Biochemical and genetic characterization of the Saccharomyces cerevisiae Hsp110 molecular chaperone Sse1

The Ssel/Hsp110 molecular chaperones are a poorly understood subgroup of the Hsp70 chaperone family. Hsp70 can refold denatured polypeptides via a carboxyl-terminal peptide binding domain (PBD), which is regulated by nucleotide cycling in an amino-terminal ATPase domain. However, unlike Hsp70, both Sse1 and mammalian Hsp110 bind unfolded peptide substrates but cannot refold them. To test the in vivo requirement for interdomain communication, SSE1 alleles carrying amino acid substitutions in the ATPase domain were assayed for their ability to complement sse1Δ phenotypes. Surprisingly, all mutants predicted to abolish ATP hydrolysis complemented the temperature sensitivity of sse1Δ, whereas mutations in predicted ATP binding residues were non-functional. Remarkably, the two domains of Ssel when expressed in trans functionally complement the sse1Δ growth phenotype and interact by coimmunoprecipitation analysis, indicative of a novel type of interdomain communication. ^ Relatively little is known regarding the interactions and cellular functions of Ssel. Through co-immunoprecipitation analysis, we found that Ssel forms heterodimeric complexes with the abundant cytosolic Hsp70s Ssa and Ssb in vivo. Furthermore, these complexes can be efficiently reconstituted in vitro using purified proteins. The ATPase domains of Ssel and the Hsp70s were found to be critical for interaction as inactivating point mutations severely reduced interaction efficiency. Ssel stimulated Ssal ATPase activity synergistically with the co-chaperone Ydj1 via a novel nucleotide exchange activity. Furthermore, FES1, another Ssa nucleotide exchange factor, can functionally substitute for SSE1/2 when overexpressed, suggesting that Hsp70 nucleotide exchange is the fundamental role of the Sse proteins in yeast, and by extension, the Hsp110 homologs in mammals. ^ Cells lacking SSE1 were found to accumulate prepro-α-factor, but not the cotranslationally imported protein Kar2, similar to mutants in the Ssa chaperones. This indicates that the interaction between Ssel and Ssa is functionally significant in vivo. In addition, sse10 cells are compromised for cell wall strength, likely a result of decreased Hsp90 chaperone activity with the cell integrity MAP kinase SIC. Taken together, this work established that the Hsp110 family must be considered an essential component of Hsp70 chaperone biology in the eukaryotic cell.^

Software Design Guidelines for Usability

For years, the Human Computer Interaction (HCI) community has crafted usability guidelines that clearly define what characteristics a software system should have in order to be easy to use. However, in the Software Engineering (SE) community keep falling short of successfully incorporating these recommendations into software projects. From a SE perspective, the process of incorporating usability features into software is not always straightforward, as a large number of these features have heavy implications in the underlying software architecture. For example, successfully including an “undo” feature in an application requires the design and implementation of many complex interrelated data structures and functionalities. Our work is focused upon providing developers with a set of software design patterns to assist them in the process of designing more usable software. This would contribute to the proper inclusion of specific usability features with high impact on the software design. Preliminary validation data show that usage of the guidelines also has positive effects on development time and overall software design quality.

Programmed design of ship forms

This paper describes a new category of CAD applications devoted to the definition and parameterization of hull forms, called programmed design. Programmed design relies on two prerequisites. The first one is a product model with a variety of types large enough to face the modeling of any type of ship. The second one is a design language dedicated to create the product model. The main purpose of the language is to publish the modeling algorithms of the application in the designer knowledge domain to let the designer create parametric model scripts. The programmed design is an evolution of the parametric design but it is not just parametric design. It is a tool to create parametric design tools. It provides a methodology to extract the design knowledge by abstracting a design experience in order to store and reuse it. Programmed design is related with the organizational and architectural aspects of the CAD applications but not with the development of modeling algorithms. It is built on top and relies on existing algorithms provided by a comprehensive product model. Programmed design can be useful to develop new applications, to support the evolution of existing applications or even to integrate different types of application in a single one. A three-level software architecture is proposed to make the implementation of the programmed design easier. These levels are the conceptual level based on the design language, the mathematical level based on the geometric formulation of the product model and the visual level based on the polyhedral representation of the model as required by the graphic card. Finally, some scenarios of the use of programmed design are discussed. For instance, the development of specialized parametric hull form generators for a ship type or a family of ships or the creation of palettes of hull form components to be used as parametric design patterns. Also two new processes of reverse engineering which can considerably improve the application have been detected: the creation of the mathematical level from the visual level and the creation of the conceptual level from the mathematical level. © 2012 Elsevier Ltd. All rights reserved. 1. Introduction

A platform for real-time control education with LEGO MINDSTORMS.

A set of software development tools for building real-time control systems on a simple robotics platform is described in the paper. The tools are being used in a real-time systems course as a basis for student projects. The development platform is a low-cost PC running GNU/Linux, and the target system is LEGO MINDSTORMS NXT, thus keeping the cost of the laboratory low. Real-time control software is developed using a mixed paradigm. Functional code for control algorithms is automatically generated in C from Simulink models. This code is then integrated into a concurrent, real-time software architecture based on a set of components written in Ada. This approach enables the students to take advantage of the high-level, model-oriented features that Simulink oers for designing control algorithms, and the comprehensive support for concurrency and real-time constructs provided by Ada.

On the automatic integration of hardware accelerators into FPGA-based embedded systems

This paper proposes an automatic framework for the seamless integration of hardware accelerators, starting from an OpenMP-based application and an XML file describing the HW/SW partitioning. It extends a fully software architecture by generating and integrating the cores, along with the proper interfaces, and the code for scheduling and synchronization. Experimental results show that it is possible to validate different solutions only by varying the input code.

MultiPARTES: Multicore Virtualization for Mixed-Criticality Systems

Modern embedded applications typically integrate a multitude of functionalities with potentially different criticality levels into a single system. Without appropriate preconditions, the integration of mixed-criticality subsystems can lead to a significant and potentially unacceptable increase of engineering and certification costs. A promising solution is to incorporate mechanisms that establish multiple partitions with strict temporal and spatial separation between the individual partitions. In this approach, subsystems with different levels of criticality can be placed in different partitions and can be verified and validated in isolation. The MultiPARTES FP7 project aims at supporting mixed- criticality integration for embedded systems based on virtualization techniques for heterogeneous multicore processors. A major outcome of the project is the MultiPARTES XtratuM, an open source hypervisor designed as a generic virtualization layer for heterogeneous multicore. MultiPARTES evaluates the developed technology through selected use cases from the offshore wind power, space, visual surveillance, and automotive domains. The impact of MultiPARTES on the targeted domains will be also discussed. In a number of ongoing research initiatives (e.g., RECOMP, ARAMIS, MultiPARTES, CERTAINTY) mixed-criticality integration is considered in multicore processors. Key challenges are the combination of software virtualization and hardware segregation and the extension of partitioning mechanisms to jointly address significant non-functional requirements (e.g., time, energy and power budgets, adaptivity, reliability, safety, security, volume, weight, etc.) along with development and certification methodology.

Change-Impact driven Agile Architecting.

Software architecture is a key factor to scale up Agile Software Development ASD in large softwareintensive systems. Currently, software architectures are more often approached through mechanisms that enable to incrementally design and evolve software architectures aka. agile architecting. Agile architecting should be a light-weight decision-making process, which could be achieved by providing knowledge to assist agile architects in reasoning about changes. This paper presents the novel solution of using change-impact knowledge as the main driver for agile architecting. The solution consists of a Change Impact Analysis technique and a set of models to assist agile architects in the change -decision-making- process by retrieving the change-impact architectural knowledge resulting from adding or changing features iteration after iteration. To validate our approach, we have put our solution into practice by running a project of a metering management system in electric power networks in an i-smart software factory.

A taxonomy of the quality attributes for distributed applications

The software engineering community has paid little attention to non-functional requirements, or quality attributes, compared with studies performed on capture, analysis and validation of functional requirements. This circumstance becomes more intense in the case of distributed applications. In these applications we have to take into account, besides the quality attributes such as correctness, robustness, extendibility, reusability, compatibility, efficiency, portability and ease of use, others like reliability, scalability, transparency, security, interoperability, concurrency, etc. In this work we will show how these last attributes are related to different abstractions that coexist in the problem domain. To achieve this goal, we have established a taxonomy of quality attributes of distributed applications and have determined the set of necessary services to support such attributes.

Engineering privacy requirements valuable lessons from another realm

The Privacy by Design approach to systems engineering introduces privacy requirements in the early stages of development, instead of patching up a built system afterwards. However, 'vague', 'disconnected from technology', or 'aspirational' are some terms employed nowadays to refer to the privacy principles which must lead the development process. Although privacy has become a first-class citizen in the realm of non-functional requirements and some methodological frameworks help developers by providing design guidance, software engineers often miss a solid reference detailing which specific, technical requirements they must abide by, and a systematic methodology to follow. In this position paper, we look into a domain that has already successfully tackled these problems -web accessibility-, and propose translating their findings into the realm of privacy requirements engineering, analyzing as well the gaps not yet covered by current privacy initiatives.

Evaluación de patrones de programación de usabilidad para tres casos de estudio

La calidad es uno de los principales retos de la construcción de software. En la Ingeniería del Software (IS) se considera a la usabilidad como un atributo de calidad. Al principio se veía a la usabilidad como un requisito no funcional.Se asumía que la usabilidad era una propiedad exclusiva de la presentación de la información.Se creía que separando la capa de presentación del resto, se podía desarrollar un producto software usable.Debido a la naturaleza del sistema y a las necesidades del usuario, a menudo se debe ir más lejos y no basta con tener en cuenta la presentación para obtener un software usable. La comunidad de la Interacción Personar Ordenador (IPO) ha propuesto recomendaciones para mejorar la usabilidad. Algunas de esas recomendaciones tienen impacto directo en la funcionalidad del producto software. En estudios recientes también se ha evaluado la relación entre la usabilidad y los requisitos funcionales. Estas investigaciones sugieren que la usabilidad debe ser tenida en cuenta desde las etapas iniciales de la construcción para evitar costosos cambios posteriores. La incorporación de las características de usabilidad agrega cierta complejidad al proceso de desarrollo. El presente trabajo evalúa la posibilidad de usar patrones para la incorporación de usabilidad en el desarrollo de un producto software. Concretamente se evalúan los siguientes patrones de programación de usabilidad (PPUs): Abort Operation,Progress Feedback y Preferences. Se utilizan unas Pautas de Desarrollo de Mecanismos de Usabilidad(PDMUs) para estos tres mecanismos de usabilidad. Estas pautas poponen patrones para la educción y posterior incorporación de la usabilidad en las distintas fases de la programación. En esta investigación se aborda el desarrollo de un producto software desde la deducción de requisitos hasta la implementación. En cada fase se incorporan los mecanismos de usabilidad de acuerdo a las recomendaciones de las PDMUs. Mediante el desarrollo de un software real se ha evaluado la factibilidad del uso de las PDMUs obteniendo como resultado propuestas de mejoras en estas pautas. Se evalúa asimismo el esfuerzo de incorporación de los mecanismos de usabilidad. Cada evaluación aporta datos que proporcionan una estimación del esfuerzo adicional requerido para incorporar cada mecanismo de usabilidad en el proceso de desarrollo del software.---ABSTRACT---Quality is a major challenge in software construction. Software engineers consider usability to be a quality attribute. Originally, usability was viewed as a nonr functional requirement. Usability was assumed to be simply an information presentation property. There was a belief that a usable software product could be developed by separating the presentation layer from the rest of the system. Depending on the system type and user needs, however, usability often runs deeper, and it is not enough to consider just presentation to build usable software. The humanrcomputer interaction (HCI) community put forward a list of recommendations to improve usability. Some such recommendations have a direct impact on software product functionality. Recent studies have also evaluated the relationship between usability and functional requirements. This research suggests that usability should be taken into account as of the early stages of software construction to prevent costly rework later on. The inclusion of usability features is an added complication to the development process. The research reported here evaluates the possibility of using patterns to incorporate usability into a software product. Specifically, it evaluates the following usability programming patterns (UPPs): Abort Operation, Progress Feedback and Preferences. Usability Mechanism Development Guides (USDG) are applied to these three usability mechanisms. These guides propose patterns for eliciting and later incorporating usability into the different software development phases, including programming. The reported research addresses the development of a software product from requirements elicitation through to implementation. Usability mechanisms are incorporated into each development phase in accordance with USDG recommendations. A real piece of software was developed to test the feasibility of using USDGs, outputting proposals for improving the guides. Each evaluation yields data providing an estimate of the additional workload required to incorporate each usability mechanism into the software development process.

Funicularity and equilibrium for high-performance conceptual structural design

Las estructuras que trabajan por forma se caracterizan por la íntima e indisociable relación entre geometría y comportamiento estructural. Por consiguiente, la elección de una apropiada geometría es el paso previo indispensable en el diseño conceptual de dichas estructuras. En esa tarea, la selección de las posibles geometrías antifuniculares para las distribuciones de cargas permanentes más habituales son más bien limitadas y, muchas veces, son criterios no estructurales (adaptabilidad funcional, estética, proceso constructivo, etc.) los que no permiten la utilización de dichas geometrías que garantizarían el máximo aprovechamiento del material. En este contexto, esta tesis estudia la posibilidad de obtener una estructura sin momentos flectores incluso si la geometría no es antifunicular para sus cargas permanentes. En efecto, esta tesis presenta un procedimiento, basado en la estática gráfica, que demuestra cómo un conjunto de cargas adicionales, introducidas a través de un sistema de pretensado exterior con elementos post-tesos, puede eliminar los momentos flectores debidos a cargas permanentes en cualquier geometría plana. Esto se traduce en una estructura antifunicular que proporciona respuestas innovadoras a demandas conjuntas de versatilidad arquitectónica y optimización del material. Dicha metodología gráfica ha sido implementada en un software distribuido libremente (EXOEQUILIBRIUM), donde el análisis estructural y la variación geométrica están incluidos en el mismo entorno interactivo y paramétrico. La utilización de estas herramientas permite más versatilidad en la búsqueda de nuevas formas eficientes, lo cual tiene gran importancia en el diseño conceptual de estructuras, liberando al ingeniero de la limitación del propio cálculo y de la incomprensión del comportamiento estructural, facilitando extraordinariamente el hecho creativo a la luz de una metodología de este estilo. Esta tesis incluye la aplicación de estos procedimientos a estructuras de cualquier geometría y distribución inicial de cargas, así como el estudio de diferentes posibles criterios de diseño para optimizar la posición del sistema de post-tesado. Además, la metodología ha sido empleada en el proyecto de maquetas a escala reducida y en la construcción de un pabellón hecho enteramente de cartón, lo que ha permitido obtener una validación física del procedimiento desarrollado. En definitiva, esta tesis expande de manera relevante el rango de posibles geometrías antifuniculares y abre enormes posibilidades para el diseño de estructuras que combinan eficiencia estructural y flexibilidad arquitectónica.Curved structures are characterized by the critical relationship between their geometry and structural behaviour, and selecting an appropriate shape in the conceptual design of such structures is important for achieving materialefficiency. However, the set of bending-free geometries are limited and, often, non-structural design criteria (e.g., usability, architectural needs, aesthetics) prohibit the selection of purely funicular or antifunicular shapes. In response to this issue, this thesis studies the possibility of achieving an axial-only behaviour even if the geometry departs from the ideally bending-free shape. This dissertation presents a new design approach, based on graphic statics that shows how bending moments in a two-dimensional geometry can be eliminated by adding forces through an external post-tensioning system. This results in bending-free structures that provide innovative answers to combined demands on versatility and material optimization. The graphical procedure has been implemented in a free-downloadable design-driven software (EXOEQUILIBRIUM) where structural performance evaluations and geometric variation are embedded within an interactive and parametric working environment. This provides greater versatility in finding new efficient structural configurations during the first design stages, bridging the gap between architectural shaping and structural analysis. The thesis includes the application of the developed graphical procedure to shapes with random curvature and distribution of loads. Furthermore, the effect of different design criteria on the internal force distribution has been analyzed. Finally, the construction of reduced- and large-scale models provides further physical validation of the method and insights about the structural behaviour of these structures. In summary, this work strongly expands the range of possible forms that exhibit a bending-free behaviour and, de facto, opens up new possibilities for designs that combine high-performing solutions with architectural freedom.

Framework para el desarrollo con el DNIe

El proyecto se trata de una API de desarrollo para el DNI electrónico que permita crear de forma sencilla aplicaciones cuya funcionalidad se apoye en el uso del DNI electrónico. De esta forma, el framework facilita el acceso a las principales operaciones soportadas por el DNIe mediante la invocación de métodos sencillos. Una de las funcionalidades es la de realizar un proceso de autenticación con el DNIe utilizando para ello las capacidades criptográficas del chip que incorpora y el certificado de autenticación. Esta funcionalidad puede ser accedida también de forma dividida en dos pasos, para dar soporte a aplicaciones con arquitectura cliente-servidor. El framework también ofrece la funcionalidad de firma electrónica con el DNIe, una firma legalmente válida y que permite chequear también la integridad del mensaje firmado. También se soporta por el framework la comprobación de un certificado mediante el protocolo OCSP, funcionalidad que si bien no implica directamente al DNIe, sí que es importante en el marco de procesos que se ven involucrados en cualquier Infraestructura de Clave Pública. ABSTRACT The project is a development API for DNIe card that allows easily create applications whose functionality is supported in the use of DNIe. Thus, the framework provides access to the main operations supported by the DNIe by invoking simple methods. One of the features is to perform an authentication process with the DNIe using its chip’s capabilities and authentication certificate. This functionality can also be accessed so divided into two steps, to support applications with client-server architecture. The framework also provides the functionality of electronic signatures with DNIe, a legally valid signature and allows also check the integrity of the signed message. Verification of a certificate using OCSP, functionality but does not imply directly to DNIe is also supported by the framework, yes it is important in the context of processes that are involved in any Public Key Infrastructure.

Diseño e implementación de un controlador de velocidad PID multivariable para un robot con configuración de triciclo

La robótica móvil constituye un área de desarrollo y explotación de interés creciente. Existen ejemplos de robótica móvil de relevancia destacada en el ámbito industrial y se estima un fuerte crecimiento en el terreno de la robótica de servicios. En la arquitectura software de todos los robots móviles suelen aparecer con frecuencia componentes que tienen asignadas competencias de gobierno, navegación, percepción, etcétera, todos ellos de importancia destacada. Sin embargo, existe un elemento, difícilmente prescindible en este tipo de robots, el cual se encarga del control de velocidad del dispositivo en sus desplazamientos. En el presente proyecto se propone desarrollar un controlador PID basado en el modelo y otro no basado en el modelo. Dichos controladores deberán operar en un robot con configuración de triciclo disponible en el Departamento de Sistemas Informáticos y deberán por tanto ser programados en lenguaje C para ejecutar en el procesador digital de señal destinado para esa actividad en el mencionado robot (dsPIC33FJ128MC802). ABSTRACT Mobile robotics constitutes an area of development and exploitation of increasing interest. There are examples of mobile robotics of outstanding importance in industry and strong growth is expected in the field of service robotics. In the software architecture of all mobile robots usually appear components which have assigned competences of government, navigation, perceptionetc., all of them of major importance. However, there is an essential element in this type of robots, which takes care of the speed control. The present project aims to develop a model-based and other non-model-based PID controller. These controllers must operate in a robot with tricycle settings, available from the Department of Computing Systems, and should therefore be programmed in C language to run on the digital signal processor dedicated to that activity in the robot (dsPIC33FJ128MC802).

International conference paper presentations: A multimodal analysis to determine effectiveness

International conference presentations represent one of the biggest challenges for academics using English as a Lingua Franca (ELF). This paper aims to initiate exploration into the multimodal academic discourse of oral presentations, including the verbal, written, non-verbal material (NVM) and body language modes. It offers a Systemic Functional Linguistic (SFL) and multimodal framework of presentations to enhance mixed-disciplinary ELF academics' awareness of what needs to be taken into account to communicate effectively at conferences. The model is also used to establish evaluation criteria for the presenters' talks and to carry out a multimodal discourse analysis of four well-rated 20-min talks, two from the technical sciences and two from the social sciences in a workshop scenario. The findings from the analysis and interviews indicate that: (a) a greater awareness of the mode affordances and their combinations can lead to improved performances; (b) higher reliance on the visual modes can compensate for verbal deficiencies; and (c) effective speakers tend to use a variety of modes that often overlap but work together to convey specific meanings. However, firm conclusions cannot be drawn on the basis of workshop presentations, and further studies on the multimodal analysis of ‘real conferences’ within specific disciplines are encouraged.

Farmacogenética em toxicologia forense : estudo do gene CYP2D6 em amostras post mortem com tramadol

Tese de mestrado, Medicina Legal e Ciências Forenses, Universidade de Lisboa, Faculdade de Medicina, 2016