301 research outputs found
Using parametric model order reduction for inverse analysis of large nonlinear cardiac simulations
Predictive high-fidelity finite element simulations of human cardiac mechanics commonly require a large number of structural degrees of freedom. Additionally, these models are often coupled with lumped-parameter models of hemodynamics. High computational demands, however, slow down model calibration and therefore limit the use of cardiac simulations in clinical practice. As cardiac models rely on several patient-specific parameters, just one solution corresponding to one specific parameter set does not at all meet clinical demands. Moreover, while solving the nonlinear problem, 90% of the computation time is spent solving linear systems of equations. We propose to reduce the structural dimension of a monolithically coupled structure-Windkessel system by projection onto a lower-dimensional subspace. We obtain a good approximation of the displacement field as well as of key scalar cardiac outputs even with very few reduced degrees of freedom, while achieving considerable speedups. For subspace generation, we use proper orthogonal decomposition of displacement snapshots. Following a brief comparison of subspace interpolation methods, we demonstrate how projection-based model order reduction can be easily integrated into a gradient-based optimization. We demonstrate the performance of our method in a real-world multivariate inverse analysis scenario. Using the presented projection-based model order reduction approach can significantly speed up model personalization and could be used for many-query tasks in a clinical setting
Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022
Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we used time series approaches to separate the direct contribution of SARS-CoV-2 infections on mortality from the indirect consequences of pandemic interventions and behavior changes in the United States. We estimated deaths occurring in excess of seasonal baselines stratified by state, age, week and cause (all causes, COVID-19 and respiratory diseases, Alzheimer’s disease, cancer, cerebrovascular disease, diabetes, heart disease, and external causes, including suicides, opioids, accidents) from March 1, 2020 to April 30, 2021. Our estimates of COVID-19 excess deaths were highly correlated with SARS-CoV-2 serology, lending support to our approach. Over the study period, we estimate an excess of 666,000 (95% Confidence Interval (CI) 556000, 774000) all-cause deaths, of which 90% could be attributed to the direct impact of SARS-CoV-2 infection, and 78% were reflected in official COVID-19 statistics. Mortality from all disease conditions rose during the pandemic, except for cancer. The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer’s, and heart diseases, and in age groups over 65 years. In contrast, the largest indirect consequences of the pandemic were seen in deaths from external causes, which increased by 45,300 (95% CI 30,800, 59,500) and were statistically linked to the intensity of non-pharmaceutical interventions. Within this category, increases were most pronounced in mortality from accidents and injuries, drug overdoses, and assaults and homicides, while the rate of death from suicides remained stable. Younger age groups suffered the brunt of these indirect effects. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups, in periods of stricter interventions, and in mortality from external causes. Further research on the drivers of indirect mortality is warranted to optimize interventions in future pandemics
Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies
Measurements of the cross section for exclusive virtual-photoproduction of
rho^0 mesons from hydrogen are reported. The data were collected by the HERMES
experiment using 27.5 GeV positrons incident on a hydrogen gas target in the
HERA storage ring. The invariant mass W of the photon-nucleon system ranges
from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the
virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with
most of the previous data at W > 4 GeV are well described by a model that
infers the W-dependence of the cross section from the dependence on the Bjorken
scaling variable x of the unpolarized structure function for deep-inelastic
scattering. In addition, a model calculation based on Off-Forward Parton
Distributions gives a fairly good account of the longitudinal component of the
rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class.
Revisions: curves added to Fig. 1, several clarifications added to tex
Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering
Polarized deep--inelastic scattering data on longitudinally polarized
hydrogen and deuterium targets have been used to determine double spin
asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for
the production of positive and negative pions from hydrogen were obtained in a
re--analysis of previously published data. Inclusive and semi--inclusive
asymmetries for the production of negative and positive pions and kaons were
measured on a polarized deuterium target. The separate helicity densities for
the up and down quarks and the anti--up, anti--down, and strange sea quarks
were computed from these asymmetries in a ``leading order'' QCD analysis. The
polarization of the up--quark is positive and that of the down--quark is
negative. All extracted sea quark polarizations are consistent with zero, and
the light quark sea helicity densities are flavor symmetric within the
experimental uncertainties. First and second moments of the extracted quark
helicity densities in the measured range are consistent with fits of inclusive
data
Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction
Evidence for a narrow baryon state is found in quasi-real photoproduction on
a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is
observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1
(syst) MeV. Depending on the background model,the naive statistical
significance of the peak is 4--6 standard deviations and its width may be
somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This
state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s))
pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed
in the pK^+ invariant mass distribution. The absence of such a signal indicates
that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure
Low level constraints on dynamic contour path integration
Contour integration is a fundamental visual process. The constraints on integrating
discrete contour elements and the associated neural mechanisms have typically been
investigated using static contour paths. However, in our dynamic natural environment
objects and scenes vary over space and time. With the aim of investigating the
parameters affecting spatiotemporal contour path integration, we measured human
contrast detection performance of a briefly presented foveal target embedded in
dynamic collinear stimulus sequences (comprising five short 'predictor' bars appearing
consecutively towards the fovea, followed by the 'target' bar) in four experiments. The
data showed that participants' target detection performance was relatively unchanged
when individual contour elements were separated by up to 2° spatial gap or 200ms
temporal gap. Randomising the luminance contrast or colour of the predictors, on the
other hand, had similar detrimental effect on grouping dynamic contour path and
subsequent target detection performance. Randomising the orientation of the
predictors reduced target detection performance greater than introducing misalignment
relative to the contour path. The results suggest that the visual system integrates
dynamic path elements to bias target detection even when the continuity of path is
disrupted in terms of spatial (2°), temporal (200ms), colour (over 10 colours) and
luminance (-25% to 25%) information. We discuss how the findings can be largely
reconciled within the functioning of V1 horizontal connections
UBR2 of the N-End Rule Pathway Is Required for Chromosome Stability via Histone Ubiquitylation in Spermatocytes and Somatic Cells
The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells
Impact of Rapid Urbanization on the Rates of Infection by Vibrio cholerae O1 and Enterotoxigenic Escherichia coli in Dhaka, Bangladesh
Bangladesh is a country where acute dehydrating diarrhea or cholera is common and is seen at least two times every year and additionally in natural disasters. In addition cholera cases have increased in the country, especially in urban settings such as in the capital city, Dhaka, where the number of hospitalized patients with more severe disease has tremendously increased. In the present observation, we have concentrated on determining the occurrence of diarrhoea caused by the two most common bacterial agents V. cholerae O1 and enterotoxigenic Escherichia coli (ETEC) in a densely populated, disease prone area Mirpur in Dhaka for two years from March 2008 to February 2010. Stool or rectal specimens from diarrheal patients coming to the ICDDR,B hospital from Mirpur were tested for the two bacterial pathogens. We found that V. cholerae O1 was the major bacterial pathogen and a cause of severe cholera disease in 23% of patients (2,647 of a total of 11,395 patients) from Mirpur. We surmise that cholera vaccines, as well as other public health tools that can target such high risk groups in the country, will be able to reduce the disease morbidity and the transmission of pathogens to improve the quality of life in urban settings
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