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Friday, November 30, 2012
A Spidernaut Spent 100 Days in Space and Returned Home a Hero
Remembering Lake George's Lost Ski Areas | Lake George Mirror ...
By Anthony F. Hall
Friday, November 30, 2012
New Book Documents the Days When Lake George was a Winter Destination
In the years between the 1932 Winter Olympic games in Lake Placid and the outbreak of World War II, small, single lift ski areas abounded in the Lake George area. Only a few remain.
According to Jeremy Davis, the author of the newly published Lost Ski Areas of the Adirondacks,
?The Adirondacks are filled with the ghosts of former ski areas. They range from the first J-bar in New York State in Lake George to large, planned resorts that were never completed.?
Davis, a meteorologist by profession, is a historian of vanished ski centers by avocation.
?This is my third book. The first was Lost Ski Areas of the White Mountains, the second, published in 2010, was Lost Ski Areas of Southern Vermont,? said Davis. ?I?ve been collecting brochures, guides and newspaper clippings about former ski areas for twenty years, starting in college. I first posted my research on a website. The editors at History Press saw it, and they said this material should be published in book form. I didn?t set out to be an author.?
In Lost Ski Areas of the Adirondacks, Davis writes about ski areas in Bolton, Lake George and Warrensburg, in addition to approximately 30 others spread throughout the Adirondack Park.
?In Bolton, a rope tow was installed at the Sagamore Golf Club. Warrensburg had a ski area between the Schroon River and Harrington Hill known as Hull?s Slope. And Lake George had a J-bar at Prospect Mountain and a ski jump at Top of the World, as well as rope tows at lesser known areas near the present sites of Travel Lodge and Magic Forest,? said Davis.
Skiing in Lake George was promoted by a Winter Sports Club and served by Snow Trains from Albany.
While only two hotels ? the Worden and the Ballos ? remained open year-round, there were several rooming houses within walking distance of the slopes, which were just a few blocks away from Canada Street. ?Experienced skiers consider Lake George facilities the equal of the most popular winter resorts in New York State,? claimed a January, 1938 issue of the Knickerbocker News.
The Prospect Mountain slope, which opened in 1938, boasted the only overhead cable ski tow in New York State and, for a short time at least, the longest lift of that type in the US.
According to Davis, the Prospect Mountain slope was developed by Fred Pabst, the brewery heir who built the first ski centers in eastern Canada and New England.
?What?s interesting is that even small areas like Top of the World hired European ski instructors and famous ski jumpers,? said Davis.
Prior to the outbreak of World War II, Pabst dismantled the J-bar and moved it to Vermont, where he opened Big Bromley, Davis said.
The 1932 Winter Olympics in Lake Placid made skiing a popular sport for the first time, said Davis.
?Equipment was inexpensive, even during the depression,? said Davis. ?People could even make their own skis and bindings if necessary.?
After World War II, skiing became a big business as investors and developers created ski resorts in the Rockies and in southern Vermont. The days of the single lift, owner and sometimes community operated ski area were over.
Davis said his goal is ?to get the histories of these ski areas on the record before it?s too late, and no one is left who will remember them.?
Davis acknowledges that some people might regard his interest in vanished ski areas as ?a peculiar hobby.?
?But,? he says, ?you?d be surprised by how many thousands of people have responded to the web site and books and have contributed photos and their own personal accounts.?
?The lost ski areas are like other lost pieces of roadside Americana: the amusement parks, the drive-ins, the diners. People are nostalgic about them because they associate them with their families and their own childhoods,? he said.
Davis does not merely collect ephemera about ski areas; he tramps through the woods to find what evidence he can of their brief existence.
?These are modern day archaeological sites,? he said. ?It?s amazing how quickly the ski slopes revert to wilderness. It?s almost instantaneous.?
He notes, for example, that the engine that powered the rope tow at the Ski Bowl in North Creek is now all but hidden in the woods a few hundred feet from the access road to the state-owned Gore Mountain Ski Center.
?It was the first rope tow in New York State,? he says. ?Would people be interested to know that they?re driving by it every time they go to Gore? At least a few of us find that fascinating.?
Lost Ski Areas of the Adirondacks is available at Trees in Bolton Landing, the Lake George Historical Museum and the Lake George Steamboat Company in Lake George, the Warrensburg Historical Museum and Miller?s Art and Frame in Warrensburg and the Ticonderoga Historical Society in Ticonderoga.
Source: http://www.lakegeorgemirrormagazine.com/2012/11/30/remembering-lake-george%E2%80%99s-lost-ski-areas/
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Thursday, November 29, 2012
Everything.me, The Search App That Bridges The Native And HTML5 Divide, Gets $25M From Telefonica, Mozilla And Singtel
Native apps are stealing the show when it comes to usage and functionality on mobile devices these days, but a lot of companies continue to hold out hope that more open HTML5-based mobile web services will ultimately win the day.?In the meantime, those who can straddle the two worlds beautifully and effectively may end up the winners.Source: http://feedproxy.google.com/~r/Techcrunch/~3/Yn122lleV8o/
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Scientists identify key biological mechanism in multiple sclerosis
ScienceDaily (Nov. 29, 2012) ? Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS) -- a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.
Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.
MS, which afflicts more than two million people worldwide, develops when the body's immune system attacks the brain. This attack damages nerve cells, leading to a host of symptoms including numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease's underlying cause -- which researchers are only just beginning to understand.
"To successfully treat MS, we must first identify what triggers the disease and what enables its progression," said Dr. Akassoglou, who also directs the Gladstone Center for In Vivo Imaging Research and is a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we have shown that the leakage of blood in the brain acts as an early trigger that sets off the brain's inflammatory response -- creating a neurotoxic environment that damages nerve cells."
Dr. Akassoglou and her team reached this conclusion by using advanced imaging techniques to monitor the disease's progression in the brain and spinal cord of mice modified to mimic the signs of MS. Traditional techniques only show "snapshots" of the disease's pathology. However, this analysis allows researchers to study individual cells within the living brain -- and to monitor in real-time what happens to these cells as the disease worsens over time.
"In vivo imaging analysis let us observe in real-time which molecules crossed the blood-brain barrier," said Dimitrios Davalos, PhD, Gladstone staff research scientist, associate director of the imaging center and the paper's lead author. "Importantly, this analysis helped us identify the protein fibrinogen as the key culprit in MS, by demonstrating how its entry into the brain through leaky blood vessels impacted the health of individual nerve cells."
Fibrinogen, a blood protein that is involved in coagulation, is not found in the healthy brain. In vivo imaging over different stages of disease revealed, however, that a disruption in the blood-brain barrier allows blood proteins -- and specifically fibrinogen -- to seep into the brain. Microglia -- immune cells that act as the brain's first line of defense -- initiate a rapid response to fibrinogen's arrival. They release large amounts of chemically reactive molecules called 'reactive oxygen species.' This creates a toxic environment within the brain that damages nerve cells and eventually leads to the debilitating symptoms of MS.
Importantly, the team found a strategy to halt this process by genetically modifying fibrinogen in the animal models. This strategy disrupted the protein's interaction with the microglia without affecting fibrinogen's essential role as a blood coagulant. In these models, the microglia did not react to fibrinogen's arrival and did not create a toxic environment. As a result, the mice failed to show the type of progressive nerve cell damage seen in MS.
"Dr. Akassoglou's work reveals a novel target for treating MS -- which might protect nerve cells and allow early intervention in the disease process," said Ursula Utz, PhD, MBA, a program director at The National Institutes of Health's National Institute of Neurological Disorders and Stroke, which provided funding for this research.
"Indeed, targeting the fibrinogen-microglia interactions to halt nerve-cell damage could be a new therapeutic strategy," said Dr. Akassoglou. "At present we are working to develop new approaches that specifically target the damaging effects of fibrinogen in the brain. We also continue to use in vivo imaging techniques to further enhance our understanding of what triggers the initiation and progression of MS. "
Jae Kyu Ryu, PhD, Mario Merlini, PhD, Kim Baeten, PhD, Natacha Le Moan, PhD, Mark Petersen, MD, Dimitri Smirnoff, Catherine Bedard, MSc, Sara Gonias Murray, MD, and Jennie Ling also participated in this research at Gladstone. Funding came from a variety of sources, including the National Multiple Sclerosis Society, the American Heart Association, the Howard Hughes Medical Institute, the Nancy Davis Foundation for Multiple Sclerosis, the Dana Program in Brain and Immuno-Imaging, H. Lundbeck A/S and the National Institutes of Health.
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The above story is reprinted from materials provided by Gladstone Institutes.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- Dimitrios Davalos, Jae Kyu Ryu, Mario Merlini, Kim M. Baeten, Natacha Le Moan, Mark A. Petersen, Thomas J. Deerinck, Dimitri S. Smirnoff, Catherine Bedard, Hiroyuki Hakozaki, Sara Gonias Murray, Jennie B. Ling, Hans Lassmann, Jay L. Degen, Mark H. Ellisman, Katerina Akassoglou. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nature Communications, 2012; 3: 1227 DOI: 10.1038/ncomms2230
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/eTY-XRbwnTU/121129173952.htm
Determining Quantum: How Much $$ Is Needed ... - Elder Caring Inc.
Originally published at allaboutestates.ca
Last week, I attended an excellent session organized by my fellow blogger, Paul Fensom from Scotia Private Client Group. The topic was on guardianship, the important role of the guardian, the management plan and the understanding or expectation on how the money should be spent.
Working with defence and plaintiff lawyers, and with individuals who have been catastrophically injured, I am very aware of how these impairments (physical and / or cognitive / behavioural) can significantly impact one?s day to day functioning. The definition I use for ?functioning? is global and may include their role as: student, employee, spouse, parent, caregiver and what they did in terms of their livelihood, role within their family, recreational, academic and/or (a)vocational pursuits and interests. The Life Care Plan [defined by the International Academy of Life Care Planners, (2002), Standards of Practice, Journal of Life Care Planning, 1 (1), 49-57] is ?a dynamic document based upon published standards of practice, comprehensive assessment, data analysis, and research, which provides an organized, concise plan for current and future needs, with associated costs, for individuals who have experienced catastrophic injury or have chronic health needs?. It is an important document that quantifies the goods and services needed to addresses the losses that the injured party has sustained. It identifies the client?s medical, rehabilitation and social needs and it provides a present day dollar to each of the goods and services. It is recommended that the report then be given to an actuary, accountant or economist, who can then forecast the present day value over the individual?s projected lifetime.
When a young person is injured, projected costs over a lifetime can generate very large numbers, similarly for those who may have congenital rather than acquired impairments. Financial and estate and trust officers can assist their older or disabled clients by understanding and quantifying the full extent of anticipated care needs which may include housing, (accessible or alternative) purchased in home care, assistive devices, equipment, transportation issues and a host of other items. For a senior, it can make the difference to ensure they have dignity and resources to live out their life.
The Life Care Plan (or Future Cost of Care Plan) preferably prepared by a Canadian Certified Life Care Planner can be used as a working tool which in addition to calculating the costs based on medical information, should be referenced regularly. It can be used as a blueprint for planning purposes.
Speak with an expert including a lawyer who specializes in the field, financial advisors/institutions who can responsibly manage these monies and a Certified Life Care Planner who has been trained to systematically review, analyse, research and quantify the current and anticipated required goods and services that are and will be needed, on behalf of your client.
Source: http://www.eldercaring.ca/2012/11/29/determining-quantum-how-much-is-needed-to-live-well/
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Wednesday, November 28, 2012
Montana Army National Guard Recognizes Troops (UNCLASSIFIED)
Date:? 27 November 2012
?
For More Information Contact:
Maj. Tim Crowe
MTNG Public Affairs Officer
406-461-6889
Timothy.crowe@us.army.mil <mailto:Timothy.crowe@us.army.mil>
?
FOR IMMEDIATE RELEASE
?
Montana National Guard Recognizes Returning Combat Veterans
?
?
?
Helena, Mont. ? Sunday, December 2, 2012 the Montana Army National Guard will recognize 19 Soldiers and their families from several Montana National Guard Units who have recently return from deployment overseas, in a Freedom Salute Ceremony, at Trinity Lounge, Trinity Hall on the campus of Carroll College at 1:30 p.m.?
?
The Soldiers are members of four different Montana National Guard units who deployed in support of Operation Enduring Freedom. The ceremony is designed to publicly acknowledge Montana Army National Guard Soldiers and those who supported them during the President?s call to duty for recent military operations.
?
?The Freedom Salute ceremony provides us a way to show our appreciation for the service and sacrifice our Soldiers and their families make when they volunteer to deploy for long periods of time,? said Major Tim Crowe, public affairs officer for the Montana National Guard.
?
The public is invited and encouraged to attend the ceremony.? For more information, contact Maj. Tim Crowe at 461-6889
?
?
??????????????????????????????????????????????????????????????????????????????? ##MTNG##
?
?
?
Tim Crowe, Maj, MTANG
Chief of Public Affairs for Montana
Montana Joint Force Headquarters
Fort Harrison, Mt
DSN -324-3009
Comm - 406-324-3009
Cell - 406-461-6889
Fac - 406-324-4800
timothy.crowe@us.army.mil
Source: http://metnet.mt.gov/Newslinks/I0330587A
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Google Launches ?VetNet? To Help Military Veterans Re-Enter The Civilian Life, With Google+ As The ?Plumbing?
For the men and women that serve our country, coming back from that life isn't easy. I don't have experience with it, but do know many veterans who are going through that. Today, Google launched a new initiative called VetNet, to help people connect and re-enter the working life. The company is putting its social backend, Google+, to work on this project.Source: http://feedproxy.google.com/~r/Techcrunch/~3/7AfFzTqBYAw/
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Kate Moss, Naomi Campbell Go Topless For Interview Russia (NSFW PHOTO)
If we had a nickel for every topless photo shoot that Kate Moss has posed in, we'd have... well, let's just say more change than could fit into one of the model's Longchamp totes.
For her latest au naturale venture, the 38-year-old is joined by fellow '90s supermodel Naomi Campbell on the cover of Interview Russia. The Mert and Marcus-lensed snap features the two gals doe-eyed (those lashes...) and reclining sans clothes. But since it's just another topless day at work for the two ladies, we're going to go out on a limb here and say that approximately nobody is shocked.
In the past year alone we've seen Kate pose for Spanish Vogue, Elle, Another Man, the 2012 Pirelli Calendar and even charity without anything covering her top half. Looks like she's come a long way since the "nervous breakdowns" she suffered during her early topless shoots... As for Naomi, the 42-year-old is probably too busy prepping for the upcoming premiere of her new modeling show "The Face" to be shy about this latest gig.
Until next time, ladies!
Check out the NSFW cover below and tell us what you think.
NSFW PHOTO:
See more Kate Moss covers!
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Tuesday, November 27, 2012
Elton John dedicates Beijing show to dissident
BEIJING (AP) ? Pop icon Elton John publicly dedicated his only concert in Beijing to Chinese artist and political critic Ai Weiwei, sending a murmur of shock through an audience accustomed to tight censorship of entertainment.
Minutes into a more than two-hour show Sunday night, John told the audience that the performance was dedicated "to the spirit and talent of Ai Weiwei," according to several audience members. They said the crowd rumbled in recognition that Ai remains a touchy subject for the Chinese government.
An internationally acclaimed sculptor and installation artist, Ai has used his art and his renown to draw attention to social injustice. He was detained for nearly three months last year, and he remains barred from leaving China.
Ai and John met each other briefly on Sunday before the concert. "I super like him," Ai said on his feed on Twitter, which is banned in China but on which he has 180,000 followers.
China-based online media sites reported on John's Beijing show, as they did on a Friday night performance in Shanghai, but they did not report John's remark about Ai.
The Chinese government exercises tight control of live performances, requiring artists to submit detailed lists of songs, casts and crew members before approval is given. Censors further tightened scrutiny after singer Bjork shouted "Tibet, Tibet" at the close of a song titled "Declare Independence" at a Shanghai performance in 2008.
Source: http://news.yahoo.com/elton-john-dedicates-beijing-show-dissident-070518523.html
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Chandlery - The Meaning Of The Phrase | Sports n Recreation Info ...
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Source: http://sports-recreation-info.blogspot.com/2012/11/chandlery-meaning-of-phrase.html
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kuttarpora: Heavy Equipment & Tools, Home Improvement: Skid ...
Skid & the Too Tiny Tunnel (Hardcover)
By Jeffery Stoddard
By Jeffery Stoddard
Review & Description
Skid, the littlest yellow tractor in the equipment yard, wants to be mighty like the giant bulldozers, tall cranes, and massive diggers who tower over him. But all the big machines tell him he is just a dinky tractor with a putt-putt engine. While they are busy building a new road through the mountain, Skid is left behind to take out the garbage.
When disaster strikes and a tunnel the machines are digging collapses, Pillar, the biggest bulldozer, is left trapped in the rubble. Only a small opening is left at the tunnel entrance and the only one who can fit through the opening is Skid who is afraid of the dark.
Now it's up to the tiniest tractor to save the day. Can Skid find the courage to do what he was made to do and prove that he doesn't have to be big to be mighty? Be strong and courageous. Do not be afraid or terrified because of them, for the LORD your God goes with you; he will never leave you nor forsake you. Deuteronomy 31:6 NIV
Read moreFind out More for the best price at Amazon
Source: http://heavy-equipment-tools-home.blogspot.com/2012/11/skid-too-tiny-tunnel-hardcover.html
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Source: http://ramgopall987456.blogspot.com/2012/11/heavy-equipment-tools-home-improvement.html
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Source: http://kuttarpora.blogspot.com/2012/11/heavy-equipment-tools-home-improvement.html
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Source: http://harshi37.typepad.com/blog/2012/11/kuttarpora-heavy-equipment-tools-home-improvement-skid.html
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94% The Sessions
All Critics (144) | Top Critics (39) | Fresh (136) | Rotten (8)
Achieves its sunny disposition by pulling punches.
A funny, tender and mostly unsentimentalized movie about physical and emotional triumph.
Forced to do all his acting with his face, Hawkes displays the kind of camera-arresting capability that has earned others Oscar nominations.
This is a crowd-pleaser of the finest sort.
Using only his tilted head, his eyes, nose, and mouth and that quizzical voice, Hawkes brings O'Brien to life.
Raw, unrestrained and sympathetic without giving in to melodrama, 'The Sessions' is about a man facing a physical challenge who decides he wants to become intimate with a woman.
An intelligent, funny, insightful film that offers a frank examination of sex. It's not prurient or titillating, just truthful.
A remarkable actor, John Hawkes, gives a remarkable performance as a remarkable character.
Surprisingly funny and touching.
Presents the sensitive O'Brien as a brave, funny, unselfish and unlikely romantic-fantasy dream hero for disappointed, weary or jaded older female moviegoers.
The uplifting struggle for living a life of dignity for paralyzed from the neck down polio victim Mark O'Brien.
The sex scenes are frank and explicit, but never cheap and exploitative. (Yes, they get naked. Grow up.) The nudity isn't airbrushed pin-up perfection, but raw and real - and all the more lovely and moving because of it.
Taking the good with the bad, this isn't a terrible movie, though it is being rather overhyped. I found myself laughing a lot and enjoying the transformations the actors go through, but an unengaging story only serves to drag it down.
A film, inspired by the life of the late poet-journalist Mark O'Brien, that celebrates the relationship between physical and emotional intimacy.
Not just another weepy drama of overcoming odds, a My Left Foot with a different appendage. The Sessions is often brazenly funny, not from shocking dialogue but characters reacting the way people do, especially with such a flustering subject as sex.
an unusually frank and frequently humorous meditation on the transformative power of connection
Take away the nudity and the frank sex talk and you'd pretty much be left with a high-minded TV movie -- with unusually good actors.
Hunt's tangible disregard for false modesty does justice to the misunderstood surrogacy profession, while Hawkes' committed yet matter-of-fact portrayal of O'Brien masterfully avoids theatricality or sappy heartstring tugging.
Lewin has never had talent like Hawkes, Hunt, and Macy as his instruments before, and he makes the best of them.
Popular sex therapist Dr. Ruth once said that sexual surrogates are "illegal." The Sessions makes them mainstream.
An adult film that approaches the serious subject of sex with refreshingly explicit honesty.
The honest performances and assured direction makes The Sessions an extremely accomplished film that celebrates sexuality.
John Hawkes and Helen Hunt generate an endearing chemistry, here, turning in a couple of virtuoso performances deserving of serious consideration come Oscar season.
Writer-director Ben Lewin has made the decision to position the film somewhere between the comedic and dramatic genres.... and it works.
Source: http://www.rottentomatoes.com/m/the_sessions/
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Monday, November 26, 2012
Metabolic protein launches sugar feast that nurtures brain tumors
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Public release date: 26-Nov-2012[ | E-mail |
Share ] Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
PKM2 slips into nucleus to promote cancer; potential biomarker and drug approach discovered
HOUSTON - Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein's pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which brain tumors thrive.
They also found a vital spot along the protein's journey that can be attacked with a type of drug not yet deployed against glioblastoma multiforme, the most common and lethal form of brain cancer. Published online by Nature Cell Biology, the paper further illuminates the importance of pyruvate kinase M2 (PKM2) in cancer development and progression.
"PKM2 is very active during infancy, when you want rapid cell growth, and eventually it turns off. Tumor cells turn PKM2 back on - it's overexpressed in many types of cancer," said Zhimin Lu, M.D., Ph.D., the paper's senior author and an associate professor in MD Anderson's Department of Neuro-Oncology.
Lu and colleagues showed earlier this year that PKM2 in the nucleus also activates a variety of genes involved in cell division. The latest paper shows how it triggers aerobic glycolysis, processing glucose into energy, also known as the Warburg effect, upon which many types of solid tumors rely to survive and grow.
"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Lu said. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles' heel for cancer."
By pinpointing the complicated steps necessary for PKM2 to penetrate the nucleus, Lu and colleagues found a potentially druggable target that could keep the protein locked in the cell's cytoplasm.
MEK, ERK emerge as targets
The process begins when the epidermal growth factor connects to its receptor on the cell surface. This leads to:
- Activation of the MEK protein, which in turn activates ERK.
- ERK sticking a phosphate group to a specific spot on PKM2.
- Phosphorylation priming PKM2 for a series of steps that culminate in its binding to the protein importin, which lives up to its name by taking PKM2 through the nuclear membrane.
Once in the nucleus, the team showed that PKM2 activates two genes crucial to aerobic glycolysis and another that splices PKM RNA to make even more PKM2.
An experiment applying several kinase-inhibiting drugs to human glioblastoma cell lines showed that only a MEK/ERK inhibitor prevented EGF-induced smuggling of PKM2 into the nucleus. ERK activation then is mandatory for PKM2 to get into the nucleus.
"MEK/ERK inhibitors have not been tried yet in glioblastoma multiforme," Lu said. Phosporylated PKM2 is a potential biomarker to identify patients who are candidates for MEK/ERK inhibitors once those drugs are developed.
MEK inhibitor blocks tumor growth
The researchers also found that the two glycolysis genes activated by PKM2, called GLUT1 and LDHA, are required for glucose consumption and conversion of pyruvate to lactate, crucial factors in the Warburg Effect. Depleting PKM2 in tumor cell lines reduced glucose consumption and lactate production.
In mice, depleting PKM2 blocked the growth of brain tumors. Re-expressing the wild type protein caused tumors to grow. However, re-expression of a PKM2 mutant protein that lost its ability to get into the nucleus failed to promote tumor formation. Experiments in human glioblastoma cell lines showed the same effect.
Injecting the MEK inhibitor selumetinib into tumors inhibited tumor growth, reduced ERK phosphorylation, PKM2 expression and lactate production in mice. In 48 human tumor samples, the team found that activity of EGFR, ERK1/2 and PKM2 were strongly correlated.
Cause of PKM2 overexpression
Lu and colleagues also published a paper in Molecular Cell that revealed a mechanism for overexpression of PKM2 in glioblastoma. They found that EGF receptor activation turns on NF-?B, which leads to a series of events culminating in PKM2 gene activation.
PKM2 levels were measured in tumor samples from 55 glioblastoma patients treated with standard of care surgery, radiation and chemotherapy. The 20 with low PKM2 expression had a median survival of 34.5 months, compared to 13.6 months for the 35 patients with high levels of PKM2.
Level of PKM2 expression in 27 low-grade astrocytomas was about half of the expression found in higher grade glioblastomas.
"In these two papers, we show how PKM2 is overexpressed in tumors, how it gets into the nucleus, that nuclear entry is essential to tumor development, and identified potential drugs and a biomarker that could usefully treat people," Lu said.
###
Co-authors of the Nature Cell Biology paper are first author Weiwei Yang, Ph.D., Yanhua Zheng, Ph.D., Yan Xia, Ph.D., and Haitao Ji, Ph.D., of MD Anderson's Department of Neuro-Oncology and Brain Tumor Center; Xiaomin Chen, Ph.D., of MD Anderson's Department of Biochemistry and Molecular Biology; Ken Aldape, M.D., MD Anderson's Department of Pathology; Fang Guo, Ph.D., Nanomedicine Center, Shanghai Research Institute, China Academy of Science; Costas Lyssiotis, Ph.D., and Lewis Cantley, Ph.D., Beth Israel Deaconess Medical Center, Harvard Medical School.
This research was funded by grants from the National Institutes of Health (numbers 2RO1CA109035, RO1GM068566 and RO1GM56302), MD Anderson's Cancer Center Support Grant (CA16672) from the National Cancer Institute; and a research grant from the Cancer Prevention and Research Institute of Texas.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For nine of the past 11 years, including 2012, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
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Public release date: 26-Nov-2012[ | E-mail |
Share ] Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
PKM2 slips into nucleus to promote cancer; potential biomarker and drug approach discovered
HOUSTON - Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein's pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which brain tumors thrive.
They also found a vital spot along the protein's journey that can be attacked with a type of drug not yet deployed against glioblastoma multiforme, the most common and lethal form of brain cancer. Published online by Nature Cell Biology, the paper further illuminates the importance of pyruvate kinase M2 (PKM2) in cancer development and progression.
"PKM2 is very active during infancy, when you want rapid cell growth, and eventually it turns off. Tumor cells turn PKM2 back on - it's overexpressed in many types of cancer," said Zhimin Lu, M.D., Ph.D., the paper's senior author and an associate professor in MD Anderson's Department of Neuro-Oncology.
Lu and colleagues showed earlier this year that PKM2 in the nucleus also activates a variety of genes involved in cell division. The latest paper shows how it triggers aerobic glycolysis, processing glucose into energy, also known as the Warburg effect, upon which many types of solid tumors rely to survive and grow.
"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Lu said. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles' heel for cancer."
By pinpointing the complicated steps necessary for PKM2 to penetrate the nucleus, Lu and colleagues found a potentially druggable target that could keep the protein locked in the cell's cytoplasm.
MEK, ERK emerge as targets
The process begins when the epidermal growth factor connects to its receptor on the cell surface. This leads to:
- Activation of the MEK protein, which in turn activates ERK.
- ERK sticking a phosphate group to a specific spot on PKM2.
- Phosphorylation priming PKM2 for a series of steps that culminate in its binding to the protein importin, which lives up to its name by taking PKM2 through the nuclear membrane.
Once in the nucleus, the team showed that PKM2 activates two genes crucial to aerobic glycolysis and another that splices PKM RNA to make even more PKM2.
An experiment applying several kinase-inhibiting drugs to human glioblastoma cell lines showed that only a MEK/ERK inhibitor prevented EGF-induced smuggling of PKM2 into the nucleus. ERK activation then is mandatory for PKM2 to get into the nucleus.
"MEK/ERK inhibitors have not been tried yet in glioblastoma multiforme," Lu said. Phosporylated PKM2 is a potential biomarker to identify patients who are candidates for MEK/ERK inhibitors once those drugs are developed.
MEK inhibitor blocks tumor growth
The researchers also found that the two glycolysis genes activated by PKM2, called GLUT1 and LDHA, are required for glucose consumption and conversion of pyruvate to lactate, crucial factors in the Warburg Effect. Depleting PKM2 in tumor cell lines reduced glucose consumption and lactate production.
In mice, depleting PKM2 blocked the growth of brain tumors. Re-expressing the wild type protein caused tumors to grow. However, re-expression of a PKM2 mutant protein that lost its ability to get into the nucleus failed to promote tumor formation. Experiments in human glioblastoma cell lines showed the same effect.
Injecting the MEK inhibitor selumetinib into tumors inhibited tumor growth, reduced ERK phosphorylation, PKM2 expression and lactate production in mice. In 48 human tumor samples, the team found that activity of EGFR, ERK1/2 and PKM2 were strongly correlated.
Cause of PKM2 overexpression
Lu and colleagues also published a paper in Molecular Cell that revealed a mechanism for overexpression of PKM2 in glioblastoma. They found that EGF receptor activation turns on NF-?B, which leads to a series of events culminating in PKM2 gene activation.
PKM2 levels were measured in tumor samples from 55 glioblastoma patients treated with standard of care surgery, radiation and chemotherapy. The 20 with low PKM2 expression had a median survival of 34.5 months, compared to 13.6 months for the 35 patients with high levels of PKM2.
Level of PKM2 expression in 27 low-grade astrocytomas was about half of the expression found in higher grade glioblastomas.
"In these two papers, we show how PKM2 is overexpressed in tumors, how it gets into the nucleus, that nuclear entry is essential to tumor development, and identified potential drugs and a biomarker that could usefully treat people," Lu said.
###
Co-authors of the Nature Cell Biology paper are first author Weiwei Yang, Ph.D., Yanhua Zheng, Ph.D., Yan Xia, Ph.D., and Haitao Ji, Ph.D., of MD Anderson's Department of Neuro-Oncology and Brain Tumor Center; Xiaomin Chen, Ph.D., of MD Anderson's Department of Biochemistry and Molecular Biology; Ken Aldape, M.D., MD Anderson's Department of Pathology; Fang Guo, Ph.D., Nanomedicine Center, Shanghai Research Institute, China Academy of Science; Costas Lyssiotis, Ph.D., and Lewis Cantley, Ph.D., Beth Israel Deaconess Medical Center, Harvard Medical School.
This research was funded by grants from the National Institutes of Health (numbers 2RO1CA109035, RO1GM068566 and RO1GM56302), MD Anderson's Cancer Center Support Grant (CA16672) from the National Cancer Institute; and a research grant from the Cancer Prevention and Research Institute of Texas.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For nine of the past 11 years, including 2012, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
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Source: http://www.eurekalert.org/pub_releases/2012-11/uotm-mpl112612.php
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Phoenix Truck Auctions: Buying & Selling | Hugo Hosting - Kirk ...
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Are you pondering about buying a employed truck at a Phoenix truck auction? This write-up is developed to supply you with the facts on how car auctions work and how they can get you the finest deal on a great employed truck. Specifics might vary from auction to auction nevertheless, the following info includes helpful and critical tips from which everyone can advantage.
Phoenix truck auctions are one of the best locations to choose up a used truck, particularly substantial finish luxury vans at a portion of its initial retail cost. Have you ever pulled up following to a totally loaded Escalade at a cease light, glanced in excess of and observed that the driver is scarcely out of large university? How could they perhaps afford the truck charge on that variety of experience? Effectively, they probably ordered the motor vehicle at a Phoenix truck auction and received a wonderful bargain.
If you have ever dreamed about possessing a high-end luxury truck or a personalized automobile loaded with aftermarket elements and add-ons, you have probably completed just that ? dreamed about it. Paying retail cost for a truck like that can put a huge dent in your wallet or your personal savings account. Nonetheless, you can get a truck like that for considerably less.
There are numerous various sorts of Phoenix truck auctions, but two of the most popular happen to be police confiscated car auctions and federal government surplus automobile auctions.
Police confiscated vehicle auctions feature vehicles that have been seized due to asset forfeiture in addition to surplus vehicles that have been utilized by the neighborhood police department. Police truck auctions are one particular of the best locations to select up a utilised truck. Several people think that the only vehicles accessible at police truck auctions are real police vans. Effectively, they are appropriate ? but only partially!
Government automobile auctions get their offer from criminals. When someone is convicted of a criminal offense, like drug trafficking, the federal government can seize their belongings, including their motor vehicle. Negative for the criminals but very good for you! Authorities seized vehicles are usually luxury vehicles ? BMW, Cadillac, Mercedes, Infiniti, Lexus ? and at times you may possibly even occur throughout and unique import! Not several men and women can afford a truck like this, but it?s possible if you attend a Phoenix truck auction.
Govt car auctions might also characteristic their own surplus autos, or people no longer necessary. These can be passenger autos, decoy vans, large gear or even bikes, bicycles and ATVs. Other trucks showcased at authorities auctions are retired fleet autos. These kinds of vehicles are changed routinely by their respective agencies and are generally domestic trucks with higher mileage that have been meticulously preserved. You are a lot far more likely to get car background with a government-owned and operated motor vehicle than you are a seized vehicle. Keep this in head if vehicle history is critical to you. Even so most cars can have a carfax report run to verify on any likely ownership troubles or maintenance troubles.
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Please don?t forget: Inspecting trucks being sold at a police seized truck auction is a must! Trucks bought at police seized auctions are bought ?As-Is? with no guarantee or assure except if nonetheless under suppliers warranty. In an ?As-Is? auction, there is no warranty on the items and the bidder is liable for removal from the auction location. This implies that the bidder should count on their individual inspection and knowledge to make bidding decisions. Some auction residences, however, permit bidder to bring their own mechanic for automobile inspections.
Irregardless of the frequency of a Phoenix truck auction, you can typically find the celebration in the regional newspaper or printed on an on-line auction site that performs with the police departments in your area. The advertisement or itemizing will give the date, time and location of the auction as nicely as a synopses of the vans that will be auctioned off. They may possibly also give a date in which fascinated get-togethers are invited to inspect the vehicles so that they can make selections about what to purchase and how significantly to commit.
If you happen to be in the market for a good bargain on a employed truck, it?s undoubtedly really worth your time to see what is actually obtainable at your next Phoenix truck auction.
Related posts:
- Auto Auctions ? Car Auctions
- Government Auctions Sales
- State Auctions
- Open Door Auctions Lays Out Blueprint for Buying Homes Using Auction Model
- Police Auctions and Government Auctions Website PoliceAuctions.com to Auction Superior Sports Memorabilia
Source: http://www.hugohosting.com/phoenix-truck-auctions-buying-selling.html
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Sunday, November 25, 2012
Refresh Roundup: week of November 19th, 2012
Your smartphone and / or tablet is just begging for an update. From time to time, these mobile devices are blessed with maintenance refreshes, bug fixes, custom ROMs and anything in between, and so many of them are floating around that it's easy for a sizable chunk to get lost in the mix. To make sure they don't escape without notice, we've gathered every possible update, hack, and other miscellaneous tomfoolery we could find during the last week and crammed them into one convenient roundup. If you find something available for your device, please give us a shout at tips at engadget dawt com and let us know. Enjoy!
Continue reading Refresh Roundup: week of November 19th, 2012
Filed under: Cellphones, Tablets, Software, Mobile, Samsung
Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/wqQdnXol7Og/
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New Hampshire Child Falls Down Laundry Chute ... - AOL Real Estate
A New Hampshire couple has a lot to be thankful for: Their 2-year-old son miraculously survived tumbling down a two-story laundry chute and getting trapped inside the walls of their home on Thanksgiving Day.
Melissa Pendlebury and Eric Leger of Manchester, N.H., told WHDH-TV in Boston that they woke up to "a bloodcurdling scream" around 7 a.m. Thursday and heard their son, Cayden (pictured below after the incident), crying.
"My sister said, 'Oh my God, he's in the wall!'" Pendlebury recalled.
Cayden had crawled through a 10-inch-wide latch on the second floor of their home. The latch opened to a shaft leading to the basement that used to be used as a laundry chute. The family now uses it to store cables and Internet wires.
Cayden dropped about 20 feet, FOX 25 in Boston reported, and became tangled in the wires, dangling by his legs.
"The screams that came out of him -- I never want to hear that again," Leger told TV station WCVB. "[I wasn't] able to do anything."
But there was one thing he did to try and calm his son.
"I just punched a hole in the wall so I could get to him and at least hold his hand," Leger added in an interview with WHDH.
Firefighters rushed to the home after the family alerted them and had to cut wires and remove plaster to rescue the toddler through an opening in the basement. Cayden was taken to the hospital but released shortly thereafter with nothing more than a couple of bumps and bruises.
The family quickly nailed the latch shut and covered it with plaster after the incident, but that didn't stop little Cayden's young curiosity. In a video on FOX 25's website, Cayden is shown still attempting to open the latch door after it was sealed.
"Never doubt a child whatsoever 'cause they'll get into things you'd never even think about," Leger said.
Pendlebury was able to look back on the mishap with relief and a little laugh. She said they had been planning a nontraditional Thanksgiving with movies at home and Chinese takeout.
"I guess he really did start it off nontraditional," she said of her son.
Shafts and chutes in homes and buildings aren't perilous only for curious little boys like Cayden. In August, a San Diego woman lost her balance in the shower and fell out her bathroom window and down the 15-foot light shaft of her apartment building.
Boston News, Weather, Sports | FOX 25 | MyFoxBoston
See also:
Woman Almost Loses Arm When Struck by Construction Debris in Storm
Do Guard Dogs Protect Homes From Burglars? These Pooches Didn't
Indianapolis Homeowner Whose House Exploded, Damaging Nearly 80 Other Homes, Bereft Over Tragedy
More on AOL Real Estate:
Find out how to calculate mortgage payments.
Find homes for sale in your area.
Find foreclosures in your area.
Find homes for rent in your area.
Follow us on Twitter at @AOLRealEstate or connect with AOL Real Estate on Facebook.
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Saturday, November 24, 2012
Real Estate Investing ? Consider Purchasing In foreclosure Properties
Some individuals purchase property for their personal use. On the other hand, you will find others who make investments in property and try to make long-term earnings from their particular assets. Do not necessarily permit the recent property situation discourage you absent from the property market. One revolutionary alternative available for home purchasers will be to move in for in foreclosure process properties that are available at a discount. The concept of purchasing property at a discount may appear unusual. However, discounts are available contemplating the drastic increase in the quantity of house foreclosures in the country.
A property foreclosure occurs when the debtor is not in a place to pay back the mortgage loan correctly. Right after default, banking institutions as well as finance institutions take over ownership and title of properties as well as continue to sell the identical to recuperate their investment. In the event that the property market is depressed, financial institutions may consider providing a discount to recuperate a part of their particular investment.
In this kind of a scenario, a person can very easily make investments in real estate by ordering in foreclosure properties up for public sale. These kinds of bargains can enable you to buy property at good special discounts. Customers can effortlessly protected a 7-8% discount on the value of foreclosed properties. In August 2009, customers had been experiencing special discounts in excessive of 23%. Envision buying a property really worth $100,000 for $75,000 just? Your investment will instantly appreciate a $25,000 income. This kind of number is just going to ascend higher since the worth of property raises.
The housing market offers improved upon and also circumstances of this kind of special discounts are becoming rarer. Nonetheless, financial institutions have not halted offering special discounts completely. Quantity of foreclosures in October 2012 flower in comparison to the prior month. While there has been a 19% lower in foreclosures from October 2011 to October 2012, there is a 3% increase from September to October.
There is no harm in taking advantage of the improve to find excellent investment options available at a discount. Hence, you should emphasis on says that still have a high foreclosures fee to enjoy significant discounts on property bargains. Nonetheless, you need to take into account various other elements just before deciding on your investment.
To begin with, getting an in foreclosure home just isn?t the identical to getting any other home. A home that has been foreclosed more than a dozen months in the past may require several fixes to make it fit for habitation once more. An individual may not require to invest money immediately but you will possess to spend on renovation to get great returns on your own investment. Make positive you consider the expense of maintenance as well as refurbishments any time finalizing the investment.
The steer clear of most is to buy a $100,000 property at $75,000 and then spend $30,000 on remodeling the property. A person will end up with a loss of $5000 from such a package. Consider this expense even if you are not necessarily organizing to spend on renovation instantly.
Secondly, make positive you take into account different costs and also responsibilities billed through banks for shifting the in foreclosure process property in your business. Financial institutions usually offer you a discount only to attempt to increase their earnings simply by upon additional fees on the customer. Do not necessarily think twice to step away from the purchase if you believe it?s not appealing adequate.
For more info, go to invest in real estate and also real estate investors
Related posts:
- It?s not all the time that you?re going to commit your hard earned money in purchasing a home. So before making a choice of these magnitude, you have to be sure that you?re completely educated. Acquiring real estate is obviously risky, although the tips in the following paragraphs will help you make the right choice.House consumers or some other sort of real-estate purchaser would do well to aim for fixer-uppers as opposed to new, immaculate houses. If you?re happy to provide you with the doing touches on a house, it will save you thousands upon thousands of money by putting in the project oneself. Buying new signifies you?ll spend far more.Try not to over-evaluate. It is advisable to be careful when buying a home. Just don?t be also mindful. In the event you commit too much time weighing the advantages and disadvantages, you are able to lose out on some excellent offers. You might find yourself the need to be satisfied with a thing that is way less attractive.While you do want to buy if the market is lower, it is crucial that you do not hang on too much time or perhaps the costs may well climb and you will find yourself losing the opportunity come up with a good income. Ensure you shop very low and that you usually do not use to very long to acquire.Although a house may appear perfect it is important that you can work with an inspector into the future and check out the home before you purchase something. Things like electric and plumbing related troubles can not be discovered through the untrained eyes all the time so it vital that you employ someone who knows what you should be aware of.It is important that you go to the residence more often than once so you obtain an accurate feeling for your local community. A neighborhood can be totally different dependant upon the time of the week or perhaps the time through the day. It can be necessary that you just understand what you will be getting yourself into.When deciding if you can pay for a house, acquire outdoor maintenance expenses into mind. A property having a little lawn and a large outdoor patio will need cheaper care than a single with acreage and several plants. If you can find poor bushes that require elimination, get quotations for the operate, and component the charge in your value choices.In case you are thinking of getting a home in a local community that has a lot of new building occurring, you really should reconsider that. Most new development is not completed for several weeks, and in some cases, yrs. This could make slumbering a hardship on you and your family.When viewing properties to acquire, you should always consider an investing in a home that has been forclosed on. With all the economic climate moving downhill, more people have been dropping their houses as they are not able to make your mortgage repayments. Forclosed properties can sometimes be less expensive and might stay in far better form then newer homes.Remember, purchasing residence isn?t an issue that you?re going to do every single day. Make sure that you?re generally taking your time to make the best decision achievable. Real estate charges lots of money, so make use of the tips you figured out in this post to be sure that you?re investing it smartly.
- Investment Properties ? Can A person Develop Positive Cash Flow Swiftly?
- Advice On Purchasing Real Estate
- Commercial Real Estate Agents ? A Marketing System for Today
- Can a Foreclosure Lawyer Support?
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people in need of loan - belylotos - LiveJournal
How will you obtain loan or perhaps advance loan?
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Depending on your problem associated with residence, work status and profits, it is possible to be eligible for a a loan up to $1500, however some loan companies may lend no more than $500. You'll have a possiblity to observe how much you be eligible for a prior to accepting virtually any bank loan contract.
There's an essential legal big difference from the gift and also a loan. A really nice relative or even good friend could give you $5000 with regard to vehicle repairs, as an example. When there isn't any hope associated with repayment, the amount of money could be a present. The actual giver could not take legal action against regarding repayment later within a city fit. When the borrowed funds provider designates the amount of money like a loan and also the customer will pay back again a buck, the bucks may very well be a real loan and also the loan company may need repayment anytime. Small claims legal courts invest a lot of period determining regardless of whether the deal including cash will be a gift as well as bank loan. Because of this paperwork is important when designing private lending options to close friends or family members.
The needs to get a loan are quite obvious. If you are employed, having a month-to-month earnings of $800 or even more, and also a checking account, you fulfill the basic requirements. A number of creditors within our network might have additional needs.
Money lending products are usually unsecured financial loans eliminated upon the following salary. Because they're short-term financial loans, they may be little; various from $100 to $1500 and payment comes to your next pay day. They could be very helpful for overcoming a quick fiscal crisis, but really should not be regarded as the long-term monetary option.
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The majority of home loan programs are addressed through banking institutions or other professional lenders. They might use a various criteria to find out if the potential customer is qualified for a financial loan. Previous credit rating is virtually usually deemed, together with current earnings as well as assets. The objective of the borrowed funds can also be a great issue-a established expense chance may have much more appeal as compared to a good misdirected concept for any new restaurant. One particular essential consideration could be the revenue to credit card debt percentage through the customer. May the customer have the ability to pay the bank loan back again with interest? Skilled loan companies basically 'sell' income, so debtors should know simply how much financing truly 'costs' in relation to real cash.
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Payday Loan Kcmo No faxing! Fast and Easy! All online real time. Choose your state 83214 ID
Cant Get Loan Cash in many cases. Select state 52347 IA
Payday Loans Online For Unemployed Where to get emergency cash? Choose your zip or state e.g. 77305 TX
Source: http://belylotos.livejournal.com/396471.html
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Newsletter Marketing | imm1.com - gracegrant3s posterous ...
One particularly effective affiliate marketing solution is ezine or newsletter marketing. This is a paid method of advertising your business and your site by laser targeting the type of people that you feel would be interested in your product or service.
There are ezines or newsletters out there written on any topic that you can think of, the challenge is finding the specific ezine or newsletter that deals with your particular subject and making sure there is a loyal subscriber base that is not inundated with advertising from the publisher. You can do a simple search on Google or Yahoo to find different ezines or newsletters that deal with the topic that you are looking for and contact the publisher about their subscriber base and their advertising methods and frequency.
Some guidelines to use when making a decision which publication to choose for advertising are:
1) Number of subscribers ? typically above 20,000 is a good number.
2) Number of new subscribers per week ? 1000 to 5000 is good.
3) How often the publisher sends out solo ads ? no more than one per week.
You will want to focus on placing solo ads, ads that go out to all or part of the subscribers as an email that contains only your ad and link to your site. This is the most expensive form of advertising that newsletters will offer, but the best conversion by far.
Having trouble finding an ezine or newsletter with the right content and the right number of subscribers that offers solo advertising? Check out ?Directory of Ezines? online for an up-to-date, comprehensive list of ezines with details of number of subscribers, types of advertising available and cost, links to the ezine site so you can check out back issues, and contact information for the publisher to ask further questions.
Once you have chosen an ezine or newsletter that fits with your business, you can purchase a solo ad and provide the copy and link that you would like to send to the subscriber base. Make sure this ad is short and sweet (some ezine publishers limit the amount of words you can submit), and peaks the interest of the reader wanting to learn more about your product or service. The most successful solo ads are also the shortest, so keep it brief to get the clicks to your site
Some general guidelines for solo ads:
In the subject line, identify a big goal or a big problem facing your target market (ex. ?build massive wealth online? ? or ? ?can?t get your web business going??).
Then in the body of ad, address the big goal or big problem briefly (ex. ?internet novice builds massive wealth using simple methods outlined in this program? ? or ? ?get your business rolling with simple methods outlined in this program?).
Then type something like, ?click the link to learn how to build massive wealth online?. Simple as 1-2-3, keep it short and not a ton of detail to get the clicks.
Dave Altman is an experienced internet marketer leveraging and teaching the latest internet tools and technology to build wealth on the web. Taking pride in keeping up with the latest tools on the web to reach people and expose your business online. Learn more at [http://www.easywebcashsite.com].
Source: http://imm1.com/newsletter-marketing/
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