Structural Basis for Interaction of Inhibitors with Cyclin-Dependent Kinase 2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controle automático com estrutura variável utilizando sistemas ERP e LMI

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Crystallization and preliminary X-ray diffraction of malate dehydrogenase from Plasmodium falciparum

The expression, purification, crystallization and preliminary X-ray diffraction characterization of malate dehydrogenase (MDH) from the malarial parasite Plasmodium falciparum (PfMDH) are reported. In order to gain a deeper understanding of the function and role of PfMDH, the protein was purified to homogeneity. The purified protein crystallized in space group P1, with unit-cell parameters a = 72, b = 157, c = 159 angstrom, a = 105, beta = 101, ? = 95 degrees. The resulting crystals diffracted to a maximal resolution of 2.24 angstrom and the structure has been solved by molecular replacement, with 16 monomers in the asymmetric unit. The 16 monomers are arranged into four independent tetramers, in agreement with previous reports demonstrating the tetrameric solution state of PfMDH. The X-ray structure of PfMDH is expected to clarify the differences in catalysis by PfMDH compared with other MDH family members and to provide a basis for the structure-based design of specific PfMDH inhibitors as well as general MDH inhibitors.

Estudo comparativo entre as novas ferramentas digitais utilizadas no desenho à mão livre

This paper makes an analysis on the new technological resources related to architectural drawing that make use of the hand drawing. It tests and evaluates the use of new tools such as tablets (e.g. Wacom Bamboo), graphic tablets (e.g. iPad), tablet/screen hybrids (e.g. Wacom Cintiq) and electronic pens (e.g. Wacom Inkling) in the making of free drawings oriented for the developing of graphic products related to the projective act in architecture and design. The paper makes a comparative e interpretative analysis through the reading of those products.

A linguagem de programação aliada ao desenho na criação de jogos digitais como instrumento de arquitetura patrimonial

This research studies the use of digital games as a playful tool approach of knowledge in architecture heritage. We emphasize the potential of digital games as a tool and importance of digital drawing combined with programming language, the means by which the making of the games became possible. The models developed are based on the properties of historical and cultural interest in the city of São Carlos, Brasil.

Creazione e sviluppo di un sistema di controllo in tempo reale per un sistema fuel cell

The control of a proton exchange membrane fuel cell system (PEM FC) for domestic heat and power supply requires extensive control measures to handle the complicated process. Highly dynamic and non linear behavior, increase drastically the difficulties to find the optimal design and control strategies. The objective is to design, implement and commission a controller for the entire fuel cell system. The fuel cell process and the control system are engineered simultaneously; therefore there is no access to the process hardware during the control system development. Therefore the method of choice was a model based design approach, following the rapid control prototyping (RCP) methodology. The fuel cell system is simulated using a fuel cell library which allowed thermodynamic calculations. In the course of the development the process model is continuously adapted to the real system. The controller application is designed and developed in parallel and thereby tested and verified against the process model. Furthermore, after the commissioning of the real system, the process model can be also better identified and parameterized utilizing measurement data to perform optimization procedures. The process model and the controller application are implemented in Simulink using Mathworks` Real Time Workshop (RTW) and the xPC development suite for MiL (model-in-theloop) and HiL (hardware-in-the-loop) testing. It is possible to completely develop, verify and validate the controller application without depending on the real fuel cell system, which is not available for testing during the development process. The fuel cell system can be immediately taken into operation after connecting the controller to the process.

Valutazione della risposta sismica di edifici mediante modelli anelastici equivalenti

Nella presente tesi è proposta una metodologia per lo studio e la valutazione del comportamento sismico di edifici a telaio. Il metodo prevede la realizzazione di analisi non-lineari su modelli equivalenti MDOF tipo stick, in accordo alla classificazione data nel report FEMA 440. Gli step per l’applicazione del metodo sono descritti nella tesi. Per la validazione della metodologia si sono utilizzati confronti con analisi time-history condotte su modelli tridimensionali dettagliati delle strutture studiate (detailed model). I parametri ingegneristici considerati nel confronto, nell’ottica di utilizzare il metodo proposto in un approccio del tipo Displacement-Based Design sono lo spostamento globale in sommità, gli spostamenti di interpiano, le forze di piano e la forza totale alla base. I risultati delle analisi condotte sui modelli stick equivalenti, mostrano una buona corrispondenza, ottima in certi casi, con quelli delle analisi condotte sui modelli tridimensionali dettagliati. Le time-history realizzate sugli stick model permettono però, un consistente risparmio in termini di onere computazionale e di tempo per il post-processing dei risultati ottenuti.

Application of crescent shaped braces for reinforced concrete structures

The work done is about the seismic analysis of an existing reinforced concrete structure that is equipped with a special bracing device. The main objective of the research is to provide a simple procedure that can be followed in order to design the lateral bracing system in such a way that the actual behavior of the structure matches the desired pre-defined objective curve. a great attention is devoted to the internal actions in the structural elements produced by the braces. The device used is called: Crescent shaped braces. This device is a special type of bracing because it has a banana-like geometry that allows the designer to have more control over the stiffness of the structure, especially under cyclic behavior, Unlike the conventional bracing that resists only through its axial stiffness. This device has been installed in a hospital in Italy. However, it has not been exposed to any ground motion so far. Different analysis methods, such as static pushover and dynamic time-history have been used in the analysis of the structure.

The course of chronic and recurrent low back pain in the general population

Using latent class analysis (LCA), a previous study on patients attending primary care identified four courses of low back pain (LBP) over the subsequent 6 months. To date, no studies have used longitudinal pain recordings to examine the "natural" course of recurrent and chronic LBP in a population-based sample of individuals. This study examines the course of LBP in the general population and elaborates on the stability and criterion-related validity of the clusters derived. A random sample of 400 individuals reporting LBP in a population-based study was asked to complete a comprehensive questionnaire at the start and end of the year's survey, and 52 weekly pain diaries in between. The latter were analyzed using LCA. 305 individuals returned more than 50% of the diaries. Four clusters were identified (severe persistent, moderate persistent, mild persistent, and fluctuating). The clusters differed significantly with regards to pain and disability. Assessment of cluster stability showed that a considerable proportion of patients in the "fluctuating" group changed their classification over time. Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care. Due to the population-based design, this study achieves, for the first time, a close insight into the "natural" course of chronic and recurrent low back pain, including individuals that did not necessarily visit the general practitioner. The findings will help to understand better the nature of this pain in the general population.

Stochastic knock detection model for spark ignited engines

This report presents the development of a Stochastic Knock Detection (SKD) method for combustion knock detection in a spark-ignition engine using a model based design approach. Knock Signal Simulator (KSS) was developed as the plant model for the engine. The KSS as the plant model for the engine generates cycle-to-cycle accelerometer knock intensities following a stochastic approach with intensities that are generated using a Monte Carlo method from a lognormal distribution whose parameters have been predetermined from engine tests and dependent upon spark-timing, engine speed and load. The lognormal distribution has been shown to be a good approximation to the distribution of measured knock intensities over a range of engine conditions and spark-timings for multiple engines in previous studies. The SKD method is implemented in Knock Detection Module (KDM) which processes the knock intensities generated by KSS with a stochastic distribution estimation algorithm and outputs estimates of high and low knock intensity levels which characterize knock and reference level respectively. These estimates are then used to determine a knock factor which provides quantitative measure of knock level and can be used as a feedback signal to control engine knock. The knock factor is analyzed and compared with a traditional knock detection method to detect engine knock under various engine operating conditions. To verify the effectiveness of the SKD method, a knock controller was also developed and tested in a model-in-loop (MIL) system. The objective of the knock controller is to allow the engine to operate as close as possible to its border-line spark-timing without significant engine knock. The controller parameters were tuned to minimize the cycle-to-cycle variation in spark timing and the settling time of the controller in responding to step increase in spark advance resulting in the onset of engine knock. The simulation results showed that the combined system can be used adequately to model engine knock and evaluated knock control strategies for a wide range of engine operating conditions.

STATISTICAL METHODS FOR RARE AND COMMON VARIANT ASSOCIATION STUDIES

Complex human diseases are a major challenge for biological research. The goal of my research is to develop effective methods for biostatistics in order to create more opportunities for the prevention and cure of human diseases. This dissertation proposes statistical technologies that have the ability of being adapted to sequencing data in family-based designs, and that account for joint effects as well as gene-gene and gene-environment interactions in the GWA studies. The framework includes statistical methods for rare and common variant association studies. Although next-generation DNA sequencing technologies have made rare variant association studies feasible, the development of powerful statistical methods for rare variant association studies is still underway. Chapter 2 demonstrates two adaptive weighting methods for rare variant association studies based on family data for quantitative traits. The results show that both proposed methods are robust to population stratification, robust to the direction and magnitude of the effects of causal variants, and more powerful than the methods using weights suggested by Madsen and Browning [2009]. In Chapter 3, I extended the previously proposed test for Testing the effect of an Optimally Weighted combination of variants (TOW) [Sha et al., 2012] for unrelated individuals to TOW &ndash F, TOW for Family &ndash based design. Simulation results show that TOW &ndash F can control for population stratification in wide range of population structures including spatially structured populations, is robust to the directions of effect of causal variants, and is relatively robust to percentage of neutral variants. In GWA studies, this dissertation consists of a two &ndash locus joint effect analysis and a two-stage approach accounting for gene &ndash gene and gene &ndash environment interaction. Chapter 4 proposes a novel two &ndash stage approach, which is promising to identify joint effects, especially for monotonic models. The proposed approach outperforms a single &ndash marker method and a regular two &ndash stage analysis based on the two &ndash locus genotypic test. In Chapter 5, I proposed a gene &ndash based two &ndash stage approach to identify gene &ndash gene and gene &ndash environment interactions in GWA studies which can include rare variants. The two &ndash stage approach is applied to the GAW 17 dataset to identify the interaction between KDR gene and smoking status.

Medicinal Chemistry of ureido derivatives as Antiinfectives

Ureides are compounds, which essentially incorporate urea as a substructural component either in open or cyclic form. Ureido derivatives are one of the oldest classes of bioactives, widely used as antiinfective agents. Several of these compounds, including aminoquinuride, aminocarbalide, imidurea, cloflucarban, nitrofurazone, urosulfan, viomycin are used in clinical situations. One of the ureides, the triclocarban is compulsorily used as antibacterial agent in cleansing and disinfecting solutions in hospital, household, cosmetics, toys, textile and plastics. It disables the activity of ENR, an enzyme vital for building the cell wall of the bacteria and fungus. Besides, the ureido-penicillins in clinical use there have been several ureido-lactam derivatives which have been reported to exhibit significant antibacterial activity. A urea containing dipeptide TAN-1057A isolated from Flexibacter spp. has potent bioactivity against MRSA. The metal complexes of sulphonyl ureido derivatives are effective antifungal agents by inhibiting the activity of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls. There have been number of ureides including the cyclic ureas which are potent HIV protease inhibitors and display significant anti-HIV activity. The urea derivative, merimepodip that has been derived using structure based design, is potent inhibitor of IMPDH and is active against Hepatitis-C infection. This review will primarily focus on the significant work reported for this class of compounds including design, synthesis and biological activity.

High-Level Modeling of Multimodal Interaction Techniques Using NiMMiT

The past few years, multimodal interaction has been gaining importance in virtual environments. Although multimodality renders interacting with an environment more natural and intuitive, the development cycle of such an application is often long and expensive. In our overall field of research, we investigate how modelbased design can facilitate the development process by designing environments through the use of highlevel diagrams. In this scope, we present ‘NiMMiT’, a graphical notation for expressing and evaluating multimodal user interaction; we elaborate on the NiMMiT primitives and demonstrate its use by means of a comprehensive example.

Proyectar dibujando: Una aproximación fenomenológica al estado naciente del proyecto. Un estudio entre dos culturas arquitectónicas

La acción del dibujar intenta presentarse en este texto como lenguaje mudo, práctica común general y práctica común en el campo arquitectónico en concreto; y también como acción, apertura, exploración (no representación) en el estado naciente del proyecto. La tesis se presenta como un estudio basado en la experiencia directa, la observación in situ (Practice Based Design Doctórate) intentando reflexionar no desde sus productos alcanzados al dibujar, sino desde la propia acción, enfatizando la dinamicidad del cuerpo como productor de gestos dinámicos. El trabajo busca describir la acción del trazar como apertura, exploración (no representación) en el estado naciente del proyecto. Es el cruce entre la acción experienciada y el pensamiento crítico respecto al hacer con aproximaciones a la artesanía (Sennett, 2010), al placer del dibujar (Nancy, 2013) y la aventura de conformar (Badiou, 2006). La experiencia en el dibujar que este estudio recoge es la desarrollada por la autora en el contexto pedagógico del D.I.G.A. de la E.T.S.A. de Madrid en concreto en las asignaturas “Dibujo Avanzado e Interpretación Gráfica (DAII) I y II” y “Dibujo del Natural” ambas impartidas por el profesor Antonio Verd Herrero y en la participación en los trabajos del Grupo de Investigación y de Innovación Educativa denominado: “Hypermedia” dirigidos por el profesor Javier Seguí, en el periodo que va del año 2007 a la actualidad. La colección de acontecimientos que surgió de esta experiencia y se formó de aproximaciones sucesivas presenta algunos rasgos característicos de la acción del dibujar. Los acontecimientos abordan la acción del dibujar desde una experiencia muda, un tipo de lenguaje, escritura y comunicación común, intercultural pero a la vez impersonal, desde su relación con la escritura, la palabra, el movimiento, el gesto y su imagen. El dibujar se presenta como modo de exploración en la investigación proyectual basada en la arbitrariedad que requiere voluntad, compromiso, ir en contra para participar en cualquier transformación de los límites (físicos, nacionales, sociales, de género, religión, sentido). El dibujar no representativo se presenta como técnica imaginaria radical, “terapia” configural con capacidad para la experimentación con uno mismo (Sloderdijk, 2003), un modo de comunicación intercultural que, sin embargo, siempre recurre al lenguaje verbal, leída e interpretada para cobrar sentido. ABSTRACT The action of drawing is intended to be presented in this text as a mute language, a common practice in general and a common practice in the field of architecture specifically; and also as an action, opening, exploration (not representation) at the birth stage of a project. The thesis forms a study based on a direct observation in an in situ experience (Practice Based Design Doctórate), which intends to reflect not on the products produced by drawing, but on the action itself, emphasizing on the dynamics of the body as a generator of dynamic gestures. The work is the intersection of experienced action and critical thinking related with the making with an approach to a path on craftsmanship (Sennett, 2010), the pleasure in drawing (Nancy, 2013) and the adventure of compromise/ conciliation (Badiou, 2006). The experience in drawing was collected and developed for this study by the author in the context of D.I.G.A. at the E.T.S.A. of Madrid and in particular at the courses of “Advanced Drawing and Graphic Interpretation” (DAII) I y II” and “Life drawing”, together with the active participation and the work of the investigation and Innovation Educational Group “Hypermedia”, coordinated by professor Javier Seguí, during the period starting the year 2007 until the present (2013). The collection of the events derives from a process of successive attempts to approach some characteristic aspects of the action of drawing. The events approach the action of drawing as a mute experience, a kind of language, common communication, writing, gesture and image. Drawing is presented as a way of exploration for a project's investigation, based on arbitrarily and on the asking “what if”. At the same time this process requires will, compromise, opposition in order to participate in a transformation of any kind of limits (physical, national, social, genre, religion, sense). This thesis aims to present non-representative drawing as a radical imaginary technique, a configurational ‘therapy’ with the capacity to experiment with oneself (Sloderdijk, 2003). It can also be considered as a way of intercultural communication which always uses the verbal, readable and interpreted language in order to charge sense.

Combining Text and Graphics for Interactive Exploration of Behavior Datasets

Modern sensor technologies and simulators applied to large and complex dynamic systems (such as road traffic networks, sets of river channels, etc.) produce large amounts of behavior data that are difficult for users to interpret and analyze. Software tools that generate presentations combining text and graphics can help users understand this data. In this paper we describe the results of our research on automatic multimedia presentation generation (including text, graphics, maps, images, etc.) for interactive exploration of behavior datasets. We designed a novel user interface that combines automatically generated text and graphical resources. We describe the general knowledge-based design of our presentation generation tool. We also present applications that we developed to validate the method, and a comparison with related work.