Functional interpretation of single cell similarity maps.

We present Vision, a tool for annotating the sources of variation in single cell RNA-seq data in an automated and scalable manner. Vision operates directly on the manifold of cell-cell similarity and employs a flexible annotation approach that can operate either with or without preconceived stratification of the cells into groups or along a continuum. We demonstrate the utility of Vision in several case studies and show that it can derive important sources of cellular variation and link them to experimental meta-data even with relatively homogeneous sets of cells. Vision produces an interactive, low latency and feature rich web-based report that can be easily shared among researchers, thus facilitating data dissemination and collaboration

Age-related influence of hypothyroidism on caveolins and nitric oxide modulation

Introduction: Hypothyroidism and age impact on cardiac and renal nitricoxide (NO) production. Caveolins, which are negativemodulators of NO synthase (NOS) activity, are affected byboth factors. Objectives: The aim of this study was to evaluate caveolin (CAV) participationin the modulation of renal and cardiac NOS activityin adult hypothyroid animals. Methods: Euthyroid and hypothyroid [methimazole 0.02% (v/v) in thedrinking water during 28 days] male Sprague-Dawley ratswere used. Animals were sacrificed to remove the heart andkidneys. Results: Right atrial NOS activity decreased with age and hypothyroidism.Caveolin-1 expression increased with age andhypothyroidism. Conversely, left ventricular NOS activityincreased with aging and hypothyroidism and the expressionof both CAV isoforms decreased in adult and hypothyroidgroups. In the renal medulla, hypothyroidism reducedNOS activity in young and raised it in adult animals andCAV-1 expression decreased with age and in hypothyroidyoung animals. Caveolin-3 protein levels decreased in adulthypothyroid animals. Conclusions: Hypothyroidism impacts on NOS activity and on that ofits modulators, caveolins, in the cardiovascular and renalsystems. Hypothyroidism enhances the effects of aging inboth systems.Fil: Detomaso, Florencia M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Braga, Paula. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rodríguez, Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Arreche, Noelia Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sarati, Lorena Ivonne. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Balaszczuk, Ana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fellet, Andrea L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

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

Innesco. Progettare spazi di coesione e rigenerazione urbana in stazione: dal vuoto all’impatto sociale.

Il fenomeno dell’impresenziamento è strettamente correlato all’innovazione tecnologica degli impianti ferroviari che ha introdotto un sistema di gestione centralizzata. Non essendo più indispensabile la presenza umana le stazioni sono rimaste impresenziate in modo direttamente proporzionale al numero di chilometri della rete ferroviaria dotata di questo nuovo sistema. Le cosiddette 'Stazioni Impresenziate' mantengono quindi l’operatività ferroviaria, ma prive di personale. Per trent’anni questi luoghi sono rimasti abbandonati. Nell’ultimo decennio Rete Ferroviaria Italiana ha avviato un progetto di recupero e ri-valorizzazione di questi spazi, concedendoli in comodato d’uso a enti locali e associazioni no-profit per l'utilizzo a fini sociali, la riqualificazione del territorio e la creazione di valore condiviso. La particolarità di questo intervento è che, pur trattandosi di spazi privati, essi esercitano un impatto rilevante sul pubblico. Infatti, le proposte di recupero attuate in questo contesto si basano sull’associazionismo. Tuttavia, le territorialità sono sia terreno fertile che ostile che oscillano tra realtà illuminate e realtà commissariate per mafia. Ripercussione dell’aleatorietà dei territori è il carattere isolato e parziale delle iniziative che si sviluppano su scala locale anche se inserite in un quadro di portata nazionale. In quest’ottica, la partecipazione può consolidare la rete territoriale e, apportando un valore inclusivo ai territori, contrasta la tendenza alla frammentazione sociale e alla segregazione spaziale. Può, quindi, la partecipazione della cittadinanza essere veicolo di coesione sociale e strumento di rigenerazione urbana? Rigenerare un territorio significa potenziare sia la sua struttura materiale che immateriale, facendo riferimento alla struttura fisica e sociale degli spazi. Obiettivo della presente tesi è ridisegnare le relazioni del sistema attuale, al fine di renderlo maggiormente partecipativo e coeso per i territori

An Arrhenius-based one-step reaction mechanism for hydrogen-air flames simulations in an extended range of operating conditions

An Arrhenius-based one-step scheme is derived for hydrogen-air combustion simulations. A Pre-Exponential Adjustment approach, based on an explicit analytical dependence of reaction rate parameters on equivalence ratio and pressure is adopted, together with a correction to improve the prediction of thermal flame thickness. The reduced scheme is validated by computations of one-dimensional unstrained and strained laminar premixed flames for a wide range of pressures ([1; 30] atm), unburned gas temperatures ([300; 800] K), and equivalence ratios ([0.4; 6.0]), with a good agreement of predicted main flame parameters between reduced and reference kinetic schemes. Coupled to a high-fidelity Navier–Stokes compressible solver, the reduced scheme is successfully proved for the numerical simulation of canonical configurations such as one-dimensional and two-dimensional premixed flames under several mixture conditions, with a significant improvement of computational efficiency

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

Tetraethyl orthosilicate and acrylic acid forming robust carboxylic functionalities on plastic surfaces for biodiagnostics

Surface functionalisation and effects related to non-specific binding of the detection molecules are the key aspects to be considered for fluorescence-linked bioassays. Here, we present a deposition of polymeric structures with carboxylic acid functionalities by plasma enhanced chemical vapour deposition. We report on characterisation and some unique properties of the film formed as a result of sequential, plasma assisted fragmentation and deposition from vapours of acrylic acid (AA) and tetraethyl orthosilicate (TEOS). TEOS serves as an adhesion layer to the plastic substrate and also as a network building layer for further cross-linking with AA, the sequential plasma deposition resulting in a film of composition graded from inside to outside. The presence of silanols (Si-OH) can facilitate large uptake of water molecules and cause significant hydration of the layer, which in combination with high total negative charge lowers the non-specific binding of biomolecules. Furthermore, the specific combination of TEOS and AA significantly increased the proportion of carboxyl groups in the layer, above that found from deposition of AA alone. The availability and reactivity of the carboxyl functionalities for covalent attachment of specific bioreceptor molecules was confirmed by a total internal reflection ellipsometry technique in a reaction with amino terminated ssDNA. The combination of low non-specific binding and high specific binding amount gave a high signal/noise ratio. Ageing studies of the film showed long-term stability over 50 d. Carboxylic acid coatings have been deposited by PECVD onto cyclic olefin polymer substrates from an acrylic acid monomer. Carboxy properties are enhanced through the addition of TEOS as a base layer to the substrate, results are compared to coatings without this adhesion layer. A thorough analysis of the deposited surface and a comprehensive characterisation of the surface is investigated. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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