Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs

The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the beta-CoV spike protein family, using sequence information alone, can provide valuable insights on the molecular basis of the specificity of beta-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptor adaptation of circulating and future novel b-CoVs. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology

FEM simulation of a crack propagation in a round bar under combined tension and torsion fatigue loading

An edge crack propagation in a steel bar of circular cross-section undergoing multiaxial fatigue loads is simulated by Finite Element Method (FEM). The variation of crack growth behaviour is studied under axial and combined in phase axial+torsional fatigue loading. Results show that the cyclic Mode III loading superimposed on the cyclic Mode I leads to a fatigue life reduction. Numerical calculations are performed using the FEM software ZENCRACK to determine the crack path and fatigue life. The FEM numerical predictions have been compared against corresponding experimental and numerical data, available from literature, getting satisfactory consistencyN/

Aromatase immunoreactivity in fetal ovine neuronal cell cultures exposed to oxidative injury

A lot of evidence testifies that aromatase is expressed in the central nervous system where it has been detected not only in hypothalamic and limbic regions but also in the cerebral cortex and spinal cord. In physiological conditions, aromatase is expressed exclusively by neurons, where it has been mainly found in cell bodies, processes and synaptic terminals. Moreover, primary cultured cortical astrocytes from female rats are more resistant to oxidant cell death than those from males, suggesting a protective role of estradiol. The aim of this study was to evaluate changes in aromatase expression in response to 3-nitro-L-tyrosine, a marker of oxidative stress, in primary neuronal cell cultures from brains of 60-day old sheep fetuses. Cells were identified as neurons by using class III β-tubulin, a marker of neuronal cells. Two morphological types were consistently recognizable: i) bipolar cells with an oval cell body; ii) multipolar cells whose processes formed a wide net with those of adjacent cells. In situ hybridization technique performed on 60-day old fetal neurons revealed that in baseline conditions aromatase gene expression occurs. Importantly, cells exposed to 360 µM 3-nitro-L-tyrosine were fewer and showed more globular shape and shorter cytoplasmic processes in comparison to control cells. The immunocytochemical study with anti-aromatase antibody revealed that cells exposed to 360 µM 3-nitro-L-tyrosine were significantly more immunoreactive than control cells. Thus, it can be postulated that the oxidant effects of the amino acid analogue 3-nitro-L-tyrosine could be counterbalanced by an increase in aromatase expression that in turn can lead to the formation of neuroprotective estradiol via aromatization of testosterone

Experimental evaluation of an advanced Space Shuttle main engine hot-gas manifold design concept

This study, using an extensively modified, full-scale space shuttle main engine (SSME) hot-gas manifold (HGM), established a detailed aerodynamic data base to support development of an advanced, three-dimensional, fluid-dynamic analysis computer model. In addition, the advanced SSME hot-gas manifold design used in this study demonstrated improved flow environment (uniformity) in the fuel side turbine exit and transfer duct exit regions. Major modifications were incorporated in the full-scale HGM flow test article model using two large transfer ducts on the fuel turbine side of the HGM in place of the three small transfer ducts in the present design. Other model features included an increases in the flow areas downstream of the 180-degree turn and in the fishbowl regions

Development of an electrostatic precipitator prototype to reduce exposure to radon progeny in poorly ventilated workplaces

Electrostatic precipitation is a well-known technology to reduce public exposure to radon daughters. A custom electrostatic precipitator (ESP) prototype has been designed and built to study the effectiveness of such a removal technique in specific workplaces having low-to-zero air exchange rates with external environments. An appropriate mathematical model has been set up in order to simulate the behavior of environmental and nuclear data throughout the ESP operation, to optimize the design for the prototype to be built, to estimate its effectiveness in terms of effective dose reduction. Reference detectors have been used to measure both the radon concentration and the potential alpha energy concentration of its decay products. After a full calibration procedure, two main experiments have been performed in a room satisfying the requirements of very low ventilation rate and high radon concentration. The effective dose rate after an ESP continuous working period of either 3 h or 5 h turned out to be 50% lower than the value measured before ESP switching ON. The main contribution to dose reduction was found to be given by the first 2 hours of operation

New methodologies to analyze and study the Hellenistic-Roman quarter in Agrigento

The Agrigento: insula III Project began in 2016 thanks to an agreement between the Parco Archeologico e Paesaggistico Valle dei Templi di Agrigento and DiSCi - Bologna University; it aims to document an entire sector of the Hellenistic-Roman quarter, in a three-year period. The main goal is to start a systematic study of private housing from the Archaic period to Late Antiquity and, at the same time, provide a critical understanding of the town planning scheme in this part of the town, which still lacks a modern archaeological and topographical documentation. The interpretation of the previous documentation is the starting point, along with new mapping with laser scanning and a systematic campaign of geophysical investigations to obtain a BIM. As the Bologna University tradition teaches, modern technologies can answer precise historical and archaeological questions: what are the primary phases of the town map? Which one is the starting module of each lot and what are the changes in different ages? Is it possible to reconstruct the original architecture of Hellenistic houses? What is the relationship between this quarter and the rest of the town? The integration of traditional investigational techniques with more recent ones is the methodological assumption of the project, in order to solve the analysis of the complex stratigraphy of the setting, which was inhabited for at least a millennium, from the Archaic to the Middle Ages

Physically based modeling of rainfall-triggered landslides: a case study in the Luquillo forest, Puerto Rico

This paper presents the development of a rainfall-triggered landslide module within an existing physically based spatially distributed ecohydrologic model. The model, tRIBS-VEGGIE (Triangulated Irregular Networks-based Real-time Integrated Basin Simulator and Vegetation Generator for Interactive Evolution), is capable of a sophisticated description of many hydrological processes; in particular, the soil moisture dynamics are resolved at a temporal and spatial resolution required to examine the triggering mechanisms of rainfall-induced landslides. The validity of the tRIBS-VEGGIE model to a tropical environment is shown with an evaluation of its performance against direct observations made within the study area of Luquillo Forest. The newly developed landslide module builds upon the previous version of the tRIBS landslide component. This new module utilizes a numerical solution to the Richards' equation (present in tRIBS-VEGGIE but not in tRIBS), which better represents the time evolution of soil moisture transport through the soil column. Moreover, the new landslide module utilizes an extended formulation of the factor of safety (FS) to correctly quantify the role of matric suction in slope stability and to account for unsaturated conditions in the evaluation of FS. The new modeling framework couples the capabilities of the detailed hydrologic model to describe soil moisture dynamics with the infinite slope model, creating a powerful tool for the assessment of rainfall-triggered landslide risk.United States. National Aeronautics and Space Administration (Project NNX07AD29G

Assessing the accuracy of contact and distance predictions in CASP14

We present the results of the assessment of the intramolecular residue-residue contact and distance predictions from groups participating in the 14th round of the CASP experiment. The performance of contact prediction methods was evaluated with the measures used in previous CASPs, while distance predictions were assessed based on a new protocol, which considers individual distance pairs as well as the whole predicted distance matrix, using a graph-based framework. The results of the evaluation indicate that predictions by the tFold framework, TripletRes and DeepPotential were the most accurate in both categories. With regards to progress in method performance, the results of the assessment in contact prediction did not reveal any discernible difference when compared to CASP13. Arguably, this could be due to CASP14 FM targets being more challenging than ever before.We present the results of the assessment of the intramolecular residue-residue contact and distance predictions from groups participating in the 14th round of the CASP experiment. The performance of contact prediction methods was evaluated with the measures used in previous CASPs, while distance predictions were assessed based on a new protocol, which considers individual distance pairs as well as the whole predicted distance matrix, using a graph-based framework. The results of the evaluation indicate that predictions by the tFold framework, TripletRes and DeepPotential were the most accurate in both categories. With regards to progress in method performance, the results of the assessment in contact prediction did not reveal any discernible difference when compared to CASP13. Arguably, this could be due to CASP14 FM targets being more challenging than ever before