Inactive conformation of the serpin α1-antichymotrypsin indicates two-stage insertion of the reactive loop: Implications for inhibitory function and conformational disease

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into β-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by β-strand exchange between the reactive loop of one molecule and β-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55–Pro) of the plasma serpin α1-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into β-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma α1-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55–Pro mutation.

A modifier screen in the eye reveals control genes for Krüppel activity in the Drosophila embryo

Irregular facets (If) is a dominant mutation of Drosophila that results in small eyes with fused ommatidia. Previous results showed that the gene Krüppel (Kr), which is best known for its early segmentation function, is expressed ectopically in If mutant eye discs. However, it was not known whether ectopic Kr activity is either the cause or the result of the If mutation. Here, we show that If is a gain-of-function allele of Kr. We then used the If mutation in a genetic screen to identify dominant enhancers and suppressors of Kr activity on the third chromosome. Of 30 identified Kr-interacting loci, two were cloned, and we examined whether they also represent components of a natural Kr-dependent developmental pathway of the embryo. We show that the two genes, eyelid (eld) and extramacrochaetae (emc), which encode a Bright family-type DNA binding protein and a helix-loop-helix factor, respectively, are necessary to achieve the singling-out of a unique Kr-expressing cell during the development of the Malpighian tubules, the excretory organs of the fly. The results indicate that the Kr gain-of-function mutation If provides a tool to identify genes that are active during eye development and that a number of them function also in the control of Kr-dependent developmental processes.

Multi-responsiveness of single anterior pituitary cells to hypothalamic-releasing hormones: A cellular basis for paradoxical secretion

The classic view for hypothalamic regulation of anterior pituitary (AP) hormone secretion holds that release of each AP hormone is controlled specifically by a corresponding hypothalamic-releasing hormone (HRH). In this scenario, binding of a given HRH (thyrotropin-, growth hormone-, corticotropin-, and luteinizing hormone-releasing hormones) to specific receptors in its target cell increases the concentration of cytosolic Ca2+ ([Ca2+]i), thereby selectively stimulating the release of the appropriate hormone. However, “paradoxical” responses of AP cells to the four well-established HRHs have been observed repeatedly with both in vivo and in vitro systems, raising the possibility of functional overlap between the different AP cell types. To explore this possibility, we evaluated the effects of HRHs on [Ca2+]i in single AP cells identified immunocytochemically by the hormone they stored. We found that each of the five major AP cell types contained discrete subpopulations that were able to respond to several HRHs. The relative abundance of these multi-responsive cells was 59% for lactotropes, 33% for thyrotropes, and in the range of 47–55% for gonadotropes, corticotropes, and somatotropes. Analysis of prolactin release from single living cells revealed that each of the four HRHs tested were able to induce hormone release from a discrete lactotrope subpopulation, the size of which corresponded closely to that in which [Ca2+]i changes were induced by the same secretagogues. When viewed as a whole, our diverse functional measurements of multi-responsiveness suggest that hypothalamic control of pituitary function is more complicated than previously envisioned. Moreover, they provide a cellular basis for the so-called “paradoxical” behavior of pituitary cells to hypothalamic hypophysiotropic agents.

Stepwise Photoinhibition of Photosystem II1 : Studies with Synechocystis Species PCC 6803 Mutants with a Modified D-E Loop of the Reaction Center Polypeptide D1

Several mutant strains of Synechocystis sp. PCC 6803 with large deletions in the D-E loop of the photosystem II (PSII) reaction center polypeptide D1 were subjected to high light to investigate the role of this hydrophilic loop in the photoinhibition cascade of PSII. The tolerance of PSII to photoinhibition in the autotrophic mutant ΔR225-F239 (PD), when oxygen evolution was monitored with 2,6-dichloro-p-benzoquinone and the equal susceptibility compared with control when monitored with bicarbonate, suggested an inactivation of the QB-binding niche as the first event in the photoinhibition cascade in vivo. This step in PD was largely reversible at low light without the need for protein synthesis. Only the next event, inactivation of QA reduction, was irreversible and gave a signal for D1 polypeptide degradation. The heterotrophic deletion mutants ΔG240-V249 and ΔR225-V249 had severely modified QB pockets, yet exhibited high rates of 2,6-dichloro-p-benzoquinone-mediated oxygen evolution and less tolerance to photoinhibition than PD. Moreover, the protein-synthesis-dependent recovery of PSII from photoinhibition was impaired in the ΔG240-V249 and ΔR225-V249 mutants because of the effects of the mutations on the expression of the psbA-2 gene. No specific sequences in the D-E loop were found to be essential for high rates of D1 polypeptide degradation.

A loop-loop "kissing" complex is the essential part of the dimer linkage of genomic HIV-1 RNA.

RNA-RNA interactions govern a number of biological processes. Several RNAs, including natural sense and antisense RNAs, interact by means of a two-step mechanism: recognition is mediated by a loop-loop complex, which is then stabilized by formation of an extended intermolecular duplex. It was proposed that the same mechanism holds for dimerization of the genomic RNA of human immunodeficiency virus type 1 (HIV-1), an event thought to control crucial steps of HIV-1 replication. However, whereas interaction between the partially self-complementary loop of the dimerization initiation site (DIS) of each monomer is well established, formation of the extended duplex remained speculative. Here we first show that in vitro dimerization of HIV-1 RNA is a specific process, not resulting from simple annealing of denatured molecules. Next we used mutants of the DIS to test the formation of the extended duplex. Four pairs of transcomplementary mutants were designed in such a way that all pairs can form the loop-loop "kissing" complex, but only two of them can potentially form the extended duplex. All pairs of mutants form heterodimers whose thermal stability, dissociation constant, and dynamics were analyzed. Taken together, our results indicate that, in contrast with the interactions between natural sense and antisense RNAs, no extended duplex is formed during dimerization of HIV-1 RNA. We also showed that 55-mer sense RNAs containing the DIS are able to interfere with the preformed HIV-1 RNA dimer.

MEGARA control system

MEGARA (Multi-Espectrografo en GTC de Alta Resolucion para Astronomia) is an optical Integral-Field Unit (IFU) and Multi-Object Spectrograph (MOS) designed for the GTC 10.4 m telescope in La Palma. The MEGARA Control System will provide the capabilities to move the different mechanisms of the instrument, to readout the data from the detector controller and the necessary routines for the Inspector Panels, the MEGARA Observing Preparation Software Suite, the Data Factory and the Sequencer strategies.

Uma formulação por média-variância multi-período para o erro de rastreamento em carteiras de investimento.

Neste trabalho, deriva-se uma política de escolha ótima baseada na análise de média-variância para o Erro de Rastreamento no cenário Multi-período - ERM -. Referindo-se ao ERM como a diferença entre o capital acumulado pela carteira escolhida e o acumulado pela carteira de um benchmark. Assim, foi aplicada a metodologia abordada por Li-Ng em [24] para a solução analítica, obtendo-se dessa maneira uma generalização do caso uniperíodo introduzido por Roll em [38]. Em seguida, selecionou-se um portfólio do mercado de ações brasileiro baseado no fator de orrelação, e adotou-se como benchmark o índice da bolsa de valores do estado de São Paulo IBOVESPA, além da taxa básica de juros SELIC como ativo de renda fixa. Dois casos foram abordados: carteira composta somente de ativos de risco, caso I, e carteira com um ativo sem risco indexado à SELIC - e ativos do caso I (caso II).

Un sistema de control autónomo para personajes de videojuegos basado en el modelo cognitivo Creencia-Deseo-Intención

La industria del videojuego ha avanzado a grandes pasos durante los últimos años respecto a la creación de "inteligencia artificial" para sus personajes, afirmando siempre que la utilizan para dotar de realismo y credibilidad a sus personajes. Sin embargo este concepto ha variado sustancialmente año tras año, y aún hoy, la inteligencia que encontramos en los personajes está lejos de lo que uno podría esperar de ello, incluso lejos de lo ya estudiado y conocido en la correspondiente disciplina académica. En el afán por desarrollar personajes que sean realmente autónomos y tomen sus propias decisiones tras razonar acerca de lo que ocurre en el juego, en este trabajo porponemos un sistema capaz de dotar de control autónomo a los personajes de un videojuego y con potencial para mostrar una mayor inteligencia. Para ello conectamos un armazón de desarrollo de videojuegos llamado IsoUnity, desarrollado sobre el entorno Unity, con un sistema multi-agente llamado Jason e implementado en Java, que utiliza el conocido modelo cognitivo Creencia-Deseo-Intención para representar el estado interno de la mente de los agentes, que en nuestro caso serán personajes de videojuego. A la hora de producir un videojuego, se implementa mediante un sistema de agentes inteligentes, con información subjetiva sobre el mundo, objetivos y planes y tareas que realizar, el jugador tendrá una experiencia más plena. Nuestra visión es la de adoptar este sistema en el desarrollo de videojuegos independientes de perspectiva isométrica y recursos sencillos de estilo retro, de ahí el uso de IsoUnity. En esta memoria, además de explicar en detalle nuestro sistema de control, documentamos las pruebas y las adaptaciones que proponemos para llevar a la práctica este concepto, sentando las bases tecnológicas para producir un videojuego completo utilizando este sistema. Siguiendo el camino iniciado en anteriores Trabajos de Fin de Grado de esta Facultad, queríamos continuar en esa línea de trabajo afinando más el concepto y abordando un tema nuevo, el de dotar a los personajes de videojuegos creados con IsoUnity de una autonomía mayor y mejores herramientas de toma de decisión para poder interactuar con su entorno y con otros personajes.

Um método de otimização da relação desempenho/consumo de energia para arquiteturas multi-cores heterogêneas em FPGA

Devido às tendências de crescimento da quantidade de dados processados e a crescente necessidade por computação de alto desempenho, mudanças significativas estão acontecendo no projeto de arquiteturas de computadores. Com isso, tem-se migrado do paradigma sequencial para o paralelo, com centenas ou milhares de núcleos de processamento em um mesmo chip. Dentro desse contexto, o gerenciamento de energia torna-se cada vez mais importante, principalmente em sistemas embarcados, que geralmente são alimentados por baterias. De acordo com a Lei de Moore, o desempenho de um processador dobra a cada 18 meses, porém a capacidade das baterias dobra somente a cada 10 anos. Esta situação provoca uma enorme lacuna, que pode ser amenizada com a utilização de arquiteturas multi-cores heterogêneas. Um desafio fundamental que permanece em aberto para estas arquiteturas é realizar a integração entre desenvolvimento de código embarcado, escalonamento e hardware para gerenciamento de energia. O objetivo geral deste trabalho de doutorado é investigar técnicas para otimização da relação desempenho/consumo de energia em arquiteturas multi-cores heterogêneas single-ISA implementadas em FPGA. Nesse sentido, buscou-se por soluções que obtivessem o melhor desempenho possível a um consumo de energia ótimo. Isto foi feito por meio da combinação de mineração de dados para a análise de softwares baseados em threads aliadas às técnicas tradicionais para gerenciamento de energia, como way-shutdown dinâmico, e uma nova política de escalonamento heterogeneity-aware. Como principais contribuições pode-se citar a combinação de técnicas de gerenciamento de energia em diversos níveis como o nível do hardware, do escalonamento e da compilação; e uma política de escalonamento integrada com uma arquitetura multi-core heterogênea em relação ao tamanho da memória cache L1.

Buscando la correlación instrumental y visual óptima para colores goniocromáticos mediante cabinas de iluminación y multi-gonio-espectrofotómetros

En la búsqueda de la modelización y cuantificación óptimas de la correlación instrumental y visual de materiales goniocromáticos (pinturas y plásticos, principalmente) en los procesos de control de calidad típicos del sector automovilístico, se presenta aquí una comparación de las prestaciones de diversos tipos actuales de instrumentos de medida del color y cabinas de iluminación. Los multi-gonioespectrofotómetros analizados fueron: Datacolor FX10®, X-Rite MA98® y BYK-mac®, y, las cabinas de iluminación direccional: gonio-vision-box® y byko-spectra effect®. Las propiedades ópticas, básicamente fotométricas y colorimétricas, evaluadas fueron: geometrías de medida, fuente de luz, distancia de observación y dirección visual a la muestra. Los resultados aportados mostraron que actualmente dicha correlación instrumental y visual no es óptima debido a desajustes en las cabinas.

Control framework for dexterous manipulation using dynamic visual servoing and tactile sensors’ feedback

Tactile sensors play an important role in robotics manipulation to perform dexterous and complex tasks. This paper presents a novel control framework to perform dexterous manipulation with multi-fingered robotic hands using feedback data from tactile and visual sensors. This control framework permits the definition of new visual controllers which allow the path tracking of the object motion taking into account both the dynamics model of the robot hand and the grasping force of the fingertips under a hybrid control scheme. In addition, the proposed general method employs optimal control to obtain the desired behaviour in the joint space of the fingers based on an indicated cost function which determines how the control effort is distributed over the joints of the robotic hand. Finally, authors show experimental verifications on a real robotic manipulation system for some of the controllers derived from the control framework.

Application of multi-sensor advanced DInSAR analysis to severe land subsidence recognition: Alto Guadalentín Basin (Spain)

Multi-sensor advanced DInSAR analyses have been performed and compared with two GPS station measurements, in order to evaluate the land subsidence evolution in a 20-year period, in the Alto Guadalentín Basin where the highest rate of man-induced subsidence (> 10 cm yr−1) of Europe had been detected. The control mechanisms have been examined comparing the advanced DInSAR data with conditioning and triggering factors (i.e. isobaths of Plio-Quaternary deposits, soft soil thickness and piezometric level).

MODELADO MULTI-DOMINIO DE MÁQUINAS ELÉCTRICAS.

El objetivo general de este proyecto es desarrollar nuevos modelos multi-dominio de máquinas eléctricas para aplicaciones al control y al diagnóstico de fallas. Se propone comenzar con el modelo electromagnético del motor de inducción en base a circuitos magnéticos equivalentes (MEC) validándolo por medio de simulación y de resultados experimentales. Como segundo paso se pretende desarrollas modelos térmicos y mecánicos con el objetivo que puedan ser acoplados al modelo electromagnético y de esta estudiar la interacción de los dominios y se validará mediante resultados de simulación y experimentales el modelo completo. Finalmente se pretende utilizar el modelo multi-dominio como una herramienta para la prueba de nuevas estrategias de control y diagnóstico de fallas.

BIDIRECTIONAL AC-DC CONVERTERS USING ONE CYCLE CONTROL (OCC) FOR ELECTRIC VEHICLES

The electric vehicle (EV) market has seen a rapid growth in the recent past. With an increase in the number of electric vehicles on road, there is an increase in the number of high capacity battery banks interfacing the grid. The battery bank of an EV, besides being the fuel tank, is also a huge energy storage unit. Presently, it is used only when the vehicle is being driven and remains idle for rest of the time, rendering it underutilized. Whereas on the other hand, there is a need of large energy storage units in the grid to filter out the fluctuations of supply and demand during a day. EVs can help bridge this gap. The EV battery bank can be used to store the excess energy from the grid to vehicle (G2V) or supply stored energy from the vehicle to grid (V2G ), when required. To let power flow happen, in both directions, a bidirectional AC-DC converter is required. This thesis concentrates on the bidirectional AC-DC converters which have a control on power flow in all four quadrants for the application of EV battery interfacing with the grid. This thesis presents a bidirectional interleaved full bridge converter topology. This helps in increasing the power processing and current handling capability of the converter which makes it suitable for the purpose of EVs. Further, the benefit of using the interleaved topology is that it increases the power density of the converter. This ensures optimization of space usage with the same power handling capacity. The proposed interleaved converter consists of two full bridges. The corresponding gate pulses of each switch, in one cell, are phase shifted by 180 degrees from those of the other cell. The proposed converter control is based on the one-cycle controller. To meet the challenge of new requirements of reactive power handling capabilities for grid connected converters, posed by the utilities, the controller is modified to make it suitable to process the reactive power. A fictitious current derived from the grid voltage is introduced in the controller, which controls the converter performance. The current references are generated using the second order generalized integrators (SOGI) and phase locked loop (PLL). A digital implementation of the proposed control ii scheme is developed and implemented using DSP hardware. The simulated and experimental results, based on the converter topology and control technique discussed here, are presented to show the performance of the proposed theory.

Fuzzy control of a water pump for an agricultural plant growth system

At the present time there is a high pressure toward the improvement of all the production processes. Those improvements can be sensed in several directions in particular those that involve energy efficiency. The definition of tight energy efficiency improvement policies is transversal to several operational areas ranging from industry to public services. As can be expected, agricultural processes are not immune to this tendency. This statement takes more severe contours when dealing with indoor productions where it is required to artificially control the climate inside the building or a partial growing zone. Regarding the latter, this paper presents an innovative system that improves energy efficiency of a trees growing platform. This new system requires the control of both a water pump and a gas heating system based on information provided by an array of sensors. In order to do this, a multi-input, multi-output regulator was implemented by means of a Fuzzy logic control strategy. Presented results show that it is possible to simultaneously keep track of the desired growing temperature set-point while maintaining actuators stress within an acceptable range.