Borazineâ CF3â Adducts for Rapid, Room Temperature, and Broad Scope Trifluoromethylation

A fluoroformâ derived borazine CF3â transfer reagent is used to effect rapid nucleophilic reactions in the absence of additives, within minutes at 25â °C. Inorganic electrophiles spanning seven groups of the periodic table can be trifluoromethylated in high yield, including transition metals used for catalytic trifluoromethylation. Organic electrophiles included (hetero)arenes, enabling Câ H and Câ X trifluoromethylation reactions. Mechanistic analysis supports a dissociative mechanism for CF3â transfer, and cation modification afforded a reagent with enhanced stability.A trifluoromethylating matter: A stable fluoroformâ derived reagent facilitates the nucleophilic trifluoromethylation of a broad array of inorganic and organic electrophiles (E) at room temperature. The reaction scope includes 18 inorganic elements, nucleophilic aromatic substitution, and CF3â addition to carbonyl and imine compounds. Kinetic analysis supports a dissociative mechanism.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141342/1/anie201711316_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141342/2/anie201711316.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141342/3/anie201711316-sup-0001-misc_information.pd

Borazineâ CF3â Adducts for Rapid, Room Temperature, and Broad Scope Trifluoromethylation

A fluoroformâ derived borazine CF3â transfer reagent is used to effect rapid nucleophilic reactions in the absence of additives, within minutes at 25â °C. Inorganic electrophiles spanning seven groups of the periodic table can be trifluoromethylated in high yield, including transition metals used for catalytic trifluoromethylation. Organic electrophiles included (hetero)arenes, enabling Câ H and Câ X trifluoromethylation reactions. Mechanistic analysis supports a dissociative mechanism for CF3â transfer, and cation modification afforded a reagent with enhanced stability.Von Fluoroform abgeleitet wurde ein stabiles Reagenz für nukleophile Trifluormethylierungen anorganischer und organischer Elektrophile (E) bei Raumtemperatur. Das Reaktionsspektrum umfasst 18 anorganische Elemente, nucleophile aromatische Substitutionen sowie CF3â â Additionen an Carbonylverbindungen und Imine. Kinetische Studien sprechen für einen dissoziativen Mechanismus.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141871/1/ange201711316-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141871/2/ange201711316.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141871/3/ange201711316_am.pd

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Non-local heat transport in Alcator C-Mod ohmic L-mode plasmas

Non-local heat transport experiments were performed in Alcator C-Mod ohmic L-mode plasmas by inducing edge cooling with laser blow-off impurity (CaF2) injection. The non-local effect, a cooling of the edge electron temperature with a rapid rise of the central electron temperature, which contradicts the assumption of 'local' transport, was observed in low collisionality linear ohmic confinement (LOC) regime plasmas. Transport analysis shows this phenomenon can be explained either by a fast drop of the core diffusivity, or the sudden appearance of a heat pinch. In high collisionality saturated ohmic confinement (SOC) regime plasmas, the thermal transport becomes 'local': the central electron temperature drops on the energy confinement time scale in response to the edge cooling. Measurements from a high resolution imaging x-ray spectrometer show that the ion temperature has a similar behaviour as the electron temperature in response to edge cooling, and that the transition density of non-locality correlates with the rotation reversal critical density. This connection may indicate the possible connection between thermal and momentum transport, which is also linked to a transition in turbulence dominance between trapped electron modes (TEMs) and ion temperature gradient (ITG) modes. Experiments with repetitive cold pulses in one discharge were also performed to allow Fourier analysis and to provide details of cold front propagation. These modulation experiments showed in LOC plasmas that the electron thermal transport is not purely diffusive, while in SOC the electron thermal transport is more diffusive like. Linear gyrokinetic simulations suggest the turbulence outside r/a = 0.75 changes from TEM dominance in LOC plasmas to ITG mode dominance in SOC plasmas.United States. Dept. of Energy (DoE Contract No DE-FC02-99ER54512)Oak Ridge Institute for Science and Education (DOE Fusion Energy Postdoctoral Research Program

BCL11A enhancer edited hematopoietic stem cells persist in rhesus monkeys without toxicity

Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from sickle cell disease (SCD) patients induces fetal hemoglobin (HbF) without detectable toxicity as assessed by mouse xenotransplant. Here, we evaluated autologous engraftment and HbF induction potential of erythroid-specific BCL11A enhancer edited HSPCs in four non-human primates. We utilized a single guide RNA (sgRNA) with identical human and rhesus target sequences to disrupt a GATA1 binding site at the BCL11A +58 erythroid enhancer. Cas9 protein and sgRNA ribonucleoprotein complex (RNP) was electroporated into rhesus HSPCs, followed by autologous infusion after myeloablation. We found that gene edits persisted in peripheral blood (PB) and bone marrow (BM) for up to 101 weeks similarly for BCL11A enhancer or control locus (AAVS1) targeted cells. Biallelic BCL11A enhancer editing resulted in robust gamma-globin induction, with the highest levels observed during stress erythropoiesis. Indels were evenly distributed across PB and BM lineages. Off-target edits were not observed. Non-homologous end-joining repair alleles were enriched in engrafting HSCs. In summary, we find that edited HSCs can persist for at least 101 weeks post-transplant, and biallelic edited HSCs provide substantial HbF levels in PB red blood cells, together supporting further clinical translation of this approach

Comparative Analysis of Chromosome Counts Infers Three Paleopolyploidies in the Mollusca

The study of paleopolyploidies requires the comparison of multiple whole genome sequences. If the branches of a phylogeny on which a whole-genome duplication (WGD) occurred could be identified before genome sequencing, taxa could be selected that provided a better assessment of that genome duplication. Here, we describe a likelihood model in which the number of chromosomes in a genome evolves according to a Markov process with one rate of chromosome duplication and loss that is proportional to the number of chromosomes in the genome and another stochastic rate at which every chromosome in the genome could duplicate in a single event. We compare the maximum likelihoods of a model in which the genome duplication rate varies to one in which it is fixed at zero using the Akaike information criterion, to determine if a model with WGDs is a good fit for the data. Once it has been determined that the data does fit the WGD model, we infer the phylogenetic position of paleopolyploidies by calculating the posterior probability that a WGD occurred on each branch of the taxon tree. Here, we apply this model to a molluscan tree represented by 124 taxa and infer three putative WGD events. In the Gastropoda, we identify a single branch within the Hypsogastropoda and one of two branches at the base of the Stylommatophora. We also identify one or two branches near the base of the Cephalopoda

Mapping disparities in education across low- and middle-income countries

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations. Educational attainment is an important social determinant of maternal, newborn, and child health(1-3). As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting(4-6). The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness(7,8); however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health(9-11). Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries(12-14). By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.Peer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe