Niobium uptake and release by bacterial ferric ion binding protein

Ferric ion binding proteins (Fbps) transport FeIII across the periplasm and are vital for the virulence of many Gram negative bacteria. Iron(III) is tightly bound in a hinged binding cleft with octahedral coordination geometry involving binding to protein side chains (including tyrosinate residues) together with a synergistic anion such as phosphate. Niobium compounds are of interest for their potential biological activity, which has been little explored. We have studied the binding of cyclopentadienyl and nitrilotriacetato NbV complexes to the Fbp from Neisseria gonorrhoeae by UV-vis spectroscopy, chromatography, ICP-OES, mass spectrometry, and Nb K-edge X-ray absorption spectroscopy. These data suggest that NbV binds strongly to Fbp and that a dinuclear NbV centre can be readily accommodated in the interdomain binding cleft. The possibility of designing niobium-based antibiotics which block iron uptake by pathogenic bacteria is discussed

Patients' self-assessed functional status in heart failure by New York Heart Association class: a prognostic predictor of hospitalizations, quality of life and death.

BACKGROUND: Clinician-assigned New York Heart Association (NYHA) class is an established predictor of outcomes in heart failure. This study aims to test whether patients' self-assessment of functional status by NYHA class predicts hospital admissions, quality of life, and mortality. METHODS AND RESULTS: This was an observational study within a randomized controlled trial. A total of 293 adult patients diagnosed with heart failure were recruited after an emergency admission at 3 acute hospitals in Norfolk, UK. Outcome measures included number of emergency admissions over 6 months, self-assessed quality of life measured with the Minnesota Living with Heart Failure questionnaire (MLHFQ) and EQ-5D at 6 months, and deaths up to 20 months' follow-up. Patients were grouped into 3 NYHA groups (I/II, III, and IV) based on patients' self-assigned NYHA class (SA-NYHA). A Poisson model indicated an increased readmission rate associated with higher SA-NYHA class (adjusted rate ratio 1.21; 95% CI 1.04-1.41; P=.02). Higher SA-NYHA class at baseline predicted worse quality of life at 6 months' follow-up (P=.002 for MLHFQ; P=.047 for EQ-5D), and was associated with higher mortality rate (adjusted hazard ratio 1.84; 95% CI 1.10-3.06; P=.02). CONCLUSIONS: SA-NYHA class is predictive of hospitalization, quality of life, and mortality among patients with heart failure

Membrane-Templated Flexible Semiconductor Package

Membrane-templated deformable carrier and elastomeric encapsulant enable flexible semiconductor package in support of the demands of wearables and flexible electronic gadgets. The selectively pore-filled membrane, with metal particle suspension, is mechanically reinforced by a thin elastomeric material layer to protect the newly formed leads, and to give structure to withstand package assembly. Package assembly is achieved by attaching a silicon die via a die attach process, electrically connecting the silicon to the carrier via wirebonding, and encapsulating the package using an elastomeric material via elastomeric molding process. The elastomeric support is then peeled off, exposing the terminal surface of the leads. The deformable carrier and the elastomeric encapsulant ensure package flexibility and conformity to distortio

Psychrometric Properties of Humid Air from Multi-Fluid Helmholtz-Energy-Explicit Models

Psychrometric properties of humid air are widely used in the analysis and modeling of thermal systems. In this work we present a method for obtaining these properties from the multi-fluid mixture formulation of the GERG mixture model. This mixture model was originally developed to model the thermodynamics of natural gas mixtures, and now has been extended to model thermodynamic properties relevant for carbon capture and storage. The primary advantage of this formulation is that the dry air composition is not fixed, and can be adjusted to suit the application, for instance in submarines, for Martian atmospheres, etc. We present an algorithm that can be used to calculate the saturated vapor water composition in vapor-liquid equilibrium, and other properties that arise out of this equilibrium calculation, such as relative humidity and dewpoints. Solid-vapor equilibrium is not considered, and neither is the calculation of wet-bulb temperatures

Modelling Ecosystem Processes Acting On Upper Trophic Level Managed Species in the Salish Sea – Lessons Learned and Future Goals

Ecosystem models provide a means to examine how large-scale drivers and food web interactions can influence change in marine species. Coho and Chinook salmon are iconic species in the Salish Sea and have been significant components of ecosystem models developed for its sub-basins. We present results from models of three regions in the Salish Sea: the Strait of Georgia, the Central Basin of Puget Sound, and the Southern Basin of Puget Sound. Each of these models provides reasonable simulations of how ecosystem-level mechanisms can influence changes in target managed species. While there is some overlap in these models’ ability to explore changes in mammals and fished species, regional differences remain that make it difficult to integrate knowledge at the scale of the Salish Sea as a whole. For example, the Strait of Georgia and Puget Sound models all suggest that bottom-up type dynamics have influenced the dynamics of many species. Significant contrast, however, can be seen in the dominance of the Central basin of Puget Sound by ratfish, approximately a third of all fish biomass whereas, in the Strait of Georgia, Pacific herring and small pelagic species account for a third of all fish biomass. Understanding these similarities and differences will help researchers explain why significant species like Coho and Chinook salmon can exhibit quite different population dynamics in regions of the Salish Sea. As part of an integrated project spearheaded by the Pacific Salmon Foundation and Long Live the Kings, we hope to increase the overlap in both species and mechanisms modelled in future iterations of these modelling efforts

Molluscum contagiosum virus MC80 sabotages MHC-I antigen presentation by targeting tapasin for ER-associated degradation

The human specific poxvirus molluscum contagiosum virus (MCV) produces skin lesions that can persist with minimal inflammation, suggesting that the virus has developed robust immune evasion strategies. However, investigations into the underlying mechanisms of MCV pathogenesis have been hindered by the lack of a model system to propagate the virus. Herein we demonstrate that MCV-encoded MC80 can disrupt MHC-I antigen presentation in human and mouse cells. MC80 shares moderate sequence-similarity with MHC-I and we find that it associates with components of the peptide-loading complex. Expression of MC80 results in ER-retention of host MHC-I and thereby reduced cell surface presentation. MC80 accomplishes this by engaging tapasin via its luminal domain, targeting it for ubiquitination and ER-associated degradation in a process dependent on the MC80 transmembrane region and cytoplasmic tail. Tapasin degradation is accompanied by a loss of TAP, which limits MHC-I access to cytosolic peptides. Our findings reveal a unique mechanism by which MCV undermines adaptive immune surveillance.</div

The Multiple Subnetwork Hypothesis: Enabling Multidomain Learning by Isolating Task-Specific Subnetworks in Feedforward Neural Networks

Neural networks have seen an explosion of usage and research in the past decade, particularly within the domains of computer vision and natural language processing. However, only recently have advancements in neural networks yielded performance improvements beyond narrow applications and translated to expanded multitask models capable of generalizing across multiple data types and modalities. Simultaneously, it has been shown that neural networks are overparameterized to a high degree, and pruning techniques have proved capable of significantly reducing the number of active weights within the network while largely preserving performance. In this work, we identify a methodology and network representational structure which allows a pruned network to employ previously unused weights to learn subsequent tasks. We employ these methodologies on well-known benchmarking datasets for testing purposes and show that networks trained using our approaches are able to learn multiple tasks, which may be related or unrelated, in parallel or in sequence without sacrificing performance on any task or exhibiting catastrophic forgetting