14 Currently, the expansion of the novel human respiratory coronavirus (known as: SARS-CoV-2, 15 COVID-2019, or 2019-nCoV) has stressed the need for therapeutic alternatives to alleviate and 16 stop this new epidemic. The previous epidemics of high-morbidity human coronaviruses, such 17 as the acute respiratory syndrome coronavirus (SARS-CoV) in 2003, and the Middle East 18 respiratory syndrome corona virus (MERS-CoV) in 2012, prompted the characterization of 19 compounds that could be potentially active against the currently emerging novel coronavirus 20 SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog 21 prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the 22

Unbiased next-generation sequencing (NGS) approaches enable comprehensive pathogen detection in the clinical microbiology laboratory and have numerous applications for public health surveillance, outbreak investigation, and the diagnosis of infectious diseases. However, practical deployment of the technology is hindered by the bioinformatics challenge of analyzing results accurately and in a clinically relevant timeframe. Here we describe SURPI (''sequence-based ultrarapid pathogen identification''), a computational pipeline for pathogen identification from complex metagenomic NGS data generated from clinical samples, and demonstrate use of the pipeline in the analysis of 237 clinical samples comprising more than 1.1 billion sequences. Deployable on both cloud-based and standalone servers, SURPI leverages two state-of-the-art aligners for accelerated analyses, SNAP and RAPSearch, which are as accurate as existing bioinformatics tools but orders of magnitude faster in performance. In fast mode, SURPI detects viruses and bacteria by scanning data sets of 7-500 million reads in 11 min to 5 h, while in comprehensive mode, all known microorganisms are identified, followed by de novo assembly and protein homology searches for divergent viruses in 50 min to 16 h. SURPI has also directly contributed to real-time microbial diagnosis in acutely ill patients, underscoring its potential key role in the development of unbiased NGS-based clinical assays in infectious diseases that demand rapid turnaround times.

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Total meniscectomies are commonly thought to cause progressive degenerative arthrosis pathology in articular cartilage in a period of a few years because of alteration of the biomechanical environment including increased joint instability. This concern has lead to a preference for partial meniscectomies, although lateral partial meniscectomies sometimes lead to catastrophic results. We performed a three-dimensional finite element model of the human tibiofemoral joint to examine the effect of lateral meniscectomy on knee biomechanics. The results were compared to those from modeling a medial meniscectomy. Under axial femoral compressive loads, the peak contact stress and maximum shear stress in the articular cartilage increased 200% more after a lateral than a medial meniscectomy. These increased stresses could partly explain the higher cartilage degeneration observed after a lateral meniscectomy. ß

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Neutralizing monoclonal antibodies (nMAbs) elicited against foot-and-mouth disease virus (FMDV) of serotype C were assayed with field isolates and variant FMDVs using several immunoassays. Of a total of 36 nMAbs tested, 23 recognized capsid protein VP1 and distinguished at least 13 virion conformationindependent epitopes involved in neutralization of FMDV C. Eleven epitopes of FMDV C-S8cl have been located in segments 138-156 or 192-209 of VP1 by quantifying the reactivity of nMAbs with synthetic peptides and with nMAb-resistant mutants of FMDV C-S8cl carrying defined amino acid substitutions. The main antigenic site of FMDV C-S8cl (VP1 residues 138 to 150) consists of multiple (at least 10), distinguishable, overlapping epitopes. Some amino acid replacements abolished one of the epitopes, whereas other replacements affected several epitopes in this region. The conservative substitution His(146) --, Arg, found in many nMAb-resistant mutants analysed, abolished the reactivity of the virus with all nMAbs that recognized epitopes in the main antigenic site of FMDV C-S8cl. This indicates that a minimum genetic change can result in a highly amplified phenotypic effect, as regards the antigenicity of FMDV.

SUMMARYIn this paper we present a fully three-dimensional finite-strain damage model for fibrous soft tissue. Continuum damage mechanics is used to describe the softening behaviour of soft tissues under large deformation. The structural model is formulated using the concept of internal variables that provides a very general description of materials involving irreversible effects. We considered the internal variables associated to damage to correspond to separated contributions of the matrix and fibres. In order to show clearly the performance of the constitutive model, we present 3D simulations of the behaviour of the human medial collateral ligament and of a coronary artery. Results show that the model is able to capture the typical stress-strain behaviour observed in fibrous soft tissues and seems to confirm the soundness of the proposed formulation.

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