Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

Radar observation and recontruction of Cosmos 1408 fragmentation

The population of objects in space has increased dramatically over recent decades. Space debris now represents the majority of objects in space resulting from inactive satellites, breakups, collisions and fragmentations. It has become a concern for institutions all over the world and, as such, it has led to the fostering of several programmes to counter the issues. Among these, the use of ground-based sensors for Space Surveillance Tracking (SST) activities and services and tools for analysing fragmentations play a crucial role. This work presents the activities carried out by Politecnico di Milano, Italian Space Agency and Italian National Institute of Astrophysics in this framework, using data from SST networks and the observation measurements from Bistatic Radar for LEo Survey (BIRALES), an Italian bistatic radar belonging to the EUropean Space Surveillance and Tracking (EUSST), which contributed most to the monitoring of the cloud of fragments. Exploiting Two-Line Elements (TLEs) of observed fragments, a reverse engineering approach is used to reconstruct a fragmentation in orbit through the use of the software suite PUZZLE developed at Politecnico di Milano. The analyses focus on studying the fragmentation of the Cosmos 1408 satellite, which occurred on November 15th 2021 following an Anti-SATellite (ASAT) missile test. More than 1000 trackable pieces and millions of smaller debris (estimated from numerical analysis) were produced by this event, increasing the population of inactive objects around the Earth, and threatening nearby orbiting objects. First, the processing method adopted from BIRALES in observing Cosmos debris is presented and discussed and a critical analysis about the derivable information is conducted. Then, these data and those from SST network observations are used to identify the epoch and the location of the fragmentation. In this procedure, the software toolkit PUZZLE, developed by Politecnico di Milano within a project funded by the Italian Space Agency and extended through the European Research Council, is used

Metabolic modeling of single Th17 cells reveals regulators of autoimmunity

Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T cells and attenuated tissue inflammation in CNS autoimmunity

Pyrite-induced hydroxyl radical formation and its effect on nucleic acids

BACKGROUND: Pyrite, the most abundant metal sulphide on Earth, is known to spontaneously form hydrogen peroxide when exposed to water. In this study the hypothesis that pyrite-induced hydrogen peroxide is transformed to hydroxyl radicals is tested. RESULTS: Using a combination of electron spin resonance (ESR) spin-trapping techniques and scavenging reactions involving nucleic acids, the formation of hydroxyl radicals in pyrite/aqueous suspensions is demonstrated. The addition of EDTA to pyrite slurries inhibits the hydrogen peroxide-to-hydroxyl radical conversion, but does not inhibit the formation of hydrogen peroxide. Given the stability of EDTA chelation with both ferrous and ferric iron, this suggests that the addition of the EDTA prevents the transformation by chelation of dissolved iron species. CONCLUSION: While the exact mechanism or mechanisms of the hydrogen peroxide-to-hydroxyl radical conversion cannot be resolved on the basis of the experiments reported in this study, it is clear that the pyrite surface promotes the reaction. The formation of hydroxyl radicals is significant because they react nearly instantaneously with most organic molecules. This suggests that the presence of pyrite in natural, engineered, or physiological aqueous systems may induce the transformation of a wide range of organic molecules. This finding has implications for the role pyrite may play in aquatic environments and raises the question whether inhalation of pyrite dust contributes to the development of lung diseases

UV degradation of carbofuran insecticide in aqueous solution: identification and toxicity evolution of by-products

The paper reports the results of an investigation about the UV degradation of carbofuran, a widely used insecticide in Europe. Specific objectives were the identification of the by-products formed and the evaluation of the toxicity of the irradiated solution compared to that of carbofuran. The experimental results, obtained treating an aqueous carbofuran solution (50 mg/L) by high pressure UV lamp (125 W), show that the insecticide is completely removed within 120 min. Several intermediate by-products have been identified by liquid chromatography-mass spectrometry (LC-MS) as a result of hydroxylation process of the 2,3-dihydro benzofurane ring and other reactions such as the cleavage of the carbamate group, the hydrolysis of ethereal moiety, radical coupling and decarboxylation processes. After 270 min of reaction the identified by-products were completely degraded and COD and TOC removals of 35 and 20% were measured, respectively. Toxicological analyses performed using the comparison procedure of the MicrotoxTM assay provided interesting clues concerning toxic effects of the photodegradation by-products. The results revealed a substantial increase of the toxicity during the first 15 min proving that photodegradation of organic contaminant could even lead to an increase of the toxicity of treated solution.</jats:p

Pd Nanoparticle Catalyzed Heck Arylation of 1,1-Disubstituted Alkenes in Ionic Liquids. Study on Factors Affecting the Regioselectivity of the Coupling Process

The Heck reaction of neutral or electron-rich aryl bromides with the 1,1-disubstituted olefins butyl methacrylate and R-methylstyrene catalyzed by Pd nanoparticles in tetrabutylammonium bromide as solvent and tetrabutylammonium acetate as base leads to a prevalent formation of the terminal olefin. In contrast, reaction of p-bromoacetophenone leads to the internal olefin. Whereas the solvent stabilizes the metal nanoclusters, the base is responsible for a fast neutralization of the PdH impeding the hydride readdition to reaction products and avoiding the olefin interconversion. The terminal olefins are efficiently converted into the more stable internal E isomers by using tetrabutylammonium pivalate as catalyst