Preclinical safety and efficacy of a therapeutic antibody that targets SARS-CoV-2 at the sotrovimab face but is escaped by Omicron

The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2

A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors

IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole. The main goal of IceCube is the detection of astrophysical neutrinos and the identification of their sources. High-energy muon neutrinos are observed via the secondary muons produced in charge current interactions with nuclei in the ice. Currently, the best performing muon track directional reconstruction is based on a maximum likelihood method using the arrival time distribution of Cherenkov photons registered by the experiment's photomultipliers. A known systematic shortcoming of the prevailing method is to assume a continuous energy loss along the muon track. However at energies $>1$ TeV the light yield from muons is dominated by stochastic showers. This paper discusses a generalized ansatz where the expected arrival time distribution is parametrized by a stochastic muon energy loss pattern. This more realistic parametrization of the loss profile leads to an improvement of the muon angular resolution of up to $20\%$ for through-going tracks and up to a factor 2 for starting tracks over existing algorithms. Additionally, the procedure to estimate the directional reconstruction uncertainty has been improved to be more robust against numerical errors

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

L’anagrafe dell’handicap della Provincia autonoma di Trento: aggiornamento dei dati al 31 dicembre 2016

[The register of the handicap of the Autonomous Province of Trento: updating the data as of December 31, 2016] The Authors, examining the Italian welfare system and the contents of Law 104/92 (“Framework Law for assistance, social integration, and rights of the handicapped”), present a statistical analysis of the handicap database in Province of Trento.The Law 104/92 aims, among others, at guaranteeing the respect for human dignity, as well as the rights to freedom and autonomy of persons with disabilities, while promoting their integration in families, schools, work and society; preventing and removing negative conditions that stop the human development, the highest possible level of autonomy and participation in social life, as well as the enjoyment of civil, political and patrimonial rights; achieving a functional and social rehabilitation of people with physical and sensory impairment, while ensuring adequate services and prevention, care and rehabilitation measures, as well as a legal and economic protection; preparing adequate initiatives to overcome marginalization and social exclusion

MEO dynamics and GNSS disposal strategies

In the last years significant understandings in theknowledge of the dynamics of the MEO satellites wereachieved. Much work was done in the analysis of viabledisposal strategies and technologies for the spacecraftbelonging to the Global Navigation Satellite Systems(GNSS), with particular emphasis on the EuropeanGalileo system. In the framework of an ESA-ESOCContract an extensive numerical simulations of differentlong term evolution scenarios, implementing differentdisposal strategies were performed. A detailed analysisof the collision risk and manoeuvres need, related to thedifferent scenarios, was performed. In terms of the longterm evolution, the scenarios where the orbitalinstabilities are exploited to remove the objects from theoperational regions seems favourite. That is, if the focusis on the long term sustainability of the spaceenvironment, the possibility to dilute the collision riskand to aim at the re-entry in the atmosphere of a subset ofthe disposed GNSS spacecraft is the most attractive. Themost "problematic" constellations are Glonass andBeidou. This conclusion is driven by the future launchtraffic hypothesized for these constellations and by thepast practices that left already a significant number oflarge uncontrolled spacecraft in the constellation orbitalzone, in the case of Glonass. On the other hand, theGalileo constellation is well detached from the others andfaces the lowest collision risks. The Stable scenariosseems to minimize the interactions (crossings) with theoperational constellations and, therefore, might bepreferred for operational reasons. In particular, in theStable scenarios the inter-constellations interaction isnegligible. Particular care should be devoted to theefficiency and reliability of the disposal manoeuvers. Asignificant share of the collision risk faced by theoperational satellites in every simulated scenario can betraced back to the "failed'' satellites (the success rate ofthe disposal manoeuvers was assumed to be 90 % for allthe constellations)

Nitrate respiration and diel migration patterns of diatoms are linked in sediments underneath a microbial mat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/1/emi15345-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/2/emi15345_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/3/emi15345.pd

Nitrate respiration and diel migration patterns of diatoms are linked in sediments underneath a microbial mat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/1/emi15345-sup-0001-supinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/2/emi15345_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167035/3/emi15345.pd