Systematic structural studies of iron superoxide dismutases from human parasites and a statistical coupling analysis of metal binding specificity

Superoxide dismutases (SODs) are a crucial class of enzymes in the combat against intracellular free radical damage. They eliminate superoxide radicals by converting them into hydrogen peroxide and oxygen. In spite of their very different life cycles and infection strategies, the human parasites Plasmodium falciparum, Trypanosoma cruzi and Trypanosoma brucei are known to be sensitive to oxidative stress. Thus the parasite Fe-SODs have become attractive targets for novel drug development. Here we report the crystal structures of FeSODs from the trypanosomes T. brucei at 2.0 angstrom and T. cruzi at 1.9 angstrom resolution, and that from P. falciparum at a higher resolution (2.0 angstrom) to that previously reported. The homodimeric enzymes are compared to the related human MnSOD with particular attention to structural aspects which are relevant for drug design. Although the structures possess a very similar overall fold, differences between the enzymes at the entrance to the channel which leads to the active site could be identified. These lead to a slightly broader and more positively charged cavity in the parasite enzymes. Furthermore, a statistical coupling analysis (SCA) for the whole Fe/MnSOD family reveals different patterns of residue coupling for Mn and Fe SODs, as well as for the dimeric and tetrameric states. In both cases, the statistically coupled residues lie adjacent to the conserved core surrounding the metal center and may be expected to be responsible for its fine tuning, leading to metal ion specificity.

Adhesion as a tool for in-built nanotechnology design in cementitious materials

Confined water, such as those molecules in nanolayers of 2-3 nm in length, plays an important role in the adhesion of hydrophilic materials, mainly in cementitious ones. In this study, the effects of water containing kosmotropic substances on adhesion, known for their ability of enhancing the hydrogen bond (H-bond) network of confined water, were evaluated using mechanical strength tests. Indeed, to link adhesion provided by water confined in nanolayers to a macro-response of the cementitious samples, such as the bending strength, requires the evaluation of local water H-bond network configuration in the presence of kosmotropes, considering their influences on the extent and the strength of H-bonds. Among the kosmotropes, trimethylamine and sucrose provided a 50% increase in bending strength compared to the reference samples, the latter just using water as an adhesive, whereas trehalose was responsible for reducing the bending strength to a value close to the samples without any adhesive. The results attained opened up perspectives regarding exploring the confined water behavior which naturally occurs throughout the hydration process in cement-based materials.

Synthesis Optimization of Hydroxymethylnitrofurazone, an Antichagasic Candidate, Using 3(2) Factorial Design

Hydroxymethylnitrofurazone presents in vitro activity against Trypanosoma cruzi. The optimization of the synthesis of this compound was performed through a 3(2) factorial statistical design. Quadratic model produced the best response surface predicting a maximum yield (82%) close to the center design point with a seven hours reaction and a 1:1.5 (NF:K(2)CO(3)) ratio.

Conceptual Product Development in Small Corporations

The main objective of the thesis “Conceptual Product Development in Small Corporations” is by the use of a case study test the MFD™-method (Erixon G. , 1998) combined with PMM in a product development project. (Henceforth called MFD™/PMM-method). The MFD™/PMM-method used for documenting and controlling a product development project has since it was introduced been used in several industries and projects. The method has been proved to be a good way of working with the early stages of product development, however, there are almost only projects carried out on large industries which means that there are very few references to how the MFD™/PMM-method works in a small corporation. Therefore, was the case study in the thesis “Conceptual Product Development in Small Corporations” carried out in a small corporation to find out whether the MFD™/PMM-method also can be applied and used in such a corporation.The PMM was proposed in a paper presented at Delft University of Technology in Holland 1998 by the author and Gunnar Erixon. (See appended paper C: The chart of modular function deployment.) The title “The chart of modular function deployment” was later renamed as PMM, Product Management Map. (Sweden PreCAD AB, 2000). The PMM consists of a QFD-matrix linked to MIM (Module Indication Matrix) via a coupling matrix which makes it possible to make an unbroken chain from the customer domain to the designed product/modules. The PMM makes it easy to correct omissions made in creating new products and modules.In the thesis “Conceptual Product Development in Small Corporations” the universal MFD™/PMM-method has been adapted by the author to three models of product development; original-, evolutionary- and incremental development.The evolutionary adapted MFD™/PMM-method was tested as a case study at Atlings AB in the community Ockelbo. Atlings AB is a small corporation with a total number of 50 employees and an annual turnover of 9 million €. The product studied at the corporation was a steady rest for supporting long shafts in turning. The project team consisted of management director, a sales promoter, a production engineer, a design engineer and a workshop technician, the author as team leader and a colleague from Dalarna University as discussion partner. The project team has had six meetings.The project team managed to use MFD™ and to make a complete PMM of the studied product. There were no real problems occurring in the project work, on the contrary the team members worked very well in the group, having ideas how to improve the product. Instead, the challenge for a small company is how to work with the MFD™/PMM-method in the long run! If the MFD™/PMM-method is to be a useful tool for the company it needs to be used continuously and that requires financial and personnel resources. One way for the company to overcome the probable lack of recourses regarding capital and personnel is to establish a good cooperation with a regional university or a development centre.

Studies of Design and Assembly Defects on Integrated and Modular Architectures

It is known that despite companies’ efforts to improve the quality of their products, design and assembly defects results in large repair costs both in terms of repair and providing feedback to the origin of the defect. The purpose of this paper is to study these types of defects and the defect rates in design and assembly. The paper presents a web based questionnaire answered by 29 companies. The result shows that the defect rate (defects per product) spanned from 0.01 to 10. Also, design and assembly defects covered 46%, 23% respectively, of all occurred defects. A case study is also presented, performed at a company who recently implemented a modular architecture. In this company, defects from 5 700 integrated product architectures are compared with defects from 431 modular architectures. The average defect rate increased by 21.5% – from 0.65 to 0.79 – when a more modular architecture has been implemented. Furthermore, the study showed that the assembly defects have decreased while the design defects increased. The results presented in this paper will also support the development of the MPV (Module Property Verification) method which is briefly described.

Design industrial como fonte de vantagem estratégica: estudo de caso na indústria moveleira

This research was based on the lack of academic investigations which recognize industrial design as an strategic advantages source. It was chosen to adopt a wide approach, not common in administration researches, through which aspects frequently ignored by most of the strategy and marketing literature could be recognized. The investigation took place at a big brazilian company, from the furniture industry, more specifically from the office furniture segment. Two product development cases were selected: one of them classified by the company as an example of success and the other as a failure case. It is an exploratory study. Some important topics were identified, and they may be developed in future researches: the existence of intra-organizational conflicts between marketing and engineering; the big companies' power over market configuration, and the State influence over local markets dinamics.

Government actions to support coffee producers - an investigation of possible measures from the European Union

We outline possible actions to be adopted by the European Union to ensure a better share of total coffee revenues to producers in developing countries. The way to this translates, ultimately, in producers receiving a fair price for the commodity they supply, i.e., a market price that results from fair market conditions in the whole coffee producing chain. We plead for proposals to take place in the consuming countries, as market conditions in the consuming-countries side of the coffee producing chain are not fair; market failures and ingenious distortions are responsible for the enormous asymmetry of gains in the two sides. The first of three proposals for consumer government supported actions is to help in the creation of domestic trading companies for achieving higher export volumes. These tradings would be associated to roasters that, depending on the final product envisaged, could perform the roasting in the country and export the roasted – and sometimes ground – coffee, breaking the increasing importers-exporters verticalisation. Another measure would be the systematic provision of basic intelligence on the consuming markets. Statistics of the quantities sold according to mode of consumption, by broad “categories of coffee” and point of sale, could be produced for each country. They should be matched to the exports/imports data and complemented by (aggregate) country statistics on the roasting sector. This would extremely help producing countries design their own market and producing strategies. Finally, a fund, backed by a common EU tax on roasted coffee – created within the single market tax harmonisation programme, is suggested. This European Coffee Fund would have two main projects. Together with the ICO, it would launch an advertising campaign on coffee in general, aimed at counterbalancing the increasing “brandification” of coffee. Basic information on the characteristics of the plant and the drink would be passed, and the effort could be extended to the future Eastern European members of the Union, as a further assurance that EU processors would not have a too privileged access to these new markets. A quality label for every coffee sold in the Union could complement this initiative, helping to create a level playing field for products from outside the EU. A second project would consist in a careful diversification effort, to take place in selected producing countries.

Study of the innovation management process in the development of a discontinuous product case: Motorola RAZR V3

This study will collaborate by bringing some detailed analysis and findings on a special case study of a discontinuous product development process, trying to answer how the discontinuous product development process takes place and the main factors that influence this process. Additionally, it tried to explore some explanations for the difficulties generally faced by the companies to sustain innovation. The case is about the Motorola cell phone RAZR V3, launched in 2004. RAZR V3 was noted by industry experts as game-changing feat of design and engineering, selling more than 110 million units by end of 2008 and recognized as one of the fastest selling products in the industry. The study uses a single case methodology, which is appropriate given the access to a phenomenon that happened inside corporate dominium and it is not easily accessed for academic studies, besides being a rare case of success in the cellular phone industry. In order to magnify the understanding of the phenomenon, the exploration was extended to contrast the RAZR development process and the standard product development process in Motorola. Additionally, it was integrated a longitudinal reflection of the company product development evolution until the next breakthrough product hitting the cellular phone industry. The result of the analysis shows that discontinuous products do not fit well traditional product development process (in this case, stage-gate). This result reinforces the results obtained on previous studies of discontinuous product development conducted by other authors. Therefore, it is clear that the dynamics of discontinuous product development are different from the continuous product development, requiring different treatment to succeed. Moreover, this study highlighted the importance of the management influence in all the phases of the process as one of the most important factors, suggesting a key component to be carefully observed in future researches. Some other findings of the study that were considered very important for a discontinuous product development process: have champions (who believe and protect the project) and not only one champion; create a right atmosphere to make flow the creative process; question paradigms to create discontinuous products; simple guiding light to focus the team; company culture that accepts and knows how to deal with risks; and undoubtedly, have a company strategy that understands the different dynamics of continuous and discontinuous product development processes and treat them accordingly.

Contribuição do design thinking para o processo de inovação de produtos

Este trabalho visa identificar práticas de design thinking (DT), isto é, as abordagens características da disciplina do design para criação de inovações, que possam ser incorporadas ao processo de desenvolvimento de novos produtos (DNP). Cinco dessas práticas – abordagem centrada em pessoas, estilo de trabalho colaborativo, pensar fazendo, visualização e combinação de abordagens divergente e convergente – foram analisadas por meio do estudo de caso em profundidade de três empresas polares: um escritório profissional de design, uma empresa de produtos para cuidados pessoais e um fabricante de ferramentas profissionais. A discussão teórica apoiou-se em autores de DNP e de DT que estudaram a evolução desses campos em gerações de maturidade, trazendo também visões bem recentes que apontam para a relevância das mudanças em curso. Entre os achados da pesquisa, observou-se que o modelo de gestão e a estrutura organizacional – orientada por projetos com times multifuncionais ou por processos com estrutura funcional – tem influência na adoção das práticas de DT. Outro achado, esse menos evidente, mostrou que a forma como a empresa se relaciona com clientes e usuários, guarda semelhança com a forma como trata seus profissionais de DNP. Uma descoberta interessante é a função moderadora do alinhamento de propósitos entre empresa e colaborador, para a adoção dessas práticas. Como contribuição ao campo de estudo, apresenta-se um diagrama de cinco gerações de evolução da oferta de novos produtos (ONP), termo utilizado para incorporar não só os produtos com inovações desenvolvidas e de propriedade da empresa focal, mas também aquelas desenvolvidas pelos próprios usuários e as inovações construídas nas redes sociais e oferecidas pela empresa focal.

Convexity in multidimensional mechanism design

The present article initiates a systematic study of the behavior of a strictly increasing, C2 , utility function u(a), seen as a function of agents' types, a, when the set of types, A, is a compact, convex subset of iRm . When A is a m-dimensional rectangle it shows that there is a diffeomorphism of A such that the function U = u o H is strictly increasing, C2 , and strictly convexo Moreover, when A is a strictly convex leveI set of a nowhere singular function, there exists a change of coordinates H such that B = H-1(A) is a strictly convex set and U = u o H : B ~ iR is a strictly convex function, as long as a characteristic number of u is smaller than a characteristic number of A. Therefore, a utility function can be assumed convex in agents' types without loss of generality in a wide variety of economic environments.