In silico screening of HIV-1 non-nucleoside reverse transcriptase and protease inhibitors

Two targets, reverse transcriptase (RT) and protease from HIV-1, were used during the past two decades to the discovery of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) that belong to the arsenal of the antiretroviral therapy. Herein these enzymes were chosen as templates for conducting a computer-aided ligand design. Ligand and structure-based drug designs were the starting points to select compounds from a database bearing more than five million compounds by means of cheminformatic tools. New promising lead structures are retrieved from the database, which are open to acquisition and test. Classes of molecules already described as NNRTI or PI in the literature also came out and were useful to prove the reliability of the workflow, and thus validating the work carried out so far. (c) 2007 Elsevier Masson SAS. All rights reserved.

Package models and the information crisis of prebiotic evolution

The coexistence between different types of templates has been the choice solution to the information crisis of prebiotic evolution, triggered by the finding that a single RNA-like template cannot carry enough information to code for any useful replicase. In principle, confining d distinct templates of length L in a package or protocell, whose Survival depends on the coexistence of the templates it holds in, could resolve this crisis provided that d is made sufficiently large. Here we review the prototypical package model of Niesert et al. [1981. Origin of life between Scylla and Charybdis. J. Mol. Evol. 17, 348-353] which guarantees the greatest possible region of viability of the protocell population, and show that this model, and hence the entire package approach, does not resolve the information crisis. In particular, we show that the total information stored in a viable protocell (Ld) tends to a constant value that depends only on the spontaneous error rate per nucleotide of the template replication mechanism. As a result, an increase of d must be followed by a decrease of L, so that the net information gain is null. (C) 2008 Elsevier Ltd. All rights reserved.

Natural products biological screening and ligand-based virtual screening for the discovery of new antileishmanial agents

In the course of our research program to discover novel antileishmanial agents, a biological screening of natural products against Leishmania major promastigotes allowed the identification of a furoquinoline alkaloid (1) and a furanocoumarin (2) as new hits. Subsequently, an integrated ligand-based virtual screening approach was employed to search for new antileishmanial compounds using these naturally occurring molecules as templates. Fourteen out of 40 compounds selected from a database of about 800,000 compounds (extracted from ZINC, a free database for virtual screening) were experimentally confirmed to possess significant in vitro antileishmanial properties. The application of ligand-based virtual screening as a complementary approach to experimental natural product screening was a useful strategy to facilitate the identification of new promising lead candidates.

Sequencing of Spodoptera frugiperda midgut trehalases and demonstration of secretion of soluble trehalase by midgut columnar cells

Both soluble (SfTre1) and membrane-bound (SfTre2) trehalases occur along the midgut of Spodoptera frugiperda larvae. Released SfTre2 was purified as a 67 kDa protein. Its K(m) (1.6 mM) and thermal stability (half life 10 min at 62 degrees C) are different from the previously isolated soluble trehalase (K(m) = 0.47 mM; 100% stable at 62 degrees C). Two cDNAs coding for S. frugiperda trehalases have been cloned using primers based on consensus sequences of trehalases and having as templates a cDNA library prepared from total polyA-containing RNA extracted from midguts. One cDNA codes for a trehalase that has a predicted transmembrane sequence and was defined as SfTre2. The other, after being cloned and expressed, results in a recombinant trehalase with a K(m) value and thermal stability like those of native soluble trehalase. This enzyme was defined as SfTre1 and, after it was used to generate antibodies, it was immunolocalized at the secretory vesicles and at the glycocalyx of columnar cells. Escherichia coli trehalase 3D structure and sequence alignment with SfTre1 support a proposal regarding the residue modulating the pKa value of the proton donor.

Development of Highly Selective Enzymatic Devices Based on Deposition of Permselective Membranes on Aligned Nanowires

We describe a simple and efficient strategy to fabricate enzymatic devices based on the deposition of glucose oxidase on aligned and highly oriented CoNiMo metallic nanowires. CoNiMo nanowires with an average diameter of 200 nm and length of 50 mu m were electrodeposited on Au-covered alumina substrates via electrodeposition, using alumina membranes as templates. Enzyme-modified electrodes were fabricated via enzyme immobilization using a cross-linker. To minimize nonspecific reactions in the presence of interfering agents, a permselective membrane composed of poly(vinylsulfonic acid) and polyamidoamine dendrimer was deposited via electrostatic interaction. The formation of hydrogen peroxide as a product of the enzymatic reaction was monitored at low overpotential, 0.0 V (vs Ag/AgCl). The detection limit was estimated at 22 mu M under an applied potential of 0.0 V. The apparent Michaelis-Menten constant determined from the Lineweaver-Burke plot was 2 mM.

Studie av web to print samt kartläggning av kunders behov för tillämpning av systemet CiPublisher

Customers put their printing suppliers to severe claims for shorter production time and faster deliveries.Printers always look for new solutions to increase the satisfaction of their customers. Oneexample of such a solution is web to print, where the customers book their printed matters atInternet.The solution involves design of printed matter by using templates that are made unique for thecustomer's printed matter. Web to print is suitable for reiterated printed matters. By using templatesthe customer doesn´t have to redo their layout for every new edition. Bromma tryck AB hasinvested the system CiPublisher, which is applied for the customer to make their printed matter atInternet.The purpose of the examination work is to investigate the needs of the customers of Brommatryck for a web to print solution and how such a system should be adapted.The result shows that the customer who is in need of a web to print solution wish such a system tobe easy managed and also usable. The customer inquiry also shows that most of the customers primarydesire for start using such a solution is that it will save time and also simplify the process formanufacturing of printing matters.

Grafisk profilering som en del avvarumärkesarbetet

A strong brand can help a company to be easier to recognize and be remembered by their customers. Part of branding is to create a visual appearance which is called a graphic profile and contains information on for instance a logo, colours or typography.The objective of this thesis was to create a graphic profile for Stjørdal Tannhelsesenter that could serve as a base for a brand work in the future. It was important to analyze how the clinic wants to be perceived and how it is perceived today. The methods used to carry out this study were questionnaires, researches and a focus group.The work resulted in the generation of a graphic profile that included a new logo, colours, decorative elements, fonts, templates for stationery, business card / badge, imagery, and examples of some publications.According to the test which was made to examine the results of the project showed that I was successful and that the new design meets all the requests from the previous questionnaires.

En beskrivning av manuellt test : Svagheter och styrkor med och utan stöd avett testverktyg

Test is an area in system development. Test can be performed manually or automated. Test activities can be supported by Word documents and Excel sheets for documenting and executing test cases and as well for follow up, but there are also new test tools designed to support and facilitate the testing process and the activities of the test. This study has described manual test and identified strengths and weaknesses of manual testing with a testing tool called Microsoft Test Manager (MTM) and of manual testing using test cases and test log templates developed by the testers at Sogeti. The result that emerged from the problem and strength analysis and the analysis of literature studies and firsthand experiences (in terms of creating, documenting and executing test cases) addresses the issue of the following weaknesses and strengths. Strengths of the test tool is that it contains needed functionality all in one place and it is available when needed without having to open up other programs which saves many steps of activity. Strengths with test without the support of test tools is mainly that it is easy to learn and gives a good overview, easy to format text as desired and flexible to changes during execution of a test case. Weaknesses in test with the support of test tools include that it is difficult to get a good overview of the entire test case, that it is not possible to format the text in the test steps. It is as well not possible to modify the test steps during execution. It is also difficult to use some of the test design techniques of TMap, for example a checklist, when using the test tool MTM. Weaknesses with test without the support of the testing tool MTM is that the tester gets many more steps of activities to do compared to doing the same activities with the support of the testing tool MTM. There is more to remember because the documents the tester use are not directly linked. Altogether the strengths of the test tool stands out when it comes to supporting the testing process.

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.

Fred: An approach to generating real, correct, reusable programs from proofs

In this paper we describe our system for automatically extracting "correct" programs from proofs using a development of the Curry-Howard process. Although program extraction has been developed by many authors, our system has a number of novel features designed to make it very easy to use and as close as possible to ordinary mathematical terminology and practice. These features include 1. the use of Henkin's technique to reduce higher-order logic to many-sorted (first-order) logic; 2. the free use of new rules for induction subject to certain conditions; 3. the extensive use of previously programmed (total, recursive) functions; 4. the use of templates to make the reasoning much closer to normal mathematical proofs and 5. a conceptual distinction between the computational type theory (for representing programs)and the logical type theory (for reasoning about programs). As an example of our system we give a constructive proof of the well known theorem that every graph of even parity, which is non-trivial in the sense that it does not consist of isolated vertices, has a cycle. Given such a graph as input, the extracted program produces a cycle as promised.

Intercâmbio de dados entre aplicativos utilizando XML/XSLT

A integração de aplicações heterogêneas é uma tarefa constante entre empresas do mundo moderno. A grande quantidade de fornecedores de software, aliada à extensa variedade de técnicas e linguagens computacionais utilizadas, fazem desta integração uma tarefa trabalhosa e cara para as organizações. As alternativas existentes para a integração de sistemas de diferentes fornecedores podem variar, desde acesso compartilhado a uma base de dados comum, uso de replicadores de dados entre bases de dados distintas, troca de mensagens entre aplicações, ou o uso de programas exportadores/importadores, gerando arquivos em um formato previamente protocolado entre os desenvolvedores dos softwares envolvidos. Este trabalho visa propor uma alternativa para a integração de sistemas heterogêneos, fazendo uso da tecnologia XML para representar os dados que são trocados entre os aplicativos. Para tanto, sugere um framework a ser utilizado no planejamento da arquitetura dos softwares. O objetivo principal da adoção de um framework é a utilização de uma metodologia previamente desenvolvida e certificada, economizando tempo de análise para a solução de um problema. O framework proposto subtrai dos desenvolvedores a necessidade de alteração do código fonte dos seus programas cada vez que a integração com um novo fornecedor de software se faz necessária, ou que há alteração no formato dos dados trocados entre os aplicativos. Este efeito é conseguido através da utilização de XSLT para a conversão de formatos de documentos XML trocados pelos softwares. Tal conversão é realizada por um processador XSLT externo aos programas envolvidos. Para simplificar o processo, foi desenvolvido o protótipo de uma ferramenta para a geração de templates XSLT. Templates são elementos da especificação XSLT capazes de realizar a transformação entre estruturas representadas em XML. O gerador de templates XSLT é uma ferramenta gráfica capaz de converter mapeamentos realizados entre estruturas XML em templates XSLT, podendo aplicar as transformações geradas a documentos XML, com a finalidade de teste ou transformação.

Geração de modelos de co-simulação distribuída para a arquitetura DCB

O aumento na complexidade dos sistemas embarcados, compostos por partes de hardware e software, aliado às pressões do mercado que exige novos produtos em prazos cada vez menores, tem levado projetistas a considerar a possibilidade de construir sistemas a partir da integração de componentes já existentes e previamente validados. Esses componentes podem ter sido desenvolvidos por diferentes equipes ou por terceiros e muitas vezes são projetados utilizando diferentes metodologias, linguagens e/ou níveis de abstração. Essa heterogeneidade torna complexo o processo de integração e validação de componentes, que normalmente é realizado através de simulação. O presente trabalho especifica mecanismos genéricos e extensíveis que oferecem suporte à cooperação entre componentes heterogêneos em um ambiente de simulação distribuída, sem impor padrões proprietários para formatos de dados e para a descrição do comportamento e interface dos componentes. Esses mecanismos são baseados na arquitetura DCB (Distributed Co-Simulation Backbone), voltada para co-simulação distribuída e heterogênea e inspirada nos conceitos de federado (componente de simulação) e federação (conjunto de componentes) que são definidos pelo HLA (High Level Architecture), um padrão de interoperabilidade para simulações distribuídas. Para dar suporte à co-simulação distribuída e heterogênea, esse trabalho descreve mecanismos que são responsáveis pelas tarefas de cooperação e distribuição, chamados de embaixadores, assim como o mecanismo gateway, que é responsável pela interoperabilidade entre linguagens e conversão de tipos de dados. Também é apresentada uma ferramenta de suporte à geração das interfaces de co-simulação, que são constituídas de dois embaixadores configuráveis e um gateway para cada federado, gerado a partir de templates pré-definidos.

FrameworkDoc : ferramenta de documentação e geração de artefatos de software

Atualmente, um dos grandes desafios para qualquer desenvolvedor de software é projetar um sistema que reutilize ao máximo elementos de código e de projeto existentes, visando diminuir o tempo e o esforço exigidos na produção do software. Entre as inúmeras formas de possibilitar reuso no contexto do desenvolvimento segundo o paradigma da orientação a objetos, destaca-se a abordagem de frameworks. A grande importância da documentação de software utilizada no processo de desenvolvimento aliada às características de frameworks serviram como motivação para este trabalho. A documentação dentro do processo de desenvolvimento de software não faz parte de uma fase definida, mas ocorre durante toda sua existência, em paralelo com outras fases do ciclo de vida. A abordagem de frameworks dentro deste contexto enfoca o tratamento de templates e definições das características dos artefatos de software (incluindo não somente código mas também produtos de análise, projeto, frameworks, componentes, diagramas, entre outros), facilitando e acelerando o processo de documentação. Um framework, devido a suas características peculiares que serão examinadas e explicitadas no trabalho, contém uma série de informações que podem, além de apoiar a documentação, ser úteis para produção de outros artefatos (por exemplo, planejamentos de teste, scripts de bancos de dados, padrões de codificação, entre outros) do processo de desenvolvimento. Assim, em um processo de desenvolvimento evolutivo, que utiliza a geração de artefatos como recurso, a manutenção pode ser integralmente realizada somente na especificação e não diluída nos artefatos gerados. O objetivo deste trabalho é investigar, propor e desenvolver uma ferramenta de documentação e geração de artefatos de software, denominado FrameworkDoc. O termo documentação de software aqui utilizado se refere a documentação de desenvolvimento de software, incluindo artefatos, arquiteturas, ferramentas entre outros. Serão abordados dois principais aspectos: primeiramente, a geração automática de documentação dentro do processo de desenvolvimento de software e depois a geração de outros artefatos deste processo, a partir das definições de alto nível disponíveis através do framework. Exemplos de aplicações do FrameworkDoc em projetos reais são apresentados. No entanto, os documentos e artefatos de software considerados foram definidos de forma suficientemente genérica para serem aproveitados em outros contextos.

A percepção dos riscos na atividade pericial: um estudo de caso, considerando a cultura da organização com um breve olhar fenomenológico à gestão

A pesquisa objetivou analisar e compreender, considerando os aspectos culturais da organização, como os servidores do Instituto de Criminalística percebem os riscos em seus ambientes interno e externo. A integração das dimensões investigadas (cultura, risco, percepção e gestão) a última sob um breve olhar fenomenológico, possibilitou desvelar até que ponto os valores da organização policial interferem na percepção dos riscos, adicionando uma contribuição às escassas publicações sobre o tema. Em busca da cultura da organização policial, uma incursão histórica esquadrinhou a linhagem da polícia e da Criminalística. No caminho metodológico, deparou-se com raras publicações sobre o tema, demandando um desenho específico para o estudo de caso, considerando o seu contexto atual, em caráter exploratório sobre o foco investigado. Uma abordagem qualitativa, acompanhada de dados estatísticos obtidos na própria instituição, favoreceu a compreensão do problema, envolvendo valores e riscos. Foram desenhadas planilhas ajustadas à realidade da unidade e orientadas aos gestores das seções internas e externas, configurando um mapa de risco do Instituto, resultando em um documento, sem precedentes, tipológico dos riscos na atividade pericial. Levantamento bibliográfico, documental, entrevistas e questionários, garantiram integridade à pesquisa. Em termos práticos, as identificações dos riscos (incluindo o mapa) e os esclarecimentos sobre a cultura, favorecerão, aos administradores, a programação de ações de gestão, visando à redução de instabilidades e tensões que contribuem para a ocorrência de acidentes e perdas no âmbito da criminalística. Concluiu-se, que a percepção e a própria gestão dos riscos são sensíveis às influências de valores culturais, exigindo dos gestores e administrados, em ação participativa, a construção de um ambiente redutor de instabilidades e tensões com a relevância do humano cuja essencialidade representou a senda de partida, de chegada e para retomada, na gestão organizacional.