Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors. (C) 2003 Elsevier Science (USA). All rights reserved.

The Main Determinants of the Use of the Cost Accounting System in Portuguese Local Government

This paper explores the main determinants of the use of the cost accounting system (CAS) in Portuguese local government (PLG). Regression analysis is used to study the fit of a model of accounting changes in PLG, focused on cost accounting systems oriented to activities and outputs. Based on survey data gathered from PLG, we have found that the use of information in decision-making and external reporting is still a mirage. We obtain evidence about the influence of the internal organizational context (especially the lack of support and difficulties in the CAS implementation) in the use for internal purposes, while the institutional environment (like external pressures to implement the CAS) appears to be more deterministic of the external use. Results strengthen the function of external reporting to legitimate the organization’s activities to external stakeholders. On the other hand, some control variables (like political competition, usefulness and experience) also evidence some explanatory power in the model. Some mixed results were found that appeal to further research in the future. Our empirical results contribute to understand the importance of interconnecting the contingency and institutional approaches to gain a clear picture of cost accounting changes in the public sector.

A model of destination competitiveness/sustainability: Brazilian perspectives

This paper reviews the understanding I have gained from several years of research, and from several more years of ongoing discussions with industry leaders regarding the nature of competitiveness among tourism destinations. This understanding has been captured, in summary form, in the model of Destination Competitiveness/Sustainability (Ritchie and Crouch, 2003). This model contains seven (7) components which we have found to play a major role, from a policy perspective, in determining the competitiveness/sustainability of a tourism destination. In addition to the valuable understanding which these seven components provide from a policy perspective, the specific elements of each the major components provide a more useful/practical guidance to those who are responsible for the ongoing management of a DMO (Destination Management Organization). With this overview in mind, this paper will provide a detailed review and explanation of the model that I have developed with colleague, Dr. Geoffrey I. Crouch of Latrobe University in Melbourne, Australia. Based on previous presentations throughout the world, it has proven very helpful to both academics and practitioners who seek to understand the complex nature of tourism destination competitiveness/sustainability.

Conceptual model for decomposing the value for the customer

Value has been defined in different theoretical contexts as need, desire, interest, standard /criteria, beliefs, attitudes, and preferences. The creation of value is key to any business, and any business activity is about exchanging some tangible and/or intangible good or service and having its value accepted and rewarded by customers or clients, either inside the enterprise or collaborative network or outside. “Perhaps surprising then is that firms often do not know how to define value, or how to measure it” (Anderson and Narus, 1998 cited by [1]). Woodruff echoed that we need “richer customer value theory” for providing an “important tool for locking onto the critical things that managers need to know”. In addition, he emphasized, “we need customer value theory that delves deeply into customer’s world of product use in their situations” [2]. In this sense, we proposed and validated a novel “Conceptual Model for Decomposing the Value for the Customer”. To this end, we were aware that time has a direct impact on customer perceived value, and the suppliers’ and customers’ perceptions change from the pre-purchase to the post-purchase phases, causing some uncertainty and doubts.We wanted to break down value into all its components, as well as every built and used assets (both endogenous and/or exogenous perspectives). This component analysis was then transposed into a mathematical formulation using the Fuzzy Analytic Hierarchy Process (AHP), so that the uncertainty and vagueness of value perceptions could be embedded in this model that relates used and built assets in the tangible and intangible deliverable exchange among the involved parties, with their actual value perceptions.

Day-ahead resource scheduling in smart grids considering Vehicle-to-Grid and network constraints

Energy resource scheduling becomes increasingly important, as the use of distributed resources is intensified and massive gridable vehicle use is envisaged. The present paper proposes a methodology for dayahead energy resource scheduling for smart grids considering the intensive use of distributed generation and of gridable vehicles, usually referred as Vehicle- o-Grid (V2G). This method considers that the energy resources are managed by a Virtual Power Player (VPP) which established contracts with V2G owners. It takes into account these contracts, the user´s requirements subjected to the VPP, and several discharge price steps. Full AC power flow calculation included in the model allows taking into account network constraints. The influence of the successive day requirements on the day-ahead optimal solution is discussed and considered in the proposed model. A case study with a 33 bus distribution network and V2G is used to illustrate the good performance of the proposed method.

The problems of the european union film industry: an evolution from "subsidy trap" to the advent of "virtual print fee" model

Dissertação de Mestrado, Gestão de Empresa (MBA), 16 de Julho de 2013, Universidade dos Açores.

Evaluation of 99mTc-Sestamibi as a potential tool to investigate PgP activity in inflammation

Introduction: In the XXI Century ’s Society the scientific investigation process has been growing steadily , and the field of the pharmaceutical research is one of the most enthusiastic and relevant . Here, it is very important to correlate observed functional alterations with possibly modified drug bio distribution patterns . Cancer, inflammation and inf ection are processes that induce many molecular intermediates like cytokines, chemokines and other chemical complexes that can alter the pharmacokinetics of many drugs. One cause of such changes is thought to be the modulator action of these complexes in t he P - Glyco p rotein activity, because they can act like inducers/inhibitors of MDR - 1 expression. This protein results from the expression of MDR - 1 gene, and acts as an ATP energy - dependent efflux pump, with their substrates including many drugs , like antiretrovirals, anticancers, anti - infectives, immunosuppressants, steroids or opioids . Objectives: Because of the lack of methods to provide helpful information in the investigation of in vivo molecular changes in Pgp activity during infection/infl ammation processes, and its value in the explanation of the altered drug pharmacokinetic, this paper want to evaluate the potential utility of 99m Tc - Sestamibi scintigraphy during this kind of health sciences investigation. Although the a im is indeed to create a technique to the in vivo study of Pgp activity, this preliminary Project only reaches the in vitro study phase, assumed as the first step in a n evaluation period for a new tool development. Materials and Methods: For that reason , we are performing in vitro studies of influx and efflux of 99m Tc - Sestamibi ( that is a substrate of Pgp) in hepatocytes cell line (HepG2). We are interested in clarify the cellular behavior of this radiopharmaceutical in Lipopolysaccharide(LPS) stimulated cells ( well known in vitro model of inflammation) to possibly approve this methodology. To validate the results, the Pgp expression will be finally evaluated using Western Blot technique. Results: Up to this moment , we still don’t have the final results, but we have already enough data to let us believe that LPS stimulation induce a downregulation of MDR - 1, and consequently Pgp, which could conduce to a prolonged retention of 99m Tc - Sestamibi in the inflamed cells . Conclusions: If and when this methodology demonstrate the promising results we expect, one will be able to con clude that Nuclear Medicine is an important tool to help evidence based research also on this specific field .

Consumo de eletricidade nas famílias na Região Autónoma dos Açores

Tese de Doutoramento em Ciências Económicas e Empresariais, especialidade em Desenvolvimento Regional.

Performance of a Brazilian population on the test of functional health literacy in adults

OBJECTIVE: To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS: The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS: The mean age of the sample was 47.3 years(sd=16.8) and the mean education was 9.7 years(sd=5; range: 1 - 17). A total of 32.4% of the sample showed literacy/numeracy deficits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; p<0.01) and a negative correlation between age and the scores (r=-0.259; p<0.01). The correlation between the scores and age was not significant when the effects of education were held constant (rp=-0.031, p=0.584). A significant association (B=3.877, Beta =0.733; p<0.001) was found between schooling and scores. Age was not a significant predictor in this model (B=-0.035, Beta=-0.22; p=0.584). CONCLUSIONS: The short version of the Test of Functional Health Literacy in Adults was a suitable tool to assess health literacy in the study population. The high number of individuals classified as functional illiterates in this test highlights the importance of special assistance to help them properly understand directions for healthcare.

Self-assembly in chains, rings, and branches: a single component system with two critical points

Agências financiadoras: FCT - PEstOE/FIS/UI0618/2011; PTDC/FIS/098254/2008 ERC-PATCHYCOLLOIDS e MIUR-PRIN

Association between tooth loss and obesity in Brazilian adults: a population-based study

OBJECTIVE: To examine the association between tooth loss and general and central obesity among adults. METHODS: Population-based cross-sectional study with 1,720 adults aged 20 to 59 years from Florianópolis, Southern Brazil. Home interviews were performed and anthropometric measures were taken. Information on sociodemographic data, self-reported diabetes, self-reported number of teeth, central obesity (waist circumference [WC] > 88 cm in women and > 102 cm in men) and general obesity (body mass index [BMI] ≥ 30 kg/m²) was collected. We used multivariable Poisson regression models to assess the association between general and central obesity and tooth loss after controlling for confounders. We also performed simple and multiple linear regressions by using BMI and WC as continuous variables. Interaction between age and tooth loss was also assessed. RESULTS: The mean BMI was 25.9 kg/m² (95%CI 25.6;26.2) in men and 25.4 kg/m2 (95%CI 25.0;25.7) in women. The mean WC was 79.3 cm (95%CI 78.4;80.1) in men and 88.4 cm (95%CI 87.6;89.2) in women. A positive association was found between the presence of less than 10 teeth in at least one arch and increased mean BMI and WC after adjusting for education level, self-reported diabetes, gender and monthly per capita income. However, this association was lost when the variable age was included in the model. The prevalence of general obesity was 50% higher in those with less than 10 teeth in at least one arch when compared with those with 10 or more teeth in both arches after adjusting for education level, self-reported diabetes and monthly per capita family income. However, the statistical significance was lost after controlling for age. CONCLUSIONS: Obesity was associated with number of teeth, though it depended on the participants' age groups.

Applicability of SERVQUAL in restaurants: an exploratory study in a Portuguese resort

SERVQUAL is the most popular instrument to ascertain service quality. However, some debate exists about its ability to characterize different service environments. Furthermore, there is not a consensus about the inclusion of customer expectations in the model. The research presented in this paper intends to discuss the applicability of SERVQUAL to restaurant services and to analyze the inclusion of customer expectations in such environment. The research was developed in a Portuguese resort and more than 300 customers, from two different restaurants, were invited to participate in the study.

Association between sleep quality and quality of life in nursing professionals working rotating shifts

OBJECTIVE To analyze the association between sleep quality and quality of life of nursing professionals according to their work schedules.METHODS A prospective, cross-sectional, observational study was conducted between January and December 2010, with 264 nursing professionals, drawn from 989 subjects at Botucatu General Hospital and stratified by professional category. The Pittsburg Sleep Quality Index and the WHOQOL-bref were administered to evaluate sleep quality and quality of life, respectively. Self-reported demographic data were collected with a standard form. Continuous variables were reported as means and standard deviations, and categorical variables were expressed as proportions. Associations were evaluated using Spearman’s correlation coefficient. The association of night-shift work and gender with sleep disturbance was evaluated by logistic regression analysis using a model adjusted for age and considering sleep disturbance the dependent variable. The level of significance was p < 0.05.RESULTS Night-shift work was associated with severe worsening of at least one component of sleep quality in the model adjusted for age (OR = 1.91; 95%CI 1.04;3.50; p = 0.036). Female gender was associated with sleep disturbance (OR = 3.40; 95%CI 1.37;8.40; p = 0.008). Quality of life and quality of sleep were closely correlated (R = -0.56; p < 0.001).CONCLUSIONS Characteristics of the nursing profession affect sleep quality and quality of life, and these two variables are associated.

Lightweight amorphous silicon photovoltaic modules on flexible plastic substrate

Solar cells on lightweight and flexible substrates have advantages over glass-or wafer-based photovoltaic devices in both terrestrial and space applications. Here, we report on development of amorphous silicon thin film photovoltaic modules fabricated at maximum deposition temperature of 150 degrees C on 100 mu m thick polyethylene-naphtalate plastic films. Each module of 10 cm x 10 cm area consists of 72 a-Si:H n-i-p rectangular structures with transparent conducting oxide top electrodes with Al fingers and metal back electrodes deposited through the shadow masks. Individual structures are connected in series forming eight rows with connection ports provided for external blocking diodes. The design optimization and device performance analysis are performed using a developed SPICE model.

Factors associated with arterial stiffness in children aged 9-10 years

OBJECTIVE To analyze the factors associated with stiffness of the great arteries in prepubertal children.METHODS This study with convenience sample of 231 schoolchildren aged 9-10 years enrolled in public and private schools in Vitória, ES, Southeastern Brazil, in 2010-2011. Anthropometric and hemodynamic data, blood pressure, and pulse wave velocity in the carotid-femoral segment were obtained. Data on current and previous health conditions were obtained by questionnaire and notes on the child’s health card. Multiple linear regression was applied to identify the partial and total contribution of the factors in determining the pulse wave velocity values.RESULTS Among the students, 50.2% were female and 55.4% were 10 years old. Among those classified in the last tertile of pulse wave velocity, 60.0% were overweight, with higher mean blood pressure, waist circumference, and waist-to-height ratio. Birth weight was not associated with pulse wave velocity. After multiple linear regression analysis, body mass index (BMI) and diastolic blood pressure remained in the model.CONCLUSIONS BMI was the most important factor in determining arterial stiffness in children aged 9-10 years.