SNAVA—A real-time multi-FPGA multi-model spiking neural network simulation architecture

© . This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Spiking Neural Networks (SNN) for Versatile Applications (SNAVA) simulation platform is a scalable and programmable parallel architecture that supports real-time, large-scale, multi-model SNN computation. This parallel architecture is implemented in modern Field-Programmable Gate Arrays (FPGAs) devices to provide high performance execution and flexibility to support large-scale SNN models. Flexibility is defined in terms of programmability, which allows easy synapse and neuron implementation. This has been achieved by using a special-purpose Processing Elements (PEs) for computing SNNs, and analyzing and customizing the instruction set according to the processing needs to achieve maximum performance with minimum resources. The parallel architecture is interfaced with customized Graphical User Interfaces (GUIs) to configure the SNN's connectivity, to compile the neuron-synapse model and to monitor SNN's activity. Our contribution intends to provide a tool that allows to prototype SNNs faster than on CPU/GPU architectures but significantly cheaper than fabricating a customized neuromorphic chip. This could be potentially valuable to the computational neuroscience and neuromorphic engineering communities.Peer ReviewedPostprint (author's final draft

Electrical compatibility of transmission fluids in electric vehicles

The in electrical vehicles, where the electric motor is inside the transmissielectrical compatibility of the automatic transmission fluids (ATFs) is very important on and in contact with the ATF. This work studies the influence of factors like temperature, time, and air exposition on the oxidation of three ATFs and their changes in electrical conductivity. The results showed that the higher content of additive the lower variations of electrical conductivity with the oxidation; the measurements of electrical conductivity are better than FT-IR ones for monitoring oil thermo-oxidative degradation at initial periods; the conventional ATFs could maintain good electrical compatibility in electrified drivelines, although their materials compatibility and copper corrosion protection of electrical components should be also tested

Structural, NMR Spectroscopic and Computational Investigation of Hemin Loading in the Hemophore HasAp from Pseudomonas aeruginosa

Heat shock protein 90 (Hsp90) inhibition by modulation of the N-or C-terminal binding site has become an attractive strategy for the development of anti-cancer chemotherapeutics. The first Hsp90 C-terminus inhibitor, novobiocin, manifested a relatively high IC50 value of ~700 μM. Therefore, investigation of the novobiocin scaffold has led to analogs with improved antiproliferative activity (nanomolar concentrations) against several cancer cell lines. During these studies, novobiocin analogs that do not inhibit Hsp90 were identified; however, these analogs demonstrated potent anti-proliferative activity. Compound 2, a novobiocin analog, was identified as a MAPK pathway signaling disruptor that lacked Hsp90 inhibitory activity. In addition, structural modifications of compound 2 were identified that segregated Hsp90 inhibition from MAPK signaling disruption. These studies indicate that compound 2 represents a novel scaffold for disruption of MAPK pathway signaling and may serve as a useful structure for the generation of new anti-cancer agents

Childhood Obesity among Puerto Rican Children: Discrepancies Between Child’s and Parent’s Perception of Weight Status

Public concern about childhood obesity and associated health problems calls for the identification of modifiable factors that could halt this epidemic. Parental perceptions of their children’s weight status could be associated to how parents influence children’s eating patterns. We aimed to identify the perceptions Puerto Rican parents have of their children’s weight and children’s own perceptions of weight status as compared to real weight. A cross sectional survey was performed in a representative sample of 1st–6th grade students. Only half of the children correctly identified their weight, and only 62.4% of the parents correctly classified their children’s weight. Most obese/overweight children did not perceive themselves as such. Almost half of obese/overweight children were identified by the parents as normal weight while over half of the underweight children were perceived by their parents at normal weight. More girls than boys perceived themselves as obese/overweight and more parents of girls than of boys perceived them as such. Higher-educated parents were better at recognizing overweight/obesity among their children compared to less-educated parents. This study suggests an influence of parents’ SES characteristics on their perceptions of children’s weight status as well as on children’s own perceptions of their weight status

Edible films based on black chia (Salvia hispanica l.) seed mucilage containing Rhus microphylla fruit phenolic extract

Functional films based on black chia (Salvia hispanica L.) seed mucilage (BCm) containing Rhus microphylla (Rm) fruit phenolic extract were built and characterized. A hydro-alcohol extract (HAE) of Rm was incorporated as the bioactive agent due to its noteworthy phenolic profile, and good antioxidant and antifungal activities. The effects of the BCm concentration (0.2% and 0.4%, w/v), HAE incorporation, and their interaction with glycerol (1.0%, w/v) and calcium chloride (0.05%, w/v) on the films physicochemical properties were evaluated. The filmogenic solutions successfully fitted to the HerschelBulkley model (R2 0.05) changed by the HAE addition, but their surface tension was enhanced (p < 0.05), which could favor their coating ability. The polyanionic nature of the systems (zeta potential-Zp values from 26.9 to 33.3 mV) allowed them to interact with Ca2+ cations, thus forming stable and resistant films. All the films showed low water solubility (15.0% to 22.3%) and high permeability (3.7 to 4.0 × 1010 g m1 s1 Pa1), as well as high biodegradability (moisture content from 66.0% to 80.9%); although the moisture content was reduced (p < 0.05) with HAE addition. The combination of higher BCm ratio and HAE addition (BCm0.4+Rm) led to a more resistant, thick, opaque, and dark film compared with the others obtained. This study reveals the BCm-based films potential, highlighting those with HAE, representing a novel alternative to improve the quality of food products.Financial support from Universidad Autónoma Agraria Antonio Narro (UAAAN) is gratefully acknowledged by the authors. Zlatina Genisheva thanks to Foundation for Science and Technology (FCT) for the financial support (ref. SFRH/BPD/108868/2015) and to the project COMPETE 2020 (POCI-01-0145-FEDER-029145). This study was supported by FCT under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors would also like to thank to Pablo Virgen of Biocampo S.A. de C.V. and MSc Fidel Peña-Ramos from UAAAN, for their assistance during this study.info:eu-repo/semantics/publishedVersio

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

BACKGROUND: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia

Prediction of the disease course in Friedreich ataxia

We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors. We used modelling techniques including generalised linear models, support-vector-machines and decision trees. The scale for rating and assessment of ataxia (SARA) and the activities of daily living (ADL) could be predicted with predictive errors quantified by root-mean-squared-errors (RMSE) of 6.49 and 5.83, respectively. Also, we were able to achieve reasonable performance for loss of ambulation (ROC-AUC score of 0.83). However, predictions for the SCA functional assessment (SCAFI) and presence of cardiological symptoms were difficult. In conclusion, we demonstrate that some clinical features of FRDA can be predicted with reasonable error; being a first step towards future clinical applications of predictive modelling. In contrast, targets where predictions were difficult raise the question whether there are yet unknown variables driving the clinical phenotype of FRDA

Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)

Introduction: Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown. Methods: The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4) to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1 (placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examinations including cardiological signs. The primary outcome is the change in the Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the upregulation of the frataxin protein level, safety and survival/death. Perspective: The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide treatment in patients with Friedreich ataxia