Prospects for Studies of Stellar Evolution and Stellar Death in the JWST Era

I review the prospects for studies of the advanced evolutionary stages of low-, intermediate- and high-mass stars by the JWST and concurrent facilities, with particular emphasis on how they may help elucidate the dominant contributors to the interstellar dust component of galaxies. Observations extending from the mid-infrared to the submillimeter can help quantify the heavy element and dust species inputs to galaxies from AGB stars. JWST's MIRI mid-infrared instrument will be so sensitive that observations of the dust emission from individual intergalactic AGB stars and planetary nebulae in the Virgo Cluster will be feasible. The Herschel Space Observatory will enable the last largely unexplored spectral region, the far-IR to the submillimeter, to be surveyed for new lines and dust features, while SOFIA will cover the wavelength gap between JWST and Herschel, a spectral region containing important fine structure lines, together with key water-ice and crystalline silicate bands. Spitzer has significantly increased the number of Type II supernovae that have been surveyed for early-epoch dust formation but reliable quantification of the dust contributions from massive star supernovae of Type II, Type Ib and Type Ic to low- and high-redshift galaxies should come from JWST MIRI observations, which will be able to probe a volume over 1000 times larger than Spitzer.Comment: 24 pages, 19 figures. To appear in `Astrophysics in the Next Decade: JWST and Concurrent Facilities' (JWST Conference Proceedings), edited by H. A. Thronson, M. Stiavelli and A. G. G. M. Tielens; Springer Series: Astrophysics and Space Science Proceeding

Palaeoenvironmental control on distribution of crinoids in the Bathonian (Middle Jurassic) of England and France

Bulk sampling of a number of different marine and marginal marine lithofacies in the British Bathonian has allowed us to assess the palaeoenvironmental distribution of crinoids for the first time. Although remains are largely fragmentary, many species have been identified by comparison with articulated specimens from elsewhere, whilst the large and unbiased sample sizes allowed assessment of relative proportions of different taxa. Results indicate that distribution of crinoids well corresponds to particular facies. Ossicles of Chariocrinus and Balanocrinus dominate in deeper-water and lower-energy facies,with the former extending further into shallower-water facies than the latter. Isocrinus dominates in shallower water carbonate facies, accompanied by rarer comatulids, and was also present in the more marine parts of lagoons. Pentacrinites remains are abundant in very high-energy oolite shoal lithofacies. The presence of millericrinids within one, partly allochthonous lithofacies suggests the presence of an otherwise unknown hard substrate from which they have been transported. These results are compared to crinoid assemblages from other Mesozoic localities, and it is evident that the same morphological ad-aptations are present within crinoids from similar lithofacies throughout the Jurassic and Early Cretaceous

Hypoxic Pulmonary Vasoconstriction in Humans:Tale or Myth

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism

Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS CoV 2 Main Protease Inhibitors

The spread of SARS CoV 2 keeps threatening human life and health, and small molecule antivirals are in demand. The main protease Mpro is an effective and highly conserved target for anti SARS CoV 2 drug design. Herein, we report the discovery of potent covalent non peptide derived Mpro inhibitors. A series of covalent compounds with a piperazine scaffold containing different warheads were designed and synthesized. Among them, GD 9 was identified as the most potent compound with a significant enzymatic inhibition of Mpro IC50 0.18 amp; 956;M and good antiviral potency against SARS CoV 2 EC50 2.64 amp; 956;M , similar to that of remdesivir EC50 2.27 amp; 956;M . Additionally, GD 9 presented favorable target selectivity for SARS CoV 2 Mpro versus human cysteine proteases. The X ray co crystal structure confirmed our original design concept showing that GD 9 covalently binds to the active site of Mpro. Our nonpeptidic covalent inhibitors provide a basis for the future development of more efficient COVID 19 therapeutic

Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

Contains fulltext : 185528.pdf (publisher's version ) (Open Access)BACKGROUND: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. METHODS: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. RESULTS: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). CONCLUSIONS: In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B

Desensitisation of neutrophil responses by systemic interleukin 8 in cystic fibrosis.

BACKGROUND--Inflammation associated with neutrophil infiltration is a commonly observed feature of children with cystic fibrosis. Production of the major neutrophil chemotactic cytokine interleukin 8 (IL-8) is potentially of great importance in the pathology of cystic fibrosis. Concentrations of IL-8 in both sputum and bronchoalveolar lavage fluid have been found to be higher in children with cystic fibrosis than in controls. The IL-8 induced chemotactic response and numbers of IL-8 receptors on peripheral neutrophils obtained from children with cystic fibrosis have been compared with a control group of children. METHODS--Cells were isolated from 18 patients with cystic fibrosis (aged 4-20 years) and 13 controls (aged 5-12 years) by dextran centrifugation followed by separation on Lymphoprep. Chemotaxis was assayed using multiwell microchemotaxis chambers and 5 microns polycarbonate filters. Filters were fixed and stained with Haema-Gurr for counting. Results were expressed as numbers of neutrophils per high power field (HPF). RESULTS--At the optimum concentration (1 x 10(-8) mol/l) the number of cells migrating were similar for controls (150 (12)/HPF) and for the cystic fibrosis group (140 (14)/HPF)). At lower concentrations the numbers of neutrophils migrating were lower for the cystic fibrosis group. Scatchard analysis of 125I-labelled IL-8 binding revealed lower numbers of receptors on neutrophils from patients with cystic fibrosis (22,000 per cell) than from controls (75,000 per cell). CONCLUSIONS--Reduced responsiveness to IL-8 of neutrophils from patients with cystic fibrosis is associated with receptor desensitisation as a result of exposure to high systemic levels of IL-8