Time Dynamics of the Down-Coupling Phenomenon in 3-D NAND Strings

We present a detailed analysis of the time dynamics of the down-coupling phenomenon (DCP) in 3-D NAND Flash memory strings. The transient time dynamics of the channel potential following the wordline (WL) bias transition fromthe pass voltage to zero is studied via numerical simulation, highlighting the existence of three temporal regimes controlledby different physical processes: electron emission from traps, hole injection from the string edges followed by capture, and propagation along the string. The impact of these processes is separately studied, followed by an analysis of the dependence of the DCP recovery time on architectural parameters. Results highlight the relevant physics and can be used as a design guideline for NAND strings with reduced sensitivity to the DCP

Clinical significance of diabetes likely induced by statins : Evidence from a large population-based cohort

Aim: To provide information on the extent to which type 2 diabetes more likely induced by statins affects the risk of macrovascular complications compared to diabetes unlikely induced by statins. Methods: The 84,828 residents in the Italian Lombardy Region who were newly treated with statins between 2003 and 2005 were followed from the index statin prescription until 2009 (step-1 follow-up) to identify those starting antidiabetic therapy. The proportion of days of follow-up covered by statins measured adherence with statins. Cohort members who experienced diabetes were 1: 3 matched with those who did not developed diabetes for gender, age and previous adherence with statin treatment. The 3321 diabetic - non-diabetic sets, were followed from the initial antidiabetic therapy until 2012 (step-2 follow-up) to estimate the hazard ratio (HR), and 95% Confidence Interval (CI), for macrovascular complications (proportional hazard models) associated with diabetes separately in each category of adherence with statins. Results: During the step-1 follow-up, the risk of new-onset diabetes increased progressively with increasing adherence with statins. During the step-2 follow-up, the risk of macrovascular complications associated with diabetes decreased progressively from 1.70 (1.18-2.44), 1.41 (1.17-1.70), 1.30 (1.07-1.57) until 1.10 (0.40-2.80) as adherence with statins during the step-1 follow-up increased. Conclusions: Type 2 diabetes lost its association with increasing macrovascular risk when previous adherence with statins was very high, and thus the chance of its induction by the drug greater. Statin-dependent type 2 diabetes might be prognostically less adverse than diabetes unlikely induced by statins

Electrode-dependent asymmetric conduction mechanisms in K0.5Na0.5NbO3 micro-capacitors

The ultimate performance of devices employing lead-free piezoelectrics is determined not only by the intrinsic properties of the piezo, but also by processes and materials employed to create the electric contacts. In this paper, we investigate the impact of different metallic electrodes with increasing chemical reactivity (Pt, Ni, Ti, Cr), on the asymmetric behavior of the leakage current in M/K0.5Na0.5NbO3/Pt(111) micro-capacitors, where M stands for the top metallic electrode. For all electrodes we found a marked leakage asymmetry that we ascribed to the presence of a Schottky-like rectifying junction at the M/K0.5Na0.5NbO3/Pt(111) bottom interface, while the corresponding junction at the top interface is deeply affected by the creation of oxygen vacancies due to oxygen scavenging during the growth of the top metallic electrodes, leading to an almost ohmic top contact. The leakage increases with the reactivity of the electrodes, while the asymmetry decreases, thus suggesting that the creation of the top metal/K0.5Na0.5NbO3 interface generates oxygen vacancies diffusing down to the bottom interface and impacting on the rectifying behavior of the Schottky-like junction. Noteworthy, this asymmetric conduction can reflect in an asymmetric piezoelectric and ferroelectric behavior, as a sizable portion of the applied voltage drops across the rectifying junction in reverse bias, thus hampering symmetric bipolar operation, especially in leaky materials

Neurofascin (NFASC) gene mutation causes autosomal recessive ataxia with demyelinating neuropathy

Introduction: Neurofascin, encoded by NFASC, is a transmembrane protein that plays an essential role in nervous system development and node of Ranvier function. Anti-Neurofascin autoantibodies cause a specific type of chronic inflammatory demyelinating polyneuropathy (CIDP) often characterized by cerebellar ataxia and tremor. Recently, homozygous NFASC mutations were recently associated with a neurodevelopmental disorder in two families. Methods: A combined approach of linkage analysis and whole-exome sequencing was performed to find the genetic cause of early-onset cerebellar ataxia and demyelinating neuropathy in two siblings from a consanguineous Italian family. Functional studies were conducted on neurons from induced pluripotent stem cells (iPSCs) generated from the patients. Results: Genetic analysis revealed a homozygous p.V1122E mutation in NFASC. This mutation, affecting a highly conserved hydrophobic transmembrane domain residue, led to significant loss of Neurofascin protein in the iPSC-derived neurons of affected siblings. Conclusions: The identification of NFASC mutations paves the way for genetic research in the developing field of nodopathies, an emerging pathological entity involving the nodes of Ranvier, which are associated for the first time with a hereditary ataxia syndrome with neuropathy

Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that affects several areas of the CNS, whose pathogenesis is still widely unclear and for which an effective treatment is lacking. We have generated induced pluripotent stem cell-derived dopaminergic neurons from four MSA patients and four healthy controls and from two monozygotic twins discordant for the disease. In this model, we have demonstrated an aberrant autophagic flow and a mitochondrial dysregulation involving respiratory chain activity, mitochondrial content, and CoQ10 biosynthesis. These defective mechanisms may contribute to the onset of the disease, representing potential therapeutic targets. Monzio Compagnoni et al. present an iPSC-based neuronal in vitro model of multiple system atrophy. Patients' dopaminergic neurons display a dysregulation of mitochondrial functioning and autophagy, suggesting new hints for the comprehension of the pathogenesis of the disease

Insight from an Italian Delphi Consensus on EVAR feasibility outside the instruction for use: the SAFE EVAR Study

BACKGROUND: The SAfety and FEasibility of standard EVAR outside the instruction for use (SAFE-EVAR) Study was designed to define the attitude of Italian vascular surgeons towards the use of standard endovascular repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) outside the instruction for use (IFU) through a Delphi consensus endorsed by the Italian Society of Vascular and Endovascular Surgery (Societa Italiana di Chirurgia Vascolare ed Endovascolare - SICVE). METHODS: A questionnaire consisting of 26 statements was developed, validated by an 18 -member Advisory Board, and then sent to 600 Italian vascular surgeons. The Delphi process was structured in three subsequent rounds which took place between April and June 2023. In the first two rounds, respondents could indicate one of the following five degrees of agreement: 1) strongly agree; 2) partially agree; 3) neither agree nor disagree; 4) partially disagree; 5) strongly disagree; while in the third round only three different choices were proposed: 1) agree; 2) neither agree nor disagree; 3) disagree. We considered the consensus reached when >70% of respondents agreed on one of the options. After the conclusion of each round, a report describing the percentage distribution of the answers was sent to all the participants. RESULTS: Two -hundred -forty-four (40.6%) Italian Vascular Surgeons agreed to participate the first round of the Delphi Consensus; the second and the third rounds of the Delphi collected 230 responders (94.3% of the first -round responders). Four statements (15.4%) reached a consensus in the first rounds. Among the 22 remaining statements, one more consensus (3.8%) was achieved in the second round. Finally, seven more statements (26.9%) reached a consensus in the simplified last round. Globally, a consensus was reached for almost half of the proposed statements (46.1%). CONCLUSIONS: The relatively low consensus rate obtained in this Delphi seems to confirm the discrepancy between Guideline recommendations and daily clinical practice. The data collected could represent the source for a possible guidelines' revision and the proposal of specific Good Practice Points in all those aspects with only little evidence available

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A Noise-Resilient Neuromorphic Digit Classifier Based on NOR Flash Memories with Pulse-Width Modulation Scheme

In this work, we investigate the implementation of a neuromorphic digit classifier based on NOR Flash memory arrays as artificial synaptic arrays and exploiting a pulse-width modulation (PWM) scheme. Its performance is compared in presence of various noise sources against what achieved when a classical pulse-amplitude modulation (PAM) scheme is employed. First, by modeling the cell threshold voltage (VT) placement affected by program noise during a program-and-verify scheme based on incremental step pulse programming (ISPP), we show that the classifier truthfulness degradation due to the limited program accuracy achieved in the PWM case is considerably lower than that obtained with the PAM approach. Then, a similar analysis is carried out to investigate the classifier behavior after program in presence of cell VT instabilities due to random telegraph noise (RTN) and to temperature variations, leading again to results in favor of the PWM approach. In light of these results, the present work suggests a viable solution to overcome some of the more serious reliability issues of NOR Flash-based artificial neural networks, paving the way to the implementation of highly-reliable, noise-resilient neuromorphic systems