A new code for following the evolution and emissions of proto-neutron stars during the first minute of their lives is developed and tested. The code is one dimensional, fully implicit, and general ...relativistic. Multi-group, multi-flavor neutrino transport is incorporated that makes use of variable Eddington factors obtained from a formal solution of the static general relativistic Boltzmann equation with linearized scattering terms. The timescales of neutrino emission and spectral evolution obtained using the new code are broadly consistent with previous results. Unlike other recent calculations, however, the new code predicts that the neutrino-driven wind will be characterized, at least for part of its existence, by a neutron excess. This change, potentially consequential for nucleosynthesis in the wind, is due to an improved treatment of the charged current interactions of electron-flavored neutrinos and anti-neutrinos with nucleons. A comparison is also made between the results obtained using either variable Eddington factors or simple equilibrium flux-limited diffusion. The latter approximation, which has been frequently used in previous studies of proto-neutron star cooling, accurately describes the total neutrino luminosities (to within 10%) for most of the evolution, until the proto-neutron star becomes optically thin.
We investigate the possibility that long tidal tails formed during compact object mergers may produce optical transients powered by the decay of freshly synthesized r-process material. Precise ...modeling of the merger dynamics allows for a realistic determination of the thermodynamic conditions in the ejected debris. We combine hydrodynamic and full nuclear network calculations to determine the resultant r-process abundances and the heating of the material by their decays. The subsequent homologous structure is mapped into a radiative transfer code to synthesize emergent model light curves and determine how their properties (variability and color evolution) depend on the mass ratio and orientation of the merging binary. The radiation emanating from the ejected debris, though less spectacular than a typical supernova, should be observable in transient surveys and we estimate the associated detection rates. We find that it is unlikely that photometry alone will be able to distinguish between different binary mass ratios and the nature of the compact objects, emphasizing the need for spectroscopic follow-up of these events. The case for (or against) compact object mergers as the progenitors of short gamma-ray bursts can be tested if such electromagnetic transients are detected (or not) in coincidence with some bursts, although they may be obscured by on-axis afterglows.
Although they are but a small fraction of the mass ejected in core-collapse supernovae, neutrino-driven winds (NDWs) from nascent proto-neutron stars (PNSs) have the potential to contribute ...significantly to supernova nucleosynthesis. In previous works, the NDW has been implicated as a possible source of r-process and light p-process isotopes. In this paper, we present time-dependent hydrodynamic calculations of nucleosynthesis in the NDW which include accurate weak interaction physics coupled to a full nuclear reaction network. Using two published models of PNS neutrino luminosities, we predict the contribution of the NDW to the integrated nucleosynthetic yield of the entire supernova. For the neutrino luminosity histories considered, no true r-process occurs in the most basic scenario. The wind driven from an older 1.4 M{sub sun} model for a PNS is moderately neutron-rich at late times however, and produces {sup 87}Rb, {sup 88}Sr, {sup 89}Y, and {sup 90}Zr in near solar proportions relative to oxygen. The wind from a more recently studied 1.27 M{sub sun} PNS is proton-rich throughout its entire evolution and does not contribute significantly to the abundance of any element. It thus seems very unlikely that the simplest model of the NDW can produce the r-process. At most, it contributes to the production of the N = 50 closed shell elements and some light p-nuclei. In doing so, it may have left a distinctive signature on the abundances in metal-poor stars, but the results are sensitive to both uncertain models for the explosion and the masses of the neutron stars involved.
Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates ...(TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models.
hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry.
Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair.
Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.
Background and Purpose
Sphingosine1‐phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 ...receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non‐selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases.
Experimental Approach
The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6‐trinitrobenzenesulfonic acid colitis and CD4+CD45RBhi T cell adoptive transfer colitis) was assessed.
Key Results
RPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7+ T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half‐life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models.
Conclusions and Implications
S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic.
This book serves as a sourcebook to enhance and evaluate safety programs, generate new solutions and interventions, comply with new legislation, and present practical steps and guidelines to ...establish best practices. It pays particular attention to the factors that may give rise to crime, considering high-risk drinking and examining the intersection between hate crimes and violence. Devoting chapters to discrimination in all its forms, whether against international students, students of color, or on the basis of ethnicity or sexual orientation, it reviews the range of issues relating to harassment and violence against women and engages with hazing and the presence of guns on campus. The authors pay attention to the different circumstances that may apply in specific institutional types, such as community colleges and minority-serving institutions. They offer perspectives from administrators, campus security, student affairs personnel, faculty and policy makers. The purpose is to provide readers with the context and tools to devise a comprehensive safety plan. For administrators operating with few formal support systems, advice is given on how to co-opt individuals and resources from around the campus and the local community to assist in maintaining a safe and welcoming campus. Click here for press release.
The β-decay half-lives of 94 neutron-rich nuclei 144−151Cs, 146−154Ba, 148−156La, 150−158Ce, 153−160Pr, 156−162Nd, 159−163Pm, 160−166Sm, 161−168Eu, 165−170Gd, 166−172Tb, 169−173Dy, 172−175Ho, and two ...isomeric states 174mEr, 172mDy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of β-decay half-lives are observed at neutron-number N=97 for 58Ce, 59Pr, 60Nd, and 62Sm, and N=105 for 63Eu, 64Gd, 65Tb, and 66Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.
Abstract Age is a primary risk factor for Parkinson's disease (PD); however, the effects of aging on the Parkinsonian brain remain poorly understood, particularly for deep brain structures. We ...investigated intraoperative micro‐electrode recordings from the subthalamic nucleus (STN) of PD patients aged between 42 and 76 years. Age was associated with decreased oscillatory beta power and non‐oscillatory high‐frequency power, independent of PD‐related variables. Single unit firing and burst rates were also reduced, whereas the coefficient of variation and the structure of burst activity were unchanged. Phase synchronization (debiased weighed phase lag index dWPLI) between sites was pronounced in the beta band between electrodes in the superficial STN but was unaffected by age. Our results show that aging is associated with reduced neuronal activity without changes to its temporal structure. We speculate that the loss of activity in the STN may mediate the relationship between PD and age.
Summary
The present study examines the temporal dynamics of macrophage activation marker expression in response to variations in stimulation. We demonstrate that markers can be categorized as ‘early’ ...(expressed most abundantly at 6 h post‐stimulation) or ‘late’ (expressed at 24 h post‐stimulation). Thus nos2 and p40 (IL‐12/IL‐23) are early markers of innate and classical activation, while dectin‐1 and mrc‐1 are early markers and fizz1 (found in inflammatory zone‐1) and ym1 are late markers of alternative activation. Furthermore, argI is a late marker of both innate and alternative activation. The ability of interferon (IFN)‐γ to alter these activation markers was studied at both the protein level and gene level. As reported previously, IFN‐γ was able to drive macrophages towards the classical phenotype by enhancing nos2 gene expression and enzyme activity and p40 (IL‐12/IL‐23) gene expression in lipopolysaccharide (LPS)‐stimulated macrophages. IFN‐γ antagonized alternative macrophage activation, as evident by reduced expression of dectin‐1, mrc‐1, fizz1 and ym1 mRNA transcripts. In addition, IFN‐γ antagonized arginase activity irrespective of whether macrophages were activated innately or alternatively. Our data explain some apparent contradictions in the literature, demonstrate temporal plasticity in macrophage activation states and define for the first time ‘early’ and ‘late’ markers associated with anti‐microbial/inflammatory and wound healing responses, respectively.
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