Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity

Nanostructured Submicron Block Copolymer Dots by Sacrificial Stamping: A Potential Preconcentration Platform for Locally Resolved Sensing, Chemistry, and Cellular Interactions

Classical contact lithography involves patterning of surfaces by embossing or by transfer of ink. We report direct lithographic transfer of parts of sacrificial stamps onto counterpart surfaces. Using sacrificial stamps consisting of the block copolymer polystyrene-<i>block</i>-poly­(2-pyridine) (PS-<i>b</i>-P2VP), we deposited arrays of nanostructured submicron PS-<i>b</i>-P2VP dots with heights of ∼100 nm onto silicon wafers and glass slides. The sacrificial PS-<i>b</i>-P2VP stamps were topographically patterned with truncated-pyramidal contact elements and penetrated by spongy-continuous nanopore systems. The spongy nature of the sacrificial PS-<i>b</i>-P2VP stamps supported formation of adhesive contact to the counterpart surfaces and the rupture of the contact elements during stamp retraction. The submicron PS-<i>b</i>-P2VP dots generated by sacrificial stamping can be further functionalized; examples include loading submicron PS-<i>b</i>-P2VP dots with dyes and attachment of gold nanoparticles to their outer surfaces. The arrays of submicron PS-<i>b</i>-P2VP dots can be integrated into setups for advanced optical microscopy, total internal reflection fluorescence microscopy, or Raman microscopy. Arrays of nanostructured submicron block copolymer dots may represent a preconcentration platform for locally resolved sensing and locally resolved monitoring of cellular interactions or might be used as microreactor arrays in lab-on-chip configurations

Ordered Topographically Patterned Silicon by Insect-Inspired Capillary Submicron Stamping

Insect-inspired capillary submicron stamping and subsequent surface-limited metal-assisted chemical etching (MACE) with ammonium bifluoride as a HF source are employed for the high-throughput production of ordered topographically patterned silicon (tpSi). Insect feet often possess hairy contact elements through which adhesive secretion is deployed. Thus, arrays of adhesive secretion drops remain as footprints on contact surfaces. Stamps for insect-inspired capillary submicron stamping having surfaces topographically patterned with contact elements mimic the functional principles of such insect feet. They contain spongy continuous nanopore networks penetrating the entire stamps. Any ink (organic or aqueous) may be supplied from the backside of the nanoporous stamps to the contact elements. We generated ordered arrays of submicron AgNO₃ dots extending square millimeters on Si by manual stamping with cycle times of a few seconds under ambient conditions; at higher load, ordered holey AgNO₃ films were obtained. Surface-limited MACE correspondingly yielded either macroporous tpSi or Si pillar arrays. Inkjet printing of polymer solutions onto the tpSi yielded patterns of polymer blots conformally covering the tpSi. Such blot patterns could potentially represent a starting point for the development of persistent and scratch-resistant identity labels or quick response codes on silicon surfaces

Calcium-Induced Molecular Rearrangement of Peptide Folds Enables Biomineralization of Vaterite Calcium Carbonate

Proteins can control mineralization of CaCO₃ by selectively triggering the growth of calcite, aragonite or vaterite phases. The templating of CaCO₃ by proteins must occur predominantly at the protein/CaCO₃ interface, yet molecular-level insights into the interface during active mineralization have been lacking. Here, we investigate the role of peptide folding and structural flexibility on the mineralization of CaCO₃. We study two amphiphilic peptides based on glutamic acid and leucine with β-sheet and α-helical structures. Though both sequences lead to vaterite structures, the β-sheets yield free-standing vaterite nanosheet with superior stability and purity. Surface-spectroscopy and molecular dynamics simulations reveal that reciprocal structuring of calcium ions and peptides lead to the effective synthesis of vaterite by mimicry of the (001) crystal plane

How Gold Nanoparticles Influence Crystallization of Polyethylene in Rigid Cylindrical Nanopores

Even high amounts of gold nanoparticles (AuNPs) only moderately influence crystallization of bulk polyethylene (PE). However, under the rigid two-dimensional confinement of aligned cylindrical nanopores in anodic aluminum oxide (AAO) the presence of Au turns nucleation-dominated crystallization of PE at high supercooling into growth-dominated crystallization at lower supercooling. Transmission electron microscopy investigations revealed formation of larger Au crystals from AuNPs by Ostwald ripening. These larger Au crystals apparently acted as heterogeneous nucleation sites initiating PE crystallization in AAO nanopores. Thus, PE/Au composites in AAO exhibited significantly higher crystallization and melting onset temperatures as well as significantly weaker dependence of crystallization half-times on crystallization temperatures. X-ray texture analysis revealed for pure PE in AAO the existence of two copopulations of crystals with different orientations (indicative of nucleation-dominated crystal growth); PE/Au composites showed uniform alignment of the fastest growing PE crystal direction with the AAO nanopore axes (indicative of growth-dominated crystallization). The prevailing alignment of the [020] direction of orthorhombic PE with the AAO nanopore axes suggests that properly oriented crystals may form on pre-existing crystal surfaces by secondary nucleation. These secondary crystals grow along the AAO nanopores if, under the conditions of growth-dominated crystallization, competing crystals clogging the growth path are absent while the confinement of the AAO nanopore walls stabilizes the (020) growth faces

Surface Oxidation of Stainless Steel: Oxygen Evolution Electrocatalysts with High Catalytic Activity

The cheap stainless commodity steel AISI 304, which basically consists of Fe, Ni, and Cr, was surface-oxidized by exposure to Cl₂ gas. This treatment turned AISI 304 steel into an efficient electrocatalyst for water splitting at pH 7 and pH 13. The overpotential of the anodic oxygen evolution reaction (OER), which typically limits the efficiency of the overall water-splitting process, could be reduced to 260 mV at 1.5 mA/cm² in 0.1 M KOH. At pH 7, overpotentials of 500–550 mV at current densities of 0.65 mA/cm² were achieved. These values represent a surprisingly good activity taking into account the simplicity of the procedure and the fact that the starting material is virtually omnipresent. Surface-oxidized AISI 304 steel exhibited outstanding long-term stability of its electrocatalytic properties in the alkaline as well as in the neutral regime, which did not deteriorate even after chronopoteniometry for 150 000 s. XPS analysis revealed that surface oxidation resulted in the formation of Fe oxide and Cr oxide surface layers with a thickness in the range of a few nanometers accompanied by enrichment of Cr in the surface layer. Depending on the duration of the Cl₂ treatment, the purity of the Fe oxide/Cr oxide mixture lies between 95% and 98%. Surface oxidation of AISI 304 steel by chlorination is an easy and scalable access to nontoxic, cheap, stable, and efficient electrocatalysts for water splitting

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous

Search for supersymmetry in hadronic final states with missing transverse energy using the variables αT and b-quark multiplicity in pp collisions at √s = 8 TeV

Submitted by Vitor Silverio Rodrigues ([email protected]) on 2014-05-27T11:30:34Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:49Z : No. of bitstreams: 1 2-s2.0-84883824987.pdf: 1540579 bytes, checksum: be6bbff5192436d9fcdbc367ffd1650e (MD5) Made available in DSpace on 2014-05-27T11:30:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-01 An inclusive search for supersymmetric processes that produce final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of 8 TeV. The data sample corresponds to an integrated luminosity of 11.7 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, αT, is used to discriminate between events with genuine and misreconstructed missing transverse energy. The search is based on an examination of the number of reconstructed jets per event, the scalar sum of transverse energies of these jets, and the number of these jets identified as originating from bottom quarks. No significant excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of simplified models, with a special emphasis on both compressed-spectrum scenarios and direct or gluino-induced production of third-generation squarks. For the case of gluino-mediated squark production, gluino masses up to 950-1125 GeV are excluded depending on the assumed model. For the direct pair-production of squarks, masses up to 450 GeV are excluded for a single light first- or second-generation squark, increasing to 600 GeV for bottom squarks. © 2013 CERN for the benefit of the CMS collaboration. CERN, Geneva Yerevan Physics Institute, Yerevan Institut für Hochenergiephysik der OeAW, Wien National Centre for Particle and High Energy Physics, Minsk Universiteit Antwerpen, Antwerpen Vrije Universiteit Brussel, Brussel Université Libre de Bruxelles, Bruxelles Ghent University, Ghent Université Catholique de Louvain, Louvain-la-Neuve Université de Mons, Mons Centro Brasileiro de Pesquisas Fisicas, Rio de Janeiro Universidade do Estado do Rio de Janeiro, Rio de Janeiro Universidade Estadual Paulista, São Paulo Universidade Federal do ABC, São Paulo Institute for Nuclear Research and Nuclear Energy, Sofia University of Sofia, Sofia Institute of High Energy Physics, Beijing State Key Laboratory of Nuclear Physics and Technology Peking University, Beijing Universidad de Los Andes, Bogota Technical University of Split, Split University of Split, Split Institute Rudjer Boskovic, Zagreb University of Cyprus, Nicosia Charles University, Prague Academy of Scientific Research and Technology of the Arab Republic of Egypt Egyptian Network of High Energy Physics, Cairo National Institute of Chemical Physics and Biophysics, Tallinn Department of Physics University of Helsinki, Helsinki Helsinki Institute of Physics, Helsinki Lappeenranta University of Technology, Lappeenranta DSM/IRFU CEA/Saclay, Gif-sur-Yvette Laboratoire Leprince-Ringuet, Ecole Polytechnique IN2P3-CNRS, Palaiseau Institut Pluridisciplinaire Hubert Curien, Universite de Strasbourg, Universite de Haute Alsace Mulh CNRS/IN2P3, Strasbourg CNRS-IN2P3, Institut de Physique Nucléaire de Lyon Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne Institute of High Energy Physics and Informatization Tbilisi State University, Tbilisi I. Physikalisches Institut RWTH Aachen University, Aachen III. Physikalisches Institut A RWTH Aachen University, Aachen III. Physikalisches Institut B RWTH Aachen University, Aachen Deutsches Elektronen-Synchrotron, Hamburg University of Hamburg, Hamburg Institut für Experimentelle Kernphysik, Karlsruhe Institute of Nuclear and Particle Physics (INPP) NCSR Demokritos, Aghia Paraskevi University of Athens, Athens University of Ioánnina, Ioánnina KFKI Research Institute for Particle and Nuclear Physics, Budapest Institute of Nuclear Research ATOMKI, Debrecen University of Debrecen, Debrecen Panjab University, Chandigarh University of Delhi, Delhi Saha Institute of Nuclear Physics, Kolkata Bhabha Atomic Research Centre, Mumbai Tata Institute of Fundamental Research - EHEP, Mumbai Tata Institute of Fundamental Research - HECR, Mumbai Institute for Research in Fundamental Sciences (IPM), Tehran INFN Sezione di Bari, Bari Università di Bari, Bari Politecnico di Bari, Bari INFN Sezione di Bologna, Bologna Università di Bologna, Bologna INFN Sezione di Catania, Catania Università di Catania, Catania INFN Sezione di Firenze, Firenze Università di Firenze, Firenze INFN Laboratori Nazionali di Frascati, Frascati INFN Sezione di Genova, Genova Università di Genova, Genova INFN Sezione di Milano-Bicocca, Milano Università di Milano-Bicocca, Milano INFN Sezione di Napoli, Napoli Università di Napoli 'Federico II', Napoli Università della Basilicata (Potenza), Napoli Università G. 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