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Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. see more To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Escherichia coli. Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour. We show that iVAX-synthesized vaccines against Francisella tularensis subsp. tularensis (type A) strain Schu S4 protected mice from lethal intranasal F. tularensis challenge. The iVAX platform promises to accelerate development of new conjugate vaccines with increased access through refrigeration-independent distribution and portable production.Streptophyte algae emerged as a land plant with adaptations that eventually led to terrestrialization. Land plants encounter a range of biotic and abiotic stresses that elicit anaerobic stress responses. Here, we show that acetaldehyde, a toxic metabolite of anaerobic stress, targets and generates ethyl adducts on aminoacyl-tRNA, a central component of the translation machinery. However, elongation factor thermo unstable (EF-Tu) safeguards l-aminoacyl-tRNA, but not d-aminoacyl-tRNA, from being modified by acetaldehyde. We identified a unique activity of archaeal-derived chiral proofreading module, d-aminoacyl-tRNA deacylase 2 (DTD2), that removes N-ethyl adducts formed on d-aminoacyl-tRNAs (NEDATs). Thus, the study provides the molecular basis of ethanol and acetaldehyde hypersensitivity in DTD2 knockout plants. We uncovered an important gene transfer event from methanogenic archaea to the ancestor of land plants. While missing in other algal lineages, DTD2 is conserved from streptophyte algae to land plants, suggesting its role toward the emergence and evolution of land plants.Quickly obtaining optimal solutions of combinatorial optimization problems has tremendous value but is extremely difficult. Thus, various kinds of machines specially designed for combinatorial optimization have recently been proposed and developed. Toward the realization of higher-performance machines, here, we propose an algorithm based on classical mechanics, which is obtained by modifying a previously proposed algorithm called simulated bifurcation. Our proposed algorithm allows us to achieve not only high speed by parallel computing but also high solution accuracy for problems with up to one million binary variables. Benchmarking shows that our machine based on the algorithm achieves high performance compared to recently developed machines, including a quantum annealer using a superconducting circuit, a coherent Ising machine using a laser, and digital processors based on various algorithms. Thus, high-performance combinatorial optimization is realized by massively parallel implementations of the proposed algorithm based on classical mechanics.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium ( less then 100), and small ( less then 20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.Dysregulations in the inflammatory response of the body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and associated with increased severity and mortality. Hence, there is a need for identifying therapeutic targets to modulate this pathological immune response. Here, we propose a single cell-based computational methodology for predicting proteins to modulate the dysregulated inflammatory response based on the reconstruction and analysis of functional cell-cell communication networks of physiological and pathological conditions. We validated the proposed method in 12 human disease datasets and performed an in-depth study of patients with mild and severe symptomatology of the coronavirus disease 2019 for predicting novel therapeutic targets. As a result, we identified the extracellular matrix protein versican and Toll-like receptor 2 as potential targets for modulating the inflammatory response. In summary, the proposed method can be of great utility in systematically identifying therapeutic targets for modulating pathological immune responses.On Mars, seasonal martian flow features known as recurring slope lineae (RSL) are prevalent on sun-facing slopes and are associated with salts. On Earth, subsurface interactions of gypsum with chlorides and oxychlorine salts wreak havoc instigating sinkholes, cave collapse, debris flows, and upheave. Here, we illustrate (i) the disruptive potential of sulfate-chloride reactions in laboratory soil crust experiments, (ii) the formation of thin films of mixed ice-liquid water "slush" at -40° to -20°C on salty Mars analog grains, (iii) how mixtures of sulfates and chlorine salts affect their solubilities in low-temperature environments, and (iv) how these salt brines could be contributing to RSL formation on Mars. Our results demonstrate that interactions of sulfates and chlorine salts in fine-grained soils on Mars could absorb water, expand, deliquesce, cause subsidence, form crusts, disrupt surfaces, and ultimately produce landslides after dust loading on these unstable surfaces.
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