1,505 research outputs found
Parallel single cell analysis on an integrated microfluidic platform for cell trapping, lysis and analysis
We report here a novel and easily scalable microfluidic platform for the parallel analysis of hundreds of individual cells, with controlled single cell trapping, followed by their lysis and subsequent retrieval of the cellular content for on-chip analysis. The device consists of a main channel and an array of shallow side channels connected to the main channel via trapping structures. Cells are individually captured in dam structures by application of a negative pressure from an outlet reservoir, lyzed on site and the cellular content controllably extracted and transported in the individual side channels for on-chip analysis.\u
A probabilistic approach to Zhang's sandpile model
The current literature on sandpile models mainly deals with the abelian
sandpile model (ASM) and its variants. We treat a less known - but equally
interesting - model, namely Zhang's sandpile. This model differs in two aspects
from the ASM. First, additions are not discrete, but random amounts with a
uniform distribution on an interval . Second, if a site topples - which
happens if the amount at that site is larger than a threshold value
(which is a model parameter), then it divides its entire content in equal
amounts among its neighbors. Zhang conjectured that in the infinite volume
limit, this model tends to behave like the ASM in the sense that the stationary
measure for the system in large volumes tends to be peaked narrowly around a
finite set. This belief is supported by simulations, but so far not by
analytical investigations.
We study the stationary distribution of this model in one dimension, for
several values of and . When there is only one site, exact computations
are possible. Our main result concerns the limit as the number of sites tends
to infinity, in the one-dimensional case. We find that the stationary
distribution, in the case , indeed tends to that of the ASM (up
to a scaling factor), in agreement with Zhang's conjecture. For the case ,
we provide strong evidence that the stationary expectation tends to
.Comment: 47 pages, 3 figure
Improved stability regions for ground states of the extended Hubbard model
The ground state phase diagram of the extended Hubbard model containing
nearest and next-to-nearest neighbor interactions is investigated in the
thermodynamic limit using an exact method. It is found that taking into account
local correlations and adding next-to-nearest neighbor interactions both have
significant effects on the position of the phase boundaries. Improved stability
domains for the -pairing state and for the fully saturated ferromagnetic
state at half filling have been constructed. The results show that these states
are the ground states for model Hamiltonians with realistic values of the
interaction parameters.Comment: 21 pages (10 figures are included) Revtex, revised version. To be
published in Phys. Rev. B. E-mail: [email protected]
Dark Matter and the CACTUS Gamma-Ray Excess from Draco
The CACTUS atmospheric Cherenkov telescope collaboration recently reported a
gamma-ray excess from the Draco dwarf spheroidal galaxy. Draco features a very
low gas content and a large mass-to-light ratio, suggesting as a possible
explanation annihilation of weakly interacting massive particles (WIMPs) in the
Draco dark-matter halo. We show that with improved angular resolution, future
measurements can determine whether the halo is cored or cuspy, as well as its
scale radius. We find the relevant WIMP masses and annihilation cross sections
and show that supersymmetric models can account for the required gamma-ray
flux. The annihilation cross section range is found to be not compatible with a
standard thermal relic dark-matter production. We compute for these
supersymmetric models the resulting Draco gamma-ray flux in the GLAST energy
range and the rates for direct neutralino detection and for the flux of
neutrinos from neutralino annihilation in the Sun. We also discuss the
possibility that the bulk of the signal detected by CACTUS comes from direct
WIMP annihilation to two photons and point out that a decaying-dark-matter
scenario for Draco is not compatible with the gamma-ray flux from the Galactic
center and in the diffuse gamma-ray background.Comment: 24 pages, 10 figures; version accepted for publication in JCA
Black Holes as Effective Geometries
Gravitational entropy arises in string theory via coarse graining over an
underlying space of microstates. In this review we would like to address the
question of how the classical black hole geometry itself arises as an effective
or approximate description of a pure state, in a closed string theory, which
semiclassical observers are unable to distinguish from the "naive" geometry. In
cases with enough supersymmetry it has been possible to explicitly construct
these microstates in spacetime, and understand how coarse-graining of
non-singular, horizon-free objects can lead to an effective description as an
extremal black hole. We discuss how these results arise for examples in Type II
string theory on AdS_5 x S^5 and on AdS_3 x S^3 x T^4 that preserve 16 and 8
supercharges respectively. For such a picture of black holes as effective
geometries to extend to cases with finite horizon area the scale of quantum
effects in gravity would have to extend well beyond the vicinity of the
singularities in the effective theory. By studying examples in M-theory on
AdS_3 x S^2 x CY that preserve 4 supersymmetries we show how this can happen.Comment: Review based on lectures of JdB at CERN RTN Winter School and of VB
at PIMS Summer School. 68 pages. Added reference
BPS dyons and Hesse flow
We revisit BPS solutions to classical N=2 low energy effective gauge
theories. It is shown that the BPS equations can be solved in full generality
by the introduction of a Hesse potential, a symplectic analog of the
holomorphic prepotential. We explain how for non-spherically symmetric,
non-mutually local solutions, the notion of attractor flow generalizes to
gradient flow with respect to the Hesse potential. Furthermore we show that in
general there is a non-trivial magnetic complement to this flow equation that
is sourced by the momentum current in the solution.Comment: 25 pages, references adde
Microenvironment involved in FPR1 expression by human glioblastomas
Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.</p
PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY
BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards
BPS Spectrum, Indices and Wall Crossing in N=4 Supersymmetric Yang-Mills Theories
BPS states in N=4 supersymmetric SU(N) gauge theories in four dimensions can
be represented as planar string networks with ends lying on D3-branes. We
introduce several protected indices which capture information on the spectrum
and various quantum numbers of these states, give their wall crossing formula
and describe how using the wall crossing formula we can compute all the indices
at all points in the moduli space.Comment: LaTeX file, 33 pages, 15 figure
Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)
Background: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. Aims: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. Methods: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. Baseline results: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. Conclusion: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856)
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