Evaluation of physical carrier sense based spanner construction and maintenance as well as broadcast and convergecast in ad hoc networks

While the use of physical carrier sensing for medium access control in ad hoc wireless networks is well established, exploiting physical carrier sensing directly for network layer functions is largely unexplored. We conduct extensive simulation evaluations of recently proposed algorithms that directly exploit physical carrier sensing for backbone network (spanner) construction, broadcast, and convergecast in wireless ad hoc networks. Our algorithms accommodate interference ranges larger than transmission ranges, explicitly incorporate the medium access control and packet collisions, and do not require any prior knowledge of the network. For spanner construction, our algorithms include three self-stabilizing phases that establish leader nodes able to reach all nodes in one hop, assign the leaders non-interfering transmission rounds, and connect the leaders through gateway nodes. We evaluate the backbone construction and maintenance as well as broadcast and convergecast through simulations. We find that over 75% of the control messages for backbone network construction are received from physical carrier sensing. While the number of backbone nodes is relatively large, the backbone is very robust, quickly self-stabilizing, and only a fraction of the backbone nodes are used for broadcast.     

Antimicrobial Gallium‐Doped Phosphate‐Based Glasses

Novel quaternary gallium‐doped phosphate‐based glasses (1, 3, and 5 mol % Ga₂O₃) were synthesized using a conventional melt quenching technique. The bactericidal activities of the glasses were tested against both Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, and Clostridium difficile) bacteria. Results of the solubility and ion release studies showed that these glass systems are unique for controlled delivery of Ga³⁺. ⁷¹Ga NMR measurements showed that the gallium is mostly octahedrally coordinated by oxygen atoms, whilst FTIR spectroscopy provided evidence for the presence of a small proportion of tetrahedral gallium in the samples with the highest gallium content. FTIR and Raman spectra also afford an insight into the correlation between the structure and the observed dissolution behavior via an understanding of the atomic‐scale network bonding characteristics. The results confirmed that the net bactericidal effect was due to Ga³⁺, and a concentration as low as 1 mol % Ga₂O₃ was sufficient to mount a potent antibacterial effect. The dearth of new antibiotics in development makes Ga³⁺ a potentially promising new therapeutic agent for pathogenic bacteria including MRSA and C. difficile.     

The Distribution of Fatty Acid Biomarkers of Dairy Intake across Serum Lipid Fractions: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort

Circulating fatty acids (FA) derived largely from dairy consumption have most commonly been measured in total human serum or phospholipid (PL) fractions, and have been used as validated biomarkers of dairy intake in a growing number of epidemiological studies. Nevertheless, measurement and characterization of a wider spectrum of FA biomarkers of dairy across the four major serum lipid fractions is lacking. This study aimed to (1) quantify FA biomarkers of dairy in PL, triacylglycerol (TAG), cholesteryl ester (CE), and unesterified fatty acid (FFA) serum lipid fractions; and (2) identify potential demographic and metabolic factors that may modify the proportions of these FA across serum fractions. Baseline data from 444 adults in the PROMISE cohort were analyzed. FA biomarkers, 15:0, t16:1n-7, 18:2-c9,t11, and t18:1n-7 were quantified from serum. Dairy intake was estimated using the validated Canadian Diet History Questionnaire. Our results show that t18:1n-7 was the most abundant FA biomarker in all fractions except CE, where 18:2-c9,t11 was the most abundant. Positive correlations within fractions, and across FA in the PL, CE, and FFA fractions were found, however, TAG FA were negatively correlated with the other fractions. PL and CE FA were positively associated with dairy intake, and negatively associated with markers of dysmetabolism while, in contrast, these markers were predictors of higher TAG dairy FA. This study is the first to demonstrate distinct proportions of dairy FA in different serum lipid fractions. PL and CE FA marked dairy intake in this cohort, while TAG FA appeared to be markers of dysmetabolism.     

Crops that feed the world 4. Barley: a resilient crop? Strengths and weaknesses in the context of food security

Barley is cultivated both in highly productive agricultural systems and also in marginal and subsistence environments. Its distribution is worldwide and is of considerable economic importance for animal feed and alcohol production. The overall importance of barley as a human food is minor but there is much potential for new uses exploiting the health benefits of whole grain and beta-glucans. The barley supply chains are complex and show added value at many stages. Germplasm resources for barley are considerable, with much potential for exploitation of its biodiversity available through the use of recently developed genomic and breeding tools. Consequently, substantial gains in crucial sustainability characteristics should be achievable in the future, together with increased understanding of the physiological basis of many agronomic traits, particularly water and nutrient use efficiency. Barley’s ability to adapt to multiple biotic and abiotic stresses will be crucial to its future exploitation and increased emphasis on these traits in elite germplasm is needed to equip the crop for environmental change. Similarly, resource use efficiency should become a higher priority to ensure the crop’s sustainability in the long-term. Clearly barley is a resilient crop with much potential which can be realised in the future.     

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.     

Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach

Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the Maybridge^TM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action.     

Crystal Plasticity Modeling of Hydrogen and Hydrogen-Related Defects in Initial Yield and Plastic Flow of Single-Crystal Stainless Steel 316L

Understanding of and accounting for various mechanisms that affect inelastic deformation of crystalline metals in the presence of hydrogen remains an unsettled issue. Macroscopic experimental observations contradict limited atomistic simulations, complicating the situation. In this work, we extend a recent physically based crystal viscoplasticity framework to include constitutive equations with a direct dependence on relevant hydrogen and hydrogen-related defect concentrations. Focusing on initial yield and post-yield strain hardening, we consider hydrogen solute drag on mobile dislocations as well as the role of dilute concentrations of hydrogen-vacancy complexes as obstacles to dislocation motion. Furthermore, the evolution of hydrogen and hydrogen-affected defect concentrations is explicitly considered via evolving hydrogen trap concentrations. The resulting framework is used to investigate hydrogen effects on the quasistatic, monotonic, strain-controlled uniaxial loading of single-crystal stainless steel 316L smooth specimens at room temperature in an attempt to connect atomistic insight and the resulting mesoscale model framework with experimental interpretations. Attributing the primary role of hydrogen in this manner is shown to produce good agreement with experiments in the initial yield and post-yield regime. The dominance of various hydrogen effects mechanisms is discussed.