T-cell Subsets and Antifungal Host Defenses

It has been long appreciated that protective immunity against fungal pathogens is dependent on activation of cellular adaptive immune responses represented by T lymphocytes. The T-helper (Th)1/Th2 paradigm has proven to be essential for the understanding of protective adaptive host responses. Studies that have examined the significance of regulatory T cells in fungal infection, and the recent discovery of a new T-helper subset called Th17 have provided crucial information for understanding the complementary roles played by the various T-helper lymphocytes in systemic versus mucosal antifungal host defense. This review provides an overview of the role of the various T-cell subsets during fungal infections and the reciprocal regulation between the T-cell subsets contributing to the tailored host response against fungal pathogens

Knowledge Graphs Evolution and Preservation -- A Technical Report from ISWS 2019

One of the grand challenges discussed during the Dagstuhl Seminar "Knowledge Graphs: New Directions for Knowledge Representation on the Semantic Web" and described in its report is that of a: "Public FAIR Knowledge Graph of Everything: We increasingly see the creation of knowledge graphs that capture information about the entirety of a class of entities. [...] This grand challenge extends this further by asking if we can create a knowledge graph of "everything" ranging from common sense concepts to location based entities. This knowledge graph should be "open to the public" in a FAIR manner democratizing this mass amount of knowledge." Although linked open data (LOD) is one knowledge graph, it is the closest realisation (and probably the only one) to a public FAIR Knowledge Graph (KG) of everything. Surely, LOD provides a unique testbed for experimenting and evaluating research hypotheses on open and FAIR KG. One of the most neglected FAIR issues about KGs is their ongoing evolution and long term preservation. We want to investigate this problem, that is to understand what preserving and supporting the evolution of KGs means and how these problems can be addressed. Clearly, the problem can be approached from different perspectives and may require the development of different approaches, including new theories, ontologies, metrics, strategies, procedures, etc. This document reports a collaborative effort performed by 9 teams of students, each guided by a senior researcher as their mentor, attending the International Semantic Web Research School (ISWS 2019). Each team provides a different perspective to the problem of knowledge graph evolution substantiated by a set of research questions as the main subject of their investigation. In addition, they provide their working definition for KG preservation and evolution

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Can we accelerate medicinal chemistry by augmenting the chemist with Big Data and artificial intelligence?

It is both the best of times and the worst of times to be a medicinal chemist. Massive amounts of data combined with machine-learning and/or artificial intelligence (AI) tools to analyze it can increase our capabilities. However, drug discovery faces severe economic pressure and a high level of societal need set against challenging targets. Here, we show how improving medicinal chemistry by better curating and exchanging knowledge can contribute to improving drug hunting in all disease areas. Although securing intellectual property (IP) is a critical task for medicinal chemists, it impedes the sharing of generic medicinal chemistry knowledge. Recent developments enable the sharing of knowledge both within and between organizations while securing IP. We also explore the effects of the structure of the corporate ecosystem within drug discovery on knowledge sharing

Structure, doping and superconductivity in HgBa2CaCu2O6+δ (Tc ≤ 128 K)

We have studied the defect structure and superconducting properties of HgBa2CaCu2O6+δ by neutron powder diffraction, AC susceptibility and DC resistivity. An as-synthesized sample has an onset Tc of 128 K, the highest yet reported for this material. The critical temperature decreases slightly (126 K) after oxygenation, and drops to 92 K after reduction in flowing argon. Neutron diffraction data give evidence that the primary doping mechanism in this material is provided by oxygen atoms in an interstitial position, similar to the case of the one-layer compound HgBa2CaO4+δ. The occupancy of this site varies from 0.08 (1) for the argon-reduced sample to 0.22(1) for the oxygenated sample. Unlike the case of the one-layer compound, no evidence of an additional defect site was found in these samples, HgBa2CaCu2O6+δ has remarkably long copper-apical oxygen distances and almost perfectly flat CuO2 planes

Optically Immersed Bolometer IR Detectors Based on V2O5 Thin Films with Polyimide Thermal Impedance Control Layer for Space Applications

Optically immersed bolometer IR detectors were fabricated using electron beam evaporated vanadium oxide as the sensing material. Spin-coated polyimide was used as medium to optically immerse the sensing element to the flat surface of a hemispherical germanium lens. This optical immersion layer also serves as the thermal impedance control layer and decides the performance of the devices in terms of responsivity and noise parameters. The devices were packaged in suitable electro-optical packages and the detector parameters were studied in detail. Thermal time constant varies from 0.57 to 6.0 ms and responsivity from 75 to 757 V W-1 corresponding to polyimide thickness in the range 2 to 70 mu m for a detector bias of 9 V in the wavelength region of 14-16 mu m. Highest D* obtained was 1.2x10(8) cmHz(1/2) W-1. Noise equivalent temperature difference (NETD) of 20 mK was achieved for devices with polyimide thickness more than 32 mu m. The figure of merit, NETD x tau product which describes trade-off between thermal time constant and sensitivity is also extensively studied for devices having different thickness of thermal impedance layers