916 resultados para ER retention motif


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Insulin stimulates glucose transport in fat and muscle cells by triggering exocytosis of the glucose transporter GLUT4. To define the intracellular trafficking of GLUT4, we have studied the internalization of an epitope-tagged version of GLUT4 from the cell surface. GLUT4 rapidly traversed the endosomal system en route to a perinuclear location. This perinuclear GLUT4 compartment did not colocalize with endosomal markers (endosomal antigen I protein, transferrin) or TGN38, but showed significant overlap with the TGN target (t)-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) Syntaxins 6 and 16. These results were confirmed by vesicle immunoisolation. Consistent with a role for Syntaxins 6 and 16 in GLUT4 trafficking we found that their expression was up-regulated significantly during adipocyte differentiation and insulin stimulated their movement to the cell surface. GLUT4 trafficking between endosomes and trans-Golgi network was regulated via an acidic targeting motif in the carboxy terminus of GLUT4, because a mutant lacking this motif was retained in endosomes. We conclude that GLUT4 is rapidly transported from the cell surface to a subdomain of the trans-Golgi network that is enriched in the t-SNAREs Syntaxins 6 and 16 and that an acidic targeting motif in the C-terminal tail of GLUT4 plays an important role in this process.

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Purpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log K-oct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm(3))(1/2). Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log K-oct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

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Purpose. As reductions in dermal clearance increase the residence time of solutes in the skin and underlying tissues we compared the topical penetration of potentially useful vasoconstrictors (VCs) through human epidermis as both free bases and ion-pairs with salicylic acid (SA). Methods. We determined the in vitro epidermal flux of ephedrine, naphazoline, oxymetazoline, phenylephrine, and xylometazoline applied as saturated solutions in propylene glycol: water (1: 1) and of ephedrine, naphazoline and tetrahydrozoline as 10% solutions of 1: 1 molar ratio ion-pairs with SA in liquid paraffin. Results. As free bases, ephedrine had the highest maximal flux, Jmax = 77.4 +/- 11.7 mug/cm(2)/h, being 4-fold higher than tetrahydrozoline and xylometazoline, 6-fold higher than phenylephrine, 10-fold higher than naphazoline and 100-fold higher than oxymetazoline. Stepwise regression of solute physicochemical properties identified melting point as the most significant predictor of flux. As ion-pairs with SA, ephedrine and naphazoline had similar fluxes (11.5 +/- 2.3 and 12.0 +/- 1.6 mug/cm(2)/h respectively), whereas tetrahydrozoline was approximately 3-fold slower. Corresponding fluxes of SA from the ion-pairs were 18.6 +/- 0.6, 7.8 +/- 0.8 and 1.1 +/- 0.1 respectively. Transdermal transport of VC's is discussed. Conclusions. Epidermal retention of VCs and SA did not correspond to their molar ratio on application and confirmed that following partitioning into the stratum corneum, ion-pairs separate and further penetration is governed by individual solute characteristics.

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Nitrate leaching below the crop root-zone in variable charge soils may be adsorbed at anion exchange sites, thereby temporarily reducing the risk of contamination of water bodies. The objectives of this study were (i) to investigate whether nitrate adsorption, accumulation, and retention in the Johnstone River Catchment of Far North Queensland wet tropics is widespread; (ii) to assess the capacity of soil in the Johnstone River Catchment to retain nitrate; and (iii) to deduce the consequences of nitrate adsorption/desorption on contamination of water bodies. Soil cores ranging from 8 to 12.5 m depth were taken from 28 sites across the catchment, representing 9 Ferrosol soil types under sugarcane (Saccharum officinarum-S) cultivation for at least 50 years and from rainforest. The cores were segmented at 0.5-m depth increments and subsamples were analysed for nitrate-N, cation and anion exchange capacities, pH, exchangeable cations (Ca, Mg, K, Na), soil organic C, electrical conductivity, sulfate-S, and chloride. Nitrate-N concentration under sugarcane ranged from 0 to 72.5 mg/kg, compared with 0 to 0.31 mg/kg under rainforest, both Pin Gin soils. The average N load in 1-12 m depth across 19 highly oxidic profiles of the Pin Gin soil series was 1550 kg/ha, compared with 185 kg/ha under 8 non-Pin Gin soils and 11 kg/ha in rainforest on a Pin Gin soil. Most of the nitrate retention was observed at depth of 2-12 m, particularly at 4-10 m, indicating that the accumulation was well below the crop root-zone. The average maximum potential nitrate retention capacity was 10.8 t/ha for the Pin Gin and 4.7 t/ha for the non-Pin Gin soil. Compared with the current N load, the soils still possess a large capacity to adsorb and retain nitrate in profiles. Retention of large quantities of the leached nitrate deep in most of the profiles has reduced the risk of contamination of water bodies. However, computations show that substantial quantities of the nitrate leached below the root-zone were not adsorbed and remain unaccounted for. This unaccounted nitrate might have entered both on- and off-site water bodies and/or have been denitrified.

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Vegetative propagation of lavender offers several advantages over sexual propagation, among them crop homogeneity and yield of higher quality essential oil. However, Lavandula species have been propagated mostly by seeds and are said to be recalcitrant to rooting when propagated by cuttings. During cutting propagation, one of the important variables that influence the rooting capacity of cuttings is the leaf retention. The objective of this work was to evaluate the influence of leaf retention on rooting of L. dentata cuttings. Apical cuttings of L. dentata of 10 cm in length, keeping approximately 1/3, 1/2 or 2/3 of their leaves were planted in commercial substrate Plantmax HT® under intermittent mist. After two months, averages of root number, length of the longest root, root fresh and dry weights, and the survival percentage were evaluated. Root length and fresh weight were statistically greater with 2/3 of leaf retention and when fewer leaves were kept on the cuttings, lower means of root dry weight was observed. Under the conditions applied in this study, greater leaf retention was better for rooting of L. dentata cuttings.

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This paper examines the relationship between the level of satisfaction towards Human Resources Management practices among repatriates and the decision to remain on the home company after expatriation. Data was collected through semi-structured interviews of 28 Portuguese repatriates who remain and 16 organisational representatives from eight companies located in Portugal. The results show that (1) compensation system during the international assignment; (2) permanent support during the international assignment and; (3) recognition upon the return of the work and effort of expatriates during the international assignment are the most important HRM practices for promoting satisfaction among repatriates. Moreover, it is at repatriation phase that repatriates show higher dissatisfaction with HRM support. These findings will be discussed in detail and implications and suggestions for future research will be proposed as well.

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This investigation reviews literature on human resource management practices that influence the retention of repatriates. The processes of selection and training/preparation before the departure, the role of the mentor and of communication during the international assignment, a program of readjustment to repatriation and a career development plan after return to the home firm are the practices identified in the literature as the main promoters of repatriates’ retention. Evidence suggests that greater responsibility on the part of the firms before, during and after the international assignment allows for more efficiency in the management of their repatriates.

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Dissertation to obtain a Master Degree in Biotechnology

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Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Línguas Literatura e Cultura

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A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

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A presente dissertação aborda a problemática da reabilitação de taludes de escavação em maciços de baixa resistência. Para o efeito foi estudado um trecho da estrada regional 266 (ER 266), executada nos anos 40 do século passado, que deve a sua construção à necessidade de ligação da estação de caminhos-de-ferro de Luzianes Gare à vila algarvia de Monchique. Esta estrada insere-se em terrenos xistentos/pelíticos da Formação de Mira (Grupo de Flysch do Baixo Alentejo), desenrolando-se o traçado em grande parte da sua extensão em escavação, sendo frequentes os taludes com altura superior a 5 m e com pendentes da ordem de 50º, cuja estabilidade é essencialmente comandada pela compartimentação do maciço rochoso e pelas especificidades das rochas de baixa resistência que os constituem É analisada a situação de estabilidade dos taludes de escavação em vários trechos da ER 266, quer de taludes já intervencionados, onde se verificou a ocupação da via pelos materiais deslocados, quer de outros cujo reforço ainda não foi implementado. Definem-se as características geométricas, físicas e mecânicas dos taludes analisados, efectua-se uma análise expedita da susceptibilidade ao movimento para cada um, com uma avaliação quantitativa do factor de segurança global e do risco associado ao evento. Posteriormente, estabelece-se uma metodologia de intervenção para as situações mais relevantes estudadas, propondo-se um conjunto de potenciais soluções para as mesmas, abordando a adequação da técnica de estabilização ao maciço em causa, e às características da via em estudo (tipo de via, a sua localização e o respectivo tráfego), tendo por objectivo ser um contributo válido na gestão da manutenção de taludes rodoviários. Por fim, referem-se as principais conclusões relativas a intervenções de reabilitação de taludes de escavação em condições similares, em terrenos de baixa resistência.

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Organizations are undergoing serious difficulties to retain talent. Authors argue that Talent Management (TM) practices create beneficial outcomes for individuals and organizations. However, there is no research on the leaders’ role in the functioning of these practices. This study examines how LMX and role modeling influence the impact that TM practices have on employees’ trust in their organizations and retention. The analysis of two questionnaires (Nt1=175; Nt2=107) indicated that TM only reduced turnover intentions, via an increase in trust in the organization, when role modeling was high and not when it was low. Therefore, we can say that leaders are crucial in the TM context, and in sustaining a competitive advantage for organizations.

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Continente Online (COL) is the market leader of online grocery retailing in Portugal. Aiming at sustaining this position, it has been focusing its promotional efforts in acquiring and retaining customers. This report intakes an extensive study on the impact of COL’s exclusive promotional efforts (free delivery offers and ten percent discounts on loyalty card) on customer acquisition and retention, as well as, a cost analysis on these offers. Two econometric models were developed and the results were interesting. It was concluded that free delivery offers have a significant impact both in terms of customer acquisition and retention, having also a lower cost in comparison with ten percent on loyalty card discounts.

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The ability of a company to be able to do a precisely churn prediction, so it can act on it, is paramount. For this reason, Deloitte addressed me the challenge of characterizing the client’s retention in the telecom companies. To do so, it was created a comprehensive tool that enables Deloitte to evaluate the churn management maturity level of a telecom operator and highlight its strengths and weaknesses. The development of this matrix was based on a depth churn research, a market research based on 40 interviews and 2 focus group and the valuable feedback from Deloitte consultants.

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Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge.