Natural and amyloid self-assembly of S100 proteins: structural basis of functional diversity

The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca2+ binding through EF-hand motifs and binding of Zn2+ and Cu2+ at additional sites, usually at the homodimer interfaces. Ca2+ binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.

Strategic Drivers for Implementing Sustainability Programs in Portuguese Organizations– Let’s Listen to Aristotle: From Triple to Quadruple Bottom Line

This article describes a study that investigated the main strategic drivers that influence the implementation of sustainability/social responsibility programs. An online survey was administered to managers of Portuguese organizations with certified management systems. The findings suggest that the implementation of such programs is mainly correlated to: 1.) the approach to understanding and working toward the satisfaction of the community’s needs (in the broad sense of social responsibility); 2.) how systematically sustainability within the organization is identified and managed (e.g., pollution prevention, improved environmental performance, and compliance with the applicable environmental laws); and 3.) the degree to which the organization tries to understand the needs of the employees and works toward satisfying them. In addition to the survey, five interviews with top managers of the surveyed organizations provided some useful insights. There was no consensus on the meaning of sustainability and social responsibility: some described it as an instrumental approach for obtaining better organizational results, while others regarded it as the right thing to do (i.e., it is values driven). In all cases, however, the managers supported a kind of umbrella construct under which different size corporations use different models (for example, the Dow Jones Sustainability Index (DJSI), Global Reporting Initiative (GRI), ISO 14001 environmental management systems), although some managers reported that they simply do not know what to do. All of those surveyed agreed that the lack of a systematic approach could represent a major threat to their organization, making them willing to pay more attention and take more action on the issue of sustainability. An additional suggestion made by managers was to change from a triple bottom line (economic dimension, environmental dimension, social equity dimension) to a quadruple bottom line by adding another dimension: personal and family happiness. This fourth dimension was recognized by the Greek philosopher/thinker Aristotle (384-322 BCE) who thought of happiness as the highest good (virtue) and ultimate goal and purpose of life, achieved through living well, in harmony. Such harmony suggests a balance and a lack of excess—in other words a sustainable existence.

McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication

Several studies have recently shown the use of recombinant rabies virus as potential vector-viral vaccine for HIV-1. The sequence homology between gp 120 and rabies virus glycoprotein has been reported. The McCoy cell line has therefore been used to show CD4+ or CD4+ like receptors. Samples of HIV-1 were isolated, when plasma of HIV-1 positive patients was inoculated in the McCoy cell line. The virus infection was then studied during successive virus passages. The proteins released in the extra cellular medium were checked for protein activity, by exposure to SDS Electrophoresis and blotting to nitro-cellulose filter, then reacting with sera of HIV positive and negative patients. Successive passages were performed, and showed viral replication, membrane permeabilization, the syncytium formation, and the cellular lysis (cytopathic effect). Flow cytometry analysis shows clear evidence that CD4+ receptors are present in this cell line, which enhances the likelihood of easy isolation and replication of HIV. The results observed allow the use of this cell line as a possible model for isolating HIV, as well as for carrying out studies of the dynamics of viral infection in several situations, including exposure to drugs in pharmacological studies, and possibly studies and analyses of the immune response in vaccine therapies.

A learning environment for robotic production line simulation

This paper presents a framework for a robotic production line simulation learning environment using Autonomous Ground Vehicles (AGV). An eLearning platform is used as interface with the simulator. The objective is to introduce students to the production robotics area using a familiar tool, an eLearning platform, and a framework that simulates a production line using AGVs. This framework allows students to learn about robotics but also about several areas of industrial management engineering without requiring an extensive prior knowledge on the robotics area. The robotic production line simulation learning environment simulates a production environment using AGVs to transport materials to and from the production line. The simulator allows students to validate the AGV dynamics and provides information about the whole materials supplying system which includes: supply times, route optimization and inventory management. The students are required to address several topics such as: sensors, actuators, controllers and an high level management and optimization software. This simulator was developed with a known open source tool from robotics community: Player/Stage. This tool was extended with several add-ons so that students can be able to interact with a complex simulation environment. These add-ons include an abstraction communication layer that performs events provided by the database server which is programmed by the students. An eLearning platform is used as interface between the students and the simulator. The students can visualize the effects of their instructions/programming in the simulator that they can access via the eLearning platform. The proposed framework aims to allow students from different backgrounds to fully experience robotics in practice by suppressing the huge gap between theory and practice that exists in robotics. Using an eLearning platform eliminates installation problems that can occur from different computers software distribution and makes the simulator accessible by all students at school and at home.

Redução dos Temmpos de Paragem não Programada numa Linha de Maquinação

A Dissertação que se pretende desenvolver decorre em ambiente industrial numa empresa, em que as principais áreas de actuação dizem respeito à injecção e maquinação de alumínio. Os componentes aí injectados e maquinados, são componentes que servirão posteriormente a indústria automóvel num vasto leque de aplicações, desde componentes para sistemas hidráulicos de travagem e componentes para sistemas de lubrificação. Nesta dissertação foi abordada a temática da redução do tempo de paragem não planeada numa linha de maquinação, pelo que se elencaram as principais causas que originavam essas paragens. Recorrendo à metodologia SMED, e a um vasto conjunto de técnicas auxiliares de determinação de causas como os 5 WHY´s, diagrama de Ishikawa, 5S e Kaizen, foram propostas diversas melhorias para a optimização do procedimento de troca de modelo, incluindo um conjunto de regras que visam a sustentabilidade do processo a médio e longo prazo. Com as melhorias adoptadas, verificou-se uma redução de 27,9% no tempo total de troca de modelo comparativamente com o tempo registado antes da implementação da metodologia SMED. Destaca-se a redução de 75% no tempo de montagem e desmontagem dos dispositivos no 3ºProcesso da linha em estudo. Revelou-se também crucial que para a implementação da técnica SMED ser bem sucedida em termos de eficiência e sustentabilidade, devem ser adoptadas um conjunto de diversas ferramentas “Lean Management” e de normalização do trabalho.

Utilização de Cabos de alta Temperatura em linhas Aéreas em Média Tensão

A presente dissertação teve como objetivo fazer uma análise da viabilidade técnica da utilização dos condutores de alta temperatura nas linhas aéreas de MT, identificar vantagens, analisar inconvenientes, e estabelecer um comparativo a custos médios com as soluções convencionais. Foi efetuado o estudo de um caso real da EDP Distribuição que consistia na necessidade do aumento da capacidade de transporte de energia da linha aérea a 15 kV Espinho-Sanguedo. Neste foi ponderada a solução onde se poderia efetuar passagem de linha simples para linha dupla em alumínio-aço (AA) 160 mm2 ou a solução alternativa e inovadora de substituição dos condutores existentes por condutores de alta temperatura ACCC 182 mm2. Para isso foram efetuados cálculos e também criada uma ferramenta de apoio à decisão, para validação dos mesmos, com o intuito de mais tarde poder ser aplicada nas linhas aéreas em Média Tensão em todo o país e, sempre que necessário, se possa fazer um estudo de ponderação técnica de forma sistemática e estruturada. Neste trabalho estão identificadas as vantagens, foram relatados os inconvenientes, e estabeleceu-se um comparativo a custos médios da utilização de condutores de alta temperatura com as soluções convencionais. Antes de poder ser realizado um estudo do caso concreto da Linha aérea Espinho-Sanguedo foi necessário um aprofundamento do estado da arte no que diz respeito à comparação entre o cabo de alta temperatura ACCC e o cabo convencional ACSR, sendo este o mais utilizado nas linhas aéreas em MT. Os cabos de alta temperatura trouxeram inovações neste tema de transporte de energia, e como tal surgiu a necessidade de um estudo mais aprofundado da sua constituição, destacando o seu núcleo formado pelo compósito de fibra de carbono e fibra de vidro. Foi também analisado vantagens e desvantagens do cabo de alta temperatura e até mesmo situações onde a sua aplicação poderá ser vantajosa, de modo a tirar proveito das suas caraterísticas em que se destacam altas temperaturas de funcionamento e flechas reduzidas. Para elaborar um projeto de uma linha aérea em média tensão é necessário considerar a legislação em vigor, os aspetos ambientais e económicos, respeitando e garantindo as premissas do cálculo elétrico e mecânico. Economicamente este tipo de cabo (ACCC) é mais dispendioso do que os convencionais, no entanto o estudo realizado permitiu perceber que a sua implementação técnica é vantajosa em linhas aéreas de elevada capacidade de transporte de energia, sobretudo nos casos onde serão necessárias instalar linhas duplas ou linhas simples de seções elevadas. Devido às suas caraterísticas mecânicas, estes cabos permitem melhorar as linhas na sua dimensão, podendo diminuir o número de apoios a instalar, podendo diminuir a robustez dos apoios e permitir maior facilidade na montagem. Estas vantagens traduzem-se em menores impactos ambientais e permitem sobretudo reduzir os constrangimentos com os proprietários dos terrenos onde os apoios são implantados.

Evaluating vehicle painting plans in an automobile assembly plant using an integrated AHP-PROMETHEE approach

The painting activity is one of the most complex and important activities in automobile manufacturing. The inherent complexity of the painting activity and the frequent need for repainting usually turn the painting process into a bottleneck in automobile assembly plants, which is reflected in higher operating costs and longer overall cycle times. One possible approach for optimizing the performance of the paint shop is to improve the efficiency of the color planning. This can be accomplished by evaluating the relative merits of a set of vehicle painting plans. Since this problem has a multicriteria nature, we resort to the multicriteria decision analysis (MCDA) methodology to tackle it. A recent trend in the MCDA field is the development of hybrid approaches that are used to achieve operational synergies between different methods. Here we apply, for the first time, an integrated approach that combines the strengths of the analytic hierarchy process (AHP) and the Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE), aided by Geometrical Analysis for Interactive Aid (GAIA), to the problem of assessing alternative vehicle painting plans. The management of the assembly plant found the results of value and is currently using them in order to schedule the painting activities such that an enhancement of the operational efficiency of the paint shop is obtained. This efficiency gain has allowed the management to bid for a new automobile model to be assembled at this specific plant.

Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line

Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 μg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on 1O2 mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 μg/mL. This effect was found to be related to a direct antioxidant effect (involving 1O2) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 μg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin.

Vale a pena reflectir quando se aprende on-line? Auto-regulação em e-English

Trabalho de Projecto apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Gestão de Sistemas de e-Learning

Modeling assembly program with constraints. A contribution to WCET problem

Dissertação para obtenção do Grau de Mestre em Lógica Computacional

Spatiotemporal mechanisms for actomyosin ring assembly and contraction in budding yeast cell division

Dissertation presented to obtain the Ph.D degree in Molecular Medicine

On-line system for faults detection in induction motors based on PCA

Dissertation to obtain the degree of Master in Electrical and Computer Engineering

Derivation and consistency checking of models in early software product line engineering

Dissertação para obtenção do Grau de Doutor em Engenharia Informática