Characterization of the retinoid orphan-related receptor-alpha coactivator binding interface: A structural basis for ligand-independent transcription

The retinoid orphan-related receptor-alpha (RORalpha) is a member of the ROR subfamily of orphan receptors and acts as a constitutive activator of transcription in the absence of exogenous ligands. To understand the basis of this activity, we constructed a homology model of Rill using the closely related TRbeta as a template. Molecular modeling suggested that bulky hydrophobic side chains occupy the RORa ligand cavity leaving a small but distinct cavity that may be involved in receptor stabilization. This model was subject to docking simulation with a receptor-interacting peptide from the steroid receptor coactivator, GR-interacting protein-1, which delineated a coactivator binding surface consisting of the signature motif spanning helices 3-5 and helix 12 [activation function 2 (AF2)]. Probing this surface with scanning alanine mutagenesis showed structural and functional equivalence between homologous residues of RORalpha and TRbeta. This was surprising (given that Rill is a ligand-independent activator, whereas TRbeta has an absolute requirement for ligand) and prompted us to use molecular modeling to identify differences between Rill and TRbeta in the way that the All helix interacts with the rest of the receptor. Modeling highlighted a nonconserved amino acid in helix 11 of RORa (Phe491) and a short-length of 3.10 helix at the N terminus of AF2 which we suggest i) ensures that AF2 is locked permanently in the holoconformation described for other liganded receptors and thus 2) enables ligand-independent recruitment of coactivators. Consistent with this, mutation of RORa Phe491 to either methionine or alanine (methionine is the homologous residue in TRbeta), reduced and ablated transcriptional activation and recruitment of coactivators, respectively. Furthermore, we were able to reconstitute transcriptional activity for both a deletion mutant of Ill lacking All and Phe491 Met, by overexpression of a GAL-AF2 fusion protein, demonstrating ligand-independent recruitment of AF2 and a role for Phe491 in recruiting AF2.

Structural variations and formation constants of first-row transition metal complexes of biologically active aroylhydrazones

Iron chelators of the 2-pyridinecarbaldehyde isonicotinoylhydrazone (HPCIH) class show high potential for the treatment of iron overload diseases. In the present study, selected first-row transition metal (from Mn to Zn) complexes with HPCIH and 2-pyridinecarbaldehyde (4'-aminobenzoyl)hydrazone (HPCAH) were synthesised and characterised. Crystallography reveals that HPCAH exclusively forms bis complexes with divalent transition metals, with each ligand coordinating meridionally through its pyridine-N, imine-N and carbonyl-O atoms, forming distorted octahedral cis-MN4O2 complexes. Complexes of HPCIH were more varied and unpredictable, with metal/ligand ratios of 1:1, 1:2, 2:2 and 3:2 obtained with different metal ions. The isonicotinoyl ring N-atom in HPCIH was found to be an effective ligand, and this resulted in the varied metal/ligand ratios observed. The formation constants of divalent metal complexes with HPCIH were determined by potentiometric titrations and the values obtained were consistent with similar tridentate ligands and with the Irving-Williams order. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Interface Multimodal com Predição de Movimentos para Uso em Reabilitação de Membros Inferiores

Esta dissertação apresenta o desenvolvimento de uma plataforma multimodal de aquisição e processamento de sinais. O projeto proposto insere-se no contexto do desenvolvimento de interfaces multimodais para aplicação em dispositivos robóticos cujo propósito é a reabilitação motora adaptando o controle destes dispositivos de acordo com a intenção do usuário. A interface desenvolvida adquire, sincroniza e processa sinais eletroencefalográficos (EEG), eletromiográficos (EMG) e sinais provenientes de sensores inerciais (IMUs). A aquisição dos dados é feita em experimentos realizados com sujeitos saudáveis que executam tarefas motoras de membros inferiores. O objetivo é analisar a intenção de movimento, a ativação muscular e o início efetivo dos movimentos realizados, respectivamente, através dos sinais de EEG, EMG e IMUs. Para este fim, uma análise offline foi realizada. Nessa análise, são utilizadas técnicas de processamento dos sinais biológicos e técnicas para processar sinais provenientes de sensores inerciais. A partir destes, os ângulos da articulação do joelho também são aferidos ao longo dos movimentos. Um protocolo experimental de testes foi proposto para as tarefas realizadas. Os resultados demonstraram que o sistema proposto foi capaz de adquirir, sincronizar, processar e classificar os sinais combinadamente. Análises acerca da acurácia dos classificadores utilizados mostraram que a interface foi capaz de identificar intenção de movimento em 76, 0 ± 18, 2% dos movimentos. A maior média de tempo de antecipação ao movimento foi obtida através da análise do sinal de EEG e foi de 716, 0±546, 1 milisegundos. A partir da análise apenas do sinal de EMG, este valor foi de 88, 34 ± 67, 28 milisegundos. Os resultados das etapas de processamento dos sinais biológicos, a medição dos ângulos da articulação, bem como os valores de acurácia e tempo de antecipação ao movimento se mostraram em conformidade com a literatura atual relacionada.

A laparoscopic surgery training interface

Laparoscopy is a surgical procedure on which operations in the abdomen are performed through small incisions using several specialized instruments. The laparoscopic surgery success greatly depends on surgeon skills and training. To achieve these technical high-standards, different apprenticeship methods have been developed, many based on in vivo training, an approach that involves high costs and complex setup procedures. This paper explores Virtual Reality (VR) simulation as an alternative for novice surgeons training. Even though several simulators are available on the market claiming successful training experiences, their use is extremely limited due to the economic costs involved. In this work, we present a low-cost laparoscopy simulator able to monitor and assist the trainee’s surgical movements. The developed prototype consists of a set of inexpensive sensors, namely an accelerometer, a gyroscope, a magnetometer and a flex sensor, attached to specific laparoscopic instruments. Our approach allows repeated assisted training of an exercise, without time constraints or additional costs, since no human artificial model is needed. A case study of our simulator applied to instrument manipulation practice (hand-eye coordination) is also presented.

A mobile systems interface protocol

Recent progresses in the software development world has assisted a change in hardware from heavy mainframes and desktop machines to unimaginable small devices leading to the prophetic "third computing paradigm", Ubiquitous Computing. Still, this novel unnoticeable devices lack in various capabilities, like computing power, storage capacity and human interface. Connectivity associated to this devices is also considered an handicap which comes generally associated expensive and limited protocols like GSM and UMTS. Considering this scenario as background, this paper presents a minimal communication protocol introducing better interfaces for limited devices. Special attention has been paid to the limitations of connectivity, storage capacity and scalability of the developed software applications. Illustrating this new protocol, a case-study is presented addressing car sensors communicating with a central

Energy harvesting performance of piezoelectric electrospun polymer fibers and polymer/ceramic composites

The energy harvesting efficiency of electrospun poly(vinylidene fluoride), its copolymer vinylidene fluoride-trifluoroethylene and composites of the later with piezoelectric BaTiOon interdigitated electrodes has been investigated. Further, a study of the influence of the electrospinning processing parameters on the size and distribution of the composites fibers has been performed. It is found that the best energy harvesting performance is obtained for the pure poly(vinylidene fluoride) fibers, with power outputs up to 0.03 W and 25 W under low and high mechanical deformation. The copolymer and the composites show reduced power output due to increased mechanical stiffness. The obtained values, among the largest found in the literature, the easy processing and the low cost and robustness of the polymer, demonstrate the applicability of the developed system.

Thermal degradation of Pb(Zr0.53Ti0.47)O3/poly(vinylidene fluoride) composites as a function of ceramic grain size and concentration

Poly(vinylidene fluoride)/Pb(Zr0.53Ti0.47)O3,([PVDF]1−x/[PZT]x) composites of volume fractions x and (0–3) type connectivity were prepared in the form of thin films. PZT powders with average grain sizes of 0.2, 0.84, and 2.35 μm in different volume fraction of PZT up to 40 % were mixed with the polymeric matrix. The influence of the inorganic particle size and its content on the thermal degradation properties of the composites was then investigated by means of thermo-gravimetric analysis. It is observed that filler size affects more than filler concentration the degradation temperature and activation energy of the polymer. In the same way and due to their larger specific area, smaller particles leave larger solid residuals after the polymer degradation. The polymer degradation mechanism is not significantly modified by the presence of the inorganic fillers. On the other hand, an inhibition effect occurs due to the presence of the fillers, affecting particularly the activation energy of the process.

GUIsurfer: A Reverse Engineering Framework for User Interface Software

GUIsurfer: A Reverse Engineering Framework for User Interface Software

An approach for graphical user interface bad smells detection

In the context of an e ort to develop methodologies to support the evaluation of interactive system, this paper investigates an approach to detect graphical user interface bad smells. Our approach consists in detecting user interface bad smells through model-based reverse engineering from source code. Models are used to de ne which widgets are present in the interface, when can particular graphical user interface (GUI) events occur, under which conditions, which system actions are executed, and which GUI state is generated next.

Heavy metal toxicity in rice and soybean plants cultivated in contaminated soil

Heavy metals can accumulate in soil and cause phytotoxicity in plants with some specific symptoms. The present study evaluated the specific symptoms on rice and soybeans plants caused by excess of heavy metals in soil. Rice and soybean were grown in pots containing soil with different levels of heavy metals. A completely randomized design was used, with four replications, using two crop species and seven sample soils with different contamination levels. Rice and soybean exhibited different responses to the high concentrations of heavy metals in the soil. Rice plants accumulated higher Cu, Mn, Pb and Zn concentrations and were more sensitive to high concentrations of these elements in the soil, absorbing them more easily compared to the soybean plants. However, high available Zn concentrations in the soil caused phytotoxicity symptoms in rice and soybean, mainly chlorosis and inhibited plant growth. Further, high Zn concentrations in the soil reduced the Fe concentration in the shoots of soybean and rice plants to levels considered deficient.