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.

The use of stochastic dynamic programming in optimal landscape reconstruction for metapopulations

A decision theory framework can be a powerful technique to derive optimal management decisions for endangered species. We built a spatially realistic stochastic metapopulation model for the Mount Lofty Ranges Southern Emu-wren (Stipiturus malachurus intermedius), a critically endangered Australian bird. Using diserete-time Markov,chains to describe the dynamics of a metapopulation and stochastic dynamic programming (SDP) to find optimal solutions, we evaluated the following different management decisions: enlarging existing patches, linking patches via corridors, and creating a new patch. This is the first application of SDP to optimal landscape reconstruction and one of the few times that landscape reconstruction dynamics have been integrated with population dynamics. SDP is a powerful tool that has advantages over standard Monte Carlo simulation methods because it can give the exact optimal strategy for every landscape configuration (combination of patch areas and presence of corridors) and pattern of metapopulation occupancy, as well as a trajectory of strategies. It is useful when a sequence of management actions can be performed over a given time horizon, as is the case for many endangered species recovery programs, where only fixed amounts of resources are available in each time step. However, it is generally limited by computational constraints to rather small networks of patches. The model shows that optimal metapopulation, management decisions depend greatly on the current state of the metapopulation,. and there is no strategy that is universally the best. The extinction probability over 30 yr for the optimal state-dependent management actions is 50-80% better than no management, whereas the best fixed state-independent sets of strategies are only 30% better than no management. This highlights the advantages of using a decision theory tool to investigate conservation strategies for metapopulations. It is clear from these results that the sequence of management actions is critical, and this can only be effectively derived from stochastic dynamic programming. The model illustrates the underlying difficulty in determining simple rules of thumb for the sequence of management actions for a metapopulation. This use of a decision theory framework extends the capacity of population viability analysis (PVA) to manage threatened species.

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

GUIsurfer: A Reverse Engineering Framework for User Interface Software

GUIsurfer: A Reverse Engineering Framework for User Interface Software

GUI Behavior from Source Code Analysis

When developing interactive applications, considering the correctness of graphical user interfaces (GUIs) code is essential. GUIs are critical components of today's software, and contemporary software tools do not provide enough support for ensuring GUIs' code quality. GUIsurfer, a GUI reverse engineering tool, enables evaluation of behavioral properties of user interfaces. It performs static analysis of GUI code, generating state machines that can help in the evaluation of interactive applications. This paper describes the design, software architecture, and the use of GUIsurfer through an example. The tool is easily re-targetable, and support is available to Java/Swing, and WxHaskell. The paper sets the ground for a generalization effort to consider rich internet applications. It explores the GWT web applications' user interface programming toolkit.

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.

Robosonic: Randomness-Based Manipulation of Sounds Assisted by Robots

In this text, we intend to explore the possibilities of sound manipulation in a context of augmented reality (AR) through the use of robots. We use the random behaviour of robots in a limited space for the real-time modulation of two sound characteristics: amplitude and frequency. We add the possibility of interaction with these robots, providing the user the opportunity to manipulate the physical interface by placing markers in the action space, which alter the behaviour of the robots and, consequently, the audible result produced. We intend to demonstrate through the agents, programming of random processes and direct manipulation of this application, that it is possible to generate empathy in interaction and obtain specific audible results, which would be difficult to otherwise reproduce due to the infinite loops that the interaction promotes.

Projecto timecloud: software de gestão de tempo laboral numa plataforma cloud

O presente projecto tem como objectivo a disponibilização de uma plataforma de serviços para gestão e contabilização de tempo remunerável, através da marcação de horas de trabalho, férias e faltas (com ou sem justificação). Pretende-se a disponibilização de relatórios com base nesta informação e a possibilidade de análise automática dos dados, como por exemplo excesso de faltas e férias sobrepostas de trabalhadores. A ênfase do projecto está na disponibilização de uma arquitectura que facilite a inclusão destas funcionalidades. O projecto está implementado sobre a plataforma Google App Engine (i.e. GAE), de forma a disponibilizar uma solução sob o paradigma de Software as a Service, com garantia de disponibilidade e replicação de dados. A plataforma foi escolhida a partir da análise das principais plataformas cloud existentes: Google App Engine, Windows Azure e Amazon Web Services. Foram analisadas as características de cada plataforma, nomeadamente os modelos de programação, os modelos de dados disponibilizados, os serviços existentes e respectivos custos. A escolha da plataforma foi realizada com base nas suas características à data de iniciação do presente projecto. A solução está estruturada em camadas, com as seguintes componentes: interface da plataforma, lógica de negócio e lógica de acesso a dados. A interface disponibilizada está concebida com observação dos princípios arquitecturais REST, suportando dados nos formatos JSON e XML. A esta arquitectura base foi acrescentada uma componente de autorização, suportada em Spring-Security, sendo a autenticação delegada para os serviços Google Acounts. De forma a permitir o desacoplamento entre as várias camadas foi utilizado o padrão Dependency Injection. A utilização deste padrão reduz a dependência das tecnologias utilizadas nas diversas camadas. Foi implementado um protótipo, para a demonstração do trabalho realizado, que permite interagir com as funcionalidades do serviço implementadas, via pedidos AJAX. Neste protótipo tirou-se partido de várias bibliotecas javascript e padrões que simplificaram a sua realização, tal como o model-view-viewmodel através de data binding. Para dar suporte ao desenvolvimento do projecto foi adoptada uma abordagem de desenvolvimento ágil, baseada em Scrum, de forma a implementar os requisitos do sistema, expressos em user stories. De forma a garantir a qualidade da implementação do serviço foram realizados testes unitários, sendo também feita previamente a análise da funcionalidade e posteriormente produzida a documentação recorrendo a diagramas UML.

Scheduling of head-dependent cascaded hydro systems: Mixed-integer quadratic programming approach

This paper is on the problem of short-term hydro, scheduling, particularly concerning head-dependent cascaded hydro systems. We propose a novel mixed-integer quadratic programming approach, considering not only head-dependency, but also discontinuous operating regions and discharge ramping constraints. Thus, an enhanced short-term hydro scheduling is provided due to the more realistic modeling presented in this paper. Numerical results from two case studies, based on Portuguese cascaded hydro systems, illustrate the proficiency of the proposed approach.