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Street party at Burnhearts benefits Bay View neighborhoods
They'll be dancing in the streets from noon to 8 p.m. Saturday outside Burnhearts, 2599 S. Logan Ave. No worries: They've been doing this for six years. They've got it down. The idea is to raise funds for the Bay View Neighborhood Association.
Restaurants Honey Pie and Classic Slice will be selling food, and there will be an art and craft fair with goods from local artists, plus live screenpainting with Redwall. Braid, Mama Digdown's Brass Band and the Championship will provide the music. DJ WHY B will be on hand. »Read Full Article
Live Blog: DJ Bizzon & Klassik open for Kendrick Lamar
What up peoples? Myself and Klassik will be opening for Kendrick Lamar in Champaign, IL today. We are driving together so we thought it would be cool to live blog the experience. Check here throughout the day for the updates via twitter and instagram. Yes.
Blind Boys of Alabama return to Wisconsin for show at Pabst Theater
"I'll Find a Way," the newest Blind Boys of Alabama album, is "one of the best we have ever made," said band co-founder Jimmy Carter.
Considering the gospel group has five Grammys and has released nearly an album a year since 1948, that's really saying something. »Read Full Article
Trapper Schoepp & The Shades guitarist focuses on new group
Graham Hunt had a great thing going as lead guitarist for Trapper Schoepp & The Shades. The Americana act is one of Milwaukee's most successful bands, with an album on SideOneDummy Records and a history of gigs around the country with Jakob Dylan's The Wallflowers.
But Hunt (disclosure: he's the son of Milwaukee Journal Sentinel sports columnist Michael Hunt) also had his own band to tend to, as songwriter, singer and guitarist for garage-pop rock group Midnight Reruns. »Read Full Article
The battle inside country music?
Kacey Musgraves and Taylor Swift lead the CMA Award nominees with six nods each. »Read Full Blog Post(3)
Miley Cyrus to play BMO Harris Bradley Center
Pop-music behemoth Miley Cyrus is bringing her tour to Milwaukee's BMO Harris Bradley Center March 9, according to the venue's website Wednesday.
Tickets for the show go on sale to the general public at 10 a.m. Nov. 16. No other ticket information was available Wednesday. Cyrus unveiled her 2014 tour, which starts on Feb. 14 in Vancouver, British Columbia, on her website Tuesday. »Read Full Article(1)
Large trove of art taken by Nazis recovered
Wonderful works of art secreted away by the Nazis as "degenerate" keep turning up "like bottles washed ashore," writes Micheal Kimmelman for The New York Times this morning, reporting on the latest trove of works discovered and unveiled in Augsburg, Germany, Tuesday.
About 1,500 pictures, a particularly large stash, were discovered in the Munich apartment of an old man whose father was a dealer in the Nazi era. From the initial reports and some blurry online reproductions, the collection appears to include works by Matisse, Courbet, Franz Marc, Max Liebermann, Marc Chagall, Max Beckmann and Ernst Ludwig Kirchner. »Read Full Blog Post(2)
Reading the John Updike stories: 'Snowing in Greenwich Village'
The Library of America recently published 'John Updike: The Collected Stories,' a two-volume boxed set of 186 stories arranged in chronological order. I'm reading one or more a week and commenting on them each Wednesday until I finish the collection or give up.
In "Snowing in Greenwich Village," John Updike introduces Richard and Joan Maple, a young married couple whose love, struggle, infidelity and divorce he will chronicle through a series of stories until they become grandparents. Published in 1956 in The New Yorker, "Snowing in Greenwich Village" is the only Maples story published in this collection; the Library of America is holding the others back for a future book. »Read Full Blog Post
Perform your original holiday song for Tap Milwaukee
Tap Milwaukee is looking for four local bands to spread some holiday cheer and perform original holiday songs for a series of videos. Journal Sentinel photo illustration by Zeina Makky. »Read Full Blog Post(1)
On Tap Today: Bucks, kite flying, Updike and disclaimers
You have successfully reached the middle of your week. What does the day have in store?
The Milwaukee Bucks play the Cleveland Cavaliers right here in Milwaukee. Los Lonely Boys and Jonny Lang are playing Potawatomi. Then, there are a few Wednesday traditions worth considering. »Read Full Blog Post


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Republic® Vegetable Bowl by Lenox
Great design needs to be beautiful and practical. The Republic Covered Vegetable Bowl will keep vegetables and side dishes warm at the table with its securely fitted lid. The elegant herringbone banded design and classic scroll-and-leaf motif make this dinnerware pattern an elegant work of sophistication and style.
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subset: commoncrawl


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In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection. Case reports of these patients follow.
Last week, the State Department performed a small but smart gesture towards countering the continued outbreak of the Ebola virus in West Africa by releasing a video featuring President Barack Obama speaking to the people of Liberia, Sierra Leone, Guinea, and Nigeria.
This may come as a total shock, but pure forms of illicit drugs can be hard to come by. Certain controlled substances are frequently adulterated, if not outright contaminated, by products that range from the household to the industrial to the pharmaceutical. Of course, some substances are more easily, frequently, and profitably adulterated than others: cocaine purchased on the retail level is on average 31%, well, not cocaine, while the purity of heroin on the street is even lower, resting around 65% (1).
Unbeknownst to many of the public, August was National Immunization Awareness Month. I know, I know: it's been overshadowed by some very exotic and thrilling headliners this month. The Ebola epidemic blazing defiantly in West Africa. The jaw-dropping videos shown on Discovery Channel's "Shark Week." The ALS Ice Bucket Challenge clogging everyone's social feeds. Vaccines are just not as sexy or as flamboyant as these issues. Truthfully, they're a bit dull to talk about, not a topic you would tend to bring up at cocktail parties or at the water cooler. Read More
Just as we jetsetters and nomads wander the wide world's winding roads and byways by foot, on horseback, atop a bicycle or packed into an automobile, so too do infectious diseases make use of our ever-improving networks of thoroughfares. They ride along in human bodies, their journeys fueled by our social mobility and contact, two factors unavoidably intensified anytime we embark upon a voyage. But as these pathogens travel new routes and encounter new bodies, they can change and mutate. Luckily for researchers, by examining commonly traveled routes where we once naively believed that only humans trod, the active evolution and epidemiology of a pathogen can be revealed, providing insight into the development and patterns of disease affecting mankind.
In the twentieth century, men toiling in British and American coal mines relied on a primitive alert system for imperceptible dangers: the bright canary bird. Miners toted the caged birds into the depths of the earth to serve as early warnings against poisonous and potentially fatal gas leaks. If the tiny birds suddenly slumped in their cages due to the presence of odorless and colorless carbon monoxide, miners would beat a hasty retreat to safer, cleaner air.
It's one of the easiest ways to care for your health, a ritual we participate in daily: brushing those osseous outcroppings, our teeth. For those of us who heed the pleas of our dentists, flossing is a part of our routines, too. But the state of affairs of our glistening maws – the density of plaque, the presence of gingivitis, a full set of chompers – is important beyond mere aesthetics. Good oral fitness, particularly steps taken to limit the bacterial status quo, plays an important role in the goings-on of our body as a whole; a dirty mouth – and not the kind prone to sailor-like profanity – can provide important clues as to how susceptible you are to heart attacks and strokes.
Medicine is an imperfect science, its history shot through with barbaric and dubious practices from grave robbing to bloodletting. Since even before the time of that father of modern medicine, it can seem that physicians have more often violated Hippocrates' decree "above all, do no harm" than abided by it.
Microbial Misadventures is a recurring series on Body Horrors looking at instances and incidents where human meets microbe in novel and unusual circumstances that challenge our assumptions about how infections are spread.
Shout "fire" in a crowded room and watch the occupants fly for the exits. Speak the word "malaria" and watch as all within earshot reach for the nearest can of DEET. The incontrovertible fact of malaria's relationship with mosquitos is one that has been known since Sir Ronald Ross discovered the parasite nesting within the belly of a mosquito in 1897. Such is the natural order, an incontestable necessity of the protozoan parasite's life cycle. Humans, however, are rather adept at bucking that system – see cronuts, labradoodles, and the college bowl ranking system for examples. Also due to the interference of mankind, as a 1995 Taiwanese medical mystery proved, malaria can indeed be spread without the assistance of their obnoxious arthropod cronies.
Hanuman is a pivotal and memorable character in the Hindu epic poem, the Ramayana. Known for his faithful devotion to Rama, the monkey-king is famous for rescuing Lord Rama's bride Sita after she is kidnapped by the demon king Ravana, all the while defeating his demon army as commander of his monkey army. Hanuman is revered throughout south and southeast Asia not only for his devotion to Rama, but also for his steadfast spirit, his indefatigable strength, and his noble humility. He is also something of a rogue – the Coyote, the Loki, the trickster of Hindu mythology, the mischievous troublemaking deity with a heart of gold and a glint in his eye. Read More


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Nicholas Charles Sparks was born in Omaha, Nebraska. He is the #1 New York times bestselling author of Message in a Bottle, and The Notebook. He lives in North Carolina with his wife and family.
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#NeverTrump nut jobs last hope… Gary Johnson - The Erick Erickson-Bill Kristol losers have one last hope. Getting Gary Johnson up to 15% before the second and third
14 hours ago
"One should either write ruthlessly what one believes to be the truth, or else shut up." -- Arthur Koestler


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Optimum Technologies (IND) Pvt Ltd is a fast growing telecommunication support company, actively involved in different telecommunications and infrastructure projects in INDIA.
Optimum Technologies (IND) Pvt Ltd is providing quality services to meet requirements of major telecom players in India. This has been achieved by taking special care in bringing resources with appropriate skills for required projects.
Today Optimum Technologies (IND) Pvt Ltd has reached the critical mass, from where it is ideally suited to provide boundless service in major areas of telecom technology.
Human capital is a key factor at OPTIMUM. The nature of our services means that quality depends on staff expertise. For this reason, and in order to keep up with the rapid organic growth, policy is directed towards the active recruitment of talented people, continuous investment in improving our staff's level of expertise and retaining staff by offering OPTIMUM terms of employment and working conditions.


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Dangerous new drug in Rutland City, police warnAugust 01,2013Staff Report
Rutland Police say there is a new and dangerous combination of drugs in the city - a pill capsule mixture of methamphetamine, ecstasy, heroin and perhaps crack cocaine as well.
Less than a week after police seized 18 pills filled with that mixture during a traffic stop in Rutland, a rapid-fire number of drug overdoses Wednesday have city police worrying that drug cocktail is gaining a foothold in the community and that more overdoses might follow.
None of the six overdoses reported Wednesday proved fatal but city police Detective Sgt. James Tarbell said it was only a matter of time until the combination killed someone.
"When you introduce a depressant and a stimulant into you body at the same time, your body isn't built for that," Tarbell said.
"It's gonna be a mess."MORE IN This Just InMONTPELIER After sitting on the Vermont Supreme Court for nearly 30 years, Justice John Dooley... Full StoryBRATTLEBORO Entergy Nuclear says it has found a potential source of water infiltration into... Full StoryMANCHESTER A little more than a week after it was shut down, the website for the town of... Full Story
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Department of Theater
The Freshman ExperienceTheater students talk life at UCLAWatch video
The Two Cities Project UCLA TFT and LAMDA acting students collaborate via the Internet. Watch video
- Theater Course Descriptions Current course descriptions taken from the UCLA Registrar's Office General Course Catalog.Learn more
- Theater Internships The UCLA Theater Internship Program is open to enrolled students from the UCLA School of Theater, Film and Television and the UCLA College. Only juniors, seniors and graduate students are permitted to take theater internships.Learn more
- Theater Season Explore what's in store for the Department of Theater's 2015-16 Season, including performances of Lainie's Cabaret at UCLA, A Midsummer Night's Dream and Rodgers & Hammerstein's Carousel — just to name a few!Learn more
- Actor Showcases Annual events that spotlight the talents of undergraduate and graduate students enrolled in the UCLA TFT Acting program.Read more


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25 years of experience
Parma Medical Center
12301 Snow Rd
Cleveland, OH 44130 Phone number & directions
A medical license is required for a doctor to practice medicine in a particular state. Requirements vary by state but most require, at a minimum, post-graduate training in the doctor's specific specialty. An NPI number is a national identifier unique to an individual health care provider and is managed by the Center for Medicare & Medicaid Services (CMS).
Learn more about Dr. Allan Love:
View the full profile to get information on:
- Qualifications
- What's important to you
View full profile
Patient Reviews
The overall average patient rating of Dr. Allan Love is Good.
Prepare before visiting Dr. Love
Urge Incontinence Patient Education Urinary incontinence patient education guide covers all aspects concerning overactive bladder diagnosis and treatment options.Before Visiting Dr. Love Learn More
|More Patient Guides & Topics
Erectile Dysfunction
Implant Contraception
Overactive Bladder
Prostate Cancer
Urinary Incontinence
Specialties & Research
Dr. Allan Love, MD is board certified in Urology.
- He has special expertise in 1 area:
- Overactive Urinary Bladder
Education & Awards
Dr. Love graduated from Albany Medical College. He has 1 awards.
Dr. Love has 3 hospital affiliations:
- Parma Community General Hospital
- Cleveland Clinic HS - Fairview Hospital
- Marymount Hospital
- English
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Dr. Irina Grigorev
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- Additional Information
- Dr. Allan Shelton Love MD is a male Urologist, has 25 years of experience and practices in Urology.
- Where does Dr. Allan S. Love practice?
- Dr. Allan Love has 1 office location.
Dr. Allan Love practices Urology near Cleveland, OH.
See Cleveland Urologists.


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Ville_Valo AsianzI just thought I'd say thanks for the signing. Back in December 2008. What can I say I don't check my GB so often.
Jun 14, 09 2:40pm
I may have already returned the favor, I dunno, but here goes anyway. Thanks guy
Ville_Valo AsianzBut Fat Joe has been telling me to Lean Back ever since that song on NFS:U2! Now who should I trust, a guy named Fat Joe, or you?
Feb 10, 09 7:04pm
Leaning forward seems like a great idea actually
Thanks for the comment.
Happy New Year!
Don't have a Stamp with Happy New Year on it, so instead, I post this drawing I made, hope that's good enough, too. lol.
Anyway, I see you're a FMA fan. Good point for you! I'm eager to read the new chapter with hoping to see more Major Gen. Armstrong, even if my favorite female character is Riza.
Happy New Year!
luffyluffy AsianzRestamping everybody who stamped me!
Mar 8, 08 6:14am
You'll be good with a few carrots >.>
Ragnarok352 AsianzLoL nice stamp , i dont have one atm but ill get a new one soon.
Sep 7, 06 10:50am
Till then xD
This is to short so im making it longer ............
kalika_aryn Asianz
May 31, 06 7:09am
Just had to say, FLCL owns. Keep up with the good work of spreading the word. - kali
Ragnarok352 Asianzcool sig ive seen u around the forums so i guess ill sign ur gb so here ya go[URL=http://img463.imageshack.us/my.php?image=ff87883me.jpg]cya around
Mar 13, 06 9:47am
bubblegum194 AsianzHeres a stamp.
Feb 23, 06 1:11pm
See you around the forums!
SunnyDelight AsianzHere`s my kh stamp, Enjoy the stamp and see you around!
May 30, 05 1:17am
brandoni16 AsianzI saw you in the Tales of symphonia forum. Wud up man. Dosent ToS rock!?! Please sign my guest book back! PM me if you wanna be NeoFriends!
Apr 10, 05 10:35am
Angel Blade Asianz
Nov 27, 04 1:16am
I just woke up from sleeping, yet trying to avoid his ghost at the same time. I stayed up till 3 AM for once. Must be from the turkey and Apple Cider. Have fun and see ya around.
Angel Blade27
Satokasu Suki AsianzHey there,
Sep 18, 04 7:51pm
You're still sort of new to Neoseeker - welcome! Also, welcome to the Tales of Symphonia forum. I hope you're having a nice time!
It's a pleasure to meet you.
See you around the forums and take care,
~ Satokasu Suki


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Illinois Public Media News
In-depth reporting from WILL, NPR, the Associated Press, and other sources
Contact WILL News at email@example.com
(Charles Krupa/AP)
April 16, 2013
(AP Photo File)
April 15, 2013
UI Prof: "42" Brings Accurate Story of Racist Abuse Within Baseball
Page 590 of 1063 pages ‹ First < 588 589 590 591 592 > Last ›
WILL Newscast audio
NPR News
Aleppo Under The Most Intense Air Bombardment Since Syrian War Began, U.N. Says
Marlins Pitcher José Fernández Dies In Boating Accident
Suspect Arrested In Fatal Washington State Mall Shooting Of 5
Amid Mounting Pressure, Charlotte Police Release Video Of Shooting
Sinister 'Clowns' Are Scaring People In Multiple States
National Museum of African American History Opens Its Doors
#NPRreads: Get Below The Surface This Weekend With These 3 Stories
5 Killed In Shooting At A Washington State Mall; Manhunt Underway
Obama Vetoes Bill To Allow Sept. 11 Victims To Sue Saudi Government
Native Hawaiians Now Have A Pathway To Form A Government
More NPR News
WILL Highlights
Vintage Vinyl is back!
Huge sale of used vinyl records, DVDs, CDs, and other musical ephemera to benefit Illinois Radio Reader returns on Oct. 1.
The Bandwagon
Not your typical sports podcast. Forget the "hot takes" and meet us at the intersection of sports and culture every two weeks.
Classic Mornings
Get more out of your classical music experience and check out Vic Di Geronimo's blog.


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The three men who escaped from Orsainville prison earlier this month are now at the top of Interpol's Red Notice List. That is basically the list of the world's most wanted fugitives.
The trio's mugshots appeared on the Interpol website early today.
The Red Notices for Yves Denis, Denis Lefebvre and Serge Pomerleau be an indication that police believe the men are no longer in Canada after their helicopter prison break June 7th.
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Lavater and Lessing Visit Moses Mendelssohn (1856), by Moritz Daniel Oppenheim (1800-1882)
The painting by Moritz Daniel Oppenheim (1800-1882), portraying an imagined meeting among scholars Mo
Passover Haggadah Collection (הגדה של פסח)
The Haggadah (Heb. הגדה, "narrative;" pl.
National Jewish Hospital miscellany, 1915 and 1967-1968.
Hospital in Denver, Colorado established in 1899 to help "consumptives" (i.e., people suffering from tuberculosis).
Neustadter (Bernhard) family papers, 1873-1900
Correspondence that Bernhard Neustadter (who lived in California in the late 1880s) received from his family in Berlin and Posen (now Poznań, in Poland) and a letter which he sent to his wife, Ad
Nowinski (Ira) photographs of Northern California Jewish Life, 1983-1984
Ira Nowinski is a photographer based in the San Francisco Bay Area.
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Herta Silbermann Rapp fled Germany in 1939 with her first husband, Walter Fabian, and went to Bolivia.
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Reuben Rinder served as the cantor of San Francisco's Congregation Emanu-El (1913-1959) and as its cantor emeritus (1959-1966).
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Aaron Rogat was a member of the Furriers Union in Los Angeles. His son, Yosal, became an attorney.


text: Page Content 1Babson leadership academy The Babson Leadership Academy intentionally meets students where they are at and creates experiences that allow students to develop and live as entrepreneurial leaders. The Babson Leadership Academy is committed to Student Activities and Leadership's mission to foster and develop educational, social and leadership opportunities in an engaging environment that produces dedicated leaders and active citizens at Babson and everywhere. As such, the Babson Leadership Academy is an opportunity for students at all levels to experience leadership learning that will aid them at Babson and beyond. Built on the foundations of Emotional Intelligence and the concept of Entrepreneurial Thought and Action, students participating in the Babson Leadership Academy will develop their leadership skills by thinking, acting, reflecting and acting again through programs with purpose, learning and network behind them. The Babson Leadership Academy has two main components: leadership seminars & class-specific programming. Leadership Seminars are a series of workshops that are tailored to provide students (no matter their academic status) with skills that are needed to be successful in and out of the classroom. These seminars are presented a member of the Babson College community. 2015-2016 Leadership Seminars topic include:Personal Branding through Social Media Leadership Styles Group Dynamics Productivity and Wellness Diversity and Inclusion Transition Roundtable Marketing Yourself Positivity and Gratitude Class-specific Programming focuses on providing students with experiences that are targeted for their academic year. With the concepts of Purpose, Learning and Network, programming helps students understand First Year Programming First Year/Senior Retreat Sophomore Programming Mystery Bus Junior ProgrammingDinner with Strangers Senior Programming First Year/Senior RetreatSORA Retreat The following programs are open to any student regardless of their academic status: 4U Retreat Posse Retreat (invitation only) CWEL Retreat (invitation only)


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No Brand XHPC155YBD 15.5" Laundry Pedestal w/ Storage Drawer - Black Diamond
$214.93 - $239.99
1 year parts and labor
Find Out More »
The Whirlpool 15.5" laundry pedestal w/ storage drawer has a Chrome Trimmed Handle and ball bearing drawer slides for Easy access to stored items. The generous internal dimensions (11" H x 21"W x 18" D) to accommodate storage of different sized laundry detergent bottles or additives, and a movable divider allowing users to change the storage configuration to suit their needs.
- The Chrome Handle provides a comfortable grip to open the drawer
- The pedestal drawer offers a convenient area to store laundry essentials
- Pedestal will raise your washer and dryer to a more comfortable height for loading and unloading items
Specifications & Dimensions
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Wise® Offshore Folding Deck Chair
Item # WX2-141425
You May Also Like
Swivl - Eze® Adjustable - height PedestalNon-Member $27.99 Buyer's Club $25.19
Swivel Jon Boat Seat ClampNon-Member $27.99 Buyer's Club $25.19
Wise 8WD10 6" Trendler Ball Bearing Swivel Boat Seat BaseNon-Member $8.99 Buyer's Club $8.09
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Wise® Offshore Folding Deck Chair puts your crew in the "comfort zone"!
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- 8 legs for added strength
- Stainless steel hardware
- Measures 30"h. x 26"w. x 24"d.
Extra seating every bit as comfortable and durable as your boat's permanent seats! Order ONLINE Today!


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I just got done working out at the gym and normally I don't shower there because I live so close to the gym but I was in a bit of a hurry for no particular reason. I finshed showering and went to a corner spot of the locker room and out of nowhere c
Mother n law and our 2nd enocounter
I woke up and the first thing on my mind was the amazing handjob my mother-n-law Mrs Brown had gave me yesterday afternoon. I could'nt believe it actually happend! After being obssesed with this woman for so long something happend between us and I
The mother n law, the relationship
Let me explain my mother-n-laws and my relationship before you read the stories of where her and I are now. When we first met one another she was under the assumption that her daughter and I were only friends so, when Jasmine and I moved in together
Daddy's Home
So we decided that I would meet you up in Kentucky when you got back from your deployment. I figured it would be easier for me to just drive up and meet you the day that you returned home. It was warm enough outside to dress just the way I wanted to
My mother in law and me
I would like to share my experience of fucking my mother in law here in this forum.
This incident happened a month ago. Firstly let me introduce my mother in law. Her name is Ananthi and she is 45 yrs old, fair and sexy lady. She has a slim figure o
Kate Throws A Great Party
This year Kate and Jake threw another one of their wild 4th of July parties. The highlight is usually Kate, prancing around their swimming pool in a skimpy bikini that showed off 99% of her sexy body. Last year my girlfriend and I ended up back at my
How a shy Indian bride got deflowered on her honey
Hello mates,
This is my first time on this forum. I have been reading stuff here for quite sometime and some of the stories were really good. I would like to share a real incident with you guys which somehow changed my life and perception. Consequen
Swingers Club Trip
The door of the swingers club opens and we walk downstairs into a dimly lit room where a olive skinned woman with long black hair in her mid 40s dressed in stocking, suspenders, heels and a basque greets us. She is about a size 16 and has large breas
Debbie Arrives With A Bang
Last year I reunited with Debbie who has been my best friend and occasional lover for over 10 years. Debbie is such a sexual creature by nature, a self described nymphomaniac with an attitude and body to match. I have been with my share of women in m
The Soldier and The Seaman
The day began as any other day for a deployed soldier in Iraq. Wake up take a shower in the dingy trailers provided and make your way to work. But on this day for JoLynn this day would be different. After her 15 hour shift she headed over to her best
Horney AMISHI's Extra Toppings
There was something about Horney AMISHI's recent Siliconised sudden growth. Of late AMISHI has been spotted in outfits that further accentuate her 40D sized Siliconised Twins. She has been striking postures to highlight her Assets, and she is not
Naked on the beach
We had gotten to the parking lot later than I had wanted, but were still earlier than we used to get there years ago. Judging by the number of vehicles, the beach had become much more popular than before. Obviously there weren't any parking spots in
Etta Rose's
Although it was warm out, it was at the end of October and the trees on the Cumberland mountains looked like the swirling, crystal colors in blown glass; a mixture of yellows, blues and purples. The sky a deep blue with wisp of clouds intermingled li
A wild party
my friend was having an 21st birthday party and i went,there was 6 private rooms(my friend lives in an$68,000,00000 mansion)and i decided to stay in one for the night.
we all got drunk and a chick came up to me and started touching me,she took me up
My friends dad
I waited for my friend Tanya to go to sleep,then slipped outside to where her dad was working on his boat he was so strong and tanned i had been flirting with him all night and i know he was interested as the bulge in his pants was big,so i climed up
my friends rung me and asked me if i wanted to go camping with them during the weekend ,one of my mates has a girlfriend and she was bringing all of her friends aswell as we were setting up ourtents the 4 girls arrived ,one in everlast pants and a th
When the rain comes
I had just drove to up the road for a few beers with my buddy at his place and was on my way back home. It was sunny, hot and humid. I had the top down on my convertible. My buddies place was only about ten minutes away but it was looking more and mo
Watching Darius fucking my wife Sue
When these eventful few days occurred Sue and I had been together for 9 years, we were both 33 years old, not married but we are now. I have always been very jealous especially of Sue, as she is what I describe as all woman, 5′ tall, long
Jamie was exhausted as the cheerleading coach dismissed them from practice for the day. Since transferring to City High a month ago, her life had certainly changed. She had found herself making friends easily and had won a position on the cheerleadin


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Recent renovations in the engineering wing of McQuay International's Staunton, VA facility have earned the building a LEED Silver certification. The Staunton facility is the first project in the Shenandoah Valley to become LEED Silver certified.
"The renovation has been energizing for employees at our Staunton facility and across the country," said Phillip Johnson, engineering director at McQuay International's Applied Development Center in Staunton.
Renovations have included CO2 censors to maintain air quality, air filters in critical spaces to remove particles such as copier toner dust, and a VAV rooftop system that reduces heating and cooling energy expenditure. The VAV system also users R-410A refrigerant, which has no ozone depletion potential and a low global warming potential compared to other non-HFC refrigerants.
The Staunton facility has also reduced water consumption by more than 40 percent, reused 89 percent of the building's original materials, utilized new construction materials with a high recycled content, and certified more than 50 percent of the construction wood through the Forest Stewardship Council. The facility has a recycling program and commuter friendly parking for bicycles and low emission vehicles.
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text:
SimHealth Research Awards – 2015
The University of Technology Sydney again sponsored the 2015 SimHealth Research Awards.
A prize to the value of $400 was awarded for each of:
Best Research Abstract
Thomas Loveday, Monique Crane, Mark Wiggins
The Relationship Between Recent Adversity, Affective States And Anaesthetist Diagnostic Skill Investigated Using An Online Simulation Based Assessment
Best Education Development Abstract
Ingrid Wolfsberger, Mary McCaskill, Emma McCahon, Claire Nayda, Marino Festa
Using Simulation Based Training To Inform Safe And Effective Work Practices: Lessons From A State Wide Paediatric Ebola Centre
Best Technology and Innovation Abstract
Alexander Walker, Michal Wozniak, Nirmal Menon
Enhanced Clinical-Realism In Medical Simulation Training, Flinders University
Best Poster
Nicole Stevens, Kylie Downs
Using Simulation To Evaluate Clinical Skills As Part Of The Recruitment Process In Speech Pathology
Best Works in Progress
Jessica Stokes-Parish
Does Authenticity In Moulage Matter? Exploring Participant Engagement In Simulation
Awards presented by Carolyn Hayes
Previous Award Recipients
Best Research Abstract
Brett Williams, Tracy Levett-Jones, Ehab Khasawneh
The Satisfaction with Simulation Experience Scale (SSES): A cross-cultural psychometric appraisal
Best Education Innovation
Bree Bulle, Kate Freeman, Kathy Evans, Simone Andy, Barbara Gibson-Thorpe, Kim Warde, Kasey Johnson, Jacquie Boyle, Leah Hickey, Jacquie Whitelaw, Marg Stam, Stephanie Thowtapp, Tony Ginis, Tanya Farrell
Using simulation to improve cultural safety and close the gap between professional silos in maternity care
Best Technology Innovation
Hans de Visser, David Conlan, Josh Passenger, Cedric Dumas, Olivier Salvado
A new locally developed Virtual Reality Colonoscopy Simulator
Best Poster
Caroline Zhou, Alexander Garden, Peter Watt
Evaluation of a New Crisis Management Course for Junior Anaesthetic Doctors
Best Works in Progress
Andrew Spain, Joe Lopreiato
Terminology & Concepts: A Common Language for Healthcare Simulation
Overall Best Abstract
Suzanne Gough, Abebaw Yohannes, Pennie Roberts, Judith Sixsmith
Are final year physiotherapy students able to independently recognise errors encountered in their own simulated practice?
Best Research Abstract
David Cumin, Matt J. Boyd, Nishanthi Gurusinghe, Alan F. Merry, Jennifer Weller
Creating a Multidisciplinary Operating Room Simulation Course (MORSim) for training and research: Overcoming Barriers
Best Technology Abstract
Therese Gunn
A 3D Virtual Medical Imaging Suite: Bridging the Academic-Clinical Training Boundary
Best Education Abstract
Louise Nicholls, Lisa McCoy, Davin Arthur, Dylan Campher
Simulation Coordinator Training: a standardised approach to training the technical aspects of simulation delivery.
Best Poster
Samantha Gardner and Megan Taylor
Simulation in the wilderness; enhancing learning for final year medical students


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Cheap lens, cheap results
by Enrique on 4/10/2013
Actually, this telelphoto lens deserves no stars at all! When I used it, pictures came out awful. To add insult to injury, when I was trying to unscrew the lens from my camera, it came apart, fell to the floor, and that was the end of it. Cheap, cheap,cheap.
Was this review helpful to you?YESNO


text:
Communication via a strategic mediator
This paper investigates communication between an informed expert and an uninformed principal via a strategic mediator. We demonstrate that, for any bias in the parties' preferences, there exists a strategic mediator that provides the highest expected payoff to the principal, as if the players had communicated through an optimal non-strategic mediator.
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Volume (Year): 145 (2010)
Issue (Month): 2 (March)
Pages: 869-884
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| Web page: http://www.elsevier.com/locate/inca/622869
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Celebrity Central / Top 25 Celebs
Julianne Hough
Dancing with the Stars Recap: Who Dazzled on Disney Night?
Hey, Mickey! This week, the stars channeled their favorite characters from the Mouse House
Derek Hough: Dancing with Sister Julianne Has Been 'Weird' in the Past
"I started dancing because I wanted to be around girls," the Dancing with the Stars pro tells PEOPLE
Dancing with the Stars Recap: The Stars Share Their Most Memorable Year
Noah Galloway, Willow Shields and Nastia Liukin stood out as the stars waltzed, tangoed and rumba'd down memory lane
EXCERPT: Derek Hough Admits It Used to Be 'Super Awkward' to Dance with Julianne in PEOPLE's 10 Years of Dancing with the Stars
"Now, when we dance together it's got a fun energy about it," Derek tells PEOPLE
Lip Sync Battle Preview: Derek Hough Is 'Straight-Up Traumatized' by Little Sis Julianne
The Dancing with the Stars siblings take on Sia and Akon on Spike TV's new series
Dancing with the Stars Recap: A 'Jam'-Packed Night
Patti LaBelle overcomes an injury and Rumer Willis maintains her position as one of the best in the pack in week 2
Dancing with the Stars Recap: Which Celebrity Brought Down the House – and Attracted Big Stars?
Rumer Willis shines – and Noah Galloway brings tears – on the opening night of season 20
20 Fun Facts About the Cast, Judges and Hosts of Dancing with the Stars Season 20
This year's cast includes an NYU student, a farmer and a tennis player-turned-singer
Nina Dobrev, Julianne Hough and Ashley Tisdale Enjoy a Girls' Night Out at Salon Opening
The celebs partied with stylist Riawna Capri on Melrose Place in West Hollywood last Saturday
Betty White Turns 93, Miley Cyrus Sings Karaoke & More Weekend News
Plus: How Ryan Gosling and Eva Mendes spent their night away from baby Esmeralda
Julianne Hough and Vanessa Hudgens to Star in Grease Live Musical on FOX
Julianne Hough will play Sandy in FOX's live musical, airing Jan. 31, 2016
Julianne Hough and Boyfriend Brooks Laich Have a Skate Date
The couple took to the ice during a family skate in Washington, D.C., on New Year's Eve
The Hough Family's Thanksgiving Dance Wars Returns with Kate Hudson, Maria Menounos and More
With you were in a food coma, these celebrities were shaking it off


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|Boxing Champions | Boxing Schedule | Boxing Video | Boxing History | Pound For Pound | Lounge | The Wire | Arcade
The Devil's Double
Join Date: Aug 2010
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*******s: "Manny fought a better version of JMM because JMM doesn't drink his piss anymore!"
Is that the best you guys can do?
Anyway people are using a double standard by saying Manny beat guys worst than Mayweather did. De La Hoya was a year and a half older and coming down in weight. Hatton had been knocked out and came off of two lackluster wins. But JMM was 38 and moving up in weight for a second time and Manny STILL had trouble with him. Manny had more trouble with JMM than Floyd did with De La Hoya or Hatton.
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Who's #2? Charlie Zelenoff? All he's done the past year and 1/2 is sucker punch a C Class fighter. Stop it.
I would believe Donaire or Martinez as #1 more, despite them looking less than stellar as well in their last fights.
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If flooyd wants to be known as the best p4p guy in the world he knows what hes got to do, and thats step up to the plate.
Pac didnt become no1 on the basis of one fight, so he wont lose it on the basis of one fight.
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Floyd officially retired in 2007. So Pac who had been number 2 since 2006, took his spot...If he wants it back then he has to beat Pac in the ring, or wait for him to retire, or wait for him to lose. And when I said lose, it means actually him losing, not the so called 'moral' victory of his opponents that you guys keep harping about....
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styles make fights. no one that fights from a defensive shell or runs from pac will beat him.
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OK... why can't Pac fight Berto next?
If Pacquiao is reluctant to fight Mayweather because he is coming off an iffy performance and his/his team's morale and confidence may be low, then fight Berto.
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Swine flu: preparation is essential
Published 15/05/2009
Proof that nowhere is immune from the current swine flu epidemic came with the announcement that Northern Ireland has its first confirmed case, with another possible case being investigated.
The relatively late arrival of the infection to the province meant that health authorities have had vital time to prepare and gear up their contingency plans. Already enough anti-viral drugs are available to half the population, with stocks being built up to cover 80%.
Credit is due to the health authorities and Health Minister Michael McGimpsey for the assured way they have prepared for possible widespread infection. And now that the first case has been confirmed everyone should heed the advice not to panic. Outside of Mexico, where the epidemic began, and the United States the strain of flu appears to be relatively mild and easily treated.
The simple advice on good hygiene which has been issued constantly since the alert began, is still the best protection against contracting the flu.
Those who were on a flight from London with the person confirmed to have flu are being contacted by public health officials. They should seek an examination from their GP if they display any of the flu-like symptoms and avoid contact with other people as much as possible. Having a check-up is essential both for their own health and to prevent them possibly infecting other people. Already 25 people who have been in contact with the infected person have been given medical checks.
The disease has now been confirmed in 33 countries, amounting to 6,500 cases, far from the pandemic predicted. However, it would be foolish to be complacent as some health experts think that this strain of flu could return in a stronger form in the autumn or winter when outbreaks are most common. It should be noted that ordinary winter flues cause several thousand deaths in the UK each year, usually among vulnerable people like the elderly or those whose immune systems are impaired. A more virulent strain of flu could send the death toll considerably higher so it is in everyone's interest to contain the present epidemic and to continue the search for an effective protective vaccine.
While the state of alert remains high people should take sensible precautions to protect themselves against swine flu. The most obvious is to cancel any planned travel to Mexico and also consider carefully before travelling to the US or other countries with a high incidence of the disease. Any suspicious symptoms should be investigated immediately. The health authorities are geared to deal with public concerns.
What the outbreak has demonstrated is that the world really is a global village. The ease and frequency of inter-continental travel means that infection can literally wing its way around the globe in a very short period of time.
The critical point is how the health authorities in each individual country react to the epidemic.
It does seem that many countries are quickly getting up to speed on the diagnosis and treatment of confirmed cases. In that respect Northern Ireland can regard itself as one of the best prepared.
For that, at least, we should be grateful.
Belfast Telegraph


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Mar Dioscoros Welcomes Donation to Build a Student Chapel at CoimbatoreDr. Youhanon Mar Dioscoros, Metropolitan of Madras Diocese exhorted all to donate generously to build a student chapel at Coimbatore for the benefit of Orthodox students pursuing their higher education at the Karunya University and there around. Mar Dioscoros' exhortation came out through
Posted in Diocese News,Features,News | Read More »


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Convergence (and divergence) in the biological standard of living in the USA, 1820–1900
Standard economic indicators suggest that the USA experienced long-run economic growth throughout the nineteenth century. However, biological indicators, including human stature, offer a different picture, rising early in the century, falling (on average) mid-century, and rising again at the end of the century. This pattern varied across geographical regions. Using a unique data set, consisting of mean adult stature by state, we test for convergence in stature among states in the nineteenth century. We find that during the period of declining mean stature (1820–1870), heights actually diverged. Later in the century (1870–1890) we find a type of "negative" convergence indicating that stature among states tended to converge to a new, lower steady state. Only towards the end of the century (1880–1900) do we find classic convergence behavior. We argue that the diversity of economic experiences across regions, including urbanization, industrialization, and transportation improvements, explain this pattern of divergence and then convergence.
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Volume (Year): 2 (2008)
Issue (Month): 1 (April)
Pages: 19-48
|Contact details of provider:
| Web page: http://www.cliometrie.org
More information through EDIRC
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Bluffton High kicker D.J. Chappelear broke school records for field goals made and longest field goal in the Bobcats' SCHSL Region 7-AAA opener against May River on Friday.
The United States had the lead. Rory McIlroy made sure that was all it had Friday in the Ryder Cup.
Jake Browning threw for 210 yards and three touchdowns, Myles Gaskin added 100 yards and two scores, and No. 10 Washington was dominant on both sides, overwhelming No. 7 Stanford 44-6 on Friday night.
A Giants left fielder Angel Pagan body-slammed a male fan who ran onto the field into the outfield grass at AT&T Park during the fourth inning against the Los Angeles Dodgers on Friday night.
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'Paranormal Activity' producers to terrorize audiences with eco-horror film 'The Bay'
The producers of "Paranormal Activity" have found a new way to scare horror fans. Director Barry Levinson's found footage film "The Bay" is heading to theaters later this year. Lionsgate has picked up the U.S. distribution rights.
The eco-horror film centers around a biological disaster originating in Chesapeake Bay, where a disease-ridden parasite is transferred from fish to human hosts. Like "Paranormal" (and "The Blair Witch Project" before it), the horror plays out on simulated home video and streaming Internet footage.
Levinson co-wrote the script with Michael Wallach. Levinson also produced, with Jason Blum, Steven Schneider, and Oren Peli. Brian Kavanaugh-Jones, Jason Sosnoff, Colin Strause, and Greg Strause acted as executive producers.
Although mostly known for comedies such as "Diner" and "Good Morning Vietnam," Levinson tackled sci-fi/horror before with his 1998 adaptation of Michael Crichton's "Sphere." He won an Oscar for directing "Rain Man" in 1988. Levinson was also nominated for an Emmy last year for the HBO film "You Don't Know Jack," starring Al Pacino.
"Ingenious genre films are and always will be a specialty at Lionsgate," said Lionsgate's Joe Drake in a press release. "'The Bay' is a shining example of the kind of truly fresh horror film that audiences are always ready for, and that we excel at eventizing with them. Thanks to Barry, we'll all be afraid to go in the water for years to come."
"We have been big admirers of Jason Blum, Steven Schneider and Oren Peli since their breakout hit 'Paranormal Activity,' and are thrilled to be in business with them," added Lionsgate's Jason Constantine. This film works so effectively because it establishes a very natural, everyday world, places the audience intimately within it, and then sits back as everything takes a horrific turn. Barry has incorporated found footage to the most satisfying possible effect, and it's all the scarier for not relying on anything supernatural."
"It's exciting to see a company like Lionsgate embrace 'The Bay' so enthusiastically. The found footage/multiplatform approach opened up the film to creative possibilities I hadn't encountered in my previous films, and I think these sorts of films will only continue to push boundaries as the technology changes," said director Levinson.


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US Secret Service seeks social-media monitor to identify online sarcasm
Secret Service advertises for a quick way to tell if the millions of messages monitored on social media are real threats or just ill-advised jokes
The US is looking to buy software that can identify sarcasm on social media so that it can distinguish between actual threats and ill-advised jokes.
United States government agencies and corporations have long used social media to try to get their messages out, while law-enforcement agencies increasingly monitor such sites for signs of trouble.
However, getting a computer to detect sarcasm and its linguistic complexities can be difficult, and some experts worry about attempts to interpret speech by a government agency that has the power to arrest people for posting alleged threats online.
"It does appear that it's going to be a pretty broad monitoring programme. It will likely sweep in some First Amendment-protected expression," said Ginger McCall, associate director of the Electronic Privacy Information Centre.
"It is troubling, because it really stifles people's ability to freely express themselves and it has a tendency to quell dissent to make people think twice before they express themselves online."
The Secret Service request for the software, first reported by nextgov.com was posted on Monday. The agency is accepting proposals until next Monday.
The work order asks for a long list of specific tools, including the ability to identify influential figures on social media, analyse data streams instantly and access old social-media data.
Secret Service spokesman Ed Donovan said the request would allow the agency to create its own system for monitoring Twitter, and detecting sarcasm was just a small feature of the effort.
"Our objective is to automate our social-media monitoring process," he said. "Twitter is what we analyse. This is real-time stream analysis. The ability to detect sarcasm and false positives is just one of 16 or 18 things we are looking at."
Companies already used algorithms that attempted to detect sarcasm online or over the telephone in measuring things such as customer satisfaction, said Lisa Sotto, a managing partner of Hunton and Williams in New York, who focuses on issues involving cybersecurity.
Peter Eckersley, technology projects director for the Electronic Frontier Foundation, thinks the Secret Service effort will fail because computers can't grasp the nuances of language.
"It's difficult not to be sarcastic about the idea of the Secret Service automatically, algorithmically, examining all of your social media posts to determine, among other things, that you're being sarcastic," he said.
A Texas teenager was arrested last year after posting what he said was a sarcastic comment about shooting up "a school full of kids" on Facebook.
A Twitter user also was arrested in the Netherlands in April after tweeting what she claimed was a joke bomb threat to American Airlines.
"There is a reason why they want to do this," Eckersley said. "There have been regular, tragically documented instances where a human being whose crime is being too funny winds up with a pile of agents pointing guns at them and arresting them because they made a joke."
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How to Apply
Students must complete all 5 steps in the APPLICATION PROCESS and submit a complete packet by the priority or final postmark deadline. Students submitting complete applications by the December 1, 2015 priority postmark deadline will receive full consideration for scholarships. Students submitting applications after the December 1, 2015 priority postmark deadline and by the final February 1, 2016 postmark deadline will only be considered for scholarships if the applicant pool has not been filled to capacity.To begin the application process CLICK HERE.


text:
Best of the Week's Style Bloggers: Printed Pants
Colorful stripes, vibrant florals, and so much more.By Leah Rodriguez
Colorful stripes, vibrant florals, and so much more.By Leah Rodriguez
Replaces Russian missile crisis as most notable Russian crisis.By Allison P. Davis
These are pants for winners.By Allison P. Davis
In honor of her last day at the Cut, Diana Tsui picks the trends she's never stopped wearing.By Diana Tsui
With a fitted sweater or playful trousers.By Diana Tsui
With side-butt for all to see.By Maureen O'Connor
Worn by Rita Ora, Miley Cyrus, and Jennifer Lawrence.By Maureen O'Connor
What should we call them? Who designed them? Are they cool?By Maureen O'Connor
They look pretty great, actually.By Charlotte Cowles
Some are wearing tuxes.By Amanda Dobbins and Laura Reineke
It has diamonds all over it, so it must be worth it!By Amy Odell


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ESPN Reporter/Host for NASCAR, College Football/Basketball and SuperMommy to twin boys!
Face Tags
Out for a walk and I've officially lost my wingmen! #lostnaptime
Looks like Brady had a rough night too!
I think Liam had a rough night.
I have the best husband ever!
Getting ready to go live on SportsCenter at yesterday's press conference with @martysmithespn
Love the post race press conferences...
I just received a rose from some of the German media! Thanks!
My view of the track walking in...#tooearly
Courtesy of Carl Edwards....good times!
The media outside the NASCAR hauler this morning for Kyle busch
We're off to see the Wizard. Happy Halloween.
We're off to see the Wizard! Happy Halloween!
The boys at the celebration of flight today at @ConcordAirprtNC
Cale and Dale in @CLTMotorSpdwy media center. 11 championships right there ladies and gentlemen!
Brady and Lugnut playing "peak-a-boo" at @CLTMotorSpdwy
@JamieLittleESPN better be hungry. Holy pot pie.
Bowyers press conference.
Hard at work in Chicagoland! Thanks @andyhallespn
hey @BMSupdates where is my nameplate? Looks like I'm @MartySmithESPN this weekend.
©2016 Twitpic Inc, All Rights Reserved


text:
Warhammer 40k: Dawn of War 2 - Retribution
Page 28 of 40 • First Page • Previous Page • Next Page • Last Page
Dawn of War 2: Retribution Trainer
Telumehtar posted on Jul 03, 2011 7:46:29 AM - Report post
I'm getting pretty annoyed at the moment. Can't get the super unit option to work, crashes my game everytime. The funny thing is it has worked before but now it doesn't so it's most likley faulty on my end. Oh well, have to do with out super units untill i can sort it out.
justincase_2008 posted on Jul 03, 2011 7:48:07 AM - Report post
Its something with the trainer. If i play with out it my HQ has 2500hp with it on and activated with no number pad buttons hit my HQ has 5000 so its glitching the game some how. Ill try some things and see what happens.
thats what happening to me.
thats what happening to me.
[Edited by justincase_2008, 7/3/2011 8:29:28 AM]
fire_foxxx posted on Jul 03, 2011 3:49:31 PM - Report post
Clear out your Temp folder. Super Unit works perfectly afterwards.
If confused check the other reded topic under this one.
If confused check the other reded topic under this one.
PS: Burn the heretics for an extra ticket on steam
justincase_2008 posted on Jul 03, 2011 7:11:17 PM - Report post
Dang the nids have no FIRE!!!
Delson83 posted on Jul 05, 2011 7:55:33 AM - Report post
When you enable super unit, it seems to buff the elders as well. They get super high HP. One way to work around this is to press 0, but it will reset all your units too. After that, you just got to reactivate the super unit for your units.
BioticNinja posted on Jul 11, 2011 7:02:29 PM - Report post
originally posted by Delson83
When you enable super unit, it seems to buff the elders as well. They get super high HP. One way to work around this is to press 0, but it will reset all your units too. After that, you just got to reactivate the super unit for your units.
I'm having the same thing happen with Chaos Marines when playing the Space Marine campaign. Its workable, but highly annoying to have to reset for every engagement.
Mezzed posted on Jul 15, 2011 9:39:37 AM - Report post
Wouldn't it be better to make a cheat where your units just never drop to 0 health? That way you could just stand and deliver
BioticNinja posted on Jul 15, 2011 12:30:18 PM - Report post
Might be an issue with how the game scripts the health. Could be in order to make it to where the health bars don't drop below 0, it would make all health bars not drop below 0. Obviously health between enemy and friendlies is intertwined to some extent, or we wouldn't be having these issues to start with.
I had increase health issues when using the trainer in DoW2 and CR as well but not quite to the extent as it happened in the first mission or two in Retribution.
[Edited by BioticNinja, 7/15/2011 12:30:28 PM]
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From the Department of Neurology (Drs Wu, Wang, Fang, and Murong) and the Institute of Neurological Sciences (Dr Lin), First Affiliated Hospital, Fujian Medical University, Fuzhou, and the Institute of Genetics, Fudan University, Shanghai (Dr Yu), People's Republic of China.
The defective gene (ATP7B) that causes Wilson disease (WD) codes for a putative copper-transporting P-type adenosine triphosphatase. After cloning of ATP7B, the spectrum of mutations and their clinical consequences have been investigated in patients with WD in different ethnic populations. However, the spectrum of mutations and the correlation of genotype-phenotype in the Chinese population have not been extensively studied.
To investigate the characterization of mutations of ATP7B and the correlation between genotype and phenotype in the Chinese population.
We studied 60 unrelated healthy Chinese and 65 unrelated Chinese families, including 84 patients with WD and 126 parents. Genomic DNA was prepared from peripheral blood leukocytes using a salt-precipitation method. Polymerase chain reaction single-strand conformation polymorphism and subsequent direct sequencing were used to identify the mutations and polymorphisms of ATP7B. Statistical analysis was performed using t test or χ2 test.
We identified 18 mutations (7 novel) and 11 polymorphisms (3 novel). The novel mutations are −36C→T, Trp650ter, Gln914ter, 2810delT, Thr935Met, Arg1041Pro, and Glu1173Lys. The novel polymorphisms are 1168A→G (Ile390Val), 2785A→G (Ile929Val), and 3316G→A (Val1106Ile). Two mutations, Arg778Leu and Thr935Met, are relatively frequent, representing 37.7% and 10.0% of patients, respectively. To our knowledge, we are the first to report the correlation between the genotype and phenotype of Arg778Leu. The result shows that Arg778Leu homozygotes are associated with the early onset of WD with hepatic presentation.
The Arg778Leu and Thr935Met mutations are hot spots in the Chinese population. The features of mutations of ATP7B differ between the Chinese and Western ethnic populations. The Arg778Leu mutation has severe effects on the function of ATP7B. These findings are valuable for developing a fast and effective method to diagnose the presence of the WD gene.
WILSON DISEASE (WD) is an autosomal recessive disorder of copper transport. Toxic accumulation of copper causes tissue damage, primarily in the liver, brain, and kidneys. The disease phenotype includes progressive liver degeneration and/or neurologic impairment and, frequently, kidney malfunction.1 The worldwide prevalence of the disease is estimated to be 30 per million, with a corresponding gene frequency of 0.56% and a carrier frequency of 1/90.2 Treatment involves the removal of excess copper by means of chelating agents, such as penicillamine,3 or the blocking of intestinal copper absorption with zinc salts.4
The defective gene in WD encodes a putative copper-transporting P-type adenosine triphosphatase (ATP7B) highly homologous to the protein encoded by the Menkes syndrome gene.5- 8 After the cloning of ATP7B, the repertoire of mutations and some clinical consequences have been described in affected family members of different ethnic backgrounds, and certain mutations are found to be relatively frequent in patients of European origin.9- 14 In Chinese patients with WD, the arginine-to-leucine substitution at codon 778 (Arg778Leu) and arginine-to-glutamine substitution at codon 778 (Arg778Gln) occurring at a higher frequency have been reported.15 Herein we report the identification of 18 disease mutations and 11 polymorphisms in the Chinese population, the genotypes of ATP7B, and the clinical phenotypes of WD.
We studied 60 unrelated healthy Chinese subjects (controls) and 65 unrelated Chinese families that included 84 patients with WD and 126 parents. Of the 84 patients, 44 have been described previously.16 The patients with WD and controls are from the Han ethnic group of the same geographic area in China. Eight of these families were consanguineous. The age at onset for each patient ranged from 4 to 39 years. The diagnosis of WD was based on clinical symptoms, lowered plasma ceruloplasmin and copper serum concentrations, high urinary copper concentration, and the occurrence of the characteristic copper deposition of Kayser-Fleischer rings in the corneal periphery.1 All patients with WD had Kayser-Fleischer rings. Genomic DNA was extracted from the whole blood collected in sodium EDTA by a salt-precipitation method.17
Exons 1 through 21 of ATP7B were amplified using primers complementary to the DNA sequences flanking the exon-intron boundaries. The primers used for amplification of exon 1,18 exons 2 through 21, and the lengths of polymerase chain reaction (PCR) products have been described elsewhere.10 The PCR amplifications were performed in 50-µL total volume containing 50 mmol/L of potassium chloride, 10 mmol/L of Tris (pH 8.0), 1.5 mmol/L of magnesium dichloride, 0.20 µg of genomic DNA, 0.25 µmol/L of each primer, 200 µmol/L of each deoxynucleoside triphosphate, and 2.0 units of Taq polymerase (Sogon Inc, Shanghai, China). The reactions were performed at 94°C for 2 minutes followed by 30 cycles consisting of denaturation at 94°C for 45 seconds, annealing at 64°C to 56°C for 45 seconds, and elongation at 72°C for 1 minute, with the last elongation step for 5 minutes in a programmable thermal controller (PTC-100; MJ Research, Inc, Waltham, Mass).
For single-strand conformation polymorphism (SSCP) analysis, 5 µL of the PCR product was diluted with 5 µL of loading buffer containing 95% formamide, 20 mmol/L of EDTA, and 0.05% each of bromphenol blue and xylene cyanol FF. The samples were denatured at 95°C for 5 minutes, cooled on ice, and then applied on a 8% nondenaturing polyacrylamide gel containing 5% glycerol. Electrophoresis was performed at a constant temperature of 20°C or 4°C and at a constant voltage of 500 or 200 V for 7 to 16 hours. After electrophoresis, the gels were silver stained,19,20 air dried, and stored for documentation.
Patient samples exhibiting shifts relative to control samples on SSCP findings were subjected to direct sequencing for identification of the mutations. The patient DNA samples that did not exhibit a shift pattern of SSCP in exons 5, 8, 12, 14, and 18 relative to control samples were also sequenced to detect the mutation, since mutations are more often clustered in these exons. The DNA from patients and controls were amplified according to the conditions described above. The products were purified using a quick spin column (Qiagen Inc, Valencia, Calif). The DNA sequencing was performed on a 377 DNA automatic sequencer or 3700 DNA analyzer (both from PE Applied Biosystems, Foster City, Calif) using a commercially available sequencing kit (Big Dye Terminator Ready Reaction Mix Cycle; PE Applied Biosystems). Point mutation in heterozygotes was detected reliably by means of manual inspection of characteristic double peaks. If the height of a peak in the mutated allele was shorter than 50% of the wild-type allele at the same position, the opposite strands of corresponding regions were sequenced to confirm these mutations.
Data were analyzed using a commercially available statistical package (SPSS, Version 8; SPSS Inc, Chicago, Ill). Results were presented as mean ± SD. Statistical analysis was performed using t test or χ2 test. The criterion for significant difference was P<.05.
We investigated 84 patients with WD from 65 Chinese families, and identified a total of 18 mutations (Table 1). Seven mutations are novel, and 11 have been described elsewhere.10,15,21- 23 The novel mutations include cytosine-to-thymine substitution at nucleotide 36 (−36C→T), tryptophan termination at codon 650 (Trp650ter), glutamine termination at codon 914 (Gln914ter), thymine deletion at nucleotide 2810 (2810delT), threonine- to -methionine substitution at codon 935 (Thr935Met), arginine-to-proline substitution at codon 1041 (Arg1041Pro), and glutamic acid–to-lysine substitution at codon 1173 (Glu1173Lys). The 2810delT mutation, which causes a frame shift, is predicted to produce a shortened nonfunctional protein. The Trp650ter mutation, which is caused by a guanylic acid–to–adenylic acid transition at the third nucleotide of the codon, and Gln914ter, which is caused by a cytosine-to-thymine transition at the first nucleotide of the codon, would result in truncated proteins. The −36C→T mutation identified in the 5′ untranslated region may alter the expression or translation of ATP7B. The Thr935Met, Arg1041Pro, and Glu1173Lys mutations are all missense mutations. Among 65 unrelated patients, our screening method detected 2 mutations in 36 patients (17 homozygotes and 19 compound heterozygotes) and at least 1 mutation in 23 patients. The other 6 patients escaped the detection. The sensitivity of testing is 73.1% (95/130). No mutation was detected by means of direct sequencing in exons 5, 8, 12, 14, and 18 of the patients' ATP7B that did not exhibit shifts relative to healthy samples in the SSCP analysis. All nucleotide substitutions found in ATP7B of the patients are real point mutations, because none of them were seen in 120 healthy chromosomes analyzed or in chromosomes with defined disease-causing mutations.
We have detected 11 other base substitutions in the ATP7B gene that are silent mutations or exist in healthy chromosomes and in chromosomes with defined disease-causing mutations as well as in intronic sequence. These variants should be considered polymorphisms (Table 2). We also detected 5 base substitutions, 4 of which were reported previously12,13 as polymorphisms. However, they were detected in all healthy and all WD chromosomes. Therefore, we do not consider them to be polymorphisms.
Three novel polymorphisms, adenylic acid–to–guanylic acid transition at nucleotide 1168 (1168A→G) (isoleucine-to-valine substitution at codon 390 [Ile390Val]), adenylic acid–to–guanylic acid transition at nucleotide 2785 (2785A→G) (isoleucine-to-valine substitution at codon 929 [Ile929Val]), and adenylic acid–to–guanylic acid transition at nucleotide 3316 (3316G→A) (valine-to-isoleucine substitution at codon 1106 [Val1106Ile]), that occur at highly conserved amino acid residues were found to exist in chromosomes with defined disease-causing mutations. They should be considered polymorphisms, although they were not observed in 120 healthy chromosomes. We suppose that these conservative changes may affect the clinical expressivity of disease-causing mutations, and the finding needs further investigation.
Evaluation of the correlation between genotype and phenotype is possible only in homozygotes. As so many different mutations are detected, and as most patients are compound heterozygotes, it is difficult to investigate the potential correlation between genotypes and phenotypes. In this study, 21 symptomatic patients from 17 families have been identified to be homozygous for a single mutation. The homozygotes were detected only for the following mutations: −36C→T, thymine-to–guanylic acid transversion at 3′ nucleotide 5 of intron 4 (1078-5T→G), Arg778Leu, and Arg1041Pro. The common mutation, Arg778Leu, is the only mutation that occurs at sufficient frequency to allow the evaluation in multiple individuals who are homozygous for the mutation. To evaluate the functional significance of Arg778Leu, we searched for correlation between genotypes and several phenotypic manifestations of the illness, including age at onset, neurologic vs hepatic onset of the illness, and the level of ceruloplasmin activity (Table 3 and Table 4). The remaining 3 patients were homozygous for 3 different mutations, and we could not draw meaningful conclusions because of the diverse amino acid changes.
The mutation Arg778Leu was homozygous in 18 patients from 14 families whose ages at onset ranged from 10 to 17 years. As shown in Table 4, their average age at onset was 14.2 years. Their ceruloplasmin levels ranged from 6 to 80 mg/L, with a mean value of 31.2 mg/L. Thirteen patients presented with hepatic symptoms, whereas 3 presented with neurologic symptoms at onset. Five patients died without receiving regular chelation therapy. This mutation was also found to be heterozygous in 11 patients from 9 families with WD. Each of them carried another missense mutation in the other chromosome. Their ages at onset ranged from 15 to 29 years, with the average age at onset of 22.0 years. Ceruloplasmin levels ranged from 40 to 100 mg/L, with a mean value of 54.6 mg/L. All patients except 1 presented with neurologic symptoms at onset.
Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Some mutations appear to be population specific, whereas others are common in many populations. Four mutations—adenylic acid insertion at nucleotide 523 (523insA), Arg778Leu, Arg778Gln, and glutamine-to-threonine substitution at codon 1142 (Gln1142Thr)—have been found in Chinese pedigrees from Taiwan,15,23 whereas the other 3 mutations—1708-5T→G, alanine-to-valine substitution at codon 874 (Ala874Val), and arginine-to-glycine substitution at codon 919 (Arg919Gly)—have been found in Japanese pedigrees.21,22 Those 7 mutations, however, also have been identified in the Chinese patients of our investigation. The results suggest that those mutations are most likely specific for Oriental origin. Two mutations, including guanylic acid–to-cytosine transversion at 3′ nucleotide 1 of intron 4 (1708-G→C), which was found in an Indian patient,10 and aspergine-to-serine substitution at codon 1270 (Asn1270Ser), which was identified in Sicilian,7 continental Italian and Turkish,9 and Costa Rican populations,12 were also detected in this study. Among the mutations published to date, several amino acid residues are the targets of multiple mutations. In particular, the arginine residue at position 778 was reported to be substituted with leucine,10 glycine,9 glutamine,15 or tryptophan,12 which indicates the critical role of arginine at position 778 for the function of transmembrane 4. Similarly, the glycine residue at position 943 was reported to be replaced with serine10 or asparagine.23 Regions of messenger RNA sequence between translation and transcription start sites are known to be crucial for ribosome binding. Therefore, the −36C→T mutation identified in the 5′ untranslated region may alter the expression of the WD gene. This possibility needs further investigation, and the analysis of the effects of sequence changes on the expression of a transfected reporter gene will be a useful way to do so. These new findings expand our knowledge of the spectrum of mutations in ATP7B in patients of Chinese descent and provide new information about critical DNA sequences for gene function.
The frequency of these mutations in the population confirms that the spectrum of ATP7B mutations consists of a small number of relatively frequent mutations and a large number of rare mutations. The most common ATP7B mutation, histidine-to-glutamine substitution at codon 1069 (His1069Gln), appears frequently (10%-40%) in diverse populations, including those of North America, Russia, Great Britain, Holland, Sweden, and continental Italy, and in several Mediterranean samples, but it was not detected in the 84 patients with WD in this study. As shown in Table 1, the Arg778Leu and Thr935Met mutations, which represent 37.7% and 10.0%, respectively, of the mutations in the WD chromosomes we studied, are the most common. The remaining mutations were rare and observed in only a few patients. It seems that the sites of Arg778Leu and Thr935Met mutations are the mutation hot spots in the Chinese population. The results show that the features of mutations of ATP7B are different between Chinese and Western ethnic populations. Therefore, we first should select exons 8 and 12 instead of exons 14 and 18 to detect mutations of ATP7B in Chinese patients. These findings are valuable for developing a fast and an effective genetic diagnosis of WD in Chinese patients. According to the data collected so far, WD seems to result from a limited kind of frequent mutation, common and population specific, and from a large number of rare mutations. Among the 65 unrelated patients (130 chromosomes) we investigated, there was no mutation identified in 35 chromosomes. This lack of detection may be, in part, a consequence of the limitations of SSCP analysis. Some of the undetected mutations may be located in noncoding regions such as introns, promoters, regulatory sequences, and other control regions.
We observed that the average age at onset in Arg778Leu homozygotes was significantly younger than that in compound heterozygotes (P<.001). Similarly, the ceruloplasmin levels of Arg778Leu homozygotes were lower than those of heterozygotes (P<.05). Neurologic vs hepatic onset of the illnesses showed significant difference between Arg778Leu homozygotes and compound heterozygotes (χ2 = 13.60; P<.001). This difference may be due to the combination of Arg778Leu with other mild WD missense mutations not leading to typical WD.
Functional data reported previously24 indicated that the Arg778Leu mutation had severe effects on the function of ATP7B, which confirmed it as a disease-causing mutation. Our data correlate well with these functional data. Our study on the genotypes vs phenotypes shows that Arg778Leu homozygotes are associated with the early onset of WD with hepatic symptoms at presentation. In addition, when the chromosome carries the Arg778Leu mutation in exon 8, there is a conservative change (cytosine-to–guanylic acid transversion at nucleotide 2310 [C2310G]), suggesting that a normal polymorphism is present in this region. The Arg778Leu mutation is a common one in patients of Asian descent,10,11,15 who may be regarded as a group derived from a common ancestor. These findings suggest that the Arg778Leu mutation may be useful in the prediction of disease severity. Other factors, such as dietary copper intake and the individual's capacity for dealing with copper stress, can also be expected to modulate phenotypic response.
Accepted for publication November 17, 2000.
This project was supported by grant 39740017 from the National Natural Science Foundation, Beijing, China; grant 97082 from the Ministry of Public Health, Beijing; and grant 96A032 from the Fujian Provincial Public Health Bureau, Fuzhou, China.
Corresponding author and reprints: Zhi-Ying Wu, MD, PhD, Department of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, People's Republic of China (e-mail: email@example.com).
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The season of fresh produce, lovely flowers, and yummy baked goods returns to Suwanee when the City's Farmers Market opens on Saturday, May 7. The market is in search of farmers, herb and flower growers, butchers, bakers, jams and soap makers, and others to participate in its 12th season.
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