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Cardenas Good posted an update 6 months, 3 weeks ago
lso the S-HA particles remained after 1 year, which proved its longevity of at least 1 year. CONCLUSION The topographic computer analysis using point-roughness showed improvement of all subtype acne scars at 1-month post-treatment. AZD3229 inhibitor The improvement may have resulted from dermal expansion due to the neocollagenesis and neoelastinogenesis. S-HA lasted more than 1 year in human dermis. This article is protected by copyright. All rights reserved.The shallow marine and subaerial sedimentary and hydrothermal rocks of the ~3.48 billion-year-old Dresser Formation are host to some of Earth’s oldest stromatolites and microbial remains. This study reports on texturally distinctive, spherulitic barite micro-mineralization that occur in association with primary, autochthonous organic matter within exceptionally preserved, strongly sulfidized stromatolite samples obtained from drill cores. Spherulitic barite micro-mineralization within the sulfidized stromatolites generally forms submicron-scale aggregates that show gradations from hollow to densely crystallized, irregular to partially radiating crystalline interiors. Several barite micro-spherulites show thin outer shells. Within stromatolites, barite micro-spherulites are intimately associated with petrographically earliest dolomite and nano-porous pyrite enriched in organic matter, the latter of which is a possible biosignature assemblage that hosts microbial remains. Barite spherulites are also observed within layered barite in proximity to stromatolite layers, where they are overgrown by compositionally distinct (Sr-rich), coarsely crystalline barite that may have been sourced from hydrothermal veins at depth. Micro-spherulitic barite, such as reported here, is not known from hydrothermal systems that exceed the upper temperature limit for life. Rather, barite with near-identical morphology and micro-texture is known from zones of high bio-productivity under low-temperature conditions in the modern oceans, where microbial activity and/or organic matter of degrading biomass controls the formation of spherulitic aggregates. Hence, the presence of micro-spherulitic barite in the organic matter-bearing Dresser Formation sulfidized stromatolites lend further support for a biogenic origin of these unusual, exceptionally well-preserved, and very ancient microbialites. © 2020 John Wiley & Sons Ltd.BACKGROUND In hemophilia bypass therapy, a platelet-dependent mechanism is believed to be primarily responsible for recombinant factor VIIa (rFVIIa)’s hemostatic effect. rFVIIa may also possibly interact with other cells through its binding to endothelial cell protein C receptor (EPCR) or cell surface phospholipids. OBJECTIVES We aim to investigate the relative contribution of platelet-dependent and platelet-independent mechanisms in rFVIIa-mediated thrombin generation in hemophilic conditions at the injury site. METHODS Platelets were depleted in acquired and genetic hemophilia mice using anti-platelet antibodies. The mice were subjected to the saphenous vein injury, and the hemostatic effect of pharmacological concentrations of rFVIIa was evaluated by measuring thrombin generation at the injury site. RESULTS Administration of anti-mouse CD42 antibodies to mice depleted platelets by more than 95%. As expected, hemophilia mice, compared to wild-type mice, generated only a small fraction of thrombin at the injury site. The depletion of platelets in hemophilia mice further reduced thrombin generation. However, when pharmacological doses of rFVIIa were administered to hemophilia mice, substantial amounts of thrombin were generated even in the platelet-depleted hemophilia mice. No differences in thrombin generation were detected among FVIII-/- , EPCR-deficient FVIII-/- , and EPCR-overexpressing FVIII-/- mice depleted of platelets or not. Evaluation of platelets by flow cytometry as well as immunoblot analysis showed no detectable expression of EPCR. CONCLUSIONS Our data suggest that pharmacological concentrations of rFVIIa generate thrombin in hemophilia in both platelet-dependent and platelet-independent mechanisms. This article is protected by copyright. All rights reserved.αvβ6-Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with αvβ6-integrin dependent TGF-β dysregulation, such as fibrosis. We designed a trimeric Ga-68-labeled TRAP-conjugate of the αvβ6-specific cyclic pentapeptide SDM17 (cyclo-CONH 2 ) to enhance αvβ6-integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17) 3 showed a 28-fold higher αvβ6 affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC50 of 0.26 vs. 7.4 nM, respectively), a 13-times higher IC50-based selectivity over the related integrin αvβ8 (factors of 662 vs. 49), and a 3-times higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments using H2009-tumor bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17) 3 holds promise for improved clinical PET-diagnostics of carcinomas and fibrosis. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.It seems self-evident that giving birth with the help of a skilled attendant in a health facility will reduce the risk of adverse outcome, as opposed to birthing at home. A key indicator for the Sustainable Development Goals is the ‘proportion of births attended by skilled personnel’, of particular relevance to sub-Saharan Africa, where this proportion was only 59% in 2018 (Sustainable Development Goals knowledge platform. This article is protected by copyright. All rights reserved.Radical C-H bond functionalization provides a versatile approach for elaborating heterocyclic compounds. The synthetic design of this transformation relies heavily on the knowledge of regioselectivity, while a quantified and efficient regioselectivity prediction approach is still elusive. Herein we report the feasibility of using machine learning model to predict the transition state barrier from the computed properties of isolated reactants. This enables rapid and reliable regioselectivity prediction for the radical C-H bond functionalization of heterocycles. The Random Forest model with physical organic features achieved a 94.2% site accuracy and an 89.9% selectivity accuracy in the out-of-sample test set. The prediction performance was further validated by comparing the machine learning results with additional substituents, heteroarene scaffolds and experimental observations. This work revealed that the combination of mechanism-based computational statistics and machine learning model can serve as a useful strategy for selectivity prediction of organic transformations.
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