955 research outputs found
A direct method for analyzing the nonlinear vehicle–structure interaction
This article presents an accurate, efficient and stable algorithm to analyze the nonlinear vertical
vehicle-structure interaction. The governing equilibrium equations of the vehicle and structure are
complemented with additional constraint equations that relate the displacements of the vehicle with the
corresponding displacements of the structure. These equations form a single system, with displacements
and contact forces as unknowns, that is solved using an optimized block factorization algorithm. Due to
the nonlinear nature of contact, an incremental formulation based on the Newton method is adopted. The
vehicles, track and structure are modeled using finite elements to take into account all the significant
deformations. The numerical example presented clearly demonstrates the accuracy and computational
efficiency of the proposed method
A Mathematical Model of Liver Cell Aggregation In Vitro
The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work
Development of an exoglycosidase plate-based assay for detecting α1-3,4 fucosylation biomarker in individuals with HNF1A-MODY
Maturity-onset diabetes of the young due to hepatocyte nuclear factor-1 alpha variants (HNF1A-MODY) causes monogenic diabetes. Individuals carrying damaging variants in HNF1A show decreased levels of α1-3,4 fucosylation, as demonstrated on antennary fucosylation of blood plasma N-glycans. The excellent diagnostic performance of this glycan biomarker in blood plasma N-glycans of individuals with HNF1A-MODY has been demonstrated using liquid chromatography methods. Here, we have developed a high-throughput exoglycosidase plate-based assay to measure α1-3,4 fucosylation levels in blood plasma samples. The assay has been optimized and its validity tested using 1000 clinical samples from a cohort of individuals with young-adult onset diabetes including cases with HNF1A-MODY. The α1-3,4 fucosylation levels in blood plasma showed a good differentiating power in identifying cases with damaging HNF1A variants, as demonstrated by receiver operating characteristic curve analysis with the AUC values of 0.87 and 0.95. This study supports future development of a simple diagnostic test to measure this glycan biomarker for application in a clinical setting. </p
Multimessenger astronomy with the Einstein Telescope
Gravitational waves (GWs) are expected to play a crucial role in the
development of multimessenger astrophysics. The combination of GW observations
with other astrophysical triggers, such as from gamma-ray and X-ray satellites,
optical/radio telescopes, and neutrino detectors allows us to decipher science
that would otherwise be inaccessible. In this paper, we provide a broad review
from the multimessenger perspective of the science reach offered by the third
generation interferometric GW detectors and by the Einstein Telescope (ET) in
particular. We focus on cosmic transients, and base our estimates on the
results obtained by ET's predecessors GEO, LIGO, and Virgo.Comment: 26 pages. 3 figures. Special issue of GRG on the Einstein Telescope.
Minor corrections include
Specificity of polygenic signatures across symptom dimensions in bipolar disorder: an analysis of UK Bipolar Disorder Research Network data
Background
Current definitions and clinical heterogeneity in bipolar disorder are major concerns as they obstruct aetiological research and impede drug development. Therefore, stratification of bipolar disorder is a high priority. To inform stratification, our analysis aimed to examine the patterns and relationships between polygenic liability for bipolar disorder, major depressive disorder (MDD), and schizophrenia with multidimensional symptom representations of bipolar disorder.
Methods
In this analysis, data from the UK Bipolar Disorder Research Network (BDRN) were assessed with the Operational Checklist for Psychotic Disorders. Individuals with bipolar disorder as defined in DSM-IV, of European ancestry (self-reported), aged 18 years or older at time of interview, living in the UK, and registered with the BDRN were eligible for inclusion. Psychopathological variables obtained via interview by trained research psychologists or psychiatrists and psychiatric case notes were used to identify statistically distinct symptom dimensions, calibrated with exploratory factor analysis and validated with confirmatory factor analysis (CFA). CFA was extended to include three polygenic risk scores (PRSs) indexing liability for bipolar disorder, MDD, and schizophrenia in a multiple indicator multiple cause (MIMIC) structural equation model to estimate PRS relationships with symptom dimensions.
Findings
Of 4198 individuals potentially eligible for inclusion, 4148 (2804 [67·6%] female individuals and 1344 [32·4%] male individuals) with a mean age at interview of 45 years (SD 12·03) were available for analysis. Three reliable dimensions (mania, depression, and psychosis) were identified. The MIMIC model fitted the data well (root mean square error of approximation 0·021, 90% CI 0·019–0·023; comparative fit index 0·99) and suggests statistically distinct symptom dimensions also have distinct polygenic profiles. The PRS for MDD was strongly associated with the depression dimension (standardised β 0·125, 95% CI 0·080–0·171) and the PRS for schizophrenia was strongly associated with the psychosis dimension (0·108, 0·082–0·175). For the mania dimension, the PRS for bipolar disorder was weakly associated (0·050, 0·002–0·097).
Interpretation
Our findings support the hypothesis that genetic heterogeneity underpins clinical heterogeneity, suggesting that different symptom dimensions within bipolar disorder have partly distinct causes. Furthermore, our results suggest that a specific symptom dimension has a similar cause regardless of the primary psychiatric diagnosis, supporting the use of symptom dimensions in precision psychiatry
Active Galactic Nuclei at the Crossroads of Astrophysics
Over the last five decades, AGN studies have produced a number of spectacular
examples of synergies and multifaceted approaches in astrophysics. The field of
AGN research now spans the entire spectral range and covers more than twelve
orders of magnitude in the spatial and temporal domains. The next generation of
astrophysical facilities will open up new possibilities for AGN studies,
especially in the areas of high-resolution and high-fidelity imaging and
spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These
studies will address in detail a number of critical issues in AGN research such
as processes in the immediate vicinity of supermassive black holes, physical
conditions of broad-line and narrow-line regions, formation and evolution of
accretion disks and relativistic outflows, and the connection between nuclear
activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic
Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical
Symposia Serie
Magnetic Field Amplification in Galaxy Clusters and its Simulation
We review the present theoretical and numerical understanding of magnetic
field amplification in cosmic large-scale structure, on length scales of galaxy
clusters and beyond. Structure formation drives compression and turbulence,
which amplify tiny magnetic seed fields to the microGauss values that are
observed in the intracluster medium. This process is intimately connected to
the properties of turbulence and the microphysics of the intra-cluster medium.
Additional roles are played by merger induced shocks that sweep through the
intra-cluster medium and motions induced by sloshing cool cores. The accurate
simulation of magnetic field amplification in clusters still poses a serious
challenge for simulations of cosmological structure formation. We review the
current literature on cosmological simulations that include magnetic fields and
outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure
Detector Description and Performance for the First Coincidence Observations between LIGO and GEO
For 17 days in August and September 2002, the LIGO and GEO interferometer
gravitational wave detectors were operated in coincidence to produce their
first data for scientific analysis. Although the detectors were still far from
their design sensitivity levels, the data can be used to place better upper
limits on the flux of gravitational waves incident on the earth than previous
direct measurements. This paper describes the instruments and the data in some
detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial
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Search for single top quarks in the tau+jets channel using 4.8 fb of collision data
We present the first direct search for single top quark production using tau
leptons. The search is based on 4.8 fb of integrated luminosity
collected in collisions at =1.96 TeV with the D0 detector
at the Fermilab Tevatron Collider. We select events with a final state
including an isolated tau lepton, missing transverse energy, two or three jets,
one or two of them tagged. We use a multivariate technique to discriminate
signal from background. The number of events observed in data in this final
state is consistent with the signal plus background expectation. We set in the
tau+jets channel an upper limit on the single top quark cross section of
\TauLimObs pb at the 95% C.L. This measurement allows a gain of 4% in expected
sensitivity for the observation of single top production when combining it with
electron+jets and muon+jets channels already published by the D0 collaboration
with 2.3 fb of data. We measure a combined cross section of
\SuperCombineXSall pb, which is the most precise measurement to date.Comment: 12 pages, 5 figure
b-Jet Identification in the D0 Experiment
Algorithms distinguishing jets originating from b quarks from other jet
flavors are important tools in the physics program of the D0 experiment at the
Fermilab Tevatron p-pbar collider. This article describes the methods that have
been used to identify b-quark jets, exploiting in particular the long lifetimes
of b-flavored hadrons, and the calibration of the performance of these
algorithms based on collider data.Comment: submitted to Nuclear Instruments and Methods in Physics Research
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