Sirtuins and proteolytic systems: implications for pathogenesis of synucleinopathies

Insoluble and fibrillar forms of a-synuclein are the major components of Lewy bodies, a hallmark of several sporadic and inherited neurodegenerative diseases known as synucleinopathies. a-Synuclein is a natural unfolded and aggregation-prone protein that can be degraded by the ubiquitin-proteasomal system and the lysosomal degradation pathways. a-Synuclein is a target of the main cellular proteolytic systems, but it is also able to alter their function further, contributing to the progression of neurodegeneration. Aging, a major risk for synucleinopathies, is associated with a decrease activity of the proteolytic systems, further aggravating this toxic looping cycle. Here, the current literature on the basic aspects of the routes for a-synuclein clearance, as well as the consequences of the proteolytic systems collapse, will be discussed. Finally, particular focus will be given to the sirtuins's role on proteostasis regulation, since their modulation emerged as a promising therapeutic strategy to rescue cells from a-synuclein toxicity. The controversial reports on the potential role of sirtuins in the degradation of a-synuclein will be discussed. Connection between sirtuins and proteolytic systems is definitely worth of further studies to increase the knowledge that will allow its proper exploration as new avenue to fight synucleinopathies.

Longitudinal evaluation, acceptability and long-term retention of knowledge on a horizontally integrated organic and functional systems course

Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge.

Hybrid hypervisor partially deployed on FPGA

Tese de Doutoramento em Engenharia Eletrónica e Computadores.

HEP-Frame: A software engineered framework to aid the development and efficient multicore execution of scientific code

This work was supported by FCT (Fundação para a Ciência e Tecnologia) within Project Scope (UID/CEC/00319/2013), by LIP (Laboratório de Instrumentação e Física Experimental de Partículas) and by Project Search-ON2 (NORTE-07-0162- FEDER-000086), co-funded by the North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund.

Refinement and variability techniques in model transformation of software requirements

Tese de Doutoramento em Tecnologias e Sistemas de Informação

Towards the design and implementation of aspect-oriented programming for spreadsheets

A spreadsheet usually starts as a simple and singleuser software artifact, but, as frequent as in other software systems, quickly evolves into a complex system developed by many actors. Often, different users work on different aspects of the same spreadsheet: while a secretary may be only involved in adding plain data to the spreadsheet, an accountant may define new business rules, while an engineer may need to adapt the spreadsheet content so it can be used by other software systems.Unfortunately,spreadsheetsystemsdonotoffermodular mechanisms, and as a consequence, some of the previous tasks may be defined by adding intrusive “code” to the spreadsheet. In this paper we go through the design and implementation of an aspect-oriented language for spreadsheets so that users can work on different aspects of a spreadsheet in a modular way. For example, aspects can be defined in order to introduce new business rules to an existing spreadsheet, or to manipulate the spreadsheet data to be ported to another system. Aspects are defined as aspect-oriented program specifications that are dynamically woven into the underlying spreadsheet by an aspect weaver. In this aspect-oriented style of spreadsheet development, differentusers develop,orreuse,aspects withoutaddingintrusive code to the original spreadsheet. Such code is added/executed by the spreadsheet weaving mechanism proposed in this paper.

Feature Nets: behavioural modelling of software product lines

Software product lines (SPL) are diverse systems that are developed using a dual engineering process: (a)family engineering defines the commonality and variability among all members of the SPL, and (b) application engineering derives specific products based on the common foundation combined with a variable selection of features. The number of derivable products in an SPL can thus be exponential in the number of features. This inherent complexity poses two main challenges when it comes to modelling: Firstly, the formalism used for modelling SPLs needs to be modular and scalable. Secondly, it should ensure that all products behave correctly by providing the ability to analyse and verify complex models efficiently. In this paper we propose to integrate an established modelling formalism (Petri nets) with the domain of software product line engineering. To this end we extend Petri nets to Feature Nets. While Petri nets provide a framework for formally modelling and verifying single software systems, Feature Nets offer the same sort of benefits for software product lines. We show how SPLs can be modelled in an incremental, modular fashion using Feature Nets, provide a Feature Nets variant that supports modelling dynamic SPLs, and propose an analysis method for SPL modelled as Feature Nets. By facilitating the construction of a single model that includes the various behaviours exhibited by the products in an SPL, we make a significant step towards efficient and practical quality assurance methods for software product lines.