3,962 research outputs found

    Overcoming barriers to knowledge management: Visiting the dark side of the organization

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    Like many organisational endeavours, the success of knowledge management praxis is subject to the vagaries of human nature. There are many reasons, most of which are underpinned by the need for power, why people might choose to hoard, distort and manipulate information. Recent studies undertaken by the authors have demonstrated the way in which knowledge management processes can also be manipulated to impede the distribution of power. This dark side of organisational behaviour is usually subversive, can be unconscious or conscious and always acts against the interests of the group or part of the group. It is important for those involved in knowledge management practice to be acutely aware of the dynamics of the dark side and how they may interfere with their best intentions. As well as describing this phenomenon, this paper also suggests a number of ways in which the dark side might be overcome. Chiefly, drawing on general systems theory, we suggest some techniques that facilitate both open communication and open process

    Understanding how finances impact nonresident student college enrollment decisions: a mixed methods analysis

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    The costs of American higher education continue to rise. This increase makes it difficult for students and parents to pay for college. It also presents difficulties for university administrators and leaders who must maintain enrollment and tuition revenues. Understanding how individual students respond to increases in net price by assessing their initial matriculation decision can help university administrators and policy makers understand the results of increasing college costs. This emergent sequential mixed methods study examines the price responsiveness of nonresident freshmen and transfer students admitted to a highly selective master's comprehensive university in the southeast. The findings are multi-faceted, illustrating that needy freshman students are most price-responsive and that the qualitative strand controls for omitted variable bias found in quantitative studies

    Mind Your Meds: Safe Opioid Disposal Awareness

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    Driven by the effects of the opioid epidemic on friends, family members, students, and patients, members of the 2019 GEHLI Team “Mission Possible” are dedicated to bolstering educational awareness of safe leftover opioid disposal methods to decrease the supply of opioids in our community. On average, over 2/3 of opioid prescription medications are leftover and lead to later misuse or abuse (JAMA Survey). Despite a decrease in prescription writing for pain medication over the years, the mortality rate from overdose, and the rate of infants born to mothers with opioid abuse continues to steadily increase in Virginia (VDH). Team Mission Possible seeks to promote awareness of both the need and resources available for safe opioid disposal by educating prescribers in the VCU Health system and spreading knowledge to VCU patients, students, faculty, staff, and members of the surrounding community through: educational events on the Monroe Park and Medical campuses; teaming up with Miss Virginia’s “Mind your Meds campaign”; live Facebook interviews; and educational flyers

    A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury

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    This work was supported by Chang GungMemorialHospital, Taiwan CMRPG3A1051–1054to Z.-H.L., CMDRP and Barts and the London Charity to P.K.Y. and A.T.M.-T., and the Nathalie Rose Barr PhD Studentship ISRT to L.A. andJ.V.P

    Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies

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    PURPOSE: To investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children. DESIGN: Retrospective case series. PARTICIPANTS: Patients with mutations in CEP290 identified at a single UK referral center. METHODS: Review of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing. MAIN OUTCOME MEASURES: Molecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment. RESULTS: Forty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features. CONCLUSIONS: Detailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches

    Function-informed transcriptome analysis of Drosophila renal tubule

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    BACKGROUND: Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue. RESULTS: The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution. CONCLUSIONS: From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome

    Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate

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    Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by X-ray diffraction techniques(1). A catalytic mechanism, featuring a long-lived oxo-carbenium-ion intermediate, was proposed on the basis of model-building studies(2). The `Phillips' mechanism is widely held as the paradigm for the catalytic mechanism of beta -glycosidases that cleave glycosidic linkages with net retention of configuration of the anomeric centre. Studies with other retaining beta -glycosidases, however, provide strong evidence pointing to a common mechanism for these enzymes that involves a covalent glycosyl-enzyme intermediate, as previously postulated(3). Here we show, in three different cases using electrospray ionization mass spectrometry, a catalytically competent covalent glycosyl-enzyme intermediate during the catalytic cycle of HEWL. We also show the three-dimensional structure of this intermediate as determined by Xray diffraction. We formulate a general catalytic mechanism for all retaining beta -glycosidases that includes substrate distortion, formation of a covalent intermediate, and the electrophilic migration of C1 along the reaction coordinate

    Parallel-in-time integration of kinematic dynamos

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    The precise mechanisms responsible for the natural dynamos in the Earth and Sun are still not fully understood. Numerical simulations of natural dynamos are extremely computationally intensive, and are carried out in parameter regimes many orders of magnitude away from real conditions. Parallelization in space is a common strategy to speed up simulations on high performance computers, but eventually hits a scaling limit. Additional directions of parallelization are desirable to utilise the high number of processor cores now available. Parallel-in-time methods can deliver speed up in addition to that offered by spatial partitioning but have not yet been applied to dynamo simulations. This paper investigates the feasibility of using the parallel-in-time algorithm Parareal to speed up initial value problem simulations of the kinematic dynamo, using the open source Dedalus spectral solver. Both the time independent Roberts and time dependent Galloway-Proctor 2.5D dynamos are investigated over a range of magnetic Reynolds numbers. Speedups beyond those possible from spatial parallelisation are found in both cases. Results for the Galloway-Proctor flow are promising, with Parareal efficiency found to be close to 0.3. Roberts flow results are less efficient, but Parareal still shows some speed up over spatial parallelisation alone. Parallel in space and time speed ups of ∌300 were found for 1600 cores for the Galloway-Proctor flow, with total parallel efficiency of ∌0.16
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