217 research outputs found

    Dynamics on and of Complex Networks

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    <p>Networks -- abstract objects composed of \emph{vertices} connected by \emph{edges}, are ubiquitous in the real world. </p><p>Examples such as social networks, the world wide web, and neural networks in the brain</p><p>are constantly evolving in their topology, the state of their vertices, or a combination of the two.</p><p>This dissertation presents a computational and theoretical study of three models of network dynamics, one corresponding to each of these modes of evolution.</p><p>The first study models the disintegration of a social network of voters with binary opinions, who prefer to be connected to others with the same opinion. </p><p>We study two versions of the model: the network evolves by voters in discordant ties choosing to either </p><p>adopt the opinion of their neighbors, or to rewire their ties to some randomly chosen voter of (i) the same, or (ii) any, opinion. </p><p>We examine how the probability of rewiring, and the initial fraction ρi\rho_{\textrm{i}} in the minority, </p><p>determine the final minority fraction ρf\rho_{\textrm{f}}, when the network has bifurcated. </p><p>In case (i), there is a critical probability, that is independent of ρi\rho_{\textrm{i}}, above which ρf\rho_{\textrm{f}} is unchanged from ρi\rho_{\textrm{i}}, </p><p>and below which there is full concensus. </p><p>In case (ii), the behavior above the critical probability, that now depends on ρi\rho_{\textrm{i}}, is similar; but </p><p>below it, ρf\rho_{\textrm{f}} matches the result of starting with ρi=1/2\rho_{\textrm{i}} = 1/2. Using simulations and approximate calculations, we explain why these two nearly identical </p><p>models have such dramatically different behaviors.</p><p>The second model, called the \emph{quadratic contact process} (QCP) involves ``birth'' and ``death'' events on a static network. </p><p>Vertices take on the binary states occupied(1) or vacant(0). </p><p>We consider two versions of the model -- Vertex QCP, and Edge QCP, corresponding to </p><p>birth events 1011111-0-1 \longrightarrow 1-1-1 and 110</p><p>1111-1-0 \longrightarrow</p><p>1-1-1 respectively, where `-' represents an edge. </p><p>We study the fraction of occupied vertices at steady state as a function of the birth rate, keeping </p><p>the death rate constant. To investigate the effects </p><p>of network topology, we study the QCP on homogeneous networks with a bounded or rapidly decaying degree distribution, </p><p>and those with a heavy tailed degree distribution. </p><p>From our simulation results and mean field calculations, we conclude </p><p>that on the homogeneous networks, there is a discontinuous phase transition with a</p><p>region of bistability, whereas on the heavy tailed networks, the</p><p>transition is continuous. Furthermore, the critical birth rate is positive </p><p>in the former but zero in the latter.</p><p>In the third study, we propose a general scheme for spatial networks evolving in order to reduce their total edge lengths. </p><p>We study the properties of the </p><p>equilbria of two networks from this class, one of which interpolate between two well studied objects: the Erd\H{o}s-R\'{e}nyi random graph, and the random geometric graph. </p><p>The first of our two evolutions can be used as a model for a social network where individuals have fixed opinions about a number of issues and adjust their ties to be connected to people with similar views. </p><p>The second evolution which preserves the connectivity of the network has potential applications in the design of transportation networks and other distribution systems.</p>Dissertatio

    A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.

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    We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer's disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels

    Io'S Atmospheric Freeze-Out Dynamics In The Presence Of A Non-Condensable Species

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    One dimensional direct simulation Monte Carlo (DSMC) simulations are used to examine the effect of a trace non-condensable species on the freeze-out dynamics of Io's sulfur dioxide sublimation atmosphere during eclipse and egress. Due to finite ballistic times, essentially no collapse occurs during the first 10 minutes of eclipse at altitudes above similar to 100 km, and hence immediately after ingress auroral emission morphology above 100 km should resemble that of the immediate pre-eclipse state. In the absence of a non-condensable species the sublimation SO2 atmosphere will freeze-out (collapse) during eclipse as the surface temperature drops. However, rapid collapse is prevented by the presence of even a small amount of a perfect non-condensable species due to the formation of a static diffusion layer several mean free paths thick near the surface. The higher the non-condensable mole fraction, the longer the collapse time. The effect of a weakly condensable gas species (non-zero sticking/reaction coefficient) was examined since real gas species may not be perfectly non-condensable at realistic surface temperatures. It is found that even a small sticking coefficient dramatically reduces the effect of the diffusion layer on the dynamics. If the sticking coefficient of the non-condensable exceeds similar to 0.25 the collapse dynamics are effectively the same as if there was no non-condensable present. This sensitivity results because the loss of non-condensable to the surface reduces the effective diffusion layer size and the formation of an effective diffusion layer requires that the layer be stationary which does not occur if the surface is a sink. As the surface temperature increases during egress from eclipse the sublimating SO2 gas pushes the non-condensable diffusion layer up to higher altitudes once it becomes dense enough to be collisional. This vertical species stratification should alter the auroral emissions after egress.Aerospace Engineerin

    Gastric Alimetry® test interpretation in gastroduodenal disorders : review and recommendations

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    Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut–brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising > 2000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this paper presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid and is expected to continue to evolve with further development
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