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The proces of signal acquisition was performed by a dedicated software, written specifically for the purpose of our study. From the obtained phono-angiogram, 23 features were isolated for vectors used in a decision-making algorithm, including 6 features based on the waveform of time domain, and 17 features based on the frequency spectrum. Final definition of the feature vector composition was obtained by using several selection methods the feature-class correlation, forward search, Principal Component Analysis and Joined-Pairs method. The supervised machine learning technique was then applied to develop the best classification model.Additive manufacturing promises a major transformation of the production of high economic value metallic materials, enabling innovative, geometrically complex designs with minimal material waste. The overarching challenge is to design alloys that are compatible with the unique additive processing conditions while maintaining material properties sufficient for the challenging environments encountered in energy, space, and nuclear applications. Here we describe a class of high strength, defect-resistant 3D printable superalloys containing approximately equal parts of Co and Ni along with Al, Cr, Ta and W that possess strengths in excess of 1.1 GPa in as-printed and post-processed forms and tensile ductilities of greater than 13% at room temperature. These alloys are amenable to crack-free 3D printing via electron beam melting (EBM) with preheat as well as selective laser melting (SLM) with limited preheat. Alloy design principles are described along with the structure and properties of EBM and SLM CoNi-base materials.The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion.Communicating species identity is a key component of many animal signals. However, whether selection for species recognition systematically increases signal diversity during clade radiation remains debated. Here we show that in woodpecker drumming, a rhythmic signal used during mating and territorial defense, the amount of species identity information encoded remained stable during woodpeckers' radiation. Acoustic analyses and evolutionary reconstructions show interchange among six main drumming types despite strong phylogenetic contingencies, suggesting evolutionary tinkering of drumming structure within a constrained acoustic space. Playback experiments and quantification of species discriminability demonstrate sufficient signal differentiation to support species recognition in local communities. Finally, we only find character displacement in the rare cases where sympatric species are also closely related. Overall, our results illustrate how historical contingencies and ecological interactions can promote conservatism in signals during a clade radiation without impairing the effectiveness of information transfer relevant to inter-specific discrimination.The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a worldwide emergency. Early identification of patients at risk of progression may facilitate more individually aligned treatment plans and optimized utilization of medical resource. Here we conducted a multicenter retrospective study involving patients with moderate COVID-19 pneumonia to investigate the utility of chest computed tomography (CT) and clinical characteristics to risk-stratify the patients. Our results show that CT severity score is associated with inflammatory levels and that older age, higher neutrophil-to-lymphocyte ratio (NLR), and CT severity score on admission are independent risk factors for short-term progression. The nomogram based on these risk factors shows good calibration and discrimination in the derivation and validation cohorts. These findings have implications for predicting the progression risk of COVID-19 pneumonia patients at the time of admission. CT examination may help risk-stratification and guide the timing of admission.Methods to directly inhibit gene expression using small molecules hold promise for the development of new therapeutics targeting proteins that have evaded previous attempts at drug discovery. Among these, small molecules including the drug-like compound PF-06446846 (PF846) selectively inhibit the synthesis of specific proteins, by stalling translation elongation. These molecules also inhibit translation termination by an unknown mechanism. Using cryo-electron microscopy (cryo-EM) and biochemical approaches, we show that PF846 inhibits translation termination by arresting the nascent chain (NC) in the ribosome exit tunnel. Lipopolysaccharides The arrested NC adopts a compact α-helical conformation that induces 28 S rRNA nucleotide rearrangements that suppress the peptidyl transferase center (PTC) catalytic activity stimulated by eukaryotic release factor 1 (eRF1). These data support a mechanism of action for a small molecule targeting translation that suppresses peptidyl-tRNA hydrolysis promoted by eRF1, revealing principles of eukaryotic translation termination and laying the foundation for new therapeutic strategies.The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits - TASOR, MPP8 and Periphilin - contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets.Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.Assembly of different metal-organic framework (MOF) building blocks into hybrid MOF-on-MOF heterostructures is promising in chemistry and materials science, however the development of ternary MOF-on-MOF heterostructures with controllable architectural and compositional complexity is challenging. Here we report the synthesis of three types of ternary MOF-on-MOF heterostructures via a multiple selective assembly strategy. This strategy relies on the choice of one host MOF with more than one facet that can arrange the growth of a guest MOF, where the arrangement is site-selective without homogenous growth of guest MOF or homogenous coating of guest on host MOF. The growth of guest MOF on a selected site of host MOF in each step provides the opportunity to further vary the combinations of arrangements in multiple steps, leading to ternary MOF-on-MOF heterostructures with tunable complexity. The developed strategy paves the way towards the rational design of intricate and unprecedented MOF-based superstructures for various applications.Vibrio parahaemolyticus is a major foodborne pathogen worldwide. The increasing number of cases of V. parahaemolyticus infections in China indicates an urgent need to evaluate the prevalence and genetic diversity of this pathogenic bacterium. In this paper, we introduce the Foodborne Vibrio parahaemolyticus genome database (FVPGD), the first scientific database of foodborne V. parahaemolyticus distribution and genomic data in China, based on our previous investigations of V. parahaemolyticus contamination in different kinds of food samples across China from 2011 to 2016. The dataset includes records of 2,499 food samples and 643 V. parahaemolyticus strains from supermarkets and marketplaces distributed over 39 cities in China; 268 whole-genome sequences have been deposited in this database. A spatial view on the risk situations of V. parahaemolyticus contamination in different food types is provided. Additionally, the database provides a functional interface of sequence BLAST, core genome multilocus sequence typing, and phylogenetic analysis. The database will become a powerful tool for risk assessment and outbreak investigations of foodborne pathogens in China.Bacterial nanotubes are membranous structures that have been reported to function as conduits between cells to exchange DNA, proteins, and nutrients. Here, we investigate the morphology and formation of bacterial nanotubes using Bacillus subtilis. We show that nanotube formation is associated with stress conditions, and is highly sensitive to the cells' genetic background, growth phase, and sample preparation methods. Remarkably, nanotubes appear to be extruded exclusively from dying cells, likely as a result of biophysical forces. Their emergence is extremely fast, occurring within seconds by cannibalizing the cell membrane. Subsequent experiments reveal that cell-to-cell transfer of non-conjugative plasmids depends strictly on the competence system of the cell, and not on nanotube formation. Our study thus supports the notion that bacterial nanotubes are a post mortem phenomenon involved in cell disintegration, and are unlikely to be involved in cytoplasmic content exchange between live cells.Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults, with an unknown etiology. A hallmark of TLE is the characteristic loss of layer 3 neurons in the medial entorhinal area (MEA) that underlies seizure development. One approach to intervention is preventing loss of these neurons through better understanding of underlying pathophysiological mechanisms. Here, we show that both neurons and glia together give rise to the pathology that is mitigated by the amino acid D-serine whose levels are potentially diminished under epileptic conditions. Focal administration of D-serine to the MEA attenuates neuronal loss in this region thereby preventing epileptogenesis in an animal model of TLE. Additionally, treatment with D-serine reduces astrocyte counts in the MEA, alters their reactive status, and attenuates proliferation and/or infiltration of microglia to the region thereby curtailing the deleterious consequences of neuroinflammation. Given the paucity of compounds that reduce hyperexcitability and neuron loss, have anti-inflammatory properties, and are well tolerated by the brain, D-serine, an endogenous amino acid, offers new hope as a therapeutic agent for refractory TLE.
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