1,510 research outputs found
Parameter selection and covariance updating
A simple expression is developed for covariance-matrix correction in stochastic model updating. The need for expensive forward propagation of uncertainty through the model is obviated by application of a formula based only on the sensitivity of the outputs at the end of a deterministic updating process carried out on the means of the parameters. Two previously published techniques are show to reduce to the same simple formula within the assumption of small perturbation about the mean. It is shown, using a simple numerical example, that deterministic updating of the parameter means can result in correct reconstruction of the output means even when the updating parameters are wrongly chosen. If the parameters are correctly chosen, then the covariance matrix of the outputs is correctly reconstructed, but when the parameters are wrongly chosen is found that the output covariance is generally not reconstructed accurately. Therefore, the selection of updating parameters on the basis of reconstructing the output means is not sufficient to ensure that the output covariances will be well reconstructed. Further theory is then developed by assessing the contribution of each candidate parameter to the output covariance matrix, thereby enabling the selection of updating parameters to ensure that both the output means and covariances are reconstructed by the updated model. This latter theory is supported by further numerical examples
Constraining the Radii of Neutron Stars with Terrestrial Nuclear Laboratory Data
Neutron star radii are primarily determined by the pressure of isospin
asymmetric matter which is proportional to the slope of the nuclear symmetry
energy. Available terrestrial laboratory data on the isospin diffusion in
heavy-ion reactions at intermediate energies constrain the slope of the
symmetry energy. Using this constraint, we show that the radius (radiation
radius) of a 1.4 solar mass neutron star is between 11.5 (14.4) and 13.6 (16.3)
km.Comment: 11 pages, 3 figures; version to be published in Phys. Lett.
A survey of the parameter space of the compressible liquid drop model as applied to the neutron star inner crust
We present a systematic survey the range of predictions of the neutron star
inner crust composition, crust-core transition densities and pressures, and
density range of the nuclear `pasta' phases at the bottom of the crust provided
by the compressible liquid drop model in the light of current experimental and
theoretical constraints on model parameters. Using a Skyrme-like model for
nuclear matter, we construct baseline sequences of crust models by consistently
varying the density dependence of the bulk symmetry energy at nuclear
saturation density, , under two conditions: (i) that the magnitude of the
symmetry energy at saturation density is held constant, and (ii)
correlates with under the constraint that the pure neutron matter (PNM) EoS
satisfies the results of ab-initio calculations at low densities. Such baseline
crust models facilitate consistent exploration of the dependence of crustal
properties. The remaining surface energy and symmetric nuclear matter
parameters are systematically varied around the baseline, and different
functional forms of the PNM EoS at sub-saturation densities implemented, to
estimate theoretical `error bars' for the baseline predictions. Inner crust
composition and transition densities are shown to be most sensitive to the
surface energy at very low proton fractions and to the behavior of the
sub-saturation PNM EoS. Recent calculations of the energies of neutron drops
suggest that the low-proton-fraction surface energy might be higher than
predicted in Skyrme-like models, which our study suggests may result in a
greatly reduced volume of pasta in the crust than conventionally predicted.Comment: 37 Pages, 16 figures, accepted for publication in Astrophysical
Journal Supplement Serie
Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition
Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors. For this study, the effects of MSA on viability, cell cycle, metabolism, apoptosis, protein and mRNA expression, and reactive oxygen species production were analysed in A549 cells. FOXO3a subcellular localization was examined in A549 cells and in stably transfected human osteosarcoma U2foxRELOC cells. Our results demonstrate that MSA induces FOXO3a nuclear translocation in A549 cells and in U2OS cells that stably express GFP-FOXO3a. Interestingly, sodium selenite, another selenium compound, did not induce any significant effects on FOXO3a translocation despite inducing apoptosis. Single strand break of DNA, disruption of tumour cell metabolic adaptations, decrease in ROS production, and cell cycle arrest in G1 accompanied by induction of apoptosis are late events occurring after 24h of MSA treatment in A549 cells. Our findings suggest that FOXO3a is a relevant mediator of the antiproliferative effects of MSA. This new evidence on the mechanistic action of MSA can open new avenues in exploiting its antitumour properties and in the optimal design of novel combination therapies. We present MSA as a promising chemotherapeutic agent with synergistic antiproliferative effects with cisplatin. (C) 2015 Elsevier Ltd. All rights reserved.Ministerio de Ciencia e Innovacion, Spain [SAF2011-25726]; Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR)-Generalitat de Catalunya [2014SGR1017]; Ministerio de Economia y Competitividad, Spain [SAF2014-56059-R]; Fundacao para a Ciencia e a Tecnologia (FCT) Research Center [UID/BIM/04773/2013CBMR 1334]; National Institute of Health, USA [1R01CA118434-01A2, 1P01CA163223-01A1]; National Science Foundation, USA [EPS-0447479]; FCT [SFRH/BPD/84634/2012]; prize ICREA Academia for excellence in research; ICREA Foundation-Generalitat de Cataluny
First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon
We report the first measurement of coherent elastic neutrino-nucleus
scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge
National Laboratory Spallation Neutron Source. Two independent analyses prefer
\cevns over the background-only null hypothesis with greater than
significance. The measured cross section, averaged over the incident neutrino
flux, is (2.2 0.7) 10 cm -- consistent with the
standard model prediction. The neutron-number dependence of this result,
together with that from our previous measurement on CsI, confirms the existence
of the \cevns process and provides improved constraints on non-standard
neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3:
fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6:
fix Eq 1, new fig 3, V7 final version, updated with final revision
Structure of hadron resonances with a nearby zero of the amplitude
We discuss the relation between the analytic structure of the scattering
amplitude and the origin of an eigenstate represented by a pole of the
amplitude.If the eigenstate is not dynamically generated by the interaction in
the channel of interest, the residue of the pole vanishes in the zero coupling
limit. Based on the topological nature of the phase of the scattering
amplitude, we show that the pole must encounter with the
Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the
dynamical component of the eigenstate is small if a CDD zero exists near the
eigenstate pole. We show that the line shape of the resonance is distorted from
the Breit-Wigner form as an observable consequence of the nearby CDD zero.
Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma
amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio
Specific effects of KChIP3/calsenilin/DREAM, but not KChIPs 1, 2 and 4, on calcium signalling and regulated secretion in PC12 cells
The KChIPs (K+ channel-interacting proteins) are members of the NCS (neuronal calcium sensor) protein family of Ca2+-binding proteins. It is unclear to what extent the KChIPs have distinct functions although they all interact with Kv4 K+ channels. KChIP3 has also been shown to repress transcription of specific genes via binding to DRE (downstream regulatory element) motifs and all KChIPs may share this function. In the present study, we have compared the function of isoforms of the four KChIPs. KChIPs 1–4 were found to stimulate the traffic of Kv4.2 channels to the plasma membrane. KChIP3 expression in PC12 cells resulted in an increase in exocytosis evoked by activation of purinergic receptors. In contrast, KChIPs 1, 2 and 4, although expressed to the same extent, had no effect on secretion. In addition, KChIP3 but not KChIPs 1, 2 and 4 modified the ATP-induced Ca2+ signal resulting in a delay in recovery after the peak Ca2+ elevation and also specifically resulted in down-regulation of the Na+/Ca2+ exchanger NCX3, which could explain the effects on the Ca2+ signal and secretion. Regulation of NCX3 by KChIP3 has been shown to occur via its DREAM (DRE antagonist modulator) function [Gomez-Villafuertes, Torres, Barrio, Savignac, Gabellini, Rizzato, Pintado, Gutierrez-Adan, Mellstrom, Carafoli and Naranjo (2005) J. Neurosci. 25, 10822–10830] suggesting that this activity might depend on the cellular context of expression of the various KChIPs. These results reveal a new role for KChIP3 in the regulation of Ca2+-regulated secretion and also suggest that the functions of each of the KChIPs may be more specialized than previously appreciated
Synthetic Cationic Helical Polypeptides for the Stimulation of Antitumour Innate Immune Pathways in Antigen-Presenting Cells
Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) and Toll-like receptor 9) preferentially in APCs by promoting the release of mitochondrial DNA, which led to the efficient priming of effector T cells. In syngeneic mouse models of locally advanced and metastatic breast cancers, the polypeptides led to potent DNA-sensor-mediated antitumour responses when intravenously given as monotherapy or with immune checkpoint inhibitors. The activation of multiple innate immune pathways via engineered cationic polypeptides may offer therapeutic advantages in the generation of antitumour immune responses
Power and limitations of electrophoretic separations in proteomics strategies
Proteomics can be defined as the large-scale analysis of proteins. Due to the
complexity of biological systems, it is required to concatenate various
separation techniques prior to mass spectrometry. These techniques, dealing
with proteins or peptides, can rely on chromatography or electrophoresis. In
this review, the electrophoretic techniques are under scrutiny. Their
principles are recalled, and their applications for peptide and protein
separations are presented and critically discussed. In addition, the features
that are specific to gel electrophoresis and that interplay with mass
spectrometry (i.e., protein detection after electrophoresis, and the process
leading from a gel piece to a solution of peptides) are also discussed
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