Chemically enhanced mixed region vapor stripping of TCE-contaminated saturated peat and silty clay soils

The objective of this study was to conduct further testing of MRVS, chemically enhanced with calcium oxide conditioning, on field- contaminated soils collected from beneath the NASA Michoud Rinsewater Impoundment. In this study, residual soil VOC levels as a function of vapor stripping time were measured to quantify VOC removal rates. Physical and chemical soil parameters expected to affect MRVS efficiency were measures. The effects of varying the calcium oxide loadings as well as varying the vapor stripping flow rates on VOC removal were also evaluated. The results of this study will be used to determine whether acceptable removals can be achieved within reasonable treatment times, remediation costs being directly proportional to the latter. The purpose of this report is to document the experimental results of this study, as well as to address issues that were raised after completion of the previous Michoud treatability work

Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection

Correlation between NS5A dimerization and hepatitis C virus replication

Hepatitis C virus (HCV) is the main agent of acute and chronic liver diseases leading to cirrhosis and hepatocellular carcinoma. The current standard therapy has limited efficacy and serious side effects. Thus, the development of alternate therapies is of tremendous importance. HCV NS5A (nonstructural 5A protein) is a pleiotropic protein with key roles in HCV replication and cellular signaling pathways. Here we demonstrate that NS5A dimerization occurs through Domain I (amino acids 1-240). This interaction is not mediated by nucleic acids because benzonase, RNase, and DNase treatments do not prevent NS5A-NS5A interactions. Importantly, DTT abrogates NS5A-NS5A interactions but does not affect NS5A-cyclophilin A interactions. Other reducing agents such as tris(2-carboxyethyl) phosphine and 2-mercaptoethanol also abrogate NS5A-NS5A interactions, implying that disulfide bridges may play a role in this interaction. Cyclophilin inhibitors, cyclosporine A, and alisporivir and NS5A inhibitor BMS-790052 do not block NS5A dimerization, suggesting that their antiviral effects do not involve the disruption of NS5A-NS5A interactions. Four cysteines, Cys-39, Cys-57, Cys-59, and Cys-80, are critical for dimerization. Interestingly, the four cysteines have been proposed to form a zinc-binding motif. Supporting this notion, NS5A dimerization is greatly facilitated by Zn2+ but not by Mg2+ or Mn2+. Importantly, the four cysteines are vital not only for viral replication but also critical for NS5A binding to RNA, revealing a correlation between NS5A dimerization, RNA binding, and HCV replication. Altogether our data suggest that NS5A-NS5A dimerization and/or multimerization could represent a novel target for the development of HCV therapies

phase i ii study of spartalizumab pdr001 an anti pd1 mab in patients with advanced melanoma or non small cell lung cancer

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Abundances of the elements in the solar system

A review of the abundances and condensation temperatures of the elements and their nuclides in the solar nebula and in chondritic meteorites. Abundances of the elements in some neighboring stars are also discussed.Comment: 42 pages, 11 tables, 8 figures, chapter, In Landolt- B\"ornstein, New Series, Vol. VI/4B, Chap. 4.4, J.E. Tr\"umper (ed.), Berlin, Heidelberg, New York: Springer-Verlag, p. 560-63

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Tensor polarization in elastic electron-deuteron scattering in the momentum transfer range 3.8≤Q≤4.6 fm-1

The tensor polarization of the recoil deuteron in elastic electron-deuteron scattering has been measured at the Bates Linear Accelerator Center at three values of four-momentum transfer Q=3.78, 4.22, and 4.62 fm-1, corresponding to incident electron energies of 653, 755, and 853 MeV. The scattered electrons and the recoil deuterons were detected in coincidence. The recoil deuterons were transported to a liquid hydrogen target to undergo a second scattering. The angular distribution of the d→-p scattering was measured using a polarimeter. The polarimeter was calibrated in an auxiliary experiment using a polarized deuteron beam at the Laboratoire National Saturne. A Monte Carlo procedure was used to generate interpolated calibration data because the energy spread in the deuteron energies in the Bates experiment spanned the range of deuteron energies in the calibration experiment. The extracted values of t20 are compared to predictions of different theoretical models of the electromagnetic form factors of the deuteron: nonrelativistic and relativistic nucleon-meson dynamics, Skyrme model, quark models, and perturbative quantum chromodynamics. Along with the world data the structure functions A(Q) and B(Q) are used to separate the charge monopole and charge quadrupole form factors of the deuteron. A node in the charge monopole form factor is observed at Q=4.39±0.16 fm-1

Measurement of tensor polarization in elastic electron-deuteron scattering in the momentum-transfer range 3.8≤q≤4.6 fm-1

The tensor polarization t20 of the recoil deuteron in elastic e-d scattering has been measured for three values of four-momentum transfer, q=3.78, 4.22, and 4.62 fm-1. The data have been used to locate the first node in the charge monopole form factor of the deuteron at q=4.39±0.16 fm-1. The results for t20 are in reasonable agreement with expectations based on the nucleon-meson description of nuclear dynamic

1st International consensus guidelines for advanced breast cancer (ABC 1)

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines