Connecting the time domain community with the Virtual Astronomical Observatory

The time domain has been identified as one of the most important areas of astronomical research for the next decade. The Virtual Observatory is in the vanguard with dedicated tools and services that enable and facilitate the discovery, dissemination and analysis of time domain data. These range in scope from rapid notifications of time-critical astronomical transients to annotating long-term variables with the latest modeling results. In this paper, we will review the prior art in these areas and focus on the capabilities that the VAO is bringing to bear in support of time domain science. In particular, we will focus on the issues involved with the heterogeneous collections of (ancillary) data associated with astronomical transients, and the time series characterization and classification tools required by the next generation of sky surveys, such as LSST and SKA.Comment: Submitted to Proceedings of SPIE Observatory Operations: Strategies, Processes and Systems IV, Amsterdam, 2012 July 2-

Acceleration of small intestine development and remodeling of the microbiome following hyaluronan 35 KDa treatment in neonatal mice

The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 days in mouse pups leads to increased villus length and crypt depth, and increased goblet and Paneth cells, compared to controls. We also show that HA 35 KDa leads to an increased predominance of Clostridiales Ruminococcaceae, Lactobacillales Lactobacillaceae, and Clostridiales Lachnospiraceae. In seeking the mechanisms involved in the changes, bulk RNA seq was performed on samples from the terminal ileum and identified upregulation in several genes essential for cellular growth, proliferation, and survival. Taken together, this study shows that HA 35 KDa supplemented to mouse pups promotes intestinal epithelial cell proliferation, as well as the development of Paneth cells and goblet cell subsets. HA 35 KDa also impacted the intestinal microbiota; the implications of these responses need to be determined

Transcriptomic regulation of seasonal coat color change in hares

Color molts from summer brown to winter white coats have evolved in several species to maintain camouflage year-round in environments with seasonal snow. Despite the eco-evolutionary relevance of this key phenological adaptation, its molecular regulation has only recently begun to be addressed. Here, we analyze skin transcription changes during the autumn molt of the mountain hare (Lepus timidus) and integrate the results with an established model of gene regulation across the spring molt of the closely related snowshoe hare (L. americanus). We quantified differences in gene expression among three stages of molt progression-"brown" (early molt), "intermediate," and "white" (late molt). We found 632 differentially expressed genes, with a major pulse of expression early in the molt, followed by a milder one in late molt. The functional makeup of differentially expressed genes anchored the sampled molt stages to the developmental timeline of the hair growth cycle, associating anagen to early molt and the transition to catagen to late molt. The progression of color change was characterized by differential expression of genes involved in pigmentation, circadian, and behavioral regulation. We found significant overlap between differentially expressed genes across the seasonal molts of mountain and snowshoe hares, particularly at molt onset, suggesting conservatism of gene regulation across species and seasons. However, some discrepancies suggest seasonal differences in melanocyte differentiation and the integration of nutritional cues. Our established regulatory model of seasonal coat color molt provides an important mechanistic context to study the functional architecture and evolution of this crucial seasonal adaptation

Bayes and health care research.

Bayes’ rule shows how one might rationally change one’s beliefs in the light of evidence. It is the foundation of a statistical method called Bayesianism. In health care research, Bayesianism has its advocates but the dominant statistical method is frequentism. There are at least two important philosophical differences between these methods. First, Bayesianism takes a subjectivist view of probability (i.e. that probability scores are statements of subjective belief, not objective fact) whilst frequentism takes an objectivist view. Second, Bayesianism is explicitly inductive (i.e. it shows how we may induce views about the world based on partial data from it) whereas frequentism is at least compatible with non-inductive views of scientific method, particularly the critical realism of Popper. Popper and others detail significant problems with induction. Frequentism’s apparent ability to avoid these, plus its ability to give a seemingly more scientific and objective take on probability, lies behind its philosophical appeal to health care researchers. However, there are also significant problems with frequentism, particularly its inability to assign probability scores to single events. Popper thus proposed an alternative objectivist view of probability, called propensity theory, which he allies to a theory of corroboration; but this too has significant problems, in particular, it may not successfully avoid induction. If this is so then Bayesianism might be philosophically the strongest of the statistical approaches. The article sets out a number of its philosophical and methodological attractions. Finally, it outlines a way in which critical realism and Bayesianism might work together. </p

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age‐related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, has also been shown to promote aspects of AHN. The 5:2 diet is a popular form of IF; however, its effects on AHN are not well characterised. To address this, we quantified AHN in adolescent and adult wild‐type and ghrelin‐receptor‐deficient mice following 6 weeks on a 5:2 diet. We report an age‐related decline in neurogenic processes. However, the 5:2 diet does not increase AHN nor enhance memory performance, suggesting that this specific form of IF is ineffective in promoting brain plasticity to support learning

Research priorities in the field of posttraumatic pain and disability: Results of a transdisciplinary consensus-generating workshop

© Copyright 2016 David M.Walton et al. Background. Chronic or persistent pain and disability following noncatastrophic \u27musculoskeletal\u27 (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute ofMusculoskeletalHealth and Arthritis (IMHA) has recently identified better understanding of causalmechanisms as one of three priority foci of their most recent strategic plan. Objectives. A 2-day invitation-only active participation workshop was held inMarch 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-relatedMSK pain and disability, prediction, and prevention. Methods. Conversations were recorded, explored thematically, and member-checked for accuracy. Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement. Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms