The ribosomally produced antimicrobial peptides of bacteria (bacteriocins) represent an unexplored source of membrane-active antibiotics. We designed a library of linear peptides from a circular ...bacteriocin and show that pore-formation dynamics in bacterial membranes are tunable via selective amino acid substitution. We observed antibacterial interpeptide synergy indicating that fundamentally altering interactions with the membrane enables synergy. Our findings suggest an approach for engineering pore-formation through rational peptide design and increasing the utility of novel antimicrobial peptides by exploiting synergy.
This dissertation examined the relationship between the antecedents and consequences of employee engagement in a defense acquisition organization. The objective of this study is to determine whether ...or not the eight satisfaction facets of the Index of Organizational Reactions (IOR) (1976) could be used as antecedents, engagement and consequences constructs in place of the antecedents, engagement and consequences constructs of the Saks (2006) model of employee engagement. This study used the following three research questions: (1) Are the antecedents of the IOR (kind of work, amount of work, physical work conditions, supervision and financial rewards) related to employee engagement constructs (company identification and co-workers)? (2) Are the antecedents of the IOR model (kind of work, amount of work, physical work conditions, supervision and financial rewards) related to consequences (career future)? (3) Are the employee engagement constructs (company identification and co-workers) related to consequences (career future)? This study utilized the Index of Organizational Reactions (1976) to sample a defense acquisition organization (N = 177) to assess the proposed empirical model. The quantitative data from the study was used to perform Pearson correlation on 17 hypotheses. All hypotheses were supported and indicated positive relationships were present among the variables representing the antecedents, engagement and consequences constructs of the empirical model. In addition, confirmatory factor analysis was utilized as was done in previous studies performed by Dunham, Smith and Blackburn (1977) and Lee (1984). After the initial component matrix was obtained, a varimax rotation with Kaiser normalization was applied and indicated that the same factors found in the Dunham et al. and Lee studies were found in this research, providing additional confirmation for the original validation of the IOR. Analysis of Variance (ANOVA) was used in this research and the results indicated that gender was a significant effect on the results of this study. This study utilized qualitative responses to the survey items to provide additional data to determine whether or not there were common themes amongst the comments and whether or not the comments were in agreement with the quantitative responses. Results indicated that further study is needed in the areas of supervision, kind of work, co-workers, physical work conditions and career future.
This dissertation examined the relationship between the antecedents and consequences of employee engagement in a defense acquisition organization. The objective of this study as to determine whether ...or not the eight satisfaction facets of the Index of Organizational Reactions (IOR) (1976) could be used as antecedents, engagement and consequences constructs in place of the antecedents, engagement and consequences constructs of the Saks (2006) model of employee engagement. This study used the following three research questions: 1) Are the antecedents of the IOR (kind of work, amount of work, physical work conditions, supervision and financial rewards) related to employee engagement constructs (company identification and co-workers)? 2) Are the antecedents of the IOR model (kind of work, amount of work, physical work conditions, supervision and financial rewards) related to consequences (career future)? 3) Are the employee engagement constructs (company identification and co-workers) related to consequences (career future)?
This study utilized the Index of Organizational Reactions (1976) to sample a defense acquisition organization (N = 177) to assess the proposed empirical model. The quantitative data from the study was used to perform Pearson correlation on 17 hypotheses. All hypotheses were supported and indicated positive relationships were present among the variables representing the antecedents, engagement and consequences constructs of the empirical model. In addition, confirmatory factor analysis was utilized as was done in previous studies performed by Dunham, Smith and Blackburn (1977) and Lee (1984). After the initial component matrix was obtained, a varimax rotation with Kaiser normalization was applied and indicated that the same factors that were found in the Dunham et al. and Lee studies were found in this research, providing additional confirmation for the original validation of the IOR. Analysis of Variance (ANOVA) was also used in this research and the results indicated that gender was a significant effect on the results of this study.
This study also utilized qualitative responses to the survey items to provide additional data to determine whether or not there were common themes amongst the comments and whether or not the comments were in agreement with the quantitative responses. Results indicated that further study is needed in the areas of supervision, kind of work, co-workers, physical work conditions and career future.
In this brilliant collection, literary scholars, philosophers, and teachers inquire into the connections between antifoundational philosophy and the rhetorical tradition. What happens to literary ...studies and theory when traditional philosophical foundations are disavowed? What happens to the study of teaching and writing when antifoundationalism is accepted? What strategies for human understanding are possible when the weaknesses of antifoundationalism are identified? This volume offers answers in classic essays by such thinkers as Richard Rorty, Terry Eagleton, and Stanley Fish, and in many new essays never published before.The contributors to this book explore the nexus of antifoundationalism and rhetoric, critique that nexus, and suggest a number of pedagogical and theoretical alternatives. The editors place these statements into a context that is both critical and evaluative, and they provide for voices that dissent from the antifoundational perspective and that connect specific, practical pedagogies to the broader philosophical statements. For those with an interest in rhetoric, philosophy, comparative literature, or the teaching of composition, this book sets forth a wealth of thought-provoking ideas.
Cyclosporin A (CsA)-dilauroylphosphatidylcholine (DLPC) liposome aerosol was evaluated for potential toxicity in a 28-day, acute toxicity study in rats. Rats of both sexes were housed in a nose-only ...chamber and exposed to aerosols of room air, water, DLPC liposomes (37.5 mg DLPC/ml in reservoir) or CsA-DLPC liposomes (5 mg CsA/ml and 37.5 mg DLPC in reservoir; 75.4 g CsA/L aerosol) generated by an AeroTech II nebulizer for 1 h each day for 28 consecutive days. The estimated retained dose of CsA was 1.58 mg CsA/kg body weight. The rats were monitored during the exposure period and for 2 wk after for body or organ weights, hematology, clinical chemistry, gross lesions, and histopathology of lungs, kidney, and liver. There were no differences for any of the parameters in any of the four exposure groups at any time point except for histopathology. These examinations revealed widespread chronic inflammatory lesions in all groups throughout the test period. These lesions were not associated with exposure to any of the test materials. The etiology of the pulmonary inflammation is unknown. The inflammatory lesions consisted of interstitial, perivascular, peribronchiolar, and alveolar cellular infiltrates that progressed to an organizing alveolitis with Type 2 cell hyperplasia and interstitial fibrosis. Lung lesions were observed in all experimental groups at all time points examined. The degree of severity of inflammatory lesions in the lungs increased with time through day 29 in all groups. Two weeks after final exposure to the test compounds (day 42), the average increase in severity and total number of lesions in all lobes were significantly less in the CsA-DLPC liposome-treated group (p < .04) and borderline in the DLPC group. Thus, DLPC and CsA-DLPC liposomes had no detectable adverse effects after daily inhalations over a period of 28 days, and there was a possible beneficial effect of CsA and possibly of DLPC against an opportunistic pulmonary pathogen in the rats that preexisted the aerosol exposures.
Children have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain ...unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.
Abstract Introduction The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's ...disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial. Methods In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial. Results Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. Conclusion These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD.
Background Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children. ...Objective We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years. Methods In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression. Results A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 95% CI 1.59-6.91; 2 years, 6.37 95% CI, 3.48-11.66). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not. Conclusion HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk predicts asthma and may inform management of these high-risk groups.
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