody, so he took them to his garage and showed them the Comp T/A, which clinched the deal.
"That won them over," Shar said laughing. "They said they wanted the car to go to a good home."
Shar, who has been racing at the Super Nationals since 2004, passes the winter months in his garage tinkering with the cars before taking them out for the summer. He was participating Saturday with his son Matthew, who was driving the NHRA car. As Shar waited to to roll onto the track he talked of his passion for cars and the thrill of racing.
"Working on these cars is a great hobby to get me through the winter," Shar said. "Once this time of year comes, there is nothing like getting onto the track and seeing what they can do. It's a huge 12-second rush."


text:
Top Definition
the mysterious 'fro created at the back of your head and nape of your neck while sleeping. a contraction of a.m. (for morning) and afro. the best amfros are found on people with fine, thin hair. also known as a squirrel's nest or a bird's nest.
Girl, your amfro is fierce! You better tame that beast!
от angton 25 февруари 2014
Trending Now
Can you define these popular missing words?


text:
Nigella Lawson's husband announced he's divorcing the celebrity chef, expressing disappointment she failed to publicly defend him during the fallout over their disturbing public fight.
Charles Saatchi, 70, a wealthy art collector and global ad agency co-founder, has been embroiled in a scandal since the publication of pictures showing him clutching her by the throat at a London restaurant on June 9.
"I am sorry to announce that Nigella Lawson and I are getting divorced," he said in a statement to The Mail newspaper in the UK.
"I feel that I have clearly been a disappointment to Nigella during the last year or so, and I am disappointed that she was advised to make no public comment to explain that I abhor violence of any kind against women, and have never abused her physically in any way."
Saatchi was interviewed by British police for five hours and received a formal police citation, called a caution, which means he admitted his actions. The caution ended the matter with police.
But in his statement, Saatchi downplayed the fight with Lawson, 53, with whom he has been married for 10 years.
"This is heartbreaking for both of us as our love was very deep, but in the last year we have become estranged and drifted apart," the statement said. "The row photographed at Scott's restaurant could equally have been Nigella grasping my neck to hold my attention – as indeed she has done in the past."
A rep for Lawson declined to comment.
Nigella Lawson's Husband Charles Saatchi Seeking Divorce
Aaron Davidson/Getty; Startraks
updated 07/07/2013 AT 09:30 AM EDT
•originally published 07/06/2013 AT 09:50 PM EDT


text:
Perhaps the
latest and greatest wonder of hardware overachievement is the story
of French native Fabrice Bellard, who now holds the world
record in PI calculation. He calculated Pi to 2.7 trillion
decimal digits, surpassing mark of 2.5 trillion digits set
in August by the T2K Open Supercomputer (which at the time was
the 47th most
powerful supercomputer in the world).
So what's so
impressive about Mr. Bellard's feat, aside from its basic technical
merits? He accomplished the number crunching, not on a
supercomputer, but on a Nehalem-powered desktop.
machine featured a Core i7 CPU running at 2.93 GHz, 6 GB of RAM, and
five 1.5 Terabyte Seagate Barracuda 7200.11 model hard drives (for a
total of 7.5 TB). The system ran the 64-bit Red Hat Fedora 10
distribution as its primary OS and used software RAID-0 and the ext4
file system.
The result takes up 1137 GB of storage and is
(partially) available
here. The computation took 103 days of computing time for
the modest desktop.
The only time when Mr. Bellard had
to enlist the help of other computers was during the verification.
In order to avoid being displaced from the top spot while the desktop
chugged on the results (that would have taken an additional 13 days),
he instead used a network of nine computers to verify the results in
a shorter timespan.
In order to calculate Pi, Mr. Bellard used
a software algorithm based on the well known Chudnovsky formula and
verified the resulting calculations by the Bailey-Borwein-Plouffe
algorithm which directly gives the n'th hexadecimal digits of Pi.
Checksums were used to detect errors.
The more optimized Pi
algorithm based on the Chudnovsky formula that Mr. Bellard uses is
the fastest current way to calculate Pi and has been renamed
Bellard's formula in his honor. Mr. Bellard is perhaps most
famous for writing the tiny c compiler (tcc), a popular lightweight
compiler in the Linux community.
quote: Well yeeeeah, but apart from the rabies vaccine, the parachute, the diesel engine, the altimeter, the gyroscope, the photograph and cinema, what have the french ever done for us?
quote: Diesel engine was invented by a German. Rudolf Diesel to be exact


text:
Thursday, April 18, 2013
Three Boston Marathon runners from Summerville were not injured Monday in the explosion that shocked the nation.
The Summerville runners were Maureen Bodkin, Jessica Farmer and Lauren Jaynes. Official reports show that Jaynes finished in 3:42:26 and Bodkin in 4:01:04, putting her at the finish line just minutes before the 4:09:45 explosion.
Farmer is not shown as finishing the race, although she is shown as having passed her last checkpoint at 4:21:22.
Two explosions were reported. All runners who had not finished the race before the explosions were diverted off course.
According to Dorchester School District Two Public Information Officer Pat Raynor, Bodkin is employed at Beech Hill Elementary School as a school nurse.
Raynor said that Bodkin talked to a Beech Hill staff member Monday afternoon; the staff member said that Bodkin had finished the race and was about a block from the scene of the explosion with her son, who had accompanied her to Boston.
Bodkin and her son were not injured, and Bodkin is expected back at work at Beech Hill Wednesday, Raynor said.
A total of 130 South Carolinians took part in the race, according to reports.
Summerville resident Abby Caputo said that she and her mom stood across the street from the spot where the bomb went off when they attended the Boston Marathon two years ago to cheer on her dad who was running in the race.
Caputo has completed seven marathons but has never run the Boston Marathon.
"Running the Boston Marathon is a milestone for runners," Caputo said. "I remember standing there seeing the look of excitement and happiness on the faces of the runners, and the anticipation of those waiting for them at the finish line, and the thought of that being shattered by an event such as this is heartbreaking."
According to Caputo, runners qualify for the race through an elite process by running a qualifying time in what are known as "Boston qualifiers," and that if you are a runner it is something to which you aspire.
Chris May and Jacob Driggers of Charleston finished the race about 90 minutes before the explosions. They were back in their hotel when the blasts occurred.
Julia Early of Lexington had finished the marathon and was waiting to get a bag from a bus when she heard an explosion. Early says it sounded like a cannon. She says she made it back to her hotel room and was able to let family and friends know she was safe.
Amanda Perkins of Greenville says she had come across the finish line about four minutes before the first explosion. Perkins says she turned around and saw a gray cloud. She says there was no panic until the second blast.
Three people were confirmed dead in the blast, including an 8-year-old boy who was a spectator. Over 140 people were injured, and 17 were listed in critical condition.
The Associated Press contributed to this story.
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text:
HK250GT 6Ch from a DH9116
My first CP heli, moving from a Double Horse 9116. It's a pretty big
jump, and thought I would share if someone is thinking of moving up.
My next heli would have been an MJX-F45 if it had not been for a
generous donation from another forum member (Thanks Balr14 !!).
I got it mostly assembled, just needed to install electronics.
I spent a ton of time getting the belt drive and tail to operate smoothly.
But now, she spools up like a dream. Smooth and silent. My 9116 sounds like
a dying lawnmower by comparison.
The one-way bearing is awesome to hear spool down, it spins for
quite a while. The belt drive took an hour to adjust, but now you don't
even know it's there.
The head speed is insane. I was scared to put it past 60%
Before I get heavy into the manuals and start setting it up, is there anything
that looks out of place?
United Kingdom, England, Witham
Joined Feb 2011
899 Posts
Joined May 2011
621 Posts
Why not use a 3s(3 cell) li-po ? Will your canopy fit with the esc mounted side-ways? It looks like you will have to remove your gyro every time you replace your tail boom.(to get to the screws) The HK tail boom is super thin and super fragile.
First hover today. I'm so freakin' happy. Took me forever to figure out the
setup / pitch / throttle curves / and every other thing I knew nothing about. LOL.
I have a decent beginner set I made (can still go wild 3D with
idle-up mode).
When you kick that in (idle-up).... OH MY !!! Freakin AWESOME !!!
(I only did it on the ground). And with the curve, that was only 80% throttle.
This thing is wicked. Very tricky to hover, even with a super docile custom setup.
Of course, it would be easier without the 8 Mph shifting breeze...
If anybody buys a 250GT and uses a SKY-703 radio, and Skyartec head lock gyro, you are welcome to my
setup, posted here. It's a good starting point at the very least.
It took me several hours to figure all the settings out, and this might save
you some time.
of power. Idle-up is scary
As far as the gyro, I have a huge roll of servo tape. No big deal if I have to
move it.
The only place the canopy is tight is at the battery, as I have it way forward
to try to balance it.
Joined Apr 2010
1,025 Posts
You are doing great! But, don't shift in to idle up mode on the ground. You want to be in the air at neutral throttle; much less stress on the equipment. You should probably get used to using throttle hold, rather than cutting the throttle in a crunch situation. When you cut throttle quickly you induce negative pitch, so you come down faster. There are two ways to offset this: use a pitch curve that has very little negative pitch or raise throttle trim. The downside of doing this is it reduces your ability to fight wind. But, if you use throttle trim, you can reduce it with a flick of a finger. The use of throttle trim to control flight characteristics is standard operating procedure on the Thunder Tiger Innovator. It works quite nicely on quads, too.
It doesn't get light on the skids at the curve I set until around 2 or 3 deg, so even if I completely cut the throttle it won't pancake. When I enabled idle-up mode I made sure I was at zero or very little pitch. It makes a quick 180, then sits there screaming happily
Just FYI
I'm sure that will change once I get used to the completely different flight behavior.
The high head speed makes gyroscopic forces 10 times greater on the 250GT.
The HK250GT handles wind far better than the 9116. It's just harder to fly
because I suck at it.
Broke my first part on the 250GT today. I was sliding sideways about a foot
off the ground and a gust made it dip and catch the skid.
Only broke 1 leg, so I can still fly it. But if I had been 2 feet up all
would be good. Stupid.
It can get away from you SOOO FAST... just a nudge on the sticks for a split
second is all you can give it unless you want it taking off like a freakin' rocket.
I need to get a radio with programmable rates and epa's so I can tone it down a
little while I learn.
When it starts to get out of shape, you set it down NOW.
If you have to think about it, it's too late... you've already bit the dust.
All you can do is cut the throttle and hope the blades "bounce" off the blacktop.
This thing is pure evil. Devil bird from hell, I'm not kidding.
I equate it to trying to balance a marble on top of a bowling ball.
I can't believe I have not totaled it already.
But it is so satisfying to fly... the sound, the snappy movement.
The way it holds it's position if you are on the sticks right.
It is just soooo smooth.
The spin rate of this thing is completely nuts.
The tail can spin around so fast it's a blur.
If you tipped with enough force to break a skid leg, you should check the feathering shaft. They are always the first thing to bend. When you disassemble the head, pay very close attention to the order of the bushings, bearings, rings, etc. Lots of beginners overlook this. Going from a DH9116 to a 250 clone has to be the biggest jump I've ever heard of. Ranks right up there with starting with the old Walkera 4#3B.
until I went to power down.
I was going sideways at a good clip and just nicked a crack in the blacktop.
If it wasn't for that crack, all would be well
The heli kept flying as if it weighed 200Lbs. Didn't even twitch.
Like I said, I didn't even know I broke anything until post flight.
I've ran a pack through since, and it seems ok, nothing different that I can
tell. Still smooth and snappy at the same time
I've got it sitting waiting to see if CA will bond it back together but I doubt
it, they are just too flexible.
On a different note, the 9116 is totaled... Kid was flying, got it too far away.
I took over but it was already too late, couldn't see it.
Had to throttle cut, and this time it needs battery, PCB, head, frame,
and other stuff. Not even sure I want to fix it.
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text:
C.B. Aycock fends off Cleveland
By Rudy Coggins
Published in Sports on October 5, 2011 1:49 PM
Please log in to see full story.
Other Local Sports
- Grace-Raleigh sweeps Eagles in CCC 1-A finale
- Jones scores WCS' lone goal in loss
- Local Preps Digest
- Stevens: Williamson gaining confidence with each snap
- Local preps digest
- C.B. Aycock claims cross country meet
- ECC 3-A Cross Country results
- Spring Creek bests Goldsboro soccer
- Rosewood takes down AG soccer
- Carolina 1-A Cross Country results


text:
Wall Street Decline Takes Its Toll...
LC-MS Gains Favor Due To the...
Expanding Use of NGS Has Largely...
NSCLC is "Major Battlefield" as Merck,...
Helping to ensure that the drug discovery and development process continues evolving, contract research organizations (CROs) are of increasing value to biotech and biopharma. These guardians of the pipeline keep the process alive by providing the best-in-class assay and technological support to insure that viable, new drug candidates are commercialized.
The support needed at each phase of the drug pipeline is available from a CRO, whether it be a small niche organization that has specialized in a specific assay or platform technology, or a large organization that serves as a one-stop-shop with extensive technologies/services to take an optimized lead candidate through clinical trials to full commercialization.
Indigo Biosciences was born out of expertise with a specific assay technology, in this case one focused on nuclear receptors. This small CRO was spun out of Penn State University when Jack Vanden Heuvel, Ph.D., founder and CSO, realized that his nuclear receptors expertise could be leveraged for drug discovery.
Of the 48 known human nuclear receptors, Indigo has developed a reporter gene assay system using a mammalian cell line for 25 of them. The most notable receptors in this class are the PPAR receptors, a family of nuclear receptors whose activity is associated with on target effects for many metabolic diseases including diabetes, obesity, and chronic inflammation. These receptors are also valuable as off target markers for toxicological studies and for the analysis of drug-drug interactions.
The nuclear receptor assays are now also available in kit formats, so the luciferase-based reporter assay can be run in a firm's own lab if it chooses not to outsource.
"We've come to be known as the 'Nuclear Receptor CRO'. We use a single point assay in medium to high throughput to screen tens to hundreds of compounds across a panel of up to 25 receptors in 384-well plate format," says Dr. Vanden Heuvel.
"The assay is run in 15–30 µL reaction volumes and yields results within 24 hours. We work closely with the customers on both ends of the analysis, first to develop the study plan and then to help with the interpretation of the results. The completed study is usually turned around in two weeks."
The focus of BD Biosciences' Gentest™ contract research services is on metabolism of drug candidates as measured by the induction or inhibition of cytochrome P450, a superfamily of drug-metabolizing enzymes. "BD has a large suite of drug-metabolizing enzymes with more than 50 different P450, UGT, and other enzyme products sold under the BD Gentest brand," shares Roseann Vardaro, product manager, BD Biosciences—Discovery Labware.
"The services business is closely integrated with the product business. This helps assure that datasets are comparable whether customers do the work themselves or outsource it to us." Another key focus area for both products and services is transporter proteins. Like cytochrome P450 enzymes, ATP-binding cassette and solute linked carrier transporter proteins can mediate drug-drug interactions.
"A trend that we've noticed recently is more repurposing of established drugs. These drugs often have little or no data applicable to newer standards of in vitro drug-interaction testing, such as those outlined in the FDA's 2012 drug-drug interaction guidance document," says David Stresser, Ph.D., program manager, BD Gentest contract services. "Before investing in another round of clinical trials, our customers want to confirm there are no drug-drug interaction or safety issues."
Molecular Imaging (MI) is dedicated to the use of small-animal imaging in the drug discovery process. "We use a full range of imaging modalities for anatomical, functional, and molecular outputs, enabling us to provide our customers with combined pharmacology and imaging biomarkers that assist in their go/no-go decision-making process," says Patrick McConville, Ph.D., co-founder and CSO.
"We customize our approach with every project. The customer brings us their compounds and we do the rest; we order the animals, acclimatize them on-site, induce the disease state, and interrogate the pharmacology. Imaging is then performed using one or more modalities usually over multiple time points to extract predictive biomarker(s) with the aim to perform the analysis in real time."
The increasing reliance on imaging in the pharmaceutical industry as well as parallel improvements in the technology has enabled MI to add a broad base of imaging assays. These assays are validated and applied to the noninvasive study of disease in the context of the otherwise normal physiology of the animal.
MI is currently primarily focused on oncology and inflammation diseases. The latter also extends its reach to the broader area of metabolic and cardiovascular disease. It plans to expand its offerings by developing expertise in other disease areas, and this expansion will occur in parallel to the addition of emerging imaging platforms. Using ancillary technologies such as MRI contrast agents, PET tracers, and optical probes to study these disease states, it is looking to pull together richer, more reliable datasets.
Another trend is the use of whole-animal imaging for drug safety and toxicology studies. MI is an active participant in the consortium set up by the Health & Environmental Science Institute to define guidelines and set the industry standard for imaging in preclinical safety assessment.
Avacta Analytical was spun out of the University of Leeds in 2005. The business focuses on providing extended protein-characterization services, specializing in biophysical and physico-chemical analytics. Avacta offers a range of techniques not traditionally found in every lab or even at CROs.
Its experience of using these techniques and applying them to different types of therapeutic proteins is central to its success. It provides smaller organizations with the ability to access additional analytical resource and provides extra capacity for larger multinationals.
"We mainly work in the R&D phase of drug development, looking at stability, comparability, aggregation, formulation selection, and general protein characterization," explains Richard Perkins, business development manager.
"We advise our customers on the pros and cons of various analytical techniques, making sure the package we provide is fit for purpose. Techniques such as analytical ultracentrifugation, FTIR (fourier transform infrared spectrometry), and circular dichroism are not familiar to most, so we have learned that extensive consultation and open communication with the customer before and after projects is vital."
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With the kids scooting off to school this month, it's as good a time as any to finally tackle that homework you've been putting off, Mom. We're not talking about organizing the closets, either.
We're talking about all those legal and financial matters you've been worried about for so long.
Budgets, wills, insurance, trusts — they're daunting and tedious and easy to overlook until it's too late. But we all need to make sure our families' ducks are in a row when it comes to finances and legal issues.
To help, Lowcountry Parent is bringing you a special, four-part series called "Family Matters." We hope this series – the first of its kind for our publication – will help you understand the legal and financial challenges faced by modern moms, including estate planning, divorce, children's safety and caring for aging parents.
To start the series this month, we talked with local experts about the most common situations women find themselves in when it comes to estate planning and financial matters at home… and how to move past them.
Problem No. 1: "I don't have a will. I've just never had time and it's too complicated."
Before you had kids, having a will may not have seemed so important. If you passed away before having children, all your belongings would go to your spouse, right? According to Kathryn Cockrill, managing attorney at Kuhn and Kuhn Law Firm, the answer is yes — unless you've done a prenuptial agreement.
But things change when you have kids, she said.
"When you have children, it's even more important to have a will," Cockrill said. "Because if you don't, half of your estate is going to your spouse, the other half is going to your kids.
"Now think about what that means for a house. If you have a home, half of it is going to your spouse, the other half is going to your children. What if your kids are 3 and 5 when you pass away? Now your minor children own part of your house. Most people don't want that — they want their spouse to own the home. So you have to make sure that things are set up properly to transfer to the intended beneficiaries."
A will also allows you to assign a legal guardian for your children. You may have thought about who you would want to take care of your kids if something happened to you, but have you put it in writing?
"Whoever the other parent is automatically is going to be the caretaker," Cockrill said. "But if you and your husband both pass away at the same time — you have to have a plan in place for that. You set that up in your will. You put, 'I want the guardian for my minor children to be my mother or my sister,' and you name a couple people just in case one passes away before you."
As we all know, mothers of small children don't have a lot of time on their hands to sit down and tally up their belongings and assign them out. And let's be honest, it's weird to think about dying. So tackle estate planning like you do any other preventative household chore — put in the work now so it's not a nightmare later.
"We see it time and time again, because no ones likes to think about when they're passing away and how things should go," Cockrill said. "But you really have to have these things in place. The best practice is to seek professional help. No one is expecting you to plan your estate on your own. I always say ask for help — and asking for help is not Googling it. It's calling a lawyer that's practicing in the area and they will assist you and give you good advice."
Problem No. 2: "I have a will, that's all I need."
Having a will is important, but it's actually only one document within a complete estate plan. The will comes into play after you die, but the other estate plan documents are what you use during your lifetime. According to Cockrill, a complete estate plan includes a last will and testament, a durable power of attorney, healthcare power of attorney and a living will. (For more on these documents, see Problem No. 3.)
Plenty of other options can make it even easier for your survivors to distribute your assets if you die. Consider a trust, for instance. A will, alone, simply takes possessions out of the deceased person's name and puts them into the name of the beneficiary, Cockrill said. This process plays out in probate court.
"A lot of people don't like the idea of court at all," she said. "For people who want to avoid the court system entirely, you can put your assets into a trust. People don't realize that trusts are for everybody. It's just an estate-planning tool to remove you from court and for you to have some control over your assets after you have passed away."
Cockrill said the most popular kind of trust is a revocable living trust. Basically, it sets everything up where nothing is left in your name individually, she said.
"If you don't have something in your name, then no one has to go to court to get it out of your name," Cockrill said. "All your assets are now owned by this entity — it's a trust and it's your alter ego."
Cockrill said trusts work especially well for parents for two reasons. First, parents of young children can use them to decide for themselves who they want managing their kids' money.
"If you have a life insurance policy and your spouse and you pass away in a car accident, let's say, and it's going down to your minor children, the court's not going to release the money," Cockrill said. "What they're going to do is have a conservatorship set up in the court system where the court monitors how that money is spent. You're also paying a lot fees and court costs based on the value of that life insurance policy.
"A trust, however, transcends death, which means it still exists after you pass away. The trust will pay for everything your child needs, like their education, support, health care expenses. And then you're putting somebody in charge of the trust, a trustee who's going to be the one to manage their money."
Secondly, parents of older children can use trusts to control how much money their children get after they turn 18.
"If you have a big insurance policy, you can't give an 18-year-old a quarter million dollars," Cockrill said. "That's a big no-no — they're going to spend it immediately. So you want to put a little more restrictions on it. Maybe you don't give your kids the money until they're 25 or 30, and have your sister or your brother monitor those for your kids if you've passed away."
Doing a little more advanced planning, like setting up a trust, can be expensive, Cockrill said. But the trust removes your family from the court system upon your passing, which is a huge advantage.
"Otherwise, you end up spending more money over in court than you would to just have your estate planned properly," she said.
Problem No. 3: "My husband and I have briefly talked about what we'd like done if we were hospitalized, but we've never written it down."
The other documents in an estate plan, the durable power of attorney, healthcare power of attorney and a living will, come into play if you or your spouse become incapacitated, Cockrill said. Many people think that if their spouse was hospitalized, and in a coma let's say, they could act on their spouse's behalf because they're married. That's not always so, Cockrill said.
Once a person becomes incapacitated — can no longer sign their own name — all the assets that are solely in their name become frozen, Cockrill said. Bank accounts can't be accessed, cars and houses can't be sold, unless they are also in someone else's name, she said.
"Spouses can't just access those because they're married," she said. "Let's say the wife stays home and takes care of the children and the husband is the one working and making the money. He puts a lot of money into an account that doesn't have the wife's name on it. Husband gets in a car accident and then wife can't access the account.
"So all of a sudden, the money that was used to pay for the child's tuition and the child's care, the mortgage, everything, it's frozen.
"The account won't be frozen if you have a proper document that allows you the authority to act on that person's behalf. That's the property power of attorney or durable power of attorney."
The healthcare power of attorney and living will address how you'd like to be cared for if you become incapacitated. The healthcare power of attorney names a person to make medical decision for you and gives specific instructions on your wishes concerning life-sustaining treatment, tube feeding and end of life care, Cockrill said. The living will addresses hydration and nutrition — also known as the pull-the-plug document, she said.
"Without these documents, your spouse will be able to make the decisions, it might just not be what you wanted," she said. "Does your husband even know that you don't want to be kept alive, that you don't want to go through unnecessary treatment and tube feeding?
"You want things to be clear for your family. It's easier for them to say, 'Here's the document. This is what my wife would have wanted.'"
Problem No. 4: "I don't have life insurance—I don't know how much to get."
After having children, consider getting life insurance for you and your spouse, said Diane Blackwelder, certified financial planner with Charleston Financial Advisors.
"Generally, life insurance is designed to replace the income that would be lost if a person were to pass away," she said. "So the people who are dependant on the income won't suddenly become impoverished. So you want to calculate how much money you would need if something were to happen to the other spouse."
Some recommend calculating the amount based on salary, but you should also think about the needs of the family, Blackwelder said. Maybe you choose to get enough insurance to pay off the mortgage so your partner doesn't have to, or enough for college savings for the kids.
Stay-at-home moms should also consider getting a life insurance policy, Blackwelder said. Though they don't bring in a paycheck, the work they do would have to be hired out if they were no longer around to care for the kids.
"There is value to the stay-at-home mom's job," Blackwelder said. "Without her, the dad would be left to figure out who's going to take care of the kids while he's at work, who's going to cook the food and clean the house. We always recommend there be some insurance in place on the mom to cover those things."
Problem No. 5: "We're living paycheck to paycheck, but we're getting by."
The most common mistake Blackwelder sees families make is not being long term in their thinking, she said. Just because you're making it work now, doesn't mean you shouldn't think about and plan for the future — setting goals for what 30 years from now looks like.
"Setting up that savings plan is key," she said. "It's much harder to catch up later than it is to start out in the beginning. There's certain rules of thumb—10 percent is a good number when you're young, it goes up as you get older because you don't have as much time for the money to grow."
Having an emergency fund in place is also vital, Blackwelder said. The amount in the fund is subjective, but usually three to six months of expenses is recommended. The emergency fund acts as a safety net for disability—including unpaid maternity leave— and job loss, she said.
"The emergency fund is the biggest and best thing you can do for yourself, making sure you have that nest egg," Blackwelder said. "It makes a huge difference when unexpected things happen—and they always do."
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I feel like I barely got the Christmas ornaments put away last week and already we have celebrated Martin Luther King on Monday, next week is Chinese New Year, did you see the fabulous BBQ dish we featured last week? This week we are counting down to Valentine, sheesh I feel like the year is going at the speed of light already.
Today I'm excited to feature Heidi Rew she's a Sandra Lee Junior :) luv luv her recipes and I was thrilled to have her showcase a fun and easy way to create an elegant petit four for us using Twinkies .
Please help us welcome Heidi!
Hey there! My name is Heidi Rew. I am a traffic reporter for 104.7The Fish in Atlanta, GA but I also do this little blog called PartiesforPennies.blogspot.com. I started blogging as a creative outlet & have loved every minute of it. I got married this past summer to the man of my dreams. We got married in Hawaii but had a backyard reception when we got back. Biggest party of my life & I blogged about it all.
Valentines Petit Four tutorial:
I love pretty desserts. They're like shoes. They all look so pretty but the reality is you can't have them all. Well, I guess you can...but you'd need a bigger closet & a bigger size pant. ;p Anyways...petit fours are those desserts that are so adorable looking but take a little bit of time to make. This is a super easy way to make cheap petit fours that you can do while watching the Bachelor or Jersey Shore (or if you're more refined...CNN News...but let's be real, even the refined get sucked in by the Kardashians). :p
This is all you need but I do have a slight change. I thought using the Candy Melts would work better but it was an epic fail. The first time I used white chocolate chips (the Publix brand) & those worked perfectly so ignore the candy melts in this pictures. On the petit fours in this picture I used the Ghirardelli white chocolate chips & I still liked the store brand better. Let this be a lesson to our penny pinching ways...Cheaper is Better! :p
The 20-30 minute is a guide. I'm sure up to an hour would work.
While the Twinkies are in the freezer, you can melt the chocolate chips either in the microwave or double boiler.
I left the bottom of the Twinkie chocolate-less. Call it being Twinkie mooned, if you'd like. I guess I should guard myself a little better since this is the first time you've met me. Oops.
Once the chocolate has dried, you can add sprinkles to the petit fours or you can decorate it with colored chocolate or icing. I tried to decorate mine with icing but for some reason I didn't have any decorating mojo that night.You can see here how I tried to add some more embellishments. See...no icing mojo that night. ;p
Hope you have a penny-pinching Valentines Day! I'd love to hear from you. Stop by any time to: www.PartiesforPennies.blogspot.com
**Thanks again Maggie!
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Our top 5 linking spotlight! Please click on the pictures to visit their blogs!
Beautiful card :)
Have a great weekend!
PS. Don't forget to sign up to be follower we are looking for #5600 if it's you email us at email@example.com. Follow us on Pinterest as well :) there's a small pin button now at the bottom of each post.
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Upregulation of matrix metalloproteinase-9 in murine 5T33 multiple myeloma cells by interaction with bone marrow endothelial cells
Els Van Valckenborgh 1, Marleen Bakkus 1, Carine Munaut 2, Agnes Noël 2, Yves St. Pierre 3, Kewal Asosingh 1, Ivan Van Riet 1, IMF Scientific Advisor Ben Van Camp 1, Karen Vanderkerken 1 *
1Department of Hematology and Immunology, Free University Brussels, Brussels, Belgium
2Laboratory of Tumor and Developmental Biology, University of Liège, Liège, Belgium
3Immunology Research Center, Institut Armand-Frappier, University of Quebec, Laval, Canada
International Journal of Cancer
Volume 101, Issue 6, 2002. Pages: 512-518
MM is a B-cell malignancy mainly characterized by monoclonal expansion of plasma cells in the BM, presence of paraprotein in serum and occurrence of osteolytic bone lesions. MMPs are a family of proteolytic enzymes that can contribute to cancer growth, invasion, angiogenesis, bone degradation and other processes important in the pathogenesis of MM. We investigated MMP-9 production in the 5T33MM murine model. Expression of MMP-9 protein in supernatant and cell extracts was analyzed by gelatin zymography. The in vitro, stroma-independent variant 5T33MMvt showed no protein expression of MMP-9 in contrast to in vivo growing MM cells, 5T33MMvv. However, when 5T33MMvt cells were injected into naive mice and isolated after tumor take (5T33MMvt-vv), they secreted a significant amount of MMP-9. These results were confirmed by specific staining of cytospins with an anti-MMP-9 antibody. The MMP-9 production by 5T33MMvt-vv cells disappeared when the cells were recultured in vitro. These data demonstrated that upregulation of MMP-9 occurs in vivo and that this process is dependent on the microenvironment. Cocultures of 5T33MMvt cells with STR10 BMECs induced MMP-9 in MM cells, as determined by both gelatin zymography and flow-cytometric analysis. In conclusion, our results demonstrate that MMP-9 production by MM cells is upregulated in vivo by the interaction of MM cells with BMECs. © 2002 Wiley-Liss, Inc.
BLOOD Reports Revimid™ Has Anti-Tumor Activity in Patients with Relapsed and Refractory Multiple Myeloma
Data Demonstrate Revimid Overcomes Drug Resistance and Is Well Tolerated
WARREN, N.J. -- November 1, 2002 -- The first peer-reviewed data of Revimid™ (CC-5013) in relapsed or refractory multiple myeloma was published in today's issue of Blood, the journal of the American Society of Hematology.
The article, titled "Immunomodulatory Drug CC-5013 Overcomes Drug Resistance and Is Well Tolerated in Patients with Relapsed Multiple Myeloma," reports data from a Phase I/II study of Revimid in relapsed or refractory multiple myeloma that was conducted by Celgene in partnership with the Dana-Farber Cancer Institute. The data from the trial demonstrate that 17 of 24 patients (71 percent) experienced at least a 25 percent reduction in paraprotein (a measure of their tumor burden).
"Revimid represents a novel, oral therapy for relapsed and refractory multiple myeloma that overcomes drug resistance and is well tolerated," said Kenneth C. Anderson, MD, of the Dana-Farber Cancer Institute at Harvard University.
The study published today in Blood evaluated 24 patients with relapsed and/or refractory multiple myeloma. Fifteen patients had undergone prior autologous stem cell transplantation and 16 had received prior Thalomid® (thalidomide) treatment. Patients received a daily oral dose of Revimid in one of the following fixed dose levels for four weeks: 5, 10, 25, or 50 mg/day. After the four-week formal trial, the extension phase permitted dose adjustment. Patients were evaluated by reductions in levels of paraprotein.
Paraprotein reductions of at least 25 percent were observed in 17 of 24 (71 percent) evaluable patients, including seven patients (29 percent) who achieved a greater than 50 percent reduction in paraprotein levels. Two patients experienced stable disease, which was defined by a less than 25 percent reduction in paraprotein levels. The majority of responses were observed at 25 mg/day and 50 mg/day of Revimid. Median duration of response was six (range 2-18) months.
In this study no dose-limiting toxicity was encountered within the first 28 days. Importantly, somnolence, constipation and neuropathy, which are common side effects of thalidomide treatment, were not seen. The most common adverse events observed during the first 28 days were fatigue, rash, leg cramps and neutropenia (decrease of the white blood cells). In the extension phase of the trial, 12 of 13 patients treated with 50 mg/day of Revimid developed grade three and four myelosuppression. All 12 patients were reduced to 25 mg/day of Revimid and tolerated the lower dose. Based on the adverse events observed in the extension phase of the study, the trial's lead investigators concluded that 25 mg/day is the maximum tolerated dose of Revimid.
Revimid, Celgene's lead IMiD (Immunomodulatory Drug), is an orally available compound that affects multiple pathways and multiple targets. In preclinical studies, Revimid demonstrated inhibition of inflammatory cytokines and growth factors such as tumor necrosis factor alpha (TNF alpha), basic fibroblastic growth factor (bFGF) and vascular endothelial growth factor (VEGF) that are involved in tumor development. Preclinical data indicates that Revimid enhances tumor cell death (apoptosis) and cell cycle arrest. Revimid boosts the immune system through stimulation of T-cell proliferation. Data from several Phase I/II trials suggest that Revimid has anti-tumor activity in hematological and solid tumor cancers.
"Revimid has demonstrated anti-tumor activity in preclinical and clinical studies and we believe it has significant potential in treating hematological and solid tumor cancers," said Sol J. Barer, Ph.D., President and Chief Operating Officer of Celgene Corporation. "To more fully evaluate the potential of Revimid, we have initiated pivotal programs for Revimid in multiple myeloma and metastatic melanoma and several Phase II trials in additional hematological and solid tumor cancers."
Pamidronate causes apoptosis of plasma cells in vivo in patients with multiple myeloma.
Gordon S, Helfrich MH, Sati HI, Greaves M, Ralston SH, Culligan DJ, Soutar RL, Rogers MJ.
Department of Medicine and Therapeutics, and Department of Haematology, University of Aberdeen Medical School, Aberdeen, and Haematology Department, Western Infirmary, Glasgow, UK.
British Journal of Haematology 2002 Nov;119(2):475-83
Anti-resorptive bisphosphonates, such as pamidronate, are an effective treatment for osteolytic disease and hypercalcaemia in patients with multiple myeloma, but have also been shown to cause apoptosis of myeloma cell lines in vitro. In this study, we found that a single infusion of pamidronate, in 16 newly diagnosed patients with multiple myeloma, caused a marked increase in apoptosis of plasma cells in vivo in 10 patients and a minimal increase in four patients (P < 0.05). The nitrogen-containing bisphosphonates pamidronate and zoledronic acid also induced apoptosis of authentic, human bone marrow-derived plasma cells in vitro. Apoptosis of plasma cells in vitro was probably caused by inhibition of the mevalonate pathway and loss of prenylated small GTPases, as even low concentrations (>/= 1 micro mol/l) of zoledronic acid caused accumulation of unprenylated Rap1A in cultures of bone marrow mononuclear cells in vitro. GGTI-298, a specific inhibitor of geranylgeranyl transferase I, also induced apoptosis in human plasma cells in vitro, suggesting that geranylgeranylated proteins play a role in signalling pathways that prevent plasma cell death. Our results suggest that pamidronate may have direct and/or indirect anti-tumour effects in patients with multiple myeloma, which has important implications for the further development of the more potent nitrogen-containing bisphosphonates, such as zoledronic acid, in the treatment of myeloma.
Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma.
Rajkumar SV, Hayman S, IMF Scientific Advisor Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, IMF Scientific Advisory Board Chair Kyle RA, Witzig TE. Division of Hematology, Mayo Clinic and Mayo Foundation, Rochester, MN.
J Clin Oncol 2002 Nov 1;20(21):4319-23
PURPOSE: Multiple myeloma is a malignancy of plasma cells and is characterized by increased marrow angiogenesis. Thalidomide, an agent with antiangiogenic properties, is effective in relapsed myeloma. We report the results of a study combining thalidomide and dexamethasone as initial therapy for myeloma.
PATIENTS AND METHODS: Fifty patients with newly diagnosed myeloma were studied. Thalidomide was given at a dose of 200 mg/d orally. Dexamethasone was given at a dose of 40 mg/d orally on days 1 to 4, 9 to 12, and 17 to 20 (odd cycles) and 40 mg/d on days 1 to 4 (even cycles), repeated monthly.
RESULTS: Of all 50 patients, a confirmed response was seen in 32 patients yielding a response rate of 64% (95% confidence interval, 49% to 77%). Thirty-one patients (62%) proceeded to stem-cell collection after four cycles of therapy including 26 who underwent stem-cell transplantation and five who chose stem-cell cryopreservation. Major grade 3 or 4 toxicities were observed in 16 patients (32%), and the most frequent were deep vein thrombosis (six patients), constipation (four patients), rash (three patients), and dyspnea (two patients). Three deaths occurred during active therapy because of a pancreatitis, pulmonary embolism, and infection.
CONCLUSION: We conclude that the combination of thalidomide plus dexamethasone is a feasible and active regimen in the treatment of multiple myeloma. It merits further study as an oral alternative to infusional chemotherapy with vincristine, doxorubicin, and dexamethasone and other intravenous regimens currently used as pretransplantation induction therapy for myeloma.
Role of the bone marrow microenvironment in multiple myeloma.
IMF Scientific Advisor Roodman GD.
Center for Bone Biology, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pennsylvania 15261, USA.
J Bone Miner Res 2002 Nov; 17(11):1921-5
On June 26-27, 2001, the Sixth Research Roundtable in Multiple Myeloma, entitled "The Role of the Bone Microenvironment in Multiple Myeloma," was held and focused on the biology of cell-to-cell interactions, the mediators of bone disease, and novel treatment strategies for myeloma. Studies on cell-cell interactions showed that vascular cell adhesion molecule 1, expressed by local endothelial and stromal cells, binds to tumor cell surface integrins in which expression may be increased by tumor cell-derived chemokines such as macrophage inflammatory protein (MIP) 1alpha. These adhesive interactions increase production and release of vascular endothelial growth factor (VEGF). Studies on myeloma bone disease showed the ligand for receptor activator of nuclear transcription factor-kappaB (RANKL) was expressed on tumor cells and stromal cells associated with myeloma cells and was critical for osteoclast-induced osteolysis. Blockade of RANKL suppressed osteoclast maturation, bone resorption, and tumor development. Bisphosphonates, in addition to reducing osteoclast mobility and inducing osteoclast apoptosis, also decreased tumor cell adhesion to stroma. Immunomodulatory drugs such as thalidomide analogues targeted these tumor cell-stromal cell interactions, blocking both secretion of cytokines and activation of intracellular signaling pathways required for tumor survival and growth. These agents induced tumor cell apoptosis, decreased neovascularization, and potentiated natural killer cell activity. The proteasome inhibitor PS-341 also prevented expression of adhesion molecules and cytokines and triggered tumor cell apoptosis, even in drug-resistant cell lines, while showing minimal activity in healthy cells. In addition, potential therapeutic agents under investigation, which included RANKL antagonists, protein prenylation inhibitors, and osteoblast growth factors, were discussed.
Efficient transduction of normal human B lymphocytes and non-dividing myeloma B cells with HIV-1-derived lentiviral vectors."
Bovia F, Salmon P, Matthes T, Kvell K, Nguyen TH, Werner-Favre C, Barnet M, Nagy M, Leuba F, Arrighi JF, Piguet V, Trono D, Zubler RH.
Blood 2002 Oct 24; [epub ahead of print]
We studied the transduction of normal human B lymphocytes and myeloma cells with lentiviral vectors. In peripheral blood B cells which had been activated with helper T cells (murine thymoma EL-4 B5) and cytokines, multiply attenuated HIV-1-derived vectors pseudotyped with VSV G envelope protein achieved expression of green fluorescent protein (GFP) in 27 +/- 12% (mean +/- 1 SD, median = 27%) of B cells in different experiments. When compared in parallel cultures, the transducibility of B cells from different donors exhibited very little variation. The human CMV promoter gave 4- to 6-fold higher GFP expression than did the human elongation factor-1alpha promoter. A murine retroviral vector pseudotyped with VSV-G protein proved inefficient even in mitotically active normal B cells. B cells freshly stimulated with Epstein-Barr virus were also transducible by HIV vectors (24 +/- 9%), but B cells activated with CD40 ligand and cytokines resisted transduction. Thus, different culture systems gave very different results. Freshly isolated, non-dividing myeloma cells were efficiently transduced by HIV vectors; for six myelomas the range was 14 to 77% (median of 28%) GFP(+) cells. HIV vectors with a mutant integrase led to no significant GFP signal in normal B or myeloma cells, suggesting that vector integration was required for high transduction. In conclusion, HIV vectors are promising tools for studies of gene functions in normal human B cells and myeloma cells for the purpose of research and the development of gene therapies.
Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma.
IMF Scienfic Advisor Singhal S, IMF Scientific Advisor Powles R, Sirohi B, Treleaven J, Kulkarni S, IMF Scientific Advisor Mehta J.
Myeloma Unit, The Royal Marsden Hospital, Surrey, UK.
Bone Marrow Transplant 2002 Nov;30(10):673-9
Two hundred and twenty-two myeloma patients autografted after 200 mg/m(2)melphalan were studied to examine the relationship between response to induction chemotherapy and outcome. Induction comprised cyclophosphamide, vincristine, doxorubicin and methylprednisolone (C-VAMP) every 3 weeks for one cycle beyond maximum response. 81% responded to C-VAMP (chemosensitive) with 40 complete (CR) and 139 partial (PR) remissions, and 43 did not respond (NR; <50% reduction in paraprotein; primary refractory). Overall, 130 patients (59%) attained or remained in CR post-transplant; including 40% of NR, 53% of PR, and 97% of CR after C-VAMP (P < 0.0001). Amongst these 130 patients, the 5-year OS was independent of response to C-VAMP (NR 79%, PR 74%, CR 60%; P = 0.69). Similarly, among the 69 patients in PR post-transplant, the 5-year OS was independent of response to C-VAMP. In Cox analysis, lack of response to C-VAMP did not affect outcome significantly. These data show that lack of response to induction therapy does not automatically predict poor long-term outcome in myeloma, since a substantial proportion of these patients attain CR after autograft and enjoy extended survival. Myeloma patients should not be disqualified from an autograft based upon lack of response to induction chemotherapy.
Case Report: Testicular plasmacytoma: Report of a case and review of the literature
Gabriel Anghel1 *, Nicola Petti 1, Daniele Remotti2, Carla Ruscio1, Fortunato Blandino1, Ignazio Majolino1
1Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliera S. Camillo/Forlanini, Rome,0 Italy
2Service of Pathology, Azienda Ospedaliera S. Camillo/Forlanini, Rome, Italy
Online ISSN: 1096-8652 Print ISSN: 0361-8609
American Journal of Hematology Volume 71, Issue 2, 2002. Pages: 98-104
Plasmacytomas of the testis are rare neoplasias; they may occur as isolated tumors or in concomitance with generalized multiple myeloma. We report the case of a 77-year-old man with previous clinical evidence of multiple myeloma involving skin, ribs, and lungs, and initially treated with surgery, radiotherapy, and chemotherapy attaining partial response. Fourteen months after the onset, the patient presented with left testicular enlargement due to plasmacytoma. Immunohistochemical stains showed monoclonal cytoplasmic IgA- in tumour cells; serum M component showed the same immunoglobulin. Following radiotherapy the tumour mass disappeared. Nonetheless, 2 months later while on chemotherapy, disease recurred with progressive increase of skeletal lesions. The patient is currently alive with disease progression 22 months after onset. On the basis of a review of the literature, the clinical significance of testicular myeloma localization is discussed.
EntreMed, Inc.'s (ENMD) Thalidomide Analog Receives FDA Orphan Drug Designation For Multiple Myeloma


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Free breakfast at check in (before 9.30am ) If youre looking for a cosy place to chill out after travelling... More Info »
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This place has something for everyone, from the Golden Gate Bridge to Alcatraz, Chinatown, amazing seafood and one of the oldest LGBTQ scenes in the USA. And if you're a museum-...Read more »
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