Publications by authors named "Alexander Johnston"

We study noise amplification by asymmetric dyads in freely expanding non-Hermitian optical systems. We show that modifications of the pumping strengths can counteract bias from natural imperfections of the system's hardware while couplings between dyads lead to systems with nonuniform statistical distributions. Our results suggest that asymmetric non-Hermitian dyads are promising candidates for efficient sensors and ultrafast random number generators.

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Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise-like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca , and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix-design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations.

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Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay.

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Background: Plasminogen activator inhibitor-1 (PAI-1, Serpine1) is an important circulating fibrinolysis inhibitor. PAI-1 exists in 2 pools, packaged within platelet α-granules and freely circulating in plasma. Elevated plasma PAI-1 levels are associated with cardiovascular disease.

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Background: Reintubation is associated with significant morbidity and mortality. The reintubation rate in surgical ICUs (SICUs) is ∼10% nationally but was 17.0% in our SICU.

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Background And Aim: End-stage liver disease is a leading cause of mortality. Fewer than 60% of patients with decompensated cirrhosis survive after 2 years, with patients often experiencing distressing symptoms impairing quality of life. Early advanced care planning and timely palliative care referral can improve quality of life and the end of life experience.

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Objective: This study aims to identify the association, if any, between prehospital scene time, prehospital transport time, and Injury Severity Score (ISS) with in-hospital mortality.

Methods: A retrospective analysis was performed on patients at least 18 years of age who arrived to the hospital alive via emergency medical services (EMS) after a motor vehicle collision (MVC) between 1992 and 2016. These patients were divided into groups based on minutes spent at the scene and in transport.

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Factor V Leiden ( ) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized -ethyl--nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for ( ) and haploinsufficient for tissue factor pathway inhibitor ( ). deficiency enhanced the survival of mice, demonstrating that lethality is genetically suppressible.

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If idiosyncratic drug-induced liver injury (IDILI) is immune-mediated, it is possible that an individual's prior exposure to antigens may affect their susceptibility to IDILI. An individual's repertoire of memory immune cells is shaped by every past exposure to antigens. Subsequent drug-induced adverse drug reactions may therefore involve an immune cell's cross reactivity between a prior antigen and resulting drug-modified proteins.

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Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein.

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Background And Aims: Celiac disease remains underdiagnosed at endoscopy. We aimed to assess the utility of I-Scan (virtual chromo-endoscopy) to improve sensitivity of endoscopy to detect markers of villous atrophy in this condition.

Methods: Patients from 2 UK hospitals were studied in 3 groups.

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Background & Aims: Celiac disease is underdiagnosed. Many patients are examined by endoscopy, but celiac disease is missed or not detected. We evaluated the accuracy of finger prick-based point-of-care tests in the detection of celiac disease and developed an algorithm for diagnosis.

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Introduction: Idiosyncratic drug-induced agranulocytosis (IDIAG) is a life-threatening adverse reaction characterized by an absolute neutrophil count < 500 cells/μl of blood. It shares many of the characteristics of other idiosyncratic drug reactions (IDRs), and this presumably reflects mechanistic similarities.

Areas Covered: This review describes the evidence for mechanistic hypotheses of IDIAG and new hypotheses are explored.

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Background: Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses.

Objective: To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting.

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Direct drug delivery to the cochlea is associated with the risk of irreversible damage to the ear. In this study, liposome and polymersome nanoparticles (NPs), both formed from amphiphilic molecules (lipids in liposomes and block copolymers in polymersomes), were tested as potential tools for drug delivery to the cochlea via application onto the round window membrane in adult mice (strain C3H). One day after round window membrane application, both types of NPs labeled with fluorescent markers were identified in the spiral ganglion in all cochlear turns without producing any distinct morphological or functional damage to the inner ear.

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Polymersomes are nanosized vesicles formed from amphiphilic block copolymers, and have been identified as potential drug delivery vehicles to the inner ear. The aim of this study was to provide targeting to specific cells within the inner ear by functionalizing the polymersome surface with Tet1 peptide sequence. Tet1 peptide specifically binds to the trisialoganglioside clostridial toxin receptor on neurons and was expected to target the polymersomes toward the cochlear nerve.

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Targeted delivery of treatment agents to the inner ear using nanoparticles is an advanced therapeutic approach to cure or alleviate hearing loss. Designed to target the outer hair cells of the cochlea, two 12-mer peptides (A(665) and A(666)) with affinity to prestin were identified following 3 rounds of sequential phage display. Two-round display with immobilized prestin protein was used to enrich the library for full-length prestin.

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Conclusion: Cochleostomy is the most efficient approach in delivering PEG-b-PCL polymersomes (PMs) to the inner ear. PMs can be delivered to the vestibule by transtympanic injection or cochleostomy.

Objective: To evaluate the efficiency of delivering PEG-b-PCL PMs into the inner ear using different approaches.

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Fluorescent tags and fluorophore-conjugated molecular probes have been extensively employed in histological studies to demonstrate nanoparticle distribution in inner ear cell populations. However, autofluorescence that exists in the rodent cochleae disturbs visualization of the fluorescent tags and fluorophore labeling. In the present work, we aimed to improve the visualization of fluorescently tagged nanoparticles and fluorophore-labeled molecular probes by treatment with CuSO(4) to quench autofluorescence in the rat inner ear.

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The use of second-order Jahn-Teller active Mo (VI) centers and chiral organic amines is discussed as an approach to crystallographic noncentrosymmetry. Several series of reactions, conducted under mild hydrothermal conditions, were designed to probe important reaction variables. Correlations between reagent and solvent concentrations and the molybdate structure were investigated using composition space analysis, which allows for the isolation of specific reaction variables.

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We have examined the function of a conserved serine residue (Ser670) in the S2 ligand-binding region of the NR2A N-methyl-d-aspartate (NMDA) receptor subunit, using recombinant NR1/NR2A receptors expressed in Xenopus laevis oocytes. Mutation of Ser670 to glycine (S670G) in NR2A reduced the potency of glutamate by 124-fold. Single-channel conductance and the duration of apparent open periods of NR2A(S670G) receptor mutants were, however, indistinguishable from wild-type NMDA receptors.

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Bovine sides, ovine carcasses, and porcine carcasses were individually inoculated by dipping in various suspensions of a marker organism (Escherichia coli K-12 or Pseudomonas fluorescens), alone or in combination with two meat-derived bacterial strains, and were sampled by two standard methods: cotton wet-dry swabbing and excision. The samples were examined for bacterial counts on plate count agar (PCA plate counts) and on violet red brilliant green agar (VRBGA plate counts) by standard International Organization for Standardization methods. Average bacterial recoveries by swabbing, expressed as a percentage of the appropriate recoveries achieved by excision, varied widely (2 to 100%).

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