RISC-Vlim, a RISC-V Framework for Logic-in-Memory Architectures

Most modern CPU architectures are based on the von Neumann principle, where memory and processing units are separate entities. Although processing unit performance has improved over the years, memory capacity has not followed the same trend, creating a performance gap between them. This problem is known as the "memory wall" and severely limits the performance of a microprocessor. One of the most promising solutions is the "logic-in-memory" approach. It consists of merging memory and logic units, enabling data to be processed directly inside the memory itself. Here we propose an RISC-V framework that supports logic-in-memory operations. We substitute data memory with a circuit capable of storing data and of performing in-memory computation. The framework is based on a standard memory interface, so different logic-in-memory architectures can be inserted inside the microprocessor, based both on CMOS and emerging technologies. The main advantage of this framework is the possibility of comparing the performance of different logic-in-memory solutions on code execution. We demonstrate the effectiveness of the framework using a CMOS volatile memory and a memory based on a new emerging technology, racetrack logic. The results demonstrate an improvement in algorithm execution speed and a reduction in energy consumption

Mental states modulate gaze following, but not automatically.

A number of authors have suggested that the computation of another person’s visual perspective occurs automatically. In the current work we examined whether perspective-taking is indeed automatic or more likely to be due to mechanisms associated with conscious control. Participants viewed everyday scenes in which a single human model looked towards a target object. Importantly, the model’s view of the object was either visible or occluded by a physical barrier (e.g., briefcase). Results showed that when observers were given five seconds to freely view the scenes, eye movements were faster to fixate the object when the model could see it compared to when it was occluded. By contrast, when observers were required to rapidly discriminate a target superimposed upon the same object no such visibility effect occurred. We also employed the barrier procedure together with the most recent method (i.e., the ambiguous number paradigm) to have been employed in assessing the perspective-taking theory. Results showed that the model’s gaze facilitated responses even when this agent could not see the critical stimuli. We argue that although humans do take into account the perspective of other people this does not occur automatically

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Risk of hepatocellular carcinoma development in long-term nucles(t)ide analog suppressed patients with chronic hepatitis B

Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years.Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient.Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P < .001) and good prognostic capacity (AUC 0.863) of HCC.Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects

An Integrated System for Large Scale Scanning of Nuclear Emulsions

The European Scanning System, developed to analyse nuclear emulsions at high speed, has been completed with the development of a high level software infrastructure to automate and support large- scale emulsion scanning. In one year, an average installation is capable of performing data-taking and online analysis on a total surface ranging from few m2 to tens of m2, acquiring many billions of tracks, corresponding to several TB. This paper focuses on the procedures that have been implemented and on their impact on physics measurements. The system proved robust, reliable, fault-tolerant and user- friendly, and seldom needs assistance. A dedicated relational Data Base system is the backbone of the whole infrastructure, storing data themselves and not only catalogues of data files, as in common practice, being a unique case in high-energy physics DAQ systems. The logical organisation of the system is described and a summary is given of the physics measurement that are readily available by automated processing

An integrated system for large scale scanning of nuclear emulsions

The European Scanning System, developed to analyse nuclear emulsions at high speed, has been completed with the development of a high level software infrastructure to automate and support large-scale emulsion scanning. In one year, an average installation is capable of performing data-taking and online analysis on a total surface ranging from few m2 to tens of m 2, acquiring many billions of tracks, corresponding to several TB. This paper focuses on the procedures that have been implemented and on their impact on physics measurements. The system proved robust, reliable, fault-tolerant and user-friendly, and seldom needs assistance. A dedicated relational Data Base system is the backbone of the whole infrastructure, storing data themselves and not only catalogues of data files, as in common practice, being a unique case in high-energy physics DAQ systems. The logical organisation of the system is described and a summary is given of the physics measurement that are readily available by automated processin

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

International audienceUsher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries

Background: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group