33 research outputs found

    Optimization of Combinatorial Mutagenesis

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    Abstract. Protein engineering by combinatorial site-directed mutagenesis evaluates a portion of the sequence space near a target protein, seeking variants with improved properties (stability, activity, immunogenicity, etc.). In order to improve the hit-rate of beneficial variants in such mutagenesis libraries, we develop methods to select optimal positions and corresponding sets of the mutations that will be used, in all combinations, in constructing a library for experimental evaluation. Our approach, OCoM (Optimization of Combinatorial Mutagenesis), encompasses both degenerate oligonucleotides and specified point mutations, and can be directed accordingly by requirements of experimental cost and library size. It evaluates the quality of the resulting library by oneand two-body sequence potentials, averaged over the variants. To ensure that it is not simply recapitulating extant sequences, it balances the quality of a library with an explicit evaluation of the novelty of its members. We show that, despite dealing with a combinatorial set of variants, i

    Biological Supermolecules — Learning from Nature

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    Contrapolarization, a new concept in organic reactivity

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    30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data

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    Background: There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods: This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results: In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions: This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts. © 2021, The Author(s)

    Immune-mediated Cerebellar Ataxias: Practical Guidelines and Therapeutic Challenges

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    First measurement of <math><msubsup><mi mathvariant="normal">Λ</mi><mrow><mi>c</mi></mrow><mo>+</mo></msubsup></math> production down to <math><mrow><msub><mi>p</mi><mi>T</mi></msub><mo>=</mo><mn>0</mn></mrow></math> in <math><mrow><mi>p</mi><mi>p</mi></mrow></math> and <math><mi>p</mi></math>-Pb collisions at <math><mrow><msqrt><msub><mi>s</mi><mrow><mi>N</mi><mi>N</mi></mrow></msub></msqrt><mo>=</mo><mn>5.02</mn></mrow></math> TeV

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    International audienceThe production of prompt Λc+ baryons has been measured at midrapidity in the transverse momentum interval 0&lt;pT&lt;1 GeV/c for the first time, in pp and p–Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=5.02TeV. The measurement was performed in the decay channel Λc+→pKS0 by applying new decay reconstruction techniques using a Kalman-Filter vertexing algorithm and adopting a machine-learning approach for the candidate selection. The pT-integrated Λc+ production cross sections in both collision systems were determined and used along with the measured yields in Pb–Pb collisions to compute the pT-integrated nuclear modification factors RpPb and RAA of Λc+ baryons, which are compared to model calculations that consider nuclear modification of the parton distribution functions. The Λc+/D0 baryon-to-meson yield ratio is reported for pp and p–Pb collisions. Comparisons with models that include modified hadronization processes are presented, and the implications of the results on the understanding of charm hadronization in hadronic collisions are discussed. A significant (3.7σ) modification of the mean transverse momentum of Λc+ baryons is seen in p–Pb collisions with respect to pp collisions, while the pT-integrated Λc+/D0 yield ratio was found to be consistent between the two collision systems within the uncertainties

    Light (anti)nuclei production in Pb-Pb collisions at <math><mrow><msqrt><msub><mi>s</mi><mrow><mi>N</mi><mi>N</mi></mrow></msub></msqrt><mo>=</mo><mn>5.02</mn><mo> </mo><mi>TeV</mi></mrow></math>

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    International audienceThe measurement of the production of deuterons, tritons and He3 and their antiparticles in Pb-Pb collisions at sNN=5.02TeV is presented in this article. The measurements are carried out at midrapidity (|y|&lt; 0.5) as a function of collision centrality using the ALICE detector. The pT-integrated yields, the coalescence parameters and the ratios to protons and antiprotons are reported and compared with nucleosynthesis models. The comparison of these results in different collision systems at different center-of-mass collision energies reveals a suppression of nucleus production in small systems. In the Statistical Hadronisation Model framework, this can be explained by a small correlation volume where the baryon number is conserved, as already shown in previous fluctuation analyses. However, a different size of the correlation volume is required to describe the proton yields in the same data sets. The coalescence model can describe this suppression by the fact that the wave functions of the nuclei are large and the fireball size starts to become comparable and even much smaller than the actual nucleus at low multiplicities
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