Role of Halogen Bonds in Thyroid Hormone Receptor Selectivity: Pharmacophore-Based 3D-QSSR Studies

Most physiological effects of thyroid hormones are mediated by the two thyroid hormone receptor subtypes, TR alpha and TR beta. Several pharmacological effects mediated by TR beta might be beneficial in important medical conditions such as obesity, hypercholesterolemia and diabetes, and selective TR beta activation may elicit these effects while maintaining an acceptable safety profile, To understand the molecular determinants of affinity and subtype selectivity of TR ligands, we have successfully employed a ligand- and structure-guided pharmacophore-based approach to obtain the molecular alignment of a large series of thyromimetics. Statistically reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models were obtained using the comparative molecular field analysis (CoMFA) method, and the visual analyses of the contour maps drew attention to a number of possible opportunities for the development of analogs with improved affinity and selectivity. Furthermore, the 3D-QSSR analysis allowed the identification of a novel and previously unmentioned halogen bond, bringing new insights to the mechanism of activity and selectivity of thyromimetics.

Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT(1A) receptor ligands

5-HT(1A) receptor antagonists have been employed to treat depression, but the lack of structural information on this receptor hampers the design of specific and selective ligands. In this study, we have performed CoMFA studies on a training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to produce an effective alignment of the data set, a pharmacophore model was produced using Galahad. A statistically significant model was obtained, indicating a good internal consistency and predictive ability for untested compounds. The information gathered from our receptor-independent pharmacophore hypothesis is in good agreement with results from independent studies using different approaches. Therefore, this work provides important insights on the chemical and structural basis involved in the molecular recognition of these compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

A web based decision support system for status assessment in advanced parkinson

The purpose of this work is to develop a web based decision support system, based onfuzzy logic, to assess the motor state of Parkinson patients on their performance in onscreenmotor tests in a test battery on a hand computer. A set of well defined rules, basedon an expert’s knowledge, were made to diagnose the current state of the patient. At theend of a period, an overall score is calculated which represents the overall state of thepatient during the period. Acceptability of the rules is based on the absolute differencebetween patient’s own assessment of his condition and the diagnosed state. Anyinconsistency can be tracked by highlighted as an alert in the system. Graphicalpresentation of data aims at enhanced analysis of patient’s state and performancemonitoring by the clinic staff. In general, the system is beneficial for the clinic staff,patients, project managers and researchers.

Integration av webbaserat analysprogram och kartprogram : Integration of web based analysis-software andmap-software

I takt med att GIS (Grafiska InformationsSystem) blir allt vanligare och mer användarvänligt har WM-data sett att kunder skulle ha intresse i att kunna koppla information från sin verksamhet till en kartbild. Detta för att lättare kunna ta till sig informationen om hur den geografiskt finns utspridd över ett område för att t.ex. ordna effektivare tranporter. WM-data, som det här arbetet är utfört åt, avser att ta fram en prototyp som sedan kan visas upp för att påvisa för kunder och andra intressenter att detta är möjligt att genomföra genom att skapa en integration mellan redan befintliga system. I det här arbetet har prototypen tagits fram med skogsindustrin och dess lager som inriktning. Befintliga program som integrationen ska skapas mellan är båda webbaserade och körs i en webbläsare. Analysprogrammet som ska användas heter Insikt och är utvecklat av företaget Trimma, kartprogrammet heter GIMS som är WM-datas egna program. Det ska vara möjligt att i Insikt analysera data och skapa en rapport. Den ska sedan skickas till GIMS där informationen skrivs ut på kartan på den plats som respektive information hör till. Det ska även gå att välja ut ett eller flera områden i kartan och skicka till Insikt för att analysera information från enbart de utvalda områdena. En prototyp med önskad funktionalitet har under arbetets gång tagits fram, men för att ha en säljbar produkt är en del arbeta kvar. Prototypen har visats för ett antal intresserade som tyckte det var intressant och tror att det är något som skulle kunna användas flitigt inom många områden.

A web-based system for visualizing upper limb motor performance of Parkinson’s disease patients

Objective To design, develop and set up a web-based system for enabling graphical visualization of upper limb motor performance (ULMP) of Parkinson’s disease (PD) patients to clinicians. Background Sixty-five patients diagnosed with advanced PD have used a test battery, implemented in a touch-screen handheld computer, in their home environment settings over the course of a 3-year clinical study. The test items consisted of objective measures of ULMP through a set of upper limb motor tests (finger to tapping and spiral drawings). For the tapping tests, patients were asked to perform alternate tapping of two buttons as fast and accurate as possible, first using the right hand and then the left hand. The test duration was 20 seconds. For the spiral drawing test, patients traced a pre-drawn Archimedes spiral using the dominant hand, and the test was repeated 3 times per test occasion. In total, the study database consisted of symptom assessments during 10079 test occasions. Methods Visualization of ULMP The web-based system is used by two neurologists for assessing the performance of PD patients during motor tests collected over the course of the said study. The system employs animations, scatter plots and time series graphs to visualize the ULMP of patients to the neurologists. The performance during spiral tests is depicted by animating the three spiral drawings, allowing the neurologists to observe real-time accelerations or hesitations and sharp changes during the actual drawing process. The tapping performance is visualized by displaying different types of graphs. Information presented included distribution of taps over the two buttons, horizontal tap distance vs. time, vertical tap distance vs. time, and tapping reaction time over the test length. Assessments Different scales are utilized by the neurologists to assess the observed impairments. For the spiral drawing performance, the neurologists rated firstly the ‘impairment’ using a 0 (no impairment) – 10 (extremely severe) scale, secondly three kinematic properties: ‘drawing speed’, ‘irregularity’ and ‘hesitation’ using a 0 (normal) – 4 (extremely severe) scale, and thirdly the probable ‘cause’ for the said impairment using 3 choices including Tremor, Bradykinesia/Rigidity and Dyskinesia. For the tapping performance, a 0 (normal) – 4 (extremely severe) scale is used for first rating four tapping properties: ‘tapping speed’, ‘accuracy’, ‘fatigue’, ‘arrhythmia’, and then the ‘global tapping severity’ (GTS). To achieve a common basis for assessment, initially one neurologist (DN) performed preliminary ratings by browsing through the database to collect and rate at least 20 samples of each GTS level and at least 33 samples of each ‘cause’ category. These preliminary ratings were then observed by the two neurologists (DN and PG) to be used as templates for rating of tests afterwards. In another track, the system randomly selected one test occasion per patient and visualized its items, that is tapping and spiral drawings, to the two neurologists. Statistical methods Inter-rater agreements were assessed using weighted Kappa coefficient. The internal consistency of properties of tapping and spiral drawing tests were assessed using Cronbach’s α test. One-way ANOVA test followed by Tukey multiple comparisons test was used to test if mean scores of properties of tapping and spiral drawing tests were different among GTS and ‘cause’ categories, respectively. Results When rating tapping graphs, inter-rater agreements (Kappa) were as follows: GTS (0.61), ‘tapping speed’ (0.89), ‘accuracy’ (0.66), ‘fatigue’ (0.57) and ‘arrhythmia’ (0.33). The poor inter-rater agreement when assessing “arrhythmia” may be as a result of observation of different things in the graphs, among the two raters. When rating animated spirals, both raters had very good agreement when assessing severity of spiral drawings, that is, ‘impairment’ (0.85) and irregularity (0.72). However, there were poor agreements between the two raters when assessing ‘cause’ (0.38) and time-information properties like ‘drawing speed’ (0.25) and ‘hesitation’ (0.21). Tapping properties, that is ‘tapping speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’ had satisfactory internal consistency with a Cronbach’s α coefficient of 0.77. In general, the trends of mean scores of tapping properties worsened with increasing levels of GTS. The mean scores of the four properties were significantly different to each other, only at different levels. In contrast from tapping properties, kinematic properties of spirals, that is ‘drawing speed’, ‘irregularity’ and ‘hesitation’ had a questionable consistency among them with a coefficient of 0.66. Bradykinetic spirals were associated with more impaired speed (mean = 83.7 % worse, P < 0.001) and hesitation (mean = 77.8% worse, P < 0.001), compared to dyskinetic spirals. Both these ‘cause’ categories had similar mean scores of ‘impairment’ and ‘irregularity’. Conclusions In contrast from current approaches used in clinical setting for the assessment of PD symptoms, this system enables clinicians to animate easily and realistically the ULMP of patients who at the same time are at their homes. Dynamic access of visualized motor tests may also be useful when observing and evaluating therapy-related complications such as under- and over-medications. In future, we foresee to utilize these manual ratings for developing and validating computer methods for automating the process of assessing ULMP of PD patients.

From Smart Meters To Smart Decisions: Web-Based Support For The Water Efficient Household

Smart water metering technologies for residential buildings offer, in principle, great opportunities for sustainable urban water management. However, much of this potential is as yet unrealized. Despite that several ICT solutions have already been deployed aiming at optimum operations on the water utilities side (e.g. real time control for water networks, dynamic pump scheduling etc.), little work has been done to date on the consumer side. This paper presents a web-based platform targeting primarily the household end user. The platform enables consumers to monitor, on a real-time basis, the water demand of their household, providing feedback not only on the total water consumption and relevant costs but also on the efficiency (or otherwise) of specific indoor and outdoor uses. Targeting the reduction of consumption, the provided feedback is combined with notifications about possible leakages\bursts, and customised suggestions to improve the efficiency of existing household uses. It also enables various comparisons, with past consumption or even with that of similar households, aiming to motivate further the householder to become an active player in the water efficiency challenge. The issue of enhancing the platform’s functionality with energy timeseries is also discussed in view of recent advances in smart metering and the concept of “smart cities”. The paper presents a prototype of this web-based application and critically discusses first testing results and insights. It also presents the way in which the platform communicates with central databases, at the water utility level. It is suggested that such developments are closing the gap between technology availability and usefulness to end users and could help both the uptake of smart metering and awareness raising leading, potentially, to significant reductions of urban water consumption. The work has received funding from the European Union FP7 Programme through the iWIDGET Project, under grant agreement no318272.

Entry strategies on an emerging market: Brazil: case studies of French cosmetics companies in Brazil

Este trabalho envolve as estrategias de entrada sobre um mercado emergente, o mercado brasileiro. Os estudos de casos que apoiam o assunto são de empresas francesas do setor de cosméticos. Uma revisão da literatura sobre o assunto sera comparada com os resultados dos estudos de caso. Isso para conduzir numa observação do estado atual das caractéristicos de instalação no mercado brasileiro deste setor para empresas estrangeiras de tamanho médio. O estudo da literatura que já existe sobre o assunto se concentra sobre varias problemáticas conectadas com a problemática geral: as razões para internacionalizar, o modo de entrada, os obstáculos encontrados, as estrategias especificais e as adaptações do marketing mix. Depois este trabalho se concentra sobre tres empresas francesas representativas das problematicas atuais do setor : Norlessi, LaboBio e Plains Cosmetics. Os estudos de caso são sustentados por entrevistas e coleção de dados de varios origens, descrevedo mas precisamente na parte de methodologia. Depois será feito uma cross-analysis tentando comparar as conclusões do estudo empirico e do estudo literário. As conclusões finais tem como objetivo de ser uma observação objetiva do raciocinio das empresas consideradas sobre as problemáticas escolhidas.

Leadership of portuguese community schools in the East Coast of the United States and the public policies of education: a multiple case studies

The Portuguese community schools of the United States located in the areas of larger Portuguese population concentration are social organizations that come materializing throughout decades the designs of the educative policies of the Portuguese government in relation to the expansion and preservation of the language, the culture and the history of Portugal. These designs of the educative policies are enrolled in the Constitution of the Republic (1976), in the Basic Law of Educative System (1986) and, over all, in the successive legislative norms (Decree-laws and ordinances) of the successive governments. Portuguese community schools in the United States are structuralized in analogous way to schools of the Portuguese geographic space. For this qualitative study (multiple case), four directors of Portuguese schools of the East Coast of the United States were interviewed; two schools are in the state of Rhode Island and the other two are in the state of Massachusetts. Also, it was administered the questionnaire on practices of leadership “Leadership Practices Inventory” (LPI) of Kouzes and Posner (2002) to collect additional data about practices of leadership on the directors of the schools. The LPI evaluates practices of leadership classifying them in five domains: (a) Model the way; (b) Inspire a shared vision; (c) Challenge the process; (d) Enable others to act; and, (e) Encourage the heart. Results of this qualitative research indicate that the Portuguese Government has not had an educative policy stimulant, coherent and consistent of support, incentive, maintenance and diffusion of the Portuguese language and culture and the directors of the studied schools they have a proactive and serving leadership style in conducting the management of Portuguese community schools. The five practices of leadership are highly practiced by the directors of the studied schools above all the practices “Enable others to act” and “Encourage the heart”.

Relationship between green management and environmental training in companies located in Brazil: A theoretical framework and case studies

The main objective of this study is to understand the relationship between green management and environmental training in Brazilian companies, underscoring how this relationship takes place and its most important factors. For such, 9 case studies were conducted at large ISO 14001 certified companies, leaders in their market segments. Several interviews were conducted for each case, documents were collected and visits were made for direct observation. The main contributions and results of this study were: (a) a proposal for a theoretical framework relating the evolutionary stages of green management and the characteristics of environmental training; (b) it was ascertained, as per the proposed theoretical framework, that organizational culture and teamwork, top management support and more technical green management practices are the factors that seem to connect and convert environmental training into more proactive green management, especially for companies in the proactive green management stage; (c) the identification of the co-evolution between the companies' stage of green management and their environmental training level, which is the identified relationship mechanism between environmental training and green management. In other words, the higher the level of adoption of activities recommended for green management, the more evolved the green management practiced at the companies tends to be; and (d) identification that the proposed theoretical framework tends to be useful, mainly because it can explain the relationship between green management and environmental training at the company in the proactive stage. (C) 2012 Elsevier B.V. All rights reserved.

Cogeneration for small users: case studies for Brazilian tertiary sector

In this paper we present technical and economic studies of cogeneration systems utilizing combustion engines and gas turbines, applied in two establishments of the tertiary sector, regarding Brazilian conditions (according to Silveria, 1994). In the first step cogeneration systems utilizing combustion engines associated to absorption refrigeration systems are studied, in which electricity and cold air for a university building rate produced. In the second step some possibilities of the use of the gas turbine in cogeneration systems for a hospital are shown. In this case, the exhaust gases are utilized for the production of steam in a heat recovery steam generator (HRSG) or cold water in an absorption refrigeration system (for air conditioning) for the hospital building. The dynamic increment of the energy demand of Brazilian tertiary sector in last years can increase the installation of these cogeneration system (in compact version) as well as strengthen the development of the decentralized energy generation in Brazil.

SMEs in the environmental goods and services market: identifying areas of opportunity, policies and instruments: case studies: Argentina, Chile, Colombia and Mexico

Includes bibliography

Software architecture for web-based project management system

This article presents software architecture for a web-based system to aid project managing, conceptually founded on guidelines of the Project Management Body of Knowledge (PMBoK) and on ISO/IEC 9126, as well as on the result of an empiric study done in Brazil. Based on these guidelines, this study focused on two different points of view about project management: the view of those who develop software systems to aid management and the view of those who use these systems. The designed software architecture is capable of guiding an incremental development of a quality system that will satisfy today's marketing necessities, principally those of small and medium size enterprises.

Consumer confidence and economic growth: case studies of Jamaica and Trinidad and Tobago

Includes bibliography

Restructuring in manufacturing: case studies in Chile, Mexico and Venezuela

Includes bibliography

Regulación y supervisión de la banca e instituciones financieras: estudios de caso de América Latina y el Caribe: conclusiones y recomendaciones, Santiago 3-5 diciembre 1990 y 22-23 agosto 1991 = Regulation and supervision of banks and financial institutions: case studies in Latin America and the Caribbean: conclusions and recommendations, Santiago, 3-5 December 1990 and 22-23 August 1991

Documentos presentados a dos seminarios realizados en la Sede de CEPAL en Santiago entre el 3 y 5 de diciembre de 1990 y el 22 y 23 de agosto de 1991