A framework for analyzing both linkage and association: An analysis of Genetic Analysis Workshop 16 simulated data

We examine a Bayesian Markov-chain Monte Carlo framework for simultaneous segregation and linkage analysis in the simulated single-nucleotide polymorphism data provided for Genetic Analysis Workshop 16. We conducted linkage only, linkage and association, and association only tests under this framework. We also compared these results with variance-component linkage analysis and regression analyses. The results indicate that the method shows some promise, but finding genes that have very small (<0.1%) contributions to trait variance may require additional sources of information. All methods examined fared poorly for the smallest in the simulated "polygene" range (h(2 )of 0.0015 to 0.0002)

AzTEC 1.1 mm Observations of the MBM12 Molecular Cloud

We present 1.1 mm observations of the dust continuum emission from the MBM12 high-latitude molecular cloud observed with the Astronomical Thermal Emission Camera (AzTEC) mounted on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. We surveyed a 6.34 deg$^2$ centered on MBM12, making this the largest area that has ever been surveyed in this region with submillimeter and millimeter telescopes. Eight secure individual sources were detected with a signal-to-noise ratio of over 4.4. These eight AzTEC sources can be considered to be real astronomical objects compared to the other candidates based on calculations of the false detection rate. The distribution of the detected 1.1 mm sources or compact 1.1 mm peaks is spatially anti-correlated with that of the 100 micronm emission and the $^{12}$CO emission. We detected the 1.1 mm dust continuum emitting sources associated with two classical T Tauri stars, LkHalpha262 and LkHalpha264. Observations of spectral energy distributions (SEDs) indicate that LkHalpha262 is likely to be Class II (pre-main-sequence star), but there are also indications that it could be a late Class I (protostar). A flared disk and a bipolar cavity in the models of Class I sources lead to more complicated SEDs. From the present AzTEC observations of the MBM12 region, it appears that other sources detected with AzTEC are likely to be extragalactic and located behind MBM12. Some of these have radio counterparts and their star formation rates are derived from a fit of the SEDs to the photometric evolution of galaxies in which the effects of a dusty interstellar medium have been included.Comment: 8 pages, 6 figures, The Astrophysical Journal, in pres

CHIMPS: the 13^{13}CO/C18^{18}O (J=3-2) Heterodyne Inner Milky Way Plane Survey

We present the $^{13}$CO/C$^{18}$O (J=3-2) Heterodyne Inner Milky Way Plane Survey (CHIMPS) which has been carried out using the Heterodyne Array Receiver Program on the 15 m James Clerk Maxwell Telescope (JCMT) in Hawaii. The high-resolution spectral survey currently covers |b| < 0.5 deg and 28 < l < 46 deg, with an angular resolution of 15 arcsec in 0.5 km/s velocity channels. The spectra have a median rms of $\sim$ 0.6 K at this resolution, and for optically thin gas at an excitation temperature of 10 K, this sensitivity corresponds to column densities of $N_{\mathrm{H}_{2}} \sim 3 \times 10^{20}\,$cm$^{-2}$ and $N_{\mathrm{H}_{2}} \sim 4 \times 10^{21}\,$cm$^{-2}$ for $^{13}$CO and C$^{18}$O, respectively. The molecular gas that CHIMPS traces is at higher column densities and is also more optically thin than in other publicly available CO surveys due to its rarer isotopologues, and thus more representative of the three-dimensional structure of the clouds. The critical density of the J=3-2 transition of CO is $\gtrsim 10^{4}$ cm$^{-3}$ at temperatures of $\leq 20$ K, and so the higher density gas associated with star formation is well traced. These data complement other existing Galactic plane surveys, especially the JCMT Galactic Plane Survey which has similar spatial resolution and column density sensitivity, and the Herschel infrared Galactic Plane Survey. In this paper, we discuss the observations, data reduction and characteristics of the survey, presenting integrated emission maps for the region covered. Position-velocity diagrams allow comparison with Galactic structure models of the Milky Way, and while we find good agreement with a particular four arm model, there are some significant deviations

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Focal Distribution of Hepatitis C Virus RNA in Infected Livers

Background: Hepatitis C virus (HCV) is a plus-strand RNA virus that replicates by amplification of genomic RNA from minus strands leading to accumulation of almost one thousand copies per cell under in vitro cell culture conditions. In contrast, HCV RNA copy numbers in livers of infected patients appear to be much lower, estimated at a few copies per cell. Methodology/Principal Findings: To gain insights into mechanisms that control HCV replication in vivo, we analyzed HCV RNA levels as well as expression of interferon beta (IFNb) and several interferon stimulated genes (ISGs) from whole liver sections and micro-dissected subpopulations of hepatocytes in biopsy samples from 21 HCV-infected patients. The results showed that intrahepatic HCV RNA levels range form less than one copy per hepatocyte to a maximum of about eight. A correlation existed between viral RNA levels and IFNb expression, but not between viral RNA and ISG levels. Also, IFNb expression did not correlate with ISGs levels. Replication of HCV RNA occurred in focal areas in the liver in the presence of a general induction of ISGs. Conclusion/Significance: The low average levels of HCV RNA in biopsy samples can be explained by focal distribution of infected hepatocytes. HCV replication directly induces IFNb, which then activates ISGs. The apparent lack of a correlation between levels of IFNb and ISG expression indicates that control of the innate immune response during HCV infection

Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers

Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n=18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg). Results: Thirty-seven participants completed follow-up assessments. Median class attendance was 36 (range 2 to 36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504 to 1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028 to 1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274 to 1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI -0.377 to 1.161). Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Keywords Randomized controlled trial; Exercise; Ulceration; Vascular function; Laser Doppler fluxmetry; Iontophoresi

Polarised Asymmetric Inheritance of Accumulated Protein Damage in Higher Eukaryotes

Disease-associated misfolded proteins or proteins damaged due to cellular stress are generally disposed via the cellular protein quality-control system. However, under saturating conditions, misfolded proteins will aggregate. In higher eukaryotes, these aggregates can be transported to accumulate in aggresomes at the microtubule organizing center. The fate of cells that contain aggresomes is currently unknown. Here we report that cells that have formed aggresomes can undergo normal mitosis. As a result, the aggregated proteins are asymmetrically distributed to one of the daughter cells, leaving the other daughter free of accumulated protein damage. Using both epithelial crypts of the small intestine of patients with a protein folding disease and Drosophila melanogaster neural precursor cells as models, we found that the inheritance of protein aggregates during mitosis occurs with a fixed polarity indicative of a mechanism to preserve the long-lived progeny

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV