Complex rules for allocating convention delegates mean the winner of Tuesday's Michigan primary, probably Mitt Romney or Rick Santorum, is likely to share the spoils with the runners-up.?
There will be an overall winner of the Michigan GOP primary ? either Rick Santorum or Mitt Romney will take a majority of votes statewide and give a victory speech after that margin is clear. The media will allocate momentum based on this result, saying that Mr. Romney, or Mr. Santorum, has the wind at his back heading into next week?s crucial Super Tuesday votes.
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But here?s Michigan?s secret: That result will almost certainly be overhyped. When it comes to delegates, the state is not winner-take-all. As a result of complicated allocation rules, it is possible for the popular-vote victor in the state?s Republican primary to emerge with fewer delegates than the loser.
Furthermore, it looks now as if both Santorum and Romney will win at least some of the state?s delegates to this summer's national convention in Tampa, Fla. That means that, in a strategic sense, the ?winner? of the Michigan race won?t win much of an edge at all.
?The bottom line is that barring an overwhelming victory for one candidate in Michigan, the delegate margin is very likely to be close coming out of the Great Lakes state on February 28,? writes Davidson College political scientist and voting process expert Jose Putnam on his Frontloading HQ blog.
Why is that? There are two underlying reasons. The first is that the Republican National Committee is penalizing Michigan for holding its primary earlier than the RNC wanted. The state will select 59 delegates to the Tampa convention, which will officially nominate the party?s presidential candidate. But of those 59, only 30 will get to actually vote.
The second reason is that the 30 voting Michigan delegates will be chosen proportionately, for the most part. The winner of each of the state?s 14 congressional districts will receive two delegates. (If Romney or Santorum won all 14, they?d get 28 votes, for example.) Only two delegates will be awarded to the state?s overall popular-vote winner.
And Michigan?s political geography is far from uniform. Santorum should be strong in the Upper Peninsula and thinly populated north of the Michigan mitten, and in the state?s southwest, an area that remains socially conservative due to the Dutch Reformed Church heritage of many of its inhabitants. (There?s a reason that one of the larger towns along the Lake Michigan coast is named Holland.)
Romney should be strong in Detroit itself and in the Detroit suburbs, including relatively prosperous Oakland County and Macomb County. He could do well in the college towns of central southern Michigan, Ann Arbor and East Lansing. Ron Paul could be a factor with university students, however, so that picture is less clear.
On Monday, New York Times polling analyst Nate Silver broke down Michigan?s political geography, concluding that whoever wins the popular vote there will probably win the most congressional districts, too. But that result is far from certain.
?It is possible that a candidate who takes a narrow statewide loss could carry 8 out of 14 districts, or 9 out of 14 if everything breaks exactly right,? writes Mr. Silver.
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LONG BEACH, Calif. (AP) ? The two 11-year-old girls had planned their after-school fight. When the time came, a few shoves and punches were exchanged, and it was over within a minute. But hours later one of them was dead.
The Los Angeles County coroner?s office was investigating how Joanna Ramos could leave the alley near her Long Beach elementary school with a bloody nose and end up dying in an intensive care unit.
The cause of death, and the circumstances behind it left family, friends and authorities confused and seeking answers.
?I personally don?t hear of 11-year-old fights like this especially girls. I can?t say they never happen but I think everyone was completely caught off-guard by this event.? police spokeswoman Nancy Pratt said Sunday.
Pratt urged caution about linking the fight to the girl?s death with certainty until a coroner?s report is released. Police, who have interviewed the other girl involved in the fight, were investigating and said that no arrests are immediately planned.
Joanna returned to an after-school program after the fight, but her mother was called when she wasn?t feeling well.
?My daughter started complaining, saying she doesn?t feel good, let?s go home, so we went to home and I changed her clothes, and she go to sleep, that?s the only thing that I know,? Joanna?s mother, Cecilia Villanueva told KNBC-TV. ?We took her to the hospital but it was too late. She was in a coma.?
Ramos died at a hospital at 9 p.m. Friday, about six hours after the fight near Willard Elementary, police said. Authorities have not released the girl?s name but Villanueva told KNBC the girl who died was her daughter, Joanna.
?I want to know what happened,? she said through tears.
Stephanie Guadalupe, a friend of Joanna, said the girls were fighting over a boy.
?I told the teacher and she said she would talk to all the girls on Monday,? Guadalupe said.
?They took off their backpacks, and they put their hair in a bun, and then that?s when they said ?go? and that?s when they started hitting each other,? Joanna?s friend and classmate Maggie Martinez, who watched the fight, told KNBC.
Martinez and other friends said they tried to stop the fight, but were held back by boys who were watching and wanted it to continue.
?There are times when words do not convey the sense of sadness we feel,? Mayor Bob Foster said at a press conference. ?This is one of those times.?
All good things must come to an end, and that includes the seven-week blog tour exploring the state of black science fiction in 2012. I have to thank the brilliant Alicia McCalla for coordinating the blog carnival and inviting me to participate in such a spectacular online event. It was a pleasure reading the work of my fellow scribes as we grappled with questions of race and injustice in sci-fi and speculative fiction and paid tribute to our literary [super] heroes.
To celebrate our final post, each member was asked to write a short piece using the prompt of a bracelet. My short story is below, and I encourage readers to check out the offerings of other members. I?d like to thank everyone who participated in the weekly discussions ? whether on Twitter, Facebook or on the blog. The winner of a signed copy of Escape from Beckyville and an Escape from Beckyville T-shirt is L.M. Davis.
The Scarlet Bracelet by Nicole D. Sconiers
Of all the things Jemory remembered about the body hanging from the tree, those yellow baby doll shoes haunted her the most. They were patent leather and newly polished, as if the dead woman had been on her way to a dance. From where Jemory stood at the edge of the crowd that day, she couldn?t make out the woman?s features. Her sleek black wig was askew, caressing her broken neck. Jemory wore a similar wig. The only adornment on the woman?s lifeless arm was a thin red bracelet, the size of a hospital wrist band. The mark of an outlaw.
Now as Jemory let herself into her apartment, locking and bolting the front door, she unpinned her wig as she headed to the bathroom. Her scalp itched. She longed to scratch it, to knead the knotty tendrils. Dropping the wig on the sink, she undid the braid that circled her head like a bristly crown. Several strands caught on her scarlet bracelet, and she yanked it free. She removed a small unmarked jar from the breast pocket of her jacket. Unscrewing the cap, she scooped out a dollop of pale yellow paste and massaged it into her hair. She bought the shea butter for $100 from a gap-toothed Nigerian man on Crenshaw who sold it on the black market. It was pure, unlike the chemically enhanced stuff the salons and beauty supply stores used to sell before they were shut down. She watched as he kneeled by a wooden table in his kitchen, spoke a few words in Arabic and pounded the nuts with a mortar and pestle. The constant thwok-thwok-thwok sound of shells being crushed was somehow comforting. Finally, he rose to roast the kernels in a large metal pot. It was such an intensive process for so small a bounty.
But it makes my hair feel alive, Jemory thought as she rinsed her greasy hands in the sink. She refused to weigh down her coils with the white B-9 Kreme that black women were required by law to use to permanently straighten their hair. She heard that the smelly stuff caused uterine tumors, that constant application caused the wearer to go mad. Indeed, she saw many blank-faced women stumbling through the streets of Los Angeles, their eyes as deadened as their long flowing locks.
I?ll have to take my chances. Jemory?s real hair was growing longer now ? stronger ? and soon it would be impossible to hide beneath her wig. Maybe that?s what gave away the stranger with the baby doll shoes. A woman who loved her unprocessed hair enough to risk public execution was dangerous indeed. Jemory knew of several black women who hid their fugitive locks beneath hair pieces and extensions to fool the Tuft Force or T4 as they were called. The enforcers were known to pick random women off the street, especially those wearing red bracelets, and yank their hair to see if they had submitted to the caustic silkiness of B-9 Kreme or if they dared defy the decree. Woe to the ones with woolly strands.
Jemory fingered her bracelet. It was locked and would emit radio waves if the wearer attempted to break it, alerting T4. The red wristbands were etched with serial numbers indicating women who once wore afros and kinky twisted styles and dreadlocks in public before the purges. She was serial number JF-28094579. An inmate who would never know the smell of true freedom, as smoky as raw shea butter, as yellow as baby doll shoes swaying in the wind.
Catch up on the discussion:
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Check out other participating members of this seven-week blog carnival:
Winston Blakely, Artist/Writer ? is a Fine Arts/Comic Book artist, having a career spanning 20 years, whose achievements have included working for Valiant Comics and Rich Buckler?s Visage Studios. He is also the creator of Little Miss Strange, the world?s first black alien sorceress and the all-genre anthology entitled Immortal Fantasy. Both graphic albums are available at Amazon, Barnes and Nobles and other online book store outlets. Visit him at : http://blakelyworks.blogspot.com or http://blakelyworkstudio.weebly.com.
L. M. Davis, Author ? began her love affair with fantasy in the second grade. Her first novel, Interlopers: A Shifters Novel, was released in 2010, and the follow-up Posers: A Shifters Novel will be released this spring. For more information visit her blog http://shiftersseries.wordpress.com or her website www.shiftersnovelseries.com.
Milton Davis, Author ? Milton Davis is owner/publisher of MVmedia, LLC . As an author he specializes in science fiction and fantasy and is the author of Meji Book One, Meji Book Two and Changa?s Safari. Visit him at: www.mvmediaatl.com/Wagadu and www.wagadu.ning.com.
Ja Ja (DjaDja) N Medjay , Author ? DjaDja Medjay is the author of The Renpet Sci-Fi Series. Shiatsu Practitioner. Holistic AfroFuturistic Rising in Excellence. Transmissions from The Future Earth can be found at: www.renpetscifi.com, on Facebook www.facebook.com/RenpetSciFiNovel or on Twitter https://twitter.com/#!/Khonsugo.
Margaret Fieland, Author ? lives and writes in the suburbs west of Boston, MA with her partner and five dogs. She is one of the Poetic Muselings. Their poetry anthology, Lifelines http://tinyurl.com/LifelinesPoetry is available from Amazon.com Her book, Relocated, will be available from MuseItUp Publishing in July, 2012. The Angry Little Boy will be published by 4RV publishing in early 2013. You may visit her website, http://www.margaretfieland.com.
Valjeanne Jeffers, Author ? is an editor and the author of the SF/fantasy novels: Immortal, Immortal II: The Time of Legend and Immortal III: Stealer of Souls. Her fourth and fifth novels: Immortal IV: Collision of Worlds and The Switch: Clockwork will be released this spring. Visit her at: http://valjeanne.wordpress.com and http://qandvaffordableediting.blogspot.com.
Thaddeus Howze, Author? is a veteran of the Information Technology and Communications industry with over twenty-six years of experience. His expertise is in re-engineering IT environments using process-oriented management techniques. In English, that means he studies the needs of his clients and configures their offices to optimize the use of information technology in their environment. Visit him at: http://ebonstorm.wordpress.com or http://ebonstorm.weebly.com.
Alicia McCalla, Author ? writes for both young adults and adults with her brand of multicultural science fiction, urban fantasy and futurism. Her debut novel, Breaking Free will be available February 1, 2012. The Breaking Free theme song created by Asante McCalla is available for immediate download on iTunes and Amazon. Visit her at: http://www.aliciamccalla.com.
Carole McDonnell, Author ? writes Christian, speculative fiction, and multicultural stories. Her first novel is Wind Follower. Her short fiction has appeared in many anthologies and have been collected in an ebook, Spirit Fruit: Collected Speculative Fiction. Visit Carole: http://carolemcdonnell.blogspot.com or http://writersofcolorblogtour.blogspot.com.
Balogun Ojetade, Author? of the bestselling Afrikan Martial Arts: Discovering the Warrior Within (non-fiction), Moses: The Chronicles of Harriet Tubman (Steampunk) and the feature film, A Single Link. Visit him at: http://chroniclesofharriet.wordpress.com.
Rasheedah Phillips, Author ?is the creator of The AfroFuturist Affair in Philly. She plans to debut her first spec/sci-fic novel Recurrence Plot in Spring 2012. You may catch her ruminating from time to time on her blog, AstroMythoLosophy.com.
Nicole Sconiers, Author ? is an author and screenwriter living in the sunny jungle of L.A. She holds an MFA in creative writing from Antioch University Los Angeles, and she recently published Escape from Beckyville: Tales of Race, Hair and Rage. Visit her at: http://nicolesconiers.comand http://www.nicolesconiers.com/blog.
Jarvis Sheffield, M.Ed. ? is owner and operator of TheDigitalBrothers.com, BlackScienceFictionSociety.com and BlackCommunityEntertainment.com. Visit him at: http://www.blacksciencefictionsociety.com/profiles/blog/list?user=2stjwb1h216fd.
[unable to retrieve full-text content]AP - The FBI says its probes of corporate criminals led to 241 convictions and $2.4 billion in restitution for financial victims last year as agents went after insider trading and other investment crime that defrauded thousands.
Ceramic tiles are becoming more popular as a flooring option for the home because of their stylish appearance, not to mention their easy to maintain qualities. They also come in different styles, colors, and designs, which means variety is something that you can expect with this type of flooring. Large tiles (measuring 12? x 12? and 16? x 16?) for example, are very trendy, and look good in just about any type of room. Some interior designers suggest adding smaller tiles into patterns to create a unique design or simply add texture to a room. Ceramic tiles?to put it simply?are versatile, able to blend well with the overall aesthetic of the house, whether it is contemporary, rustic, Spanish, and so on.
Cleaning is a breeze.
One thing is for sure: with ceramic tiles, you can rest assured that cleaning will be easy peasy.
Just use any generic cleanser, wipe off the tiles, and voila, you are done. It does not matter if you use a mop, a rag, or a sponge to clean ceramic floors. The whole cleansing process will take you minutes, an hour or two if you have a huge home with lots of rooms. Even water can wipe the tiles clean. You are lucky if you have tiles that are a blend of colors and textures as these hide the stains or debris quite well. Of course, this does not mean that you should forgo cleaning altogether but if you do not have time, at least you do not need to worry that your guests will notice.
D is for durable.
As long as you buy high quality ceramic tiles, you do not have to worry about them breaking or not lasting for many years to come.
The manufacturing process has improved over the years so that ceramic tile flooring are now very durable, waterproof even, which means that there will be no bubbles underneath unlike with laminate or hardwood flooring. For walkways and entry ways (read: high traffic areas), ceramic tiles are ideal, as well as for bathrooms, kitchens, and laundry rooms. Best of all, these tiles are easy to install and affordable to boot. It is not surprising at all that many homeowners prefer this type of flooring material over other the options.
Enjoying your ceramic tiles
If you are wondering how you can change the look of your home, and you want something that is going to last and be easy to clean, ceramic tile flooring is something you should consider. There are so many different styles, sizes, and colors of tile to choose from that you can create any look that you want, and not worry that your floor will be damaged any time soon. Bottom line: this is a great investment for any home or property, just super low maintenance and a breeze to install.
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Everyone has a unique and interesting story to tell. Often, those stories are a rich source of inspiration, hope and/or information for others.
Putting pen to paper (or staring at a blank word processing page) for some can be overwhelming and for others may even seem like an insurmountable challenge. Some adventurous folks may eventually overcome their anxiety about writing, but because they consider themselves poor writers they don?t take their book projects any further. If any of these scenarios sound like you, please know there are likely thousands of people that can benefit from your experience, and your story doesn?t have to remain in your head or be shared only with those closest to you. And, also know, there?s a ghostwriter out there that can advance your project.
A great way to start with your inspirational or informational story is to blog. Recently, I had a client approach me about the possibility of ghostwriting her book. She wants to share her experience and journey with her infant son?s health issues. Over the course of one year, she systematically journaled, researched, and tested a variety of solutions, including her own diet. This client is not a writer, not a child health expert, nor a dietitian. She has experiential expertise, months of research, and trial and error under her belt, which can most assuredly help other mothers facing the same or similar situations.
Shortly, I will be helping my client set up a blog so she can start sharing her story. Along the way, I?ll be guiding her in how to craft her blog posts, reviewing her content to ensure clarity of her message, and helping her build her following. Before long, her book will be well underway.
Thanks to Carole for sharing these ?kick-start? tips ?for all inspiring authors! Sabrina Espinal Sabrina&Company?
Carole Audet is a ?Certified Ghostwriter and Certified Professional Author?s Assistant at In Touch Online. ?A journalism graduate, Carole loves speaking with people to write about their unique stories. She also enjoys helping busy professionals get their expertise out of their heads and into published books.
Look, sometimes you just have to take a break and skim Etsy for cool iPad stuff. Are you thinking of picking up a new iPad 3 when they come out, or maybe just celebrating the release with a cool new case for your existing tablet? Check out this little round-up of cases collected by a felt-loving blogger on a Friday afternoon. Do you like felt, and leather, and buckles, and supporting the artisan iPad accessory community? Enter.
Not all major home improvement projects are worth the time or expense, but changing out your windows is worth it. There?s no better way to save on utility bills than to install new, energy-efficient windows. There are many windows to choose from, so finding those that match the house will make things look great.
Replacing your windows is a big job, and so it might be to your advantage to learn whatever you can about it.
If you want to get the best possible type of insulation from your windows, you should go with triple pane windows, though these of course will also be more expensive. How much you want to invest in energy-efficient windows will also depend to some degree on where you live. You do not need the added cost for the most efficient windows if you live where the climate is mild, so the looks can then be your main focus. If you?re going to have a contractor or window replacement company do the job for you, it?s a good idea to get several estimates before making your choice.
Sometimes you can receive tax credits for using specific energy efficient windows. In order to receive this offer, you need to research your local tax laws and find out which windows are allowed; plus you will be saving with the energy efficiency of the product. In the U.S., hunt for windows that are backed by the Energy Star program. Check into other tax credits while you are at it, like changing out the old doors for more efficient ones or adding insulation. This may relieve a little pressure off your monthly household expenses and you taxes as well.
When shopping for windows you will of course take your funds into account, you should think of the long term investment too. Along with adding to the assessment of your home, by purchasing the best windows you will also save a bundle on your monthly electric bill. Buying cut rate quality items in order to save on your budget might not have been a good choice later on. If you can find a bargain on good quality, energy efficient windows, that?s one thing, but you don?t want to compromise on features that are important. Due to the disorder and chaos created when you replace windows; consider choosing the product that will hold up the best. Replacing windows is going to take you quite a bit of time so make sure your plans cover every aspect. It?s best to do as much research as possible so you know what kind of windows and frames are best for your home, how much it will cost and how long it will take. The only way you?re going to be able to complete this project on schedule is to do this research and stick to the plan itself.
Bill Simonton is an editor and publicist of a private organization that conducts reviews on home improvement products and tips. Find further information about window replacement for window replacement Houston
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Just as the official ASUS Twitter account foretold, today is the day WiFi Eee Pad Transformers meet Android 4.0 in the US (3G devices and other international users are still on the waiting list). Our tipsters and posters on XDA-Developers have reported receiving the rollout OTA, and for those interested -- it apparently does not affect the status of rooted devices. Start mashing that check update button and let us know how Ice Cream Sandwich feels on your dockable slates.
Update: Outside the land of the free and the home of the Daytona 500? You may still be in luck, we're hearing it's out in Canada, ASUS' UK Twitter account confirmed today's the day across the pond, plus ASUS gave the good news to the land down under via Facebook.
In this photo provided by Greenpeace, actress Lucy Lawless joins activists in stopping a Shell-contracted drillship from departing the port of Taranaki, New Zealand, Friday, Feb. 24, 2012. Lawless, a native New Zealander, best known for her title role in "Xena: Warrior Princess," climbed the oil-drilling ship bound for the Arctic to try and stop it from leaving. (AP Photo/Greenpeace) EDITORIAL USE ONLY
In this photo provided by Greenpeace, actress Lucy Lawless joins activists in stopping a Shell-contracted drillship from departing the port of Taranaki, New Zealand, Friday, Feb. 24, 2012. Lawless, a native New Zealander, best known for her title role in "Xena: Warrior Princess," climbed the oil-drilling ship bound for the Arctic to try and stop it from leaving. (AP Photo/Greenpeace) EDITORIAL USE ONLY
In this photo provided by Greenpeace, actress Lucy Lawless, left, joins activists in stopping a Shell-contracted drillship from departing the port of Taranaki, New Zealand, Friday, Feb. 24, 2012. Lawless, a native New Zealander, best known for her title role in "Xena: Warrior Princess," climbed the oil-drilling ship bound for the Arctic to try and stop it from leaving. (AP Photo/Greenpeace, Nigel Marple) EDITORIAL USE ONLY
WELLINGTON, New Zealand (AP) ? Television actress Lucy Lawless climbed aboard an oil-drilling ship Friday in New Zealand, joining six Greenpeace activists to try to stop the vessel from setting off for the Arctic.
Speaking from atop a 174-foot (53-meter) drilling tower aboard the Noble Discoverer in Port Taranaki, Lawless told The Associated Press on Friday that wind gusts were making it difficult to stay put but that she and the other protesters planned to stay there for "as long as we possibly can." She said she had a "little bit" of food and some provisions with her.
The protesters hung banners from the drilling derrick reading "Stop Shell" and "(hashtag)SaveTheArctic."
The ship is chartered by oil company Shell. Shona Geary, the company's New Zealand spokeswoman, said the ship was due to leave over the weekend for a drilling program in the Arctic but that all operations aboard had come to a stop.
"We are taking a very calm and measured approach to this," she said.
Police spokesman Grant Ogilvie said early Friday afternoon that five police officers boarded the ship. They had made contact with the protesters and were trying to determine their intentions. The port remained open but access was restricted, Ogilvie said.
"The protesters are clearly breaking the law by trespassing on the ship," said Police Inspector Blair Telford in a statement.
Lawless, 43, a native New Zealander, is best known for her title role in "Xena: Warrior Princess." More recently she has starred in "Spartacus: Blood and Sand."
Lawless said she was taking direct protest action for the first time in her life to protest oil drilling and to draw attention to climate change.
"I've got three kids. My sole biological reason for being on this planet is to ensure that they can flourish, and they can't do that in a filthy, degraded environment," she said. "We need to stand up while we still can."
Greenpeace spokesman Nathan Argent said the ship was due to drill five exploratory wells during the Arctic summer. He said Greenpeace is concerned about the rush of companies trying to drill in the Arctic and the potential for catastrophic spills in the ecologically sensitive region.
"The oil companies are pushing the frontiers in the Arctic," he said. "There's a relentless push to get the last drops of oil."
In a statement, Shell said the actions of Greenpeace were jeopardizing everybody's safety.
"Shell has taken unprecedented steps to pursue safe, environmentally responsible exploration in shallow water off the coast of Alaska," the company said.
New class of compounds stops disease-fueling inflammation in lab testsPublic release date: 23-Feb-2012 [ | E-mail | Share ]
Contact: Nick Miller nicholas.miller@cchmc.org 513-803-6035 Cincinnati Children's Hospital Medical Center
CINCINNATI Scientists have developed a unique compound that in laboratory tests blocks inflammation-causing molecules in blood cells known to fuel ailments like cancer and cardiovascular disease without causing harmful toxicity.
Past attempts to identify new compounds that tamp down so-called reactive oxygen species (ROS) molecules in cells have been complicated by toxicity issues and a lack of specificity in targeting molecular processes. Researchers from Cincinnati Children's Hospital Medical Center report in the Feb. 24 Chemistry and Biology (a Cell Press publication) they have overcome this problem.
They did so by using computer-assisted drug design verified by laboratory tests on human and mouse inflammatory cells to precisely target a single component of an enzyme network called NOX2. The enzyme network drives ROS production in immune system white blood cells known as neutrophils. The eventual goal, researchers say, is establishing new small-molecule inhibiting drugs that can stop excessive inflammation and treat a number of inflammation-mediated diseases that need improved therapies.
"Drugs that potently and specifically target ROS production by NOX2 enzyme are an unmet clinical need that will have far-reaching implications for treatment of disease," said Yi Zheng, PhD, a lead investigator on the study and director of Experimental Hematology/Cancer Biology at Cincinnati Children's. "The lead candidate we developed, Phox-I, shows promising inflammation inhibiting activity in cells and mouse models."
The production of ROS in cells is a normal part of the body's immune system, as oxidative enzymes are generated by white blood cells to attack illness-causing microorganisms. In a number of pathologic conditions, however, various environmental stressors (like acute ischemia, chronic infections, etc.) can help trigger an overabundance of biochemical signaling. The signaling occurs through a regulatory pathway involving Rac GTPases, a family of intracellular signal transducers that amplify ROS production by the NOX2 enzyme network.
Normally, Rac GTPases maintain cell growth and survival programs in the body, including the NOX enzyme network and its activation of ROS production in cells. When signaling miscues occur they cause an unusually high burst of ROS production and release harmful superoxide chemicals. This up-regulation creates excessive inflammation that damages tissues and drives the onset of diseases like Chronic Obstructive Pulmonary Disease, ischemia-induced lung and brain damage and hypertension, among others.
Previous attempts to create compounds that target and stop harmful ROS production, including an earlier compound developed by Dr. Zheng's laboratory, have been able to reduce inflammation in cells. Unfortunately, the compounds were not specific or efficient enough in targeting the Rac GTPase regulatory pathway. This meant the compounds inhibited several different cellular processes including some that are necessary and beneficial leading to toxicity.
Zheng and his colleagues achieved greater specificity and efficiency through their design of small molecular inhibitors they named Phox-I1 and Phox-I2. The inhibitors precisely target and block the binding of a signal sensor for the NOX2 enzyme called p67-phox to Rac GTPase. P67-phox has to bind with Rac GTPase to activate the oxidase enzyme complex of NOX2 (known as NADPH) that produces superoxide and causes inflammation.
In laboratory tests involving normal human blood cells, leukemic cells and mouse blood cells, Phox-l1blocked p67-phox binding with Rac. It did so in a dose-dependent manner with enough precision to shut down ROS production without causing unwanted toxicity in the cells, the researchers report. In unpublished test results on mouse models of lung inflammation, Zheng said the investigators found that the Phox-I lead compounds are effective in blocking neutrophil mediated inflammation and damage.
The results are part of a patient application filed by Cincinnati Children's with the United States Patent Office for Phox-I inhibitors. The medical center's Center for Technology Commercialization is exploring opportunities to rapidly advance continuing research and development of the compounds that could possibly accelerate their transition to future clinical testing.
Zheng said that although the study data describe an innovative approach that shows promise, a significant amount of additional research is needed before the Phox-I can be tested in humans. The research team continues to experiment with structural alterations to Phox-I to make the compounds more potent in inhibiting excessive ROS and superoxide production without being toxic to normal cells. Researchers are also expanding their tests in mouse models to see how effective the compounds are in safely shutting down the onset of simulated human diseases caused by inflammation.
###
The research was funded by an innovation grant from CincyTech USA, and a National Institutes of Health Small Business Technology Transfer Grant.
About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center is one of just eight children's hospitals named to the Honor Roll in U.S. News and World Report's 2010-11 Best Children's Hospitals. It is ranked #1 for digestive disorders and highly ranked for its expertise in pulmonology, cancer, neonatology, heart and heart surgery, neurology and neurosurgery, diabetes and endocrinology, orthopedics, kidney disorders and urology. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for quality and transformation work by Leapfrog, The Joint Commission, the Institute for Healthcare Improvement, the federal Agency for Healthcare Research and Quality, and by hospitals and health organizations it works with globally. Additional information can be found at www.cincinnatichildrens.org.
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New class of compounds stops disease-fueling inflammation in lab testsPublic release date: 23-Feb-2012 [ | E-mail | Share ]
Contact: Nick Miller nicholas.miller@cchmc.org 513-803-6035 Cincinnati Children's Hospital Medical Center
CINCINNATI Scientists have developed a unique compound that in laboratory tests blocks inflammation-causing molecules in blood cells known to fuel ailments like cancer and cardiovascular disease without causing harmful toxicity.
Past attempts to identify new compounds that tamp down so-called reactive oxygen species (ROS) molecules in cells have been complicated by toxicity issues and a lack of specificity in targeting molecular processes. Researchers from Cincinnati Children's Hospital Medical Center report in the Feb. 24 Chemistry and Biology (a Cell Press publication) they have overcome this problem.
They did so by using computer-assisted drug design verified by laboratory tests on human and mouse inflammatory cells to precisely target a single component of an enzyme network called NOX2. The enzyme network drives ROS production in immune system white blood cells known as neutrophils. The eventual goal, researchers say, is establishing new small-molecule inhibiting drugs that can stop excessive inflammation and treat a number of inflammation-mediated diseases that need improved therapies.
"Drugs that potently and specifically target ROS production by NOX2 enzyme are an unmet clinical need that will have far-reaching implications for treatment of disease," said Yi Zheng, PhD, a lead investigator on the study and director of Experimental Hematology/Cancer Biology at Cincinnati Children's. "The lead candidate we developed, Phox-I, shows promising inflammation inhibiting activity in cells and mouse models."
The production of ROS in cells is a normal part of the body's immune system, as oxidative enzymes are generated by white blood cells to attack illness-causing microorganisms. In a number of pathologic conditions, however, various environmental stressors (like acute ischemia, chronic infections, etc.) can help trigger an overabundance of biochemical signaling. The signaling occurs through a regulatory pathway involving Rac GTPases, a family of intracellular signal transducers that amplify ROS production by the NOX2 enzyme network.
Normally, Rac GTPases maintain cell growth and survival programs in the body, including the NOX enzyme network and its activation of ROS production in cells. When signaling miscues occur they cause an unusually high burst of ROS production and release harmful superoxide chemicals. This up-regulation creates excessive inflammation that damages tissues and drives the onset of diseases like Chronic Obstructive Pulmonary Disease, ischemia-induced lung and brain damage and hypertension, among others.
Previous attempts to create compounds that target and stop harmful ROS production, including an earlier compound developed by Dr. Zheng's laboratory, have been able to reduce inflammation in cells. Unfortunately, the compounds were not specific or efficient enough in targeting the Rac GTPase regulatory pathway. This meant the compounds inhibited several different cellular processes including some that are necessary and beneficial leading to toxicity.
Zheng and his colleagues achieved greater specificity and efficiency through their design of small molecular inhibitors they named Phox-I1 and Phox-I2. The inhibitors precisely target and block the binding of a signal sensor for the NOX2 enzyme called p67-phox to Rac GTPase. P67-phox has to bind with Rac GTPase to activate the oxidase enzyme complex of NOX2 (known as NADPH) that produces superoxide and causes inflammation.
In laboratory tests involving normal human blood cells, leukemic cells and mouse blood cells, Phox-l1blocked p67-phox binding with Rac. It did so in a dose-dependent manner with enough precision to shut down ROS production without causing unwanted toxicity in the cells, the researchers report. In unpublished test results on mouse models of lung inflammation, Zheng said the investigators found that the Phox-I lead compounds are effective in blocking neutrophil mediated inflammation and damage.
The results are part of a patient application filed by Cincinnati Children's with the United States Patent Office for Phox-I inhibitors. The medical center's Center for Technology Commercialization is exploring opportunities to rapidly advance continuing research and development of the compounds that could possibly accelerate their transition to future clinical testing.
Zheng said that although the study data describe an innovative approach that shows promise, a significant amount of additional research is needed before the Phox-I can be tested in humans. The research team continues to experiment with structural alterations to Phox-I to make the compounds more potent in inhibiting excessive ROS and superoxide production without being toxic to normal cells. Researchers are also expanding their tests in mouse models to see how effective the compounds are in safely shutting down the onset of simulated human diseases caused by inflammation.
###
The research was funded by an innovation grant from CincyTech USA, and a National Institutes of Health Small Business Technology Transfer Grant.
About Cincinnati Children's:
Cincinnati Children's Hospital Medical Center is one of just eight children's hospitals named to the Honor Roll in U.S. News and World Report's 2010-11 Best Children's Hospitals. It is ranked #1 for digestive disorders and highly ranked for its expertise in pulmonology, cancer, neonatology, heart and heart surgery, neurology and neurosurgery, diabetes and endocrinology, orthopedics, kidney disorders and urology. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health. It is internationally recognized for quality and transformation work by Leapfrog, The Joint Commission, the Institute for Healthcare Improvement, the federal Agency for Healthcare Research and Quality, and by hospitals and health organizations it works with globally. Additional information can be found at www.cincinnatichildrens.org.
[ | E-mail | Share ]
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
ScienceDaily (Feb. 23, 2012) ? As scientists continue developing climate change projection models, paleontologists studying an extreme short-term global warming event have discovered direct evidence about how mammals respond to rising temperatures.
In a study appearing in Science Feb. 24, researchers from eight institutions led by scientists from the University of Florida and University of Nebraska found a correlation between temperature and body size in mammals by following the evolution of the earliest horses about 56 million years ago: As temperatures increased, their body size decreased.
"Horses started out small, about the size of a small dog like a miniature schnauzer," said co-author Jonathan Bloch, associate curator of vertebrate paleontology at the Florida Museum of Natural History on the UF campus. "What's surprising is that after they first appeared, they then became even smaller and then dramatically increased in size, and that exactly corresponds to the global warming event, followed by cooling. It had been known that mammals were small during that time and that it was warm, but we hadn't understood that temperature specifically was driving the evolution of body size."
Sifrhippus, the earliest-known horse, first appeared in the North American fossil record during the Paleocene-Eocene Thermal Maximum. During this 175,000-year climate event, increased concentrations of carbon dioxide in the atmosphere and oceans caused average global temperatures to rise 10 to 20 degrees. By analyzing the size and isotopes of fossils collected in Wyoming's Bighorn Basin, researchers traced the evolution of Sifrhippus from an estimated 12-pound animal that shrank during a 130,000-year period about 30 percent to 8.5 pounds -- the size of a small house cat -- then increased to about 15 pounds during the next 45,000 years.
"This is the highest-resolution terrestrial record of its kind from anywhere in the world and it shows how climate changed in Wyoming at that time," said lead author Ross Secord, who began geochemical analysis of the horse teeth and other mammals as a postdoctoral researcher with Bloch before joining the University of Nebraska-Lincoln in 2008. "When Jon and I started plotting oxygen data from the mass spectrometer, we could immediately see that the shifts in size of horses and temperature were mirror images of each other."
Bloch said the project began about seven years ago when former UF student and study co-author Stephen Chester, now an anthropology doctoral candidate at Yale University, measured horse teeth that seemed to be too large for their age and became smaller through the geologic section. The findings raise important questions about how animals might respond to future rapid climate change.
"We're seeing about a third of the mammals getting smaller and some of them getting a lot smaller, by as much as half of their original body size," Secord said. "Because warming happened much slower during the Paleocene-Eocene Thermal Maximum, mammals had more time to adjust their body size. So, it's not clear that we're going to see the same thing happening in the near future, but we might."
Philip Gingerich, who first recorded the phenomenon of decreasing body size during the Paleocene-Eocene Thermal Maximum in 1989, said the study documentation clearly demonstrates the relationship between temperature and body size. He agrees this may occur as a result of current warming patterns.
"I joke about this all the time -- we're going to be walking around 3 feet tall if we keep going the way we're going," said Gingerich, a researcher at the University of Michigan and director of its Museum of Paleontology. "Maybe that's not all bad and if that's the worst it gets, it will be fine. You can either adapt, or you go extinct, or you can move, and there's not a lot of place to move anymore, so I think it's a matter of adaptation and becoming smaller."
Researchers also analyzed correlations with aridity and carbon dioxide levels but found temperature to be the most likely driving factor in body size. Although little is known about how animals arrived in North America at that time, the Paleocene-Eocene Thermal Maximum is a significant event in geologic time in terms of mammalian history, Bloch said.
"The PETM is really important because it marks the beginning for the first appearance of several major groups of mammals, including crown-group primates (ancestors of modern primates) and the first even- and odd-toed modern ungulates (mammals with hooves)," Bloch said. "This sets the scene for the entire diversity of animals we see on the planet today."
Study co-authors include Doug Boyer of Brooklyn College, Aaron Wood of South Dakota School of Mines and Technology and the Florida Museum, Scott Wing of the Smithsonian Institution National Museum of Natural History, Mary Kraus of the University of Colorado, Francesca McInerney of Northwestern University and John Krigbaum of UF.
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The above story is reprinted from materials provided by University of Florida, via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
R. Secord, J. I. Bloch, S. G. B. Chester, D. M. Boyer, A. R. Wood, S. L. Wing, M. J. Kraus, F. A. McInerney, J. Krigbaum. Evolution of the Earliest Horses Driven by Climate Change in the Paleocene-Eocene Thermal Maximum. Science, 2012; 335 (6071): 959 DOI: 10.1126/science.1213859
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
New York Knicks guard Jeremy Lin (17) goes up for a layup next to Atlanta Hawks center Zaza Pachulia (27) in the first quarter of an NBA basketball game at Madison Square Garden in New York, Wednesday, Feb. 22, 2012. Hawks forward Josh Smith is at right. (AP Photo/Kathy Willens)
New York Knicks guard Jeremy Lin (17) goes up for a layup next to Atlanta Hawks center Zaza Pachulia (27) in the first quarter of an NBA basketball game at Madison Square Garden in New York, Wednesday, Feb. 22, 2012. Hawks forward Josh Smith is at right. (AP Photo/Kathy Willens)
New York Knicks guard J.R. Smith (8) knocks down a rebound from Atlanta Hawks forward Josh Smith (5) in the second quarter of an NBA basketball game at Madison Square Garden in New York, Wednesday, Feb. 22, 2012. (AP Photo/Kathy Willens)
Atlanta Hawks forward Josh Smith (5) steals the ball from New York Knicks center Tyson Chandler (6) as Hawks center Zaza Pachulia (27) watches during the first half of an NBA basketball game at Madison Square Garden in New York, Wednesday, Feb. 22, 2012. (AP Photo/Kathy Willens)
New York Knicks forward Amare Stoudemire (1) shoots over Atlanta Hawks forward Marvin Williams (24) as Hawks forward Josh Smith (5) watches in the first half of an NBA basketball game at Madison Square Garden in New York, Wednesday, Feb. 22, 2012. (AP Photo/Kathy Willens)
NEW YORK (AP) ? Not much heat from the Hawks for Jeremy Lin and the New York Knicks.
That's likely to change Thursday night when the show travels to Miami for Lin versus LeBron and some real Heat.
Lin had 17 points and nine assists, sitting out most of the fourth quarter in a rare easy game during his remarkable run, and the Knicks tuned up for their trip by beating Atlanta 99-82 on Wednesday.
Carmelo Anthony scored 15 points in his second game back from injury for the Knicks, who led the depleted Hawks by 25 points at halftime. New York bounced back from a loss to New Jersey on Monday and won for the ninth time in 11 games since Lin joined the rotation.
The Knicks visit Miami on Thursday in their final game before the All-Star break, and Lin's emergence has the Heat's attention.
"It's going to be a lot of, a lot of anticipation about this game," Anthony said. "We're going down there to win. Miami is playing great basketball right now. One of the hottest teams, if not the hottest team in the NBA.
"It'll be a great game."
LeBron James, Dwyane Wade and teammates have been asked repeatedly in recent days about the ex-Harvard guard, and coach Mike D'Antoni was told the word out of Miami is the Heat will be waiting for the Knicks' back-to-back Sports Illustrated cover boy.
"At the airport?" he joked.
Not quite. But whatever they do will provide more resistance than the Hawks, who trailed by as many as 30.
Jeff Teague scored 18 points for the Hawks. They played without All-Star guard Joe Johnson, who left their loss at Chicago on Monday with a sore left knee and had to pull out of Sunday's game in Orlando, and have lost three straight and five of six.
"Coming into this game, being as depleted as we were, I still was hoping we could come out and just put together four solid quarters. We just didn't do that," Hawks coach Larry Drew said.
The Knicks shot 52 percent in the first half, scored 30 points in both periods, and led 60-35 at the break.
"We are professionals. They just came out and they attacked us," Teague said. "That's all I can really say."
The Knicks lost their focus briefly midway through the third before pulling away again to lead 78-56 heading into the fourth. Lin watched the first 6-plus minutes of the final period before D'Antoni curiously put him back in leading by 20 with 5:13 left. Lin still played only 33 minutes after he logged at least 36 in all but one of the previous 10 games.
He'll likely need to do more against the Heat, who have won seven in a row and have the NBA's best record at 26-7.
The Heat have been the NBA's biggest story since building their Big Three in 2010, but even they've been playing in Lin's shadow the last two weeks. That will change Thursday in a nationally televised game that James said could be "one of the most watched games we've had in a long time, especially with what Jeremy Lin is doing."
But Lin isn't getting caught up in the hype.
"I think for us, we want to make sure what we're thinking about is we want to build momentum going into the All-Star break and we want to make a push after the All-Star break. And I think this is a good opportunity to build momentum," he said.
"It's a big game, don't get me wrong. We're playing a great team, and it's going to be a good evaluation of where we're at. So from that end obviously we're excited and ready for the challenge. But besides that, we're just going try to stay consistent."
The game against Atlanta came on the one-year anniversary of the Knicks' acquisition of Anthony from Denver in a blockbuster trade that cost them four of their top six players. The results have been underwhelming ? 14-14 last season and 17-17 this season, and D'Antoni acknowledged the high price the Knicks paid for the All-Star forward "depleted a lot of things."
However, he said they've built their depth back, and the potential was obvious in the first half, when all nine players who played scored.
New additions Baron Davis and J.R. Smith could be an explosive second-team backcourt, and teamed up on a pretty alley-oop that Smith dropped in with his back to the hoop. Steve Novak is the 3-point specialist needed to space the floor so Lin and Anthony have room to drive into the lane.
"The things are developing and we'll get our guys, everybody up to par, and if that happens then we should be fairly good," D'Antoni said.
Novak made five 3-pointers and scored 17 points. Landry Fields had 16, and Smith finished with 12. Davis had six assists in 14 minutes.
Notes: Drew was disappointed that Josh Smith was passed over in favor of Boston's Rajon Rondo when Commissioner David Stern chose the injury replacement for Johnson. Smith averages 16 points and 9.6 rebounds, is top 15 in the league in blocks, rebounds and steals, and was already considered perhaps the biggest snub when reserves were chosen. "I really thought that he would get the invite once word was that Joe wouldn't be able to play," Drew said. "I mean, you look at Josh's numbers, he has good numbers. His numbers are good enough to be where he should be an All-Star. Why he didn't make it, I don't know." ... Knicks assistant Mike Woodson was the Hawks' head coach from 2004-10. ... Lansdowne Road, an Irish pub in the Hell's Kitchen section of New York, announced it was changing its name to LINsdowne Road
All good things must come to an end, and that includes the seven-week blog tour exploring the state of black science fiction in 2012. I have to thank the brilliant Alicia McCalla for coordinating the blog carnival and inviting me to participate in such a spectacular online event. It was a pleasure reading the work of my fellow scribes as we grappled with questions of race and injustice in sci-fi and speculative fiction and paid tribute to our literary [super] heroes.
Of all the things Jemory remembered about the body hanging from the tree, those yellow baby doll shoes haunted her the most. They were patent leather and newly polished, as if the dead woman had been on her way to a dance. From where Jemory stood at the edge of the crowd that day, she couldn?t make out the woman?s features. Her sleek black wig was askew, caressing her broken neck. Jemory wore a similar wig. The only adornment on the woman?s lifeless arm was a thin red bracelet, the size of a hospital wrist band. The mark of an outlaw.
Everyone has a unique and interesting story to tell. Often, those stories are a rich source of inspiration, hope and/or information for others.
Carole Audet is a ?Certified Ghostwriter and Certified Professional Author?s Assistant at In Touch Online. ?A journalism graduate, Carole loves speaking with people to write about their unique stories. She also enjoys helping busy professionals get their expertise out of their heads and into published books.
Look, sometimes you just have to take a break and skim Etsy for cool iPad stuff. Are you thinking of picking up a new iPad 3 when they come out, or maybe just celebrating the release with a cool new case for your existing tablet? Check out this little round-up of cases collected by a felt-loving blogger on a Friday afternoon. Do you like felt, and leather, and buckles, and supporting the artisan iPad accessory community? Enter.
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Public release date: 23-Feb-2012
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