128 research outputs found

    Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

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    A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

    Conformational Changes and Slow Dynamics through Microsecond Polarized Atomistic Molecular Simulation of an Integral Kv1.2 Ion Channel

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    Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins—not to mention numerous applications in drug design. Here, we present a full 1 µs atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120° rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation (∼35°) of the extracellular end of all S4 segments is present also in a reference 0.5 µs simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 310 helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4–lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5–1 µs). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations

    Synthesis of 2-azidoethyl α-d-mannopyranoside orthogonally protected and selective deprotections

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    4 páginas, 1 figura, 2 esquemas.We present the synthesis of a fully orthogonally protected mannosyl glycoside 1 and the corresponding methods for selective deprotections. Mannosyl glycoside 1 contains a functionalized linker at the anomeric position to allow for the attachment of carbohydrate units to scaffolds in order to prepare carbohydrate multivalent systems.We would like to thank FIS (PI030093), for financial supportPeer reviewe

    Keratan sulphate in the tumour environment

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    Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes

    Repercussões da Lei Maria da Penha no enfrentamento da violência doméstica em Porto Alegre

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    O presente estudo procurou analisar as repercussões da Lei Maria da Penha no enfrentamento da violência domésticacontra mulheres, na cidade de Porto Alegre, a partir da visão dos profissionais que constituem a rede de atendimentoa elas. Foram entrevistados sete profissionais que atuam na rede de atendimento a mulheres vítimas de violência.Os dados sugerem que a Lei promoveu mudanças nos campos da prevenção da violência, da assistência a mulherese da punição aos agressores, com aumento da visibilidade conferida a esse fenômeno e empoderamento feminino.Conclui-se que o fortalecimento das medidas preconizadas pela Lei Maria da Penha ainda depende de investimentosna qualificação dos profissionais, de ações articuladas entre os locais de atendimento e de crescente utilização daatenção básica para a promoção da saúde de mulheres e famílias expostas à violência

    Regulatory Environment, Linguistic Inequalities, and New Opportunities for Hungarian Minority Interest Representation in Romania

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    In an interdisciplinary approach, the study discusses the legal and socioeconomic aspects of Hungarian minority language use in the northwestern part of Romania, Transylvania. It presents traditional and innovative models of language activism in the region and discusses how supranational rules and market deregulation that followed the EU membership of the country opened up new possibilities for a “grassroots,” spontaneous expansion of multilingualism in the economy and in society in general
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