5,769 research outputs found

    Learning from openness : the dynamics of breadth in external innovation linkages

    Get PDF
    We explore how openness in terms of external linkages generates learning effects, which enable firms to generate more innovation outputs from any given breadth of external linkages. Openness to external knowledge sources, whether through search activity or linkages to external partners in new product development, involves a process of interaction and information processing. Such activities are likely to be subject to a learning process, as firms learn which knowledge sources and collaborative linkages are most useful to their particular needs, and which partnerships are most effective in delivering innovation performance. Using panel data from Irish manufacturing plants, we find evidence of such learning effects: establishments with substantial experience of external collaborations in previous periods derive more innovation output from openness in the current period

    Ultrasound characteristics of foot and ankle structures in healthy, coper, and chronically unstable ankles

    Get PDF
    Objective: Ankle sprains constitute approximately 85% of all ankle injuries and up to 70% of people experience residual symptoms. Whilst the injury to ligaments is well understood the potential role of other foot and ankle structures has not been explored. The objective was to characterise and compare selected ankle structures in participants with and without a history of lateral ankle sprain. Methods: 71 participants were divided into 31 healthy, 20 coper, and 20 chronic ankle instability groups. Ultrasound images of the anterior talofibular and calcaneofibular ligaments, fibularis tendons and muscles, tibialis posterior and Achilles tendon were obtained. Thickness, length, and cross sectional areas were measured and compared between groups. Results: When under tension the anterior talofibular ligament was longer in copers and chronic ankle instability groups compared to healthy participants (p < 0.001 and p = 0.001 respectively). The chronic ankle instability group had the thickest ATFL and CFL among the three groups (p < 0.001). No significant differences (p > 0.05) in tendons and muscles were observed between the three groups. Conclusions: The ultrasound protocol proved reliable and was used to evaluate the length, thickness, and CSA of selected ankle structures. The length of the ATFL and the thickness of the ATFL and CFL were longer and thicker in injured groups compared to healthy

    Peroxiredoxin Catalysis at Atomic Resolution

    Get PDF
    Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases that guard cells against oxidative damage, are virulence factors for pathogens, and are involved in eukaryotic redox regulatory pathways. We have analyzed catalytically active crystals to capture atomic resolution snapshots of a PrxQ-subfamily enzyme (from Xanthomonas campestris) proceeding through thiolate, sulfenate, and sulfinate species. These analyses provide structures of unprecedented accuracy for seeding theoretical studies, and show novel conformational intermediates giving insight into the reaction pathway. Based on a highly non-standard geometry seen for the sulfenate intermediate, we infer that the sulfenate formation itself can strongly promote local unfolding of the active site to enhance productive catalysis. Further, these structures reveal that preventing local unfolding, in this case via crystal contacts, results in facile hyperoxidative inactivation even for Prxs normally resistant to such inactivation. This supports previous proposals that conformation-specific inhibitors may be useful for achieving selective inhibition of Prxs that are drug targets

    Mine, Yours, Ours? Sharing Data on Human Genetic Variation

    Get PDF
    The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing

    Silver(I) N-Heterocyclic Carbene Complexes Derived from Clotrimazole: Antiproliferative Activity and Interaction with an Artificial Membrane-Based Biosensor

    Get PDF
    With the aim of combining the potential anticancer properties of both clotrimazole, an imidazole based antifungal agent, and silver(I) N-heterocyclic carbenes, 13 novel silver(I) N-heterocyclic carbene complexes derived from clotrimazole were synthesized. The complexes were fully characterized, and the partition coefficient of each was determined to provide a measure of hydrophobicity. The antiproliferative properties of the complexes against cancerous and noncancerous cell lines found optimum cytotoxicity when the complex displays an “intermediate lipophilicity”, which describes a complex that possesses both water-soluble groups and lipophilic aromatic groups. The silver complexes were screened on a synthetic biomembrane-like device using a chip-based phospholipid-coated Pt/Hg electrode embedded in a flow cell system. The results are recorded as rapid cyclic voltammograms (RCVs), which give insight into the interactions of the complexes with a cell membrane. Interestingly the principle of “intermediate lipophilicity” also applies to the monolayer interaction to which the silver atom significantly implements an irreversibility

    Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up

    Get PDF
    BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers’ Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1–14), medium (15–24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation

    Organizational factors and depression management in community-based primary care settings

    Get PDF
    Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe

    Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury

    Get PDF
    Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition
    corecore