Non-reversible Gaussian processes for identifying latent dynamical structure in neural data

A common goal in the analysis of neural data is to compress large population recordings into sets of interpretable, low-dimensional latent trajectories. This problem can be approached using Gaussian process (GP)-based methods which provide uncertainty quantification and principled model selection. However, standard GP priors do not distinguish between underlying dynamical processes and other forms of temporal autocorrelation. Here, we propose a new family of “dynamical” priors over trajectories, in the form of GP covariance functions that express a property shared by most dynamical systems: temporal non-reversibility. Non-reversibility is a universal signature of autonomous dynamical systems whose state trajectories follow consistent flow fields, such that any observed trajectory could not occur in reverse. Our new multi-output GP kernels can be used as drop-in replacements for standard kernels in multivariate regression, but also in latent variable models such as Gaussian process factor analysis (GPFA). We therefore introduce GPFADS (Gaussian Process Factor Analysis with Dynamical Structure), which models single-trial neural population activity using low-dimensional, non-reversible latent processes. Unlike previously proposed non-reversible multi-output kernels, ours admits a Kronecker factorization enabling fast and memory-efficient learning and inference. We apply GPFADS to synthetic data and show that it correctly recovers ground truth phase portraits. GPFADS also provides a probabilistic generalization of jPCA, a method originally developed for identifying latent rotational dynamics in neural data. When applied to monkey M1 neural recordings, GPFADS discovers latent trajectories with strong dynamical structure in the form of rotations

Individual susceptibility to hexavalent chromium of workers of shoe, hide, and leather industries. Immunological pattern of HLA-B8,DR3-positive subjects

Background. This study was designed to examine the effects of hexavalent chromium [Cr(VI)] on the immunological pattern of shoe, hide, and leather industry workers, moving from the hypothesis that some haplotypes (HLA-B8,DR3) can be important hidden risk cofactors. Methods. Workplaces of 20 firms were monitored for total and respirable dusts and for total and hexavalent chromium. Cr(VI) on materials was also measured. Assay of chromium levels in blood and urine of 44 serological human leukocytes antigen (HLA)-typed workers (20 exposed, 15 HLA-B 8,DR3-negative/5-positive and 24 non-exposed, 18 HLA-B8,DR3-negative/6-positive subjects) was performed by atomic absorption, and lymphocyte subsets (FACS-analysis), mitogen-mediate lympho-proliferation ([H-3]thymidine incorporation), cytokine levels (ELISA), natural killer (NK) cytotoxic activity (Cr-51-release assay) were determined. Results. The environmental parameter levels are lower than threshold limit value-time-weighted average (TLV-TWA); in the materials, the Cr(VI) values exceeded the levels allowed. The peripheral blood mononuclear cells (PBMC) proliferation and the T-helper1 (TH1) cytokine pattern of subjects chronically exposed were significantly raised; addition in vitro of Cr(VI) further stimulated these parameters and in general the entire TH1 system and NK activity. The TH2 system was unaltered. In the HLA-B8,DR3-positive workers, immunologically "low responders", the addition of Cr(VI) in vitro caused a further reduction of the considered parameters in the exposed subjects with a dramatic deficit of the TH1 system. Conclusions. Results indicate the unsuitability of TLV-TWA as a line of demarcation between safe and dangerous Cr(VI) concentrations and the importance of individual genetic susceptibility for occupational and preventative medicine. In particular, the presence of the HLA-138,DR3 alleles can represent an important cofactor of immunotoxic susceptibility consequent to chronic low-dose Cr(VI) exposure. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved

Spatial expression of DNA topoisomerase I genes during cell proliferation in Daucus carota

The spatial expression of carrot (Daucus carota L.) top1 genes encoding the two isoforms of the enzyme DNA topoisomerase I (EC 5.99.1.2) was investigated. In situ hybridization analysis performed with a probe recognizing both top1 transcripts provided evidence that in explanted hypocotyls induced to proliferate in vitro by the addition of the growth regulator 2,4-dichlorophenoxyacetic acid (2,4-D), the mRNA accumulation parallels the proliferation of provascular cells of the stelar cylinder. During somatic embryogenesis, the histological distribution of top1 transcripts was strongly evident at the stage of torpedo-shaped embryos, but gene expression was not only restricted to meristematic regions. When the spatial localization was extended to carrot vegetative apices and the investigation was carried out with specific probes for top1a and top1b, both transcripts preferentially accumulated in tissues having mitotic activity

Reconstruction of Acinetobacter johnsonii ICE_NC genome using hybrid de novo genome assemblies and identification of the 12α-hydroxysteroid dehydrogenase gene

Aims: The role of a Acinetobacter johnsonii strain, isolated from a soil sample, in the biotransformation of bile acids (BAs) was already described but the enzymes responsible for these transformations were only partially purified and molecularly characterized. Methods and Results: This study describes the use of hybrid de novo assemblies, that combine long-read Oxford Nanopore and short-read Illumina sequencing strategies, to reconstruct the entire genome of A. johnsonii ICE_NC strain and to identify the coding region for a 12α-hydroxysteroid dehydrogenase (12α-HSDH), involved in BAs metabolism. The de novo assembly of the A. johnsonii ICE_NC genome was generated using Canu and Unicycler, both strategies yielded a circular chromosome of about 3.6 Mb and one 117 kb long plasmid. Gene annotation was performed on the final assemblies and the gene for 12α-HSDH was detected on the plasmid. Conclusions: Our findings illustrate the added value of long read sequencing in addressing the challenges of whole genome characterization and plasmid reconstruction in bacteria. These approaches also allowed the identification of the A. johnsonii ICE_NC gene for the 12α-HSDH enzyme, whose activity was confirmed at the biochemical level. Significance and impact or the study: At present, this is the first report on the characterization of a 12α-HSDH gene in an A. johnsonii strain able to biotransform cholic acid into ursodeoxycholic acid, a promising therapeutic agent for several diseases. © 2022 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology

Etiquetado de eficiencia energética de calefacción para edificios - IRAM 11900:2009 : Correlaciones con la IRAM 11604:2001 y validación mediante modelos de simulación

Un modo de clasificar la envolvente del edificio mediante su eficiencia energética es siguiendo los lineamientos de la Norma IRAM 11900:2010. El presente trabajo compara las clases de eficiencia energética que define ese etiquetado con lo que resultaría al aplicar la Norma IRAM 11604:2001, basada en el cálculo del coeficiente volumétrico G de pérdidas de calor y su relación con el G correspondiente al Nivel B de confort higrotérmico. Finalmente, también interesa asociar las correlaciones que se concluyen, con los consumos en calefacción que surgen del modelo del edificio simulado. El concepto del kWh/m²-año en calefacción también resulta útil para informar al consumidor. Estos cálculos se han aplicado a cinco edificios públicos en el ámbito de la Ciudad Autónoma de Buenos Aires y a uno de reciente construcción ubicado en el Parque Tecnológico Miguelete del INTI, partido de General San Martín, provincia de Buenos Aires.Following guidelines of IRAM 11900:2009 standard is a way to classify the thermal efficiency of building envelope. The present work compares classes of energy efficiency defined by that label to those resulting from the application of IRAM 11604:2001 standard which is based on the calculation of volumetric heat loss coefficient (G) and its relationship with the G volumetric coefficient of Level B of thermal comfort. Finally, it is also interesting to associate the concluded correlations to heating consumption of simulated building. The concept based on heating kWh/year-m² is also attractive to report to the user. These calculations have been applied to five public buildings in Autonomous City of Buenos Aires and to a recent building sited at Parque Tecnológico Miguelete, San Martín City, Buenos Aires.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Self-reported symptoms of SARS-CoV-2 infection in a non-hospitalized population : results from the large Italian web-based EPICOVID19 cross-sectional survey. (Preprint)

Background: Understanding the occurrence of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)-like symptoms in a large non-hospitalized population, when the epidemic peak was occurring in Italy, is of paramount importance but data are scarce. Objective: Aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test in non-hospitalized individuals and to estimate the occurrence of COVID-19-like symptoms in a larger non-tested population. Methods: This is an Italian countrywide self-administered cross-sectional web-based survey on voluntary adults who completed an anonymous questionnaire in the period 13-21 April 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios with 95% confidence intervals (aOR, 95%CI) by means of multiple logistic regression analysis controlling for age, sex, education, smoking habits, and the number of co-morbidities. Thereafter, for each symptom and for their combination, we calculated sensitivity, specificity, accuracy and AUC in a ROC analysis to estimate the occurrence of COVID-19-like infections in the non-tested population. Results: A total of 171,310 responded to the survey (59.9% females, mean age 47.4 years). Out of the 4,785 respondents with known NPS test result, 4,392 were not hospitalized. Among them, the NPS positive respondents (n=856) most frequently reported myalgia (61.6%), olfactory and/or taste disorders (OTDs, 59.2%), cough (54.4%), and fever (51.9%) whereas 7.7% were asymptomatic. Multiple regression analysis showed that OTDs (aOR 10.3, [95%CI 8.4-12.7]), fever (2.5, 95%CI 2.0-3.1), myalgia (1.5, 95%CI 1.2-1.8), and cough (1.3, 95%CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95%CI, 5.6-9.7) to 35.5 (95%CI, 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95%CI 0.795-0.825) in classifying NPS-P, and was applied to the non-hospitalized and non-tested sample (n=165,782). We found that from 4.4% to 12.1% of respondents had experienced symptoms suggestive of COVID-19 infection. Conclusions: Our results suggest that self-reported symptoms may be reliable indicators of SARS-CoV-2 infection in a pandemic context. A not negligible part (up to 12.1%) of the symptomatic respondents were left undiagnosed and potentially contributed to the spread of the infection

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50\u2009mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19

Continuous Attractors with Morphed/Correlated Maps

Continuous attractor networks are used to model the storage and representation of analog quantities, such as position of a visual stimulus. The storage of multiple continuous attractors in the same network has previously been studied in the context of self-position coding. Several uncorrelated maps of environments are stored in the synaptic connections, and a position in a given environment is represented by a localized pattern of neural activity in the corresponding map, driven by a spatially tuned input. Here we analyze networks storing a pair of correlated maps, or a morph sequence between two uncorrelated maps. We find a novel state in which the network activity is simultaneously localized in both maps. In this state, a fixed cue presented to the network does not determine uniquely the location of the bump, i.e. the response is unreliable, with neurons not always responding when their preferred input is present. When the tuned input varies smoothly in time, the neuronal responses become reliable and selective for the environment: the subset of neurons responsive to a moving input in one map changes almost completely in the other map. This form of remapping is a non-trivial transformation between the tuned input to the network and the resulting tuning curves of the neurons. The new state of the network could be related to the formation of direction selectivity in one-dimensional environments and hippocampal remapping. The applicability of the model is not confined to self-position representations; we show an instance of the network solving a simple delayed discrimination task