7 research outputs found

    BBF RFC 105: The Intein standard - a universal way to modify proteins after translation

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    This Request for Comments (RFC) proposes a new standard that allows for easy and flexible cloning of intein constructs and thus makes this technology accessible to the synthetic biology community

    Liquid–Liquid Equilibria of Systems with Linear Aldehydes. Experimental Data and Modeling with PCP-SAFT

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    Liquid–liquid equilibrium (LLE) data were measured for the binary system propylene carbonate/decane (288.15 to 403.15 K) as well as for the ternary systems propylene carbonate/decane + linear aldehyde (C4, C8, C10, C12, C13) and DMF/decane + linear aldehyde (C4, C8, C10, C13) at 298.15 K using the analytic method. The reliability of the ternary LLE data is ascertained by employing Othmer–Tobias plots. Concerning the aldehyde distribution coefficients in the ternary systems, a distinctive dependency on the chain length of the aldehyde was observed. The LLE data were modeled with the Perturbed Chain Polar Statistical Associating Fluid Theory (PCP-SAFT) equation of state using a heterosegmented approach for describing the aldehyde molecules

    Hydroformylation of 1‑Dodecene in the Thermomorphic Solvent System Dimethylformamide/Decane. Phase Behavior–Reaction Performance–Catalyst Recycling

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    An economically meaningful hydroformylation of long-chain olefins requires an efficient combination of both a high-yield reaction step and efficient catalyst recycling. The application of thermomorphic multicomponent solvent (TMS) systems allows for optimal reaction as well as catalyst-recycling conditions. In this work, the TMS concept was applied to the homogeneously rhodium-catalyzed hydroformylation of 1-dodecene in the TMS system dimethylformamide (DMF)/decane using Rh­(acac)­(CO)<sub>2</sub>/Biphephos as the catalyst system. Thermodynamic investigations focused on the influence of the olefin (hydroformulation educt) and the aldehyde (hydroformylation product) on the phase behavior of the TMS system. Temperature dependent liquid–liquid equilibrium (LLE) data were measured for the binary systems DMF/decane and DMF/1-dodecene and for the ternary systems DMF/decane/1-dodecene and DMF/decane/dodecanal. Additionally, the corresponding LLE data were modeled applying the Perturbed Chain Polar Statistical Associating Fluid Theory (PCP-SAFT) using a heterosegmented approach for modeling the long-chain aldehyde. On the basis of the LLE data, adequate working points for hydroformylation experiments in the TMS system were selected. In these experiments, aldehyde yields of up to 87% with an n/iso ratio of up to 99:1 were achieved. Moreover, the TMS system was successfully applied to catalyst recycling in eight recycling runs with a catalyst leaching of 7 ppm rhodium at lowest

    Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

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    Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55-98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04-117·73]) than in those in the lowest risk category (aged 18-38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57-38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67-104·02) for those with obesity in the highest risk category and OR 20·07 (12·73-31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron

    A deep neural network to search for new long-lived particles decaying to jets

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    International audienceA tagging algorithm to identify jets that are significantly displaced from the proton-proton (pp) collision region in the CMS detector at the LHC is presented. Displaced jets can arise from the decays of long-lived particles (LLPs), which are predicted by several theoretical extensions of the standard model. The tagger is a multiclass classifier based on a deep neural network, which is parameterised according to the proper decay length cτ0\mathrm{c}\tau_0 of the LLP. A novel scheme is defined to reliably label jets from LLP decays for supervised learning. Samples of pp collision data, recorded by the CMS detector at a centre-of-mass energy of 13 TeV, and simulated events are used to train the neural network. Domain adaptation by backward propagation is performed to improve the simulation modelling of the jet class probability distributions observed in pp collision data. The potential performance of the tagger is demonstrated with a search for long-lived gluinos, a manifestation of split supersymmetric models. The tagger provides a rejection factor of 10 000 for jets from standard model processes, while maintaining an LLP jet tagging efficiency of 30-80% for gluinos with 1 mm \leq cτ0c\tau_0 \leq 10 m. The expected coverage of the parameter space for split supersymmetry is presented
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