499 research outputs found
Spoken word recognition without a TRACE
International audienceHow do we map the rapid input of spoken language onto phonological and lexical representations over time? Attempts at psychologically-tractable computational models of spoken word recognition tend either to ignore time or to transform the temporal input into a spatial representation. TRACE, a connectionist model with broad and deep coverage of speech perception and spoken word recognition phenomena, takes the latter approach, using exclusively time-specific units at every level of representation. TRACE reduplicates featural, phonemic, and lexical inputs at every time step in a large memory trace, with rich interconnections (excitatory forward and backward connections between levels and inhibitory links within levels). As the length of the memory trace is increased, or as the phoneme and lexical inventory of the model is increased to a realistic size, this reduplication of time-(temporal position) specific units leads to a dramatic proliferation of units and connections, begging the question of whether a more efficient approach is possible. Our starting point is the observation that models of visual object recognition-including visual word recognition-have grappled with the problem of spatial invariance, and arrived at solutions other than a fully-reduplicative strategy like that of TRACE. This inspires a new model of spoken word recognition that combines time-specific phoneme representations similar to those in TRACE with higher-level representations based on string kernels: temporally independent (time invariant) diphone and lexical units. This reduces the number of necessary units and connections by several orders of magnitude relative to TRACE. Critically, we compare the new model to TRACE on a set of key phenomena, demonstrating that the new model inherits much of the behavior of TRACE and that the drastic computational savings do not come at the cost of explanatory power
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The Fully Commutative Elements of G(d,1,n) and a 2-paneled window presentation
Fully commutative elements of Coxeter groups were introduced in 1996 by Stembridge and have since been studied extensively in algebraic combinatorics and representation theory. In 2018, Feinberg, Kim, Lee and Oh extended the notion of fully commutative elements from Coxeter groups to certain families of complex reflection groups, notably the groups and which are a natural generalization of Coxeter groups. In this thesis we give a simple test for determining whether an element in is fully commutative in terms of a so-called two-panel notation. We finally discuss some future directions for work explored in this thesis.</p
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Flow Model Development for the Idaho National Laboratory OU 10-08 Sitewide Groundwater Model
A two-dimensional (2D), steady-state groundwater flow model was developed for the Idaho National Laboratory (INL) sitewide groundwater model. A total of 224 wells inside the model domain were used to calibrate the 2D flow model. Three different calibration techniques, zonation approach, pilot point approach and coupled zonation/pilot point approach, were explored and applied during the model development. The pilot point approach allows modelers to model aquifer heterogeneities at various scales, and extract the maximum amount of data from available monitoring data, permitting the best possible representation of flow and transport at the INL
ERp29 triggers a conformational change in polyomavirus to stimulate membrane binding
Funding Information: We thank Tom Rapoport and Kristen Verhey for critically reading the manuscript. B.T. is a Biological Scholar at the University of Michigan Medical School. E.K.R. is supported by a training grant from the National Science Foundation. S.M. was supported by the Swedish Medical Research Council and the Swedish Society of Medicine. M.B. received a scholarship from the Royal Swedish Academy. The work was supported in part by a grant to T.B. from the National Cancer Institute (CA 082395). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic reticulum (ER), a step that precedes its transport into the cytosol. We show that a PDI-like protein, ERp29, exposes the C-terminal arm of Py's VP1 protein, leading to formation of a hydrophobic particle that binds to a lipid bilayer; this reaction likely mimics initiation of Py penetration across the ER membrane. Expression of a dominant-negative ERp29 decreases Py infection, indicating ERp29 facilitates viral infection. Interestingly, cholera toxin, another toxic agent that crosses the ER membrane into the cytosol, is unfolded by PDI in the ER. Our data thus identify an ER factor that mediates membrane penetration of a nonenveloped virus and suggest that PDI family members are generally involved in ER remodeling reactions.publishersversionPeer reviewe
Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism
<p>Abstract</p> <p>Background</p> <p>Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM).</p> <p>Methods</p> <p>Forty-five severely obese adults (36 women) without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) and pancreatic beta-cell function (HOMA-B).</p> <p>Results</p> <p>Both increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (<it>P </it>= 0.003). In subjects with NGM (n = 30), OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS) independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; <it>P </it>= 0.001) in women with NGM and with IL-6 (rho=-0.55; <it>P </it>= 0.035) in women with IGM (n = 15) matched individually for age, adiposity, and AHI.</p> <p>Conclusions</p> <p>OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-α and IL-6 in previous studies.</p
Role of High total protein in gallbladder bile in the formation of cholesterol gallstones.
While it is generally accepted that cholesterol supersaturation of bile is of key importance in the rapid formation of cholesterol crystals, the role of total biliary protein and pH in the pathogenesis of cholesterol gallstones is less well understood. The relation of cholesterol saturation, total protein, and pH was studied in 73 gallbladder bile samples with and 35 gallbladder bile samples without cholesterol crystals. In samples containing crystals, a trend to higher values of cholesterol and to a higher cholesterol saturation index was observed. However, significantly (P = 0.02) higher concentrations of total protein were found in samples with crystals [0.80 +/- 0.40 g/dL (8.0 +/- 4.0 g/L)] than in samples without crystals [0.63 +/- 0.26 g/dL (6.3 +/- 2.6 g/L)]. Moreover, of 22 bile samples with total protein concentrations greater than 10.0 g/L, cholesterol crystals were detected in all but 2. Total lipids, bile acids, phospholipids, and pH values were not significantly different in the two groups of bile samples. It was concluded that high biliary protein concentrations are frequently associated with cholesterol crystals and may, therefore, be a possible risk factor in the pathogenesis of cholesterol gallstones
Low molecular weight organic acid salts, markers of old fungi activity in wall paintings
Micro-Infrared Spectroscopy (mSR-FTIR) and X-ray diffraction (mSR-XRD) with synchrotron light, Gas
Chromatography/Mass Spectrometry (CG/MS), Optical Microscopy (OM) and Scanning Electron
Microscopy (SEM/EDS) were used to identify and obtain the distribution of complex mixtures of calcium
salts of low molecular weight organic acids (LMWOA) in micro-layered micro-samples. Filamentous fungi
produce LMWOA that can react with metal cations producing stable salts. These substances were found
in the dark spots covering the surfaces of Saint Michael's Chapel wall paintings of the Royal Monastery of
Pedralbes in Barcelona linking them to old fungi activity. The presence of glycerol likewise related to the
fungi activity is also identified in the layers.Postprint (author's final draft
Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: One-year results from the SYNTAX trial
Objectives: To evaluate the cost-effectiveness of alternative approaches to revascularization for patients with three-vessel or left main coronary artery disease (CAD). Background: Previous studies have demonstrated that, despite higher initial costs, long-term costs with bypass surgery (CABG) in multivessel CAD are similar to those for percutaneous coronary intervention (PCI). The impact of drug-eluting stents (DES) on these results is unknown. Methods: The SYNTAX trial randomized 1,800 patients with left main or three-vessel CAD to either CABG (n = 897) or PCI using paclitaxel-eluting stents (n = 903). Resource utilization data were collected prospectively for all patients, and cumulative 1-year costs were assessed from the perspective of the U.S. healthcare system. Results: Total costs for the initial hospitalization were 2,282/patient higher with PCI due mainly to more frequent revascularization procedures and higher outpatient medication costs. Total 1-year costs were thus 43,486 per quality-adjusted life-year gained. Conclusions: Among patients with three-vessel or left main CAD, PCI is an economically attractive strategy over the first year for patients with low and moderate angiographic complexity, while CABG is favored among patients with high angiographic complexity
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