Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.

Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect

Laser irradiation of parylene disks with a 1.06 mumum laser

Parylene disks supported on glass stalks were irradiated with 1.06 $mu$m wavelength laser light pulses focused to flux intensities in the range from 10$sup 15$ to 10$sup 17$ W/cm$sup 2$. According to photodiode measurements the fraction of laser light absorbed, 25 to 50 percent, increased slightly as the laser intensity was increased. However, box calorimeter measurements implied that the fraction absorbed was approximately 30 percent and insensitive to irradiation intensity. Some x-ray spectra are discussed. (MOW

Effecten bodem- en structuurverbeteraars : onderzoek op klei-, zand- en dal grond 2010

Om de bodemstructuur te verbeteren worden door industrie en handel zogeheten bodemverbeteraars en kalkmeststoffen aangeboden. Er is een grote variatie in type producten, de wijze waarop ze werken en de mate waarin ze een directe dan wel indirecte invloed op de bodemvruchtbaarheid hebben. Om de invloed van bodemverbeteraars op verschillende grondsoorten te toetsen zijn proeven aangelegd op drie kleilocaties, één dalgrond- en één zandlocatie. In 2010 is de uit gangssituatie van de bodem in de diverse testlocaties bepaald (nulmeting). Er waren in 2010 geen of nauwelijks betrouwbare verschillen in opbrengst tussen de div erse behandelingen. Per locatie lijken er wel verschillen in effecten te zijn van bodemverbeteraars. Het onderzoek van de komende jaren zal moet en uitwijzen of er significante verschillen zijn tussen bodemverbeteraars en of bodemverbeteraars significante toegevoegde waarde hebben voor het verbeteren van de bodemstructuur

Effecten bodem- en structuurverbeteraars : onderzoek op klei-, zand- en dalgrond 2011

Onderzoek op klei-, zand- en dalgrond 201

Stochastic Production Of Kink-Antikink Pairs In The Presence Of An Oscillating Background

We numerically investigate the production of kink-antikink pairs in a $(1+1)$ dimensional $\phi^4$ field theory subject to white noise and periodic driving. The twin effects of noise and periodic driving acting in conjunction lead to considerable enhancement in the kink density compared to the thermal equilibrium value, for low dissipation coefficients and for a specific range of frequencies of the oscillating background. The dependence of the kink-density on the temperature of the heat bath, the amplitude of the oscillating background and value of the dissipation coefficient is also investigated. An interesting feature of our result is that kink-antikink production occurs even though the system always remains in the broken symmetry phase.Comment: Revtex, 21 pages including 7 figures; more references adde

Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events

Objective We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Participants and methods Four clinical trials randomly assigned treatment-naive participants to efavirenzcontaining regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Results Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7 × 10-4). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9 × 10-27). Conclusion Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

Sensitivity to millicharged particles in future proton-proton collisions at the LHC with the milliQan detector

We report on the expected sensitivity of dedicated scintillator-based detectors at the LHC for elementary particles with charges much smaller than the electron charge. The dataset provided by a prototype scintillator-based detector is used to characterise the performance of the detector and provide an accurate background projection. Detector designs, including a novel slab detector configuration, are considered for the data taking period of the LHC to start in 2022 (Run 3) and for the high luminosity LHC. With the Run 3 dataset, the existence of new particles with masses between 10 MeV and 45 GeV could be excluded at 95% confidence level for charges between 0.003e and 0.3e, depending on their mass. With the high luminosity LHC dataset, the expected limits would reach between 10 MeV and 80 GeV for charges between 0.0018e and 0.3e, depending on their mas

What can comparative genomics tell us about species concepts in the genus Aspergillus?

Understanding the nature of species” boundaries is a fundamental question in evolutionary biology. The availability of genomes from several species of the genus Aspergillus allows us for the first time to examine the demarcation of fungal species at the whole-genome level. Here, we examine four case studies, two of which involve intraspecific comparisons, whereas the other two deal with interspecific genomic comparisons between closely related species. These four comparisons reveal significant variation in the nature of species boundaries across Aspergillus. For example, comparisons between A. fumigatus and Neosartorya fischeri (the teleomorph of A. fischerianus) and between A. oryzae and A. flavus suggest that measures of sequence similarity and species-specific genes are significantly higher for the A. fumigatus - N. fischeri pair. Importantly, the values obtained from the comparison between A. oryzae and A. flavus are remarkably similar to those obtained from an intra-specific comparison of A. fumigatus strains, giving support to the proposal that A. oryzae represents a distinct ecotype of A. flavus and not a distinct species. We argue that genomic data can aid Aspergillus taxonomy by serving as a source of novel and unprecedented amounts of comparative data, as a resource for the development of additional diagnostic tools, and finally as a knowledge database about the biological differences between strains and species

Azimuthal asymmetries of charged hadrons produced by high-energy muons scattered off longitudinally polarised deuterons

Azimuthal asymmetries in semi-inclusive production of positive (h^+) and negative hadrons (h^-) have been measured by scattering 160 GeV muons off longitudinally polarised deuterons at CERN. The asymmetries were decomposed in several terms according to their expected modulation in the azimuthal angle phi of the outgoing hadron. Each term receives contributions from one or several spin and transverse-momentum-dependent parton distribution and fragmentation functions. The amplitudes of all phi-modulation terms of the hadron asymmetries integrated over the kinematic variables are found to be consistent with zero within statistical errors, while the constant terms are nonzero and equal for h^+ and h^- within the statistical errors. The dependencies of the phi-modulated terms versus the Bjorken momentum fraction x, the hadron fractional momentum z, and the hadron transverse momentum p_h^T were studied. The x dependence of the constant terms for both positive and negative hadrons is in agreement with the longitudinal double-spin hadron asymmetries, measured in semi-inclusive deep-inelastic scattering. The x dependence of the sin phi-modulation term is less pronounced than that in the corresponding HERMES data. All other dependencies of the phi-modulation amplitudes are consistent with zero within the statistical errors.Comment: 12 pages, 11 Figures; revision 1 signs in Eq 5 corrected, polishe