1,194 research outputs found

    Dislocation strain as the mechanism of phonon scattering at grain boundaries

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    Thermal conductivities of polycrystalline thermoelectric materials are satisfactorily calculated by replacing the commonly used Casimir model (freqeuncy-independent) with grain boundary dislocation strain model (frequency-dependent) of Klemens. It is demonstrated that the grain boundaries are better described as a collection of dislocations rather than perfectly scattering interfaces

    A Tool for Multiple Targeted Genome Deletions that Is Precise, Scar-Free, and Suitable for Automation.

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    Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences), or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1) a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2) software to design the method's primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs) from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome

    Severe hyperkalaemia: demographics and outcome

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    Background. Few studies have evaluated the prevalence of severe hyperkalaemia in unselected patient populations.We identified all episodes of severe hyperkalaemia occurring in 1 year, and described patient demographics, clinical response and outcome. We also assessed junior doctor knowledge of its causes and significance. Materials and methods. A retrospective interrogation of the database of the regional biochemical laboratory identified all episodes of severe hyperkalaemia (K ≥ 6.5 mmol/L) occurring in 2011. The understanding of trainee doctors of the importance, causes and treatment of severe hyperkalaemia was assessed by structured questionnaire. Results. Severe hyperkalaemia was recorded in 433 samples (365 patients) giving a prevalence of 0.11%. Thirty-six per cent of episodes occurred in patients under the care of a nephrologist, who were significantly younger than those not under the care of a nephrologist. In the nephrology cohort, 86% occurred in patients with chronic kidney disease (CKD), the majority of which had CKD Stage 5. In the non-nephrology cohort, only 65% occurred in the context of CKD, which was equally distributed between Stages 3 and 5 CKD. In both patient groups, roughly 50% of episodes occurred in association with acute kidney injury (AKI). Acute mortality (death within 48 h of documented severe hyperkalaemia) was higher in the non-nephrology compared with the nephrology cohort. Time to repeat serum potassium was influenced by the clinical setting with shorter time to repeat for acute care compared with ward settings. Assessment of trainee doctor’s knowledge suggested significant deficiencies in relation to severe hyperkalaemia. Conclusions. The prevalence of severe hyperkalaemia was low and occurred predominantly in the context of CKD and/or AKI. The majority of episodes occurred in patients not under the care of a nephrologist. Variability in time to repeat serum potassium levels suggested deficiencies in care, and assessment of trainee doctor’s knowledge suggests the need for further educational initiatives to highlight its importance

    Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: synthesis, antibacterial evaluation and preliminary mechanism of action studies

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    Synthetic small molecular antimicrobial peptidomimetics represent a promising new class of potential antibiotics due to their membrane-disrupting ability and their decreased propensity for bacterial resistance. A library of 43 mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics was designed and synthesized based upon previously established lead biarylpeptidomimetics and a known pharmacophore. A reliable, facile and modular synthetic pathway allowed for the efficient synthesis of multiple unique scaffolds which were subjected to divergent derivatization to furnish the amphiphilic compounds. In vitro testing revealed enhanced antibacterial efficacy against a range of pathogenic bacteria, including bacterial isolates with methicillin, vancomycin, daptomycin, or multi-drug resistance. Preliminary time-kill kinetics and membrane-disruption assays revealed a likely membrane-active mechanism for the tested peptidomimetics. An optimal balance between hydrophobicity and cationic charge was found to be essential for reduced cytotoxicity/haemolysis (i.e. membrane selectivity) and enhanced Gram-negative activity. The cationic biaryl amphiphile 81 was identified as a potent, broad-spectrum peptidomimetic with activity against Gram-positive (methicillin-resistant Staphylococcus aureus - MIC = 2 μg/mL) and Gram-negative (Escherichia coli - MIC = 4 μg/mL) pathogenic bacteria

    Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles: synthesis, antibacterial evaluation and preliminary mechanism of action studies

    Get PDF
    Synthetic small molecular antimicrobial peptidomimetics represent a promising new class of potential antibiotics due to their membrane-disrupting ability and their decreased propensity for bacterial resistance. A library of 43 mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics was designed and synthesized based upon previously established lead biarylpeptidomimetics and a known pharmacophore. A reliable, facile and modular synthetic pathway allowed for the efficient synthesis of multiple unique scaffolds which were subjected to divergent derivatization to furnish the amphiphilic compounds. In vitro testing revealed enhanced antibacterial efficacy against a range of pathogenic bacteria, including bacterial isolates with methicillin, vancomycin, daptomycin, or multi-drug resistance. Preliminary time-kill kinetics and membrane-disruption assays revealed a likely membrane-active mechanism for the tested peptidomimetics. An optimal balance between hydrophobicity and cationic charge was found to be essential for reduced cytotoxicity/haemolysis (i.e. membrane selectivity) and enhanced Gram-negative activity. The cationic biaryl amphiphile 81 was identified as a potent, broad-spectrum peptidomimetic with activity against Gram-positive (methicillin-resistant Staphylococcus aureus - MIC = 2 μg/mL) and Gram-negative (Escherichia coli - MIC = 4 μg/mL) pathogenic bacteria. © 2019 Elsevier Masson SA

    Dislocation strain as the mechanism of phonon scattering at grain boundaries

    Get PDF
    Thermal conductivities of polycrystalline thermoelectric materials are satisfactorily calculated by replacing the commonly used Casimir model (freqeuncy-independent) with grain boundary dislocation strain model (frequency-dependent) of Klemens. It is demonstrated that the grain boundaries are better described as a collection of dislocations rather than perfectly scattering interfaces

    Criteria for the diagnosis of corticobasal degeneration

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    Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed

    The New Mexico State University Satellite (NMSUSat) Mission

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    The New Mexico State University Satellite (NMSUSat) is part of the University Nanosat 3 program managed by the Air Force Research Laboratory and it is being developed at New Mexico State University. The planned Science Mission for the satellite is to perform Near Ultra Violet emission intensity measurements of the earth\u27s upper atmosphere over the night side of the earth. The Engineering Mission is to demonstrate techniques for distributed data relaying over the Internet and to conduct an energy storage experiment to assess the operational characteristics of double layer capacitors. The Educational Mission of the program to assist in the further development of the aerospace engineering concentration area in the College of Engineering and to develop multi-disciplinary capstone and design classes for students in engineering departments, computer science, and the engineering physics program. This paper will discuss the preliminary design for the satellite components and how the mission segments will be worked among the participating departments at New Mexico State University

    End-of-life care decisions for haemodialysis patients – ‘We only tend to have that discussion with them when they start deteriorating’

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    Background Haemodialysis patients receive very little involvement in their end-of-life care decisions. Issues relating to death and dying are commonly avoided until late in their illness. This study aimed to explore the experiences and perceptions of doctors and nurses in nephrology for involving haemodialysis patients in end-of-life care decisions. Methods A semi-structured qualitative interview study with 15 doctors and five nurses and thematic analysis of their accounts was conducted. The setting was a large teaching hospital in Wales, UK. Results Prognosis is not routinely discussed with patients, in part due to a difficulty in estimation and the belief that patients do not want or need this information. Advance care planning is rarely carried out, and end-of-life care discussions are seldom initiated prior to patient deterioration. There is variability in end-of-life practices amongst nephrologists; some patients are felt to be withdrawn from dialysis too late. Furthermore, the possibility and implications of withdrawal are not commonly discussed with well patients. Critical barriers hindering better end-of-life care involvement for these patients are outlined. Conclusions The study provides insights into the complexity of end-of-life conversations and the barriers to achieving better end-of-life communication practices. The results identify opportunities for improving the lives and deaths of haemodialysis patients
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