Identification of a novel determinant for membrane association in hepatitis C virus nonstructural protein 4B.

Nonstructural protein 4B (NS4B) plays an essential role in the formation of the hepatitis C virus (HCV) replication complex. It is a relatively poorly characterized integral membrane protein predicted to comprise four transmembrane segments in its central portion. Here, we describe a novel determinant for membrane association represented by amino acids (aa) 40 to 69 in the N-terminal portion of NS4B. This segment was sufficient to target and tightly anchor the green fluorescent protein to cellular membranes, as assessed by fluorescence microscopy as well as membrane extraction and flotation analyses. Circular dichroism and nuclear magnetic resonance structural analyses showed that this segment comprises an amphipathic alpha-helix extending from aa 42 to 66. Attenuated total reflection infrared spectroscopy and glycosylation acceptor site tagging revealed that this amphipathic alpha-helix has the potential to traverse the phospholipid bilayer as a transmembrane segment, likely upon oligomerization. Alanine substitution of the fully conserved aromatic residues on the hydrophobic helix side abrogated membrane association of the segment comprising aa 40 to 69 and disrupted the formation of a functional replication complex. These results provide the first atomic resolution structure of an essential membrane-associated determinant of HCV NS4B.

Sistemes integrats de gestió (Integrated Management Systems - IMS): Anàlisi empíric a les empreses de Catalunya

Projecte de recerca elaborat a partir d’una estada al Auditing and Integration of Management Systems Research Laboratory de la Universitat d’Alberta, Canadà, des de maig fins a setembre del 2007. Aquest centre porta a terme recerca de caire teòrica i bàsica aplicada a l’assegurament de la qualitat, i més concretament a l’estandardització i integració de sistemes de gestió. En primer lloc, s’han analitzat les dades obtingudes en l’estudi empíric descriptiu realitzat a Catalunya durant l’any 2005, focalitzat en els estàndards de gestió més utilitzats per les empreses catalanes, en que s’hi incloïen les normes ISO 9001, ISO 14001, OSHAS 18001 així com els nous estàndards de suport de la sèrie ISO 10000. En segon terme, i a partir d’aquest anàlisis previ, s’ha iniciat el disseny d’una metodologia flexible per a la integració dels sistemes de gestió basats en estàndards internacionals.

Algebraic properties of isochronous centers of polynomial quadratic-like Hamiltonian systems

Projecte de recerca elaborat a partir d’una estada a la School of Mathematics and Statistics de la University of Plymouth, United Kingdom, entre abril juliol del 2007.Aquesta investigació és encara oberta i la memòria que presento constitueix un informe de la recerca que estem duent a terme actualment. En aquesta nota estudiem els centres isòcrons dels sistemes Hamiltonians analítics, parant especial atenció en el cas polinomial. Ens centrem en els anomenats quadratic-like Hamiltonian systems. Diverses propietats dels centres isòcrons d'aquest tipus de sistemes van ser donades a [A. Cima, F. Mañosas and J. Villadelprat, Isochronicity for several classes of Hamiltonian systems, J. Di®erential Equations 157 (1999) 373{413]. Aquell article estava centrat principalment en el cas en que A; B i C fossin funcions analítiques. El nostre objectiu amb l'estudi que estem duent a terme és investigar el cas en el que aquestes funcions són polinomis. En aquesta nota formulem una conjectura concreta sobre les propietats algebraiques que venen forçades per la isocronia del centre i provem alguns resultats parcials.

Shaping fission yeast with microtubules.

For cell morphogenesis, the cell must establish distinct spatial domains at specified locations at the cell surface. Here, we review the molecular mechanisms of cell polarity in the fission yeast Schizosaccharomyces pombe. These are simple rod-shaped cells that form cortical domains at cell tips for cell growth and at the cell middle for cytokinesis. In both cases, microtubule-based systems help to shape the cell by breaking symmetry, providing endogenous spatial cues to position these sites. The plus ends of dynamic microtubules deliver polarity factors to the cell tips, leading to local activation of the GTPase cdc42p and the actin assembly machinery. Microtubule bundles contribute to positioning the division plane through the nucleus and the cytokinesis factor mid1p. Recent advances illustrate how the spatial and temporal regulation of cell polarization integrates many elements, including historical landmarks, positive and negative controls, and competition between pathways.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets.

An ammonium chloride erythrocyte-lysing procedure was used to prepare a bacterial pellet from positive blood cultures for direct matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry analysis. Identification was obtained for 78.7% of the pellets tested. Moreover, 99% of the MALDI-TOF identifications were congruent at the species level when considering valid scores. This fast and accurate method is promising.

Point-occurrence self-similarity in crackling-noise systems and in other complex systems

It has been recently found that a number of systems displaying crackling noise also show a remarkable behavior regarding the temporal occurrence of successive events versus their size: a scaling law for the probability distributions of waiting times as a function of a minimum size is fulfilled, signaling the existence on those systems of self-similarity in time-size. This property is also present in some non-crackling systems. Here, the uncommon character of the scaling law is illustrated with simple marked renewal processes, built by definition with no correlations. Whereas processes with a finite mean waiting time do not fulfill a scaling law in general and tend towards a Poisson process in the limit of very high sizes, processes without a finite mean tend to another class of distributions, characterized by double power-law waiting-time densities. This is somehow reminiscent of the generalized central limit theorem. A model with short-range correlations is not able to escape from the attraction of those limit distributions. A discussion on open problems in the modeling of these properties is provided.

Codex Search: propuesta e implementación de un sistema de recuperación de información de ámbito local basado en casos

CODEX SEARCH es un motor de recuperación de información especializado en derecho de extranjería que está basado en herramientas y conocimiento lingüísticos. Un motor o Sistema de Recuperación de Información (SRI) es un software capaz de localizar información en grandes colecciones documentales (entorno no trivial) en formato electrónico. Mediante un estudio previo se ha detectado que la extranjería es un ámbito discursivo en el que resulta difícil expresar la necesidad de información en términos de una consulta formal, objeto de los sistemas de recuperación actuales. Por lo tanto, para desarrollar un SRI eficiente en el dominio indicado no basta con emplear un modelo tradicional de RI, es decir, comparar los términos de la pregunta con los de la respuesta, básicamente porque no expresan implicaciones y porque no tiene que haber necesariamente una relación 1 a 1. En este sentido, la solución lingüística propuesta se basa en incorporar el conocimiento del especialista mediante la integración en el sistema de una librería de casos. Los casos son ejemplos de procedimientos aplicados por expertos a la solución de problemas que han ocurrido en la realidad y que han terminado en éxito o fracaso. Los resultados obtenidos en esta primera fase son muy alentadores pero es necesario continuar la investigación en este campo para mejorar el rendimiento del prototipo al que se puede acceder desde &http://161.116.36.139/~codex/&.

Brittle cornea syndrome: recognition, molecular diagnosis and management.

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.

AIMS/HYPOTHESIS: MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease. METHODS: MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat diet was performed by microarray. The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cells. RESULTS: MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. Functional studies indicate that these expression changes have positive effects on beta cell activities and mass. In contrast, modifications in the levels of miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 primarily occur in diabetic mice and result in increased beta cell apoptosis. These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function, and that additional microRNA deregulation negatively impacting on insulin-secreting cells may cause beta cell demise and diabetes manifestation. CONCLUSIONS/INTERPRETATION: We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs.

Geography of resonances and Arnold diffusion in a priori unstable Hamiltonian systems

"Vegeu el resum a l'inici del document del fitxer adjunt."

Fast numerical algorithms for the computation of invariant tori in Hamiltonian systems

In this paper, we develop numerical algorithms that use small requirements of storage and operations for the computation of invariant tori in Hamiltonian systems (exact symplectic maps and Hamiltonian vector fields). The algorithms are based on the parameterization method and follow closely the proof of the KAM theorem given in [LGJV05] and [FLS07]. They essentially consist in solving a functional equation satisfied by the invariant tori by using a Newton method. Using some geometric identities, it is possible to perform a Newton step using little storage and few operations. In this paper we focus on the numerical issues of the algorithms (speed, storage and stability) and we refer to the mentioned papers for the rigorous results. We show how to compute efficiently both maximal invariant tori and whiskered tori, together with the associated invariant stable and unstable manifolds of whiskered tori. Moreover, we present fast algorithms for the iteration of the quasi-periodic cocycles and the computation of the invariant bundles, which is a preliminary step for the computation of invariant whiskered tori. Since quasi-periodic cocycles appear in other contexts, this section may be of independent interest. The numerical methods presented here allow to compute in a unified way primary and secondary invariant KAM tori. Secondary tori are invariant tori which can be contracted to a periodic orbit. We present some preliminary results that ensure that the methods are indeed implementable and fast. We postpone to a future paper optimized implementations and results on the breakdown of invariant tori.

Older persons' perceptions of general practitioner or specialist primary care physicians : same point of view?

BACKGROUND: Identification of a Primary Care Physician (PCP) by older patients is considered as essential for the coordination of care, but the extent to which identified PCPs are general practitioners or specialists is unknown. This study described older patients' experiences with their PCP and tested the hypothesis of differences between patients who identify a specialist as their PCP (SP PCP) and those who turn to a general practitioner (GP PCP). METHODS: In 2012, a cross-sectional postal survey on care was conducted in the 68+ year old population of the canton of Vaud. Data was provided by 2,276 participants in the ongoing Lausanne cohort 65+ (Lc65+), a study of those born between 1934 and 1943, and by 998 persons from an additional sample drawn to include the population outside of Lausanne or born before 1934. RESULTS: Participants expressed favourable perceptions, at rates exceeding 75% for most items. However, only 38% to 51% responded positively for out-of-hours availability, easy access and at home visits, likelihood of prescribing expensive medication if needed, and doctors' awareness of over-the-counter drugs. 12.0% had an SP PCP, in 95.9% specialised in a discipline implying training in internal medicine. Bivariate and multivariate analyses did not result in significant differences between GP and SP PCPs regarding perceptions of accessibility/availability, doctor-patient relationship, information and continuity of care, prevention, spontaneous use of the emergency department or ambulatory care utilisation. CONCLUSIONS: Experiences of old patients were mostly positive despite some lack in reported hearing, memory testing, and colorectal cancer screening. We found no differences between GP and SP PCP groups.

Grothendieck topologies from unique factorisation systems

This article presents a way to associate a Grothendieck site structure to a category endowed with a unique factorisation system of its arrows. In particular this recovers the Zariski and Etale topologies and others related to Voevodsky's cd-structures. As unique factorisation systems are also frequent outside algebraic geometry, the same construction applies to some new contexts, where it is related with known structures dened otherwise. The paper details algebraic geometrical situations and sketches only the other contexts.

Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.

OBJECTIVES: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. METHODS: Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. RESULTS: In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. CONCLUSIONS: The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

How collaboration could contribute to make Catalan journals visible on the Internet?

Cooperation between libraries is a universal language spoken in different dialects. In 1996 the libraries of the state-funded universities and the National Library of Catalonia (Spain) formed the Consortium of Academic Libraries of Catalonia (CBUC) to act as a channel for cooperation. The organization and activities of CBUC are an example of how this universal language has been adapted to the specific characteristics of the Libraries of Catalonia. Catalonia is an autonomous region of Spain with 7 million inhabitants with its own language, history and traditions and with a strong feeling of own identity that facilitates the cooperation. Thanks to this (and also to the hard work of the member libraries), since then, CBUC has created a union catalogue, an interlibrary lending program, the Digital Library of Catalonia, a cooperative store, different cooperatives repositories and other cooperation programs. One of these cooperatives repositories is RACO (Catalan Journals in Open Access, www.raco.cat) where can be consulted, in open access, the full-text articles of scientific, cultural and scholar Catalan journals. The main purpose of RACO is to increase the visibility and searches of the journals included and to spread the scientific and academic production published in Catalonia. This purpose makes specific in three aims: encourage the electronic edition of Catalan journals; be the interface that allows the whole search of all the journals and provide the instruments for its preservation. There are currently 244 journals in RACO, that includes more than 85.000 articles (80% in OA) from 50 publishing institutions. Since it got into operation it has had more than 4 millions of queries. These 244 journals offer the full-text of all the published issues. Nevertheless, some journal can have a delay between the introduction of the table of contents and the full-text for the recent issues. From 2005 we have a plan of retrospective digitization that has allowed to digitize more than 350.000 pages of back issues. The RACO repository works with the open source program OJS (Open Journal Systems, http://pkp.sfu.ca/ojs/) and uses Dublin Core Metadata and the interoperability protocol created by Open Archives Initiative (OAI) which allows to increase the visibility of the articles published in journals offering oneself together with other international repositories.