Joint Genetic Analysis of Conception and Maintenance of Pregnancy in Dairy Cattle Using a Linear-Threshold Model

A joint analysis of days open and calving success was implemented to further enhance the identification of cows with greater genetic merit for reproductive performance. Calving success is a categorical trait with similar genetic variation as days open and is analyzed jointly with days open to make effective use of the positive genetic correlation between these two traits. The joint analysis can identify cows with greater genetic merit for conception at an earlier stage of lactation and greater success at maintenance of pregnancy. The joint analysis also enhances the reliability of detecting true genetic differences between cows for fertility because it makes more effective use of all data

Genetic Analyses of Days Open Using a Random Regression Model

The purpose of this study was to investigate the feasibility of using a linear random regression model for the analysis of female fertility as expressed by days open. The analysis provided insight about the kind and amount of variation over the trajectory for age at calving from 24 to 72 mo. Correlations between permanent environmental effects changed from positive to negative values with greater distance between days open in young cows and days open in older cows; r(24,36)=0.88, r(24,72)=-.65. The random regression animal model proved to be a better alternative to a repeatability animal model for prediction of breeding values for days open. Random regression enables breeders to pick the optimum age at calving to select female replacements with enhanced fertility or fewer days open per lactation. Further research is needed to evaluate the advantages of using random regression model on the genetic analysis of days open

PTF10fqs: A Luminous Red Nova in the Spiral Galaxy Messier 99

The Palomar Transient Factory (PTF) is systematically charting the optical transient and variable sky. A primary science driver of PTF is building a complete inventory of transients in the local Universe (distance less than 200 Mpc). Here, we report the discovery of PTF10fqs, a transient in the luminosity "gap" between novae and supernovae. Located on a spiral arm of Messier 99, PTF 10fqs has a peak luminosity of Mr = -12.3, red color (g-r = 1.0) and is slowly evolving (decayed by 1 mag in 68 days). It has a spectrum dominated by intermediate-width H (930 km/s) and narrow calcium emission lines. The explosion signature (the light curve and spectra) is overall similar to thatof M85OT2006-1, SN2008S, and NGC300OT. The origin of these events is shrouded in mystery and controversy (and in some cases, in dust). PTF10fqs shows some evidence of a broad feature (around 8600A) that may suggest very large velocities (10,000 km/s) in this explosion. Ongoing surveys can be expected to find a few such events per year. Sensitive spectroscopy, infrared monitoring and statistics (e.g. disk versus bulge) will eventually make it possible for astronomers to unravel the nature of these mysterious explosions.Comment: 12 pages, 12 figures, Replaced with published versio

Lysosome-mediated processing of chromatin in senescence

Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

ASASSN-15lh: a superluminous ultraviolet rebrightening observed by Swift and Hubble

We present and discuss ultraviolet and optical photometry from the Ultraviolet/Optical Telescope and X-ray limits from the X-Ray Telescope on Swift and imaging polarimetry and ultraviolet/optical spectroscopy with the Hubble Space Telescope of ASASSN-15lh. It has been classified as a hydrogenpoor superluminous supernova (SLSN I) more luminous than any other supernova observed. ASASSN- 15lh is not detected in the X-rays in individual or coadded observations. From the polarimetry we determine that the explosion was only mildly asymmetric. We find the flux of ASASSN-15lh to increase strongly into the ultraviolet, with a ultraviolet luminosity a hundred times greater than the hydrogen-rich, ultraviolet-bright SLSN II SN 2008es. We find objects as bright as ASASSN-15lh are easily detectable beyond redshifts of ∼4 with the single-visit depths planned for the Large Synoptic Survey Telescope. Deep near-infrared surveys could detect such objects past a redshift of ∼20 enabling a probe of the earliest star formation. A late rebrightening – most prominent at shorter wavelengths – is seen about two months after the peak brightness, which is itself as bright as a superluminous supernova. The ultraviolet spectra during the rebrightening are dominated by the continuum without the broad absorption or emission lines seen in SLSNe or tidal disruption events and the early optical spectra of ASASSN-15lh. Our spectra show no strong hydrogen emission, showing only Lyα absorption near the redshift previously found by optical absorption lines of the presumed host. The properties of ASASSN-15lh are extreme when compared to either SLSNe or tidal disruption events

[Comment] Redefine statistical significance

The lack of reproducibility of scientific studies has caused growing concern over the credibility of claims of new discoveries based on “statistically significant” findings. There has been much progress toward documenting and addressing several causes of this lack of reproducibility (e.g., multiple testing, P-hacking, publication bias, and under-powered studies). However, we believe that a leading cause of non-reproducibility has not yet been adequately addressed: Statistical standards of evidence for claiming discoveries in many fields of science are simply too low. Associating “statistically significant” findings with P < 0.05 results in a high rate of false positives even in the absence of other experimental, procedural and reporting problems. For fields where the threshold for defining statistical significance is P<0.05, we propose a change to P<0.005. This simple step would immediately improve the reproducibility of scientific research in many fields. Results that would currently be called “significant” but do not meet the new threshold should instead be called “suggestive.” While statisticians have known the relative weakness of using P≈0.05 as a threshold for discovery and the proposal to lower it to 0.005 is not new (1, 2), a critical mass of researchers now endorse this change. We restrict our recommendation to claims of discovery of new effects. We do not address the appropriate threshold for confirmatory or contradictory replications of existing claims. We also do not advocate changes to discovery thresholds in fields that have already adopted more stringent standards (e.g., genomics and high-energy physics research; see Potential Objections below). We also restrict our recommendation to studies that conduct null hypothesis significance tests. We have diverse views about how best to improve reproducibility, and many of us believe that other ways of summarizing the data, such as Bayes factors or other posterior summaries based on clearly articulated model assumptions, are preferable to P-values. However, changing the P-value threshold is simple and might quickly achieve broad acceptance

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

Background: Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Methods: Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.Results: RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. Conclusion: These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma. © 2010 Sadikovic et al; licensee BioMed Central Ltd

Spectra of Hydrogen-poor Superluminous Supernovae from the Palomar Transient Factory

Most Type I superluminous supernovae (SLSNe-I) reported to date have been identified by their high peak luminosities and spectra lacking obvious signs of hydrogen. We demonstrate that these events can be distinguished from normal-luminosity SNe (including Type Ic events) solely from their spectra over a wide range of light-curve phases. We use this distinction to select 19 SLSNe-I and four possible SLSNe-I from the Palomar Transient Factory archive (including seven previously published objects). We present 127 new spectra of these objects and combine these with 39 previously published spectra, and we use these to discuss the average spectral properties of SLSNe-I at different spectral phases. We find that Mn II most probably contributes to the ultraviolet spectral features after maximum light, and we give a detailed study of the O II features that often characterize the early-time optical spectra of SLSNe-I. We discuss the velocity distribution of O II, finding that for some SLSNe-I this can be confined to a narrow range compared to relatively large systematic velocity shifts. Mg II and Fe II favor higher velocities than O II and C II, and we briefly discuss how this may constrain power-source models. We tentatively group objects by how well they match either SN 2011ke or PTF12dam and discuss the possibility that physically distinct events may have been previously grouped together under the SLSN-I label