Contributo para o desenvolvimento de um Instrumento de Investigação Neuropsicológica

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

On Learning Counting Functions With Queries

We investigate the problem of learning disjunctions of counting functions, which are general cases of parity and modulo functions, with equivalence and membership queries. We prove that, for any prime number p, the class of disjunctions of integer-weighted counting functions with modulus p over the domain Znq (or Zn) for any given integer q ≥ 2 is polynomial time learnable using at most n + 1 equivalence queries, where the hypotheses issued by the learner are disjunctions of at most n counting functions with weights from Zp. The result is obtained through learning linear systems over an arbitrary field. In general a counting function may have a composite modulus. We prove that, for any given integer q ≥ 2, over the domain Zn2, the class of read-once disjunctions of Boolean-weighted counting functions with modulus q is polynomial time learnable with only one equivalence query, and the class of disjunctions of log log n Boolean-weighted counting functions with modulus q is polynomial time learnable. Finally, we present an algorithm for learning graph-based counting functions.

Trajectory Guided Tracking and Recognition of Actions

A combined 2D, 3D approach is presented that allows for robust tracking of moving people and recognition of actions. It is assumed that the system observes multiple moving objects via a single, uncalibrated video camera. Low-level features are often insufficient for detection, segmentation, and tracking of non-rigid moving objects. Therefore, an improved mechanism is proposed that integrates low-level (image processing), mid-level (recursive 3D trajectory estimation), and high-level (action recognition) processes. A novel extended Kalman filter formulation is used in estimating the relative 3D motion trajectories up to a scale factor. The recursive estimation process provides a prediction and error measure that is exploited in higher-level stages of action recognition. Conversely, higher-level mechanisms provide feedback that allows the system to reliably segment and maintain the tracking of moving objects before, during, and after occlusion. The 3D trajectory, occlusion, and segmentation information are utilized in extracting stabilized views of the moving object that are then used as input to action recognition modules. Trajectory-guided recognition (TGR) is proposed as a new and efficient method for adaptive classification of action. The TGR approach is demonstrated using "motion history images" that are then recognized via a mixture-of-Gaussians classifier. The system was tested in recognizing various dynamic human outdoor activities: running, walking, roller blading, and cycling. Experiments with real and synthetic data sets are used to evaluate stability of the trajectory estimator with respect to noise.

NETEMBED: A Network Resource Mapping Service for Distributed Applications

Emerging configurable infrastructures such as large-scale overlays and grids, distributed testbeds, and sensor networks comprise diverse sets of available computing resources (e.g., CPU and OS capabilities and memory constraints) and network conditions (e.g., link delay, bandwidth, loss rate, and jitter) whose characteristics are both complex and time-varying. At the same time, distributed applications to be deployed on these infrastructures exhibit increasingly complex constraints and requirements on resources they wish to utilize. Examples include selecting nodes and links to schedule an overlay multicast file transfer across the Grid, or embedding a network experiment with specific resource constraints in a distributed testbed such as PlanetLab. Thus, a common problem facing the efficient deployment of distributed applications on these infrastructures is that of "mapping" application-level requirements onto the network in such a manner that the requirements of the application are realized, assuming that the underlying characteristics of the network are known. We refer to this problem as the network embedding problem. In this paper, we propose a new approach to tackle this combinatorially-hard problem. Thanks to a number of heuristics, our approach greatly improves performance and scalability over previously existing techniques. It does so by pruning large portions of the search space without overlooking any valid embedding. We present a construction that allows a compact representation of candidate embeddings, which is maintained by carefully controlling the order via which candidate mappings are inserted and invalid mappings are removed. We present an implementation of our proposed technique, which we call NETEMBED – a service that identify feasible mappings of a virtual network configuration (the query network) to an existing real infrastructure or testbed (the hosting network). We present results of extensive performance evaluation experiments of NETEMBED using several combinations of real and synthetic network topologies. Our results show that our NETEMBED service is quite effective in identifying one (or all) possible embeddings for quite sizable queries and hosting networks – much larger than what any of the existing techniques or services are able to handle.

FLT3-driven redox signalling in acute myeloid leukaemia

Acute myeloid leukaemia refers to cancer of the blood and bone marrow characterised by the rapid expansion of immature blasts of the myeloid lineage. The aberrant proliferation of these blasts interferes with normal haematopoiesis, resulting in symptoms such as anaemia, poor coagulation and infections. The molecular mechanisms underpinning acute myeloid leukaemia are multi-faceted and complex, with a range of diverse genetic and cytogenetic abnormalities giving rise to the acute myeloid leukaemia phenotype. Amongst the most common causative factors are mutations of the FLT3 gene, which codes for a growth factor receptor tyrosine kinase required by developing haematopoietic cells. Disruptions to this gene can result in constitutively active FLT3, driving the de-regulated proliferation of undifferentiated precursor blasts. FLT3-targeted drugs provide the opportunity to inhibit this oncogenic receptor, but over time can give rise to resistance within the blast population. The identification of targetable components of the FLT3 signalling pathway may allow for combination therapies to be used to impede the emergence of resistance. However, the intracellular signal transduction pathway of FLT3 is relatively obscure. The objective of this study is to further elucidate this pathway, with particular focus on the redox signalling element which is thought to be involved. Signalling via reactive oxygen species is becoming increasingly recognised as a crucial aspect of physiological and pathological processes within the cell. The first part of this study examined the effects of NADPH oxidase-derived reactive oxygen species on the tyrosine phosphorylation levels of acute myeloid leukaemia cell lines. Using two-dimensional phosphotyrosine immunoblotting, a range of proteins were identified as undergoing tyrosine phosphorylation in response to NADPH oxidase activity. Ezrin, a cytoskeletal regulatory protein and substrate of Src kinase, was selected for further study. The next part of this study established that NADPH oxidase is subject to regulation by FLT3. Both wild type and oncogenic FLT3 signalling were shown to affect the expression of a key NADPH oxidase subunit, p22phox, and FLT3 was also demonstrated to drive intracellular reactive oxygen species production. The NADPH oxidase target protein, Ezrin, undergoes phosphorylation on two tyrosine residues downstream of FLT3 signalling, an effect which was shown to be p22phox-dependent and which was attributed to the redox regulation of Src. The cytoskeletal associations of Ezrin and its established role in metastasis prompted the investigation of the effects of FLT3 and NADPH oxidase activity on the migration of acute myeloid leukaemia cell lines. It was found that inhibition of either FLT3 or NADPH oxidase negatively impacted on the motility of acute myeloid leukaemia cells. The final part of this study focused on the relationship between FLT3 signalling and phosphatase activity. It was determined, using phosphatase expression profiling and real-time PCR, that several phosphatases are subject to regulation at the levels of transcription and post-translational modification downstream of oncogenic FLT3 activity. In summary, this study demonstrates that FLT3 signal transduction utilises a NADPH oxidase-dependent redox element, which affects Src kinase, and modulates leukaemic cell migration through Ezrin. Furthermore, the expression and activity of several phosphatases is tightly linked to FLT3 signalling. This work reveals novel components of the FLT3 signalling cascade and indicates a range of potential therapeutic targets.

The lived experience of Irish diocesan priests. A qualitative study of clerical identity, obedience and celibacy.

The main aim of this thesis is to document and explore the lived experience of Irish diocesan priests and former priests, in order to explore the reality of diocesan priesthood in contemporary Ireland, and to investigate how, if at all, diocesan priesthood has changed in Ireland during the past fifty years. It sought to do this by interrogating the stories of thirty-three diocesan priests and former priests, and by placing their individual stories within the broader context of Irish society and the Catholic Church, during the fifty-year period, 1962–2012. The research focused on three core areas of priesthood – identity, obedience, and celibacy – and it addressed the following questions. First, how do Irish diocesan priests understand their priesthood and how has this understanding changed over time, if at all? I will argue that three paradigms of priesthood co-exist in the contemporary Irish Church, and that each of these models corresponds with a distinct period in contemporary Irish Church history. I will also demonstrate the existence of underlying similarities in the cultural practice of priesthood that transcend the different generations of priests. Second, how do Irish diocesan priests negotiate their priesthood within a large and complex institution? My study suggests that Irish diocesan priests are typically loyal and obedient. However, they are not necessarily subservient. Third, how do Irish diocesan priests understand and experience celibacy in their day-to-day lives? My study demonstrates that celibacy is typically understood and experienced along a continuum, ranging from total acceptance to total rejection, with most priests somewhere in between. Fourth, I will argue that while priests are experiencing many difficulties in their lives, there is insufficient evidence from the present study to indicate they are experiencing a crisis.

Characterisation and application of fruit by-products as novel ingredients in gluten-free products

The physicochemical and nutritional properties of two fruit by-products were initially studied. Apple pomace (AP) contained a high level of fibre and pectin. The isolated AP pectin had a high level of methylation which developed viscous pastes. Orange pomace also had high levels of fibre and pectin, and it was an abundant source of minerals such as potassium and magnesium. Due to the fibrous properties of orange pomace flour, proofing and water addition were studied in a bread formulation. When added at levels greater than 6%, the loaf volume decreased. An optimised formulation and proofing time was derived using the optimisation tool; these consisted of 5.5% orange pomace, 94.6% water inclusion and with 49 minutes proofing. These optimised parameters doubled the total dietary fibre content of the bread compared to the original control. Pasting results showed how orange pomace inclusions reduced the final viscosity of the batter, reducing the occurrence of starch gelatinisation. Rheological properties i.e. the storage modulus (G') and complex modulus (G*) increased in the orange pomace batter compared to the control batter. This demonstrates how the orange pomace as an ingredient improved the robustness of the formulation. Sensory panellists scored the orange pomace bread comparably to the control bread. Milled apple pomace was studied as a potential novel ingredient in an extruded snack. Parameters studied included apple pomace addition, die head temperature and screw speed. As screw speed increased the favourable extrudate characteristics such as radical expansion ratio, porosity and specific volume decreased. The inclusion of apple pomace had a negative effect on extrudate characteristics at levels greater than 8% addition. Including apple pomace reduced the hardness and increased the crispiness of the snack. The optimised and validated formulation and extrusion process contained the following parameters: 7.7% apple pomace, 150°C die head temperature and a screw speed of 69 rpm.

"Ladyes, damesels, and jantilwomen": female autonomy and authority in Sir Thomas Malory's Morte Darthur

Popular medieval English romances were composed and received within the social consciousness of a distinctly patriarchal culture. This study examines the way in which the dynamic of these texts is significantly influenced by the consequences of female endeavour, in the context of an autonomous feminine presence in both the real and imagined worlds of medieval England, and the authority with which this is presented in various narratives, with a particular focus on Sir Thomas Malory’s Morte Darthur. Chapter One of this study establishes the social and economic positioning of the female in fifteenth-century England, and her capacity for literary engagement; I will then apply this model of female autonomy and authority to a wider discussion of texts contemporary with Malory in Chapters Two and Three, in anticipation of a more detailed study of Le Morte Darthur in Chapters Four and Five. My research explores the female presence and influence in these texts according to certain types: namely the lover, the victim, the ruler, and the temptress. In the case of Malory, the crux of my observations centres on the paradox of the capacity for power in perceived vulnerability, incorporating the presentation of women in this patriarchal culture as being vulnerable and in need of protection, while simultaneously acting as a significant threat to chivalric society by manipulating this apparent fragility, to the detriment of the chivalric knight. In this sense, women can be perceived as being an architect of the romance world, while simultaneously acting as its saboteur. In essence, this study offers an innovative interpretation of female autonomy and authority in medieval romance, presenting an exploration of the physical, intellectual, and emotional placement of women in both the historical and literary worlds of fifteenth-century England, while examining the implications of female conduct on Malory’s Arthurian society.

Practice-based personas: integrated user and practice models

Practices are routinised behaviours with social and material components and complex relationships over space and time. Practice-based design goes beyond interaction design to consider how these components and their relationships impact on the formation and enactment of a practice, where technology is just one part of the practice. Though situated user-centred design methods such as participatory design are employed for the design of practice, demand exists for additional methods and tools in this area. This paper introduces practice-based personas as an extension of the persona approach popular in interaction design, and demonstrates how a set of practice-based personas was developed for a given domain – academic practice. The three practice-based personas developed here are linked to a catalogue of forty practices, offering designers both a user perspective and a practice perspective when designing for the domain.

Totality of experience: sound, music and mythology in Gus Van Sant’s “Death Quartet”

Reflecting on Gus Van Sant’s films Gerry (2003) Elephant (2004) and Last Days (2005), the director’s long-term sound-designer Leslie Shatz observed that “You have to get into the totality of the experience and not just the dialogue”. Shatz’s comment expresses something fundamental about the experimental approach to cinema and to soundscapes undertaken by Van Sant in these three films, unofficially known as the “Death Trilogy”. This thesis contends that Van Sant makes deliberate aesthetic choices which do indicate a distinctly “auteurist” leaning. However, I also argue that intertextual elements, prior knowledge, and audience participation in meaningmaking enhance the experience of, and reveal the nuances in, the soundtracks themselves. This thesis aims to contribute to a growing body of work within filmmusic scholarship concerned with resisting a traditional bias in the field: that film music should be understood as a means of characterisation and as emotional signifier. The films of the “Death Quartet”, which includes Paranoid Park (2007), I believe, offer fertile ground on which to explore these new approaches. It is my contention that these films deconstruct the traditional approach to soundtracking and the relationship between soundtrack and character, and that only an approach sensitive to the aesthetic and philosophical functions of music and sound can adequately acknowledge their unique cinematic qualities.

Developing executive capability — banking and beyond

The transition to becoming a leader is perhaps the least understood and most difficult in business. This Portfolio of Exploration examines the development of conscious awareness and meaning complexity as key transformational requirements to operate competently at leadership level and to succeed in a work environment characterised by change and complexity. It recognises that developing executive leadership capability is not just an issue of personality increasing what we know or expertise. It requires development of complexity in terms of how we know ourselves, relate to others, construe leadership and organisation, problem solve in business and understand the world as a whole. The exploration is grounded in the theory of adult mental development as outlined by Robert Kegan (1982, 1994) and in his collaborations with Lisa Laskow Lahey (2001, 2009). The theory points to levels of consciousness which impact on how we make meaning of and experience the world around us and respond to it. Critically it also points to transformational processes which enable us to evolve how we make meaning of our world as a means to close the mismatch between the demands of this world and our ability to cope. The exploration is laid out in three stages. Using Kegan’s (1982, 1994) theory as a framework it begins with a reflection of my career to surface how I made meaning of banking, management and subsequently leadership. In stage two I engage with a range of source thinkers in the areas of leadership, decision making, business, organisation, growth and complexity in a transformational process of developing greater conscious and complex understanding of organisational leadership (also recognising ever increasing complexity in the world). Finally, in stage three, I explore how qualitative changes as a result of this transformational effort have benefitted my professional, leadership and organisational capabilities.

Antibiotic resistance-the need for global solutions.

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

The past, present, and future of human centromere genomics.

The centromere is the chromosomal locus essential for chromosome inheritance and genome stability. Human centromeres are located at repetitive alpha satellite DNA arrays that compose approximately 5% of the genome. Contiguous alpha satellite DNA sequence is absent from the assembled reference genome, limiting current understanding of centromere organization and function. Here, we review the progress in centromere genomics spanning the discovery of the sequence to its molecular characterization and the work done during the Human Genome Project era to elucidate alpha satellite structure and sequence variation. We discuss exciting recent advances in alpha satellite sequence assembly that have provided important insight into the abundance and complex organization of this sequence on human chromosomes. In light of these new findings, we offer perspectives for future studies of human centromere assembly and function.

Synchrony between sensory and cognitive networks is associated with subclinical variation in autistic traits

© 2015 Young, Smith, Coutlee and Huettel.Individuals with autistic spectrum disorders exhibit distinct personality traits linked to attentional, social, and affective functions, and those traits are expressed with varying levels of severity in the neurotypical and subclinical population. Variation in autistic traits has been linked to reduced functional and structural connectivity (i.e., underconnectivity, or reduced synchrony) with neural networks modulated by attentional, social, and affective functions. Yet, it remains unclear whether reduced synchrony between these neural networks contributes to autistic traits. To investigate this issue, we used functional magnetic resonance imaging to record brain activation while neurotypical participants who varied in their subclinical scores on the Autism-Spectrum Quotient (AQ) viewed alternating blocks of social and nonsocial stimuli (i.e., images of faces and of landscape scenes). We used independent component analysis (ICA) combined with a spatiotemporal regression to quantify synchrony between neural networks. Our results indicated that decreased synchrony between the executive control network (ECN) and a face-scene network (FSN) predicted higher scores on the AQ. This relationship was not explained by individual differences in head motion, preferences for faces, or personality variables related to social cognition. Our findings build on clinical reports by demonstrating that reduced synchrony between distinct neural networks contributes to a range of subclinical autistic traits.

Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes. In order to identify quantitative trait loci (QTLs) that influence the binding of a transcription factor in humans, we measured binding of the multifunctional transcription and chromatin factor CTCF in 51 HapMap cell lines. We identified thousands of QTLs in which genotype differences were associated with differences in CTCF binding strength, hundreds of them confirmed by directly observable allele-specific binding bias. The majority of QTLs were either within 1 kb of the CTCF binding motif, or in linkage disequilibrium with a variant within 1 kb of the motif. On the X chromosome we observed three classes of binding sites: a minority class bound only to the active copy of the X chromosome, the majority class bound to both the active and inactive X, and a small set of female-specific CTCF sites associated with two non-coding RNA genes. In sum, our data reveal extensive genetic effects on CTCF binding, both direct and indirect, and identify a diversity of patterns of CTCF binding on the X chromosome.