PROTACs (Proteolysis Targeting Chimeras), heterobifunctional molecules, exhibit selectivity in degrading target proteins through E3 ubiquitin ligases. Designing effective PROTACs requires a deep understanding of the intricate binding interactions in the ternary complex (POI/PROTAC/E3 ligase), crucial for efficient target protein degradation. To address this challenge, we introduce a novel computational virtual screening method that considers essential amino acid interactions between the protein of interest and the chosen E3 ligase.
View Article and Find Full Text PDFThis study applies the theory of planned behaviors to evaluate economic outcomes resulting from planned innovation and dynamic entrepreneurship of Vietnamese firms. The analysis uses data on Vietnamese small and medium manufacturing firms from surveys conducted by United Nations University World Institute for Development Economics Research (UNU-WIDER) during 2005-2015. Employing various estimation techniques including normal standard one-side regressions (fixed effect models, panel robust model, and Pds-lasso) and two-side structural two-stage models (extended regression model, treatment effect model, and IV-Lasso), we analyze the impacts of innovation activities on firm profitability in connection to the role of dynamic entrepreneurship and planned innovation.
View Article and Find Full Text PDFImportance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective.
Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis.
Design, Setting, And Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017.
Background: While circulation of respiratory syncytial virus (RSV) results in high rates of hospitalization, particularly among young children and elderly individuals, little is known about the role of different age groups in propagating annual RSV epidemics.
Methods: We evaluate the roles played by individuals in different age groups during RSV epidemics in the United States between 2001 and 2012, using the previously defined relative risk (RR) statistic estimated from the hospitalization data from the Healthcare Cost and Utilization Project. Transmission modeling was used to examine the robustness of our inference method.
The blood-brain barrier, formed by microvessel endothelial cells, is the restrictive barrier between the brain parenchyma and the circulating blood. Arachidonic acid (ARA; 5,8,11,14-cis-eicosatetraenoic acid) is a conditionally essential polyunsaturated fatty acid [20:4(n-6)] and is a major constituent of brain lipids. The current study examined the transport processes for ARA in confluent monolayers of human brain microvascular endothelial cells (HBMEC).
View Article and Find Full Text PDFContext: Serum total calcium (tCa) is routinely measured for diagnosing calcium disorders but may not reflect levels of biologically active ionized calcium (iCa) in disease or detect all cases of primary hyperparathyroidism.
Objective: We investigated the utility of measuring iCa and tCa for diagnosing primary hyperparathyroidism.
Design: This was an observational, retrospective, cross-sectional study.
Background: Etomidate is a sedative hypnotic that is often used in critically ill patients because it provides superior hemodynamic stability. However, it also binds with high affinity to 11beta-hydroxylase, potently suppressing the synthesis of steroids by the adrenal gland that are necessary for survival. The authors report the results of studies to define the pharmacology of (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), a pyrrole analog of etomidate specifically designed not to bind with high affinity to 11beta-hydroxylase.
View Article and Find Full Text PDFBackground: Etomidate is a rapidly acting sedative-hypnotic that provides hemodynamic stability. It causes prolonged suppression of adrenocortical steroid synthesis; therefore, its clinical utility and safety are limited. The authors describe the results of studies to define the pharmacology of (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), the first etomidate analogue designed to be susceptible to ultra-rapid metabolism.
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