On the theory of diamagnetism in granular superconductors

We study a highly disordered network of superconducting granules linked by weak Josephson junctions in magnetic field and develop a mean field theory for this problem. The diamagnetic response to a slow {\it variations} of magnetic field is found to be analogous to the response of a type-II superconductor with extremely strong pinning. We calculate an effective penetration depth $\lambda_g$ and critical current $j_c$ and find that both $\lambda_g^{-1}$ and $j_c$ are non-zero but are strongly suppressed by frustration.Comment: REVTEX, 12 pages, two Postscript figure

Phase space geometry and slow dynamics

We describe a non-Arrhenius mechanism for slowing down of dynamics that is inherent to the high dimensionality of the phase space. We show that such a mechanism is at work both in a family of mean-field spin-glass models without any domain structure and in the case of ferromagnetic domain growth. The marginality of spin-glass dynamics, as well as the existence of a `quasi equilibrium regime' can be understood within this scenario. We discuss the question of ergodicity in an out-of equilibrium situation.Comment: 23 pages, ReVTeX3.0, 6 uuencoded postscript figures appende

On the Out of Equilibrium Relaxation of the Sherrington - Kirkpatrick model

We derive analytical results for the large-time relaxation of the Sherrington - Kirkpatrick model in the thermodynamic limit, starting from a random configuration. The system never achieves local equilibrium in any fixed sector of phase-space, but remains in an asymptotic out of equilibrium regime. We propose as a tool, both numerical and analytical, for the study of the out of equilibrium dynamics of spin-glass models the use of `triangle relations' which describe the geometry of the configurations at three (long) different times.Comment: 42 Pages + 3 Figures upon reques

An open secret in porcine acute myocardial infarction models: The relevance of anaesthetic regime and breed in ischaemic outcomes.

Large animal models of acute myocardial infarction (AMI) play a crucial role in translating novel therapeutic approaches to patients as denoted by their use in the right-before-human testing platform. At present, the porcine model of AMI is used most frequently as it mimics the human condition and its anatomopathological features accurately. We want to describe to, and share with, the translational research community our experience of how different anaesthetic protocols (sevoflurane, midazolam, ketamine+xylazine+midazolam, and propofol) and pig breeds [Large White and Landrace x Large White (LLW)] can dramatically modify the outcomes of a well-established porcine model of closed-chest AMI. Our group has extensive experience with the porcine model of reperfused AMI and, over time, we reduced the time of ischaemia used to induce the disease from 90 to 50 min to increase the salvageable myocardium for cardioprotection studies. For logistical reasons, we changed both the anaesthetic protocol and the pig breed used, but these resulted in a dramatic reduction in the size of the myocardial infarct, to almost zero in some cases (sevoflurane, 50-min ischaemia, LLW, 2.4 ± 3.9% infarct size), and the cardiac function was preserved. Therefore, we had to re-validate the model by returning to 90 min of ischaemia. Here, we report the differences in infarct size and cardiac function, measured by different modalities, for each combination of anaesthetic protocol and pig breed we have used. Furthermore, we discuss these combinations and the limited literature pertaining to how these two factors influence cardiac function and infarct size in the porcine model of AMI.This research was funded by a grant (PI18/00277) from Instituto de Salud Carlos III (ISCIII), Spain—Fondo Europeo de Desarrollo Regional (FEDER). FJ is the recipient of the Ayudas para la formación de profesorado Universitario (FPU19/04925) grant from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya.S

Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

Sensitivity of a tonne-scale NEXT detector for neutrinoless double beta decay searches

The Neutrino Experiment with a Xenon TPC (NEXT) searches for the neutrinoless double-beta decay of Xe-136 using high-pressure xenon gas TPCs with electroluminescent amplification. A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of neutrinoless double-beta decay decay better than 1E27 years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.Comment: 22 pages, 11 figure

Ventricular arrhythmias in patients with functional mitral regurgitation and implantable cardiac devices: implications of mitral valve repair with Mitraclip

Background: Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods: We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR) grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results: Ninety-three patients (68.2+/-10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-month follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0+/-17.8 vs. 2.7+/-13.5, P=0.002), sustained VT or ventricular fibrillation (0.9+/-2.5 vs. 0.5+/-2.9, P=0.012) and ICD antitachycardia therapies (2.5+/-12.0 vs. 0.9+/-5.0, P=0.033) were observed. Conclusions: PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort