259 research outputs found
Epstein-Barr virus induces adhesion molecule CD226 (DNAM-1) expression during primary B cell transformation into lymphoblastoid cell lines
Continued fraction solution of Krein's inverse problem
The spectral data of a vibrating string are encoded in its so-called
characteristic function. We consider the problem of recovering the distribution
of mass along the string from its characteristic function. It is well-known
that Stieltjes' continued fraction provides a solution of this inverse problem
in the particular case where the distribution of mass is purely discrete. We
show how to adapt Stieltjes' method to solve the inverse problem for a related
class of strings. An application to the excursion theory of diffusion processes
is presented.Comment: 18 pages, 2 figure
Evaluation of onset, cessation and seasonal precipitation of the Southeast Asia rainy season in CMIP5 regional climate models and HighResMIP global climate models
Representing the rainy season of the maritime continent is a challenge for global and regional climate models. Here, we compare regional climate models (RCMs) based on the coupled model intercomparison project phase 5 (CMIP5) model generation with high-resolution global climate models with a comparable spatial resolution from the HighResMIP experiment. The onset and the total precipitation of the rainy season for both model experiments are compared against observational datasets for Southeast Asia. A realistic representation of the monsoon rainfall is essential for agriculture in Southeast Asia as a delayed onset jeopardizes the possibility of having three annual crops. In general, the coupled historical runs (Hist-1950) and the historical force atmosphere run (HighresSST) of the high-resolution model intercomparison project (HighResMIP) suite were consistently closer to the observations than the RCM of CMIP5 used in this study. We find that for the whole of Southeast Asia, the HighResMIP models simulate the onset date and the total precipitation of the rainy season over the region closer to the observations than the other model sets used in this study. High-resolution models in the HighresSST experiment showed a similar performance to their low-resolution equivalents in simulating the monsoon characteristics. The HighresSST experiment simulated the anomaly of the onset date and the total precipitation for different El Niño-southern oscillation conditions best, although the magnitude of the onset date anomaly was underestimated. © 2021 The Authors. International Journal of Climatology published by John Wiley Sons Ltd on behalf of Royal Meteorological Society
Lyapunov exponents, one-dimensional Anderson localisation and products of random matrices
The concept of Lyapunov exponent has long occupied a central place in the
theory of Anderson localisation; its interest in this particular context is
that it provides a reasonable measure of the localisation length. The Lyapunov
exponent also features prominently in the theory of products of random matrices
pioneered by Furstenberg. After a brief historical survey, we describe some
recent work that exploits the close connections between these topics. We review
the known solvable cases of disordered quantum mechanics involving random point
scatterers and discuss a new solvable case. Finally, we point out some
limitations of the Lyapunov exponent as a means of studying localisation
properties.Comment: LaTeX, 23 pages, 3 pdf figures ; review for a special issue on
"Lyapunov analysis" ; v2 : typo corrected in eq.(3) & minor change
An ATM/Chk2-mediated DNA damage responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells
SummaryEpstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as a major component of the underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to lytic viral replication, nor did the DDR marks colocalize with latent episomes. Rather, a transient period of EBV-induced hyperproliferation correlated with DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased transformation efficiency of primary B cells. Further, the viral latent oncoprotein EBNA3C was required to attenuate the EBV-induced DDR. We propose that heightened oncogenic activity in early cell divisions activates a growth-suppressive DDR that is attenuated by viral latency products to induce cell immortalization
Oscillatory surface rheotaxis of swimming E. coli bacteria
Bacterial contamination of biological conducts, catheters or water resources
is a major threat to public health and can be amplified by the ability of
bacteria to swim upstream. The mechanisms of this rheotaxis, the reorientation
with respect to flow gradients, often in complex and confined environments, are
still poorly understood. Here, we follow individual E. coli bacteria swimming
at surfaces under shear flow with two complementary experimental assays, based
on 3D Lagrangian tracking and fluorescent flagellar labelling and we develop a
theoretical model for their rheotactic motion. Three transitions are identified
with increasing shear rate: Above a first critical shear rate, bacteria shift
to swimming upstream. After a second threshold, we report the discovery of an
oscillatory rheotaxis. Beyond a third transition, we further observe
coexistence of rheotaxis along the positive and negative vorticity directions.
A full theoretical analysis explains these regimes and predicts the
corresponding critical shear rates. The predicted transitions as well as the
oscillation dynamics are in good agreement with experimental observations. Our
results shed new light on bacterial transport and reveal new strategies for
contamination prevention.Comment: 12 pages, 5 figure
Arrhythmic Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity treat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator (ICD) represent the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centered risk stratification approach. A novel risk calculator algorithm estimating the 5 year risk of arrhythmias of patients with ARVC have been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient
Arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity threat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator represents the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centred risk stratification approach. A novel risk calculator algorithm estimating the 5-year risk of arrhythmias of patients with ARVC has been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient
International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework
Background - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive ventricular dysfunction. Genetic testing is recommended and a pathogenic variant in an ARVC-associated gene is a major criterion for diagnosis according to the 2010 Task Force Criteria (TFC). As incorrect attribution of a gene to ARVC can contribute to misdiagnosis, we assembled an international multidisciplinary ARVC ClinGen Gene Curation Expert Panel to reappraise all reported ARVC genes. / Methods - Following a comprehensive literature search, six two-member teams conducted blinded independent curation of reported ARVC genes using the semi-quantitative ClinGen framework. /Results - Of 26 reported ARVC genes, only six (PKP2, DSP, DSG2, DSC2, JUP, TMEM43) had strong evidence and were classified as definitive for ARVC causation. There was moderate evidence for two genes, DES and PLN. The remaining 18 genes had limited or no evidence. RYR2 was refuted as an ARVC gene since clinical data and model systems exhibited a catecholaminergic polymorphic ventricular tachycardia (CPVT) phenotype. In ClinVar, only 5 pathogenic / likely pathogenic (P/LP) variants (1.1%) in limited evidence genes had been reported in ARVC cases in contrast to 450 desmosome gene variants (97.4%). / Conclusions - Using the ClinGen approach to gene-disease curation, only eight genes, (PKP2, DSP, DSG2, DSC2, JUP, TMEM43, PLN, DES) had definitive or moderate evidence for ARVC and these genes accounted for nearly all P/LP ARVC variants in ClinVar. Therefore, only P/LP variants in these eight genes should yield a major criterion for ARVC diagnosis. P/LP variants identified in other genes in a patient should prompt further phenotyping as variants in many of these genes are associated with other cardiovascular conditions
Predicting arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis
While many studies evaluate predictors of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC), a systematic review consolidating this evidence is currently lacking. Therefore, we searched MEDLINE and Embase for studies analyzing predictors of ventricular arrhythmias (sustained ventricular tachycardia/fibrillation (VT/VF), appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death) in patients with definite ARVC, patients with borderline ARVC, and ARVC-associated mutation carriers. In the case of multiple publications on the same cohort, the study with the largest population was included. This yielded 45 studies with a median cohort size of 70 patients (interquartile range 60 patients) and a median follow-up of 5.0 years (interquartile range 3.3 - 6.7 years). The average proportion of arrhythmic events observed was 10.6%/y in patients with definite ARVC, 10.0%/y in patients with borderline ARVC, and 3.7%/y with mutation carriers. Predictors of ventricular arrhythmias were population dependent: consistently predictive risk factors in patients with definite ARVC were male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF; in patients with borderline ARVC, 2 additional predictors—inducibility during electrophysiology study and strenuous exercise—were identified; and with mutation carriers, all aforementioned predictors as well as ventricular ectopy, multiple ARVC-related pathogenic mutations, left ventricular dysfunction, and palpitations/presyncope determined arrhythmic risk. Most evidence originated from small observational cohort studies, with a moderate quality of evidence. In conclusion, the average risk of ventricular arrhythmia ranged from 3.7 to 10.6%/y depending on the population with ARVC. Male sex, syncope, T-wave inversion in lead >V3, right ventricular dysfunction, and prior (non)sustained VT/VF consistently predict ventricular arrhythmias in all populations with ARVC
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