Burst and persistent emission properties during the recent active episode of the anomalous x-ray pulsar 1E 1841-045

Copyright American Astronomical SocietyThe Swift/Burst Alert Telescope detected the first burst from 1E 1841-045 in 2010 May with intermittent burst activity recorded through at least 2011 July. Here we present Swift and Fermi/Gamma-ray Burst Monitor observations of this burst activity and search for correlated changes to the persistent X-ray emission of the source. The T-90 durations of the bursts range between 18 and 140 ms, comparable to other magnetar burst durations, while the energy released in each burst ranges between (0.8-25) x 10(38) erg, which is on the low side of soft gamma repeater bursts. We find that the bursting activity did not have a significant effect on the persistent flux level of the source. We argue that the mechanism leading to this sporadic burst activity in 1E 1841-045 might not involve large-scale restructuring (either crustal or magnetospheric) as seen in other magnetar sources.Peer reviewedFinal Accepted Versio

Testing the Asteroseismic Mass Scale Using Metal-Poor Stars Characterized with APOGEE and Kepler

Fundamental stellar properties, such as mass, radius, and age, can be inferred using asteroseismology. Cool stars with convective envelopes have turbulent motions that can stochastically drive and damp pulsations. The properties of the oscillation frequency power spectrum can be tied to mass and radius through solar-scaled asteroseismic relations. Stellar properties derived using these scaling relations need verification over a range of metallicities. Because the age and mass of halo stars are well-constrained by astrophysical priors, they provide an independent, empirical check on asteroseismic mass estimates in the low-metallicity regime. We identify nine metal-poor red giants (including six stars that are kinematically associated with the halo) from a sample observed by both the Kepler space telescope and the Sloan Digital Sky Survey-III APOGEE spectroscopic survey. We compare masses inferred using asteroseismology to those expected for halo and thick-disk stars. Although our sample is small, standard scaling relations, combined with asteroseismic parameters from the APOKASC Catalog, produce masses that are systematically higher (=0.17+/-0.05 Msun) than astrophysical expectations. The magnitude of the mass discrepancy is reduced by known theoretical corrections to the measured large frequency separation scaling relationship. Using alternative methods for measuring asteroseismic parameters induces systematic shifts at the 0.04 Msun level. We also compare published asteroseismic analyses with scaling relationship masses to examine the impact of using the frequency of maximum power as a constraint. Upcoming APOKASC observations will provide a larger sample of ~100 metal-poor stars, important for detailed asteroseismic characterization of Galactic stellar populations.Comment: 4 figures; 1 table. Accepted to ApJ

Performance of high-efficiency photovoltaic systems in a maritime climate

Today more than 80% of all installed PV power in the UK is generated from grid-connected photovoltaic (PV) systems [1]. Currently the energy generated is not remunerated preferentially in the UK, but in the future the energy yield of photovoltaics will gain in importance over an ideal-case power rating. The challenge here is to design highly efficient systems in order to arrive at cost-effective PV solutions. Advances in PV have resulted in new high-efficiency modules being introduced into the marketplace, promising superior performance in terms of efficiency (i.e. kWh/m2) as well as specific energy yield (i.e. kWh/kWp). These promises can only be fulfilled if the complete system is able to capitalise on the advances in the module technology, as the BOS components play possibly the most significant role in the energy production in maritime climates. A programme to validate these promises has been started and initial work is reported. The long term aim of this research is to model not only the module performance with regard to irradiation, temperature and spectrum, but also their performance in grid-connected systems. The model will cover the whole system, from single modules, to DC-AC generation and mismatch. A measurement campaign has been designed to allow validation of the model

A Systems Approach for Tumor Pharmacokinetics

Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.National Institutes of Health (U.S.) (grant T32 CA079443

The K2 Galactic Archaeology Program Data Release 3: Age-abundance Patterns in C1–C8 and C10–C18

© 2022. The Author(s). Published by the American Astronomical Society. Content from this work may be used under the terms of the Creative Commons Attribution 4.0 license. https://creativecommons.org/licenses/by/4.0/Abstract: We present the third and final data release of the K2 Galactic Archaeology Program (K2 GAP) for Campaigns C1–C8 and C10–C18. We provide asteroseismic radius and mass coefficients, κ R and κ M , for ∼19,000 red giant stars, which translate directly to radius and mass given a temperature. As such, K2 GAP DR3 represents the largest asteroseismic sample in the literature to date. K2 GAP DR3 stellar parameters are calibrated to be on an absolute parallactic scale based on Gaia DR2, with red giant branch and red clump evolutionary state classifications provided via a machine-learning approach. Combining these stellar parameters with GALAH DR3 spectroscopy, we determine asteroseismic ages with precisions of ∼20%–30% and compare age-abundance relations to Galactic chemical evolution models among both low- and high-α populations for α, light, iron-peak, and neutron-capture elements. We confirm recent indications in the literature of both increased Ba production at late Galactic times as well as significant contributions to r-process enrichment from prompt sources associated with, e.g., core-collapse supernovae. With an eye toward other Galactic archeology applications, we characterize K2 GAP DR3 uncertainties and completeness using injection tests, suggesting that K2 GAP DR3 is largely unbiased in mass/age, with uncertainties of 2.9% (stat.) ± 0.1% (syst.) and 6.7% (stat.) ± 0.3% (syst.) in κ R and κ M for red giant branch stars and 4.7% (stat.) ± 0.3% (syst.) and 11% (stat.) ± 0.9% (syst.) for red clump stars. We also identify percent-level asteroseismic systematics, which are likely related to the time baseline of the underlying data, and which therefore should be considered in TESS asteroseismic analysis.Peer reviewedFinal Published versio

Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

Purpose: Tumor microenvironments show remarkable tumor pO_{2} heterogeneity, as seen in prior EPR pO_{2} images (EPROI). pO_{2} correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures: To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO_{2}. Results: Quantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO_{2}, median pO_{2}, and the fraction of voxels in the biopsy volume with pO_{2} less than 3, 6, and 10 Torr. Conclusions: This validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival