1,212 research outputs found

    A semiconductor source of triggered entangled photon pairs?

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    The realisation of a triggered entangled photon source will be of great importance in quantum information, including for quantum key distribution and quantum computation. We show here that: 1) the source reported in ``A semiconductor source of triggered entangled photon pairs''[1. Stevenson et al., Nature 439, 179 (2006)]} is not entangled; 2) the entanglement indicators used in Ref. 1 are inappropriate, relying on assumptions invalidated by their own data; and 3) even after simulating subtraction of the significant quantity of background noise, their source has insignificant entanglement.Comment: 5 pages in pre-print format, 1 tabl

    Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

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    Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

    Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

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    Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-lengthMsegment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/ PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV crossneutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model

    Genome-Wide Expression Analysis of a Spinal Muscular Atrophy Model: Towards Discovery of New Drug Targets

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    Spinal Muscular Atrophy is a recessive genetic disease and affects lower motor neurones and muscle tissue. A single gene is disrupted in SMA: SMN1 activity is abolished but a second copy of the gene (SMN2) provides limited activity. While the SMN protein has been shown to function in the assembly of RNA-protein complexes, it is unclear how the overall reduction in SMN activity specifically results in the neuromuscular phenotypes. Similar to humans, reduced smn activity in the fly causes earliest phenotypes in neuromuscular tissues. To uncover the effects of reduced SMN activity, we have studied gene expression in control and diseased fly tissues using whole genome micro-arrays. A number of gene expression changes are recovered and independently validated. Identified genes show trends in their predicted function: several are consistent with the function of SMN, in addition some uncover novel pathways. This and subsequent genetic analysis in the fly indicates some of the identified genes could be taken for further studies as potential drug targets for SMA and other neuromuscular disorders

    Towards the clinical implementation of pharmacogenetics in bipolar disorder.

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    BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

    Interventional radiography and mortality risks in U.S. radiologic technologists

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    With the exponential increase in minimally invasive fluoroscopically guided interventional radiologic procedures, concern has increased about the health effects on staff and patients of radiation exposure from these procedures. There has been no systematic epidemiologic investigation to quantify serious disease risks or mortality. To quantify all-cause, circulatory system disease and cancer mortality risks in U.S. radiologic technologists who work with interventional radiographic procedures, we evaluated mortality risks in a nationwide cohort of 88,766 U.S. radiologic technologists (77% female) who completed a self-administered questionnaire during 1994–998 and were followed through 31 December 2003. We obtained information on work experience, types of procedures (including fluoroscopically guided interventional procedures), and protective measures plus medical, family cancer history, lifestyle, and reproductive information. Cox proportional hazards regression models were used to compute relative risks (RRs) with 95% confidence intervals (CIs). Between completion of the questionnaire and the end of follow-up, there were 3,581 deaths, including 1,209 from malignancies and 979 from circulatory system diseases. Compared to radiologic technologists who never or rarely performed or assisted with fluoroscopically guided interventional procedures, all-cause mortality risks were not increased among those working on such procedures daily. Similarly, there was no increased risk of mortality resulting from all circulatory system diseases combined, all cancers combined, or female breast cancer among technologists who daily performed or assisted with fluoroscopically guided interventional procedures. Based on small numbers of deaths (n=151), there were non-significant excesses (40%–0%) in mortality from cerebrovascular disease among technologists ever working with these procedures. The absence of significantly elevated mortality risks in radiologic technologists reporting the highest frequency of interventional radiography procedures must be interpreted cautiously in light of the small number of deaths during the relatively short follow-up. The present study cannot rule out increased risks of cerebrovascular disease, specific cancers, and diseases with low case-fatality rates or a long latency period preceding death

    Maintenance of bone mineral density after implantation of a femoral neck hip prosthesis

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    <p>Abstract</p> <p>Background</p> <p>Stress shielding of the proximal femur has been observed in a number of conventional cementless implants used in total hip arthroplasty. Short femoral-neck implants are claiming less interference with the biomechanics of the proximal femur. The goal of this study was to investigate the changes of bone-mineral density in the proximal femur and the clinical outcome after implantation of a short femoral-neck prosthesis.</p> <p>Methods</p> <p>We prospectively assessed the clinical outcome and the changes of bone mineral density of the proximal femur up to one year after implantation of a short femoral neck prosthesis in 20 patients with a mean age of 47 years (range 17 to 65). Clinical outcome was assessed using the Harris Hip Score. The WOMAC was used as a patient-relevant outcome-measure. The bone mineral density was determined using dual energy x-ray absorptiometry, performed 10 days, three months and 12 months after surgery.</p> <p>Results</p> <p>The Harris Hip Score improved from an average preoperative score of 46 to a postoperative score at 12 months of 89 points, the global WOMAC index from 5,3 preoperatively to 0,8 at 12 months postoperatively. In contrast to conventional implants, the DEXA-scans overall revealed a slight increase of bone mineral density in the proximal femur in the 12 months following the implantation.</p> <p>Conclusion</p> <p>The short femoral neck stem lead to a distinct bone reaction. This was significantly different when compared to the changes in bone mineral density reported after implantation of conventional implants.</p

    X-Ray Spectroscopy of Stars

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    (abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag
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