Dissertations / Theses on the topic 'Origin'

Origin Unknown is a 15-minute, single-movement work for orchestra. The piece maintains an understated, meditative quality throughout, and adheres to the principle of perpetual variation of a very limited amount of material. The form of the work is process-oriented: the music unfolds slowly, according to a consistent, yet flexible, dialectic. Two basic materials—one that is tonally stable, and another that modulates—alternate throughout the piece and form a harmonic backdrop. A type of respiration occurs, as the lengths of the stable sections expand and contract, while the modulatory passages get progressively longer each time they recur. A surface layer of triplet melodies is superimposed onto this background structure, forming a subtle counterpoint. Percussive, bell-like sounds (glockenspiel, vibraphone, celesta, harp, and piano) articulate most of the pitches in the work. As these sounds decay, they often meld into a wind or string timbre which sustains the pitch after its percussive attack has faded. Eventually, these sustained sounds fade out, just as their percussive attack did, but at a slower rate with a long diminuendo. A regular rotation of the percussive timbres produces a kaleidescopic effect, while the wind and string choirs often alternate in an antiphonal fashion. As the alternating wind and string passages expand and contract in length, the orchestration of the piece effects a "respiration" in the timbral domain analogous to that built into the harmonic structure of the piece.

The twentieth century has seen a continuous process of redefinition of scientific understanding of the process by which life appeared on planet earth, and the emergence of a trans-disciplinary scientific field concerned with the question of the origin of life. The thesis explores the scientific, historical and conceptual issues relevant to this research field, and provides a novel analysis of the interrelated development of theories and experiments within it. The thesis will argue for a discovery-driven and technology-driven view of research into the origins of life, rather than a primarily hypothesis-driven endeavour. The thesis will also explore the influence exerted on research into the origin of life by its prime financial backer - the United States government’s National Aeronautics and Space Administration (NASA). Lastly, the theory will present research into the origin of life as an indicator of more general trends in the natural and life sciences.

Many previous studies have examined the effects of goal attributes on subsequent behavior and performance, with consistently positive findings. However, there are few studies of goal processes, i.e., how reactions to goal origin and subsequent shifts in goal origin are exhibited in behavioral and subjective domains. The present research viewed reactions to goal origins (self-set or assigned) and to shifts in goal origin within a theory of personal control/psychological reactance. In addition, two individual difference constructs, locus of control and Type A Behavior Pattern, were measured to study their relationships with the dependent variables. A laboratory experiment was conducted to examine several hypotheses drawn from the psychological reactance literature concerning the joint effects of Initial Goal Origin and subsequent Shifted Goal Origin on subjective and behavioral responses. The subjective responses included task and performance satisfaction, goal acceptance, preferences for increasing employee self-control in the workplace, and preferred method of goal-setting. Behavioral measures included two different operational definitions of performance: quantity and goal attainment. The analyses revealed weak support for the hypotheses. The manipulation check composite revealed that the groups perceived the manipulations along the Initial Goal Origin dimension. There were statistically significant differences for goal acceptance, with the two shift groups displaying a crossover pattern between trial blocks. Simple interaction effect analyses conducted at each level of the Shifted Goal Origin factor revealed a statistically significant interaction between Initial Goal Origin and Trial Blocks for the Shift level only. Goal attainment scores revealed an apparently practical, yet statistically nonsignificant, effect for the three-way interaction of the manipulated factors over trial blocks. Moreover, the pattern of correlations between goals and performance reversed in the predicted direction over trial blocks for the two shift groups. However, there were no significant differences for the factors on the raw performance, satisfaction, or preference variables. The individual difference variables did not make a significant contribution to the prediction of the dependent variables after the effects of group membership were statistically controlled. The results are discussed in terms of the limitations of the method used, the weak support for the framework which guided the research, and implications for further research and implementation of goal-setting systems in organizations.
Ph. D.

Charles Darwin has achieved both notoriety and fame for his evolutionary ideas encapsulated principally in The Origin of Species and The Descent of Man. Although credited for much originality in his writings, Darwin's legacy borrowed extensively from many who had propounded similar speculations centuries before him. His naturalistic argument for origin and species reveals both logical and theological problems with his thesis, and further unavoidable ramifications. The contention is that even Darwin himself could not, and did not, live by the ideas he boldly espoused. His ideas, if true, would destroy the very basis upon which his thesis depended. His evolutionary paradigm had to take for granted a world he could give no account for. Yet his antipathy of Biblical Christianity, and its God, inspired him to pursue his personal naturalistic agenda with little regard to the logical consequences. Modern evolutionary science may look back today with pride on its founder, Charles Darwin, yet the problems which were intrinsic to his thesis remain unanswered yet.
Thesis (M.Th. (Dogmatics))--North-West University, Potchefstroom Campus, 2011.

The inflationary universe scenario provides an appealing explanation for the riddles of why the observed universe is so flat and isotropic, and it neatly provides a causal mechanism for generating the primordial inhomogeneities which seed the large-scale structure we observe today. However, the 01igin of inflation is still unclear, mainly since we have no compelling evidence for a pe1iod of inflation from M-theory. Moreover, whether inflation actually occurs within a given theory is known to depend strongly on the initial conditions. These conceptual problems of inflation are the driving force behind the research presented in this thesis. We study inflation driven by higher de1ivative quantum effects and show how theories of initial conditions may provide observational discriminants between different inflationary scenarios. First we consider scalar field inflation and develop the techniques to calculate c01Telators of physical observables on a spacelike surface directly from the Euclidean no boundary path integral. We perturbatively evaluate the path integral for metric fluctuations around both regular and singular instanton saddle points. The real-space Euclidean two-point correlator is analytically continued into the Lorentzian universe, where it describes the quantum mechanical vacuum fluctuations of the graviton field in the state described by no boundary initial conditions. Unlike the usual approach to inflationary perturbations, the Euclidean path integral unambiguously specifies the graviton propagators with no additional assumptions. From our results for the two-point c01Telation functions we deduce predictions for the cosmic microwave background (CMB) anisotropies and compare this with what is observed today. It is shown that the long wavelength gravity waves would allow us to probe the initial state, if there were sufficient curvature left in the present-day universe. The lack of compelling theoretical evidence casts doubt on the claim that the potential energy of a scalar field could be the 01igin of an inflationary pe1iod in the early universe. It is therefore of the utmost importance to study realisations of inflation which do not require fundamental scalar fields that emerge more naturally from fundamental physics. In the second part of this thesis we revive an old idea of Starobinsky in which inflation is driven by the trace anomaly of a large number of conformally coupled matter fields. We argue that in contrast to scalar field inflation, trace anomaly driven inflation has a sound motivation in particle physics. We include in our action higher derivative counterterms, which arise naturally in the renormalisation of the conformal field theory (CFf). We discuss in detail how correlators of observables should be obtained from the path integral in a higher derivative theory. It is emphasised that the final boundary condition on the fields in the path integral is crucial to extract correct predictions for observations. Using the AdS/CFf correspondence, we present the first calculation of scalar and tensor metric propagators for trace anomaly inflation, taking full account of the back-reaction of matter fields. It is found that the primordial inhomogeneities are naturally suppressed, provided there are suffiently many matter fields, and that the higher derivative terms can play an important role in further reducing the fluctuations to the level we observe. The non-local part of the matter effective action has the effect of strongly suppressing fluctuations on small scales. This suggests that any small-scale modifications to four dimensional Einstein gravity would be unobservable in the CMB, since matter fields would dominate the graviton propagator at the scales at which such modifications might be expected to become important. To illustrate this point we consider a Randall-Sundrum (RS) brane world analogue of trace anomaly driven inflation, in which our universe is regarded as a domain wall in five dimensional anti-de Sitter (AdS) space with a large N conformal field theory living on the wall. It is shown that the effects of the matter fields dominate the RS corrections, rendering them unobservable. This result is probably not restricted to trace anomaly driven inflation, since it is a consequence of the presence of a large number of matter fields. We return to the problem of initial conditions for inflation at the end of the thesis. We provide evidence that the no boundary path integral predicts the Lorentzian inflationary phase in trace anomaly driven inflation to occur by semiclassical tunnelling via a four sphere instanton.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O projeto de estudo em questÃo visa aprofundar-se na obra de Walter Benjamin, concentrando-se na idÃia delimiar como uma noÃÃo estruturante que perpassa as mÃltiplas fases de seu pensamento. O modo de alegorese presente e expressivo na escrita deste autor, onde se articula uma teoria das imagens dialÃticas, à importante para nossa interpretaÃÃo pois a prÃpria escrita benjaminiana apresenta-se como um medium- de-reflexÃo onde revela-se as suas concepÃÃes epistemolÃgicas acerca do carÃter da IdÃia, suas reflexÃes estÃticas e sua crÃtica de carÃter historiogrÃfico. Toda sua escrita que traz em si tais questÃes à a expressÃo e zona de limiar a respeito da relaÃÃo belo/verdade, forma/conteÃdo, linguagem/imagem, sensÃvel/inteligÃvel, tempo/histÃria. Sugere-se entÃo que a partir da relaÃÃo entre verdade e beleza, Benjamin desenvolve em sua crÃtica o conceito de sem-expressÃo, elemento este que desfaz a falsa totalidade da aparÃncia para revelar um fragmento verdadeiro do mundo, pela obra de arte, conectando a arte enquanto aparÃncia ao campo da verdade revelando-a como lei essencial para o pensamento. O trabalho propÃe-se a refletir, juntamente com essas questÃes, o vÃnculo entre o conceito de sem-expressÃo e o aspecto intrinsecamente fragmentÃrio do conhecimento histÃrico-linguÃstico deste pensador berlinense no intuito de apresentar nesta reflexÃo a forÃa fisiognÃmica da linguagem, ou seja, sua expressÃo imagÃtica na relaÃÃo entre sÃmbolo e alegoria que constituem um limiar de crÃtica imanente do conhecimento em Walter Benjamin.

The etymology of the business term dita, which survives in America and in Andalusia, is still considered unresolved in the online version of the dictionary of the Real Academia. Over a hundred years ago, Cuervo proposed an Italian origin, while Corominas later preferred a Catalan origin. In this article, I intend to show that the term indeed has Italian roots, but entered Spanish via Catalan. I will also argue that the hypotheses put forward by Cuervo and Corominas concerning the concrete word that served as a model were incorrect. The correct etymon is Italian detta, which in the Middle Ages referred to the words pronounced by a banker when transferring Money from one account to another.

From a developmental perspective, propositional logical reasoning has been often characterized either as the peak of cognitive development or as an innate property of human cognition. Our ignorance of the origin of logical thinking in part depends on its primary source of evidence. Overt linguistic logical behavior does not begin to arise before the second birthday. As a result, the first 2 years of human development remain completely uncharted by psychologists of logical reasoning. The aim of this dissertation is to contribute to the beginning of the exploration of preverbal logical abilities. We developed methodology based on entirely non-linguistic logical tasks, implicit measures of scene processing such as cumulative looking time in a violation of expectancy paradigm, and automatic eye-tracking procedures. The joint use of these techniques offers preliminary evidence that basic logical representations might be tracked at least from the beginning of the second year of life.
Desde una perspectiva del desarrollo, el razonamiento lógico proposicional se ha considerado como el cénit del desarrollo cognitivo o como una propiedad innata de la cognición humana. Nuestra ignorancia con respecto al origen del pensamiento lógico depende, en parte, de su fuente principal de evidencia. En efecto, el comportamiento lógico lingüístico no se hace evidente antes del segundo cumpleaños. Como resultado, los primeros dos años de desarrollo humano se mantienen completamente inexplorados para la psicología del razonamiento lógico. El objetivo de esta tesis es contribuir al inicio de la exploración de las capacidades lógicas preverbales. Para ello hemos desarrollado nuevos métodos basados en tareas lógicas completamente no lingüísticas, incluyendo medidas implícitas de procesamiento de escenas como el tiempo de mirada acumulado en un paradigma de violación de expectativas, así como procedimientos automáticos de captura de movimientos oculares (eye-tracking). El uso combinado de estas técnicas ofrece evidencia preliminar de que el rastro de las representaciones lógicas básicas podría remontarse al menos desde el comienzo del segundo año de vida.

Successful chromosome segregation is crucial for the survival of a cell and to avoid diseases such as cancer. Anaphase bridges are a type of segregation defect that can arises from structurally compromised chromosomes. Little is known about the mechanisms that normally prevent them. In this study I screened for genes that normally prevent anaphase bridges in order to learn more about their origin. I found anaphase bridges to arise in replication mutants and it is possible to trigger these bridges by exposing cells to replication stress. Thus, impaired replication is one cause for anaphase bridges. Further I identified a role for the mitotic exit network (MEN) in chromosome segregation. MEN mutants display anaphase bridges and I present evidence that these bridges arise from telomeric regions and may involve un-replicated DNA.
La correcta segregació dels cromosomes és esencial per la supervivencia de la cèl·lula i per evitar l’aparició de certes malalties com el càncer. Els ponts anafàsics són un tipus d’error de segregació que pot ser originat per defectes estructurals dels cromosomes. Es coneix molt poc sobre els mecanismes que eviten la formació d’aquests ponts anafàsics. En aquest estudi he fet un análisis global dels diferents gens que normalment eviten la formació d’aquests ponts, per abançar en la comprensió del seu origen. He vist que el ponts anaphasics es formen en mutants que tenen afectat el proces de replicació i que és posible de provocar la formació d’aquests ponts exposant les cèl·lules a estrés replicatiu. Per tant, els problemes en la replicació són una de les causes dels ponts d’anafase. He identificat el rol de “mitotic exit network (MEN)” en la segregació cromosómica. Els mutants per MEN formen ponts anafàsics i mostren evidències que aquests ponts probenen de regions telomèriques i podrien incloure DNA no replicat.

The electronic computer is the most significant tecnological product of the 20th Century. It has changed the lives of a vast number of people beyond recognition. It has changed our work, our leisure, and our relationships with each other. Its development has taken place in a period where an increasing amount of information is documented and recorded, and yet elements of its history, particularly its social history are distinct. A number of histories have been written about the computer. Mostly, these address the technical developments and economic or business histories behind the products rather than the designed form of the computer itself. They have tended to view the development of computing from a technologically deterministic perspective. By presenting the computer as the reseult of inevitable technological progress, they have ignored the social agency of their users and the cultural contexts in which they operate. Over the past ten years, i have researched and published on vaious aspects of computing technology from a social construction perspective. Using a novel methodology developed and tested over a significant period, this body of work has considered the acceptance and use of computers by different social groups, exploring the role of a computer as a tool of production, a means of control, and as an indicator of status. It has considered the design form and the depiction of computers in the mass media and popular culture to assess the influences on its design and its role in social relations, and in the process has made an original contribution to knowledge in the field of design history. This submission draws together five published articles from this body of work, which individually trace the history of the conception, production, representation and consumption of different types of computer. Collectively, these articles construct a coherent account exploring the design history of the computer as a social and cultural artefact.

Austerity is one of the most controversial policies in Europe. Fiscal rules are a key political institution that entrench austerity as a permanent feature of government budgetary policy. These rules fix numerical targets to constrain government budgets under the assumption that, in the long run, this might help to prevent fiscal crisis. In the last 30 years, the number of countries using fiscal rules has exploded. This thesis studies the political process leading to the creation of fiscal rules. Contrary to previous research, this thesis considers explanations coming both from national and international politics. It is composed of three articles. The first uses time series analysis in a European panel to arbitrate between different mechanisms that could lead political actors to adopt fiscal rules. It finds that fiscal rules are strengthened when countries are facing fiscal stress over an extended period or when governments are in a position of relative weakness toward European institutions. The latter result suggests that fiscal rules might diffuse through coercive diplomacy. The second paper uses a process tracing approach to test the possibility that the creation of fiscal rules is driven by the coercive diplomacy of the IMF and the EU. Our conclusion is that the coercive diplomacy of these two actors explains a large proportion of all fiscal rules existing in the world today. The final paper takes this result and compares the impact of fiscal rules on debt and bond yields between those that are externally-coerced and those that are nationally-driven. The conclusion is that externally-coerced fiscal rules do not help to control government debt and favour fiscal gimmickry. The main conclusion of the thesis is that a large fraction of fiscal rules are the result of coercive diplomacy and that these rules are less efficient than those which result from national politics.
Arts, Faculty of
Political Science, Department of
Graduate

Interstellar dust affects our view of the Universe, with half of the starlight emitted since the Big Bang being absorbed by dust grains and re-radiated in the Infra-Red. This thesis is concerned with understanding the origin of interstellar dust and determining the relative importance of different dust formation sites in the Universe. The sources and maximum amount of dust in early galaxies are investigated using published extended atmosphere models, stellar evolution tracks and nucleation conditions. A chemical evolution model is modified to include the estimated condensation efficiencies. The implications are investigated and we show that a supernovae source is required to produce large amounts of dust in galaxies. The atmospheres of AGB stars evolve too slowly to be responsible for high redshift dust. If SNe are not responsible for dust, then significant dust masses can only be generated at z > 5 by galaxies with very efficient star formation and no dust destruction. The first sub-millimetre analysis of the galactic remnant Kepler is presented with 0.3 3 M0 of dust, depending on the absorption properties. This a 1000 times more than previous Infra-red observations found. The sub-mm emission anti-correlates with the other wavelengths, including the warm dust and the most likely origin is from freshly synthesised dust in the supernova and dust formed from the interaction of the supernova shock with the ambient medium. Iron needles as a possible origin of the sub-mm emission are investigated. Finally, the sub-mm observations of the massive LBV star, rj Carinae are presented to show that the winds of massive stars may also be important contributors to the dust budget. We conclude that supernovae, or their massive star progenitors, are a dominant contributor to interstellar dust and make suggestions for future work.

In this thesis we use mathematical techniques to model two biological systems. First, we examine the growth dynamics of the antibiotic producing bacteria Streptomyces coelicolor and present a system of PDEs. We study the system both numerically and analytically. Due to oscillations in the numerical solution when solved using NAG, which uses a finite difference discretization, we change to a finite element discretization which corrects the oscillations. S. coelicolor also produces anticancer drugs, these can be encapsulated during the self-assembly of nanometre-sized vesicles, BPVs (biomimetic polymer vesicles) which are used as a novel targeted cancer therapy. We present a system of ODEs that focuses on the binding kinetics between cell-surface receptors and targeting molecules (ligands) on the BPV. We solve the system numerically, showing there is an optimal number of ligands per BPV for optimal uptake by tumour cells. We extend the model to allow for the infiltration of BPVs into tumour spheroids. Numerical solutions show that the growth of the spheroid is linear if the therapeutic BPVs are absent, and slows in the other case (for some parameter values). Using large time asymptotics we explore regions of parameter space where either steady states or travelling waves will occur.

Over the last several decades, Mexican origin immigrants have dispersed across the United States (Massey, Durand and Malone 2002). One community that has experienced particular growth in its Mexican origin population is Sunnyside, an agricultural city in the Yakima Valley. In this new destination community, Mexican origin families confront problems of gangs, violence, concentrated poverty and drug abuse, along with the challenges of surviving in a community that offers few pathways for mobility to Latinos.

In this study, I draw on 43 qualitative interviews and participant observer data to consider how Mexican origin parents, in two parent homes, go about the act of parenting in the context of Sunnyside. I query couples' parenting styles, with attention to how they develop aspirations for their children and to what models they use to inform their parenting. I look at how the structure of the community helps to perpetuate gendered parenting practices. Finally, I explore how these parenting approaches operate in the school system.

I argue that while much of the parenting that I observed deviates from that advocated by child development specialists (e.g. Baumrind 1968; 2012), the parenting was well designed to protect children from the particular forms of risk that were prominent in Sunnyside. The parenting was typically authoritarian and drew on models that families brought with them from Mexico. Other research on immigrant acculturation suggests this was probably an effective way to keep children safe by promoting selective acculturation (Portes and Rumbaut 2001; Zhou 1997). The parenting, however, was ill-designed to help the children to succeed educationally. Although parents wanted their children to get an education, they could offer little direct help to their children around educational tasks. Instead, they used discipline and engaged their children in physical labor to encourage the children to want to do well in school. This descriptive study helps to demonstrate how the characteristics of one particular new immigrant destination shape family life, parenting styles and children's life chances.

The following PhD thesis will explore the connection between autobiography and myth of origin: On the one hand, I am concerned with the ways in which women autobiographers rewrite classical myths of origin; on the other hand, I contend that autobiography itself is a myth of origin, a recreation of the forces that created the narrator. Throughout this thesis, I will develop two main themes: the first is the use of myth as a framework for autobiographical writing. This is possible because of myth's characteristic double focus on the universal and on the particular version, the historical context. Myth allows feminist autobiographers to connect themselves to universal truths from which they are barred by patriarchal tradition and to carve out their own, highly personal version. The second theme is that the autobiographers depict the origin as the core of the self and utterly Other. First, the narrator has to rely on the stories of other people, or a 'family memory'. Second, the past can be seen as connected to or leaving traces in the present; at the same time, it can be completely Other and incompehensible. Third, the autobiographical I is often cut off from her origins, and a constructive return that integrates the past and the present self is only possible through a deliberate act of mythmaking: It is mythmaking and storytelling that provides a connection between self and Other. I hope to make a contribution to feminist theory of autobiography as well as to feminist theory. Reading autobiography as myth of origin approaches the persistent problem of the relationship between the historical author and the autobiographical self. Moreover, I will explore the the specific relation between women and origins, and address the necessity for feminist theory to develop a framework where self and Other are intimately connected.

Nickel laterites account for ?40 % of global nickel production and contain 60 % of the world's total land based nickel resources. Despite the importance of these deposits published studies, detailing their morphology and formation processes are relatively few and the interaction of variables responsible for the formation of different nickel laterites are poorly understood. To better understand the process of nickel laterite formation, the Caldag and Bitincke paleodeposits were studied and their geological history established. The Caldag laterite, western Turkey, formed by intense chemical weathering of a serpentinite protolith in a region with a high water table and relatively low topography, resulting in the formation of an oxide deposit. In addition silica precipitation is common in the upper horizons of the deposit, where it creates an indurated layer, protecting the deposit from erosion. The Bitincke Nickel laterite, Albania is composed of two distinct zones characterized by silicate nickel and iron oxide phases. At Bitincke laterite formation and variations in thickness were controlled by the interaction between topography, faulting and protolith fracture density. The morphological and geochemical study of the Caldag and Bitincke paleodeposits indicates that there is a complex interplay between structures, topography, water table height and climate. Therefore nickel laterite deposits developed on very similar protoliths can form deposits with distinct and different characteristics. By comparing climatic data for regions where suitable ultramafic rocks are exposed and defining the climatic conditions favourable for the formation of nickel laterite deposits, the optimum temperatures and precipitation rates for nickel laterite development can be identified. A compilation of paleoclimatic data from western Turkey and Albania allows for the optimum periods of laterite formation within these regions to be established. Calculation of temperatures of formation from goethite oxygen and hydrogen isotopes could provide additional data on paleoclimaitc conditions. However due to the heterogeneity of laterite deposits and an extended weathering history, data gained from goethite appears not to provide a robust measure of paleotemperature. The study of the Caldag and Bitincke deposits combined with the analysis of the optimum conditions for nickel laterite formation has shown that there are four main factors which effect laterite formation: 1) Exposure of a suitable protolith; 2) Optimum climatic condition; 3) Geological variables; 4) Environment of preservation. Knowledge of these variables will assist in future laterite studies and will improve predictability of the location of new deposits.

It is very important for human kind that architecture should move by its beauty; if there are many equally valid technical solutions to a problem, the one which offers the users a message of beauty and emotion, that one is architecture. - Barragan - A simple shelter can fulfill the needs of the body, and the placement of the elements of construction in their relative positions can provide for the needs of the mind, but only the profound interrelationship of the elements of construction and the elements of experience can touch the spirit and move us deep within. Le Corbusier stated that: the purpose of construction is to hold things together and of architecture to move us. I hope that by applying these thoughts to my architecture, I may discover the point of intersection where the eternal and the finite meet, where the forming of finite elements awakens the spirit within man and causes him to dwell on the eternal. I hope to use the creation as a source of information to transform a material reality into a spiritual experience.
Master of Architecture

Doutoramento em Biologia Marinha
Market globalization and recurrent alerts on food safety issues resulted in a growing awareness of consumers on the need for food traceability. Determining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. This study used as target species the common cockle (Cerastoderma edule) and focused in the use of biochemical and geochemical tools, like fatty acid (FA) profiles and shells’ trace element fingerprints (TEF), respectively, to determine the geographic origin. This bivalve species represents a high commercial importance and supports a number of fisheries in European coastal waters and, in the particular case of Ria de Aveiro, a lagoon located in the western Atlantic coastal of Portugal, the harvesting of cockle exceeds 1000 tons per year. The first step of the present study was to evaluate the potential use of FA profiles of the adductor muscle (AM) of C. edule traded as fresh seafood for tracing their harvesting location. Results showed, for the first time, that it is possible to achieve the geographic origin with a spatial resolution < 10 Km without the complimentary use of stable isotope signatures. Besides, FA profile of the AM of fresh cockles showed to be able to discriminate the origin of specimens collected in close areas with different classifications according to European regulation (EC) No 1379/2013 for the capture/production of bivalves. This approach is paramount for traceability, expose fraud and ensure food safety. The way how the spatial distribution of C. edule among eight ecosystems along the Portuguese coast affects the FA profiles of the AM of this species and the temporal variability of FA profile between two consecutive years in areas within the same ecosystem were also tested. Data obtained from this research enable to differentiate cockles cultured in different Portuguese ecosystems, playing a key role for fishermen / producers willing to differentiate and add value to their products. Besides, this approach was able to discriminate the ecosystems which are microbiologically safer. The FA profiles presented inter-annual variability which must be considered for traceability as it compromise the discrimination of the geographic origin. In other attempt to ensure food safety, this study determined if the FA profile of the AM of live cockles displayed any significant shifts during the shelf-life (seven days post-harvest under a refrigerated environment) and how long post-harvest can these FA profiles be used to reliably trace their geographic origin. Results indicated that FA profiles remained stable until the third day post-harvest being able to be used to reliably trace geographic origin. After this period cockles started to exhibit contrasting FA profiles on their AM, namely a higher percentage of heptadecanoic acid (17:0), associated with the growth of pathogenic microorganisms responsible for food spoilage. In this study, was also evaluated and validated the efficiency of TEF of shells from fresh bivalves as a proxy to discriminate the origin of specimens collected from adjacent areas of the same estuarine system. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells. Results showed, for the first time, that this method can be used to achieve a reliable and accurate certification of origin for bivalves with a spatial resolution < 1 Km. TEF was also approached in the sense of evaluate if TEF of cockle shells from specimens captured in eight different ecosystems along the Portuguese Atlantic coastline can be used to successfully discriminate their geographic origin and if the temporal stability of TEF in cockle shells changes between two consecutive years in areas within the same ecosystem but displaying different classifications. TEF displayed by cockle shells successfully traced the geographic origin of cockles along the Portuguese coast and a periodical verification of TEF (> 6 months and < 1 year) is required to control temporal variability whenever comparing specimens originating from the same area collected more than six months apart. The molecular tools developed during this study represent an economic benefit if and when applied to the bivalve production sector. The transfer of this technology to the bivalve’s production constitutes a form of product’s safety, promotion and differentiation, as well as a tool against fraud
A globalização da indústria de comercialização de produtos alimentares e os recorrentes alertas sobre questões de segurança alimentar, resultaram numa crescente consciencialização dos consumidores sobre a necessidade de rastrear estes produtos. Determinar a origem geográfica de produtos alimentares de origem marinha é fundamental para controlar a sua qualidade e salvaguardar o interesse dos consumidores. Este estudo utilizou como espécie alvo o berbigão (Cerastoderma edule), focando-se na utilização de ferramentas bioquímicas e geoquímicas, tais como perfis de ácidos gordos e a assinatura elementar de conchas, respetivamente, para a determinação da origem geográfica. Esta espécie de bivalve representa uma grande importância comercial e suporta uma série de pescarias nas águas costeiras europeias e, no caso particular da Ria de Aveiro, uma lagoa localizada na costa ocidental atlântica de Portugal, onde a apanha de berbigão é superior a 1000 toneladas por ano. O primeiro passo do presente estudo consistiu na avaliação do potencial uso dos perfis de ácidos gordos do músculo adutor de C. edule comercializados frescos para rastrear seu local de origem. Os resultados mostraram, pela primeira vez, que é possível determinar a origem geográfica com resolução espacial < 10 km sem o uso complementar de assinaturas de isótopos estáveis. Além disso, o perfil de ácidos gordos do músculo adutor de berbigão fresco mostrou ser capaz de discriminar a origem dos espécimes recolhidos em áreas próximas com diferentes classificações de acordo com o Regulamento Europeu (CE) n. º 1379/2013 para a captura/produção de bivalves. Esta abordagem é primordial para a rastreabilidade, de modo a combater a fraude e a segurança alimentar. Os perfis de ácidos gordos do músculo adutor de C. edule foram avaliados ao longo da costa Portuguesa, bem como a sua variabilidade interanual dentro do mesmo ecossistema. Os resultados obtidos permitiram diferenciar os berbigões produzidos em diferentes ecossistemas ao longo a costa portuguesa, desempenhando um papel fundamental para os mariscadores/produtores dispostos a diferenciar e agregar valor aos seus produtos. Além disso, esta abordagem foi capaz de discriminar os ecossistemas que são microbiologicamente mais seguros. Os perfis de ácidos gordos do músculo adutor apresentaram variabilidade inter-anual devendo ser considerada para a rastreabilidade, na medida em que compromete a discriminação da origem geográfica. Numa outra tentativa de garantir a segurança alimentar, este estudo determinou se o perfil de ácidos gordos do músculo adutor de berbigão vivo apresentava mudanças significativas durante o tempo de prateleira (sete dias pós-colheita em ambiente refrigerado) e quanto tempo pós-colheita esses perfis de ácidos gordos poderiam ser utilizados para rastrear com fiabilidade a sua origem geográfica. Os resultados indicaram que os perfis de ácidos gordos permanecem estáveis até ao terceiro dia pós-colheita, podendo ser usados para rastrear com fiabilidade a origem geográfica. Após este período, os berbigões começaram a exibir perfis contrastantes de ácidos gordos no seu músculo adutor, nomeadamente uma elevada percentagem do ácido heptadecanóico (17:0), associado ao crescimento de microrganismos patogénicos responsáveis pela deterioração dos alimentos. Neste estudo foi também avaliada e validada a eficiência da assinatura elementar das conchas de bivalves frescos como um proxy para discriminar a origem de espécimes coletados em áreas adjacentes no mesmo sistema estuarino, tendo sido quantificados Bário (Ba), manganês (Mn), magnésio (Mg), estrôncio (Sr) e chumbo (Pb). Os resultados mostraram, pela primeira vez, que este método pode ser utilizado para obter uma certificação confiável e precisa da origem para bivalves com resolução espacial < 1 km. A análise elementar também foi abordada no sentido de avaliar se a assinatura elementar das conchas de espécimes capturados em oito ecossistemas diferentes ao longo da costa atlântica portuguesa pode ser usado para discriminar com sucesso a sua origem geográfica. Além disso, foi também testado se a assinatura elementar das conchas se altera em dois anos consecutivos, em áreas com classificações diferentes dentro do mesmo ecossistema. A assinatura elementar exibida pelas conchas de berbigão determinou com sucesso a origem geográfica dos berbigões ao longo da costa portuguesa, necessitando, no entanto, de uma verificação periódica (> 6 meses e < 1 ano) para controlar a variabilidade temporal sempre que comparados espécimes provenientes da mesma área recolhidos com mais de seis meses de diferença. As ferramentas moleculares desenvolvidas durante este estudo representam um benefício económico se e quando aplicadas ao setor de produção de bivalves. A transferência desta tecnologia para a produção de bivalves constitui uma forma de segurança do produto, promoção e diferenciação, bem como uma ferramenta de combate à fraude.

L’origine des éléments volatils, éléments avec des températures de condensation très basses comme l’eau, l’azote, le carbone et les gaz rares, sur Terre et sur les autres planètes telluriques reste mal comprise. Comprendre comment ces éléments sont arrivés sur Terre permettra de mieux appréhender les mécanismes de formation du système solaire. De par leur caractère inerte, les gaz rares (He, Ne, Ar, Kr, Xe) constituent des traceurs uniques des sources d’éléments volatils. L’étude de la composition en gaz rares du manteau terrestre s’avère donc essentielle afin de déterminer l’origine de ces éléments. L’objectif de ces travaux était de mesurer précisément la composition des isotopes stables et non-radiogéniques des gaz rares dans le manteau à partir de verres basaltiques. Ces derniers étant très souvent contaminés par l’air, des techniques d’analyse des gaz rares ont été mises en place pour s’affranchir de cette contamination. Des échantillons du volcan Fernandina du point chaud des Galápagos ont été étudiés par ablation laser. Les résultats montrent que le rapport 20Ne/22Ne des bulles est en moyenne de 12,65 ± 0,04 (1σ), ce qui est proche de la valeur estimée pour le pôle d’implantation du vent solaire (~ 12,7). Cette étude suggère donc que l’implantation du vent solaire sur les grains précurseurs de la Terre serait à l’origine des éléments volatils légers du manteau.Des données d’échantillons de popping rocks, aussi analysés par cette technique, indiquent que le manteau supérieur est hétérogène à petite échelle et pourraient impliquer le recyclage de gaz rares dans le manteau, y compris He, Ne, lors de la subduction. Un nouveau protocole d’analyse du Kr et Xe a été développé. Les résultats montrent les plus forts excès en 124Xe, 126Xe et 128Xe mesurés pour le manteau et suggèrent une source chondritique. Les isotopes fissiogéniques du xénon ont permis de dater le début du recyclage des éléments volatils dans le manteau aux alentours de 3 Ga
The origin of volatiles, elements with low condensation temperatures such as water, nitrogen, carbon and noble gases, on Earth and other terrestrial planets is still misunderstood. Determining how these elements were delivered to the Earth will allow a better understanding of the processes of solar system formation. Due to their inertness, noble gases (He, Ne, Ar, Kr, Xe) constitute unique tracers of volatiles sources. Studying the noble gas composition of the Earth’s mantle is hence critical to unravel volatile origin. The aim of this PhD was to measure precisely the composition of non-radiogenic, stable noble gas isotopes in the mantle from basaltic glasses. The latter being very often contaminated by air, analytical techniques were thus set up to overcome this contamination.Samples from Fernandina volcano from the Galápagos hotspot were studied with laser ablation. The results show that the mean 20Ne/22Ne ratio in the vesicles is 12.65 ± 0.04 (1σ), close to the estimated value of the solar wind implanted end-member (~ 12,7). This study suggests that light volatiles in the mantle would originate from implantation of solar wind on the Earth’s precursors grains. Data from popping rock samples, also analyzed with this technique, indicate that the upper mantle is heterogeneous at small scale and that noble gases, included He, Ne, could be recycled into the mantle in subduction zones. A new protocol to analyse Kr and Xe was set up. The results show the highest measured excess in 124Xe, 126Xe and 128Xe for the mantle and suggest a chondritic source. The xenon fissiogenic isotopes allowed us to constrain the onset of volatile recycling in the mantle to around 3 Ga

The origin of eukaryotic compartmentalization stands as a major conundrum in biology. Current evidence indicates that the last eukaryotic common ancestor (LECA) already possessed many eukaryotic hallmarks, including a complex subcellular organization. The lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Central in the discussion is the exogenous origin of mitochondria, ubiquitous eukaryotic organelles derived from an α-proteobacterial endosymbiont. Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto-eukaryote. In this thesis, I have used phylogenomic methods to address different questions on the origin and evolution of subcellular compartmentalization in Eukaryotes. We provide evidence for extensive retargeting of proteins between the different compartments, and suggest an evolutionary link between mitochondria and peroxisomes. We focus on the evolution of calcium homeostasis in mitochondria and reveal strong co-evolution patterns among the components of the recently identified mitochondrial calcium uniporter complex. Through alternative methodologies we analyze the phylogenetic signal carried by LECA-inferred gene families. Our analyses indicate that the ancestral eukaryotic proteome is a composite of genes originating from different prokaryotic sources. Finally, our work provides strong support for the late acquisition of mitochondria by a complex host. Altogether, our findings shed light on long-standing questions on the origin of Eukaryotes and provide new grounds for further advancements, as new data become available.
El origen de la compartimentación celular en Eucariotas se presenta como uno de los enigmas más importantes de la biología. Las evidencias actuales indican que el último ancestro común eucariota (LECA) ya poseía muchas de sus características avanzadas, incluyendo una organización subcelular compleja. Además, la falta de intermediarios evolutivos desafía la elucidación del orden en el que las características eucariotas aparecieron. En el centro de la discusión está el origen exógeno de las mitocondrias, orgánulos eucariotas derivados de α-proteobacteria vía endosimbiosis. Las diferentes hipótesis discrepan sobre si las mitocondrias fueron adquiridas al principio o al final durante el proceso de eucariogénesis. Del mismo modo, se debate la naturaleza y complejidad del hospedador, con modelos que van desde un simple hospedador procariota hasta un proto-eucariota dotado de cierta complejidad. En esta tesis, se han utilizado métodos filogenómicos para contestar a diferentes preguntas sobre la evolución de la compartimentación eucariota. Proporcionamos evidencia de una amplia relocalización de proteínas entre los diferentes compartimentos y sugerimos un vínculo evolutivo entre las mitocondrias y los peroxisomas. Nos centramos en la evolución de la homeostasis del calcio en las mitocondrias y observamos patrones de coevolución entre los componentes del sistema transportador mitocondrial de calcio. A través de metodologías diferentes se analiza la señal filogenética de familias de genes del ancestro común de Eucariotas. Nuestros análisis demuestran que el proteoma ancestral eucariota es un mosaico de genes de diferentes fuentes procariotas. Por último, nuestro trabajo proporciona un fuerte soporte a las hipótesis que la adquisición de la mitochondria tuvo lugar hacia el final de la eucariogénesis por parte de un hospedador complejo. En conjunto, nuestros resultados aclaran cuestiones que llevaban mucho tiempo abiertas sobre el origen de los Eucariotas y proporcionan nuevas bases para avances adicionales.

At the end of the 20th century, experiments studying neutrinos coming from the Sun and cosmic rays hitting the atmosphere revealed that these particles can change their flavour, behaving in a way that the Standard Model (SM) explicitly forbids. The quest for understanding the properties of neutrinos, which may reveal the next underlying structure of Nature, has since then led thousands of scientists. The scenario when this thesis was initiated was driven by the latest experimental surprise that neutrinos provided: the initial hints towards their strong violation of the particle-antiparticle CP symmetry. Characterising the statistical significance, robustness and physical origin of that hint is the main goal that this work pursuits. For that, there is a rich programme of present and future long baseline (LBL) accelerator neutrino experiments. At the beginning of the development of this thesis, the LBL accelerator neutrino experiment NOvA released its first data. To obtain a global picture, this work combines it with the results of other relevant neutrino experiments. The status of leptonic mixing and CP violation is quantitatively assessed as LBL accelerator neutrino experiments kept releasing data. As the unknowns start getting clarified, the data points towards maximal CP violation. This hint is driven by an excess of electron neutrino appearance events in the LBL accelerator experiment T2K. In the three massive neutrino paradigm and with the other leptonic mixing parameters accurately measured by different experiments, the excess can only be accommodated by large CP violation. Nevertheless, three massive neutrinos is just a minimal extension of the SM: other new physics could be present, masking the results as direct leptonic CP violation has not yet been conclusively observed. This thesis confronts with data the scenario that is less bounded by other experiments: neutral current Non-Standard Interactions (NSI) among neutrinos and matter. Physically, they are generated by new interactions among neutrinos and matter mediated by potentially light particles. Due to the large parameter space involved, first just CP-conserving NSI (i.e., their moduli) are explored. Current bounds are evaluated, as well as the synergies and complementarity among different experiments. Thanks to the experiments working with various neutrino energies and travelled distances, the determination of leptonic mixing parameters is found to be quite robust. Thus, it is possible to move on and evaluate the current sensitivity to leptonic CP violation assuming the most generic CP-violating NSI are present. CP violation induced by neutrino masses and leptonic mixing is found to be quite robust, due to the large amount of neutrino flavour transition data collected along three decades. Nevertheless, the next generation LBL accelerator experiments are aimed at precision measurements that could be more severely affected. Luckily, in the last years the COHERENT experiment has provided independent constraints on NSIs. This experiment measures neutral current coherent neutrino-nucleus elastic scattering, a low momentum transfer process quite sensitive to NSI induced by potentially light mediators. In the final chapter of the thesis, the data from the COHERENT experiment is analysed and integrated into the global analyses from previous chapters. Particular attention is paid to how the results depend on the assumptions about the experiment background, nuclear structure, and detector response. Combining COHERENT data with flavour transition experiments unveils its incipient role in increasing the robustness of their interpretation. These first results could be greatly improved by increasing the statistics of the signal and/or by performing the measurements with different nuclei sensitive to different NSI models. For that, the European Spallation Source is an ideal future facility. It will produce a neutrino beam one order of magnitude more intense than the one used at COHERENT, and as it is still under construction there is potential space for various modern detectors. Its prospects for bounding NSI are also explored. In summary, this thesis deals with the current experimental hint for large CP violation in the leptonic sector. It first quantifies its global significance, and then moves on to checking its robustness against the framework in which the experimental data is interpreted. For that, complementary experiments on neutrino-nucleus coherent scattering play, and will keep on playing in the future, a significant role. Thus, a global approach is taken to rigorously assess whether cutting-edge leptonic flavour measurements are pointing towards a new strong violation of a symmetry of Nature.
A finales del siglo XX, una serie de experimentos que estudiaban neutrinos provenientes del Sol o de rayos cósmicos que colisionaban contra la atmósfera terrestre mostraron que estas partículas pueden cambiar su sabor, comportándose de una manera que el Modelo Estándar prohíbe explícitamente. El camino hacia la comprensión de las propiedades de los neutrinos, que podría revelar la siguiente estructura subyacente de la naturaleza, ha guiado desde entonces a miles de científicos. El escenario al inicio de esta tesis estaba impulsado por la última sorpresa experimental de los neutrinos: los primeros indicios que apuntan hacia su fuerte violación de la simetría materia-antimateria o CP. El objetivo de este trabajo es abordar el problema desde una perspectiva global para evaluar rigurosamente si las medidas punteras de física de sabor leptónico están apuntando hacia una nueva violación fuerte de una simetría de la naturaleza. Para ello, se combinan los resultados de todos los experimentos de neutrinos relevantes. Se evalúa cuantitativamente el estatus de la mezcla leptónica y de la violación de CP, que los datos apuntan a que podría ser máxima. Este indicio está dominado por un exceso de neutrinos electrónicos en el experimento de neutrinos con acelerador a larga distancia T2K. Dentro del paradigma de tres neutrinos masivos, y con el resto de parámetros de mezcla leptónica medidos con precisión en varios experimentos, el exceso solamente se puede acomodar mediante una violación de CP grande. A pesar de esto, tres neutrinos masivos es solamente una extensión mínima del Modelo Estándar: podría haber otra nueva física enmascarando los resultados, ya que la violación de CP leptónica aún no se ha medido de manera directa y concluyente. Por ello, esta tesis confronta la nueva física que podría afectar a los experimentos de transiciones de sabor de neutrinos con datos experimentales. La violación de CP inducida por las masas de los neutrinos y por la mezcla leptónica resulta ser bastante robusta. Tal y como se explora en este trabajo, los experimentos complementarios de interacción coherente entre neutrinos y núcleos juegan, y continuarán jugando en el futuro, un papel importante a este respecto.

Post-transcriptional networks control multiple aspects of neuronal biology and their deregulation has been associated with human neurological disorders. This thesis focuses on regulation at the level of pre-mRNA splicing, particularly on a recently described programme of neural microexons implicated in autism. In the search for the evolutionary origins of this splicing programme we discovered neural microexons in non-vertebrate animals and a novel protein domain responsible for their regulation, the ‘enhancer of microexons’ or eMIC domain. This domain represents a neofunctionalization of an ancestral splicing factor that originated and was restricted to the neural system in bilaterian ancestors. We provide biochemical evidence for a role of the eMIC domain in 3’ splice site recognition, and profile the regulatory features associated with its mode of splicing regulation in the fruitfly Drosophila melanogaster. Ongoing experiments with loss- and gain-of-function flies for the eMIC domain are unravelling how the microexon programme evolved to control fundamental aspects of neuronal biology in animals.
Las redes génicas post-transcripcionales controlan múltiples aspectos del funcionamiento de las neuronas y han sido asociadas a diversos trastornos neurológicos. En esta tesis estudiamos la regulación a nivel del splicing alternativo del ARN mensajero y en concreto, un programa génico de microexones neurales que puede verse afectado en pacientes con autismo. La búsqueda del origen evolutivo de esta red de splicing nos llevó a encontrar microexones neurales en animales invertebrados y un nuevo dominio proteico encargado de la regulación de microexones al que nombramos eMIC, por sus siglas en inglés. La aparición de este dominio se trata de un caso de neofuncionalización de un factor de splicing ancestral, que se originó y restringió al sistema nervioso en el ancestro común de los animales bilaterales. A su vez, aportamos evidencias bioquímicas del papel del dominio eMIC en el reconocimiento del sitio 3’ de splicing y una caracterización de los elementos reguladores involucrados en la regulación de exones alternativos por el dominio eMIC en la mosca de la fruta Drosophila melanogaster. Actualmente estamos realizando experimentos de pérdida y ganancia de función de este dominio en moscas encaminados a comprender cómo este programa de microexones evolucionó para controlar funciones neuronales esenciales de los animales.

Thesis (Ph. D.) -- University of Maryland, College Park, 2004.
Thesis research directed by: Cell Biology & Molecular Genetics. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

Gliomas are the most common primary tumors of the central nervous system believed to arise from glial cells. Invasive growth and inherent propensity for malignant progression make gliomas incurable despite extensive treatment. I have developed a life-like orthotopic glioma model and used this and other in vivo models to study basic mechanisms of glioma development and treatment. Previous studies had indicated that experimental gliomas could arise from glial stem cells and astrocytes. The present thesis describes the making and characterization of a novel mouse model, Ctv-a, where gliomas are induced from oligodendrocyte progenitor cells (OPCs). Our study shows that OPCs have the capacity to give rise to gliomas and suggests in light of previous data that the differentiation state of the cell of origin affects tumor malignancy. CDKN2A encodes p16INK4a and p14ARF (p19Arf in mouse) commonly inactivated in malignant glioma. Their roles in experimental glioma have been extensively studied and both proteins have tumor suppressor functions in glial stem cells and astrocytes. Here, we demonstrate that p19Arf only could suppress gliomagenesis in OPCs while p16Ink4a had no tumor suppressive effect. Functional DNA repair is pivotal for maintaining genome integrity, eliminating unsalvageable cells and inhibiting tumorigenesis. We have studied how RAD51, a central protein of homology-directed repair, affected experimental glioma development and have found that expression of RAD51 may protect against genomic instability and tumor development. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a central feature of malignant progression in glioma. Antiangiogenic treatment by inhibition of vascular endothelial growth factor receptor signaling is used in the clinic for treatment of some cancers. We have investigated the effect of an alternative antiangiogenic protein, histidine-rich glycoprotein (HRG), on glioma development and found that HRG could inhibit the formation of malignant gliomas and completely prevent the formation of glioblastoma.

This study presents mitochondrial genome sequences from 22 Egyptian house cats with the aim of resolving the uncertain origin of the contemporary world-wide population of Domestic cats. Together with data from earlier studies it has been possible to confirm some of the previously suggested haplotype identifications and phylogeny of the Domestic cat lineage. Moreover, by applying a molecular clock, it is proposed that the Domestic cat lineage has experienced several expansions representing domestication and/or breeding in pre-historical and historical times, seemingly in concordance with theories of a domestication origin in the Neolithic Middle East and in Pharaonic Egypt. In addition, the present study also demonstrates the possibility of retrieving long polynucleotide sequences from hair shafts and a time-efficient way to amplify a complete feline mitochondrial genome.

Tensoring the field content of two super-Yang-Mills theories results in the field content of a certain supergravity theory, a procedure we call squaring. This thesis investigates how both the local and global internal symmetries enjoyed by the supergravity theory are inherited from the super-Yang-Mills factors. This is part of a much larger framework for studying a supergravity theory through its factorisation into simpler theories. The thesis begins by introducing local and global symmetries in the general context of relativistic field theory. The introduction is a short review on spacetime and internal symmetries in both gravitational and non-gravitational theories with particular focus on the supersymmetric regime. This is followed by the squaring idea and its appearance in various different contexts. After providing a unified description of all super-Yang-Mills theories over the four Normed Division Algebras R,C,H,O, the global internal supergravity symmetries are built with the help of the mathematical construction of the magic square, generalised to what we call the magic pyramid of supergravities. A physical interpretation of the formula reveals the Yang-Mills origin of the symmetries and demonstrates how simultaneous supersymmetry transformations on both factors can contribute to bosonic generators. The analysis is then extended to accommodate more exotic squarings by allowing for the coupling of matter multiplets to the super-Yang-Mills factors. Finally, the focus shifts to local internal symmetries whose linear form is derived directly from the corresponding linear factors. After a general treatment of off-shell squaring in various spacetime dimensions, the possibility of extending the construction to non-linear gravity is discussed.

Some Welsh Nonconformist chapels, particularly those having two doors in the entrance facade, have been characterised as an indigenous vernacular building type, distinguishing them from the more grandiose chapels of the later nineteenth century that were associated with urbanisation and industrialisation. This thesis questions this characterisation, firstly through a comparison of chapel buildings with their contemporary domestic vernacular and with chapels built elsewhere and secondly through the presentation of a new architectural history of Welsh Nonconformist chapels. The architectural history of Welsh chapels is constructed with reference to specific chapel buildings and through a synthesis of social and religious history and literary evidence. It is shown that the buildings would have carried meaning and symbolism evident to contemporaries, since the arrangement of chapel facades was representative of a non-ritualistic, sermon-centred religious practice. Welsh chapels were built by congregations with aspirations for social improvement and always designed to be recognisable and distinguishable from their contemporary domestic vernacular buildings. There is no discontinuity between the more simply-expressed lateral-facade chapels and the later gable-ended designs, a division that supports a particular interpretation of Welsh identity. The plan of the worship space is the same in both and Nonconformist congregations always built chapels that were intended to be recognisable as such and distinguishable from their contemporary domestic vernacular. Rather than adaptations of domestic architecture, chapels should be thought of as vernacular interpretations of a formal and theorised design.

Recent natural disasters have highlighted the need to evacuate people as quickly as possible. During hurricane Rita in 2005, people were stuck in queue buildups and large scale congestions, due to improper use of capacity, planning and inadequate response to vehicle breakdown, flooding and accidents. Every minute is precious in situation of such disaster scenarios. Understanding evacuation demand loading is an essential part of any evacuation planning. One of the factors often understood to effect evacuation, but not modeled has been the effect of a previous hurricane. This has also been termed as the 'Katrina Effect', where, due to the devastation caused by hurricane Katrina, large number of people decided to evacuate during Hurricane Rita, which hit Texas three weeks after Katrina hit Louisiana. An important aspect influencing the rate of evacuation loading is Evacuation Preparation Time also referred to as 'Mobilization time' in literature. A methodology to model the effect of a recent past hurricane on the mobilization times for evacuees in an evacuation has been presented utilizing simultaneous estimation techniques. The errors for the two simultaneously estimated models were significantly correlated, confirming the idea that a previous hurricane does significantly affect evacuation during a subsequent hurricane. The results show that the home ownership, number of individuals in the household, income levels, and level/risk of surge were significant in the model explaining the mobilization times for the households. Pet ownership and number of kids in the households, known to increase the mobilization times during isolated hurricanes, were not found to be significant in the model. Evacuation operations are marred by unexpected blockages, breakdown of vehicles and sudden flooding of transportation infrastructure. A fast and accurate simulation model to incorporate flexibility into the evacuation planning procedure is required to react to such situations. Presently evacuation guidelines are prepared by the local emergency management, by testing various scenarios utilizing micro-simulation, which is extremely time consuming and do not provide flexibility to evacuation plans. To gain computational speed there is a need to move away from the level of detail of a micro-simulation to more aggregated simulation models. The Cell Transmission Model which is a mesoscopic simulation model is considered, and compared with VISSIM a microscopic simulation model. It was observed that the Cell Transmission Model was significantly faster compared to VISSIM, and was found to be accurate. The Cell Transmission model has a nice linear structure, which is utilized to construct Linear Programming Problems to determine optimal strategies. Optimization models were developed to determine strategies for optimal scheduling of evacuation orders and optimal crossover locations for contraflow operations on freeways. A new strategy termed as 'Dynamic Crossovers Strategy' is proposed to alleviate congestion due to lane blockages (due to vehicle breakdowns, incidents etc.). This research finds that the strategy of implementing dynamic crossovers in the event of lane blockages does improve evacuation operations. The optimization model provides a framework within which optimal strategies are determined quickly, without the need to test multiple scenarios using simulation. Destination networks are the cause of the main bottlenecks for evacuation routes, such aspects of transportation networks are rarely studied as part of evacuation operations. This research studies destination networks from a macroscopic perspective. Various relationships between network level macroscopic variables (Average Flow, Average Density and Average speed) over the network were studied. Utilizing these relationships, a "Network Breathing Strategy" was proposed to improve dissipation of evacuating traffic into the destination networks. The network breathing strategy is a cyclic process of allowing vehicles to enter the network till the network reaches congestion, which is followed by closure of their entry into the network until the network reaches an acceptable state. After which entrance into the network is allowed again. The intuitive motivation behind this methodology is to ensure that the network does not remain in congested conditions. The term 'Network Breathing' was coined due to the analogy seen between this strategy to the process of breathing, where vehicles are inhaled by the network (vehicles allowed in) and dissipated by the network (vehicles are not allowed in). It is shown that the network breathing improves the dissipation of vehicle into the destination network. Evacuation operations can be divided into three main levels: at the origin (region at risk), routes and destination. This research encompasses all the three aspects and proposes a framework to assess the whole system in its entirety. At the Origin the demand dictates when to schedule evacuation orders, it also dictates the capacity required on different routes. These breakthroughs will provide a framework for a real time Decision Support System which will help emergency management official make decisions faster and on the fly.
Ph.D.
Department of Civil and Environmental Engineering
Engineering and Computer Science
Civil Engineering PhD

Lyme borreliosis (LB) is the most frequent vectorborne disease in the Northern Hemisphere. It is a complex bacterial zoonosis involving vertebrate hosts and hard ticks of the genus Ixodes. The causative agents, bacteria of the LB group of spirochaetes, form a species complex comprising 17 named species. As is the case for most microbial pathogens, epidemiological and ecological studies require appropriate genotyping. Although the use of single loci may provide rapid results, there are serious disadvantages, in particular when inferring evolutionary relationships or geographic population structure. A novel multilocus sequence analysis (MLSA) system of the LB group spirochaetes has been developed based on housekeeping genes to overcome these problems. Here, the system is optimized and tested using extracted spirochaetal DNA directly from ticks and then utilized to obtain insights into the migration and spread of individual species as well as to investigate the evolutionary origins of the species complex. Species belonging to the LB group of spirochetes display different patterns and levels of host specialisation which makes this an ideal system to study the impact of host associations on spread of zoonotic tickborne diseases. For example, Borrelia valaisiana and B. garinii are transmitted exclusively by birds while B. afzelii is transmitted by rodents. I demonstrate that the migration of the LB species is dependent on, and limited by, the migration of their respective hosts. I also show the presence of B. afzelii strains in England and, through the use of the MLSA scheme, demonstrate that the strains are highly structured. A close evolutionary relationship between B. afzelii and its rodent host species is shown. Furthermore, through phylogenetic analyses, some evidence of a coevolutionary relationship between the LB group species and their major group of vector species, the Ixodes persulcatus species complex, is presented and a Eurasian origin for the species group is suggested.

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, Factor VII and in small amounts in its activated form, Factor VIIa. However, the mechanism of initial generation of Factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases Factor VII activating protease, and hepsin play a role in activating Factor VII, however, it has remained controversial. In this work I estimated the levels of Factor VIIa and Factor VII for the first time in adult zebrafish plasma and also reevaluated the role of the above two serine proteases in activating Factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease did not reduce Factor VIIa levels while hepsin knockdown reduced Factor VIIa levels. After identifying role of hepsin in Factor VII activation in zebrafish, I wanted to identify novel serine proteases playing a role in Factor VII activation. However, a large scale knockdown of all serine proteases in zebrafish genome using available knockdown techniques is prohibitively expensive. Hence, I developed an inexpensive gene knockdown method which was validated with IIb gene knockdown, and knockdown all serine proteases in zebrafish genome. On performing the genetic screen I identified 2 novel genes, hepatocytes growth factor like and prostasin involved in Factor VII activation.

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
Neural stem/progenitor cells (NSPC) can differentiate into neurons and glial cells in the central nervous system. Interestingly, NSPC biology is being applied to the study of human brain tumours, since these cells share some common features with glioma cells. However, it is not known the developmental stage with more similarities to glioma cells, or the most susceptible to malignant transformation. We aimed to identify the stage(s) in the NSPC differentiation process towards astrocytes where cells acquire phenotype characteristics comparable to glioma cells. NSPC that were obtained from E15 mouse brain, were grew as neurospheres (NS) and induced to astroglial differentiation until 7 days in vitro (DIV). After the cellular characterization of NS and differentiating cells, tumour-related factors were evaluated and their behavior compared to the one of GL261 mouse glioma cells. Astroglial differentiation led to a decrease in progenitor cells, as expected. Multidrug resistance-associated protein 1 expression decreased and autophagy marker increased with differentiation. The vascular endothelial growth factor (VEGF), matrix metalloproteinases and S100B protein increased until 2/3 DIV, while the 1 DIV cells showed the highest migratory potential towards the chemotactic VEGF or GL261-conditioned media. Comparison of data with glioma cells characteristics point to the first and second days of NSPC differentiation to astrocytes as the stages closing matching GL261 cells, and likely the most vulnerable to malignancy transformation.

In modern science there are several definitions of synergy as a science of self-organization. Well-known scientist I. Pryhozhyn, one of the founders of synergistic research, believes that this science should be defined as “theory of dissipative structures”, while in the US the same science is called a “theory of dynamic chaos” (M. Feigenbaum), in Latin America - theory autopoeza (self-construction, self-reproduction of living beings) (U.R. Maturana). In our literature it becomes increasingly oftener found and more applied.

Hornbills (Aves: family Bucerotidae) are a charismatic group of Palaeotropical birds recognised for their distinctive morphology (casque) and behaviour (nest-sealing). Hornbill diet, habitat use, distribution and social system display pronounced interspecific variation, and their mutualistic interactions with tropical fruits provide vital ecosystem services. A wide range of species of hornbills across the Afrotropics, Indo-Malaya and Melanesia are of conservation concern. However, the evolutionary history of hornbills remains unclear and there are conflicting hypotheses about their origin, tempo of diversification and biogeography. Despite a comprehensive cladistic analysis of phenotypic data, there are unresolved taxonomic uncertainties within the family, and although a gradual accumulation of molecular data has revealed interesting phylogenetic relationships, methodological limitations, and incomplete sampling, has left gaps and produced incongruent results. Hence the evolutionary framework against which to interpret the diversity of this group is incomplete. The aim of this thesis was to construct a well-resolved molecular phylogeny of hornbills, and to use it to address longstanding questions about the evolution and diversification of these remarkable birds. This thesis presents a broad phylogenetic and biogeographic analysis of the family Bucerotidae, based on a coalescence of molecular methods and comparative analyses, largely using historical samples and recently-developed bioinformatic approaches. I provide the first complete species-level molecular phylogeny of hornbills, derived from nuclear adenylate kinase 1 intron 5 and mitochondrial (mtDNA) cytochrome b genes, and also a comprehensive mtDNA phylogeny covering 98% of the taxa, with extensive sampling of Asian geo-isolates. Using these two phylogenetic trees, I sought to determine the tempo of divergence, trace the evolution of traits, identify ancestral areas and colonisation routes, and also calculate genetic divergence. In this part of the work, I stress the importance of (1) using historical samples, (2) calibrating time-trees with fossil and molecular anchor-points, and (3) the use of a complete tree to test models of diversification and reconstruct ancestral states. My findings confirm the monophyly of Bucerotidae, showing nearly distinct African and Asian lineages, with relatively congruent topologies across different phylogenetic methods and genes. In turn, these gene trees were comparable with previous cladistic analysis based on phenotypic data. As a result, I was able to resolve some taxonomic issues and propose generic changes. Comparative analyses of social behaviour revealed that cooperative breeding is an ancestral trait, and its evolution in hornbills (in contrast with some other taxa) is associated with stable environments in combination with frugivory, territoriality and reduced body size. Analysis of the evolution of diet with diversification showed that the shift to frugivory from faunivorous African ancestors influenced the rapid diversification of Afro-Asian forest hornbills, facilitated by their preference for humid forests and mutualistic interactions with , hornbill-dispersed fruits (HDF). This dispersal of frugivorous lineages via the Palaeotropical Biotic Interchange promoted colonisation of Asia, with Sundaland being the centre of radiation for continental and insular Asian species. The gradual eastward colonisation from India to Melanesia matches palaeo-tectonic events that allowed dispersal across Huxley's, Wallace's and Lydekker's lines, and was congruent with historical biogeography of some HDFs. Finally, I used a combined analysis of genetic divergence and a standard scoring system for phenotypic data of Asian geo-isolates to provide evidence for quantitative delineation of species and propose changes in conservation status. My findings reveal the evolutionary history of horn bills from their emergence in the Late Oligocene from African origins, with a switch to frugivory influencing successful colonisation of hornbills and HDFs in Asian forests, which combined to promote sociality. Overall, this thesis demonstrates that access to novel environments and innovations to ecological niche facilitate rapid diversification in an avian lineage, and that this process is further promoted by the interplay of these birds in complex mutualistic interactions with their food, as well as palaeo-climatic and palaeo-tectonic changes.