The bacterial type III secretion system, or injectisome, is a syringe shaped nanomachine essential for the virulence of many disease causing Gram-negative bacteria. At the core of the injectisome ...structure is the needle complex, a continuous channel formed by the highly oligomerized inner and outer membrane hollow rings and a polymerized helical needle filament which spans through and projects into the infected host cell. Here we present the near-atomic resolution structure of a needle complex from the prototypical Salmonella Typhimurium SPI-1 type III secretion system, with local masking protocols allowing for model building and refinement of the major membrane spanning components of the needle complex base in addition to an isolated needle filament. This work provides significant insight into injectisome structure and assembly and importantly captures the molecular basis for substrate induced gating in the giant outer membrane secretin portal family.
The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of ...multiple days is considered to be an accurate method.
We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.
Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval CI, 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).
Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).
Powerful terahertz (THz) radiation is observed from large-scale underdense preplasmas in front of a solid target irradiated obliquely with picosecond relativistic intense laser pulses. The radiation ...covers an extremely broad spectrum with about 70% of its energy located in the high frequency regime over 10 THz. The pulse energy of the radiation is found to be above 100 μJ per steradian in the laser specular direction at an optimal preplasma scale length around 40-50 μm. Particle-in-cell simulations indicate that the radiation is mainly produced by linear mode conversion from electron plasma waves, which are excited successively via stimulated Raman scattering instability and self-modulated laser wakefields during the laser propagation in the preplasma. This radiation can be used not only as a powerful source for applications, but also as a unique diagnostic of parametric instabilities of laser propagation in plasmas.
Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can ...inhibit primary and metastatic tumors through enhanced oncolytic activity and HSP-mediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 x 10(7) to 3.0 x 10(12) viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 x 10(12) VP and transient grade IV thrombocytopenia at the dose of 3.0 x 10(12) VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4(+) and CD8(+) T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.
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► LSP can generate high-level compressive residual stresses and refine original grains. ► Massive LSP impacts can effectively prevent the SCC initiation of the U-bend sample. ► ...Mechanism of massive LSP impacts on SCC was also entirely revealed.
The effects of massive laser peening (LP) impacts on surface residual stress, micro-structure, and stress corrosion cracking (SCC) behaviour of U-bend samples were investigated by X-ray diffraction (XRD) technology, optical microscope (OM) and transmission electron microscope (TEM) observations. Two important factors to influence SCC initiation, residual stress and grain refinement, were discussed in detail by using different types of treatment processes. Results showed massive LP impacts can induce both deep compressive residual stress and refined grains in the surface layer of ANSI 304 stainless steel, and the corrosion mechanism of massive LP impacts on SCC was also analysed and revealed.
Electrochemical impedance spectroscopy (EIS) is widely used to probe the physical and chemical processes in lithium (Li)‐ion batteries (LiBs). The key parameters include state‐of‐charge, rate ...capacity or power fade, degradation and temperature dependence, which are needed to inform battery management systems as well as for quality assurance and monitoring. All‐solid‐state batteries using a solid‐state electrolyte (SE), promise greater energy densities via a Li metal anode as well as enhanced safety, but their development is in its nascent stages and the EIS measurement, cell set‐up and modelling approach can be vastly different for various SE chemistries and cell configurations. This review aims to condense the current knowledge of EIS in the context of state‐of‐the‐art solid‐state electrolytes and batteries, with a view to advancing their scale‐up from the laboratory to commercial deployment. Experimental and modelling best practices are highlighted, as well as emerging impedance methods for conventional LiBs as a guide for opportunities in the solid‐state.
Materials to devices: Electrochemical impedance spectroscopy (EIS) is a powerful technique used in electrochemical research to interrogate materials, full cell devices and packs. This review summarizes the latest developments in EIS for sulfur, oxide and polymer solid‐state electrolytes in blocking electrode, symmetric and full cell configurations, with an outlook on how its applicability in this field can be improved.
Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. ...Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids.
Although synaptic behaviours of memristors have been widely demonstrated, implementation of an even simple artificial neural network is still a great challenge. In this work, we demonstrate the ...associative memory on the basis of a memristive Hopfield network. Different patterns can be stored into the memristive Hopfield network by tuning the resistance of the memristors, and the pre-stored patterns can be successfully retrieved directly or through some associative intermediate states, being analogous to the associative memory behaviour. Both single-associative memory and multi-associative memories can be realized with the memristive Hopfield network.
The Australian and African continents, regions prone to hydroclimate extremes (e.g., droughts and floods), but with sparse distribution of rain-gauge that are limited in time, rely heavily on ...complementary satellite and reanalysis data to provide important crucial information necessary for informing policies and management. The problem, however, is that satellite products suffer from systematic biases while reanalysis products carry over uncertainties from their forcing parameters. Multi-Source Weighted-Ensemble Precipitation (MSWEP) is a new global rainfall-product that merges satellite, rain-gauge and re-analysis data to exploit their advantages and minimise their disadvantages. Although MSWEP has been validated globally, this product, together with its potential applications, e.g., in water storage fluxes, river discharge and climate impacts studies over Australia and Africa, regions with urgent need of reliable products, has however, not been verified. Using GRACE satellite products, GLDAS model data, GRDC runoff products, and ENSO/IOD climate indices; five rainfall products - FLUXNET, BoM, GPCC, CHIRPS, and AgCFSR; and a suite of statistical methods (Pearson, Kolmogorov-Smirnov, PCA and Three-Corner-Hat (TCH)), this study (i) evaluates monthly MSWEP-V2.1 data (1981–2016), and (ii), assesses its potential applications to water storage flux (within the water balance framework), river discharge analysis, and climate impacts studies. The results show good MSWEP correlations and cumulative distribution with BoM product over most of Australia except in regions with heavy monsoonal rainfall, e.g., northern and north-western Australia where it tends to underestimate. Over Africa, MSWEP has no obvious advantages compared to insitu-GPCC, satellite-CHIRPS or reanalysis-AgCFSR. Furthermore, it is unable to reflect on major hydro-climate extremes over west, east and southern Africa, where it underestimates compared to CHIRPS. Its potential applications to water storage flux, discharge and climate impacts over the two continents show better suitability for water storage flux in Africa, while no advantages are seen compared to other rainfall products on other aspects.
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•MSWEP underestimates monsoon rainfall in northern Australia.•Large uncertainties of MSWEP remain in the eastern and southern Africa.•MSWEP has no advantageous use for water storage flux and discharge applications.•MSWEP captures extremes but missed the Southern and West Africa (1997–1998) one.
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