9,831 research outputs found

    Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021

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    É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio

    Learning disentangled speech representations

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    A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody. The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions. In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks. This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    Building body identities - exploring the world of female bodybuilders

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    This thesis explores how female bodybuilders seek to develop and maintain a viable sense of self despite being stigmatized by the gendered foundations of what Erving Goffman (1983) refers to as the 'interaction order'; the unavoidable presentational context in which identities are forged during the course of social life. Placed in the context of an overview of the historical treatment of women's bodies, and a concern with the development of bodybuilding as a specific form of body modification, the research draws upon a unique two year ethnographic study based in the South of England, complemented by interviews with twenty-six female bodybuilders, all of whom live in the U.K. By mapping these extraordinary women's lives, the research illuminates the pivotal spaces and essential lived experiences that make up the female bodybuilder. Whilst the women appear to be embarking on an 'empowering' radical body project for themselves, the consequences of their activity remains culturally ambivalent. This research exposes the 'Janus-faced' nature of female bodybuilding, exploring the ways in which the women negotiate, accommodate and resist pressures to engage in more orthodox and feminine activities and appearances

    Socio-endocrinology revisited: New tools to tackle old questions

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    Animals’ social environments impact their health and survival, but the proximate links between sociality and fitness are still not fully understood. In this thesis, I develop and apply new approaches to address an outstanding question within this sociality-fitness link: does grooming (a widely studied, positive social interaction) directly affect glucocorticoid concentrations (GCs; a group of steroid hormones indicating physiological stress) in a wild primate? To date, negative, long-term correlations between grooming and GCs have been found, but the logistical difficulties of studying proximate mechanisms in the wild leave knowledge gaps regarding the short-term, causal mechanisms that underpin this relationship. New technologies, such as collar-mounted tri-axial accelerometers, can provide the continuous behavioural data required to match grooming to non-invasive GC measures (Chapter 1). Using Chacma baboons (Papio ursinus) living on the Cape Peninsula, South Africa as a model system, I identify giving and receiving grooming using tri-axial accelerometers and supervised machine learning methods, with high overall accuracy (~80%) (Chapter 2). I then test what socio-ecological variables predict variation in faecal and urinary GCs (fGCs and uGCs) (Chapter 3). Shorter and rainy days are associated with higher fGCs and uGCs, respectively, suggesting that environmental conditions may impose stressors in the form of temporal bottlenecks. Indeed, I find that short days and days with more rain-hours are associated with reduced giving grooming (Chapter 4), and that this reduction is characterised by fewer and shorter grooming bouts. Finally, I test whether grooming predicts GCs, and find that while there is a long-term negative correlation between grooming and GCs, grooming in the short-term, in particular giving grooming, is associated with higher fGCs and uGCs (Chapter 5). I end with a discussion on how the new tools I applied have enabled me to advance our understanding of sociality and stress in primate social systems (Chapter 6)

    The influence of complex volcanic vent morphology on eruption dynamics

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    Vulkanausbrüche gelten als eine der spektakulärsten Naturgewalten unserer Erde. Gleichzeitig stellen sie jedoch auch eine Gefahr für die menschliche Gesundheit und Infrastruktur dar. Aufgrund ihrer Dynamik und ihres unberechenbaren Charakters geht von explosiven Vulkanausbrüchen eine besonders große Gefährdung des Menschen und seiner Umwelt aus. Im Zuge eines explosiven Ausbruchs werden heiße Gase und Pyroklasten in die Atmosphäre ausgeworfen. Obwohl das Monitoring aktiver Vulkane in den letzten Jahren immer weiter verbessert wurde, ist es immer noch schwierig eine konkrete Vorhersage zu den Ausbrüchen zu erstellen. Aufgrund ihrer Komplexität ist das Verhalten von Vulkanen nicht kalkulierbar. Bis heute ist weder eine Beobachtung, noch eine Messung der unterirdischen Rahmenbedingungen möglich, welche den Ausbruch steuern. Trotz dieser Unwägbarkeiten unterliegen Vulkanausbrüche dennoch physikalischen Gesetzmäßigkeiten, sodass die Möglichkeit besteht, die Prozesse im Untergrund eines Vulkans zu modellieren oder durch Experimente zu beschreiben. Aufgrund der Komplexität der Wechselwirkungen innerhalb des Systems Vulkan ist es erforderlich Experimente zunehmend realistischer zu gestalten. Sobald das ausgeworfene Material aus dem Krater austritt können wir den Ausbruch visuell Beobachten. In diesem Bereich ist das Verhalten des Ausbruchs vollständig von den Prozessen im Untergrund und von der Geometrie des Kraters abhängig. Im Vergleich zu den symmetrischen Kraterformen, welche in Experimenten und Modellen oft angenommen werden, sind die Krater in der Natur deutlich unregelmäßiger geformt. Ihre Geometrien sind oft eingekerbt und haben eine schräge Oberfläche. Zudem können sich die Kratergeometrien innerhalb kürzester Zeit verändern. Um den Einfluss der Prozesse im Untergrund zu verstehen müssen wir zuerst den Einfluss der beobachtbaren Parameter (z. B. Kratergeometrie) ergründen. Schlussendlich wird ein tiefergehendes Verständnis der Parameter, die Vulkanausbrüche steuern, zu einem Fortschritt und der Verbesserung der Gefährdungsanalysen führen. Um dies zu erreichen, habe ich Beobachtungen aus Feldkampagnen und Laborexperimenten kombiniert. Zunächst habe ich die Geometrien von Vulkankratern erfasst und deren zeitliche Entwicklung dokumentiert. Dazu haben ich die Geometrie der Krater in der Kraterterrasse des Strombolis in einer hohen Auflösung vermessen und die jeweils zugehörigen Explosionen beobachtet. Dabei konnte ich feststellen, dass sowohl die Intensität, als auch die Art und die Richtung der Ausbrüche durch Formveränderungen der Oberflächentopografie beeinflusst werden. Mittels Drohneneinsatz habe ich innerhalb eines Zeitraums von neun Monaten (Mai 2019–Januar 2020) fünf topografische Datensätze erstellt. In diesem Zeitraum war es möglich „normale“ Strombolianische Aktivität, starke Ausbrüche und sogar zwei Paroxysmen zu beobachten (3. Juli und 28. August 2019), sodass es möglich war, die verschiedenen Ausbruchstypen mit den vorherrschenden Ablagerungs- und Abtragungsprozessen zu verknüpfen. Zudem konnte ich die Anzahl der aktiven Krater, deren Positionen sowie deren Umgestaltung nachverfolgen. Da Veränderungen der Kratergeometrie und der Kraterposition auf eine Modifikation des Ausbruchsgeschehens hinweisen können, sind auch dies wichtige Faktoren für eine Gefährdungsanalyse. Die aus den Feldforschungen gewonnenen Daten zeigen deutlich die Komplexität, Vielseitigkeit und Variabilität der Formen vulkanischer Krater in einer nie da gewesenen zeitlichen und räumlichen Auflösung. Darüber hinaus haben die Beobachtungen der Vulkanausbrüche deutlich gemacht, wie stark die Beziehung zwischen dem Krater, der Kratergeometrie und dem Auswurf von pyroklastischem Material ist. Diese Erkenntnis hat eine große Bedeutung für die Gefährdungsanalyse, vor allem für Gebiete, die potentiell durch vulkanische Bomben und pyroklastischem Fallout bedroht sind. Im Anschluss habe ich eine Reihe von Dekompressionsexperimenten mit Kratergeometrien durchgeführt, welche auf den Beobachtungen am Stromboli aufbauen. Durch diese Experimente wurde der Zusammenhang zwischen Kratergeometrie und Ausbruchsdynamik bestätigt. Die verwendeten Geometrien haben eine geneigte Oberfläche mit einem Winkel von 5°, 15° und 30° und jeweils einer zylindrischen und einer trichterförmigen inneren Geometrie. Daraus ergeben sich sechs experimentelle Krater die mit folgenden experimentellen Bedingungen getestet wurden: Vier unterschiedliche Startdrücke (5, 8, 15 und 25 MPa) und zwei Gasvolumina (127.4cm3, 31.9cm3). Alle Experimente wurden bei Raumtemperatur und mit Argon durchgeführt. Trotz des vertikalen Aufbaus konnte man auf beiden Seiten des Kraters unterschiedlich große Winkel des austretenden Gases beobachten. Weiterhin war der Gasstrahl geneigt. Die Richtung der Neigung wurde durch die innere Geometrie be- stimmt. Bei einer zylindrischen Geometrie neigte sich der Gasstrahl in die Einfallsrichtung der geneigten Oberfläche. Im Falle einer trichterförmigen inneren Geometrie neigt sich der Gasstrahl entgegen der Einfallsrichtung. Der Winkel des Gasaustritts war bei einer zylindrischen inneren Geometrie immer größer als bei der trichterförmigen Geometrie. Sowohl die Winkel des Gasaustritts als auch die Neigung des Gasstrahls zeigten eine starke Reaktion auf eine Veränderung der Druckbedingung und Oberflächenneigung. Dabei zeigten sowohl der Austrittswinkel als auch die Neigung eine positive Korrelation mit dem Druck und der Oberflächenneigung. Hohe Druckbedingungen haben außerdem dafür gesorgt, dass für einen längeren Zeitraum Überdruckverhältnisse am Kraterausgang herrschten. Ein höheres Gasvolumen hat größere Gasaustrittswinkel ermöglicht. Zuletzt habe ich die Dekompressionsexperimente durch den Einsatz von Partikeln ergänzt, um so den Auswurf von Gas und Partikeln während eines explosiven Vulkanausbruchs nachzustellen. Dabei habe ich die beiden experimentellen Kratergeometrien aus den vorangegangenen Experimenten ausgewählt, welche den stärksten Einfluss auf die Gasdynamik aufgezeigt haben. Zusätzlich habe ich eine dritte Kratergeometrie verwendet, die dem aktiven Krater S1 auf Stromboli nachempfunden ist. Die Geometrie entspricht der Kratergeometrie aus der Vermessung im Mai 2019. Die S1 Geometrie zeichnet sich durch einen asymmetrischen Öffnungswinkel aus (~10° auf einer Seite, ~40° auf der anderen Seite). Zusätzlich zu den drei Kratergeometrien wurden unterschiedliche Partikel verwendet (Schlacke und Bims), mit jeweils drei unterschiedlichen Korngrößen (0.125–0.25, 0.5–1 und 1–2mm) und zwei Druckstufen (8 und 15MPa). Die Partikeldynamik, in der Nähe des experimentellen Kraters, wurde anhand der Winkel des Partikelauswurfs und der Geschwindigkeit der Partikel definiert und beschrieben. Dabei wurde festgestellt, dass die Geometrie des Kraters die Richtung und Neigung des Partikelauswurfswinkels und die Geschwindigkeit der Partikel bestimmt. Bei allen Kratergeometrien kam es zu einem asymmetrischen Partikelauswurf und im Falle von Bimspartikeln zudem zu einer ungleichmäßigen Geschwindigkeitsverteilung. Die Kombination aus Daten aus Feldkampagnen, Experimenten mit Gas und Experimenten mit zusätzlichen Partikeln zeigte deutlich den starken Einfluss der Kratergeometrie auf Eruptionen. In der Natur, führt eine modifizierte Kratergeometrie zu einem verändertem Auswurfsmuster der Pyroklasten. Im Labor haben komplexe Kratergeometrien zu geneigten Gasstrahlen, asymmetrischen Auswurfswinkeln von Gas- und Gaspartikeln und einer asymmetrischen Verteilung der Geschwindigkeit von Partikeln geführt. Auf Basis dieser Beobachtungen komme ich zu dem Schluss, dass asymmetrische Vulkankrater eine asymmetrische Verteilung von pyroklastischem Auswurf hervorrufen. Das führt zu einer bevorzugten Richtung für vulkanischen Fallout — und falls es zu einer kollabierenden Ausbruchsäule kommt — zu einer bevorzugten Richtung für pyroklastische Ströme. Der technische Fortschritt durch Drohnen, Photogrammmetrie und 3D Druck bietet einige Chancen für die Vulkanologie. Luftaufnahmen durch Drohnen ermöglichen eine schnelle, günstige und sichere Vermessung von Vulkankratern, auch in Zeiten erhöhter Aktivität. Zusammen mit Photogrammmetrie und 3D Druck lassen sich realitätsnahe Kratergeometrien erzeugen, für zunehmend realistische skalierte Laborexperimente.Volcanic eruptions are among the most violent displays of the Earth’s natural forces and threaten human health and infrastructure. Explosive eruptions are hazardous due to their impulsive and dynamic nature, ejecting gas and pyroclasts at high velocity and temperature into the atmosphere. In recent years, monitoring efforts have increased, but forecasting eruptions is still challenging as volcanoes are complex systems with the potential for inherently unpredictable behaviours. To date, the underlying boundary conditions are beyond observation and quantification. Still, they are constrained by physical laws and can be described through models and experiments. The complexity and interdependency of the parameters governing the dynamics of volcanic eruptions ask for increasingly realistic experiments to investigate the sub-surface conditions driving volcanic eruptions. Above the vent, in the near-vent region, the dynamics of explosive eruptions can first be visually observed. The characteristics at this stage are purely the result of the underlying boundary conditions and the exit (vent) geometry. Volcanic vents are rarely the symmetric features that are often assumed in models and experiments. They often exhibit highly irregular shapes with notched or slanted rims that can be transient. To eventually understand the unobservable boundary conditions, it is necessary to initially gain knowledge about the effect of the observable factors (i.e. vent geometry). This knowledge will ultimately improve the understanding of the parameters affecting an explosive event to develop accurate probabilistic hazard maps. To this end, a combination of field observations and laboratory experiments was used. First, I characterised vent and crater shape changes at a frequently erupting volcano (Stromboli) to collect high-resolution geometric data of volcanic vents and observe the related explosion dynamics. As a result of topographic changes, variable eruption intensity, style and directionality could be detected. Five topographic data sets were acquired by unoccupied aerial vehicles (UAVs) over nine months (May 2019-January 2020). During this period, changes associated with "normal" Strombolian activity, "major explosions" and paroxysmal episodes (3 July and 28 August 2019) occurred. Hence, the topographic data made it possible to link the predominant constructive and destructive processes to these eruption styles. Furthermore, the number and position of active vents changed significantly, which is a critical parameter for hazard assessment as vent geometry and position can be linked to shifts in eruptive mechanisms. These field surveys highlight the geometric complexity and variability of volcanic vents at an unprecedented spatiotemporal resolution. Additionally, the observations of explosions suggested the paramount influence of crater and vent geometry on pyroclast ejection characteristics, a fact that has strong implications for areas potentially affected by bomb impact and pyroclastic fall out. Secondly, I designed a series of shock-tube experiments incorporating the geometry elements observed at Stromboli to quantify the influence of vent geometry and several boundary conditions. These experiments validated the link between vent geometry and explosion dynamics that was observed in the field. The novel geometry element is an inclined exit plane of 5°, 15° and 30° slant angle combined with a cylindrical and diverging inner geometry resulting in six vent geometries. All experiments were conducted with gas-only (Argon) at room temperature, four different starting pressures (5, 8, 15, 25 MPa) and two reservoir volumes (127.4 cm3, 31.9 cm3). Despite the vertical setup, the slanted geometry yielded both a laterally variable gas spreading angle and an inclination of the jets. The inner geometry controlled the jet inclination towards the dip direction of the slanted exit plane (cylindrical) and against the dip direction of the slanted exit plane (diverging). Cylindrical vents produced larger gas spreading angles than diverging vents. Both gas spreading angle and jet inclination were highly sensitive to the experimental pressure and the slant angle. They had a positive correlation with maximum gas spreading angle and jet inclination. Additionally, the pressure was positively correlated with the maximum duration of underexpanded characteristics of the jet. The gas volume only showed a positive correlation with the maximum gas spreading angle. Thirdly, I added particles to the experiments to mimic the ejection of gas-particle jets during explosive volcanic eruptions. For this set of experiments, the two geometries with the 30° slant angle from the previous experimental series were used as they exhibited the strongest effect on the gas ejection dynamics. They were supplemented by a third vent that resembled the "real" geometry of Stromboli’s active S1 vent as it was mapped in May 2019 and fabricated by 3D printing. The S1’s geometry is characterised by a ~ 10° divergence on one side and a ~ 40° divergence on the other side. Besides three vent geometries, two types of particles (scoria and pumice), each with three different grain size distributions (0.125– 0.25, 0.5–1, 1–2 mm) and two starting pressures (8, 15 MPa) were used. The near-vent vent dynamics were characterised as a function of particle spreading angle and particle ejection velocity. The vent geometry governed the direction and the magnitude of particle spreading, and the velocity of particles. All geometries yielded asymmetric particle spreading as well as a non-uniform velocity distribution in experiments with pumice particles. The combination of field observations, gas-only and gas-particle experiments demonstrated the prime control exerted by vent geometry. In nature, a modification of the vent led to modified pyroclast ejection patterns. In the laboratory the complex geometries facilitated inclined gas jets, an asymmetric gas and particle spreading angle, and an asymmetric particle ejection velocity distribution. These findings suggest that the asymmetry of volcanic vents and/or craters can promote the asymmetric distribution of volcanic ejecta.Which, in turn, will lead to a preferred direction of volcanic fallout and — in case a column collapse occurs — to a preferred direction of the ensuing pyroclastic density currents. The availability of new technology like unoccupied aerial vehicles, photogrammetry and 3D printing provides several opportunities for the volcanological community. Aerial observations allow a fast, inexpensive and safe way to collect geometrical data of volcanic vents and craters, even in times of elevated volcanic activity. In combination with photogrammetry and 3D printing, "real" vents can be produced for increasingly realistic scaled laboratory experiments

    Investigating PAX6 and SOX2 dynamic interactions at the single molecule level in live cells

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    The abundance of transcription factor (TF) molecules in the nuclei of eukaryotic cells are in the range of thousands. However, the functional binding sites of most TFs lie in the range of hundreds. This suggests that there is a surplus of the number of molecules for many TFs, relative to their binding sites at any given time. Nevertheless, precise TF levels are instrumental for normal development and maintenance, with haploinsufficiency (namely lowering the dosage of a TF by half) being a hallmark of many TF-related human developmental disorders. Qualitative methods assessing TF binding such as chromatin immunoprecipitation, provide static information, from fixed cell populations and so fail to provide insight into TF dynamic behaviour. Live-cell imaging methodologies such as Fluorescence Correlation Spectroscopy (FCS) offer the ability to measure kinetics of binding to chromatin, protein-protein interactions, absolute concentrations of molecules and the underlying cell-to-cell variability. SOX2 and PAX6 TFs exhibit haploinsufficiency in humans. Heterozygous point mutations, deletions or insertions in these genes can lead to a plethora of abnormal ocular developmental disorders (e.g. coloboma, aniridia, microphthalmia, anopthalmia). SOX2 encodes a high-mobility group (HMG) domain-containing TF, essential for maintaining self-renewal of embryonic stem cells and is expressed in proliferating central nervous system (CNS) progenitors. PAX6 contains two DNA binding domains; a PAIRED domain (PD) and a homeodomain (HD). Both DNA binding domains present in PAX6 (PD and HD) can function either jointly, or separately, to regulate a plethora of genes implicated in the development and maintenance of the CNS, the eye and the pancreas. Despite existing genetic and phenotypic evidence, it remains unclear how PAX6 and SOX2 influence each other at the molecular level and how sensitive their stoichiometry is during ocular development. In this thesis I investigated the dynamic interplay between PAX6/SOX2 and chromatin in live cells, at the molecular level. I compared wild-type protein function with pathogenic missense variants using advanced fluorescence microscopy techniques and assessed how these mutations quantitatively and qualitatively affected molecular behaviour. My results showed that both SOX2 and PAX6 pathogenic missense mutants display differential subnuclear localisation, as well as altered protein-protein and protein-chromatin interactions, linking molecular diffusion to pathogenic phenotype in humans. More importantly, I identified a novel role of SOX2 in stabilising PAX6- chromatin complexes in live cells, providing further insight into the complex and dynamic relation of PAX6 and SOX2 in ocular tissue specification, maintenance and development

    Industry 4.0: product digital twins for remanufacturing decision-making

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    Currently there is a desire to reduce natural resource consumption and expand circular business principles whilst Industry 4.0 (I4.0) is regarded as the evolutionary and potentially disruptive movement of technology, automation, digitalisation, and data manipulation into the industrial sector. The remanufacturing industry is recognised as being vital to the circular economy (CE) as it extends the in-use life of products, but its synergy with I4.0 has had little attention thus far. This thesis documents the first investigating into I4.0 in remanufacturing for a CE contributing a design and demonstration of a model that optimises remanufacturing planning using data from different instances in a product’s life cycle. The initial aim of this work was to identify the I4.0 technology that would enhance the stability in remanufacturing with a view to reducing resource consumption. As the project progressed it narrowed to focus on the development of a product digital twin (DT) model to support data-driven decision making for operations planning. The model’s architecture was derived using a bottom-up approach where requirements were extracted from the identified complications in production planning and control that differentiate remanufacturing from manufacturing. Simultaneously, the benefits of enabling visibility of an asset’s through-life health were obtained using a DT as the modus operandi. A product simulator and DT prototype was designed to use Internet of Things (IoT) components, a neural network for remaining life estimations and a search algorithm for operational planning optimisation. The DT was iteratively developed using case studies to validate and examine the real opportunities that exist in deploying a business model that harnesses, and commodifies, early life product data for end-of-life processing optimisation. Findings suggest that using intelligent programming networks and algorithms, a DT can enhance decision-making if it has visibility of the product and access to reliable remanufacturing process information, whilst existing IoT components provide rudimentary “smart” capabilities, but their integration is complex, and the durability of the systems over extended product life cycles needs to be further explored
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