Imaging hydrogen interactions with materials at the nanoscale: SIMS-based correlative microscopy

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Simulation of a Cold Gas Thruster System and Test Data Correlation

During developmental testing of the Ascent Abort 1 (AA-1) cold gas thruster system, unexpected behavior was detected. Upon further review the design as it existed may not have met the requirements. To determine the best approach for modifying the design, the system was modeled with a dynamic fluid analysis tool (EASY5). The system model consisted of the nitrogen storage tank, pressure regulator, thruster valve, nozzle, and the associated interconnecting line lengths. The regulator and thruster valves were modeled using a combination of the fluid and mechanical modules available in EASY5. The simulation results were then compared against actual system test data. The simulation results exhibited behaviors similar to the test results, such as the pressure regulators response to thruster firings. Potential design solutions were investigated using the analytical model parameters, including increasing the volume downstream of the regulator and increasing the orifice area. Both were shown to improve the regulator response

Ruxolitinib and interferon-alpha 2 combination therapy for patients with polycythemia vera or myelofibrosis:a phase II study

We report the final 2-year end-of-study results from the first clinical trial investigating combination treatment with ruxolitinib and low-dose pegylated interferon-α2 (PEG-IFNα2). The study included 32 patients with polycythemia vera and 18 with primary or secondary myelofibrosis; 46 patients were previously intolerant of or refractory to PEGIFNα2. The primary outcome was efficacy, based on hematologic parameters, quality of life measurements, and JAK2 V617F allele burden. We used the 2013 European LeukemiaNet and International Working Group- Myeloproliferative Neoplasms Research and Treatment response criteria, including response in symptoms, splenomegaly, peripheral blood counts, and bone marrow. Of 32 patients with polycythemia vera, ten (31%) achieved a remission which was a complete remission in three (9%) cases. Of 18 patients with myelofibrosis, eight (44%) achieved a remission; five (28%) were complete remissions. The cumulative incidence of peripheral blood count remission was 0.85 and 0.75 for patients with polycythemia vera and myelofibrosis, respectively. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score decreased from 22 [95% confidence interval (95% CI):, 16-29] at baseline to 15 (95% CI: 10-22) after 2 years. The median JAK2 V617F allele burden decreased from 47% (95% CI: 33-61%) to 12% (95% CI: 6-22%), and 41% of patients achieved a molecular response. The drop-out rate was 6% among patients with polycythemia vera and 32% among those with myelofibrosis. Of 36 patients previously intolerant of PEG-IFNα2, 31 (86%) completed the study, and 24 (67%) of these received PEG-IFNα2 throughout the study. In conclusion, combination treatment improved cell counts, reduced bone marrow cellularity and fibrosis, decreased JAK2 V617F burden, and reduced symptom burden with acceptable toxicity in several patients with polycythemia vera or myelofibrosis. #EudraCT2013-003295-12

An Injection System for the CHIME/FRB Experiment

Dedicated surveys searching for Fast Radio Bursts (FRBs) are subject to selection effects which bias the observed population of events. Software injection systems are one method of correcting for these biases by injecting a mock population of synthetic FRBs directly into the realtime search pipeline. The injected population may then be used to map intrinsic burst properties onto an expected signal-to-noise ratio (SNR), so long as telescope characteristics such as the beam model and calibration factors are properly accounted for. This paper presents an injection system developed for the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst project (CHIME/FRB). The system was tested to ensure high detection efficiency, and the pulse calibration method was verified. Using an injection population of ~85,000 synthetic FRBs, we found that the correlation between fluence and SNR for injected FRBs was consistent with that of CHIME/FRB detections in the first CHIME/FRB catalog. We also noted that the sensitivity of the telescope varied strongly as a function of the broadened burst width, but not as a function of the dispersion measure. We conclude that some of the machine-learning based Radio Frequency Interference (RFI) mitigation methods used by CHIME/FRB can be re-trained using injection data to increase sensitivity to wide events, and that planned upgrades to the presented injection system will allow for determining a more accurate CHIME/FRB selection function in the near future.Comment: 13 pages, 8 figures. Submitted to A

The MOST Hosts Survey: spectroscopic observation of the host galaxies of ~40,000 transients using DESI

We present the MOST Hosts survey (Multi-Object Spectroscopy of Transient Hosts). The survey is planned to run throughout the five years of operation of the Dark Energy Spectroscopic Instrument (DESI) and will generate a spectroscopic catalog of the hosts of most transients observed to date, in particular all the supernovae observed by most public, untargeted, wide-field, optical surveys (PTF/iPTF, SDSS II, ZTF, DECAT, DESIRT). Scientific questions for which the MOST Hosts survey will be useful include Type Ia supernova cosmology, fundamental plane and peculiar velocity measurements, and the understanding of the correlations between transients and their host galaxy properties. Here, we present the first release of the MOST Hosts survey: 21,931 hosts of 20,235 transients. These numbers represent 36% of the final MOST Hosts sample, consisting of 60,212 potential host galaxies of 38,603 transients (a transient can be assigned multiple potential hosts). Of these galaxies, 40% do not appear in the DESI primary target list and therefore require a specific program like MOST Hosts. Of all the transients in the MOST Hosts list, only 26.7% have existing classifications, and so the survey will provide redshifts (and luminosities) for nearly 30,000 transients. A preliminary Hubble diagram and a transient luminosity-duration diagram are shown as examples of future potential uses of the MOST Hosts survey. The survey will also provide a training sample of spectroscopically observed transients for photometry-only classifiers, as we enter an era when most newly observed transients will lack spectroscopic classification. The MOST Hosts DESI survey data will be released through the Wiserep platform on a rolling cadence and updated to match the DESI releases. Dates of future releases and updates are available through the https://mosthosts.desi.lbl.gov website.Comment: Submitted to ApJ

Casein kinase I delta controls centrosome positioning during T cell activation

CK1delta binds and phosphorylates the microtubule plus-end–binding protein EB1 and promotes centrosome translocation to the immunological synapse in T cells

A Drosophila-centric view of protein tyrosine phosphatases

AbstractMost of our knowledge on protein tyrosine phosphatases (PTPs) is derived from human pathologies and mouse knockout models. These models largely correlate well with human disease phenotypes, but can be ambiguous due to compensatory mechanisms introduced by paralogous genes. Here we present the analysis of the PTP complement of the fruit fly and the complementary view that PTP studies in Drosophila will accelerate our understanding of PTPs in physiological and pathological conditions. With only 44 PTP genes, Drosophila represents a streamlined version of the human complement. Our integrated analysis places the Drosophila PTPs into evolutionary and functional contexts, thereby providing a platform for the exploitation of the fly for PTP research and the transfer of knowledge onto other model systems

The “Phagocytic Synapse” and Clearance of Apoptotic Cells

Apoptosis and subsequent phagocytic clearance of apoptotic cells is important for embryonic development, maintenance of tissues that require regular cellular renewal and innate immunity. The timely removal of apoptotic cells prevents progression to secondary necrosis and release of cellular contents, preventing cellular stress and inflammation. In addition, altered phagocyte behavior following apoptotic cell contact and phagocytosis engages an anti-inflammatory phenotype, which impacts upon development and progression of inflammatory and immune responses. Defective apoptotic cell clearance underlies the development of various inflammatory and autoimmune diseases. There is considerable functional redundancy in the receptors that mediate apoptotic cell clearance, highlighting the importance of this process in diverse physiological processes. A single phagocyte may utilize multiple receptor pathways for the efficient capture of apoptotic cells by phagocytes (tethering) and the subsequent initiation of signaling events necessary for internalization. In this review, we will consider the surface alterations and molecular opsonization events associated with apoptosis that may represent a tunable signal that confers distinct intracellular signaling events and hence specific phagocyte responses in a context-dependent manner. Efficient molecular communication between phagocytes and apoptotic targets may require cooperative receptor utilization and the establishment of efferocytic synapse, which acts to stabilize adhesive interactions and facilitate the organization of signaling platforms that are necessary for controlling phagocyte responses

Serum Adhesion Molecule Levels as Prognostic Markers in Patients with Early Systemic Sclerosis: A Multicentre, Prospective, Observational Study

Objective: To assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. Methods: Ninety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) -1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically. Results: At their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters. Conclusion: In patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings