The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state

Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

Reliability factors in business software: volatility, requirements and end-users

Many business-oriented software applications are subject to frequent changes in requirements. This paper shows that, ceteris paribus, increases in the volatility of system requirements decrease the reliability of software. Further, systems that exhibit high volatility during the development phase are likely to have lower reliability during their operational phase. In addition to the typically higher volatility of requirements, end-users who specify the requirements of business-oriented systems are usually less technically oriented than people who specify the requirements of compilers, radar tracking systems or medical equipment. Hence, the characteristics of software reliability problems for business-oriented systems are likely to differ significantly from those of more technically oriented systems.

Reasoning about real-time repetitions: terminating and nonterminating

It is common for a real-time system to contain a nonterminating process monitoring an input and controlling an output. Hence, a real-time program development method needs to support nonterminating repetitions. In this paper we develop a general proof rule for reasoning about possibly nonterminating repetitions. The rule makes use of a Floyd-Hoare-style loop invariant that is maintained by each iteration of the repetition, a Jones-style relation between the pre- and post-states on each iteration, and a deadline specifying an upper bound on the starting time of each iteration. The general rule is proved correct with respect to a predicative semantics. In the case of a terminating repetition the rule reduces to the standard rule extended to handle real time. Other special cases include repetitions whose bodies are guaranteed to terminate, nonterminating repetitions with the constant true as a guard, and repetitions whose termination is guaranteed by the inclusion of a fixed deadline. (C) 2002 Elsevier Science B.V. All rights reserved.

Infusing the use of seasonal climate forecasting into crop management practice in North East Australia using discussion support software

Seasonal climate forecasting offers potential for improving management of crop production risks in the cropping systems of NE Australia. But how is this capability best connected to management practice? Over the past decade, we have pursued participative systems approaches involving simulation-aided discussion with advisers and decision-makers. This has led to the development of discussion support software as a key vehicle for facilitating infusion of forecasting capability into practice. In this paper, we set out the basis of our approach, its implementation and preliminary evaluation. We outline the development of the discussion support software Whopper Cropper, which was designed for, and in close consultation with, public and private advisers. Whopper Cropper consists of a database of simulation output and a graphical user interface to generate analyses of risks associated with crop management options. The charts produced provide conversation pieces for advisers to use with their farmer clients in relation to the significant decisions they face. An example application, detail of the software development process and an initial survey of user needs are presented. We suggest that discussion support software is about moving beyond traditional notions of supply-driven decision support systems. Discussion support software is largely demand-driven and can compliment participatory action research programs by providing cost-effective general delivery of simulation-aided discussions about relevant management actions. The critical role of farm management advisers and dialogue among key players is highlighted. We argue that the discussion support concept, as exemplified by the software tool Whopper Cropper and the group processes surrounding it, provides an effective means to infuse innovations, like seasonal climate forecasting, into farming practice. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Secondary structure of the third extracellular loop responsible for ligand selectivity of a mammalian gonadotropin-releasing hormone receptor

The extracellular loop 3 (ECL3) of the mammalian gonadotropin-releasing hormone receptor (GnRH-R) contains an acidic amino acid (Glu(301) in the mouse GnRH-R,) that confers agonist selectivity for Are in mammalian GnRH. It is proposed that a specific conformation of ECL3 is necessary to orientate the carboxyl side chain of the acidic residue for interaction with Arg(8) of GnRH, which is supported by decreased affinity for Arg(8) GnRH but not Gln(8) GnRH when an adjacent Pro is mutated to Ala. To probe the structural contribution of the loop domain to the proposed presentation of the carboxyl side chain, we synthesized a model peptide (CGPEMLNRVSEPGC) representing residues 293-302 of mouse ECL3, where Cys and Gly residues are added symmetrically at the N and C termini, respectively, allowing the introduction of a disulfide bridge to simulate the distances at which the ECL3 is tethered to the transmembrane domains 6 and 7 of the receptor. The ability of the ECL3 peptide to bind GnRH with low affinity was demonstrated by its inhibition of GnRH stimulation of inositol phosphate production in cells expressing the GnRH-R. The CD bands of the ECL3 peptides exhibited a superposition of predominantly unordered structure and partial contributions from beta-sheet structure. Likewise, the analysis of the amide I and amide III bands from micro-Raman and FT Raman experiments revealed mainly unordered conformations of the cyclic and of the linear peptide. NMR data demonstrated the presence of a beta-hairpin among an ensemble of largely disordered structures in the cyclic peptide. The location of the turn linking the two strands of the hairpin was assigned to the three central residues L-296, N-297, and R-298. A small population of structured species among an ensemble of predominantly random coil conformation suggests that the unliganded receptor represents a variety of structural conformers, some of which have the potential to make contacts with the ligand. We propose a mechanism of receptor activation whereby binding of the agonist to the inactive receptor state induces and stabilizes a particular structural state of the loop domain, leading to further conformational rearrangements across the transmembrane domain and signal propagating interaction with G proteins. Interaction of the Glu(301) of the receptor with Arg(8) of GnRH induces a folded configuration of the ligand. Our proposal thus suggests that conformational changes of both ligand and receptor result from this interaction.

Nerve growth factor overexpression and autocrine loop in breast cancer cells

We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.

Digitally-implemented naturally sampled PWM suitable for multilevel converter control

For dynamic closed loop control of a multilevel converter with a low pulse number (ratio of switching frequency to synthesized fundamental), natural sampled pulse-width modulation (PWM) is the best form of modulation. Natural sampling does not introduce distortion or a delayed response to the modulating signal. However previous natural sampled PWM implementations have generally been analog. For a modular multilevel converter, a digital implementation has advantages of accuracy and flexibility. Re-sampled uniform PWM is a novel digital modulation technique which approaches the performance of natural PWM. Both hardware and software implementations for a five level multilevel converter phase are presented, demonstrating the improvement over uniform PWM.

Portal do software p??blico brasileiro

O Portal do Software P??blico Brasileiro consolida-se como uma iniciativa que conseguiu criar um ambiente comum para compartilhar solu????es de software no setor p??blico, racionalizar a gest??o dos recursos de inform??tica, reaproveitar as solu????es de software existentes para diminuir custos e atividades redundantes, estabelecer parcerias e a????es cooperadas, refor??ar a pol??tica p??blica de estimular o uso de software livre e definir uma forma de licenciamento de software que sustente o compartilhamento de solu????es entre os ??rg??os do setor p??blico de acordo com as prerrogativas legais brasileiras e a Constitui????o Federal. Esta iniciativa trouxe como inova????o o compartilhamento de ???software p??blico???, que oficializou um novo modelo de licenciamento e de gest??o das solu????es desenvolvidas na administra????o p??blica, estabelecendo parceria entre diversos ??rg??os, institui????es, empresas e cidad??os, e hoje conta com mais de 100 mil participantes

Uso do software Estradas para determinação do espaçamento entre desaguadouros em estradas não pavimentadas do interior de Goiás

Estradas não pavimentadas correspondem a aproximadamente 90% da malha rodoviária brasileira. Estas, na maioria das vezes, são construídas sem a realização de estudos prévios, estando sujeitas a vários tipos de problemas. Um dos principais fatores de deterioração dessas vias é a ineficiência do sistema de drenagem. Neste trabalho simulou-se o espaçamento entre desaguadouros em estradas não pavimentadas, utilizando-se um software desenvolvido com base num modelo matemático de dimensionamento de sistemas de drenagem em estradas não pavimentadas. Utilizaram-se valores de erodibilidade, tensão crítica de cisalhamento e massa específica para diferentes solos de estradas, localizadas no Estado de Goiás. Simularam-se cenários considerando alterações na declividade (1, 5, 10 e 15%) e na seção transversal do canal com relações entre altura e largura de 1:1, 1:2, 1:5 e 1:10. O modelo respondeu sensivelmente às alterações na declividade, na seção transversal do canal e nas de resistência do solo. Os espaçamentos obtidos indicaram que, estradas com declividades inferiores a 5%, mesmo com elevados valores de erodibilidade permitiram espaçamentos viáveis em aspectos construtivos. No entanto, para as declividades de 10 e 15%, os espaçamentos, na maioria dos casos, apresentaram dimensões reduzidas, tornando-se impraticáveis, sendo necessário, nestes casos, proteção do canal ou alteração de suas características hidráulicas.

GUIsurfer: A Reverse Engineering Framework for User Interface Software

GUIsurfer: A Reverse Engineering Framework for User Interface Software

The role of coordination analysis in software integration projects

What sort of component coordination strategies emerge in a software integration process? How can such strategies be discovered and further analysed? How close are they to the coordination component of the envisaged architectural model which was supposed to guide the integration process? This paper introduces a framework in which such questions can be discussed and illustrates its use by describing part of a real case-study. The approach is based on a methodology which enables semi-automatic discovery of coordination patterns from source code, combining generalized slicing techniques and graph manipulation

Criminal Liability of Organizations, Corporations, Legal Persons, and Similar Entities on Law of Portuguese Cybercrime: A Brief Discussion on the Issue of Crimes of “False Information,” the “Damage on Other Programs or Computer Data,” the “Computer-Software Sabotage,” the “Illegitimate Access,” the “Unlawful Interception,” and “Illegitimate Reproduction of the Protected Program”

Abstract: in Portugal, and in much of the legal systems of Europe, «legal persons» are likely to be criminally responsibilities also for cybercrimes. Like for example the following crimes: «false information»; «damage on other programs or computer data»; «computer-software sabotage»; «illegitimate access»; «unlawful interception» and «illegitimate reproduction of protected program». However, in Portugal, have many exceptions. Exceptions to the «question of criminal liability» of «legal persons». Some «legal persons» can not be blamed for cybercrime. The legislature did not leave! These «legal persons» are v.g. the following («public entities»): legal persons under public law, which include the public business entities; entities utilities, regardless of ownership; or other legal persons exercising public powers. In other words, and again as an example, a Portuguese public university or a private concessionaire of a public service in Portugal, can not commit (in Portugal) any one of cybercrime pointed. Fair? Unfair. All laws should provide that all legal persons can commit cybercrimes. PS: resumo do artigo em inglês.

Dinâmica da acumulação de capacidades inovadoras: evidências de empresas de software no Rio de janeiro e em São Paulo

São escassos estudos sobre a dinâmica da acumulação de capacidades inovadoras. Este artigo examina o tema em oito empresas de software em São Paulo e Rio de Janeiro, encontrando: diferenças inter e intraempresariais em termos da direção e taxa de acumulação de capacidade para funções tecnológicas específicas; acúmulo de capacidade tecnológica mais rápido em empresas mais jovens; e decréscimo das taxas de acumulação tecnológica à medida que as empresas se aproximam de níveis mais inovadores de capacidades, demonstrando a potencialidade para aceleração do processo. Tais evidências são relevantes para o entendimento da acumulação tecnológica e fornecem uma noção do tempo necessário para se obterem benefícios de esforços de aprendizagem e construção de capacidade inovadora.

Atratividade de projetos de software livre: importância teórica e estratégias para administração

Milhares de Projetos de Software Livre (PSL) foram e continuam sendo criados na Internet. Esse cenário aumenta as oportunidades de colaboração tanto quanto acirra a concorrência por usuários e contribuidores, que elevariam esses projetos a níveis superiores aos que seriam alcançados por seus fundadores sozinhos. E dado que o aprimoramento por meio de colaboração é o principal objetivo dos fundadores de PSL, a importância de entender e administrar a capacidade de atrair usuários e contribuidores fica estabelecida. Para auxiliar pesquisadores e fundadores nesse desafio, o conceito de atratividade é introduzido neste artigo, que desenvolve um ferramental teórico-gerencial sobre as causas, indicadores e consequências da atratividade, viabilizando sua administração estratégica.

Knowledge cities: a taxonomy for analyzing software and information service clusters

Software and information services (SIS) have become a field of increasing opportunities for international trade due to the worldwide diffusion of a combination of technological and organizational innovations. In several regions, the software industry is organized in clusters, usually referred to as "knowledge cities" because of the growing importance of knowledge-intensive services in their economy. This paper has two primary objectives. First, it raises three major questions related to the attractiveness of different cities in Argentina and Brazil for hosting software companies and to their impact on local development. Second, a new taxonomy is proposed for grouping clusters according to their dominant business segment, ownership pattern and scope of operations. The purpose of this taxonomy is to encourage further studies and provide an exploratory analytical tool for analyzing software clusters.