Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Prevention of Vitamin D deficiency in infancy: daily 400 IU vitamin D is sufficient

<p>Summary</p> <p>Aim-objective</p> <p>Vitamin D deficiency and rickets in developing countries continues to be a major health problem. Additionally, the increase of cases of rickets in children of some ethnic groups in the United States and European countries has provided this issue to be updated. Obviously, powerful strategies are necessary to prevent vitamin D deficiency nation-wide. In 2005, a nationwide prevention program for vitamin D deficiency was initiated, recommending 400 IU vitamin D per a day.</p> <p>This study was designed to evaluate the efficacy of the prevention program.</p> <p>Methods</p> <p>Eighty-five infants who were recalled as part of the national screening program for congenital hypothyroidism between February 2010 and August 2010 at Kocaeli University Children's Hospital were evaluated in terms of their vitamin D status as well. All babies had been provided with free vitamin D (Cholecalciferol) solution and recommended to receive 400 IU (3 drops) daily. Information regarding the age at start of supplementation, the dosage and compliance were obtained from the mothers with face-to-face interview. Serum 25-hydroxy vitamin D (25-OH-D), alkaline phosphatase (AP), parathormone (PTH) levels were measured.</p> <p>Results</p> <p>The mean age at which Vitamin D3 supplementation began was 16.5 ± 20.7 (3-120) days. Ninety percent of cases (n:76) were receiving 3 drops (400 IU) vitamin D3 per day as recommended; 70% of cases (n:59) were given vitamin D3 regularly, the remainder had imperfect compliance. Among those children who are older than 12 months, only 20% continued vitamin D supplementation. No subject had clinical signs of rickets. The mean 25-OH-D level was 42,5 ± 25,8 (median: 38.3) ng/ml. Ten subjects (12%) had their serum 25-OH-D levels lower than 20 ng/ml (6 between 15-20 ng/ml, 3 between 5-15 ng/ml and only one < 5 ng/ml).</p> <p>Conclusions</p> <p>400 U/day vitamin D seems adequate to prevent vitamin D deficiency. However, we believe that the program for preventing vitamin D deficiency in Turkey, needs to be reinforced to start immediately after birth, and to continue beyond 1 year of age at 400U regular daily dosage.</p

Mercury dynamics in a San Francisco estuary tidal wetland : assessing dynamics using in situ measurements

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 35 (2012): 1036-1048, doi:10.1007/s12237-012-9501-3.We used high-resolution in situ measurements of turbidity and fluorescent dissolved organic matter (FDOM) to quantitatively estimate the tidally driven exchange of mercury (Hg) between the waters of the San Francisco estuary and Browns Island, a tidal wetland. Turbidity and FDOM—representative of particle-associated and filter-passing Hg, respectively—together predicted 94 % of the observed variability in measured total mercury concentration in unfiltered water samples (UTHg) collected during a single tidal cycle in spring, fall, and winter, 2005–2006. Continuous in situ turbidity and FDOM data spanning at least a full spring-neap period were used to generate UTHg concentration time series using this relationship, and then combined with water discharge measurements to calculate Hg fluxes in each season. Wetlands are generally considered to be sinks for sediment and associated mercury. However, during the three periods of monitoring, Browns Island wetland did not appreciably accumulate Hg. Instead, gradual tidally driven export of UTHg from the wetland offset the large episodic on-island fluxes associated with high wind events. Exports were highest during large spring tides, when ebbing waters relatively enriched in FDOM, dissolved organic carbon (DOC), and filter-passing mercury drained from the marsh into the open waters of the estuary. On-island flux of UTHg, which was largely particle-associated, was highest during strong winds coincident with flood tides. Our results demonstrate that processes driving UTHg fluxes in tidal wetlands encompass both the dissolved and particulate phases and multiple timescales, necessitating longer term monitoring to adequately quantify fluxes.This work was supported by funding from the California Bay Delta Authority Ecosystem Restoration and Drinking Water Programs (grant ERP-00- G01) and matching funds from the United States Geological Survey Cooperative Research Program

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns