240 research outputs found

    Positive Workplace Dynamics: A Qualitative Exploration of Exceptional Performance in Community College Units

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    In this companion dissertation findings are reported of applied case study research on four community college organizational units that consistently meet or exceed standard performance measures. Ample prior evidence confirmed that performance extended significantly beyond what might be explained by available tangible resources alone. The case study contexts are common in higher education in general: a) an external partnership, (b) an ad hoc team, (c) a traditional, cross-divisional service unit, and (d) a grant-funded student service unit. Emerging positive organizational theory and research shows promise for revealing performance-influencing phenomena and behaviors that are not adequately represented in standard measures. Therefore, this collaborative case study research was designed to explore positive influences on the success of the four community college units. The companion dissertation consists of three manuscripts. Chapter 2, a technical report, is a collaboratively-written synthesis of findings from the four individual case studies. Key findings across the units suggest the influence on performance of: (a) a people-first culture, (b) authentic, trusting, inclusive leadership, and (c) resource richness beyond constrained tangible resources. In Chapter 3, the author presents in journal article format one of the case studies that contributed to the findings reported in Chapter 2. The academic library chosen for this research serves an urban community college campus near the geographic center of its city. The research asks how the library consistently performs well despite severe budget and staffing constraints and a series of disruptive events. Key findings in Chapter 3 include the following influences on performance: (a) valuing people and building relationships; (b) a culture of service that shares duties, resources, and expertise; and (c) leadership that effectively translates formal goals into an enabling matrix of behaviors and phenomena. In Chapter 4, a scholarly narrative, the author reflects on transformative aspects of the doctoral experience on learning and life. Practical recommendations are offered. Additional research is needed to explore causal relationships, how to influence greater resource amplification, and how to increase awareness of positive organizational dynamics

    Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

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    Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed

    Ensembles of Gustatory Cortical Neurons Anticipate and Discriminate Between Tastants in a Single Lick

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    The gustatory cortex (GC) processes chemosensory and somatosensory information and is involved in learning and anticipation. Previously we found that a subpopulation of GC neurons responded to tastants in a single lick (Stapleton et al., 2006). Here we extend this investigation to determine if small ensembles of GC neurons, obtained while rats received blocks of tastants on a fixed ratio schedule (FR5), can discriminate between tastants and their concentrations after a single 50 μL delivery. In the FR5 schedule subjects received tastants every fifth (reinforced) lick and the intervening licks were unreinforced. The ensemble firing patterns were analyzed with a Bayesian generalized linear model whose parameters included the firing rates and temporal patterns of the spike trains. We found that when both the temporal and rate parameters were included, 12 of 13 ensembles correctly identified single tastant deliveries. We also found that the activity during the unreinforced licks contained signals regarding the identity of the upcoming tastant, which suggests that GC neurons contain anticipatory information about the next tastant delivery. To support this finding we performed experiments in which tastant delivery was randomized within each block and found that the neural activity following the unreinforced licks did not predict the upcoming tastant. Collectively, these results suggest that after a single lick ensembles of GC neurons can discriminate between tastants, that they may utilize both temporal and rate information, and when the tastant delivery is repetitive ensembles contain information about the identity of the upcoming tastant delivery

    Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers.

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    Galloyl catechins, in particular (-)-epicatechin gallate (ECg), have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA); they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (-)-epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation

    Modeling timing and size of juvenile Chinook salmon out-migrants at three Elwha River rotary screw traps: a window into early life history post dam removal

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    Chinook salmon (Oncorhynchus tshawytscha) populations express diverse early life history pathways that increase habitat utilization and demographic resiliency. Extensive anthropogenic alterations to freshwater habitats along with hatchery and harvest impacts have led to marked reductions in early life history diversity across much of the species’ range. The recent removal of two Elwha River dams between 2011 and 2014 restored access to over 90% of the available habitat that had been inaccessible to Chinook salmon since the early 1900s. This provided an opportunity to investigate how renewed access to this habitat might affect life history diversity. As exotherms, egg-to-fry development, juvenile growth, and movement are influenced by water temperatures. We used spatially and temporally explicit Elwha River water temperature and Chinook salmon spawning location data, in conjunction with spawn timing, emergence, growth, and movement models, to predict observed timing and sizes of juvenile Chinook salmon captured in three rotary screw traps in the mainstem and two tributaries during four trap years. This effort allowed us to test hypotheses regarding Elwha River Chinook salmon early life history, identify potential problems with the data, and predict how emergence and growth would change with increased spawning in the upper watershed. Predicted Chinook salmon emergence timing and predicted dates that juveniles reached 65 mm differed by as much as 2 months for different river locations due to large differences in thermal regimes longitudinally in the mainstem and between tributaries. For 10 out of the 12 trap–year combinations, the model was able to replicate important characteristics of the out-migrant timing and length data collected at the three traps. However, in most cases, there were many plausible parameter combinations that performed well, and in some cases, the model predictions and observations differed. Potential problems with the data and model assumptions were identified as partial explanations for differences and provide avenues for future work. We show that juvenile out-migrant data combined with mechanistic models can improve our understanding of how differences in temperature, spawning extent, and spawn timing affect the emergence, growth, and movement of juvenile fish across diverse riverine habitats

    Frequent Heterogeneous Missense Mutations of GGAP2 in Prostate Cancer: Implications for Tumor Biology, Clonality and Mutation Analysis

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    Prostate cancer is the most common visceral malignancy in Western men and a major cause of cancer deaths. Increased activation of the AKT and NFkB pathways have been identified as critical steps in prostate cancer initiation and progression. GGAP2 (GTP-binding and GTPase activating protein 2) is a multidomain protein that contains an N-terminal Ras homology domain (GTPase), followed by a PH domain, a C-terminal GAP domain and an ankyrin repeat domain. GGAP2 can directly activate signaling via both the AKT and NFkB pathways and acts as a node of crosstalk between these pathways. Increased GGAP2 expression is present in three quarters of prostate cancers. Mutations of GGAP2 have been reported in cell lines from other malignancies. We therefore analyzed 84 prostate cancer tissues and 43 benign prostate tissues for somatic mutations in GGAP2 by direct sequencing of individual clones derived from the GAP and GTPase domains of normal and tumor tissue. Overall, half of cancers contained mutant GAP domain clones and in 20% of cancers, 30% or more of clones were mutant in the GAP domain. Surprisingly, the mutations were heterogeneous and nonclonal, with multiple different mutations being present in many tumors. Similar findings were observed in the analysis of the GTPase domain. Mutant GGAP2 proteins had significantly higher transcriptional activity using AP-1 responsive reporter constructs when compared to wild-type protein. Furthermore, the presence of these mutations was associated with aggressive clinical behavior. The presence of high frequency nonclonal mutations of a single gene is novel and represents a new mode of genetic alteration that can promote tumor progression. Analysis of mutations in cancer has been used to predict outcome and guide therapeutic target identification but such analysis has focused on clonal mutations. Our studies indicate that in some cases high frequency nonclonal mutations may need to be assessed as well

    The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

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    The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/
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