Alluvial fan records from southeast Arabia reveal multiple windows for human dispersal

The dispersal of human populations out of Africa into Arabia was most likely linked to episodes of climatic amelioration, when increased monsoon rainfall led to the activation of drainage systems, improved freshwater availability, and the development of regional vegetation. Here we present the first dated terrestrial record from southeast Arabia that provides evidence for increased rainfall and the expansion of vegetation during both glacial and interglacial periods. Findings from extensive alluvial fan deposits indicate that drainage system activation occurred during Marine Isotope Stage (MIS) 6 (ca. 160–150 ka), MIS 5 (ca. 130–75 ka), and during early MIS 3 (ca. 55 ka). The development of active freshwater systems during these periods corresponds with monsoon intensity increases during insolation maxima, suggesting that humid periods in Arabia were not confined to eccentricity-paced deglaciations, and providing paleoenvironmental support for multiple windows of opportunity for dispersal out of Africa during the late Pleistocene

Insights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum

DNA cytosine methylation is a widely conserved epigenetic mark in eukaryotes that appears to have critical roles in the regulation of genome structure and transcription. Genome-wide methylation maps have so far only been established from the supergroups Archaeplastida and Unikont. Here we report the first whole-genome methylome from a stramenopile, the marine model diatom Phaeodactylum tricornutum. Around 6% of the genome is intermittently methylated in a mosaic pattern. We find extensive methylation in transposable elements. We also detect methylation in over 320 genes. Extensive gene methylation correlates strongly with transcriptional silencing and differential expression under specific conditions. By contrast, we find that genes with partial methylation tend to be constitutively expressed. These patterns contrast with those found previously in other eukaryotes. By going beyond plants, animals and fungi, this stramenopile methylome adds significantly to our understanding of the evolution of DNA methylation in eukaryotes.Fil: Veluchamy, Alaguraj. Institut de Biologie de l'École Normale Supérieure; FranciaFil: Lin, Xin. Institut de Biologie de l'École Normale Supérieure; Francia. Xiamen University; ChinaFil: Maumus, Florian.Fil: Rivarola, Maximo Lisandro.Fil: Bhavsar, Jaysheel.Fil: Creasy, Todd.Fil: O'Brien, Kimberly.Fil: Sengamalay, Naomi A..Fil: Tallon, Luke J..Fil: Smith, Andrew D..Fil: Rayko, Edda.Fil: Ahmed, Ikhlak.Fil: Crom, Stéphane Le.Fil: Farrant, Gregory K..Fil: Sgro, Jean-Yves.Fil: Olson, Sue A..Fil: Bondurant, Sandra Splinter.Fil: Allen, Andrew.Fil: Rabinowicz, Pablo D..Fil: Sussman, Michael R..Fil: Bowler, Chris.Fil: Tirichine, Leïla

Testing the GRACE follow-on triple mirror assembly

We report on the successful testing of the GRACE follow-on triple mirror assembly (TMA) prototype. This component serves to route the laser beam in a proposed follow-on mission to the Gravity Recovery and Climate Explorer (GRACE) mission, containing an optical instrument for space-based distance measurement between satellites. As part of this, the TMA has to meet a set of stringent requirements on both the optical and mechanical properties. The purpose of the TMA prototype testing is to establish the feasibility of the design, materials choice and fabrication techniques. Here we report on co-alignment testing of this device to the arc second (5 μrad) level and thermal alignment stability testing to 1 μ rad {{K}-1}

Fluctuation Study of the Specific Heat of MgB2

The specific heat of polycrystalline Mg$^{11}$B$_{2}$ has been measured with high resolution ac calorimetry from 5 to 45 K at constant magnetic fields. The excess specific heat above T$_{c}$ is discussed in terms of Gaussian fluctuations and suggests that Mg$^{11}$B$_{2}$ is a bulk superconductor with Ginzburg-Landau coherence length $\xi_{0}=26$ \AA . The transition-width broadening in field is treated in terms of lowest-Landau-level (LLL) fluctuations. That analysis requires that $\xi_{0}=20$ \AA . The underestimate of the coherence length in field, along with deviations from 3D LLL predictions, suggest that there is an influence from the anisotropy of B$_{c2}$ between the c-axis and the a-b plane.Comment: Phys. Rev. B 66, 134515 (2002

A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.

INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786

Numerical studies of the phase diagram of layered type II superconductors in a magnetic field

We report on simulations of layered superconductors using the Lawrence-Doniach model in the framework of the lowest Landau level approximation. We find a first order phase transition with a $B(T)$ dependence which agrees very well with the experimental ``melting'' line in YBaCuO. The transition is not associated with vortex lattice melting, but separates two vortex liquid states characterised by different degrees of short-range crystalline order and different length scales of correlations between vortices in different layers. The transition line ends at a critical end-point at low fields. We find the magnetization discontinuity and the location of the lower critical magnetic field to be in good agreement with experiments in YBaCuO. Length scales of order parameter correlations parallel and perpendicular to the magnetic field increase exponentially as 1/T at low temperatures. The dominant relaxation time scales grow roughly exponentially with these correlation lengths. We find that the first order phase transition persists in the presence of weak random point disorder but can be suppressed entirely by strong disorder. No vortex glass or Bragg glass state is found in the presence of disorder. The consistency of our numerical results with various experimental features in YBaCuO, including the dependence on anisotropy, and the temperature dependence of the structure factor at the Bragg peaks in neutron scattering experiments is demonstrated.Comment: 25 pages (revtex), 19 figures included, submitted to PR

National geological screening : Bristol and Gloucester region

This report is the published product of one of a series of studies covering England, Wales and Northern Ireland commissioned by Radioactive Waste Management (RWM) Ltd. The report provides geological information about the Bristol and Gloucester region to underpin the process of national geological screening set out in the UK’s government White Paper Implementing geological disposal: a framework for the longterm management of higher activity radioactive waste (DECC, 2014). The report describes geological features relevant to the safety requirements of a geological disposal facility (GDF) for radioactive waste emplaced onshore and up to 20 km offshore at depths between 200 and 1000 m from surface. It is written for a technical audience but is intended to inform RWM in its discussions with communities interested in finding out about the potential for their area to host a GDF

GABA-A Channel Subunit Expression in Human Glioma Correlates with Tumor Histology and Clinical Outcome

GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS and is present in high concentrations in presynaptic terminals of neuronal cells. More recently, GABA has been ascribed a more widespread role in the control of cell proliferation during development where low concentrations of extrasynaptic GABA induce a tonic activation of GABA receptors. The GABA-A receptor consists of a ligand-gated chloride channel, formed by five subunits that are selected from 19 different subunit isoforms. The functional and pharmacological properties of the GABA-A channels are dictated by their subunit composition. Here we used qRT-PCR to compare mRNA levels of all 19 GABA-A channel subunits in samples of human glioma (n = 29) and peri-tumoral tissue (n = 5). All subunits except the ρ1 and ρ3 subunit were consistently detected. Lowest mRNA levels were found in glioblastoma compared to gliomas of lower malignancy, except for the θ subunit. The expression and cellular distribution of the α1, γ1, ρ2 and θ subunit proteins was investigated by immunohistochemistry on tissue microarrays containing 87 gliomas grade II. We found a strong co-expression of ρ2 and θ subunits in both astrocytomas (r = 0.86, p<0.0001) and oligodendroglial tumors (r = 0.66, p<0.0001). Kaplan-Meier analysis and Cox proportional hazards modeling to estimate the impact of GABA-A channel subunit expression on survival identified the ρ2 subunit (p = 0.043) but not the θ subunit (p = 0.64) as an independent predictor of improved survival in astrocytomas, together with established prognostic factors. Our data give support for the presence of distinct GABA-A channel subtypes in gliomas and provide the first link between specific composition of the A-channel and patient survival