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NCI Research Grant Payline Higher Than Anticipated
The R01 payline for fiscal year (FY) 2007 will be higher than expected, NCI Director Dr. John Niederhuber has announced.
Speaking to NCI's Board of Scientific Advisors (BSA) on June 28, Dr. Niederhuber explained that the end-of-year payline for R01 grants would be the 15th percentile. At the beginning of the year, the payline estimate was the 12th percentile, the same level at which NCI finished in 2006.
The payline for the R01 program for first-time investigators will be the 21st percentile, Dr. Niederhuber reported, which also is higher than what was anticipated at the beginning of the fiscal year. Read more
Guest Update by Drs. James Doroshow and Ernest Hawk
Moving Ahead with Translational Research
The recent release of the final report of the Translational Research Working Group (TRWG) and its approval by the National Cancer Advisory Board, marks an important milestone for NCI. After 2 years of work, we're hopeful that TRWG's recommendations, along with activities already taking place as a result of recommendations made 2 years ago by the Clinical Trials Working Group (CTWG), will lead to more rapid progress in translating important research findings into new, effective interventions.
TRWG was led by co-chairs Drs. Ernest Hawk of NCI's Office of Centers, Training and Resources; Lynn Matrisian of Vanderbilt University; and William Nelson of Johns Hopkins University. It's important to stress that the TRWG report - developed by some of the most well-respected translational and clinical research experts within and outside of NCI, with additional input from literally hundreds of scientists and members of the cancer community - focuses on "early translation," that is, the work done to move basic research discoveries into phase I and II clinical trials. The recommendations are a natural complement to several CTWG-related activities, which are focused on "late translation," primarily phase III clinical trials. Read more
NCI Research Grant Payline Higher Than Anticipated
The R01 payline for fiscal year (FY) 2007 will be higher than expected, NCI Director Dr. John Niederhuber has announced.
Speaking to NCI's Board of Scientific Advisors (BSA) on June 28, Dr. Niederhuber explained that the end-of-year payline for R01 grants would be the 15th percentile. At the beginning of the year, the payline estimate was the 12th percentile, the same level at which NCI finished in 2006.
The payline for the R01 program for first-time investigators will be the 21st percentile, Dr. Niederhuber reported, which also is higher than what was anticipated at the beginning of the fiscal year.
The payline represents the cutoff above which an application will be funded, as determined by its scientific review and priority scores. The payline is established based on the number of expected applications and the available funds designated for competing grants, meaning that it can change throughout the year as NCI can more accurately assess the number of incoming applications and available resources.
"In reality, we'll be funding quite above the 15th percentile after exceptions," Dr. Niederhuber said. "I don't think any of us a year ago felt we had a chance of reaching this [level]."
R01 competing grants funded as "exceptions" are those with a priority ranking that put them beyond the final payline, but were judged to be deserving of support after all other grants that met the payline were funded. Those grants are paid from a pool of competing grant funds that are set aside at the beginning of the fiscal year to fund exceptions. For 2007, that pool represented approximately 20 percent of the competing grant budget.
Dr. Niederhuber praised NCI's senior leadership team for their efforts to review programs across the institute's divisions and centers, setting the stage for the higher payline. That process, he continued, involved regular meetings of senior leaders to review programs and make decisions about "what we could slow down, what we could phase out, and really prioritize our best science, our best investigators."
Overall, NCI's current research project grant portfolio, excluding small business grants, includes well over 5,000 awarded grants. NCI received nearly 6,600 competing grant applications in FY 2007, which represents a flattening of the steady increase in grant applications that followed the doubling of NIH's budget.
"I think that should be expected as a new equilibrium gets established," Dr. Niederhuber acknowledged.
BSA Chair Dr. Robert Young, of Fox Chase Cancer Center, was concerned that, because the negative impact of budget constraints on research grants was not as great as had been expected, members of Congress might not understand the extent to which "programs aren't being funded, investigators aren't being funded."
Dr. Niederhuber responded that he and NIH Director Dr. Elias Zerhouni, in their appearances before Congress, have stressed the impact of flat budgets on research funded by NCI and NIH, and that "there is a new level of understanding at present" among legislators.That's reflected, he continued, in the budget increases for NIH and NCI in House and Senate legislation that goes beyond the administration's budget requests, and the targets for overall grants and grants to new investigators that are included in the language accompanying those bills.
- Carmen Phillips
Guest Update by Drs. James Doroshow and Ernest Hawk
Moving Ahead with Translational Research
The recent release of the final report of the Translational Research Working Group (TRWG) and its approval by the National Cancer Advisory Board, marks an important milestone for NCI. After 2 years of work, we're hopeful that TRWG's recommendations, along with activities already taking place as a result of recommendations made 2 years ago by the Clinical Trials Working Group (CTWG), will lead to more rapid progress in translating important research findings into new, effective interventions.
TRWG was led by co-chairs Drs. Ernest Hawk of NCI's Office of Centers, Training and Resources; Lynn Matrisian of Vanderbilt University; and William Nelson of Johns Hopkins University. It's important to stress that the TRWG report - developed by some of the most well-respected translational and clinical research experts within and outside of NCI, with additional input from literally hundreds of scientists and members of the cancer community - focuses on "early translation," that is, the work done to move basic research discoveries into phase I and II clinical trials. The recommendations are a natural complement to several CTWG-related activities, which are focused on "late translation," primarily phase III clinical trials.
At their core, the TRWG recommendations are intended to help define and facilitate the appropriate "handoffs" so that fundamental discoveries - such as those related to potential new imaging-based risk assessment methods, new immunotherapy approaches, or lifestyle interventions, among others - can be efficiently evaluated in early-phase clinical trials. That includes activities such as developing project management plans, establishing access to core services such as imaging libraries and well-annotated biospecimens, and developing intellectual property agreements with industry or other third parties.
The recommendations are not intended to replace or impinge upon discovery research. Quite the contrary, they are intended to create a coordinated and collaborative national enterprise focused on the distinctive needs of research that follow from promising basic discoveries.
In total, TRWG developed 15 recommendations - with suggested plans for implementing them - categorized into three main themes: coordinated management, tailored funding programs, and operational effectiveness.
Under coordinated management, for example, are specific recommendations for establishing an organizational approach to managing the diverse early translational research portfolio that exists throughout NCI's divisions and centers, and a transparent, inclusive prioritization process to identify the most promising early translational research opportunities.
Several tailored funding programs are recommended, including the establishment of special programs to advance specific projects deemed especially promising and to support collaborations between extramural investigators and industry. The former program, called the Special Translational Research Acceleration Project (STRAP), would support an integrated research and development program designed to achieve a specific clinical or product development goal.
Recommendations that fall under operational effectiveness include building a project management system that would involve staff at NCI and investigators' institutions to help oversee projects and develop enhanced approaches for negotiating with industry over issues related to intellectual property and access to investigational agents.
TRWG sees these recommendations as evolutionary, not revolutionary. This is particularly evident in how some of the recommendations dovetail with ongoing CTWG-related activities. One excellent example is the establishment of a subcommittee of the Clinical Trials Advisory Committee that will focus on translational research.
We already have received excellent feedback on the TRWG recommendations. Several foundations, for instance, have indicated they would be interested in helping to support the STRAP program, and industry representatives who met with TRWG during its deliberations were very enthusiastic about supporting and expanding collaborative efforts and working through logistic and legal hurdles to early translational work.Decisions about how NCI will address the TRWG recommendations must still be made. But we're hopeful that, combined with ongoing activities spurred by the CTWG recommendations, these recommendations will lead to measurable and meaningful progress in getting new, more effective risk assessment strategies and interventions to those at risk and those diagnosed with cancer far more quickly than has been possible in the past.
Genetic Markers of Colorectal Cancer Risk Identified
Three separate genome-wide association studies published online July 8 in Nature Genetics have identified a locus on chromosome 8 (8q24) in which several single nucleotide polymorphisms (SNPs) - changes in a single nucleotide of DNA - confer significantly increased risk of colorectal cancer (CRC). This locus has been implicated in previously published research as playing a role in prostate cancer risk.
The first study, led by a Canadian research team, used a four-stage process to identify and validate SNPs associated with CRC risk. The first stage evaluated three different sets of SNPs, containing more than 50,000 single nucleotide changes, in 1,257 people with colorectal cancer and 1,336 controls from Ottawa. The second stage tested 1,143 potential markers of risk identified in stage 1 in two different case-control populations: one from Seattle, Washington, and one from Newfoundland. The third stage tested 76 markers replicated in the previous 3 populations in a case-control population from Scotland with early-onset CRC. The nine markers further validated in this population were then tested in a fourth stage in a second, independent case-control series from Scotland.
Two of the risk associations confirmed in stage 3 were replicated in stage 4, and the investigators compared these loci, 8q24 and 9p24, with results from several European studies, leading to validation of two SNPs in 8q24 that confer significantly increased risk of CRC. This multistep replication process is in keeping with recent guidelines published in Nature by the NCI-NHGRI Working Group on Replication in Association Studies.
The second study, from the University of Southern California, directly examined 6 variants previously identified as genetic markers of prostate cancer risk in 1,124 patients with invasive CRC and 4,573 controls, all taken from a multi-ethnic study population including people of African American, Japanese American, Native Hawaiian, Latino, and European descent.
One variant on 8q24 identified as significantly associated with CRC risk in this group was then tested in 683 additional CRC cases and 938 controls in 2 substudies of patients of Japanese American and European descent. The variant was replicated as a marker of CRC risk in one study but not the other; however, the marker remained significantly associated with CRC risk in a pooled analysis of all three studies.
The third study, from the United Kingdom, successfully genotyped more than 550,000 SNPs in 930 people with familial CRC and 960 controls, designated as panel A in the study. They also identified SNPs at 8q24 as being associated with CRC risk. The investigators then tested the SNP most strongly associated with CRC risk in 3 different case-control panels (panel B comprised 4,361 patients with CRC and 3,752 controls; panel C comprised 1,901 people with CRC and 1,079 controls; and panel D comprised 1,072 people with CRC and 415 controls). Only patients in panel D had a familial history of CRC.
Pooled data from the original set of patients and the three validation panels "provided unequivocal evidence for a relationship between [the SNP] and risk of CRC," stated the authors. Further analysis of the data provided evidence that the SNP may also be associated with an elevated risk of developing adenomas - noncancerous tumors - in the colon or rectum. This observation led the investigators to suggest that the locus on chromosome 8 may be involved in tumor initiation rather than progression.
Genetic Variations Linked to Increased Prostate Cancer and Decreased Diabetes Risks
A genetic study in Icelandic men with prostate cancer and several healthy control groups uncovered two genetic variations associated with moderate increase in the risk for prostate cancer and, in the case of one variation, a simultaneously protective effect against type 2 diabetes (T2D), according to results published online July 1 in Nature Genetics.
The study involved a genome-wide association scan to search for gene sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with the disease and 11,290 control subjects. Follow-up studies with three additional case-control groups confirmed an association of two variants on chromosome 17 with prostate cancer. One of the variants is in the TCF2 gene, which the scientists demonstrated also confers protection against T2D.
The two genetic variations pose only relatively small increased risks in individuals for prostate cancer. However, because the variations are so common, they have an estimated joint population-attributable risk (PAR) of 36 percent for the disease, "which is substantial from a public health viewpoint," the researchers noted.
The scientists were "most intrigued" by the counterbalancing of risks for prostate cancer and T2D with the TCF2 variation. "The discovery of a sequence variant in the TCF2 gene that accounts for at least part of the inverse relationship between these two diseases provides a step toward understanding the complex biochemical checks and balances that result from the pleiotropic [multiple effects] impact of singular genetic variants," they commented. Previous explanations of the well-established inverse relationship between prostate cancer and T2D have centered on the impact of the metabolic and hormonal environment of diabetic men.
Second HPV Vaccine Shows Early Positive Results
Positive interim results for a candidate vaccine to prevent infections by human papillomavirus (HPV) types 16 and 18 were published online in The Lancet June 28. The vaccine Cervarix was 90 percent effective in preventing grade 2 or 3 cervical intraepithelial neoplasias (CIN2+) that contained DNA from either virus type.
The results come from a large international trial of 18,644 women aged 15-25 sponsored by the drug's manufacturer, GlaxoSmithKline Biologicals. The trial design called for analysis of early results after 23 cases of CIN2+ were detected. Two of these cases were among the 9,258 women receiving the vaccine, and 21 were among the 9,267 controls who received a hepatitis A vaccine. The mean follow-up time was 14.8 months.
In an editorial, Drs. Jessica A. Kahn of the University of Cincinnati and Robert D. Burk of the Albert Einstein College of Medicine wrote, "These interim data are encouraging." But they noted that the paper does not provide information about the public health impact of vaccination "in real world settings" because the report does not provide estimates of the reduction in overall rates of CIN2+. They stress that vaccination of young adolescents is likely to have the greatest public health benefit, but that continued screening will still be required after vaccination.
A separate phase III trial testing Cervarix, cosponsored by NCI with support from the NIH Office for Research on Women's Health and the Costa Rica Ministry of Health, is now underway in Costa Rica. This trial should provide additional information about the public health impact and efficacy of the vaccine.
International Programs Seek Applications
NCI's Office of International Affairs (OIA) is seeking applications to two projects.
The U.S.-Japan Cooperative Cancer Research Program (USJCCRP) began in 1974 and is coordinated by NCI and the Japan Society for the Promotion of Science. With the assistance of OIA, USJCCRP is establishing an annual workshop in basic, clinical, or epidemiological/behavioral science to support cancer research and clinical care.
The workshop venue will alternate between Japan and the U.S. For 2007-2008, USJCCRP will provide support for a basic science cancer workshop. Participation will be limited to 20 attendees from each country, allowing for a small number of participants from other countries. Requests for proposals (RFPs) will be conducted by an open call each June, with an application deadline in September, selection in October, and the workshop held between November and March.
The RFP for the 2007-2008 meeting was released on June 29. Individuals with the skills, knowledge, and resources to plan and conduct the proposed workshop are invited to develop an application for support. The first workshop can focus on any area of basic science. However, USJCCRP is particularly interested in receiving proposals in 1) regulation angiogenesis and lymphangiogenesis in cancer cells, 2) nanotechnology applications in cell imaging, diagnosis, and treatment, and 3) genomics and proteomics of cancer cells. More information and an application form can be found at http://www.cancer.gov/oia/US-JAPAN-CCRP.
The Ireland-Northern Ireland-NCI Cancer Consortium recently announced a call for applications in its Joint Research Projects in Cancer 2007.
This project aims to develop strong and sustainable relationships between cancer researchers and institutions in Ireland and the U.S. by supporting a shared postdoctoral researcher working on a research project of mutual interest. The project is awarded on a full-time basis over 3 years and is open to cancer researchers working on the island of Ireland or in the NCI intramural or extramural program.The closing date for applications is 5 p.m. on August 17. Full details and application guidelines can be found at http://www.allirelandnci.com/fellowships_and_training/
The Mathematics of Cancer
To most people, soil nematodes - microscopic parasites critical to the breakdown of organic matter in soil - would appear to have no relation to cancer research. But Drs. Vito Quaranta and Alexander "Sandy" Anderson might beg to differ. A collaboration between the two to develop complex mathematical models that drive computer simulations of tumor invasion began with adaptation of a model developed by Dr. Anderson designed to predict soil nematode migration.
"Mathematicians have been doing cancer modeling for 50 years," says Dr. Quaranta, director of the Vanderbilt University Integrative Cancer Biology Center. But it's only in the current decade, he adds, that cancer biologists have connected with a new generation of mathematicians like Dr. Anderson, from the University of Dundee in Scotland, to develop mathematical models intended to capture and integrate the complex factors involved in cancer development, progression, and metastasis.
This in silico movement in cancer research truly is in its nascent stages. Only a handful of laboratory and clinical cancer researchers are seriously collaborating with biological mathematicians, and in silico studies are only now breaching the upper echelons of oncology journals.
But according to Dr. Daniel Gallahan, head of NCI's Integrative Cancer Biology Program, which is supporting the development of in silico cancer research, the time and need for it have arrived.
Cancer researchers have done a remarkable job of discovering and characterizing the important biological and molecular parts of the cancer process, Dr. Gallahan stresses, including genes, intracellular signaling pathways, and, more recently, microRNA.
"But once you start trying to assemble all of those pieces, that's when it becomes daunting," Dr. Gallahan says. "That's when it becomes a real challenge for human understanding and intuitiveness to look at a situation and extrapolate what is actually happening."
Computational modeling, he continues, can help to develop a fuller picture of cancer as a complex biological system, and help better assess what factors within and around a given tumor decide its fate. Evidence to support that belief is mounting. In silico studies published over the past few years, for instance, have highlighted the tumor microenvironment's potentially critical influence on tumors.
These studies include an October 2005 study published in Clinical Cancer Research by Dr. Vittorio Cristini and a team from the University of California, Irvine, that described computational simulations of brain tumors suggesting that a tumor's aggressiveness, as indicated by its shape, or morphology, was greatly influenced by factors such as the amount of oxygen in its environment. Sufficiently oxygenated microenvironments led to spherically shaped, localized tumors, while oxygen-choked surroundings, including those created by simulated anti-angiogenic treatment, generated tumors that snaked out into nearby tissue.
And in December 2006, Drs. Quaranta and Anderson, building on a paper published in March 2005 in a mathematics journal, published computational simulations in Cell predicting that a harsh tumor microenvironment driven by tissue heterogeneity or lack of oxygen availability caused more aggressive cells to dominate the tumor and form finger-like protrusions that invade adjacent tissue.
The implication, Dr. Quaranta notes, is that malignant cells are most likely to develop in certain microenvironments and that altering the microenvironment may make tumor cells less invasive.
"These neurosurgeons are telling me that that's what they have seen over and over in their patients," he recalls. "The model predicted those [tumor shapes] and it did not use any of their data."
Now at the University of Texas School of Health Information Sciences at Houston, Dr. Cristini has begun collaborating with researchers at the University of Texas M.D. Anderson Cancer Center. Using one of the most powerful supercomputers in the world at the Texas Advanced Computing Center, they will run intensive simulations to do things like predict tumor responses to various microenvironmental conditions, including those caused by therapies, and use the simulation results to develop and test new treatment strategies.
Generally speaking, the mathematical models that drive these computational simulations use the available data - both previously published and new experimental data - to populate the "parameters" of the activities they are trying to simulate. This includes, for example, measurements over time of gene and protein activity within cells or of important cell behaviors, such as adhesion to other cells.
Although some models are devoted to whole tumor simulations, Dr. Gallahan notes, a number of models are focused strictly on intracellular signaling networks that control all cellular processes.
Dr. Thomas Deisboeck's computational modeling work, which also has involved brain tumors, represents a blended approach, with a particular focus on how the intracellular signaling pathway directed by the epidermal growth factor receptor (EGFR) influences tumor development.
Dr. Deisboeck, the principal investigator of the Center for the Development of a Virtual Tumor - housed at Massachusetts General Hospital, but composed of researchers from around the world - believes computational modeling is beginning to make important inroads.
"We're...generating exciting hypotheses that can be experimentally tackled and getting data back from those experiments that help to fine-tune and improve our models," he says.
For example, Dr. Deisboeck's team recently collaborated with researchers from the Arizona-based Translational Genomics Research Institute to conduct experiments in cell lines that followed from their in silico simulations. Those simulations assessed EGFR's role in whether brain tumor cells proliferate or migrate (it's believed they tend to do only one or the other at a given time), and the impact those cellular "decisions" have on tumor development. The results (soon to be submitted for publication), he says, "validate our in silico predictions quite nicely."
Such experimental validation is critical to expanding the in silico field and, eventually, integrating computational models into traditional wet lab experiments, clinical trials, and even clinical care, says Dr. Gallahan."It's still far off, but we can envision a time when we can establish a specific model for a specific cancer, plug in an individual's own parameters, and see…how an individual will respond to treatment before we even try it, based on a sophisticated model of the cancer process," he says. "The key will be achieving that level of sophistication."
- Carmen Phillips
An Update on Cancer Vaccines - New Paradigms
Many deadly infectious diseases that were capable of killing millions are now tamed because of vaccines, which stimulate the immune system to recognize and attack pathogens before they can cause disease. Soon it may be the same for cancer.
The first major step toward this goal came recently when the FDA approved and Merck began marketing Gardasil for the prevention of human papillomavirus (HPV) infection, a major cause of cervical cancer. HPV vaccines represent one type of cancer vaccine, which may prevent cancer before it occurs, while therapeutic cancer vaccines may help turn a patient's immune system against already-existing cancer cells.
"There is an enormous amount of progress being made in the field of cancer vaccines," says Dr. Jeffrey Schlom, chief of NCI's Laboratory of Tumor Immunology and Biology, in the Center for Cancer Research (CCR).
However, he points out, therapeutic cancer vaccines - those that attack solid tumors, rather than preventing conditions that cause cancer - will most likely be used to treat early-stage disease or metastatic disease where the overall tumor burden is low.
"There are limits to what vaccines can do," Dr. Schlom says. This is because with a large tumor mass, the lymphocytes activated by the vaccine must pit themselves against a large number of cancer cells, where the odds are unfavorable. "A good analogy is hand-to-hand combat," he explains. Research in the last few years has indicated that vaccines may be most effective following surgery to remove the bulk of the cancer and when used in conjunction with other standard treatments.
The strategy may be particularly effective if a vaccine is administered simultaneously with chemotherapy or radiation, which seems to make tumors more vulnerable to detection and attack, as well as with vaccine boosters and cytokines to augment the immune response. Dr. Schlom described this phenomenon in a review article in the July 1 issue of Clinical Cancer Research, where he contrasted the dynamic immune processes triggered by vaccines with passive therapies such as drugs or radiation.
Randomized phase II trials testing these vaccine strategies have shown an increase in median survival of 4 to 8 months over controls, with overall survival as long as 3 to 5 years at the time the data were published. Survival could be much longer, as many of these trials continue.
Dr. James Gulley of NCI's CCR is leading five phase I and II clinical vaccine trials at the NIH Clinical Research Center to test immunostimulant additives, antibodies, and viral vectors that produce tumor-associated antigens, as well as the effect of vaccines injected into tumors.
"With vaccines alone we have seen clinical responses in patients with prostate, ovarian, and breast cancer. The addition of an anti-CTLA-4 antibody to a vaccine appears to further improve the clinical benefit in a proportion of patients with metastatic prostate cancer," he notes.
Dr. Philip Arlen of CCR collaborates with Dr. Gulley and is leading two phase II trials at the Clinical Research Center to test the combination of hormones or low-dose, single-agent chemotherapy (which is less toxic than standard multidrug regimens) with vaccines in patients with prostate or breast carcinomas. Preliminary results of these studies show that the vaccine treatments are well tolerated, and some patients have received treatment for more than a year without disease progression.
"We have preliminary evidence that therapeutic cancer vaccines can provide patient benefit," Dr. Arlen says. "Here at NCI, we're able to go further with small, cutting-edge studies that address how we should utilize them - in what populations, for example, and with what combination of treatments." He is currently planning clinical trials to test hormone therapy and allogeneic stem cell transplantation as part of the vaccine treatment strategy.
More than a dozen vaccines are in or nearing phase III trials to refine their use, including dosing, booster schedules, and the site of vaccine administration. But for now, the FDA has not approved any therapeutic cancer vaccines.
"I'd like to think that cancer vaccines will be approved by the FDA within the next 5 years," says Dr. Schlom, "perhaps one or two within the next couple of years. But we can't say for sure because we need a paradigm shift, first, in the way that vaccine trials are designed and how they are evaluated."
Dr. Schlom points out the case of Provenge, a vaccine for advanced prostate cancer that was reviewed by the FDA this past spring, showing an increase in patient survival but not a reduction in tumor progression, which was the study's primary endpoint. "Most likely, this was because the vaccine was able to keep the disease in check, but not able to reduce the overall tumor load," he says.
Ethically, patients must be offered treatments with demonstrated benefit before they are offered experimental ones. So a patient who enters a therapeutic vaccine trial has likely already gone through surgery, disease metastasis, and then one or more rounds of adjuvant treatment, including chemotherapy, radiation, or hormone treatments. "By this time, many patients have large tumor masses again, which is not the ideal setting for a vaccine trial," says Dr. Schlom."We're just getting to the point where we're able to think about doing these studies in combination with or versus standard-of-care therapy," says Dr. Schlom, noting that NCI and FDA held a conference at NIH last February to discuss how vaccines and other immunotherapies can best be brought through development to licensure. "But for advanced disease," he says, "other immunotherapies will likely be more useful."
For more information about cancer vaccines, view the NCI fact sheet online.
- Brittany Moya del Pino
Biological Therapy for Advanced Kidney Cancer or Melanoma
Name of the Trial
Principal Investigator
Why This Trial Is Important
One of these proteins is called transforming growth factor beta (TGF-β), which is overproduced by many types of cancer cells. Therefore, researchers are interested in developing new drugs or biological agents that can bind to and possibly block the activity of this protein.
This trial will assess the safety and tolerability of a new biological agent called GC1008 in patients with advanced kidney cancer or melanoma. GC1008 is a monoclonal antibody specifically designed to target TGF-β and block its activity.
"TGF-β is known to play a major role in the progression of kidney cancer and melanoma, two types of cancer that are notoriously difficult to treat when advanced," said Dr. Morris. "We hope that treatment with GC1008 suppresses TGF-β in these tumors and leads to a delay in cancer progression or even causes tumors to shrink."
Who Can Join This Trial
Study Sites and Contact Information
An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.
NCI Cancer Bulletin Wins Award
Disparities Summit Scheduled for July 16-18
The summit will bring together some of the nation's top researchers in the field of cancer health disparities. NIH grantees, health professionals, and community advocates from across the country will gather to discuss their research, successful program strategies, challenges, and accomplishments.
This year's summit is sponsored by NCI's Center to Reduce Cancer Health Disparities, the National Center for Research Resources, and the National Center on Minority Health and Health Disparities. To register or obtain additional information, go to: http://cancermeetings.org/CHDSummit07/.
CCR Publishes New Magazine
Advocacy Summit Summary Available
If Memory Serves...
During its first 2 years, NCI established research fellowships to train cancer researchers from many different fields. By 1943, 40 people had completed these research fellowships. (Read more)
For more information about the birth of NCI, go to http://www. cancer.gov/aboutnci/ncia.
The first summit meeting between NCI and cancer advocates was hosted by the NCI Director's Consumer Liaison Group in June, 2006. The meeting brought together consumer advocates from 33 states and 111 cancer advocacy organizations to enhance collaborations and partnerships between the advocacy community and NCI. Copies of the summit summary and evaluation can be requested from firstname.lastname@example.com.
BSA Meets in Bethesda
Following are newly released NCI research funding opportunities:
Methods of Statistical Analysis of DNA Sequence Data for Studies Relating Variation to Disease
This funding opportunity will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3740. Inquiries: Dr. Thomas Lehner - firstname.lastname@example.com.
Reducing Health Disparities among Minority and Underserved Children
This funding opportunity will use the R21 (PA-07-391) and R01 (PA-07-392) award mechanisms. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3741. Inquiries: Dr. Shobha Srinivasan - email@example.com.
Major Journals Expand Clinical Trial Public Registration Requirements
The International Committee of Medical Journal Editors (ICMJE) - which includes the editors of many of the world's best-known, prestigious medical research publications - recently announced an expansion of its 2005 policy requiring that clinical trial investigators and sponsors provide detailed information about their studies in a publicly accessible registry before the start of patient enrollment as a prerequisite for publication of the results in an ICMJE member journal.
The expanded policy was announced last month in an editorial in the ICMJE member publication New England Journal of Medicine. Effective July 1, 2008, the expanded policy for the first time requires registration of all studies designed to investigate a medical intervention on a health-related outcome, including phase I studies and phase II studies not covered by the earlier policy. Previously, phase I studies and phase II studies that lacked a comparison or control group were exempt from trial registration requirements.
"The ICMJE recognizes the potential benefit of having information about preliminary [phase I] trials in the public domain, because these studies can guide future research or signal safety concerns," noted the editors of the 12 ICMJE member journals, which also include the Journal of the American Medical Association, The Lancet, and MEDLINE, which is published by the National Library of Medicine.
When the ICMJE announced its original policy 2 years ago, requiring the registration of some phase II trials and all phase III and phase IV trials, it generated controversy and concern that the requirements would prove cumbersome or stifle competition. Since then, however, "the research community has embraced trial registration," the editors noted. Before the ICMJE policy, ClinicalTrials.gov, the largest trial registry at the time, contained 13,153 trials. In April 2007, the registry contained more than 40,000 trials, with more than 200 new trial registrations occurring weekly.
The ICMJE's trial registration requirements have been widely adopted by non-member medical journals. "We hope that [non-ICMJE journals] will also adopt the modifications discussed in this update," the editors wrote.
The requirements have caused many investigators and trial sponsors to request that the ICMJE recognize their local databases as registries in compliance with the registration policy. In response, the ICMJE has supported efforts by the World Health Organization (WHO), through the WHO International Clinical Trials Registry Platform (ICTRP), "to develop a coordinated process for identifying, gathering, de-duplicating, and searching trials from registries around the world." In addition to the five currently approved registries, the ICMJE will now also accept registration in any of the primary, nonprofit clinical trial registries that participate in the ICTRP.
NCI, through its Physician Data Query (PDQ®) Cancer Clinical Trials Registry, has also become an active participant in the worldwide clinical trials registration movement. PDQ works with ClinicalTrials.gov to ensure that NCI-sponsored trials are registered in that registry in compliance with ICMJE requirements. Furthermore, the PDQ registry is a partner register within the ICTRP Network of Collaborating Clinical Trial Registers; Lakshmi Grama of NCI's Office of Communications and Education, who manages the PDQ registry, has recently been appointed chair of the ICTRP Registers Working Group.


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Graveside services for Maxine Seegers Rosier will be held Tuesday, June 21, 2011 at 10 a.m. at Lane Memorial Cemetery in Sibley under the direction of Rose-Neath Funeral Home. Officiating will be the Rev. Jeff Chandler. The family will receive friends from 5 until 7 p.m. today (Monday, June 20, 2011) at Rose-Neath Funeral Home in Minden.
Maxine was born March 30, 1925 in Heflin and entered into rest June 18, 2011 in Minden.
Her son, Jerry Hamm; grandson, Michael Haynie; parents, Floyd and Gussie Seegers; sister, Joy Shelton; brothers, E.M. Seegers and Floyd Seegers, Jr.; and niece, Dianne Roton Chandler preceded her in death.
She is survived by her daughter, Judy Chandler and husband, Allen Ray of Sibley; grandchildren, Dianna Monroe of Ringgold, Tony Chandler of Ringgold and Danielle and Christopher Hamm of Rayne; great-grandchild, Hailee Chandler of Ringgold; very special great-great-granddaughter, the light of her life Faithlyn Chandler, Gracie Lynn Hamm and Braydon Hamm of Rayne; nephews, Danny and Rusty Roton of Haughton; and numerous great-nieces and great-nephews.
Pallbearers will be Mark Monroe, Tony Chandler, Christopher Hamm, Ben Roton, Jacob Roton, Danny Roton and Rusty Roton.


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RT @ChrisCuomo: More government and electeds in #Ferguson trying to keep the peace and as sun goes down it is controlled if not quiet
Obama: It's not a bigger government we need, but a smarter government that sets priorities and invests in ... growth.
Obama: Let's agree, right here, right now, to keep the people's government open and pay our bills on time.
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RT @CNNPolitics: Obama speech to focus on drones, Gitmo
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U.S. Attorney General: 4 Americans have been killed in counter-terrorism drone strikes since 2009. More on .
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Chad Myers: Debris left from tornado "looks like a bowling ball" rolled through & destroyed everything in its path.
Daytona 500 will run as scheduled today despite fans being hurt Saturday when crash flung debris into grandstands.


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Flat Card Case
best complemented withPrevious Page
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Signature Leather Reversible Belt
Mobile Power Pack
Electric Grounded Adaptor
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We ask that the product be unused, in original boxes (whenever possible), and with all paperwork, parts and accessories in order to ensure credit. Sale merchandise will be issued a credit at the current selling price. Unused items purchased on www.tumi.com can also be returned to a US Tumi full price location. Please make sure to have all paperwork, parts and accessories to ensure credit. Store credit will be issued for items without documentation.
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Oct 02, 2012 | 02:54 PM
| Michael Cowden
Canadian Auto Workers,
Ken Lewenza,
Al Iacobelli,
labor contract,
General Motors
CHICAGO Canadian Auto Workers (CAW) union members have ratified a new labor contract with Chrysler Group LLC.The move finalizes a round of contract negotiations between the CAW and the Canadian operations of the Detroit-areas Big Three automakers: General Motors Co., Detroit; Ford Motor Co., Dearborn,....
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Are you stocking more inventory today than 18 months ago?
We actually don't know who his investors are. At the point when we are ready, we will investigate further. There are just so many things to handle and there are a lot of items to be considered with the project."
-- Charles C. Mitchell, Barstow city manager


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Shonia - Thank you for comment on my daughter's name, we love it. I so desperately wish she was with me though, but God had other plans. I am also a Christian and have hard times dealing with God over these last months. I am now in a place where I feel God's plan. We will never know "why", but we have to trust in His plan. Knowing one day we will all be together in His Kingdom. I try to focus on the positive things that have come out of Faith's short life and that helps. Everyday I desperately want to cry out to Him WHY, but I work hard everyday to trust in Him. Tonja's post definately expressed my feelings too.
I pray that you are able to find peace and have a wonderful pregnancy. I understand your feelings with this baby, because I know I would feel the same. We are going to try again this summer and I pray to God that His will be done if I am to have another child and I pray to Him that he puts a veil of peace upon me. God bless.
mommy to:
Tyler - almost 4
Angel baby - January 2003 (11 weeks)
Faith Kristine - 1/5/04-1/30/04 (born at 30 weeks due to severe preeclampsia, passed due to NEC (intestinal premie complication))


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A Cherokee County home was destroyed in an early morning fire.
According to authorities on the scene, the fire broke out around 6:30 a.m. on County Road 3502 at County Road 3522 near Cuney.
Fire crews and EMS responded to the scene and when they arrived the house was already fully involved.
The homeowners had taken their children to school, and when they returned the house was on fire. No one was inside the home and there were no injuries.
The cause of the fire is still under investigation.
Copyright 2012 KLTV. All rights reserved.


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With its friendly pricing, fast performance, and handy personal cloud features, the WD My Cloud EX2 is an ideal network storage device for a small connected home.
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Despite a few minor shortcomings, the DIR-880L is still one of the best 802.11ac routers on the market.
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Though feature-rich, the Skydog's hardware is too slow and limited to justify its high cost and ongoing subscription pricing.
With a full array of multicolor LEDs and promises of IFTTT compatibility, this smart-home conversation starter might prove surprisingly useful.


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Feel better Suja.
Bridget, I don't know what I would have thought if I'd have seen that & not known you! lol...what a kid!!! Bless his heart.
Jennifer, we had aplix and I found after 1 year they didn't work well. They started curling and coming undone easily. But that is after 1 year of use. I think I would have both snaps and aplix. I know snaps take longer and if the baby is squirmy, forget about it!
Shelley-mom to DS, 6
Oh that would be ok. I have mostly gotten aplix now....just seems easier to use. They only go to about 18 lbs so I figured that when I buy the size 2's (go to 40 lbs), maybe will go snaps for those if baby is one who thinks taking diapers off is fun. I'm not super concerned about resale....I might keep if we should end up with a miracle pg....or maybe if my sister has a baby after me.
I'm feeling all dizzy and woozy and nauseated from getting 2 hours of sleep, too much coffee, and on the verge of getting this illness that DH has had for the past two weeks. I've been letting the kids watch tv and draw this morning while I've been spending time on the computer and sitting down. When I got up to make breakfast I regretted it.
DS made an adorable birthday card for a party we're going to today. He drew a building full of toys that would be really fun to play in and a person and a smaller upside-down person next to it. He said that was the birthday girl, and next to her was her shadow, and it was on that side of her because the sun (also pictured) was on the other side.
I've been explaining voting more to the kids because they've been seeing a bunch of lawn signs about YES on 32 and VOTE FOR whatever and we've been getting a lot of flyers in the mail. I gave an example of how if we were going to choose the music we listened to in the car by voting, we would have some options and we could raise hands and select the music by majority. That day, rock and roll won because DS and toddler S. voted for it. They loved the idea of choosing things by voting.
The next day, DD said, "Let's vote to see who wants me to get a Barbie for Christmas." The three kids raised their hands.
She added, "Who in this car wants to BUY me a Barbie?" The two boys raised their hands. Her eyes shone, and she thanked them delightedly.
She then finalized the deal by saying, "Who WANTS to get a Barbie for Christmas?" She and toddler S. both raised their hands. She queried, "YOU want a Barbie, too?" He nodded vigorously. She said, "That's great! I'll get a Barbie from you boys, and I'll buy a Barbie for you! It will be a wonderful Christmas!"
None of them have any money, btw.
I have a feeling the voting thing is not fully understood.
L, you''ll have to explain dictatorship to the kids next. Lol
Just tell 'em it's a Momocracy until they're 18 --- a Papacracy too if you're feeling generous to J. Hee Hee.
Suja, hope you 're already feeling better.
In other news this man was caught cruising the elementary school a half mile from my house:
So scary!
(That was yesterday, btw. He's in custody now.)
L, that's great! You're kids are a hoot! So, you're really considering letting C have a Barbie?
Oh Myles. Ick. What is wrong with people? What a sick b-stard.
We went for a long joyride to look at the fall leaves and stopped at a park. I tried stopping in at my dad's at the end of all that but Conner was at his limit and wouldn't behave. We left after just 20-30 minutes. All in all, it has been a great day. I needed it to remind myself why I had kids because honestly, Bobbie has me questioning what I was thinking.
Hi ladies! It's been forever since I've gotten a chance to get on here! Life is mad crazy, but just wanted to pop in and say I miss ya'll
We were worried about you! Nice to see you in here again.
Me (40) DH (47) & furbabies * m/c 7/08 4/12 11/12
The course load this year has been insane. The Accounting courses are kicking my a$$! I don't get much PC time these days
Gah I'm irritated. My brand new van with less than 1600 miles is leaking oil. Realized it tonight when we pulled back in from a trip to Target. Called and got an appt for first thing Monday morning. Put some cardboard under it to help the garage floor not get too icky....since it's only two years old, it was basically perfect condition until today.
I'm really hoping that this is just some clamp or screw that wasn't totally tight and no big deal. Of course it's under warranty but still hate bringing him in. His name is Leo and I love him.
That schedule sounds insane! My semesters were 15 weeks, but we had 1 week breaks in the middle of them, and then a month between fall & winter semester. I think when a class is spread out over 15 weeks, the coursework is easier to manage. Especially if you have kids. I don't know how you're doing it. I'm impressed.
Hi, Xtina!! College is much harder than real life in many, many ways. Hang in there!!!
Ugh, Jennifer. That'd make me so
mad, whether major mechanical issue or not.
I have no hot water and my gas hot water heater is so cobbled together I don't dare touch it myself. I'm 75% sure it's just that the pilot went out, but because my landlords are the kind that have the 'f it, that's good enough' when they put things together, I'm afraid to try to light the pilot myself. I talked to Rich and he's gonna look at it, but I'm not sure I even want him touching it. Ugh. I really don't like living here & it's only been 5 months.
Gas water heater. Don't mess around with it, Chrissy. Can you call someone to fix it and take it off the rent?
I'm going to see what Rich says when he looks at it...if it's more than the pilot, or if he sees something that makes him leery of it, I'll have to call the landlords. I tested my carbon monoxide detector, just in case, and I couldn't get the **** thing to shut up. At least I know it works!
The time will pass fast. Soon enough, you'll be looking back wondering where the time went.
I found out, on Facebook no less, that Jesi is engaged. This is the girl that was never, ever, never going to get married. She's also sworn adamantly she'll never have kids. I told her next she'll be planning a baby, but she's sticking to that "I'll NEVER have kids!" routine. For now. There's no ring and no date set, so I'm not at all worried. If anything, I think it's more cute than anything else really. I always knew that once Jesi fell in love she'd fall hard. She was always so 'easy come, easy go' about boys. I don't think one of them ever broke her heart. The plan is for 'after college' so I anticipate this being a very long engagement.
I adopted a 16 year old cat today. There was an email out to my list at work about him. His mommy was put in a nursing home and the adult son stopped coming to care for him. He went to the neighbor's (my colleague), but they have 2 younger cats that loved to antagonize him and he'd much prefer to be alone. He doesn't care for other felines. Anyway, I saw that they were going to send him to the SPCA if no one offered a home for him, and the idea broke my heart. I miss Bobbie's cat, so it just seemed like a win/win for everybody.
I gotta say, he's a real affectionate sweetheart. After an hour-long ride in the car the first thing he did was chow down on Missy's food. I couldn't get his opened and poured fast enough. I think he'll fit in just fine.


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Dec 28, 2007 | 10:04 AM
An expanded North American presence for Australia's BlueScope Steel Ltd. would provide a strong platform for growth, a top executive at the Australian company's Butler Manufacturing Co. subsidiary said in an interview with AMM.
It's too early to disclose any specific expansion plans, Patrick J. Finan, president of Kansas City, Mo.-based Butler Manufacturing, said. But the Australian steelmaker will focus in the short term on supplying more substrate to its existing and newly acquired business, he said.
"There is a tremendous amount of leverage in the vertical supply chain—from hot-rolled coil from Australia all the way through the building products in North America," Finan said.
BlueScope is also a partner in flat-rolled producer North Star BlueScope Steel Co., Delta, Ohio.
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This site has now been superseeded by the new Shakinda Productions Website, This one will remain live here for those who still want to read posts etc. You may also be intersted in the Quartz Composer Book Site and We would love you to come say hello on the Shakinda Facebook or you can follow us on twitter thanks for all who supported the vj gigs and here's to the future!
Its been very busy at Shakinda recently and hard to know where to start on the news front. Great workshops at the Urban Arts Academy in Belfast, Fun gigs with Nakatomi towers at Stiff Kitten and continued residencies at Lush! and Yello. More production work for the new Yello visuals and DVD and Play and Wired and Belfast Exposed. We have now launched vj equipment rental services in response to popular demand!
Realtime Motion Graphics with Quartz Composer is a book and DVD project authored by Shakinda & Surya Buchwald, to be published by Pearson. Started nine months ago, this project aims to introduce Quartz Composer as a very powerful and fun graphical programming environment. Despite its massive potential for real-time audio reactive solutions, Quartz Composer is still mainly publicized for the creation screensaver, and remains woefully under-used as a visualization tool. The Mastering Quartz Composer book could change this forever.
This book and DVD shows the full potential of Quatz Composer, from taking a complete novice through the software setup process and getting to grips its interface, all the way to enabling the modelization of complex 3d audio reactive environments, midi interaction, to retrieving online database information.
After a late booking and sudden return from the slopes in France, Shakinda once more rocked the Planet love visuals. This time it was just outside dublin, shakinda vjed alongside Ferry Corsten, Judge Jules, Sander Van Doorn and Alex Kidd. The 5000 capacity gig had been sold out for weeks and everyone came to party!
Over on the dev blog Shakinda has just uploaded a new video tutorial to help vjs get up and running with quartz composer on mac osx leopard. Check it out and get VJin!
Tomorrow night will see the long anticipated beginning of Shakinda's weekly residency at the Belfast art college. A lengendary venue which was always had a big influence on the local scene will now be home to another of belfast's rising stars. Doors 9pm...


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RT @nytimes: The Lede: Live Updates on the Gun Debate
RT @thomaskaplan: Hundreds have gathered outside the Capitol in Albany to protest New York's new gun laws.
RT @nytimes: Breaking News: At Least 37 Dead in Oklahoma Tornadoes, Medical Examiner Says
RT @nytimes: Breaking News: Nicolás Maduro, Heir to Hugo Chávez, Wins Close Election for President of Venezuela
RT @nytimes: Breaking News: Former Prime Minister Margaret Thatcher of Britain Has Died
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Secret. RT @EleanorRandolph: And replacing it with what? NYT: New York Mayor Lauds Companies for Cutting Salt Content
RT @thomaskaplan: Hundreds have gathered outside the Capitol in Albany to protest New York's new gun laws.
RT @nytimesvideo: Video: Meet New York's Couch Doctor -
RT @nytimes: Graphic: The site where a NYC subway construction worker was stuck in mud
RT @nytimes: Yahoo has eliminated working from home, saying it makes workers less productive. Do you agree? Include #TellNYTBiz
RT @darlin: Lonely oil rig workers download some porn and pirated media and malware with it. Sleep well, coastal residents.
RT @greenhousenyt: In worst flu season in years, 39% of private-sector workers aren't entitled to paid sick days.
RT @nytimes: All NYC police are reminded that women may go topless
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RT @nytimes: Jerusalem bureau chief @rudoren is taking your questions about Obama's trip to Israel. Ask using #NYTworld.
RT @JenniferPreston: In Kenya, Half Brother to Obama Runs for Governor
Youngest Obama staff are moving on RT @MarkLeibovich:
RT @nytimes: Obama to Renew Drive for Cuts in Nuclear Arms
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RT @StephanieYonus: SHEETZ! Only thing that makes a trip to PA worth it :) RT @palafo: Sheetz or Wawa, you must take a side.
RT @jodikantor: Do yourself a favor: pour another mug of coffee and read @dwightgarner's account of trip on the QE2
RT @nytimes: 2 Killed When Jet Crashes in Indiana Neighborhood
RT @nytimes: Last-Lap Crash in Nationwide Race Injures Fans
RT @sbnation: The original video was blocked by NASCAR on copyright claims. Here is the crash from the stands.
RT @BuzzFeedNews: RT @nycsouthpaw: NASCAR is getting very aggressive about suppressing videos of the crash; this one was shot by a fan.
RT @nycjim: Video of final laps of Nationwide Daytona race, including huge crash at checkered flag.
RT @AntDeRosa: Video taken in the stands of Daytona NASCAR crash right where one tire landed
RT @nytimes: Jorge Mario Bergoglio of Argentina, Pope Francis I, is the first pope from the Americas
RT @RachelDonadio: I'm about to speak on Timescast about the pope's resignation!
RT @nytimes: Follow The NYT's @RachelDonadio for additional updates on Pope Benedict XVI's resignation.
RT @damiencave: The next pope? A decent chance he comes from Latin America. The candidates are:
RT @fivethirtyeight: No pope has resigned since 1415, which is also the last time the Pittsburgh Pirates had a winning record.
RT @RealClearWorld: Full text of Pope Benedict XVI's resignation statement:
RT @nytimes: Photos: 478 looks from the Oscars red carpet reaching back to 1997
RT @JoyceCarolOates: Best thing about the Oscars is that N Y Times film critics will finally have to cease writing breathlessly about who will win.
So when ARE the Oscars? Red carpet at 7pm EST, awards at 8:30pm EST. Watch related NYT video timed to commercials on your second screen. :)
RT @MartinBeck: @jeridansky @harrisj plus I would argue that that Oscars post has plenty to offer readers interested in the topic.
The icons are creepy. RT @phaoloo: Social media Oscar picks for 2013 [infographic]


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The Worx Handy cut 310W Mini-Circular Saw is handy, lightweight and powerful thanks to its 310W motor. Ideal for projects in which a standard circular saw would be awkward to handle. This product cuts materials circular saws don't, e.g. tiles, stone, aluminium, plastic, brick. Perfect for plunge cuts with an adjustable depth laser alignment and LED illumination.
*Free delivery over £50 refers to home delivery orders placed on diy.com only. Charges refer to the value of goods being delivered and excludes delivery from stores or services. Excludes bulk delivery.
B&Q accepts the above cards and also offers a range of in-store financial services. Learn more
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Recent Blogs
personally i believe tupac shaker is the greatest rapper of all time, sure he's not the most lyrical, nut in my opinion he is the greatest. for these reasons, Tupac only grew to be 25 years old and is still remembered and still thought to be the g.o.a.t just think about if Tupac lived to be 40 like eminem has then tupac would be running the rap game single handedly. this is just my opinion,...
Big Sty released what some may call an open letter to Hip Hop artists Kayne West and Jay-Z, using psuedo religion as a marketing strategy. His song is calling for the return of honesty and trueness in Hip Hop. "Make God Bleed" is a reminder to Hip Hop Icons about their simple beginnings, humble mistakes and stumbles in the industry. Big Sty's "Make God Bleed" is a reality check not just to...
WEST COAST!! ALL I REPRESENTED.. MY DREAM IS TO BE BECOME ONE OF THE BEST ARTIST IN THE MUSIC INDUSTRY.. I KNOW ITS NOT EASY, BUT IT'S ALL I GOT.. i'M A INDEPENDENT MULTI-TALENTED ARTIST.. RECENTLY DROPPING MY FIRST SOLO ALBUM.. I PRODUCED ALL MY BEATS, WROTE ALL MY SONGS, RECORDED AND MIXED ALL MY TRACKS.. SOME COMPARE MY STYLE TO SUCH ARTIST AS TUPAC, NATE DOGG, MASTER P..I'M ALSO BILINGUAL...


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Narrow your search
The Samsung Series 7 Slate 700T is the fastest Windows 7 tablet we've tested, and paired with its optional accessories, it provides a very laptop-like experience, but one marred by the typical awkward onscreen Windows typing experience.
This near-ultrabook packs in processing and graphics power, along with an optical drive, at a reasonable price. The only real knock against the Pavilion m6 is that some of HP's higher-end systems hardly cost more.
Pricing not available
The 8-inch VivoTab 8 is a Windows tablet that doesn't particularly stand out in a crowded field, until you discover the Wacom stylus tucked inside its body.
Samsung's midprice Series 5 UltraTouch looks and feels like a more expensive machine, but keeps it simple by skipping the complex hybrid mechanics of so many new Windows 8 systems.
One of the few standout products from the first wave of Windows 8 laptops, the Acer Aspire S7 proves that Apple does not have a monopoly on great design.
Budget laptop shoppers looking for pure performance for $800 should flock to the Acer Aspire V3-571G-9435, but those looking for a comfortable, easily portable laptop should look elsewhere.
The business-oriented Lenovo ThinkPad X1 has a few quirks, but is otherwise a very impressive business-oriented ultrabook with strong crossover potential.
Stuck between a budget model and a high-end, feature-filled model, this middle Asus Zenbook is a slim, slick ultrabook, but also a tough sell.
A high-end big-screen multimedia laptop that's pretty portable (for a desktop replacement), the Samsung Series 7 Chronos is what we imagine a 17-inch ultrabook would look like.
Sony's first ultrabook, the Vaio T, doesn't fall far from the tree of other thin Sony laptops like the Vaio Z, but it's far more affordable: this is ultrabook-as-budget-laptop, not ultrabook as high-end computer.


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This is a "machine-selection optional" part.Please choose a vehicle to see the options specific to your machine,choose from all of the options below and add to cart.
User Tip: If you're unsure of your vehicle type, you may skip the machine type selection box.
"Customer service is priority #1 at Rocky Mountain ATV/MC. We value our customers and strive to be the best shopping experience- when you buy from us, you are buying lifetime service."
-Dan Thomas, CEO and Founder
We take pride in offering no hassle returns. In the event of a return, please call, email or chat with us to receive a solution to the problem. For apparel that doesn't fit quite right, Click here to see our Fit Guaranteed Program.
We will stand behind all products we sell with regards to manufacturing defects in workmanship and material. Most products are limited to the manufacturer's warranty. However, we will do everything in our power to take care of the problem.
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(Leave email if after hours)
Call us: 1 800 336-5437
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Each review submitted enters you into a $100 gift card monthly drawing, and a $500 gift card quarterly drawing!
Comments On Sep 01, 2014:these babies last longer and hold the tire tighter to the wheel, they look cool to if you get a colored cap to boot. lighter than the stock ones
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Comments On Apr 11, 2014:If you like fixing flats on the trail or track this is the rim lock for you. Took a few rides and flat repairs on the trail to discover that these rim locks are JUNK. The hardware is cool but it stops there.
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Comments On Apr 03, 2014:Swapped stock Dunlop front and rr for Motion Pro Lites ,their stuff is usually good. These are Junk! Same ride same tires and tubes that I had ridden weekend before and had two front pinch flats and one rr, They are sharp on the edge!(pinch matches directly w/ the clamp) took out and threw away! Good luck.
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Comments On Jan 31, 2014:Tightened to 10 foot pounds tire slipped on rim and tore the tube so I replaced the tube and tightened to 12 foot pounds and the rim lock broke. Called Motion Pro and talked to Chris and said I shouldn't have over tightened it. No more motion pro for me
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Comments On Dec 21, 2013:These were used on a WR250R not F however that was not in the list. They work very well and do not cause any balance issues with the D606 and MT21 tires.
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Comments On Oct 24, 2013:Great locks, work well at high speeds and look good
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Comments On Aug 30, 2013:I put this on a scale and compared it to a "conventional" rim lock. 20 grams lighter. I like to balance my wheels since I do rally racing which involves a fair bit of highway miles between special stages, nice to not have the vibration.
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Comments On Aug 20, 2013:i love these run them on all my bikes. light wieght and STRONG
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Comments On Feb 28, 2013:The rim lock caused a flat front tube, the old aluminum style with the molded rubber flap are easier on tubes.
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Comments On Jan 11, 2013:Installed two of these in the rear wheel of my KTM 300 XC-W. Had to drill another hole since stock had only 1 rim lock. Before I needed 3-4 oz of weights to get the wheel balanced. Now i'm using no weights.
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Deluxe Wheeled Brief with Laptop Case
best complemented withPrevious Page
LaGuardia Wheeled Brief with Laptop Insert
Small Flap Crossbody
was: $175
Slimfold ID Wallet
Tumi T-Pass® Medium Screen Laptop Slim Brief
was: $345
- Alpha
- Deluxe Wheeled Brief with Laptop Case
- Style #: 26127
- Free Shipping! See Details
This versatile design is really two briefs in one—there is the large, expandable wheeled case and a removable laptop sleeve with shoulder strap. Use one or both to meet your changing needs. The main case features file dividers, a removable accessory pouch, and numerous organizer pockets. The exterior offers many pockets including a water bottle pocket. Holds a 17" laptop.
- Monogramming Available: Yes
- External Dimensions (wheeled items include handles and wheels) H x W x D: 15.5" x 17.5" x 10"
- Expanded Depth: 12"
- Laptop Compartment Dimensions: 12.5" x 16" x 1.5"
- Fits Screen Size: Up to 17"
- Construction Material: Fabric
- External Features:
- Front U-zip pockets
- Front zip pockets
- Bottom zip pocket
- Carry handles with leather wrap
- Telescoping handle
- Two wheel system
- Expandable main compartment
- Add-a-Bag sleeve
- Internal Features:
- Removable laptop sleeve with shoulder strap
- Removable accessory pouch
- File dividers
- Elastic organizer pockets
- Zip pockets
- Open pockets
- Card pockets
- Pen loop
Everyday Free Returns
We want you to be fully satisfied with every product that you purchase from www.tumi.com. If you are not satisfied with a product that you have purchased, you may return the product within 30 days of delivery for a full refund of the purchase price, minus the shipping, handling, gift box, and other charges. Please note, however, that monogrammed and personalized items, including Accent Your Alpha, cannot be returned. Return shipping is free. You will be provided with a pre-paid UPS domestic label to return your purchase. If you cannot find the prepaid shipping label, please call our Customer Service Department at 1-800-299-TUMI (8864) or contact us by email.
We ask that the product be unused, in original boxes (whenever possible), and with all paperwork, parts and accessories in order to ensure credit. Sale merchandise will be issued a credit at the current selling price. Unused items purchased on www.tumi.com can also be returned to a US Tumi full price location. Please make sure to have all paperwork, parts and accessories to ensure credit. Store credit will be issued for items without documentation.
Welcome to the world of Tumi – the finest international brand of travel, business and lifestyle accessories. Since our founding in 1975, Tumi has been dedicated to providing our customers with an outstanding ownership experience.
Specifically, we make three commitments to our customers:
1. You will enjoy using our innovative products that are designed and manufactured to be the best;
2. You will experience world-class, after-sales customer service;
3. For a limited time after you purchase a Tumi product from an authorized Tumi store or dealer, you will be covered by our Limited Warranty.
Tumi's warranty extends to the original owner; it is straightforward and comprehensive, and just part of the total Tumi ownership experience.
Please click here to learn more about the Tumi Warranty.
The Tumi Difference
Add-a-bag system
Quickly and easily add another travel piece or business case using our patented Add-A-Bag hook with secure fastened tab closure that holds in excess of 200 pounds. Also, many Tumi business cases and totes feature a back sleeve that slips over extended luggage handles allowing you to stack and carry heavier bags on your wheeled luggage. Used together, these features allow travelers to effortlessly carry two or three items at the same time with one hand.
Easy Glide Wheels
Our state-of-the-art in-line wheels incorporate sealed steel ball bearings and are mounted on solid steel axles in custom-designed, shock-absorbing bushings. They roll smoothly and quietly for hundreds of miles.
Omega Closure System®
Tumi's patented closure system significantly reduces the risk of damage to the zipper. The Omega zipper puller is designed to break away from the bag if it becomes caught. The puller, rather than the entire zipper, is then quickly and easily replaced.
Rib-Tech Padded Laptop Section
Weve added an extra measure of security and protection for your laptop with our exclusive Rib-Tech padding, made from high-compression, energy-absorbing molded foam, in the computer section of this case.
FXT Ballistic Nylon®
Tumi was the first to bring ballistic nylon to the consumer market over 30 years ago. Now we have perfected it with our exclusive FXT ballistic fabric, which combines a unique weave and a special coating to make it ultra-tough and virtually abrasion proof.
Tumi Tracer®
The Tumi Tracer® is an exclusive, complimentary program that helps reunite Tumi customers with their lost or stolen items. The core of the program is a unique 20-digit individual product number printed on a special metal plate that is permanently affixed to Tumi products. That number, along with the owners contact information, is entered into our Tracer database when a bag is registered with us, and used to help aid in the recovery of lost or stolen items that are reported to us.
Waterproof Pocket
This specially-designed pocket is ideal for keeping wet and damp items, including umbrellas, water bottles and workout clothes, separate from the other contents of the bag.
Aircraft Grade Aluminum Extension Handle
The tubing of our telescoping handles is made from aircraft-grade aluminum, making them both lightweight and extremely sturdy.
Removable Laptop Cover
Our removable laptop cover offers protection for your laptop and convenient carrying options. It can be carried on its own and slips easily into most travel bags, totes and business cases.


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October is the National Month of Pizza and Popcorn. I love these National Month of holidays because that means savings for us. Check out this list we gathered just for you!
Pizza Coupons
$1.00 off one Newman's Own T&C Pizza
$0.50 off one Flatout Thin Crust Pizza
$1.50 off Any 2 (Two) FRESCHETTA Pizzas
1 off With purchase of two 40-ct. Totino's pizza rolls snacks
$1 off With purchase of four 2-pk. Hot Pockets or Lean Pockets snacks
$1 off 40-ct. Bagel Bites frozen snack
$1 off With purchase of two Red Baron frozen pizzas
FREE Buy Four, Get One FREE Stouffer's Meals for One frozen entrée
1.25 off With purchase of two Archer Farms® frozen pizzas
$1 off Freschetta frozen pizza
$1/1 California Pizza Kitchen Product, exp. 10/9/12 (RP 09/09/12)
$0.40/1 Fleischmann's Pizza Crust Yeast Strip 9/30 Red Plum Insert
B4G1 Lean Cuisine Frozen Meal, excludes 4-pk pep. pizza, TARGET COUPON Smart Source 9/16 $1/1 Newman's Own Thin & Crispy Pizza Red Plum 9/16 Insert
Popcorn Coupons
$1/1 Popcorn Indiana All You, September 2012 (exp 10/28/2012)
Popcorn Indiana, family bag or multipack $0.55/1 Walmart 09/20/2012
$1/2 Jolly Time Microwave Popcorn Smart Source 9/16 Insert
Smart Balance Peanut Butter, Oil, Mayonnaise or Popcorn $0.75/1 Smart Balance 07/17/2012
Jolly Time Microwave Popcorn $1/2 Jolly Time 04/22/2010
Grab those savings!
{Related Post}
Lowe's Free Build and Grow Clinic: Ghoul Bus (10/13)
Outback Steakhouse: Free Wings Every Thursday W Purchase ( Exp. 11/8)
Disclosure: Affiliate links are embedded in this post.
Here is the video featured this morning on News on 6, News 9 , KMOV, Kens5 and WGEM:TulsaCW.com: TV To Talk About | The Tulsa CW


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There's a marble statue of Jesus standing 17 feet tall on top of a Mississippi River bluff overlooking downtown St. Paul, and the owner says it's there to stay now that the city has stopped fighting it.
"I'm very happy," Tuan Pham said.
Pham told FOX 9 News he won his battle with the City of St. Paul after years of struggling over the 4-ton statue. The stony stalemate began with an anonymous complaint in 2011.
Pham bought his home in 2007 after emigrating from Vietnam with his wife and 10 children in 1980. He commissioned the statue as a replica of the 105-foot Christ of Vung Tao statue in his native country.
Initially, the city asked Pham to remove the statue because of its proximity to the edge of the bluff. They also denied his appeal because an ordinance required a 40-foot setback from the edge of the bluff.
Yet, comments made by one City Council member about religious statues on the bluff were what set the stage for a civil rights lawsuit.
"In our view, this case wasn't about bluff setback," explained James Magnuson, of Mohrman & Kaardal. "This case was about the right for a citizen to worship as he chose."
So after losing his first fight with City Hall, Pham called upon a higher power - the U.S. Constitution.
"Fundamentally, we think this is a case about religious liberty," Magnuson said. "Tuan Pham was a man who escaped religious persecution in Vietnam and he came to this country, as he says, 'to build a better life based on ability to exercise his religion freely.'"
With legal help from the Alliance Defending Freedom, Pham ultimately settled with the city without going to court. In fact, Pham was so excited he even had the settlement agreement bronzed to confirm the statue will stay for years to come.
"My reaction was, 'Thank God,'" he said. "Here in the free country -- no matter how big you are, how small I am, how rich you are, how poor I am -- we have equal treatment."
Yet even as he struggled with the city, Pham also had to deal with an arsonist who damaged the statue by piling wood around the base and setting it alight in April 2012. While the statue escaped with a few streaks of soot and discoloration, the family was very shaken by the brazen vandal being on their property. The statue has since been restored and Pham said it looks "like new."
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Celebrities who have fallen from grace
Published On: Sep 22 2011 08:38:12 AM PDT Updated On: Sep 10 2013 07:29:16 AM PDT
Anthony Weiner is hoping for a primary win in tonight's New York City mayoral race, but his sex scandals have put him at the bottom of the pack.
The views expressed are not those of this company or its affiliated companies. By posting your comments you agree to our Terms of Use.


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Welcome to the world, Arwen Guinevere!! You made your appearance at 6:55am today, covered in vernix
,so it is obvious that you were not "OVERDUE" !!!.. even though you were 10 lbs, 4 oz!! woohoo!
The mainstream medical establishment isn't always right. Her first "due" date was Sept. 18th, but then they did an ultrasound and changed it. It sickens me to think of how many babies are forced into this world before they're ready..
by the way, my SIL did not tear or rip, even though her baby was so big! Midwives and gentle birth and water birth can prevent so much!
I haven't seen her yet. I will probably see her on Sunday... my son's 15th birthday is tomorrow and we have a ton of band stuff this weekend... so Sunday will be the first day we can make it.. plus, I think they will want to rest. They were up all night! I can't wait to hold her and see her and smell her.. and of course, I will post pics.
*note to self*
"Self, buy more memory for the camera."
It is anticlimactic to blog about food.. but I will.
I made a marinara with veggies and tvp and served it over whole wheat pasta with a dollop of basil tofu "ricotta" from VwaV.. but I also used some leftover Kale from the day...
I also steamed cauliflower and broccoli to go along with the dish. For dessert, I made a smoothie with soymilk, frozen banana, cocoa powder, stevia and coconut extract. Very good. No pic of the smoothie though.
I can't wait to hold my neice!!


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You are visiting our UK site. Click here to view our US site
The Trio 310 is a small palm sized unit that can be powered by both batteries or via an AC/DC power source, (AC adaptor optional).
The 310 can be used on the torso, legs and arms for fat burning and strengthening muscles, relaxing muscles and pain relief.
There are 10 body region specific programs as well as a user programmable function; the memory maintains the previous setting parameters and mode even when the power is switched off.
The unit is supplied in a carry pouch with 4 electrode pads, 4 gel pads, 2 lead wires, adhesive tape, belt clip and battery.CE Marking.
Weight (including packaging): 500g
Tax is not applicable to those living outside the European Economic Community. For more info click here.
99 in stock
Now: £175.00 (£210.00 inc. tax)
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You won't believe your eyes!Click Here >
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For every celebration.Shop Now >
Sprinkle sweetness. Spring bright watering container overflows with a Milk Chocolate Walnut petite apple, Triple Chocolate petite apple, Milk Chocolate pecan nut cluster and an assorted gift bag of exotic Natural Caramels. Gift Size 13� x 6.5� x 9�
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Fire investigators are calling a west Toledo house fire "suspicious."
A home on the 1300 block of West Delaware Avenue, near Ayers Avenue, went up in flames around 5 a.m. Sunday.
No one was home when the fire sparked. Fire crews believe the house is vacant.
The fire did not spread to neighboring homes.
The cause of the fire is under investigation.
Mobile users, click on the "Video" button in the app to watch this story. Download our app here.
Copyright 2013 Toledo News Now. All rights reserved.
A 12-year-old girl and an 8-year-old boy were stabbed multiple times in the attack.


text:
Sheer Polka-Dot Tunic: This sheer polka-dot top will be your closet chameleon! Pair it with jeans, pants or a skirt — it's a stylish addition to all of them thanks to features like a detachable belt and pleat-detailed sleeves
Read what customers are saying about this product:
Rating: 5.00 out of 1 votes cast
nice top
Love this top. wore with black leggings and it looks terrific. wore a white tank underneath but it really isn't see through. Received many compliments on this item. Wishing they offered it in other colors/patterns.
waterbury, ct
Click here to read all of this product's reviews


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commandlinefu.com is the place to record those command-line gems that you return to again and again.
Delete that bloated snippets file you've been using and share your personal repository with the world. That way others can gain from your CLI wisdom and you from theirs too. All commands can be commented on, discussed and voted up or down.
If you have a new feature suggestion or find a bug, please get in touch via http://commandlinefu.uservoice.com/
You can sign-in using OpenID credentials, or register a traditional username and password.
First-time OpenID users will be automatically assigned a username which can be changed after signing in.
Every new command is wrapped in a tweet and posted to Twitter. Following the stream is a great way of staying abreast of the latest commands. For the more discerning, there are Twitter accounts for commands that get a minimum of 3 and 10 votes - that way only the great commands get tweeted.
» http://twitter.com/commandlinefu
» http://twitter.com/commandlinefu3
» http://twitter.com/commandlinefu10
Use your favourite RSS aggregator to stay in touch with the latest commands. There are feeds mirroring the 3 Twitter streams as well as for virtually every other subset (users, tags, functions,…):
Subscribe to the feed for:
Site by David Winterbottom (user root).
Manages everything through one sed script instead of pipes of greps and awks. Quoting of shell variables is generally easier within a sed script.
Based on the MrMerry one, just add some visuals to differentiate files and directories
Based on the MrMerry one, just add some visuals and sort directory and files
saves one command. Needs GNU grep though :-(
The grep switches eliminate the need for awk and sed. Modifying vim with -p will show all files in separate tabs, -o in separate vim windows. Just wish it didn't hose my terminal once I exit vim!!
This will drop you into vim to edit all files that contain your grep string.
"&&" runs sed if and only if the backup completed and /bin/cp exited cleanly. Works for multiple files; just specify multiple filenames (or glob). Use -v switch for cp to play it safe.
Reverse DNS lookups, from a file with list of IP's, here the file is called lookups.txt
The coolest way I've found to backup a wordpress mysql database using encryption, and using local variables created directly from the wp-config.php file so that you don't have to type them- which would allow someone sniffing your terminal or viewing your shell history to see your info.
I use a variation of this for my servers that have hundreds of wordpress installs and databases by using a find command for the wp-config.php file and passing that through xargs to my function.
Having to escape forwardslashes when using sed can be a pain. However, it's possible to instead of using / as the separator to use : .
I found this by trying to substitute $PWD into my pattern, like so
sed "s/~.*/$PWD/" file.txt
Of course, $PWD will expand to a character string that begins with a / , which will make sed spit out an error such as "sed: -e expression #1, char 8: unknown option to `s'".
So simply changing it to
sed "s:~.*:$PWD:" file.txt
did the trick.
I wanted all the 'hidden' .flv files from the http link in the command line; wget seemed appropriate, fed with output from lynx, grep the flv files and the normalised via sed (to remove the numeric bullet). Similar to the 'Grab mp3 files' fu. Replace link with your own, grep arg with something more interesting ;) See here for something along the same lines...
Hope you find it useful! Improvements welcome, naturally.
Strangely enough, there is no option --lines=[negative] with tail, like the head's one, so we have to use sed, which is very short and clear, you see.
Strangely more enough, skipping lines at the bottom with sed is not short nor clear. From Sed one liner :
# delete the last 10 lines of a file
$ sed -e :a -e '$d;N;2,10ba' -e 'P;D' # method 1
$ sed -n -e :a -e '1,10!{P;N;D;};N;ba' # method 2
I'm pretty sure everyone has curl and sed, but not everyone has lynx.
Limited, but useful construct to extract text embedded in XML tags. This will only work if bar is all on one line.
If nobody posts an alternative for the multiline sed version, I'll figure it out later...
the f is for file and - stdout, This way little shorter.
I Like copy-directory function It does the job but looks like SH**, and this doesn't understand folders with whitespaces and can only handle full path, but otherwise fine,
function copy-directory () { ; FrDir="$(echo $1 | sed 's:/: :g' | awk '/ / {print $NF}')" ; SiZe="$(du -sb $1 | awk '{print $1}')" ; (cd $1 ; cd .. ; tar c $FrDir/ )|pv -s $SiZe|(cd $2 ; tar x ) ; }
Save the script as: sort_file
Usage: sort_file < sort_me.csv > out_file.csv
This script was originally posted by Admiral Beotch in LinuxQuestions.org on the Linux-Software forum.
I modified this script to make it more portable.
Useful if non-ascii characters in filenames have been improperly encoded. Replace "PROBLEM" with the incorrect characters (e.g. 'é'), and "FIX" with the correct ones (e.g. '?').