Europe’s most wanted? Recalibrating Trust in the European Arrest Warrant System. CEPS Paper Liberty and Security in Europe 55/21 March 2013

This paper assesses the uses and misuses in the application of the European Arrest Warrant (EAW) system in the European Union. It examines the main quantitative results of this extradition system achieved between 2005 and 2011 on the basis of the existing statistical knowledge on its implementation at EU official levels. The EAW has been anchored in a high level of ‘mutual trust’ between the participating states’ criminal justice regimes and authorities. This reciprocal confidence, however, has been subject to an increasing number of challenges resulting from its practical application, presenting a dual conundrum: 1. Principle of proportionality: Who are the competent judicial authorities cooperating with each other and ensuring that there are sufficient impartial controls over the necessity and proportionality of the decisions on the issuing and execution of EAWs? 2. Principle of division of powers: How can criminal justice authorities be expected to handle different criminal judicial traditions in what is supposed to constitute a ‘serious’ or ‘minor’ crime in their respective legal settings and ‘who’ is ultimately to determine (divorced from political considerations) when is it duly justified to make the EAW system operational? It is argued that the next generation of the EU’s criminal justice cooperation and the EAW need to recognise and acknowledge that the mutual trust premise upon which the European system has been built so far is no longer viable without devising new EU policy stakeholders’ structures and evaluation mechanisms. These should allow for the recalibration of mutual trust and mistrust in EU justice systems in light of the experiences of the criminal justice actors and practitioners having a stake in putting the EAW into daily effect. Such a ‘bottom-up approach’ should be backed up with the best impartial and objective evaluation, an improved system of statistical collection and an independent qualitative assessment of its implementation. This should be placed as the central axis of a renewed EAW framework which should seek to better ensure the accountability, impartial (EU-led) scrutiny and transparency of member states’ application of the EAW in light of the general principles and fundamental rights constituting the foundations of the European system of criminal justice cooperation.

Miocardiopatia arritmogénica do ventrículo direito : uma doença rara e um doente peculiar

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Sistemas duplos renais : revisão sistemática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Rethinking the Attractiveness of EU Labour Immigration Policies: Comparative perspectives on the EU, the US, Canada and beyond

Is Europe's immigration policy attractive? One of the priorities driving current EU debates on labour immigration policies is the perceived need to boost Europe's attractiveness vis-á-vis 'talented' and 'highly skilled' immigrants. The EU sees itself playing a role in persuading immigrants to choose Europe over other competing destinations, such as the US or Canada. This book critically examines the determinants and challenges characterising discussions focused on the attractiveness of labour migration policies in the EU as well as other international settings. It calls for re-thinking some of the most commonly held premises and assumptions underlying the narratives of ‘attractiveness’ and ‘global competition for talent’ in migration policy debates. How can an immigration policy, in fact, be made to be ‘attractive’ and what are the incentives at play (if any)? A multidisciplinary team of leading scholars and experts in migration studies address the main issues and challenges related to the role played by rights and discrimination, qualifications and skills, and matching demand and supply in needs-based migration policies. The experiences in other jurisdictions such as South America, Canada and the United States are also covered: Are these countries indeed so ‘attractive’ and ‘competitive’, and if so what makes them more attractive than the EU? On the basis of the discussions and findings presented across the various contributions, the book identifies a number of priorities for policy formulation and design in the next generation of EU labour migration policies. In particular, it highlights important initiatives that the new European Commission should focus on in the years to come.

Rule-Makers or Rule-Takers? Exploring the Transatlantic Trade and Investment Partnership

The Transatlantic Trade and Investment Partnership (TTIP) is an effort by the United States and the European Union to reposition themselves for a world of diffuse economic power and intensified global competition. It is a next-generation economic negotiation that breaks the mould of traditional trade agreements. At the heart of the ongoing talks is the question whether and in which areas the two major democratic actors in the global economy can address costly frictions generated by their deep commercial integration by aligning rules and other instruments. The aim is to reduce duplication in various ways in areas where levels of regulatory protection are equivalent as well as to foster wide-ranging regulatory cooperation and set a benchmark for high-quality global norms. In this volume, European and American experts explain the economic context of TTIP and its geopolitical implications, and then explore the challenges and consequences of US-EU negotiations across numerous sensitive areas, ranging from food safety and public procurement to economic and regulatory assessments of technical barriers to trade, automotive, chemicals, energy, services, investor-state dispute settlement mechanisms and regulatory cooperation. Their insights cut through the confusion and tremendous public controversies now swirling around TTIP, and help decision-makers understand how the United States and the European Union can remain rule-makers rather than rule-takers in a globalising world in which their relative influence is waning.

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Hyperosmotic stress memory in Arabidopsis is mediated by distinct epigenetically labile sites in the genome and is restricted in the male germline by DNA glycosylase activity

Inducible epigenetic changes in eukaryotes are believed to enable rapid adaptation to environmental fluctuations. We have found distinct regions of the Arabidopsis genome that are susceptible to DNA (de)methylation in response to hyperosmotic stress. The stress-induced epigenetic changes are associated with conditionally heritable adaptive phenotypic stress responses. However, these stress responses are primarily transmitted to the next generation through the female lineage due to widespread DNA glycosylase activity in the male germline, and extensively reset in the absence of stress. Using the CNI1/ATL31 locus as an example, we demonstrate that epigenetically targeted sequences function as distantly-acting control elements of antisense long non-coding RNAs, which in turn regulate targeted gene expression in response to stress. Collectively, our findings reveal that plants use a highly dynamic maternal 'short-term stress memory' with which to respond to adverse external conditions. This transient memory relies on the DNA methylation machinery and associated transcriptional changes to extend the phenotypic plasticity accessible to the immediate offspring.

A desregulação da homeostase do ferro: base molecular e patologias associadas

A homeostase do ferro requer um rigoroso processo de regulação, uma vez que este é um elemento essencial para alguns dos mecanismos celulares básicos mas, quando se encontra em excesso, origina profundos danos celulares e falha de órgãos. Dado que o organismo humano não possui um mecanismo ativo de excreção de ferro, é essencial que a sua homeostase seja estabelecida através de uma estreita comunicação entre os locais de absorção, utilização e armazenamento. Esta interligação é conseguida, essencialmente, através da ação de uma hormona circulante, a hepcidina. A hepcidina é sintetizada ao nível dos hepatócitos do fígado, sendo a sua expressão aumentada pelos níveis de ferro e inflamação e suprimida pela eritropoiese e hipoxia. A hepcidina regula negativamente a absorção duodenal do ferro proveniente da alimentação, a libertação pelos macrófagos do ferro resultante da fagocitose dos glóbulos vermelhos senescentes, assim como a libertação do ferro armazenado nos hepatócitos. A hemocromatose hereditátria (HH) do tipo 1 é uma doença de transmissão autossómica recessiva associada a mutações no gene HFE (p.Cys282Tyr e p.His63Asp). É a patologia humana mais comum de sobrecarga primária em ferro, apresenta penetrância incompleta, e é um dos distúrbios genéticos mais frequentes em caucasianos de ascendência Norte-Europeia. Na hemocromatose, apesar de haver um excesso de ferro no organismo, este facto não é refletido no nível de expressão da hormona hepcidina (cujos níveis deveriam aumentar). Pelo contrário, o nível de expressão da hepcidina encontra-se diminuído o que perpetua a constante absorção do ferro a nível duodenal. Os sintomas associados à doença iniciam-se geralmente na meia-idade e começam por consistir em sintomas gerais de fadiga e dores articulares. No entanto, a progressiva acumulação do ferro em vários órgãos (tais como fígado, coração e pâncreas) provoca aí graves danos, tais como cirrose, carcinoma hepatocelular, cardiomiopatias e diabetes. Para além da HH do tipo 1, podem ocorrer outros tipos de hemocromatose por mutações noutros genes relacionados com o metabolismo do ferro (tais como TFR2, HJV, HAMP, SLC40A1, etc). Mutações em genes como HAMP e HJV associam-se a hemocromatoses mais graves, de início ainda na juventude (hemocromatose juvenil). A implementação no nosso laboratório da nova metodologia de Next-Generation Sequencing permitiu-nos realizar a pesquisa de variantes simultaneamente em 6 genes relacionados com o metabolismo do ferro, em 88 doentes com fenótipo de hemocromatose hereditária não-clássica. Foram identificadas 54 variantes diferentes sendo algumas delas novas. Estudos in silico e estudos funcionais in vitro (em linhas celulares) permitiram-nos comprovar a patogenicidade de algumas das variantes novas e compreender os mecanismos moleculares subjacentes ao desenvolvimento da sobrecarga em ferro. Pelo contrário, no lado oposto do espetro das patologias relacionadas com o ferro, encontram-se as anemias por falta de ferro (anemias ferropénicas). A Organização Mundial de Saúde define anemia quando os níveis de hemoglobina no sangue são menores do que 12 g/dL na Mulher e 13 g/dL no Homem. A hemoglobina é a proteína existente nos glóbulos vermelhos do sangue, responsável pelo transporte de oxigénio no organismo, e cuja molécula é um tetrâmero formado por 4 cadeias polipeptídicas (as globinas) e 4 grupos heme que contêm 4 átomos de ferro. A falta de ferro impede que se formem as moléculas de hemoglobina a níveis normais em cerca de 20% da população portuguesa e isso é devido a carências alimentares ou a dificuldades na absorção do ferro proveniente da alimentação. Entre os fatores genéticos moduladores desta última situação parecem estar algumas variantes polimórficas no gene TMPRSS6, codificante da proteína Matriptase-2, um dos agentes envolvidos na regulação da expressão da hepcidina. Por outro lado, mutações neste gene dão origem a anemias ferropénicas graves, refratárias ao tratamento oral com ferro (Iron Refractory Iron Deficiency Anaemia - IRIDA). As Hemoglobinopatias são outro tipo de anemia hereditária. Estas não estão relacionadas com o défice de ferro mas sim com defeitos nas cadeias globínicas, constituintes da hemoglobina (α2β2). As hemoglobinopatias que estão relacionadas com um problema quantitativo, ou seja quando há ausência ou diminuição de síntese de uma cadeia globínica, denominam-se talassémias: beta-talassémia, alfa-talassémia, delta-talassémia, etc, consoante o gene afetado. Por outro lado, quando o problema é de carácter qualitativo, ou seja ocorre a síntese de uma cadeia globínica estruturalmente anómala, esta é denominada uma variante de hemoglobina. Enquadra-se neste último grupo a Anemia das Células Falciformes ou Drepanocitose. As hemoglobinopatias são das patologias genéticas mais frequentes no mundo, sendo que nalguns locais são um grave problema de saúde pública. Em Portugal foram realizados estudos epidemiológicos que permitiram determinar a frequência de portadores na população e foi implementado um programa de prevenção.

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Edge caching with mobility prediction in virtualized LTE mobile networks

Abstract Mobile Edge Computing enables the deployment of services, applications, content storage and processing in close proximity to mobile end users. This highly distributed computing environment can be used to provide ultra-low latency, precise positional awareness and agile applications, which could significantly improve user experience. In order to achieve this, it is necessary to consider next-generation paradigms such as Information-Centric Networking and Cloud Computing, integrated with the upcoming 5th Generation networking access. A cohesive end-to-end architecture is proposed, fully exploiting Information-Centric Networking together with the Mobile Follow-Me Cloud approach, for enhancing the migration of content-caches located at the edge of cloudified mobile networks. The chosen content-relocation algorithm attains content-availability improvements of up to 500 when a mobile user performs a request and compared against other existing solutions. The performed evaluation considers a realistic core-network, with functional and non-functional measurements, including the deployment of the entire system, computation and allocation/migration of resources. The achieved results reveal that the proposed architecture is beneficial not only from the users’ perspective but also from the providers point-of-view, which may be able to optimize their resources and reach significant bandwidth savings.

Intergenerational Transfer of Family Firm Control: Discount Expectations of Potential Successors

Building on institutional theory and family sociology literature we explore the logics that underlie the formation of transaction price expectations related to the intergenerational transfer of corporate ownership in private family firms. By probing a sample of 3'487 students with family business background from 20 countries we show that next generation family members expect to receive a 56.58% discount in comparison to some nonfamily buyer (i.e. the family discount) when taking over the parent's firm. We also show that the logic underlying the formation of family discount expectations is characterized by parental altruism, filial reciprocity, filial decency and parental inducement. These norms embrace both the family and market logics and accommodate the duties and demands of children and parents in determining a fair transfer price. These findings are important for institutional theory as well as for family business and entrepreneurial exit literatures.

Highly accurate RNA and DNA sequencing: Application to longstanding questions in aging and cancer

Thesis (Ph.D.)--University of Washington, 2016-06

Towards evidence-based guidelines for wise use of computers by children

This paper argues for the systematic development and presentation of evidence-based guidelines for appropriate use of computers by children. The currently available guidelines are characterised and a proposed conceptual model presented. Five principles are presented as a foundation to the guidelines. The paper concludes with a framework for the guidelines, key evidence for and against guidelines, and gaps in the available evidence, with the aim of facilitating further discussion. Relevance to industry The current generation of children in affluent countries will typically have over 10 years of computer experience before they enter the workforce. Consequently, the primary prevention of computer-related health disorders and the development of good productivity skills for the next generation of workers needs to occur during childhood. (c) 2006 Elsevier B.V. All rights reserved.

Supporting interoperable interpolation: the INTAMAP approach

In many Environmental Information Systems the actual observations arise from a discrete monitoring network which might be rather heterogeneous in both location and types of measurements made. In this paper we describe the architecture and infrastructure for a system, developed as part of the EU FP6 funded INTAMAP project, to provide a service oriented solution that allows the construction of an interoperable, automatic, interpolation system. This system will be based on the Open Geospatial Consortium’s Web Feature Service (WFS) standard. The essence of our approach is to extend the GML3.1 observation feature to include information about the sensor using SensorML, and to further extend this to incorporate observation error characteristics. Our extended WFS will accept observations, and will store them in a database. The observations will be passed to our R-based interpolation server, which will use a range of methods, including a novel sparse, sequential kriging method (only briefly described here) to produce an internal representation of the interpolated field resulting from the observations currently uploaded to the system. The extended WFS will then accept queries, such as ‘What is the probability distribution of the desired variable at a given point’, ‘What is the mean value over a given region’, or ‘What is the probability of exceeding a certain threshold at a given location’. To support information-rich transfer of complex and uncertain predictions we are developing schema to represent probabilistic results in a GML3.1 (object-property) style. The system will also offer more easily accessible Web Map Service and Web Coverage Service interfaces to allow users to access the system at the level of complexity they require for their specific application. Such a system will offer a very valuable contribution to the next generation of Environmental Information Systems in the context of real time mapping for monitoring and security, particularly for systems that employ a service oriented architecture.

Traffic based energy consumption optimisation to improve the lifetime and performance of ad hoc wireless sensor networks

Ad hoc wireless sensor networks (WSNs) are formed from self-organising configurations of distributed, energy constrained, autonomous sensor nodes. The service lifetime of such sensor nodes depends on the power supply and the energy consumption, which is typically dominated by the communication subsystem. One of the key challenges in unlocking the potential of such data gathering sensor networks is conserving energy so as to maximize their post deployment active lifetime. This thesis described the research carried on the continual development of the novel energy efficient Optimised grids algorithm that increases the WSNs lifetime and improves on the QoS parameters yielding higher throughput, lower latency and jitter for next generation of WSNs. Based on the range and traffic relationship the novel Optimised grids algorithm provides a robust traffic dependent energy efficient grid size that minimises the cluster head energy consumption in each grid and balances the energy use throughout the network. Efficient spatial reusability allows the novel Optimised grids algorithm improves on network QoS parameters. The most important advantage of this model is that it can be applied to all one and two dimensional traffic scenarios where the traffic load may fluctuate due to sensor activities. During traffic fluctuations the novel Optimised grids algorithm can be used to re-optimise the wireless sensor network to bring further benefits in energy reduction and improvement in QoS parameters. As the idle energy becomes dominant at lower traffic loads, the new Sleep Optimised grids model incorporates the sleep energy and idle energy duty cycles that can be implemented to achieve further network lifetime gains in all wireless sensor network models. Another key advantage of the novel Optimised grids algorithm is that it can be implemented with existing energy saving protocols like GAF, LEACH, SMAC and TMAC to further enhance the network lifetimes and improve on QoS parameters. The novel Optimised grids algorithm does not interfere with these protocols, but creates an overlay to optimise the grids sizes and hence transmission range of wireless sensor nodes.