Structural Insights into Recognition of MDC1 by TopBP1 in DNA Replication Checkpoint Control

SummaryActivation of the DNA replication checkpoint by the ATR kinase requires protein interactions mediated by the ATR-activating protein, TopBP1. Accumulation of TopBP1 at stalled replication forks requires the interaction of TopBP1 BRCT5 with the phosphorylated SDT repeats of the adaptor protein MDC1. Here, we present the X-ray crystal structures of the tandem BRCT4/5 domains of TopBP1 free and in complex with a MDC1 consensus pSDpT phosphopeptide. TopBP1 BRCT4/5 adopts a variant BRCT-BRCT packing interface and recognizes its target peptide in a manner distinct from that observed in previous tandem BRCT- peptide structures. The phosphate-binding pocket and positively charged residues in a variant loop in BRCT5 present an extended binding surface for the negatively charged MDC1 phosphopeptide. Mutations in this surface reduce binding affinity and recruitment of TopBP1 to γH2AX foci in cells. These studies reveal a different mode of phosphopeptide binding by BRCT domains in the DNA damage response

Temperature dependence of current self-oscillations and electric field domains in sequential tunneling doped superlattices

We examine how the current--voltage characteristics of a doped weakly coupled superlattice depends on temperature. The drift velocity of a discrete drift model of sequential tunneling in a doped GaAs/AlAs superlattice is calculated as a function of temperature. Numerical simulations and theoretical arguments show that increasing temperature favors the appearance of current self-oscillations at the expense of static electric field domain formation. Our findings agree with available experimental evidence.Comment: 7 pages, 5 figure

Effects of different probiotics on the gut microbiome and metabolites in the serum and caecum of weaning piglets

The objective of the study was to determine the effects of antibiotics, yeast culture (YC), and Lactobacillus culture (LC) on the gut microbiome and metabolites in the serum and caecum of weaning piglets. Twenty-four weaning piglets were divided into four treatment groups: control, antibiotic (1% chlortetracycline), 1.8% yeast culture (YC), and 1.6% Lactobacillus culture groups (LC). Each group had six replicated pens with one pig per pen. Feed and water were available ad libitum. Dietary supplementation with antibiotics, YC and LC increased the abundance of phylum, Firmicutes, and decreased the abundance of phylum, Proteobacteria. Beneficial bacteria such as Lactobacillus and Megasphaera in YC and LC groups increased, whereas the proportion of Shigella was decreased. Genera Alloprevotella and Lachnospira were biomarkers in the control and antibiotic groups, respectively. Phylum, Bacteroidetes, and genus, Collinsella, were biomarkers in the YC group, and Mitsuokella, Anaerotruncus, Syntrophococcus and Sharpea were biomarkers in the LC group. Dietary supplementation with different probiotics changed the serum and caecum metabolite profiles too. Antibiotic supplementation increased the levels of D-mannose, D-glucose, and hexadecanoic acid in the serum, and the levels of myo-inositol, D-mannose and benzenepropanoic acid in the caecum. LC increased the concentrations of D-mannose, cis-9-hexadecenoic acid and heptadecanoic acid in caecum compared with the control group. YC and LC supplementation in the weaning diet could improve the abundance of beneficial bacteria by changing the concentrations of some metabolites in the serum and caecum. Therefore, dietary supplementation with YC or LC could be used as additives instead of antibiotics in weaning piglets.Keywords: antibiotic; lactobacillus culture; yeast culture; high-throughput sequencing; gas chromatography mass spectrometr

SN1987A and the Status of Oscillation Solutions to the Solar Neutrino Problem (including an appendix discussing the NC and day/night data from SNO)

We study neutrino oscillations and the level-crossing probability PLZ in power-law potential profiles A(r)\propto r^n. We give local and global adiabaticity conditions valid for all mixing angles theta and discuss different representations for PLZ. For the 1/r^3 profile typical of supernova envelopes we compare our analytical to numerical results and to earlier approximations used in the literature. We then perform a combined likelihood analysis of the observed SN1987A neutrino signal and of the latest solar neutrino data, including the recent SNO CC measurement. We find that, unless all relevant supernova parameters (released binding energy, \bar\nu_e and \bar\nu_{\mu,\tau} temperatures) are near their lowest values found in simulations, the status of large mixing type solutions deteriorates considerably compared to fits using only solar data. This is sufficient to rule out the vacuum-type solutions for most reasonable choices of astrophysics parameters. The LOW solution may still be acceptable, but becomes worse than the SMA-MSW solution which may, in some cases, be the best combined solution. On the other hand the LMA-MSW solution can easily survive as the best overall solution, although its size is generally reduced when compared to fits to the solar data only.Comment: 31 pages, 32 eps figures; 5 pages, 5 eps figures addendum in v2, discussing the recent SNO NC data and changes in SN paramete

Optical properties of MgH2 measured in situ in a novel gas cell for ellipsometry/spectrophotometry

The dielectric properties of alpha-MgH2 are investigated in the photon energy range between 1 and 6.5 eV. For this purpose, a novel sample configuration and experimental setup are developed that allow both optical transmission and ellipsometric measurements of a transparent thin film in equilibrium with hydrogen. We show that alpha-MgH2 is a transparent, colour neutral insulator with a band gap of 5.6 +/- 0.1 eV. It has an intrinsic transparency of about 80% over the whole visible spectrum. The dielectric function found in this work confirms very recent band structure calculations using the GW approximation by Alford and Chou [J.A. Alford and M.Y. Chou (unpublished)]. As Pd is used as a cap layer we report also the optical properties of PdHx thin films.Comment: REVTeX4, 15 pages, 12 figures, 5 table

Metal enrichment processes

There are many processes that can transport gas from the galaxies to their environment and enrich the environment in this way with metals. These metal enrichment processes have a large influence on the evolution of both the galaxies and their environment. Various processes can contribute to the gas transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy interactions and others. We review their observational evidence, corresponding simulations, their efficiencies, and their time scales as far as they are known to date. It seems that all processes can contribute to the enrichment. There is not a single process that always dominates the enrichment, because the efficiencies of the processes vary strongly with galaxy and environmental properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 17; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Scale-free static and dynamical correlations in melts of monodisperse and Flory-distributed homopolymers: A review of recent bond-fluctuation model studies

It has been assumed until very recently that all long-range correlations are screened in three-dimensional melts of linear homopolymers on distances beyond the correlation length $\xi$ characterizing the decay of the density fluctuations. Summarizing simulation results obtained by means of a variant of the bond-fluctuation model with finite monomer excluded volume interactions and topology violating local and global Monte Carlo moves, we show that due to an interplay of the chain connectivity and the incompressibility constraint, both static and dynamical correlations arise on distances $r \gg \xi$. These correlations are scale-free and, surprisingly, do not depend explicitly on the compressibility of the solution. Both monodisperse and (essentially) Flory-distributed equilibrium polymers are considered.Comment: 60 pages, 49 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio