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.

Evaluating a model of parental influence on youth physical activity

Objective: To test a conceptual model linking parental physical activity orientations, parental support for physical activity, and children's self-efficacy perceptions with physical activity participation. Participants and Setting: The sample consisted of 380 students in grades 7 through 12 (mean age, 14.0 +/- 1.6 years) and their parents. Data collection took place during the fall of 1996. Main Outcome Measures: Parents completed a questionnaire assessing their physical activity habits, enjoyment of physical activity, beliefs regarding the importance of physical activity, and supportive behaviors for their child's physical activity. Students completed a 46-item inventory assessing physical activity during the previous 7 days and a 5-item physical activity self-efficacy scale. The model was tested via observed variable path analysis using structural equation modeling techniques (AMOS 4.0). Results: An initial model, in which parent physical activity orientations predicted child physical activity via parental support and child self-efficacy, did not provide an acceptable fit to the data. Inclusion of a direct path from parental support to child physical activity and deletion of a nonsignificant path from parental physical activity to child physical activity significantly improved model fit. Standardized path coefficients for the revised model ranged from 0.17 to 0.24, and all were significant at the p < 0.0001 level. Conclusions: Parental support was an important correlate of youth physical activity, acting directly or indirectly through its influence on self-efficacy. Physical activity interventions targeted at youth should include and evaluate the efficacy of individual-level and community-level strategies to increase parents' capacity to provide instrumental and motivational support for their children's physical activity.

The international implications of the Chinese model of development in the Global South: Asian Consensus as a network power

This paper analyzes People's Republic of China (PRC) economic and political ascendance in the 21st century focusing on the evolution of the sui generis economic development model and its significances of the evolution of relationship between China and the developing countries in the peripheral "Global South." The objective of this article is to analyze the relationship between China and the Global South (Africa and South America) in the 21st century, characterized as a new Center-periphery global network power based on trade and investment that we call as "Asian Consensus."

Travel preferences of the residents of Guimarães: a revised model of push and pull motives

The historic center of the Portuguese city of Guimarães is a world heritage site (UNESCO) since 2001, having hosted the European Capital of Culture (ECOC) in 2012. In this sense, Guimarães has made a major effort in promoting tourism, positioning itself as an urban and cultural tourism destination. The present paper has two objectives. The first, to examine if an existing push and pull motivation model finds statistical support with regard to the population of the municipality of Guimarães, a cultural tourism destination. The second, to study the role that important socio-demographic variables, such as gender, age, and education, play in determining travel motivations of residents from this municipality. Insight on tourism motivation may be an important policy tool for tourism planners and managers in the development of products and marketing strategies. The empirical analysis is undertaken based on questionnaires administered in 2012 to residents of Guimarães. The present study shows that gender, age and education make a difference with regard to travel motivations.

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.

A theoretical model of the evolution of virulence in sexually transmitted HIV/AIDS

INTRODUCTION: The evolution of virulence in host-parasite relationships has been the subject of several publications. In the case of HIV virulence, some authors suggest that the evolution of HIV virulence correlates with the rate of acquisition of new sexual partners. In contrast some other authors argue that the level of HIV virulence is independent of the sexual activity of the host population. METHODS: Provide a mathematical model for the study of the potential influence of human sexual behaviour on the evolution of virulence of HIV is provided. RESULTS: The results indicated that, when the probability of acquisition of infection is a function both of the sexual activity and of the virulence level of HIV strains, the evolution of HIV virulence correlates positively with the rate of acquisition of new sexual partners. CONCLUSION: It is concluded that in the case of a host population with a low (high) rate of exchange of sexual partners the evolution of HIV virulence is such that the less (more) virulent strain prevails.

Deep-Sea ecosystem model of the Condor seamount

Dissertação de Mestrado, Estudos Integrados dos Oceanos, 25 de Julho 2013, Universidade dos Açores.

Towards a complex model of cooperative learning

Este artigo é uma introdução à teoria do paradigma desconstrutivo de aprendizagem cooperativa. Centenas de estudos provam com evidências o facto de que as estruturas e os processos de aprendizagem cooperativa aumentam o desempenho académico, reforçam as competências de aprendizagem ao longo da vida e desenvolvem competências sociais, pessoais de cada aluno de uma forma mais eficaz e usta, comparativamente às estruturas tradicionais de aprendizagem nas escolas. Enfrentando os desafios dos nossos sistemas educativos, seria interessante elaborar o quadro teórico do discurso da aprendizagem cooperativa, dos últimos 40 anos, a partir de um aspeto prático dentro do contexto teórico e metodológico. Nas últimas décadas, o discurso cooperativo elaborou os elementos práticos e teóricos de estruturas e processos de aprendizagem cooperativa. Gostaríamos de fazer um resumo desses elementos com o objetivo de compreender que tipo de mudanças estruturais podem fazer diferenças reais na prática de ensino e aprendizagem. Os princípios básicos de estruturas cooperativas, os papéis de cooperação e as atitudes cooperativas são os principais elementos que podemos brevemente descrever aqui, de modo a criar um quadro para a compreensão teórica e prática de como podemos sugerir os elementos de aprendizagem cooperativa na nossa prática em sala de aula. Na minha perspetiva, esta complexa teoria da aprendizagem cooperativa pode ser entendida como um paradigma desconstrutivo que fornece algumas respostas pragmáticas para as questões da nossa prática educativa quotidiana, a partir do nível da sala de aula para o nível de sistema educativo, com foco na destruição de estruturas hierárquicas e antidemocráticas de aprendizagem e, criando, ao mesmo tempo, as estruturas cooperativas.

Temporal lobe epilepsy in childhood – a study model of auditory processing

TLE in infancy has been the subject of varied research. Topographical and structural evidence is coincident with the neuronal systems responsible for auditory processing of the highest specialization and complexity. Recent studies have been showing the need of a hemispheric asymmetry for an optimization in central auditory processing (CAP) and acquisition and learning of a language system. A new functional research paradigm is required to study mental processes that require methods of cognitive-sensory information analysis processed in very short periods of time (msec), such as the ERPs. Thus, in this article, we hypothesize that the TLE in infancy could be a good model for topographic and functional study of CAP and its development process, contributing to a better understanding of the learning difficulties that children with this neurological disorder have.

Prevention of electrocardiographic and histopathologic alterations in the murine model of Chagas' disease by preinoculation of an attenuated Trypanosoma cruzi strain

The effects of infection with Trypanosoma cruzi on the electrocardiographic tracings of mice were studied in 4.groups of animals: (1) normal; (2) infected with a pathogenic T. cruzi strain (TS COB); (3) immunized with 3 intraperitoneal inocula of 10(6) attenuated T. cruzi epimastigotes (TCC) and (4) immunized-infected, which sequentially received the treatments of groups 3 and 2. Infection and protection were confirmed by xenodiagnosis and histopathology. Isolated alterations such as extrasystolia, 1st degree atrioventricular block, arrhythmia and ST elevation were observed in normal as well as infected mice. However, tracings taken repeatedly on each mouse over a 293 day period revealed a set of alterations which were more frequently seen in infected (14/22) than in normal (4/27) animals (p = 0.00048). These alterations consisted of supraventricular tachycardia, sinus bradycardia and persisting, first degree AV blocks, often associated to pacemaker changes. Inoculation of attenuated T. cruzi (group 3) did not increase these alterations (2/27 mice) but significantly prevented their development after challenge with the pathogenic strain (1/19 versus 14/22 mice, p = 0.000095). Thus, preimmunization reduced not only parasitemia but also a pathogenic consequence of T. cruzi infection. This evidence is relevant for immunoprevention studies against Chagas' disease.

A case study on the improvement of eco-efficiency ratios: application to a composite processing industry

The World Business Council for Sustainable Development (WBCSD) defines Eco-Efficiency as follows: ‘Eco- Efficiency is achieved by the delivery of competitively priced-goods and services that satisfy human needs and bring quality of life, while progressively reducing ecological impacts and resource intensity throughout the life-cycle to a level at least in line with the earth’s estimated carrying capacity’. Eco-Efficiency is under this point of view a key concept for sustainable development, bringing together economic and ecological progress. Measuring the Eco-Efficiency of a company, factory or business, is a complex process that involves the measurement and control of several and relevant parameters or indicators, globally applied to all companies in general, or specific according to the nature and specificities of the business itself. In this study, an attempt was made in order to measure and evaluate the eco-efficiency of a pultruded composite processing company. For this purpose the recommendations of WBCSD [1] and the directives of ISO 14301 standard [2] were followed and applied. The analysis was restricted to the main business branch of the company: the production and sale of standard GFRP pultrusion profiles. The main general indicators of eco-efficiency, as well as the specific indicators, were defined and determined according to ISO 14031 recommendations. With basis on indicators’ figures, the value profile, the environmental profile, and the pertinent eco-efficiency’s ratios were established and analyzed. In order to evaluate potential improvements on company eco-performance, new indicators values and ecoefficiency ratios were estimated taking into account the implementation of new proceedings and procedures, both in upstream and downstream of the production process, namely: a) Adoption of new heating system for pultrusion die in the manufacturing process, more effective and with minor heat losses; b) Implementation of new software for stock management (raw materials and final products) that minimize production failures and delivery delays to final consumer; c) Recycling approach, with partial waste reuse of scrap material derived from manufacturing, cutting and assembly processes of GFRP profiles. In particular, the last approach seems to significantly improve the eco-efficient performance of the company. Currently, by-products and wastes generated in the manufacturing process of GFRP profiles are landfilled, with supplementary added costs to this company traduced by transport of scrap, landfill taxes and required test analysis to waste materials. However, mechanical recycling of GFRP waste materials, with reduction to powdered and fibrous particulates, constitutes a recycling process that can be easily attained on heavy-duty cutting mills. The posterior reuse of obtained recyclates, either into a close-looping process, as filler replacement of resin matrix of GFRP profiles, or as reinforcement of other composite materials produced by the company, will drive to both costs reduction in raw materials and landfill process, and minimization of waste landfill. These features lead to significant improvements on the sequent assessed eco-efficiency ratios of the present case study, yielding to a more sustainable product and manufacturing process of pultruded GFRP profiles.

Activity of two different triazoles in a murine model of paracoccidioidomycosis

A new orally absorbable triazole (Schering 39304) with a long serum half-life in man (60 hours), was tried in a murine model of progressive paracoccidioidomycosis and compared with itraconazole, another triazole which has proven effective in this mycosis. Only 15% of the infected, untreated mice survived while 53 to 75% of the animals receiving itraconazole survived. Mice treated with Schering 39304 exhibited higher (86 - 100%) survival rates. Statistically, the 5 mg/kg Sch 39304 was superior to the 50 mg/kg itraconazole dose. Lung cultures showed that 20 mg/kg/day of Sch achieved sterilization of the infectious foci. These results indicate that the new triazole will have a place in the treatment of paracoccidioidomycosis

Gastric acid secretion response in the Cebus apella: a monkey model of chronic Chagas disease

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 ug/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n=10; Colombian, n=4 and Tulahuen, n=4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p<0.01 and p<0.05 respectively; "t" test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophagic tropism or the necessity of a longer post-infection time to cause lesions.

Explicit series solution for a glucose-induced electrical activity model of pancreatic beta-cells

In this work, we present the explicit series solution of a specific mathematical model from the literature, the Deng bursting model, that mimics the glucose-induced electrical activity of pancreatic beta-cells (Deng, 1993). To serve to this purpose, we use a technique developed to find analytic approximate solutions for strongly nonlinear problems. This analytical algorithm involves an auxiliary parameter which provides us with an efficient way to ensure the rapid and accurate convergence to the exact solution of the bursting model. By using the homotopy solution, we investigate the dynamical effect of a biologically meaningful bifurcation parameter rho, which increases with the glucose concentration. Our analytical results are found to be in excellent agreement with the numerical ones. This work provides an illustration of how our understanding of biophysically motivated models can be directly enhanced by the application of a newly analytic method.

Flucytosine + fluconazole association in the treatment of a murine experimental model of cryptococcosis

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated. Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/ kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control. The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate. 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p<0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p<0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters. The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.