4,391 research outputs found

    Undergraduate Catalog of Studies, 2023-2024

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    Undergraduate Catalog of Studies, 2023-2024

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    Levetiracetam modulates brain metabolic networks and transcriptomic signatures in the 5XFAD mouse model of Alzheimer’s disease

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    IntroductionSubcritical epileptiform activity is associated with impaired cognitive function and is commonly seen in patients with Alzheimer’s disease (AD). The anti-convulsant, levetiracetam (LEV), is currently being evaluated in clinical trials for its ability to reduce epileptiform activity and improve cognitive function in AD. The purpose of the current study was to apply pharmacokinetics (PK), network analysis of medical imaging, gene transcriptomics, and PK/PD modeling to a cohort of amyloidogenic mice to establish how LEV restores or drives alterations in the brain networks of mice in a dose-dependent basis using the rigorous preclinical pipeline of the MODEL-AD Preclinical Testing Core.MethodsChronic LEV was administered to 5XFAD mice of both sexes for 3 months based on allometrically scaled clinical dose levels from PK models. Data collection and analysis consisted of a multi-modal approach utilizing 18F-FDG PET/MRI imaging and analysis, transcriptomic analyses, and PK/PD modeling.ResultsPharmacokinetics of LEV showed a sex and dose dependence in Cmax, CL/F, and AUC0-∞, with simulations used to estimate dose regimens. Chronic dosing at 10, 30, and 56 mg/kg, showed 18F-FDG specific regional differences in brain uptake, and in whole brain covariance measures such as clustering coefficient, degree, network density, and connection strength (i.e., positive and negative). In addition, transcriptomic analysis via nanoString showed dose-dependent changes in gene expression in pathways consistent 18F-FDG uptake and network changes, and PK/PD modeling showed a concentration dependence for key genes, but not for network covariance modeling.DiscussionThis study represents the first report detailing the relationships of metabolic covariance and transcriptomic network changes resulting from LEV administration in 5XFAD mice. Overall, our results highlight non-linear kinetics based on dose and sex, where gene expression analysis demonstrated LEV dose- and concentration-dependent changes, along with cerebral metabolism, and/or cerebral homeostatic mechanisms relevant to human AD, which aligned closely with network covariance analysis of 18F-FDG images. Collectively, this study show cases the value of a multimodal connectomic, transcriptomic, and pharmacokinetic approach to further investigate dose dependent relationships in preclinical studies, with translational value toward informing clinical study design

    Climate Change and Critical Agrarian Studies

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    Climate change is perhaps the greatest threat to humanity today and plays out as a cruel engine of myriad forms of injustice, violence and destruction. The effects of climate change from human-made emissions of greenhouse gases are devastating and accelerating; yet are uncertain and uneven both in terms of geography and socio-economic impacts. Emerging from the dynamics of capitalism since the industrial revolution — as well as industrialisation under state-led socialism — the consequences of climate change are especially profound for the countryside and its inhabitants. The book interrogates the narratives and strategies that frame climate change and examines the institutionalised responses in agrarian settings, highlighting what exclusions and inclusions result. It explores how different people — in relation to class and other co-constituted axes of social difference such as gender, race, ethnicity, age and occupation — are affected by climate change, as well as the climate adaptation and mitigation responses being implemented in rural areas. The book in turn explores how climate change – and the responses to it - affect processes of social differentiation, trajectories of accumulation and in turn agrarian politics. Finally, the book examines what strategies are required to confront climate change, and the underlying political-economic dynamics that cause it, reflecting on what this means for agrarian struggles across the world. The 26 chapters in this volume explore how the relationship between capitalism and climate change plays out in the rural world and, in particular, the way agrarian struggles connect with the huge challenge of climate change. Through a huge variety of case studies alongside more conceptual chapters, the book makes the often-missing connection between climate change and critical agrarian studies. The book argues that making the connection between climate and agrarian justice is crucial

    A Survey on Socially Aware Robot Navigation: Taxonomy and Future Challenges

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    Socially aware robot navigation is gaining popularity with the increase in delivery and assistive robots. The research is further fueled by a need for socially aware navigation skills in autonomous vehicles to move safely and appropriately in spaces shared with humans. Although most of these are ground robots, drones are also entering the field. In this paper, we present a literature survey of the works on socially aware robot navigation in the past 10 years. We propose four different faceted taxonomies to navigate the literature and examine the field from four different perspectives. Through the taxonomic review, we discuss the current research directions and the extending scope of applications in various domains. Further, we put forward a list of current research opportunities and present a discussion on possible future challenges that are likely to emerge in the field

    Neuroimaging investigations of cortical specialisation for different types of semantic knowledge

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    Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations. Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation. In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing. Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5. Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL. Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity. To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research

    Direct measurement of coating thermal noise in the AEI 10m prototype

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    A thermal noise interferometer for the characterization of thermal noise in high reflectivity mirrors has been commissioned and first direct measurements of coating thermal noise have been performed. This serves as an important step in the improvement of current and future gravitational wave detectors

    Libro de Abstracts | VIII Jornadas de Investigación y Doctorado: “Ética en la Investigación Científica”

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    El objetivo de estas Jornadas es promover el intercambio científico entre estudiantes de doctorado, fomentando la participación, el debate y la discusión, de aspectos científicos tan importantes como la ética de la investigación. Para poner en valor el papel de los doctores en la sociedad, no podemos pasar por alto las competencias transversales que estos deben adquirir en su formación como doctores. Si bien la ética es algo fundamental en todas las facetas de la vida, en el caso de los investigadores cobra especial relevancia, ya que son generadores de conocimiento sobre el que se asentarán futuros desarrollos y políticas de interés para toda la sociedad. Por lo tanto, con el fin de incrementar la proyección social de las investigaciones llevadas a cabo y la proyección profesional de los doctores, es importante incidir en su formación ética. La base de la investigación académica está construida sobre la confianza. Los investigadores confían en que los resultados informados por otros son veraces. La sociedad confía en que los resultados de la investigación reflejan un intento honesto por parte de los científicos de describir el mundo de forma precisa. Pero esta confianza sólo perdurará si la comunidad científica transmite los valores asociados a la conducta de la ética de investigación. Por este motivo, la Universidad juega un papel muy importante en la formación de los doctores en cuestiones éticas que son inherentes al método científico y a la generación de conocimiento. Dentro de las universidades, las Escuelas Internacionales de Doctorado, con nuestros recursos, aptitudes y espacio de influencia, nos convertimos en actores clave para promover actitudes éticas entre los doctorandos, y estas Jornadas son una oportunidad muy valiosa para tratar este tema. Las ramas de conocimiento que se incluyen para estas Jornadas son las derivadas de los programas de doctorado de la EIDUCAM: -Ciencias de la Salud -Tecnologías de la Computación e Ingeniería Ambiental -Ciencias Sociales -Ciencias del DeporteActividad Física y DeporteAdministración y Dirección de EmpresasAgricultura y VeterinariaArte y HumanidadesCiencias AmbientalesCiencias de la AlimentaciónCiencias de la ComunicaciónCiencias ReligiosasDerechoEducaciónEnfermeríaFarmaciaIdiomasIngeniería, Industria y ConstrucciónMedicinaOdontologíaPodologíaPsicologíaTerapia y RehabilitaciónTurism

    Fictocritical Cyberfeminism: A Paralogical Model for Post-Internet Communication

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    This dissertation positions the understudied and experimental writing practice of fictocriticism as an analog for the convergent and indeterminate nature of “post-Internet” communication as well a cyberfeminist technology for interfering and in-tervening in metanarratives of technoscience and technocapitalism that structure contemporary media. Significant theoretical valences are established between twen-tieth century literary works of fictocriticism and the hybrid and ephemeral modes of writing endemic to emergent, twenty-first century forms of networked communica-tion such as social media. Through a critical theoretical understanding of paralogy, or that countercultural logic of deploying language outside legitimate discourses, in-volving various tactics of multivocity, mimesis and metagraphy, fictocriticism is ex-plored as a self-referencing linguistic machine which exists intentionally to occupy those liminal territories “somewhere in among/between criticism, autobiography and fiction” (Hunter qtd. in Kerr 1996). Additionally, as a writing practice that orig-inated in Canada and yet remains marginal to national and international literary scholarship, this dissertation elevates the origins and ongoing relevance of fictocriti-cism by mapping its shared aims and concerns onto proximal discourses of post-structuralism, cyberfeminism, network ecology, media art, the avant-garde, glitch feminism, and radical self-authorship in online environments. Theorized in such a matrix, I argue that fictocriticism represents a capacious framework for writing and reading media that embodies the self-reflexive politics of second-order cybernetic theory while disrupting the rhetoric of technoscientific and neoliberal economic forc-es with speech acts of calculated incoherence. Additionally, through the inclusion of my own fictocritical writing as works of research-creation that interpolate the more traditional chapters and subchapters, I theorize and demonstrate praxis of this dis-tinctively indeterminate form of criticism to empirically and meaningfully juxtapose different modes of knowing and speaking about entangled matters of language, bod-ies, and technologies. In its conclusion, this dissertation contends that the “creative paranoia” engendered by fictocritical cyberfeminism in both print and digital media environments offers a pathway towards a more paralogical media literacy that can transform the terms and expectations of our future media ecology
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