2,056 research outputs found

    Investigating the Innate Immune Systems of Bats and Their Roles as Zoonotic Viral Reservoirs

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    The zoonotic spillover of viral pathogens from wild animal reservoirs into human populations remains the leading cause of emerging and re-emerging infectious diseases globally. Bats represent important viral reservoirs, notorious for the diversity and richness of the viruses they host, several of which are highly pathogenic when transmitted to humans. Remarkably, bats appear to host an abundance of these viruses without exhibiting any clinical signs of disease. A dominant hypothesis for this ability suggests that bats can control viral replication early in the innate immune response, which acts as the first line of defence against infection. However, bat immunology remains fundamentally understudied, largely due to their high species diversity and the lack of accessible reagents required for bat research. Therefore, in this work we explored and characterised key components of bat innate immunity to gain a better understanding of bats as viral reservoirs and contribute to the currently limited literature. Here, we demonstrated the in vitro transcriptomic response of the bat model species, Pteropus alecto (P.alecto) upon stimulation with the bat henipavirus Cedar virus and also with a type III bat interferon (paIFNλ). These investigations highlighted key transcripts, some of which were immune-related, in the response of bats to the separate stimuli and presents a foundation for further research into significant genes concerned in bat viral infection. Building from genome-wide transcriptomics, three distinctive bat innate immune genes representative of different stages of interferon signalling were selected for comparative genomics and functional characterisation. Our work demonstrated the conservation of genes between bats and humans, including IRF7, IFIT5 and IFI35. Specific findings for IRF7 included its successful translocation to the cell nucleus upon stimulation. IFIT5 and IFI35 were specifically selected for exploration due to previous research demonstrating the respective antiviral and conflicting anti- or pro-viral roles of these genes in humans. Significantly, our research demonstrated the direct antiviral action of P.alecto IFIT5 against negative-sense RNA viruses. Collectively, our findings offer valuable contributions to the field of bat antiviral immunity and provide the framework for future investigative studies into the role and function of the bat innate immune system and bat viral tolerance mechanisms

    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Functional characterization of the Ustilago maydis effector genes UMAG_11060 and UMAG_05306

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    Ustilago maydis causes corn smut and triggers tumor formation in all aerial parts of maize. To adapt to the host plant and promote disease progression, U. maydis uses effector proteins that exhibit organ-specific expression and adaptation during infection. This study focuses on two of these effectors, UMAG_11060 and UMAG_05306. This study characterizes UMAG_11060 (Chapter 2), which encodes the effector protein TOPLESS (TPL) interacting protein 6 (Tip6). The study shows that Tip6 interacts with the N-terminal region of ZmTPL2 through its two EAR (ethylene-responsive element binding factor-associated amphiphilic repression) motifs. These motifs are crucial for virulence function and alter the nuclear distribution pattern of ZmTPL2, disrupting host transcriptional regulation. This disruption leads to the down-regulation of 13 transcription factors in the AP2/ERF B1 subfamily. This study proposes a regulatory mechanism in which Tip6 uses repressive domains to recruit the corepressor ZmTPL2, thereby disrupting the transcriptional networks of the host plant. The second part of the thesis focuses on the characterization of UMAG_05306 (Chapter 3), which exhibits highly specific subcellular localization and appears as thick and twisted filament-like structures. The study shows that UMAG_05306 interacts with four maize dynamin related proteins (DRPs) and is able to interact with both the N- terminal and C-terminal of ZmDRP5. Three DRPs are found to interact with maize tubulin. Furthermore, UMAG_05306 directly interacts with tubulin. These findings shed light on their potential roles in U. maydis infection. In conclusion, this study provides insight into the molecular mechanisms underlying U. maydis infection and reveals the importance of UMAG_11060 and UMAG_05306 effectors for virulence and tumor formation

    Digital Traces of the Mind::Using Smartphones to Capture Signals of Well-Being in Individuals

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    General context and questions Adolescents and young adults typically use their smartphone several hours a day. Although there are concerns about how such behaviour might affect their well-being, the popularity of these powerful devices also opens novel opportunities for monitoring well-being in daily life. If successful, monitoring well-being in daily life provides novel opportunities to develop future interventions that provide personalized support to individuals at the moment they require it (just-in-time adaptive interventions). Taking an interdisciplinary approach with insights from communication, computational, and psychological science, this dissertation investigated the relation between smartphone app use and well-being and developed machine learning models to estimate an individual’s well-being based on how they interact with their smartphone. To elucidate the relation between smartphone trace data and well-being and to contribute to the development of technologies for monitoring well-being in future clinical practice, this dissertation addressed two overarching questions:RQ1: Can we find empirical support for theoretically motivated relations between smartphone trace data and well-being in individuals? RQ2: Can we use smartphone trace data to monitor well-being in individuals?Aims The first aim of this dissertation was to quantify the relation between the collected smartphone trace data and momentary well-being at the sample level, but also for each individual, following recent conceptual insights and empirical findings in psychological, communication, and computational science. A strength of this personalized (or idiographic) approach is that it allows us to capture how individuals might differ in how smartphone app use is related to their well-being. Considering such interindividual differences is important to determine if some individuals might potentially benefit from spending more time on their smartphone apps whereas others do not or even experience adverse effects. The second aim of this dissertation was to develop models for monitoring well-being in daily life. The present work pursued this transdisciplinary aim by taking a machine learning approach and evaluating to what extent we might estimate an individual’s well-being based on their smartphone trace data. If such traces can be used for this purpose by helping to pinpoint when individuals are unwell, they might be a useful data source for developing future interventions that provide personalized support to individuals at the moment they require it (just-in-time adaptive interventions). With this aim, the dissertation follows current developments in psychoinformatics and psychiatry, where much research resources are invested in using smartphone traces and similar data (obtained with smartphone sensors and wearables) to develop technologies for detecting whether an individual is currently unwell or will be in the future. Data collection and analysis This work combined novel data collection techniques (digital phenotyping and experience sampling methodology) for measuring smartphone use and well-being in the daily lives of 247 student participants. For a period up to four months, a dedicated application installed on participants’ smartphones collected smartphone trace data. In the same time period, participants completed a brief smartphone-based well-being survey five times a day (for 30 days in the first month and 30 days in the fourth month; up to 300 assessments in total). At each measurement, this survey comprised questions about the participants’ momentary level of procrastination, stress, and fatigue, while sleep duration was measured in the morning. Taking a time-series and machine learning approach to analysing these data, I provide the following contributions: Chapter 2 investigates the person-specific relation between passively logged usage of different application types and momentary subjective procrastination, Chapter 3 develops machine learning methodology to estimate sleep duration using smartphone trace data, Chapter 4 combines machine learning and explainable artificial intelligence to discover smartphone-tracked digital markers of momentary subjective stress, Chapter 5 uses a personalized machine learning approach to evaluate if smartphone trace data contains behavioral signs of fatigue. Collectively, these empirical studies provide preliminary answers to the overarching questions of this dissertation.Summary of results With respect to the theoretically motivated relations between smartphone trace data and wellbeing (RQ1), we found that different patterns in smartphone trace data, from time spent on social network, messenger, video, and game applications to smartphone-tracked sleep proxies, are related to well-being in individuals. The strength and nature of this relation depends on the individual and app usage pattern under consideration. The relation between smartphone app use patterns and well-being is limited in most individuals, but relatively strong in a minority. Whereas some individuals might benefit from using specific app types, others might experience decreases in well-being when spending more time on these apps. With respect to the question whether we might use smartphone trace data to monitor well-being in individuals (RQ2), we found that smartphone trace data might be useful for this purpose in some individuals and to some extent. They appear most relevant in the context of sleep monitoring (Chapter 3) and have the potential to be included as one of several data sources for monitoring momentary procrastination (Chapter 2), stress (Chapter 4), and fatigue (Chapter 5) in daily life. Outlook Future interdisciplinary research is needed to investigate whether the relationship between smartphone use and well-being depends on the nature of the activities performed on these devices, the content they present, and the context in which they are used. Answering these questions is essential to unravel the complex puzzle of developing technologies for monitoring well-being in daily life.<br/

    Seamless Multimodal Biometrics for Continuous Personalised Wellbeing Monitoring

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    Artificially intelligent perception is increasingly present in the lives of every one of us. Vehicles are no exception, (...) In the near future, pattern recognition will have an even stronger role in vehicles, as self-driving cars will require automated ways to understand what is happening around (and within) them and act accordingly. (...) This doctoral work focused on advancing in-vehicle sensing through the research of novel computer vision and pattern recognition methodologies for both biometrics and wellbeing monitoring. The main focus has been on electrocardiogram (ECG) biometrics, a trait well-known for its potential for seamless driver monitoring. Major efforts were devoted to achieving improved performance in identification and identity verification in off-the-person scenarios, well-known for increased noise and variability. Here, end-to-end deep learning ECG biometric solutions were proposed and important topics were addressed such as cross-database and long-term performance, waveform relevance through explainability, and interlead conversion. Face biometrics, a natural complement to the ECG in seamless unconstrained scenarios, was also studied in this work. The open challenges of masked face recognition and interpretability in biometrics were tackled in an effort to evolve towards algorithms that are more transparent, trustworthy, and robust to significant occlusions. Within the topic of wellbeing monitoring, improved solutions to multimodal emotion recognition in groups of people and activity/violence recognition in in-vehicle scenarios were proposed. At last, we also proposed a novel way to learn template security within end-to-end models, dismissing additional separate encryption processes, and a self-supervised learning approach tailored to sequential data, in order to ensure data security and optimal performance. (...)Comment: Doctoral thesis presented and approved on the 21st of December 2022 to the University of Port

    Sensing Collectives: Aesthetic and Political Practices Intertwined

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    Are aesthetics and politics really two different things? The book takes a new look at how they intertwine, by turning from theory to practice. Case studies trace how sensory experiences are created and how collective interests are shaped. They investigate how aesthetics and politics are entangled, both in building and disrupting collective orders, in governance and innovation. This ranges from populist rallies and artistic activism over alternative lifestyles and consumer culture to corporate PR and governmental policies. Authors are academics and artists. The result is a new mapping of the intermingling and co-constitution of aesthetics and politics in engagements with collective orders

    Evolutionäre Diversität der CLCA Gene zwischen Vögeln und Säugetieren

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    The chloride channel regulators, calcium activated (CLCA) gene family has mainly been associated with cancer and chronic inflammatory airway diseases but the presumably complex cellular functions of these gene products are still widely unknown. The family comprises four distinct genetic clusters in mammals, termed CLCA1 to CLCA4. It is highly complex and diverse and includes amplified or inactivated genes with a high degree of variation between species. For example, in contrast to mice with eight CLCAs including one inactivated gene, humans have only three intact CLCAs and one inactivated gene. The tissue and cellular expression patterns of different CLCA homologues within a species are also often redundant. This complexity and redundancy of the CLCA members might be a reason, why the function of this gene family has not been revealed yet based on a mammalian model organism. The complexity and redundancy of mammalian CLCAs raise two questions: Are the complexity and diversity of these genes unique features of mammals? And second, what is the evolutionary background of these peculiar developments? To address these questions, data on CLCA homologues obtained from evolutionarily more distant species are needed. Recently, a rather simple CLCA gene locus was predicted for the chicken, comprising only two CLCA genes. In a phylogenetic analysis, the first galline CLCA gene product, gCLCA1, was found closely related to mammalian CLCA1, 3 and 4. In contrast, the second one, gCLCA2, seemed more closely related to mammalian CLCA2 than to gCLCA1 or mammalian CLCA1, 3 and 4. In this cumulative thesis, the galline CLCA genes and their genomic structures were analyzed and both members were cloned. Their protein architecture and biochemical properties were investigated in silico and in vitro. In addition, their mRNA as well as their cellular protein expression patterns were analyzed. All data were compared to mammalian CLCA1, 2, 3, and 4. Both avian proteins are encoded by 14 exons and are located in a conserved locus between the Outer Dense Fiber of Sperm Tails 2-Like (ODF2L) and SH3-Domain GRB2-Like Endophilin B1 (SH3GLB1) genes. gCLCA1 combines many properties of mammalian CLCA1, 3 and 4 as it was shown to be a cleaved protein with a typical CLCA domain architecture. Despite its relatively high phylogenetic distance to mammalian CLCA4, it shares most common traits with this member. This includes heavy asparagine-linked glycosylation, the presence of a transmembrane domain in the carboxy-terminal cleavage product and protein expression in the apical membrane of enterocytes. In contrast, gCLCA2 was highly similar to mammalian CLCA2 in terms of its protein architecture, cleavage and glycosylation. These findings were in line with results from in silico analyses of CLCA2 sequences from other avian species.Furthermore, the presence of a transmembrane domain in the carboxy-terminal cleavage product and its expression in keratinocytes are traits of avian CLCA2, which are also found in mammalian CLCA2. Interestingly, and as opposed to the expression patterns of mammalian CLCA proteins, no overlapping tissue or cellular expression patterns were detected for the two galline CLCA members. Based on these findings, CLCA2 appears to be highly conserved among birds and mammals. The results allow to speculate that a hypothetical gene ancestor was expressed in keratinocytes of a common ancestral species before mammalian and avian lineages diverged. This high degree of CLCA2 conservation is in contrast to gCLCA1 and mammalian CLCA1, 3 and 4. During evolution, a hypothetical ancient ancestor of gCLCA1 / mammalian CLCA1, 3, and 4, was likely expressed by enterocytes of a common ancestral species of mammals and birds. The hypothetical ancestral gene seems to have expanded by gene duplications in the mammalian lineage, which did not occur in birds. Besides that, these findings cannot only be used to unveil the evolutionary history of the CLCA family but should be taken into account with regard to the selection of an animal model for the functional analysis of these genes. The chicken might serve as a promising species for knockout models to study CLCA2 functions in vivo. Results obtained from such a knockout chicken are likely transferable to mammalian CLCA2 due to the high degree of conservation. A chicken gCLCA1 knockout model might provide data, which might be transferred most likely to mammalian CLCA4 genes in the gut, as both share a similar cell type specific protein expression in this microenvironment, a similar protein architecture as well as similar biochemical properties. At the transition to the post-genomic era with publically accessible information on gene structures as well as nucleotide and protein sequences of various species, comprehensive analyses of gene families across species have become possible. The comparison of such data in combination with the comparison of gene related information, including cellular expression patterns and biochemical properties, is a powerful approach to enlighten the evolutionary background of proteins. Furthermore, it might be beneficial to identify the most suitable animal model for further functional and biomedical studies.Die CLCA, engl. „chloride channel regulator, calcium-activated“ Genfamilie wird hauptsächlich mit Krebserkrankungen sowie chronisch entzündlichen Atemwegserkrankungen in Zusammenhang gebracht. Die mutmaßlich komplexen Funktionen dieser Gene sind bisher jedoch noch weitgehend unbekannt. Die CLCA Genfamilie umfasst bei Säugetieren vier verschiedene Cluster, die als CLCA1 bis CLCA4 bezeichnet werden. Sie zeichnet sich durch eine außerordentliche Komplexität und Vielfältigkeit aus und beinhaltet tierartlich variierend amplifizierte und inaktivierte Gene. So besitzt der Mensch beispielsweise drei intakte CLCAs sowie ein inaktiviertes Gen, wohingegen die Maus über 8 CLCAs verfügt, von denen ebenfalls eines als inaktiviertes Gen vorliegt. Darüber hinaus sind die Gewebe- und Zellexpressionsmuster der CLCA-Homologen auch innerhalb einer Spezies häufig redundant. Diese Komplexität und Redundanz von CLCA könnten Gründe sein, welche die Aufdeckung der Funktion dieser Genfamilie im Säugetiermodell bisher erschwerte. Damit stellen sich zwei Fragen: Ist die Komplexität dieser Genfamilie eine Eigenart der Säugetiere? Und was ist der evolutionäre Hintergrund für diese Entwicklungen? Um diese Fragen zu beantworten, werden Daten über CLCA benötigt, die von evolutionär weiter entfernten Arten stammen. Kürzlich wurde für das Huhn ein relativ einfacher CLCA Genlokus vorhergesagt, welcher nur zwei CLCA Gene umfasst. Das erste CLCA Genprodukt des Huhns, gCLCA1, zeichnet sich durch eine besondere phylogenetische Nähe zu CLCA1, 3 und 4 der Säugetiere aus. Im Gegensatz dazu ist das zweite CLCA Genprodukt, gCLCA2, näher mit Säuger-CLCA2 verwandt als mit gCLCA1 oder Säuger-CLCA1, 3 oder 4. In dieser kumulativen These wurden die gallinen CLCA Gene sowie deren genomische Struktur analysiert und beide Homologe wurden kloniert. Darüber hinaus wurde deren Proteinarchitektur und die biochemischen Eigenschaften in silico und in vitro untersucht. Weiterhin wurden die mRNA- und zellulären Proteinexpressionsmuster im Vergleich zu CLCA1, 2, 3 und 4 bei Säugetieren analysiert. Beide Vogelproteine werden von 14 Exons kodiert und befinden sich an einem konservierten Ort zwischen den ODF2L, engl. „Outer Dense Fiber of Sperm Tails 2-Like” und SH3GLB1, engl „SH3-Domain GRB2-Like Endophilin B1“ Genen. gCLCA1 vereint mit seiner Proteinspaltung sowie der Proteinarchitektur viele Eigenschaften von CLCA1, 3 und 4 der Säugetiere. Trotz einer relativ großen phylogenetischen Entfernung zu Säuger-CLCA4 weist es jedoch die meisten gemeinsamen Merkmale mit diesem CLCA-Vertreter auf. Hierzu zählen eine starke, an Asparagin gekoppelte Glykosylierung, eine Transmembrandomäne im carboxyterminalen Spaltprodukt und eine Proteinexpression in der apikalen Membran von Enterozyten. Im Gegensatz dazu ist gCLCA2 dem Säugetier-CLCA2 in Bezug auf dessen Phylogenie, Proteinarchitektur, Spaltung und Glykosylierung sehr ähnlich. Diese Befunde ließen sich mittels in silico Analysen auch für weitere aviäre CLCAs nachweisen. Daneben sind die Präsenz einer Transmembrandomäne im carboxyterminalen Spaltprodukt und die Expression in Keratinozyten Merkmale des aviären CLCA2, die auch bei Säugetier-CLCA2 vorzufinden sind. Bemerkenswerterweise fanden sich im Gegensatz zu den Säuger-CLCAs bei den gallinen CLCA-Mitgliedern keine überlappenden gewebe- und zellspezifischen Expressionsmuster. Unter Betrachtung dieser Befunde erscheint CLCA2 bei Vögeln und Säugetieren stark konserviert zu sein. Weiterhin lässt sich auf Basis der in dieser kumulativen These erhobenen Daten spekulieren, dass ein hypothetischer gemeinsamer genetischer Vorfahre wahrscheinlich in Keratinozyten eines gemeinsamen Vorfahren von Vögeln und Säugern exprimiert wurde. Dieser hohe Grad an Konservierung von CLCA2 steht im Gegensatz zu demjenigen von gCLCA1 und Säugetier-CLCA1, 3 und 4. Im Laufe der Evolution scheint ein hypothetischer genetischer Vorfahre von gCLCA1/Säugetier-CLCA1, 3 und 4 vermutlich in Enterozyten eines gemeinsamen Vorfahren von Vögeln und Säugern exprimiert worden zu sein. Dieser hypothetische genetische Vorfahre scheint durch Genduplikationen bei Säugetieren expandiert zu sein, nicht jedoch bei Vögeln. Neben diesen Aussagen zu einem wahrscheinlichen evolutionären Szenario der CLCA Genfamilie zwischen Vogel und Säuger lassen sich die Ergebnisse jedoch auch zur Auswahl eines Modellorganismus zur funktionalen Analyse dieser Gene nutzen. Hierbei erscheint das Huhn zur Untersuchung der CLCA2-Funktion in vivo ein vielversprechender Kandidat für knockout-Modelle, deren Untersuchungsergebnisse durch den Grad an Konservierung mit hoher Wahrscheinlichkeit auf Säugetiere übertragbar sind. Ein gCLCA1-Knockoutmodell könnte hingegen Daten liefern, die hochwahrscheinlich auf CLCA4 Gene von Säugetieren im Darm übertragbar sind, da beide in dieser anatomischen Lokalisation ein vergleichbares zellspezifisches Expressionsmuster sowie eine ähnliche Proteinarchitektur und biochemische Eigenschaften besitzen. Im Anbruch des postgenomischen Zeitalters, in dem Genstrukturen sowie Nukleotid- und Proteinsequenzen verschiedener Spezies öffentlich leicht zugänglich sind, werden umfassende, vergleichende Analysen von Genfamilien über verschiedene Spezies hinweg möglich. In Kombination mit dem Vergleich von genbezogenen Daten wie zellulären Expressionsmustern oder biochemischen Eigenschaften der Genprodukte ist dies ein wirkungsvolles Vorgehen, um den evolutionären Hintergrund von Proteinen aufzudecken und das geeignetste Tiermodell für weitere wissenschaftliche Fragestellung auszuwählen

    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
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