377 research outputs found
Determination of the characteristic directions of lossless linear optical elements
We show that the problem of finding the primary and secondary characteristic
directions of a linear lossless optical element can be reformulated in terms of
an eigenvalue problem related to the unimodular factor of the transfer matrix
of the optical device. This formulation makes any actual computation of the
characteristic directions amenable to pre-implemented numerical routines,
thereby facilitating the decomposition of the transfer matrix into equivalent
linear retarders and rotators according to the related Poincare equivalence
theorem. The method is expected to be useful whenever the inverse problem of
reconstruction of the internal state of a transparent medium from optical data
obtained by tomographical methods is an issue.Comment: Replaced with extended version as published in JM
Current quark mass dependence of nucleon magnetic moments and radii
A calculation of the current-quark-mass-dependence of nucleon static
electromagnetic properties is necessary in order to use observational data as a
means to place constraints on the variation of Nature's fundamental parameters.
A Poincare' covariant Faddeev equation, which describes baryons as composites
of confined-quarks and -nonpointlike-diquarks, is used to calculate this
dependence The results indicate that, like observables dependent on the
nucleons' magnetic moments, quantities sensitive to their magnetic and charge
radii, such as the energy levels and transition frequencies in Hydrogen and
Deuterium, might also provide a tool with which to place limits on the allowed
variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice
The DNA Repair Gene APE1 T1349G Polymorphism and Risk of Gastric Cancer in a Chinese Population
Background: Apurinic/apyrimidinic endonuclease 1 (APE1) has a central role in the repair of apurinic apyrimidic sites through both its endonuclease and its phosphodiesterase activities. A common APE1 polymorphism, T1349G (rs3136820), was previously shown to be associated with the risk of cancers. Objective: We hypothesized that the APE1 T1349G polymorphism is also associated with risk of gastric cancer. Methods: In a hospital-based case-control study of 338 case patients with newly diagnosed gastric cancer and 362 cancerfree controls frequency-matched by age and sex, we genotyped the T1349G polymorphism and assessed its associations with risk of gastric cancer. Results: Compared with the APE1 TT genotype, individuals with the variant TG/GG genotypes had a significantly increased risk of gastric cancer (odds ratio = 1.69, 95 % confidence interval = 1.19–2.40), which was more pronounced among subgroups of aged #60 years, male, ever smokers, and ever drinkers. Further analyses revealed that the variant genotypes were associated with an increased risk for diffuse-type, low depth of tumor infiltration (T1 and T2), and lymph node metastasis gastric cancer. Conclusions: The APE1 T1349G polymorphism may be a marker for the development of gastric cancer in the Chinese population. Larger studies are required to validate these findings in diverse populations
Transmitted Drug Resistance in Persons with Acute/Early HIV-1 in San Francisco, 2002-2009
Transmitted HIV-1 drug resistance (TDR) is an ongoing public health problem, representing 10-20% of new HIV infections in many geographic areas. TDR usually arises from two main sources: individuals on antiretroviral therapy (ART) who are failing to achieve virologic suppression, and individuals who acquired TDR and transmit it while still ART-naïve. TDR rates can be impacted when novel antiretroviral medications are introduced that allow for greater virologic suppression of source patients. Although several new HIV medications were introduced starting in late 2007, including raltegravir, maraviroc, and etravirine, it is not known whether the prevalence of TDR was subsequently affected in 2008-2009.We performed population sequence genotyping on individuals who were diagnosed with acute or early HIV (<6 months duration) and who enrolled in the Options Project, a prospective cohort, between 2002 and 2009. We used logistic regression to compare the odds of acquiring drug-resistant HIV before versus after the arrival of new ART (2005-2007 vs. 2008-2009). From 2003-2007, TDR rose from 7% to 24%. Prevalence of TDR was then 15% in 2008 and in 2009. While the odds of acquiring TDR were lower in 2008-2009 compared to 2005-2007, this was not statistically significant (odds ratio 0.65, 95% CI 0.31-1.38; p = 0.27).Our study suggests that transmitted drug resistance rose from 2003-2007, but this upward trend did not continue in 2008 and 2009. Nevertheless, the TDR prevalence in 2008-2009 remained substantial, emphasizing that improved management strategies for drug-resistant HIV are needed if TDR is to be further reduced. Continued surveillance for TDR will be important in understanding the full impact of new antiretroviral medications
Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature
The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability
CMB Telescopes and Optical Systems
The cosmic microwave background radiation (CMB) is now firmly established as
a fundamental and essential probe of the geometry, constituents, and birth of
the Universe. The CMB is a potent observable because it can be measured with
precision and accuracy. Just as importantly, theoretical models of the Universe
can predict the characteristics of the CMB to high accuracy, and those
predictions can be directly compared to observations. There are multiple
aspects associated with making a precise measurement. In this review, we focus
on optical components for the instrumentation used to measure the CMB
polarization and temperature anisotropy. We begin with an overview of general
considerations for CMB observations and discuss common concepts used in the
community. We next consider a variety of alternatives available for a designer
of a CMB telescope. Our discussion is guided by the ground and balloon-based
instruments that have been implemented over the years. In the same vein, we
compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the
South Pole Telescope (SPT). CMB interferometers are presented briefly. We
conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and
Planck, to demonstrate a remarkable evolution in design, sensitivity,
resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1:
Telescopes and Instrumentatio
Variation in WNT7A is unlikely to be a cause of familial Congenital Talipes Equinovarus
<p>Abstract</p> <p>Background</p> <p>Genetic factors make an important contribution to the aetiology of congenital talipes equinovarus (CTEV), the most common developmental disorder of the lower limb. WNT7A was suggested as a candidate gene for CTEV on the basis of a genome-wide scan for linkage in a large multi-case family. WNT7A is a plausible candidate gene for CTEV as it provides a signal for pattern formation during limb development, and mutation in WNT7A has been reported in a number of limb malformation syndromes.</p> <p>Methods</p> <p>We investigated the role of WNT7A using a family-based linkage approach in our large series of European multi-case CTEV families. Three microsatellite markers were used, of which one (D3S2385) is intragenic, and the other two (D3S2403, D3S1252) are 700 kb 5' to the start and 20 kb from the 3' end of the gene, respectively. Ninety-one CTEV families, comprising 476 individuals of whom 211 were affected, were genotyped. LOD scores using recessive and incomplete-dominant inheritance models, and non-parametric linkage scores, excluded linkage.</p> <p>Results</p> <p>No significant evidence for linkage was observed using either parametric or non-parametric models. LOD scores for the parametric models remained strongly negative in the regions between the markers, and in the 0.5 cM intervals outside the marker map. No significant lod scores were obtained when the data were analysed allowing for heterogeneity.</p> <p>Conclusion</p> <p>Our evidence suggests that the WNT7A gene is unlikely to be a major contributor to the aetiology of familial CTEV.</p
Assessing Predicted HIV-1 Replicative Capacity in a Clinical Setting
HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naĂŻve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load
Deep Sequencing of MYC DNA-Binding Sites in Burkitt Lymphoma
BACKGROUND:
MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far.
METHODOLOGY/PRINCIPAL FINDINGS:
ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing.
CONCLUSION/SIGNIFICANCE:
The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology
- …