612 research outputs found

    “Portfolio Project: el dossier d’aprenentatge com a mètode d’avaluació”

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    L’assignatura "Narratives contemporànies en anglès" és una assignatura obligatòria de segon cicle -4t curs- dins el Grau d’Estudis Anglesos de la Facultat de Filologia amb un alumnat que presenta una molt bona disposició per a les actuacions d’innovació docent, donades les seves competències sòlides en diversos camps d’aprenentatge. Per aquest motiu, hem plantejat el Portfoli o dossier d’aprenentatge com una eina docent mitjançant la qual l’alumne/a ha pogut cartografiar la seva experiència de lectura d’una de les novel•les incloses en el llistat de lectures obligatòries del curs.GID INDIGOU

    La literatura inglesa del siglo XX en la España de la postguerra: la aportación de José Janés

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    [spa] Esta tesis pretende demostrar que existe una relación estrecha entre la labor de penetración de la narrativa inglesa del siglo XX llevada a cabo por las empresas editoriales dirigidas por José Janés a lo largo de los años cuarenta y el compromiso catalán de su empresario. Aventuro la hipótesis que habría que valorar la actividad editorial de postguerra no como una labor contradictoria a la de los años republicanos, sino como la "Santa Continuació" (y el eco orsiano no es en absoluto gratuito) de aquella, in situ, ajustada a la imponente realidad histórica del momento. La primera parte de este trabajo es una contribución esencialmente biográfica que cubre los años 1913 hasta el final de la guerra civil en Cataluña, es decir, desde el nacimiento de Josep Janés i Olivé hasta el éxodo de 1939. La segunda parte del trabajo pretende ser, en primer lugar, de orientación respecto a la situación político-cultural de España en relación concreta con Gran Bretaña en el decenio de los cuarenta. Esta tesis, pues, que en un principio fue destinada a abarcar las dos décadas después de terminar la guerra civil, se ha convertido forzosamente, dado la evolución peculiar del tema, en el estudio de cincuenta años de vida cultural marcados por unos acontecimientos político-sociales trascendentes para la calidad de esta vida cultural» El tema esencial del trabajo es un fenómeno de la postguerra española, pero se reitera la convicción de que no se puede entender un cierto presente sin conocer los antecedentes

    Asymmetric dearomatization/cyclization enables access to polycyclic chemotypes

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    Enantioenriched, polycyclic compounds were obtained from a simple acylphloroglucinol scaffold. Highly enantioselective dearomatization was accomplished using a Trost ligand-palladium(0) complex. A computational DFT model was developed to rationalize observed enantioselectivities and revealed a key reactant-ligand hydrogen bonding interaction. Dearomatized products were used in visible light-mediated photocycloadditions and oxidative free radical cyclizations to obtain novel polycyclic chemotypes including tricyclo[4.3.1.01,4]decan-10-ones, bicyclo[3.2.1]octan-8-ones and highly-substituted cycloheptanones.R24 GM111625 - NIGMS NIH HH

    The In Vivo Association of BiP with Newly Synthesized Proteins Is Dependent on the Rate and Stability of Folding and Not Simply on the Presence of Sequences That Can Bind to BiP

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    Immunoglobulin heavy chain-binding protein (BiP) is a member of the hsp70 family of chaperones and one of the most abundant proteins in the ER lumen. It is known to interact transiently with many nascent proteins as they enter the ER and more stably with protein subunits produced in stoichiometric excess or with mutant proteins. However, there also exists a large number of secretory pathway proteins that do not apparently interact with BiP. To begin to understand what controls the likelihood that a nascent protein entering the ER will associate with BiP, we have examined the in vivo folding of a murine λI immunoglobulin (Ig) light chain (LC). This LC is composed of two Ig domains that can fold independent of the other and that each possess multiple potential BiP-binding sequences. To detect BiP binding to the LC during folding, we used BiP ATPase mutants, which bind irreversibly to proteins, as “kinetic traps.” Although both the wild-type and mutant BiP clearly associated with the unoxidized variable region domain, we were unable to detect binding of either BiP protein to the constant region domain. A combination of in vivo and in vitro folding studies revealed that the constant domain folds rapidly and stably even in the absence of an intradomain disulfide bond. Thus, the simple presence of a BiP-binding site on a nascent chain does not ensure that BiP will bind and play a role in its folding. Instead, it appears that the rate and stability of protein folding determines whether or not a particular site is recognized, with BiP preferentially binding to proteins that fold slowly or somewhat unstably

    Visible-Light Photoredox Catalysis in Flow

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    Photoredox catalysis: A variety of organic transformations mediated by visible-light-active photoredox catalysts have been conducted in a photochemical flow reactor. The reactor design is very simple and can be easily implemented in any laboratory (see picture). In addition, this reactor afforded a marked increase in the reaction rate compared to those observed in typical batch (round bottom flask) reactors.National Science Foundation (U.S.) (Grant CHE-1056568)National Institutes of Health (U.S.) (NIGMS Grant R01-GM096129)Alfred P. Sloan FoundationAmgen Inc.Boehringer Ingelheim PharmaceuticalsAmgen Inc. (Graduate Fellowship)NMR (CHE-0619339)MS (CHE-0443618

    Synthetic approaches to pallimamine and analogues using direct imine acylation

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    The use of Direct Imine Acylation (DIA) methodology for the total synthesis of pallimamine is described, with three different synthetic routes examined. The construction of three advanced δ-lactam precursors, all utilising DIA, is described, along with attempts to progress these compounds further, using three distinct desymmetrisation strategies, two involving alcohol-aryl coupling, and a third involving an unusual diastereoselective lactonisation

    An initial evaluation of newly proposed biomarker of zinc status in humans - linoleic acid: dihomo-y-linolenic acid (LA:DGLA) ratio

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    Background: Zinc is an essential micronutrient for humans with important physiological functions. A sensitive and specific biomarker for assessing Zn status is still needed. Objective: The major aim of this study was to examine if the changes in the content of plasma phospholipid LA, DGLA and LA: DGLA ratio can be used to efficiently predict the dietary Zn intake and plasma Zn status of humans. Methods: The study was performed on healthy human volunteers, 25-55 years of age. The dietary Zn intake was assessed using 24 h recall questionnaires. Plasma phospholipid fatty acid analysis was done by gas chromatography, and plasma analysis of minerals by atomic absorption spectrometry. Biochemical, anthropometrical and hematological parameters were assessed. Results: No significant relationship was found between the dietary and plasma zinc status (r = 0.07; p = 0.6). There was a statistically significant correlation between DGLA and plasma Zn (r = 0.39, p = 0.00). No relationship was observed between the linoleic acid and plasma Zn, while there was a significant negative correlation between LA: DGLA ratio and plasma Zn status (r = 0.35, p = 0.01). Similarly, there were statistically significant difference in DGLA status (p = 0.004) and LA: DGLA ratio (p = 0.042) between the Zn formed groups. Conclusions: This study is an initial step in evaluating LA: DGLA ratio as a biomarker of Zn status in humans. The results are encouraging as they show that concentration of DGLA is decreased and LA: DGLA ratio increased in people with lower dietary Zn intake. However, additional studies are needed to fully examine the sensitivity of this biomarker

    Strategies for carbohydrate model building, refinement and validation

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    Sugars are the most stereochemically intricate family of biomolecules and present substantial challenges to anyone trying to understand their nomenclature, reactions or branched structures. Current crystallographic programs provide an abstraction layer allowing inexpert structural biologists to build complete protein or nucleic acid model components automatically either from scratch or with little manual intervention. This is, however, still not generally true for sugars. The need for carbohydrate-specific building and validation tools has been highlighted a number of times in the past, concomitantly with the introduction of a new generation of experimental methods that have been ramping up the production of protein-sugar complexes and glycoproteins for the past decade. While some incipient advances have been made to address these demands, correctly modelling and refining carbohydrates remains a challenge. This article will address many of the typical difficulties that a structural biologist may face when dealing with carbohydrates, with an emphasis on problem solving in the resolution range where X-ray crystallography and cryo-electron microscopy are expected to overlap in the next decade

    Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin

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    Receptor-type protein tyrosine phosphatases (RPTPs) of the R3 subgroup play key roles in the immune, vascular and nervous systems. They are characterised by a large ectodomain comprising multiple FNIII-like repeats, a transmembrane domain, and a single intracellular phosphatase domain. The functional role of the extracellular region has not been clearly defined and potential roles in ligand interaction, di-merization, and regulation of cell-cell contacts have been reported. Here bimolecular fluorescence complementation (BiFC) in live cells was used to examine the molecular basis for the interaction of VE-PTP with VE-cadherin, two proteins involved in endothelial cell contact and maintenance of vascu-lar integrity. The potential of other R3-PTPs to interact with VE-cadherin was also explored using this method. Quantitative BiFC analysis, using a VE-PTP construct expressing only the ectodomain and transmembrane domain, revealed a specific interaction with VE-cadherin, when compared with con-trols. Controls were sialophorin, an unrelated membrane protein with a large ectodomain, and a mem-brane anchored C-terminal Venus-YFP fragment, lacking both ectodomain and transmembrane do-mains. Truncation of the first 16 FNIII-like repeats from the ectodomain of VE-PTP indicated that re-moval of this region is not sufficient to disrupt the interaction with VE-cadherin, although it occurs predominantly in an intracellular location. A construct with a deletion of only the 17th domain of VE-PTP was, in contrast to previous studies, still able to interact with VE-cadherin, although this also was predominantly intracellular. Other members of the R3-PTP family (DEP-1, GLEPP1 and SAP-1) also exhibited the potential to interact with VE-cadherin. The direct interaction of DEP-1 with VE-cadherin is likely to be of physiological relevance since both proteins are expressed in endothelial cells. Together the data presented in the study suggest a role for both the ectodomain and transmembrane domain of R3-PTPs in interaction with VE-cadherin
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