250 research outputs found

    Using Attribute Sampling to Assess the Accuracy of a Library Circulation System

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    Auditing an Academic Library Book Collection

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    Librarians may use attribute sampling to estimate the maximum portion of a population having an attribute of interest. Advantages of the technique are that the user may examine a very small portion of the population and make an estimate with very low but measurable risk of misstatement

    Tubular free by cyclic groups act freely on CAT(0) cube complexes

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    AbstractWe identify when a tubular group (the fundamental group of a ûnite graph of groups with ℤ2 vertex and ℤ edge groups) is free by cyclic and show, using Wise’s equitable sets criterion, that every tubular free by cyclic group acts freely on a CAT(0) cube complex.</jats:p

    Optimized Multi-Frequency Spectra for Applications in Radiative Feedback and Cosmological Reionization

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    The recent implementation of radiative transfer algorithms in numerous hydrodynamics codes has led to a dramatic improvement in studies of feedback in various astrophysical environments. However, because of methodological limitations and computational expense, the spectra of radiation sources are generally sampled at only a few evenly-spaced discrete emission frequencies. Using one-dimensional radiative transfer calculations, we investigate the discrepancies in gas properties surrounding model stars and accreting black holes that arise solely due to spectral discretization. We find that even in the idealized case of a static and uniform density field, commonly used discretization schemes induce errors in the neutral fraction and temperature by factors of two to three on average, and by over an order of magnitude in certain column density regimes. The consequences are most severe for radiative feedback operating on large scales, dense clumps of gas, and media consisting of multiple chemical species. We have developed a method for optimally constructing discrete spectra, and show that for two test cases of interest, carefully chosen four-bin spectra can eliminate errors associated with frequency resolution to high precision. Applying these findings to a fully three-dimensional radiation-hydrodynamic simulation of the early universe, we find that the HII region around a primordial star is substantially altered in both size and morphology, corroborating the one-dimensional prediction that discrete spectral energy distributions can lead to sizable inaccuracies in the physical properties of a medium, and as a result, the subsequent evolution and observable signatures of objects embedded within it.Comment: 15 pages, 13 figures, 2 tables, accepted for publication in the Astrophysical Journa

    Solving the Supersymmetric Flavor Problem with Radiatively Generated Mass Hierarchies

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    The supersymmetric flavor problem may be solved if the first and second generation scalars are heavy (with multi-TeV masses) and scalars with large Higgs couplings are light (with sub-TeV masses). We show that such an inverted spectrum may be generated radiatively; that is, from initial conditions where all scalar masses are multi-TeV at some high scale, those with large Higgs couplings may be driven asymptotically to the weak scale in the infra-red. The lightness of third generation scalars is therefore a direct consequence of the heaviness of third generation fermions, and fine-tuning is avoided even though the fundamental scale of the soft supersymmetry breaking parameters is multi-TeV. We investigate this possibility in the framework of the usual Yukawa quasi-fixed point solutions. The required high scale boundary conditions are found to be simple and highly predictive. This scenario also alleviates the supersymmetric CP and Polonyi problems.Comment: 18 pages, 3 figures; typos corrected, refs added, conforms to published versio

    BACE1 activity impairs neuronal glucose oxidation:rescue by beta-hydroxybutyrate and lipoic acid

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    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or &alpha;-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD

    Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

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    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction

    Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study

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    BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged &lt;65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.ObjectiveThis study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD.MethodsParticipants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants' smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age.ResultsThe CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P&lt;.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P&lt;.001 in all cases).ConclusionsThese findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change
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