2,243 research outputs found

    Reservoir host immunology and life history shape virulence evolution in zoonotic viruses

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    This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All relevant data are available within the manuscript and Supporting information files or are deposited in our open access GitHub repository, 'brooklabteam/spillover-virulence: spillover-virulence-v1.0.0' (https://zenodo.org/record/8136864).The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms that underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, recapturing trends in virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic hypothesis to explain the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and predictions designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Asymptotics of stochastic learning in structured networks

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    Computational Approaches to Drug Profiling and Drug-Protein Interactions

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    Despite substantial increases in R&D spending within the pharmaceutical industry, denovo drug design has become a time-consuming endeavour. High attrition rates led to a long period of stagnation in drug approvals. Due to the extreme costs associated with introducing a drug to the market, locating and understanding the reasons for clinical failure is key to future productivity. As part of this PhD, three main contributions were made in this respect. First, the web platform, LigNFam enables users to interactively explore similarity relationships between ‘drug like’ molecules and the proteins they bind. Secondly, two deep-learning-based binding site comparison tools were developed, competing with the state-of-the-art over benchmark datasets. The models have the ability to predict offtarget interactions and potential candidates for target-based drug repurposing. Finally, the open-source ScaffoldGraph software was presented for the analysis of hierarchical scaffold relationships and has already been used in multiple projects, including integration into a virtual screening pipeline to increase the tractability of ultra-large screening experiments. Together, and with existing tools, the contributions made will aid in the understanding of drug-protein relationships, particularly in the fields of off-target prediction and drug repurposing, helping to design better drugs faster

    Tradition and Innovation in Construction Project Management

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    This book is a reprint of the Special Issue 'Tradition and Innovation in Construction Project Management' that was published in the journal Buildings

    Asymptotics of stochastic learning in structured networks

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    Caribbean cultural heritage and the nation:Aruba, Bonaire and Curaçao in a regional context

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    Centuries of intense migrations have deeply impacted expressions of cultural heritage on the ABC islands: Aruba, Bonaire, and Curaçao. This volume queries how cultural heritage on these Dutch Caribbean islands relates to the work of nation building and nation-branding. How does the imagining of a shared political “we” relates to images deliberately produced to market these islands to a world of capital? The contributing authors in this volume address this leading question in their essays that describe and analyze the expressions of the ABC islands. In doing so they compare and contrast nation building and branding on the ABC islands to those taking place in the wider Caribbean. The expressions of cultural heritage discussed range from the importance of sports, music, literature and visual arts to those related to the political economy of tourism, the work of museums, the activism surrounding the question of reparations, and the politics and policies affecting the Caribbean Diasporas in the North Atlantic. This volume adds to the understanding of the dynamics of nation, culture and economy in the Caribbean

    A multiscale strategy for fouling prediction and mitigation in gas turbines

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    Gas turbines are one of the primary sources of power for both aerospace and land-based applications. Precisely for this reason, they are often forced to operate in harsh environmental conditions, which involve the occurrence of particle ingestion by the engine. The main implications of this problem are often underestimated. The particulate in the airflow ingested by the machine can deposit or erode its internal surfaces, and lead to the variation of their aerodynamic geometry, entailing performance degradation and, possibly, a reduction in engine life. This issue affects the compressor and the turbine section and can occur for either land-based or aeronautical turbines. For the former, the problem can be mitigated (but not eliminated) by installing filtration systems. For what concern the aerospace field, filtration systems cannot be used. Volcanic eruptions and sand dust storms can send particulate to aircraft cruising altitudes. Also, aircraft operating in remote locations or low altitudes can be subjected to particle ingestion, especially in desert environments. The aim of this work is to propose different methodologies capable to mitigate the effects of fouling or predicting the performance degradation that it generates. For this purpose, both hot and cold engine sections are considered. Concerning the turbine section, new design guidelines are presented. This is because, for this specific component, the time scales of failure events due to hot deposition can be of the order of minutes, which makes any predictive model inapplicable. In this respect, design optimization techniques were applied to find the best HPT vane geometry that is less sensitive to the fouling phenomena. After that, machine learning methods were adopted to obtain a design map that can be useful in the first steps of the design phase. Moreover, after a numerical uncertainty quantification analysis, it was demonstrated that a deterministic optimization is not sufficient to face highly aleatory phenomena such as fouling. This suggests the use of robust or aggressive design techniques to front this issue. On the other hand, with respect to the compressor section, the research was mainly focused on the building of a predictive maintenance tool. This is because the time scales of failure events due to cold deposition are longer than the ones for the hot section, hence the main challenge for this component is the optimization of the washing schedule. As reported in the previous sections, there are several studies in the literature focused on this issue, but almost all of them are data-based instead of physics-based. The innovative strategy proposed here is a mixture between physics-based and data-based methodologies. In particular, a reduced-order model has been developed to predict the behaviour of the whole engine as the degradation proceeds. For this purpose, a gas path code that uses the components’ characteristic maps has been created to simulate the gas turbine. A map variation technique has been used to take into account the fouling effects on each engine component. Particularly, fouling coefficients as a function of the engine architecture, its operating conditions, and the contaminant characteristics have been created. For this purpose, both experimental and computational results have been used. Specifically for the latter, efforts have been done to develop a new numerical deposition/detachment model.Le turbine a gas sono una delle pricipali fonti di energia, sia per applicazioni aeronautiche che terrestri. Proprio per questa ragione, esse sono spesso costrette ad operare in ambienti non propriamente puliti, il che comporta l’ingestione di contaminanti solidi da parte del motore. Le principali implicazioni di questo problema sono spesso sottovalutate. Le particelle solide presenti nel flusso d’aria che il motore ingerisce durante il suo funzionamento possono depositarsi o erodere le superfici interne della macchina, e portare a variazioni alla sua aerodinamica, quindi a degrado di performance e, molto probabilmente, alla diminuzione della sua vita utile. Questo problema aflligge sia la parte del compressore che la parte della turbina, e si manifesta sia in applicazioni terrestri che aeronautiche. Per quanto riguarda la prima, la questione può essere mitigata (ma non eliminata) dall’installazione di sistemi di filtraggio all’ingresso della macchina. Per le applicazioni aeronautiche invece, i sistemi di filtraggio non possono essere utilizzati. Questo implica che il particolato presente ad alte quote, magari grazie ad eventi catastrofici quali eruzioni vulcaniche, o a basse quote, quindi ambienti deseritic, entra liberamente nella turbina a gas. Lo scopo principale di questo lavoro di tesi, è quello di proporre differenti metodologieallo scopo di mitigare gli effetti dello sporcamento o predirre il degrado che esso comporta nelle turbine a gas. Per questo scopo, sia la parte del compressore che quella della turbina sono state prese in considerazione. Per quanto riguarda la parte turbina, saranno presentate nuove guide progettuali volte al trovare la geometria che sia meno sensibile possibile al problema dello sporcamento. Dopo di ciò, i risultati ottenuti verranno trattati tramite tecniche di machine learning, ottenendo una mappa di progetto che potrà essere utile nelle prime fasi della progettazione di questi componenti. Inoltre, essendo l’analisi fin qui condotta di tipo deterministico, un’analisi delle principali fonti di incertezza verrà eseguita con l’utilizzo di tecniche derivanti dall’uncertainty quantification. Questo dimostrerà che l’analisi deterministica è troppo semplificativa, e che sarebbe opportuno spingersi verso una progettazione robusta per affrontare questa tipologia di problemi. D’altro canto, per quanto concerne la parte compressore, la ricerca è stata incentrata principalmente sulla costruzione di uno strumento predittivo, questo perchè la scala temporale del degrado dovuto alla deposizione a "freddo" è molto più dilatata rispetto a quella della sezione "calda". La trategia proposta in questo lavoro di tesi è un’insieme di modelli fisici e data-driven. In particolare, si è sviluppato un modello ad ordine ridotto per la previsione del comportamento del motore soggetto a degrado dovuto all’ingestione di particolato, durante un’intera missione aerea. Per farlo, si è generato un codice cosiddetto gas-path, che modella i singoli componenti della macchina attraverso le loro mappe caratteristiche. Quest’ultime vengono modificate, a seguito della deposizione, attraverso opportuni coefficienti di degrado. Tali coefficienti devono essere adeguatamente stimati per avere una corretta previsione degli eventi, e per fare ciò verrà proposta una strategia che comporta l’utilizzo sia di metodi sperimentali che computazionali, per la generazione di un algoritmo che avrà lo scopo di fornire come output questi coefficienti
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