A Bayesian analysis of the 27 highest energy cosmic rays detected by the Pierre Auger Observatory

It is possible that ultra-high energy cosmic rays (UHECRs) are generated by active galactic nuclei (AGNs), but there is currently no conclusive evidence for this hypothesis. Several reports of correlations between the arrival directions of UHECRs and the positions of nearby AGNs have been made, the strongest detection coming from a sample of 27 UHECRs detected by the Pierre Auger Observatory (PAO). However, the PAO results were based on a statistical methodology that not only ignored some relevant information (most obviously the UHECR arrival energies but also some of the information in the arrival directions) but also involved some problematic fine-tuning of the correlation parameters. Here we present a fully Bayesian analysis of the PAO data (collected before 2007 September), which makes use of more of the available information, and find that a fraction F_AGN = 0.15^(+0.10)_(-0.07) of the UHECRs originate from known AGNs in the Veron-Cetty & Veron (VCV) catalogue. The hypothesis that all the UHECRs come from VCV AGNs is ruled out, although there remains a small possibility that the PAO-AGN correlation is coincidental (F_AGN = 0.15 is 200 times as probable as F_AGN = 0.00).Comment: MNRAS, accepted; 8 pages, 7 figure

Embryo collection induces transient activation of XBP1 arm of the ER stress response while embryo vitrification does not.

Embryo cryopreservation has become a standard procedure in the practice of assisted reproduction. While routinely performed in IVF labs, the effects of embryo vitrification on the molecular mechanisms governing preimplantation development remain largely unknown. The endoplasmic reticulum stress (ER stress) response is an evolutionary conserved mechanism that cells employ to manage ER stress. ER stress can be defined as an imbalance between protein synthesis and secretion within the ER. The primary focus of this study was to investigate whether standard embryo manipulations, including embryo collection, culture and vitrification, result in activation of the ER stress pathway in vitro and to determine whether the embryo utilizes the unfolded protein response as an adaptive response. Our results indicate that the major ER stress pathway constituents are present at all stages of preimplantation development and that the activation of ER stress pathways can be induced at the 8-cell, morula and blastocyst stages. Additionally, we have demonstrated that the IRE1α arm of the ER Stress pathway is activated in freshly collected embryos but contrastingly, this ER Stress arm is not activated following embryo vitrification. It is important to understand the possible stresses that Assisted Reproductive Technologies place on the embryo and the mechanisms the embryo employs to adapt to these stresses. This study indicates that among the adaptive pathways available, cultured mammalian embryos can employ the ER stress pathway. Assisted reproduction techniques should be aware that their activities may induce the ER stress pathway in their patients\u27 early embryos

Analgesic prescribing trends in a national sample of older veterans with osteoarthritis: 2012-2017

Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre–post observational study of all older U.S. veterans (≥50 years old) with osteoarthritis of the knee or hip. All associated outpatient analgesic prescriptions and outpatient pain intensity ratings from January 1, 2012 to December 31, 2016, were analyzed with segmented regression of interrupted time series. Standardized monthly rates for each analgesic class (total, opioid, nonsteroidal anti-inflammatory drug, acetaminophen, and other study analgesics) were analyzed with segmented negative binomial regression models with overall slope, step, and slope change. Similarly, segmented linear regression was used to analyze pain intensity ratings and percentage of those reporting pain. All models were additionally adjusted for age, sex, and race. Before OSI implementation, total analgesic prescriptions showed a steady rise, abruptly decreasing to a flat trajectory after OSI implementation. This trend was primarily due to a decrease in opioid prescribing after OSI. Total prescribing after OSI implementation was partially compensated by continuing increased prescribing of other study analgesics as well as a significant rise in acetaminophen prescriptions (post-OSI). No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis

Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?

The CCN (cyr61, ctgf, nov) family of modular proteins regulate diverse biological affects including cell adhesion, matrix production, tissue remodelling, proliferation and differentiation. Recent targeted gene disruption studies have demonstrated the CCN family to be developmentally essential for chondrogenesis, osteogenesis and angiogenesis. CCN2 is induced by agents such as angiotensin II, endothelin-1, glucocorticoids, HGF, TGFβ, and VEGF, and by hypoxia and biomechanical and shear stress. Dysregulated expression of CCN2 has also been widely documented in many fibroproliferative diseases. This mini-review will focus on CCN2, and the recent progress in understanding CCN2 gene regulation in health and disease. That CCN2 should be considered a novel and informative surrogate clinical bio-marker for fibroproliferative disease is discussed

Allometry of sodium requirements and mineral lick use among herbivorous mammals

Sodium (Na) plays a critical role in the functioning of terrestrial ecosystems. In Na-poor regions, plant consumers may experience Na deficiency and adapt by seeking supplementary Na resources. This can markedly impact animal behavior, space-use, and co-existence, with concomitant impacts on ecosystems. Many studies have noted that Na-seeking behaviors, such as soil consumption from mineral licks, are predominately observed for larger-bodied herbivores. However, the mechanisms that drive interspecific variation in Na deficiency and mineral lick use remain poorly understood. Here, we examine whether allometric scaling of Na requirements can explain variation in mineral lick use by herbivorous and omnivorous mammals. We 1) collated data from published literature to derive an allometric scaling of Na requirements in mammals, 2) compared predicted Na requirements to estimated Na intake of mammal communities in three globally distant sites: the Peruvian Amazon, Kalahari Desert, and Malaysian Borneo and 3) examined the relationship between predicted Na deficiency and mineral lick use utilizing camera-trap and mammal abundance data at each site. We found that minimum daily Na maintenance requirements in mammals scaled allometrically at a higher factor (BM0.91 (CI: 0.80–1.0)) than that of food and water Na intake (BM0.71–0.79), indicating that larger species may be more susceptible to Na limitation. This aligned with a positive association between mineral lick use and body mass (BM), as well as Na deficiency, by species at all sites, and increased artificial salt and mineral lick consumption by larger-bodied mammals in the Kalahari. Our results suggest that larger herbivores may be more sensitive to anthropogenic impacts to Na availability, which may alter their functional roles in ecosystems, particularly in Na-poor regions. Further research is needed to explore the consequences of changing Na availability on animals and ecosystems, as well as advance our understanding of Na physiology in mammals

Serendipitously Detected Galaxies in the Hubble Deep Field

We present a catalog of 74 galaxies detected serendipitously during a campaign of spectroscopic observations of the Hubble Deep Field North (HDF) and its environs. Among the identified objects are five candidate Ly-alpha emitters at z > 5, a galaxy cluster at z = 0.85, and a Chandra source with a heretofore undetermined redshift of z = 2.011. We report redshifts for 25 galaxies in the central HDF, 13 of which had no prior published spectroscopic redshift. Of the remaining 49 galaxies, 30 are located in the single-orbit HDF Flanking Fields. We discuss the redshift distribution of the serendipitous sample, which contains galaxies in the range 0.10 < z < 5.77 with a median redshift of z = 0.85, and we present strong evidence for redshift clustering. By comparing our spectroscopic redshifts to optical/IR photometric studies of the HDF, we find that photometric redshifts are in most cases capable of producing reasonable predictions of galaxy redshifts. Finally, we estimate the line-of-sight velocity dispersion and the corresponding mass and expected X-ray luminosity of the galaxy cluster, we present strong arguments for interpreting the Chandra source as an obscured AGN, and we discuss in detail the spectrum of one of the candidate z > 5 Ly-alpha emitters.Comment: 18 pages, 9 figures, accepted for publication in the Astronomical Journa

Pericytes display increased CCN2 expression upon culturing

By providing a source of α-smooth muscle actin (α-SMA)-expressing myofibroblasts, microvascular pericytes contribute to the matrix remodeling that occurs during tissue repair. However, the extent to which pericytes may contribute to the fibroblast phenotype post-repair is unknown. In this report, we test whether pericytes isolated from human placenta can in principle become fibroblast-like. Pericytes were cultured in vitro for 11 passages. The Affymetrix mRNA expression profile of passage 2 and passage 11 pericytes was compared. The expression of type I collagen, thrombospondin and fibronectin mRNAs was induced by passaging pericytes in culture. This induction of a fibroblast phenotype was paralleled by induction of connective tissue growth factor (CTGF/CCN2) and type I collagen protein expression and the fibroblast marker ASO2. These results indicate that, in principle, pericytes have the capacity to become fibroblast-like and that pericytes may contribute to the population of fibroblasts in a healed wound

A Tip of the Red Giant Branch Distance to the Dark Matter Deficient Galaxy NGC1052-DF4 from Deep Hubble Space Telescope Data

Previous studies have shown that the large, diffuse galaxies NGC1052-DF2 and NGC1052-DF4 both have populations of unusually luminous globular clusters as well as a very low dark matter content. Here we present newly-obtained deep Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) imaging of one of these galaxies, NGC1052-DF4. We use these data to measure the distance of the galaxy from the location of the tip of the red giant branch (TRGB). We find a rapid increase in the number of detected stars fainter than $m_{F814W} \sim 27.3$, which we identify as the onset of the red giant branch. Using a forward modeling approach that takes the photometric uncertainties into account, we find a TRGB magnitude of $m_{F814W,\rm TRGB}=27.47 \pm 0.16$. The inferred distance, including the uncertainty in the absolute calibration, is $D_{\rm TRGB}=20.0 \pm 1.6$ Mpc. The TRGB distance of NGC1052-DF4 is consistent with the previously-determined surface brightness fluctuation distance of $D_{\rm SBF}=18.7\pm 1.7$ Mpc to NGC1052-DF2 and is consistent with the distance of the bright elliptical galaxy NGC1052. We conclude that the unusual properties of these galaxies cannot be explained by distance errors.Comment: Accepted for publication in ApJ Letters, in press. Figure 1 shows the color image of the galaxy. The main result is shown in Figure

An RNAi Screen for Genes Required for Growth of Drosophila Wing Tissue

Cell division and tissue growth must be coordinated with development. Defects in these processes are the basis for a number of diseases, including developmental malformations and cancer. We have conducted an unbiased RNAi screen for genes that are required for growth in the Drosophila wing, using GAL4-inducible short hairpin RNA (shRNA) fly strains made by the Drosophila RNAi Screening Center. shRNA expression down the center of the larval wing disc using dpp-GAL4, and the central region of the adult wing was then scored for tissue growth and wing hair morphology. Out of 4,753 shRNA crosses that survived to adulthood, 18 had impaired wing growth. FlyBase and the new Alliance of Genome Resources knowledgebases were used to determine the known or predicted functions of these genes and the association of their human orthologs with disease. The function of eight of the genes identified has not been previously defined in Drosophila The genes identified included those with known or predicted functions in cell cycle, chromosome segregation, morphogenesis, metabolism, steroid processing, transcription, and translation. All but one of the genes are similar to those in humans, and many are associated with disease. Knockdown of lin-52, a subunit of the Myb-MuvB transcription factor, or βNACtes6, a gene involved in protein folding and trafficking, resulted in a switch from cell proliferation to an endoreplication growth program through which wing tissue grew by an increase in cell size (hypertrophy). It is anticipated that further analysis of the genes that we have identified will reveal new mechanisms that regulate tissue growth during development