1,348 research outputs found

    Profinite Galois descent in K(h)-local homotopy theory

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    We investigate the category of K(h)-local spectra through the action of the Morava stabiliser group. Using condensed mathematics, we give a model for the continuous action of this profinite group on the ∞-category of K(h)-local modules over Morava E-theory, and explain how this gives rise to descent spectral sequences computing the Picard and Brauer groups of K(h)-local spectra. In the second part, we focus on the computation of these spectral sequences at height one, showing that they recover the Hopkins-Mahowald-Sadofsky computation of the Picard group, and giving a complete computation of the Brauer group relative to p-completed complex K-theory

    Automated identification and behaviour classification for modelling social dynamics in group-housed mice

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    Mice are often used in biology as exploratory models of human conditions, due to their similar genetics and physiology. Unfortunately, research on behaviour has traditionally been limited to studying individuals in isolated environments and over short periods of time. This can miss critical time-effects, and, since mice are social creatures, bias results. This work addresses this gap in research by developing tools to analyse the individual behaviour of group-housed mice in the home-cage over several days and with minimal disruption. Using data provided by the Mary Lyon Centre at MRC Harwell we designed an end-to-end system that (a) tracks and identifies mice in a cage, (b) infers their behaviour, and subsequently (c) models the group dynamics as functions of individual activities. In support of the above, we also curated and made available a large dataset of mouse localisation and behaviour classifications (IMADGE), as well as two smaller annotated datasets for training/evaluating the identification (TIDe) and behaviour inference (ABODe) systems. This research constitutes the first of its kind in terms of the scale and challenges addressed. The data source (side-view single-channel video with clutter and no identification markers for mice) presents challenging conditions for analysis, but has the potential to give richer information while using industry standard housing. A Tracking and Identification module was developed to automatically detect, track and identify the (visually similar) mice in the cluttered home-cage using only single-channel IR video and coarse position from RFID readings. Existing detectors and trackers were combined with a novel Integer Linear Programming formulation to assign anonymous tracks to mouse identities. This utilised a probabilistic weight model of affinity between detections and RFID pickups. The next task necessitated the implementation of the Activity Labelling module that classifies the behaviour of each mouse, handling occlusion to avoid giving unreliable classifications when the mice cannot be observed. Two key aspects of this were (a) careful feature-selection, and (b) judicious balancing of the errors of the system in line with the repercussions for our setup. Given these sequences of individual behaviours, we analysed the interaction dynamics between mice in the same cage by collapsing the group behaviour into a sequence of interpretable latent regimes using both static and temporal (Markov) models. Using a permutation matrix, we were able to automatically assign mice to roles in the HMM, fit a global model to a group of cages and analyse abnormalities in data from a different demographic

    Social interactions in bacteria mediated by bacteriocins and horizontal gene transfer

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    Bacteria are highly social organisms that frequently engage in cooperative and competitive interactions to successfully survive and reproduce. Examples include cell-to-cell communication, nutrient scavenging, and chemical warfare. However, the vast majority of our understanding of bacterial sociality has come from the laboratory strains of a small number of gram-negative social evolution model organisms, such as Pseudomonas spp. and Escherichia coli. In my thesis, I aim to expand our understanding of bacterial sociality in natural populations and further across the bacterial tree of life. I do this using two different approaches. Firstly, I use laboratory experiments and sequence analysis to study the evolution and ecology of bacteriocin-mediated competition in natural S. aureus populations, sampled as part of a carriage study on human nasal passages. Theory and laboratory experiments to date have provided extensive evidence that bacteriocin production plays a key role in determining the competitive dynamics of bacterial strains, however evidence from natural populations to support this hypothesis is lacking. I find that inhibitory strains were associated with the propensity to displace competing strains from the nasal cavity, which occurs despite inhibitory activity not being displayed by the majority of strains and targeting interspecific over intraspecific competitors. I also provide evidence for the genetic underpinnings of bacteriocin activity, by identifying five bacteriocin gene clusters associated with inhibition. Secondly, I use a comparative approach to study the role of horizontal gene transfer in stabilising cooperation across bacteria. Bacterial cooperation is typically mediated by the secretion of extracellular public goods, which are costly molecules that provide a fitness benefit to neighbouring cells. Cooperation can be destabilised by the invasion of selfish ‘cheats’ that reap the benefit of public good production without paying a cost. It is widely accepted that horizontal gene transfer, especially via plasmids, can allow cooperators to ‘re-infect’ cheats with the gene for a cooperative trait, thus stabilising cooperation. Although theoretical and experimental studies have provided evidence to support this hypothesis, a comprehensive genomic study that controls for phylogenetic non-independence across species remains to be conducted. The results from our analysis of plasmid genes from 51 diverse bacterial species do not support the cooperation hypothesis across bacteria and are instead supportive of environmental variability as a determining factor in the relationship between horizontal gene transfer and extracellular proteins. Taken together, this thesis provides a body of work that emphasises the importance of testing predictions from theoretical and laboratory experiments in natural populations, and across diverse species

    Talking about personal recovery in bipolar disorder: Integrating health research, natural language processing, and corpus linguistics to analyse peer online support forum posts

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    Background: Personal recovery, ‘living a satisfying, hopeful and contributing lifeeven with the limitations caused by the illness’ (Anthony, 1993) is of particular value in bipolar disorder where symptoms often persist despite treatment. So far, personal recovery has only been studied in researcher-constructed environments (interviews, focus groups). Support forum posts can serve as a complementary naturalistic data source. Objective: The overarching aim of this thesis was to study personal recovery experiences that people living with bipolar disorder have shared in online support forums through integrating health research, NLP, and corpus linguistics in a mixed methods approach within a pragmatic research paradigm, while considering ethical issues and involving people with lived experience. Methods: This mixed-methods study analysed: 1) previous qualitative evidence on personal recovery in bipolar disorder from interviews and focus groups 2) who self-reports a bipolar disorder diagnosis on the online discussion platform Reddit 3) the relationship of mood and posting in mental health-specific Reddit forums (subreddits) 4) discussions of personal recovery in bipolar disorder subreddits. Results: A systematic review of qualitative evidence resulted in the first framework for personal recovery in bipolar disorder, POETIC (Purpose & meaning, Optimism & hope, Empowerment, Tensions, Identity, Connectedness). Mainly young or middle-aged US-based adults self-report a bipolar disorder diagnosis on Reddit. Of these, those experiencing more intense emotions appear to be more likely to post in mental health support subreddits. Their personal recovery-related discussions in bipolar disorder subreddits primarily focussed on three domains: Purpose & meaning (particularly reproductive decisions, work), Connectedness (romantic relationships, social support), Empowerment (self-management, personal responsibility). Support forum data highlighted personal recovery issues that exclusively or more frequently came up online compared to previous evidence from interviews and focus groups. Conclusion: This project is the first to analyse non-reactive data on personal recovery in bipolar disorder. Indicating the key areas that people focus on in personal recovery when posting freely and the language they use provides a helpful starting point for formal and informal carers to understand the concerns of people diagnosed with bipolar disorder and to consider how best to offer support

    Molecular Control of Actin Cortex Architecture During Cell Division

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    Animal cell shape is controlled by gradients in contractile tension of the actin cortex. The cortex is a thin actomyosin network supporting the plasma membrane. At the molecular level, contractile tension is generated by myosin motors pulling on actin filaments. Along- side myosin, actin connectivity has been shown to be key to cortical tension regulation. Understanding molecular organisation of the actin cortex is thus key to understanding cortical tension. To understand how cortical composition changes when tension changes, and to identify potential molecular regulators of cortical tension, I firstly compared protein composition of interphase and mitotic cortices. Indeed, interphase and mitotic cells were previously shown to di↵er in cortical tension. I isolated cortical fractions from cells in these stages of cell cycle, by isolating cortex-enriched blebs. Using mass spectrometry, we detected over 922 proteins in blebs isolated from synchronised cells. Among 238 actin-related proteins, we showed a role for septins in the regulation of the mitotic cell shape. Overall, we created a comprehensive dataset of potential regulators of cortex mechanics. In the second part of my PhD, I focused on the role of actin crosslinkers in cortex tension regulation. In particular, I focused on the role of actin crosslinker size for their localisation and in tension regulation. To this aim, we created artificial crosslinkers, for which I was able to modulate size independently of other features. We created artificial crosslinkers between 5 and 35 nm long, which successfully localised to actin structures. I investigated the role of artificial crosslinkers in the control of cortical thickness, tension and cell division. Together, in this thesis, I investigate new levels of regulation of cortical organisation and tension at the molecular level

    Numerical Studies on Folds and related Deformation Structures in Anisotropic Viscous Materials undergoing Ductile Deformation

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    Folds are common structures in deformed rocks and ice sheets from the microscale to lithospheric scale. This thesis present numerical studies on folds and related deformation structures in anisotropic viscous materials undergoing ductile deformation with various boundary conditions. Mechanical anisotropy considered her is due to a crystallographic preferred orientation (CPO), for example by of alignment of micas or the basal planes of ice crystals. The modelling aims to numerically better understand the various fold geometries that are observed in natural rocks or ice drill cores. This thesis covers two main topics: (i) the influence of an initial CPO and intensity of anisotropy on resulting crenulation geometries in a single-phase material that deforms in moderate strain in dextral simple shear deformation, and (ii) the influence of an initial CPO, intensity of anisotropy and viscosities on evolving fold geometries of single-phase or poly-phase materials that deform in layer-parallel pure shear. The modelling is performed with the Viscoplastic Full-Field Transform (VPFFT) crystal plasticity code coupled with the two-dimensional platform modelling platform Elle. Mechanical anisotropy can enhance shear localisation and redistribute the strain, resulting in localised shear domains with strain concentration and low-strain domains in between. This strain localisation dominates the formation of structures in anisotropic materials and is visualised by foliated layers or foliations. The fold and crenulation geometries displayed in this thesis are made by systematically varying (i) the initial orientation of the anisotropy (CPO), (ii) the intensity of anisotropy, and (iii) the viscous property differences of materials. In simple shear with a CPO in the stretching field from the beginning, three types of localisation behaviour are synthetic shear localisation, antithetic shear localisation and distributed localisation. However, the resulting visible crenulation geometries are very varied and include ‘S-C’ structure (C & C’ bands), ‘anti S-C’ structure (C’’ bands), or mixes of both, or even in some cases no crenulation at all. This highlights that crenulation geometries are primarily due to the strong mechanical anisotropy of rocks. Mechanical anisotropy also affects layer-parallel pure shear shortening simulations. Here we observe two end-member geometries: The first is buckle folding and thickening of a competent layer similar to classical Biot-type buckle folds. An axial planar crenulation cleavage forms in the anisotropic matrix. In the absence of a competent layer, folds in the anisotropic matrix are self-similar with no characteristic length scale. This is observed in polar ice sheets. In this case it was also observed that fold amplification ceased after some strain, due to the rotation of the CPO. This confirms the hypothesis proposed for the shear margins of the Northeast Greenland Ice Stream (NEGIS), where fold amplification ceased about 2000 a BP. The second end member is layer-extension folding with strong amplification of fold amplitudes due to the formation of conjugate, localised bands in the matrix. Other geometries are in between
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