Enabling Blockchain Services for IoE with Zk-Rollups

The Internet of Things includes all connected objects from small embedded systems with low computational power and storage capacities to efficient ones, as well as moving objects like drones and autonomous vehicles. The concept of Internet of Everything expands upon this idea by adding people, data and processing. The adoption of such systems is exploding and becoming ever more significant, bringing with it questions related to the security and the privacy of these objects. A natural solution to data integrity, confidentiality and single point of failure vulnerability is the use of blockchains. Blockchains can be used as an immutable data layer for storing information, avoiding single point of failure vulnerability via decentralization and providing strong security and cryptographic tools for IoE. However, the adoption of blockchain technology in such heterogeneous systems containing light devices presents several challenges and practical issues that need to be overcome. Indeed, most of the solutions proposed to adapt blockchains to devices with low resources confront difficulty in maintaining decentralization or security. The most interesting are probably the Layer 2 solutions, which build offchain systems strongly connected to the blockchain. Among these, zk-rollup is a promising new generation of Layer 2/off-chain schemes that can remove the last obstacles to blockchain adoption in IoT, or more generally, in IoE. By increasing the scalability and enabling rule customization while preserving the same security as the Layer 1 blockchain, zk-rollups overcome restrictions on the use of blockchains for IoE. Despite their promises illustrated by recent systems proposed by startups and private companies, very few scientific publications explaining or applying this barely-known technology have been published, especially for non-financial systems. In this context, the objective of our paper is to fill this gap for IoE systems in two steps. We first propose a synthetic review of recent proposals to improve scalability including onchain (consensus, blockchain organization, …) and offchain (sidechain, rollups) solutions and we demonstrate that zk-rollups are the most promising ones. In a second step, we focus on IoE by describing several interesting features (scalability, dynamicity, data management, …) that are illustrated with various general IoE use case

Investigation of N-terminal domain charged residues on the assembly and stability of HIV-1CA

ABSTRACT: The human immunodeficiency virus type 1 (HIV-1) capsid protein (CA) plays a crucial role in both assembly and maturation of the virion as well as viral infectivity. Previous in vivo experiments generated two N-terminal domain charge change mutants (E45A and E128A/R132A) that showed an increase in stability of the viral core. This increase in core stability resulted in decreased infectivity, suggesting the need for a delicate balance of favorable and unfavorable interactions to both allow assembly and facilitate uncoating following infection. Purified CA protein can be triggered to assemble into tubelike structures through the use of a high salt buffer system. The requirement for high salt suggests the need to overcome charge/charge repulsion between subunits. The mutations mentioned above lie within a highly charged region of the N-terminal domain of CA, away from any of the proposed protein/protein interaction sites. We constructed a number of charge mutants in this region (E45A, E45K, E128A, R132A, E128A/ R132A, K131A, and K131E) and evaluated their effect on protein stability in addition to their effect on the rate of CA assembly. We find that the mutations alter the rate of assembly of CA without significantly changing the stability of the CA monomer. The changes in rate for the mutants studied are found to be due to varying degrees of electrostatic repulsion between the subunits of each mutant

Fifty years of the CERN Proton Synchrotron : Volume 2

This report sums up in two volumes the first 50 years of operation of the CERN Proton Synchrotron. After an introduction on the genesis of the machine, and a description of its magnet and powering systems, the first volume focuses on some of the many innovations in accelerator physics and instrumentation that it has pioneered, such as transition crossing, RF gymnastics, extractions, phase space tomography, or transverse emittance measurement by wire scanners. The second volume describes the other machines in the PS complex: the proton linear accelerators, the PS Booster, the LEP pre-injector, the heavy-ion linac and accumulator, and the antiproton rings.Comment: 58 pages, published as CERN Yellow Report https://cds.cern.ch/record/1597087?ln=e

Evaluating the Efficacy of Medication-Assisted Treatment for First Episode Psychosis: A Scoping Review

Purpose/Background The Substance Abuse and Mental Health Services Administration (SAMHSA) recommends that individuals with substance use disorder (SUD) receive medicated-assisted treatment (MAT), as a complete approach to substance use treatment (SAMHSA, 2019). However, treatment measures using combination treatment for SUD in individuals experiencing first episode psychosis (FEP) are seldom used. This scoping review assesses the efficacy of MAT in conjunction with antipsychotics compared to the use of antipsychotic monotherapy for FEP individuals on hospital readmission rates. Methods The authors conducted a literature review utilizing PubMed, EBSCO, Elsevier, Google Scholar, PsychINFO, and Medline from August 2020 to November 2022. Key phrases in the database search included: first-episode psychosis, comorbid substance use, alcohol use disorder, cannabis use disorder, medication-assisted treatment, buprenorphine, methadone, and antipsychotics. Eligibility criteria included individuals experiencing psychosis defined by hallucination, delusion, or paranoia symptoms with co-occurring substance use. Inclusion criteria include publication within the past five years, English or available English translation, full text, institutional review board-approved, and peer-reviewed. Ultimately, we selected ten articles for this scoping review. Results The ten articles demonstrated improvement of psychotic symptoms but showed mixed results in hospital readmission rates after combination therapy. The most notable restriction for this review was the paucity of published literature on MAT for FEP and comorbid substance use. Of the literature reviewed, patients experiencing comorbid FEP and SUDs were vulnerable to poor outcomes due to the illnesses, limited treatment options targeting both symptoms, and poor retention rates in MAT programs. Implications for Nursing Practice This scoping review highlights the treatment of comorbid SUD and FEP with the use of MAT to potentially reduce hospital readmission rates. There was insufficient evidence to outline targeted treatment regimens for our patient population; therefore, more research is needed in this area

Mouse models of preeclampsia with preexisting comorbidities

Preeclampsia is a pregnancy-specific condition and a leading cause of maternal and fetal morbidity and mortality. It is thought to occur due to abnormal placental development or dysfunction, because the only known cure is delivery of the placenta. Several clinical risk factors are associated with an increased incidence of preeclampsia including chronic hypertension, diabetes, autoimmune conditions, kidney disease, and obesity. How these comorbidities intersect with preeclamptic etiology, however, is not well understood. This may be due to the limited number of animal models as well as the paucity of studies investigating the impact of these comorbidities. This review examines the current mouse models of chronic hypertension, pregestational diabetes, and obesity that subsequently develop preeclampsia-like symptoms and discusses how closely these models recapitulate the human condition. Finally, we propose an avenue to expand the development of mouse models of preeclampsia superimposed on chronic comorbidities to provide a strong foundation needed for preclinical testing

Hyperthermia, radiation and chemotherapy: the role of heat in multidisciplinary cancer care.

The compelling biologic basis for combining hyperthermia with modern cancer therapies including radiation and chemotherapy was first appreciated nearly half a century ago. Hyperthermia complements radiation as conditions contributing to radio-resistance generally enhance sensitivity to heat and sensitizing effects occur through increased perfusion/tumor oxygenation and alteration of cellular death pathways. Chemosensitization with hyperthermia is dependent on the particular mechanism of effect for each agent with synergistic effects noted for several commonly used agents. Clinically, randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in treatment of a wide range of malignancies. Improvements in treatment delivery techniques, streamlined logistics, and greater understanding of the relationship of thermal dosimetry to treatment outcomes continue to facilitate wider clinical implementation. Evolving applications include thermal enhancement of immunotherapy, targeted drug delivery and application of principals of thermal biology towards integration of thermal ablation into multimodality oncologic care

Damage to tropical forests caused by cyclones is driven by wind speed but mediated by topographical exposure and tree characteristics

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world

In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions

Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors

Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the ‘TxArray’, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0211-x) contains supplementary material, which is available to authorized users