Coastal flooding from wave overtopping causes considerable damage. Presently, to model wave overtopping one can either make use of physical model tests or empirical tools such as those described in the EurOtop manual. Both these methods have limitations; therefore, a quick and reliable numerical model for wave overtopping would be a very useful tool for a coastal engineer.This research aims to test and develop a numerical model (in one horizontal dimension) for nearshore waves, runup and overtopping. The Shallow Water And Boussinesq (SWAB) model solves the Boussinesq-type equations of Madsen and Sorensen (1992) for non breaking waves and the nonlinear shallow water equations for breaking waves. Through testing against a range of physical model data using regular and random waves, the SWAB model's transfer from non-breaking to breaking waves was optimised. It was found that a wave height to water depth ratio worked consistently well as a breaking criterion.A set of physical model tests were carried out, based on previous field testing of wave overtopping that had previously taken place at Anchorsholme, Blackpool. The SWAB model was used to simulate some of these physical model tests, giving good results for mean overtopping rates. SWAB models the force imposed by steep walls and recurve walls on the incident flow; this force was found to have a significant effect on overtopping rates. A comparison was made between mean overtopping rates from the SWAB model, the physical model tests, empirically-based software (PC-Overtopping) and the field data. The physical model and SWAB results compared well with the field data, though the empirical software gave large overestimates.The SWAB model was applied to the analysis of overtopping at Walcott, Norfolk. It was found that beach levels affected overtopping rates, but not as much as different randomly phased wave trains. A simulation of a recent storm event was performed, with overtopping rates being slightly lower than those reported by local residents. A joint probability analysis showed that the predicted frequency of such an event was in line with these reports.An alternative modelling technique was also tested, where a spectral energy model was coupled with a nonlinear shallow water solver. Results for wave runup parameters were very accurate, when the coupling location is at the seaward edge of the surf zone. Extension of this modelling technique into two horizontal dimensions would be more straightforward than with the SWAB model.

No description available.

The endoplasmic reticulum (ER) facilitates the synthesis, assembly and quality control of all secretory, transmembrane, and resident proteins of the endomembrane system. An accumulation of unfolded proteins or a disruption in the specialized folding environment within the organelle causes ER stress, thus impairing the folding capacity of the ER. In response to this stress, the ER initiates a signaling cascade called the unfolded protein response (UPR) in an attempt to restore ER homeostasis. The vertebrate UPR is propagated by three ER-resident transmembrane proteins (i.e., PERK, IRE1α, and ATF6α), each initiating a signaling cascade that ultimately culminates in production of a transcriptional activator. The UPR was originally characterized as a pathway for the upregulation of ER chaperones, and a comprehensive body of subsequent work has shown that protein synthesis, folding, oxidation, trafficking, and degradation are all transcriptionally enhanced by the UPR. However, UPR activation is also accompanied by extensive mRNA suppression. The mechanisms responsible for this suppression and its consequences for physiological processes beyond the realm of ER protein folding and processing are only now beginning to be described. The overall goal of my thesis work was to explore this process of UPR-mediated gene suppression by identifying the mechanisms involved and the cellular processes affected. As a result, I characterized a novel mechanism of UPR-mediated transcriptional repression involving the translational regulation of the transcription factor C/EBPβ resulting in the suppression of the gene Il4ra, encoding an essential subunit of the IL-4/IL-13 receptor. As a consequence of this suppression, a novel effect of ER stress was identified in the impairment of IL-4/IL-13 signaling, a finding of potential significance in the study of inflammatory disease. In addition to this mechanism, I validated a novel approach to the identification of UPR-regulated transcription factors using publically available bioinformatic software. Through this analysis, I identified the transcription factor HNF4α as a novel post-translational UPR-regulated transcription factor, the regulation of which, resulted in the suppression of a number of lipid metabolic genes. This analysis not only identified a novel UPR-regulated transcription factor, but also presented a new tool for the characterization of UPR-mediated gene suppression. My work represents an independent and original investigation into the process of UPR-mediated gene suppression; and reveals that the UPR facilitates transcriptional suppression through the transcriptional, translational, and post-translational regulation of multiple transcription factors, resulting in the coordinated attenuation of physiological pathways. This function of the UPR is likely to contribute to metabolic, inflammatory, and other chronic disease states.

Le réticulum endoplasmique rugueux (RE), assure la synthèse, le repliement et la maturation des protéines de la voie de sécrétion. Les altérations des fonctions physiologiques du RE, entrainent l’accumulation de protéines mal repliées dans la lumière du RE, une condition appelée stress RE. En réponse au stress RE, un mécanisme compensatoire adaptatif appelé Unfolded Protein Response (UPR) est activé afin de restaurer l’homéostasie du RE et de permettre la survie de la cellule. Dans le cas d’un stress RE sévère ou prolongé, les altérations ne pouvant plus être compensées, la cellule est éliminée par apoptose contribuant ainsi au développement de pathologies cardiaques. Le but des recherches actuelles sur le stress RE en physiopathologie cardiaque n’est pas d’inhiber la réponse au stress RE, mais plutôt de la moduler afin de limiter l’apoptose des cardiomyocytes et de protéger le cœur. Dans ce contexte, nous avons mis en évidence que le stress RE induit une modification importante de l’architecture des cardiomyocytes associée à une altération de la fonction mitochondriale. De plus, nous avons montré que SIRT1, une désacétylase dépendante du NAD+, inhibe l’apoptose mitochondriale induite par un stress RE en limitant spécifiquement l’activation de la voie PERK de la réponse UPR via la désacétylation du facteur eIF2á sur la lysine K143. Enfin, nos résultats indiquent que SIRT1 protège les cardiomyocytes de l’apoptose induite par le stress RE en favorisant la mitophagie, via une activation de la voie de signalisation eEF2K/eEF2. Ces résultats montrent que SIRT1 est impliquée dans la régulation de la réponse autophagique et apoptotique des cardiomyocytes au stress RE et suggèrent que cette désacétylase serait une cible thérapeutique intéressante pour limiter le développement des pathologies cardiaques liées au stress RE. / The endoplasmic reticulum (ER) functions to properly synthesize, fold and process secreted and transmembrane proteins. Impairment of ER function induces an accumulation of misfolded proteins in the ER lumen, a condition termed ER stress. In response to ER stress, an adaptive compensatory mechanism called Unfolded Protein Response (UPR) is activated to restore ER homeostasis and promote cell survival. In the case of severe or prolonged ER stress, homeostasis cannot be restored and the cell is eliminated by apoptosis contributing to the development of cardiac pathologies. Currently, cardiac therapy based on ER stress modulation to conserve beneficial adaptations and to avoid cardiomyocyte apoptosis is viewed as a promising avenue towards effective therapies of ER stress-associated cardiac diseases.In this context, we demonstrated that ER stress induces architectural modifications and alterations of the mitochondrial function in cardiomyocytes. Furthermore, we showed that SIRT1, a NAD+-dependent deacetylase, inhibits mitochondrial apoptosis by modulating the activation of the PERK pathway of the UPR through deacetylation of the translation initiation factor eIF2á on lysine K143. Our results also indicate that SIRT1 protects cardiomyocyte from ER stress-induced apoptosis by activating mitophagy through eEF2K/eEF2 pathway. Collectively, these data demonstrate that SIRT1 regulates ER stress-induced autophagy and apoptosis in the heart and suggest that this deacetylase may be a therapeutic target to protect the heart against ER stress-induced injury.

Snow Spell is an interactive composition for erhu, flute, cello, piano, and Max/MSP interactive computer music system. This one-movement piece, Snow Spell, is intended to depict the beauty of a snow scene by presenting four different impressions of snow envisioned by the composer through music. The definition, history, and significance of interactive music are explored. Various modes of interactivity to control signal processing modules, and technical considerations for signal routing and level control in the interactive computer music system are also explored. Chinese music elements in Snow Spell including pentatonic scales, glissandi, and quotations from the Chinese folk tune River of Sorrow are investigated.

Thesis advisor: Baldassare Di Bartolo / Thesis advisor: Pradip Bakshi / The search for multicolored light produced by some IR laser-excited luminescent nano-powders has revealed, for laser power exceeding a threshold value, the emission of white light (WL) with black-body characteristics. I am directing my research to the study of the physical parameters that may influence the threshold power of the laser and the efficiency of the WL emission. A typical compound that I will investigate will consist of nano-powders of SrZrO3 doped with Yb. The parameters of relevance may include Yb concentration, pressure, temperature, size of nano-crystals, exciting power and wavelength of the laser, dynamical parameters such as decay and build-up patterns. The aim of my research will be both theoretical and experimental: theoretical for I will try to uncover the mechanism of the WL production and experimental for the possible application as efficient light sources of systems similar to the ones that I will investigate (oxide nano-powders doped with lanthanide or transition metal ions). The “new” light sources in the market (fluorescence lights sources, and LED lamps) beat the Edison bulbs in efficiency, but they do not produce the black-body emission of the Edison bulbs that is most pleasing to the eye. The search for efficient black-body type of sources is still on and we want to be a part of it. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

The master's thesis deals with experimental study of tribological characteristics of smart fluids. Smart fluids are substances in liquid state reacting to the presence of magnetic or electric field by change in rheological properties. For possible application in devices using conventional lubricants is necessary to choose suitable smart fluid and study the influence of excitation on formation of lubricating layer, friction and wear. Comprehensive description of excitation influence is executed using three experimental devices and theoretical model for measurements parameters specification. Assessed are lubricant film thickness, friction coefficient and wear under smart fluid activation in non-conformal contact. Results show significant observable influence of smart fluids excitation on all assessed aspects. Understanding the mechanisms of smart fluids excitation can be a key step in development of intelligent devices with active external control of lubricant behaviour and character, that could lead to maintenance cost reduction and effectivity improvement.

This thesis deals with reengineering of Erasmsus process framework and conceptual design of its information support. Analytical part is focused to description of current state of ERASMUS programme and European education system. In the same part, advantages and shortcomings of current situation are analyzed. The output of this analysis is set of strengths and weaknesses of current solution. Based on this information, the conceptual design of the information support core is designed. At the end, potential further steps of designing of this project are discussed.

Heavy ethanol use causes neurodegeneration manifested by neuronal loss and dysfunction. It is becoming imperative to delineate the underlying mechanism to promote the treatment of ethanol-induced neurodegeneration. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases. This study aims to investigate the role of ER stress in ethanol-induced neurodegeneration. In experimental design, adult mice were exposed to binge ethanol drinking by daily gavage for 1, 5, or 10 days and the response of ER stress was examined. We found the induction of ER stress appeared at 5 days and remained at 10 days. Moreover, the induction of ER stress was accompanied by an increase in neurodegeneration. With cell culture, we demonstrated that ethanol exposure resulted in neuronal apoptosis and that blocking ER stress by sodium phenylbutyrate (4-PBA) abolished ethanol-induced neuronal apoptosis, suggesting that ER stress contributes to ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in ethanol-exposed developmental mouse brains. To investigate its implication in ethanol-induced neurodegeneration, we established a central nervous system (CNS)-specific Manf knockout mouse model and examined the effects of MANF deficiency on ethanol-induced neuronal apoptosis and ER stress using a third-trimester equivalent mouse model. We found MANF deficiency worsened ethanol-induced neuronal apoptosis and ER stress and that blocking ER stress abrogated the harmful effects of MANF deficiency on ethanol-induced neuronal apoptosis. Moreover, a whole transcriptome RNA sequencing supported the involvement of MANF in ER stress modulation and revealed candidates that may mediate the ER stress-buffering capacity of MANF. Collectively, these data suggest that MANF is neuroprotective against ethanol-induced neurodegeneration via ameliorating ER stress. Because MANF is a neurotrophic factor, we also examined the effects of MANF deficiency on neurogenesis. We observed that MANF deficiency increased neurogenesis in the subgranular zone of the hippocampal dentate gyrus and subventricular zone of the lateral ventricles in the mouse brain. Mechanistically, this finding was supported by a decrease of cell cycle inhibitors (p15 and p27), an increase of G2/M marker (phospho-histone H3), and an increase of neural progenitor markers (Sox2 and NeuroD1) in the brain of conditional Manf knockout mice. Our in vitro studies demonstrated that the gain-of-function of MANF inhibited cell cycle progression, whereas the loss-of-function of MANF promoted cell cycle progression. Taken together, these data suggest that MANF may affect the process of neurogenesis through altering cell cycle progression.

Das PCSK1-Gen kodiert für die Prohormonkonvertase 1/3 (PC1/3), einem Enzym, welches eine wichtige Rolle bei der Aktivierung von Prohormonen in ihre aktive Form spielt. Unter den Substraten der PC1/3 befinden sich Proinsulin, Proglukagon, Pro-POMC und andere Schlüsselmetabolite des Energiestoffwechsels. In genomweiten Assoziationsstudien wurde eine Korrelation zwischen Varianten in PCSK1 und Übergewicht gefunden. In Einzelfällen führte eine genetische bedingte PC1/3-Defizienz zu einem multiendokrinologischen Krankheitsbild mit schwerer Adipositas. Für einige der Varianten in PCSK1 wurde eine Retention im endoplasmatischen Retikulum (ER) gefunden. Retention im ER, ausgelöst durch fehlgefaltete Proteine, verursacht ER-Stress, welcher ggf. zu Apoptose führen kann. In dieser Arbeit wurde untersucht, ob 5 ausgewählte PCSK1-Varianten die Enzymreifung/-sekretion beeinträchtigen, ob ER-Stress induziert wird und letztlich, ob Apoptose induziert wird. Es fand sich für 2 Varianten eine Retention im ER und eine Induktion von ER-Stress. Apoptose wurde durch keine der untersuchten Varianten induziert.:Abkürzungsverzeichnis 1. Einführung und Hintergrund 1.1 Prohormonkonvertase 1/3 1.1.1. Entstehung und Reifung der Prohormonkonvertase 1/3 1.1.2. Substrate der Prohormonkonvertase 1/3 1.1.3. Prohormonkonvertase 1/3-Defizienz und Krankheitsbilder 1.1.4. Die untersuchten PCSK1-Varianten 1.2. Stress im endoplasmatischen Retikulum und Unfolded protein response 1.3. Ableitung der Rationalen 2. Publikation 3. Zusammenfassung Literaturverzeichnis A. Anhang A.1. Supplemental Information A.2. Methoden A.3. Darstellung des eigenen wissenschaftlichen Beitrags A.4. Erklärung über die eigenständige Abfassung der Arbeit A.5. Lebenslauf A.6. Liste der Veröffentlichungen A.7. Danksagung