Dialing in single-site reactivity of a supported calixarene-protected tetrairidium cluster catalyst.

A closed Ir4 carbonyl cluster, 1, comprising a tetrahedral metal frame and three sterically bulky tert-butyl-calix[4]arene(OPr)3(OCH2PPh2) (Ph = phenyl; Pr = propyl) ligands at the basal plane, was characterized with variable-temperature 13C NMR spectroscopy, which show the absence of scrambling of the CO ligands at temperatures up to 313 K. This demonstration of distinct sites for the CO ligands was found to extend to the reactivity and catalytic properties, as shown by selective decarbonylation in a reaction with trimethylamine N-oxide (TMAO) as an oxidant, which, reacting in the presence of ethylene, leads to the selective bonding of an ethyl ligand at the apical Ir site. These clusters were supported intact on porous silica and found to catalyze ethylene hydrogenation, and a comparison of the kinetics of the single-hydrogenation reaction and steady-state hydrogenation catalysis demonstrates a unique single-site catalyst-with each site having the same catalytic activity. Reaction orders in the catalytic ethylene hydrogenation reaction of approximately 1/2 and 0 for H2 and C2H4, respectively, nearly match those for conventional noble-metal catalysts. In contrast to oxidative decarbonylation, thermal desorption of CO from silica-supported cluster 1 occurred exclusively at the basal plane, giving rise to sites that do not react with ethylene and are catalytically inactive for ethylene hydrogenation. The evidence of distinctive sites on the cluster catalyst leads to a model that links to hydrogen-transfer catalysis on metals-involving some surface sites that bond to both hydrocarbon and hydrogen and are catalytically engaged (so-called "*" sites) and others, at the basal plane, which bond hydrogen and CO but not hydrocarbon and are reservoir sites (so-called "S" sites)

Enhanced performance of longitudinally post-tensioned long-span LVL beams

The scope of this paper is to highlight the advantages of using longitudinally post-tensioning for long-span timber beams compared to traditional glulam or LVL solutions. The analysis is limited to serviceability limit states for gravity loads. An analtycal iterative procedure which takes into account tendon elongation within beam deflecting has been implemented and validated through experimental tests carried out at the University of Canterbury.In particular, two different static configurations have been studied and different tendon profile configurations (straight and draped) internal and external to the beam section have been investigated and compared with traditional solid timber beams. The experimental results confirm the enhanced performance in terms of deflections at serviceability limit state of the longitudinally post-tensioned solutions with respect to traditional timber beams, especially if external draped tendons are adopted

Protospacer Adjacent Motif-Induced Allostery Activates CRISPR-Cas9

CRISPR-Cas9 is a genome editing technology with major impact in life sciences. In this system, the endonuclease Cas9 generates double strand breaks in DNA upon RNA-guided recognition of a complementary DNA sequence, which strictly requires the presence of a protospacer adjacent motif (PAM) next to the target site. Although PAM recognition is essential for cleavage, it is unknown whether and how PAM binding activates Cas9 for DNA cleavage at spatially distant sites. Here, we find evidence of a PAM-induced allosteric mechanism revealed by microsecond molecular dynamics simulations. PAM acts as an allosteric effector and triggers the interdependent conformational dynamics of the Cas9 catalytic domains (HNH and RuvC), responsible for concerted cleavage of the two DNA strands. Targeting such an allosteric mechanism should enable control of CRISPR-Cas9 functionality

Trials and tribulations of designing multitasking catalysts for olefin/thiophene block copolymerizations

Block copolymers containing both insulating and conducting segments have been shown to exhibit improved charge transport properties and air stability. Nevertheless, their syntheses are challenging, relying on multiple post‐polymerization functionalization reactions and purifications. A simpler approach would be to synthesize the block copolymer in one pot using the same catalyst to enchain both monomers via distinct mechanisms. Such multitasking polymerization catalysts are rare, however, due to the challenges of finding a single catalyst that can mediate living, chain‐growth polymerizations for each monomer under similar conditions. Herein, a diimine‐ligated Ni catalyst is evaluated and optimized to produce block copolymer containing both 1‐pentene and 3‐hexylthiophene. The reaction mixture also contains both homopolymers, suggesting catalyst dissociation during and/or after the switch in mechanisms. Experimental and theoretical studies reveal a high energy switching step coupled with infrequent catalyst dissociation as the culprits for the low yield of copolymer. Combined, these studies highlight the challenges of identifying multitasking catalysts, and suggest that further tuning the reaction conditions (e.g., ancillary ligand structure and/or metal) is warranted for this specific copolymerization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 132–137Block copolymers containing insulating segments (derived from 1‐pentene) and conducting segments (derived from 3‐hexylthiophene) are synthesized in one pot using a single multitasking catalyst. Notably, this process requires different enchainment mechanisms (coordination/insertion vs. cross‐coupling) mediated by the same precatalyst. Nevertheless, the block copolymer is the minor product due to a slow switching step between the mechanisms coupled with catalyst dissociation from the polymer chain.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139919/1/pola28885_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139919/2/pola28885.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139919/3/pola28885-sup-0001-suppinfo.pd

All-Optical tunability of metalenses infiltrated with liquid crystals

Metasurfaces have been extensively engineered to produce a wide range of optical phenomena, allowing unprecedented control over the propagation of light. However, they are generally designed as single-purpose devices without a modifiable post-fabrication optical response, which can be a limitation to real-world applications. In this work, we report a nanostructured planar fused silica metalens permeated with a nematic liquid crystal (NLC) and gold nanoparticle solution. The physical properties of embedded NLCs can be manipulated with the application of external stimuli, enabling reconfigurable optical metasurfaces. We report all-optical, dynamic control of the metalens optical response resulting from thermo-plasmonic induced changes of the NLC solution associated with the nematic-isotropic phase transition. A continuous and reversible tuning of the metalens focal length is experimentally demonstrated, with a variation of 80 um (0.16% of the 5 cm nominal focal length) along the optical axis. This is achieved without direct mechanical or electrical manipulation of the device. The reconfigurable properties are compared with corroborating numerical simulations of the focal length shift and exhibit close correspondence.Comment: Main tex

Fontan-Associated Dyslipidemia

Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥ 18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8–34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P\u3c 0.0001), low‐density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P\u3c 0.0001), and high‐density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P\u3c 0.0001) than controls. In those with a Fontan, high‐density lipoprotein cholesterol was inversely correlated with body mass index (r=−0.30, P\u3c 0.0001), high‐sensitivity C‐reactive protein (r=−0.27, P=0.0006), and alanine aminotransferase (r=−0.18, P=0.02) but not with other liver disease markers. Lower high‐density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04–1.81 [P=0.03]). This relationship was attenuated when log high‐sensitivity C‐reactive protein was added to the model (HR, 1.26; 95% CI, 0.95–1.67 [P=0.10]). Total cholesterol, low‐density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high‐density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan‐associated liver disease and lipid metabolism

Cortisol metabolism, postnatal depression and weight changes in the first 12 months postpartum

Background & Objectives Postnatal depression correlates with postpartum weight retention, and dysregulated cortisol metabolism is evident in depressed individuals. Cortisol metabolism, BMI and metabolic phenotype are robustly associated, but the role of cortisol metabolism in postnatal mental health and weight loss has never been examined. Design A longitudinal observation. Patients Forty nine healthy women with uncomplicated pregnancy. Measurements BMI and urinary steroid metabolites at 1 week and 1, 3, 6 and 12 months postpartum. Validated urinary steroid metabolite ratios were measured to determine the activities of 11β‐hydroxysteroid dehydrogenases (11β‐HSD) that interconvert inactive cortisone and active cortisol and the 5α‐reductases that clear cortisol to its inactive metabolites. Postnatal depression symptoms were measured at 1, 6 and 12 months. Results Low 5α‐reductase activity was associated with greater weight loss across the first year, independent of demographics, breastfeeding and depression. Postpartum BMI change was unrelated to postnatal depression at any time. Symptoms of postnatal depression were related to higher cortisol metabolite production at 12 months, independent of demographics and breastfeeding. Conclusions Greatest weight loss in the postpartum year was associated with lower conversion of cortisone to cortisol and lower conversion of cortisol to its metabolites, supporting previous work that demonstrates the facilitative role of lower 5α‐reductase and 11β‐HSD‐1 in weight loss. Greater depression symptoms were associated with higher cortisol metabolite production rates. Whilst weight and mental health are both associated with dysregulation of the HPA axis, there may be different pathways towards depressed and obese phenotypes in healthy postpartum samples

Impaired Glucose Tolerance and Insulin Resistance Are Associated With Increased Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 Expression and Elevated Hepatic 5α-Reductase Activity

OBJECTIVE—The precise molecular mechanisms contributing to the development of insulin resistance, impaired glucose tolerance (IGT), and type 2 diabetes are largely unknown. Altered endogenous glucocorticoid metabolism, including 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which generates active cortisol from cortisone, and 5α-reductase (5αR), which inactivates cortisol, has been implicated