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The online version contains supplementary material available at 10.1007/s13755-022-00189-5.
The online version contains supplementary material available at 10.1007/s13755-022-00189-5.Clergy play significant leadership, educational, and caregiving roles in society. However, burnout is a concern for the clergy profession, those they serve, and their families. Effects include decreased ministry effectiveness, lower sense of personal accomplishment in their role, and negative impacts on quality of family life and relationships. Given these risks, knowledge of the nature of Christian clergy's current resilience and well-being in Canada may provide valuable intelligence to mitigate these challenges. In summary, the purpose of this research was to describe and analyze the status of clergy resilience and well-being in Canada, together with offering focused insights. Resilience and well-being surveys used by the co-authors with educators and nurses were adapted for use in this study. This instrument was developed to gain insight into baseline patterns of resilience and well-being and included questions across seven sections (1) demographic information. (2) health status, (3) professional quality of life, (4) Cantril Well-Being Scale, (5) Ego-Resiliency Scale, (6) Grit Scale, and (7) open-ended questions. The findings provided valuable insights into clergy well-being and resilience that can benefit individual clerics, educational institutions, denominations, and congregations. The participants' current resilience and well-being included high levels of resiliency, moderate grit, and satisfaction with health and wellness. Other significant findings included the impact of congregational flourishing and age. This study found that clergy well-being and resilience was doing well despite the increased adversity of the COVID-19 pandemic. Implications of this study are that clerics may need unique supports based on their age and also whether they serve in a congregation they perceive as flourishing.In recent years, the Chinese government and its judiciary have made a policy decision to leverage artificial intelligence in broader judicial reform efforts. The push to use AI to such a large extent in the judiciary is unique to China, influenced by chronic challenges facing the courts, including an exponential increase in casework and a shortage of qualified professionals in the judiciary. This has resulted in a number of pilot programs across the country that have produced various AI systems embedded in different areas of the judicial system. Some of these systems aim to make rote processes, such as transcription and document review, more efficient, while other more ambitious projects attempt to directly assist in the decision-making process. This piece briefly summarizes the current landscape of China's technology-driven judicial reform and highlights a number of key considerations that we believe are pivotal to whether China's investment in AI will succeed in improving the efficiency and legitimacy of the courts.Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. Tanespimycin clinical trial One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis. Notably, FabI inhibitors have advanced to clinical trials for Staphylococcus aureus infections but not for infections caused by Gram-negative bacteria. Here, we synthesize a suite of FabI inhibitors whose structures fit permeation rules for Gram-negative bacteria and leverage activity against a challenging panel of Gram-negative clinical isolates as a filter for advancement. The compound to emerge, called fabimycin, has impressive activity against >200 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, and does not kill commensal bacteria. X-ray structures of fabimycin in complex with FabI provide molecular insights into the inhibition. Fabimycin demonstrates activity in multiple mouse models of infection caused by Gram-negative bacteria, including a challenging urinary tract infection model. Fabimycin has translational promise, and its discovery provides additional evidence that antibiotics can be systematically modified to accumulate in Gram-negative bacteria and kill these problematic pathogens.Post-transcriptional modifications are crucial for RNA function and can affect its structure and dynamics. Force-field-based classical molecular dynamics simulations are a fundamental tool to characterize biomolecular dynamics, and their application to RNA is flourishing. Here, we show that the set of force-field parameters for N6-methyladenosine (m6A) developed for the commonly used AMBER force field does not reproduce duplex denaturation experiments and, specifically, cannot be used to describe both paired and unpaired states. Then, we use reweighting techniques to derive new parameters matching available experimental data. The resulting force field can be used to properly describe paired and unpaired m6A in both syn and anti conformation, which thus opens the way to the use of molecular simulations to investigate the effects of N6 methylations on RNA structural dynamics.How molecular chirality manifests at the nano- to macroscale has been a scientific puzzle since Louis Pasteur discovered biochirality. Chiral molecules assemble into meso-shapes such as twisted and helical ribbons, helicoidal scrolls (cochleates), or möbius strips (closed twisted ribbons). Here we analyze self-assembly for a series of amphiphiles, C n -K, consisting of an ionizable amino acid [lysine (K)] coupled to alkyl tails with n = 12, 14, or 16 carbons. This simple system allows us to probe the effects of electrostatic and van der Waals interactions in chiral assemblies. Small/wide-angle X-ray scattering (SAXS/WAXS) reveals that at low pH, where the headgroups are ionized (+1), C16-K forms high aspect ratio, planar crystalline bilayers. Molecular dynamics (MD) simulations reveal that tilted tails of the bilayer leaflets are interdigitated. SAXS shows that, with increasing salt concentration, C16-K molecules assemble into cochleates, whereas at elevated pH (reduced degree of ionization), helices are observed for all C n -K assemblies. The shape selection between helices and scrolls is explained by a membrane energetics model. The nano- to meso-scale structure of the chiral assemblies can be continuously controlled by solution ionic conditions. Overall, our study represents a step toward an electrostatics-based approach for shape selection and nanoscale structure control in chiral assemblies.Introducing transition-metal components to ceria (CeO2) is important to tailor the surface redox properties for a broad scope of applications. The emergence of high-entropy oxides (HEOs) has brought transformative opportunities for oxygen defect engineering in ceria yet has been hindered by the difficulty in controllably introducing transition metals to the bulk lattice of ceria. Here, we report the fabrication of ceria-based nanocrystals with surface-confined atomic HEO layers for enhanced catalysis. The increased covalency of the transition-metal-oxygen bonds at the HEO-CeO2 interface promotes the formation of surface oxygen vacancies, enabling efficient oxygen activation and replenishment for enhanced CO oxidation capabilities. Understanding the structural heterogeneity involving bulk and surface oxygen defects in nanostructured HEOs provides useful insights into rational design of atomically precise metal oxides, whose increased compositional and structural complexities give rise to expanded functionalities.The assembly of robust, modular biological components into complex functional systems is central to synthetic biology. Here, we apply modular "plug and play" design principles to a solid-phase protein display system that facilitates protein purification and functional assays. Specifically, we capture proteins on polyacrylamide hydrogel display beads (PHD beads) made in microfluidic droplet generators. These monodisperse PHD beads are decorated with predefined amounts of anchors, methacrylate-PEG-benzylguanine (BG) and methacrylate-PEG-chloroalkane (CA), that react covalently with SNAP-/Halo-tag fusion proteins, respectively, in a specific, orthogonal, and stable fashion. Anchors, and thus proteins, are distributed throughout the entire bead volume, allowing attachment of ∼109 protein molecules per bead (⌀ 20 μm) -a higher density than achievable with commercial surface-modified beads. We showcase a diverse array of protein modules that enable the secondary capture of proteins, either noncovalently (IgG and SUMO-tag) or covalently (SpyCatcher, SpyTag, SnpCatcher, and SnpTag), in mono- and multivalent display formats. Solid-phase protein binding and enzymatic assays are carried out, and incorporating the photocleavable protein PhoCl enables the controlled release of modules via visible-light irradiation for functional assays in solution. We utilize photocleavage for valency engineering of an anti-TRAIL-R1 scFv, enhancing its apoptosis-inducing potency ∼50-fold through pentamerization.Synthetic polymers have widespread applications in daily life and advanced materials applications. Making polymers efficiently and controllably is highly desired, for which modulating intramolecular and intermolecular interactions have been an effective approach. Recent real-time single-polymer growth studies uncovered nonequilibrium conformational entanglements that form stochastically under living polymerization conditions and which appear to plausibly play key roles in controlling the polymerization kinetics and dispersion. Here, using magnetic tweezers measurements, we study the real-time polymerization dynamics of single polynorbornene-based polymers in which we systematically tune the hydrogen-bonding interactions by titrating the OH content in the monomers and the formed polymers during ring opening metathesis polymerization. Using norbornenes with and without a hydroxyl group and a nonreactive monomer analogue, we show that intrachain and intermolecular hydrogen bonding compete, and both alter the microscopic properties of the nonequilibrium entanglements, leading to surprising multiphasic dependences of polymerization dynamics on the polymer's OH content. We further formulate a simple model to rationalize quantitatively the observed multiphasic behaviors by considering the different scaling relations of intrachain and intermolecular hydrogen bonding on the OH content. These results provide insights into the interconnected roles of intra-/intermolecular interactions, polymer chain conformations, and free monomers in solution in affecting polymerization kinetics and dispersion, and point to new opportunities in manipulating polymerization reactions.Dynamic coassembly of block copolymers (BCPs) with Keggin-type polyoxometalates (POMs) is developed to synthesize heteroatom-doped tungsten oxide with controllable nanostructures, including hollow hemispheres, nanoparticles, and nanowires. The versatile coassembly in dual n-hexane/THF solvent solution enables the fomation of poly(ethylene oxide)-b-polystyrene (PEO-b-PS)/POMs (e.g., silicotungstic acid, H4SiW12O40) nanocomposites with different morphologies such as spherical vesicles, inverse spherical micelles, and inverse cylindrical micelles, which can be readily converted into diverse nanostructured metal oxides with high surface area and unique properties via in situ thermal-induced structural evolution. For example, uniform silicon-doped WO3 (Si-WO3) hollow hemispheres derived from coassembly of PEO-b-PS with H4SiW12O40 were utilized to fabricate gas sensing devices which exhibit superior gas sensing performance toward acetone, thanks to the selective gas-solid interface catalytic reaction that induces resistance changes of the devices due to the high specific surface areas, abundant oxygen vacancies, and the Si-doping induced metastable ε-phase of WO3.
Homepage: https://www.selleckchem.com/products/17-AAG(Geldanamycin).html
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