7,445 research outputs found

    Studies on genetic and epigenetic regulation of gene expression dynamics

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    The information required to build an organism is contained in its genome and the first biochemical process that activates the genetic information stored in DNA is transcription. Cell type specific gene expression shapes cellular functional diversity and dysregulation of transcription is a central tenet of human disease. Therefore, understanding transcriptional regulation is central to understanding biology in health and disease. Transcription is a dynamic process, occurring in discrete bursts of activity that can be characterized by two kinetic parameters; burst frequency describing how often genes burst and burst size describing how many transcripts are generated in each burst. Genes are under strict regulatory control by distinct sequences in the genome as well as epigenetic modifications. To properly study how genetic and epigenetic factors affect transcription, it needs to be treated as the dynamic cellular process it is. In this thesis, I present the development of methods that allow identification of newly induced gene expression over short timescales, as well as inference of kinetic parameters describing how frequently genes burst and how many transcripts each burst give rise to. The work is presented through four papers: In paper I, I describe the development of a novel method for profiling newly transcribed RNA molecules. We use this method to show that therapeutic compounds affecting different epigenetic enzymes elicit distinct, compound specific responses mediated by different sets of transcription factors already after one hour of treatment that can only be detected when measuring newly transcribed RNA. The goal of paper II is to determine how genetic variation shapes transcriptional bursting. To this end, we infer transcriptome-wide burst kinetics parameters from genetically distinct donors and find variation that selectively affects burst sizes and frequencies. Paper III describes a method for inferring transcriptional kinetics transcriptome-wide using single-cell RNA-sequencing. We use this method to describe how the regulation of transcriptional bursting is encoded in the genome. Our findings show that gene specific burst sizes are dependent on core promoter architecture and that enhancers affect burst frequencies. Furthermore, cell type specific differential gene expression is regulated by cell type specific burst frequencies. Lastly, Paper IV shows how transcription shapes cell types. We collect data on cellular morphologies, electrophysiological characteristics, and measure gene expression in the same neurons collected from the mouse motor cortex. Our findings show that cells belonging to the same, distinct transcriptomic families have distinct and non-overlapping morpho-electric characteristics. Within families, there is continuous and correlated variation in all modalities, challenging the notion of cell types as discrete entities

    Novel 129Xe Magnetic Resonance Imaging and Spectroscopy Measurements of Pulmonary Gas-Exchange

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    Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy. In vivo Xenon-129 gas-exchange magnetic resonance imaging (129Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized 129Xe gas, it has different MR spectral properties as a gas, as it diffuses through the alveolar membrane and as it binds to red-blood-cells. 129Xe MR spectroscopy and imaging provides a way to tease out the different anatomic components of gas-exchange simultaneously and provides spatial information about where abnormalities may occur. In this thesis, I developed and applied 129Xe MR spectroscopy and imaging to measure gas-exchange in the lungs alongside other clinical and imaging measurements. I measured 129Xe gas-exchange in asymptomatic congenital heart disease and in prospective, controlled studies of long-COVID. I also developed mathematical tools to model 129Xe MR signals during acquisition and reconstruction. The insights gained from my work underscore the potential for 129Xe gas-exchange MRI biomarkers towards a better understanding of cardiopulmonary disease. My work also provides a way to generate a deeper imaging and physiologic understanding of gas-exchange in vivo in healthy participants and patients with chronic lung and heart disease

    Cyber Conflict and Just War Theory

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    ABC: Adaptive, Biomimetic, Configurable Robots for Smart Farms - From Cereal Phenotyping to Soft Fruit Harvesting

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    Currently, numerous factors, such as demographics, migration patterns, and economics, are leading to the critical labour shortage in low-skilled and physically demanding parts of agriculture. Thus, robotics can be developed for the agricultural sector to address these shortages. This study aims to develop an adaptive, biomimetic, and configurable modular robotics architecture that can be applied to multiple tasks (e.g., phenotyping, cutting, and picking), various crop varieties (e.g., wheat, strawberry, and tomato) and growing conditions. These robotic solutions cover the entire perception–action–decision-making loop targeting the phenotyping of cereals and harvesting fruits in a natural environment. The primary contributions of this thesis are as follows. a) A high-throughput method for imaging field-grown wheat in three dimensions, along with an accompanying unsupervised measuring method for obtaining individual wheat spike data are presented. The unsupervised method analyses the 3D point cloud of each trial plot, containing hundreds of wheat spikes, and calculates the average size of the wheat spike and total spike volume per plot. Experimental results reveal that the proposed algorithm can effectively identify spikes from wheat crops and individual spikes. b) Unlike cereal, soft fruit is typically harvested by manual selection and picking. To enable robotic harvesting, the initial perception system uses conditional generative adversarial networks to identify ripe fruits using synthetic data. To determine whether the strawberry is surrounded by obstacles, a cluster complexity-based perception system is further developed to classify the harvesting complexity of ripe strawberries. c) Once the harvest-ready fruit is localised using point cloud data generated by a stereo camera, the platform’s action system can coordinate the arm to reach/cut the stem using the passive motion paradigm framework, as inspired by studies on neural control of movement in the brain. Results from field trials for strawberry detection, reaching/cutting the stem of the fruit with a mean error of less than 3 mm, and extension to analysing complex canopy structures/bimanual coordination (searching/picking) are presented. Although this thesis focuses on strawberry harvesting, ongoing research is heading toward adapting the architecture to other crops. The agricultural food industry remains a labour-intensive sector with a low margin, and cost- and time-efficiency business model. The concepts presented herein can serve as a reference for future agricultural robots that are adaptive, biomimetic, and configurable

    International Academic Symposium of Social Science 2022

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    This conference proceedings gathers work and research presented at the International Academic Symposium of Social Science 2022 (IASSC2022) held on July 3, 2022, in Kota Bharu, Kelantan, Malaysia. The conference was jointly organized by the Faculty of Information Management of Universiti Teknologi MARA Kelantan Branch, Malaysia; University of Malaya, Malaysia; Universitas Pembangunan Nasional Veteran Jakarta, Indonesia; Universitas Ngudi Waluyo, Indonesia; Camarines Sur Polytechnic Colleges, Philippines; and UCSI University, Malaysia. Featuring experienced keynote speakers from Malaysia, Australia, and England, this proceeding provides an opportunity for researchers, postgraduate students, and industry practitioners to gain knowledge and understanding of advanced topics concerning digital transformations in the perspective of the social sciences and information systems, focusing on issues, challenges, impacts, and theoretical foundations. This conference proceedings will assist in shaping the future of the academy and industry by compiling state-of-the-art works and future trends in the digital transformation of the social sciences and the field of information systems. It is also considered an interactive platform that enables academicians, practitioners and students from various institutions and industries to collaborate

    A User Study for Evaluation of Formal Verification Results and their Explanation at Bosch

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    Context: Ensuring safety for any sophisticated system is getting more complex due to the rising number of features and functionalities. This calls for formal methods to entrust confidence in such systems. Nevertheless, using formal methods in industry is demanding because of their lack of usability and the difficulty of understanding verification results. Objective: We evaluate the acceptance of formal methods by Bosch automotive engineers, particularly whether the difficulty of understanding verification results can be reduced. Method: We perform two different exploratory studies. First, we conduct a user survey to explore challenges in identifying inconsistent specifications and using formal methods by Bosch automotive engineers. Second, we perform a one-group pretest-posttest experiment to collect impressions from Bosch engineers familiar with formal methods to evaluate whether understanding verification results is simplified by our counterexample explanation approach. Results: The results from the user survey indicate that identifying refinement inconsistencies, understanding formal notations, and interpreting verification results are challenging. Nevertheless, engineers are still interested in using formal methods in real-world development processes because it could reduce the manual effort for verification. Additionally, they also believe formal methods could make the system safer. Furthermore, the one-group pretest-posttest experiment results indicate that engineers are more comfortable understanding the counterexample explanation than the raw model checker output. Limitations: The main limitation of this study is the generalizability beyond the target group of Bosch automotive engineers.Comment: This manuscript is under review with the Empirical Software Engineering journa

    Endogenous measures for contextualising large-scale social phenomena: a corpus-based method for mediated public discourse

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    This work presents an interdisciplinary methodology for developing endogenous measures of group membership through analysis of pervasive linguistic patterns in public discourse. Focusing on political discourse, this work critiques the conventional approach to the study of political participation, which is premised on decontextualised, exogenous measures to characterise groups. Considering the theoretical and empirical weaknesses of decontextualised approaches to large-scale social phenomena, this work suggests that contextualisation using endogenous measures might provide a complementary perspective to mitigate such weaknesses. This work develops a sociomaterial perspective on political participation in mediated discourse as affiliatory action performed through language. While the affiliatory function of language is often performed consciously (such as statements of identity), this work is concerned with unconscious features (such as patterns in lexis and grammar). This work argues that pervasive patterns in such features that emerge through socialisation are resistant to change and manipulation, and thus might serve as endogenous measures of sociopolitical contexts, and thus of groups. In terms of method, the work takes a corpus-based approach to the analysis of data from the Twitter messaging service whereby patterns in users’ speech are examined statistically in order to trace potential community membership. The method is applied in the US state of Michigan during the second half of 2018—6 November having been the date of midterm (i.e. non-Presidential) elections in the United States. The corpus is assembled from the original posts of 5,889 users, who are nominally geolocalised to 417 municipalities. These users are clustered according to pervasive language features. Comparing the linguistic clusters according to the municipalities they represent finds that there are regular sociodemographic differentials across clusters. This is understood as an indication of social structure, suggesting that endogenous measures derived from pervasive patterns in language may indeed offer a complementary, contextualised perspective on large-scale social phenomena

    How Does the Chinese Political Elite Talk about Cyberpolitics? : Narrative Analysis of Authoritarian Legitimation and Regime Resilience

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    From the beginning of his reign, Chinese President Xi Jinping has emphasised the vital role of the internet and cyberspace in safeguarding regime stability and national strength. Sweeping new legislation has been introduced to reinforce the CCP’s monopoly of information and mass data control. This thesis examines the party elite’s narratives on cyberpolitics, analysing the relationship between these stories and continuing target of regime durability and resilience. China has become more confident and active in promoting its authoritarian concept of cyber sovereignty at home and abroad. This dissertation, therefore, contributes to the increased need of understanding the CCP’s vision of the future of cyberspace. The research material consists of relevant speeches and policy documents published in the Xi era, being analysed in the light of a theoretical framework combining the traditional totalitarian-authoritarian approach with newer concepts of authoritarian legitimation and digital authoritarianism. The findings support the view that Chinese leadership nurtures both performance-based and ideological claims to justify its position in front of ‘netizens’. The relationship between stories and power is widely recognised among social scientists. This thesis uses narratology as a methodological tool to provide insight into the CCP’s public legitimation claims. The baseline of the CCP’s public narrative on cyberpolitics is the continual reliance on socio-economic development made possible by the progress directly related to the internet and digital technologies. According to the official story, this kind of progress can be solely provided by the party with the visionary, exceptional General Secretary Xi as its core leader. Xi and the party’s leadership abilities are underlined, and their position is justified, by referring to the over-arching, ideological goals of the China Dream and national rejuvenation, requiring unquestioned unity from the whole nation. Kiinan presidentti Xi Jinping on valtakautensa alusta saakka korostanut internetin ja kyberavaruuden merkitystĂ€ hallinnon vakauden ja kansallisen vahvuuden edistĂ€misessĂ€. KKP:n tiedonvĂ€litys- ja datamonopolin vahvistamiseksi on tehty vaikuttavuudeltaan laajamittaisia lakiuudistuksia. TĂ€ssĂ€ tutkielmassa perehdytÀÀn puolue-eliitin kyberpolitiikkaa koskeviin narratiiveihin sekĂ€ analysoidaan nĂ€iden tarinoiden suhdetta puolueen keskeiseen tavoitteeseen koskien hallintomuodon jatkuvuutta ja resilienssiĂ€. Kiina edistÀÀ kotimaassa ja maailmalla yhĂ€ rohkeammin ja aktiivisemmin autoritaarista kybersuvereniteetin kĂ€sitettĂ€. TĂ€mĂ€ tutkielma pyrkii omalta osaltaan vastaamaan kasvaneeseen tietotarpeeseen koskien KKP:n visiota kyberavaruuden tulevaisuudesta. Tutkimusaineisto koostuu keskeisistĂ€ Xin aikana julkaistuista puheista ja poliittisista ohjelmista. SitĂ€ analysoidaan perinteistĂ€ totalitaristis-autoritarista lĂ€hestymistapaa sekĂ€ uudempia, autoritaarisen legitimaation ja digitaalisen autoritarismin kĂ€sitteitĂ€ yhdistelevĂ€n teoreettisen viitekehyksen valossa. Tulokset vahvistavat nĂ€kemystĂ€, jonka mukaan Kiinan poliittinen johto kĂ€yttÀÀ sekĂ€ suorituskykyyn pohjautuvia ettĂ€ ideologisia vĂ€itteitĂ€ perustellakseen asemansa “nettikansalaisille”. Tarinoiden ja vallan suhde on tunnustettu laajalti yhteiskuntatieteilijöiden keskuudessa. TĂ€ssĂ€ tutkielmassa narratiivinen analyysi toimii metodologisena työkaluna, jonka avulla tarkastellaan KKP:n julkisia legitimaatiovĂ€itteitĂ€. KKP:n julkiset kyberpolitiikkaa koskevat narratiivit perustuvat vahvasti yhteiskunnallis-taloudelliseen kehitykseen, jonka kerrotaan mahdollistuvan internetin ja digitaalisen edistyksellisyyden kautta. Virallisen tarinan mukaan tĂ€llaista edistystĂ€ voi tarjota vain kommunistinen puolue johdossaan visionÀÀrinen ja poikkeuksellinen ydinjohtaja, pÀÀsihteeri Xi Jinping. Xin ja puolueen johtamistaitoja korostetaan, ja asema maan johdossa pyritÀÀn perustelemaan viittaamalla kaikenkattaviin ideologisiin tavoitteisiin kiinalaisesta unelmasta sekĂ€ kansallisesta uudelleenherÀÀmisestĂ€. KKP:n narratiivin mukaan nĂ€mĂ€ tavoitteet edellyttĂ€vĂ€t ehdotonta yhtenĂ€isyyttĂ€ koko kansakunnalta

    Making Presentation Math Computable

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    This Open-Access-book addresses the issue of translating mathematical expressions from LaTeX to the syntax of Computer Algebra Systems (CAS). Over the past decades, especially in the domain of Sciences, Technology, Engineering, and Mathematics (STEM), LaTeX has become the de-facto standard to typeset mathematical formulae in publications. Since scientists are generally required to publish their work, LaTeX has become an integral part of today's publishing workflow. On the other hand, modern research increasingly relies on CAS to simplify, manipulate, compute, and visualize mathematics. However, existing LaTeX import functions in CAS are limited to simple arithmetic expressions and are, therefore, insufficient for most use cases. Consequently, the workflow of experimenting and publishing in the Sciences often includes time-consuming and error-prone manual conversions between presentational LaTeX and computational CAS formats. To address the lack of a reliable and comprehensive translation tool between LaTeX and CAS, this thesis makes the following three contributions. First, it provides an approach to semantically enhance LaTeX expressions with sufficient semantic information for translations into CAS syntaxes. Second, it demonstrates the first context-aware LaTeX to CAS translation framework LaCASt. Third, the thesis provides a novel approach to evaluate the performance for LaTeX to CAS translations on large-scaled datasets with an automatic verification of equations in digital mathematical libraries. This is an open access book

    Evaluating footwear “in the wild”: Examining wrap and lace trail shoe closures during trail running

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    Trail running participation has grown over the last two decades. As a result, there have been an increasing number of studies examining the sport. Despite these increases, there is a lack of understanding regarding the effects of footwear on trail running biomechanics in ecologically valid conditions. The purpose of our study was to evaluate how a Wrap vs. Lace closure (on the same shoe) impacts running biomechanics on a trail. Thirty subjects ran a trail loop in each shoe while wearing a global positioning system (GPS) watch, heart rate monitor, inertial measurement units (IMUs), and plantar pressure insoles. The Wrap closure reduced peak foot eversion velocity (measured via IMU), which has been associated with fit. The Wrap closure also increased heel contact area, which is also associated with fit. This increase may be associated with the subjective preference for the Wrap. Lastly, runners had a small but significant increase in running speed in the Wrap shoe with no differences in heart rate nor subjective exertion. In total, the Wrap closure fit better than the Lace closure on a variety of terrain. This study demonstrates the feasibility of detecting meaningful biomechanical differences between footwear features in the wild using statistical tools and study design. Evaluating footwear in ecologically valid environments often creates additional variance in the data. This variance should not be treated as noise; instead, it is critical to capture this additional variance and challenges of ecologically valid terrain if we hope to use biomechanics to impact the development of new products
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