1,071 research outputs found

    The beginnings of geography teaching and research in the University of Glasgow: the impact of J.W. Gregory

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    J.W. Gregory arrived in Glasgow from Melbourne in 1904 to take up the post of foundation Professor of Geology in the University of Glasgow. Soon after his arrival in Glasgow he began to push for the setting up of teaching in Geography in Glasgow, which came to pass in 1909 with the appointment of a Lecturer in Geography. This lecturer was based in the Department of Geology in the University's East Quad. Gregory's active promotion of Geography in the University was matched by his extensive writing in the area, in textbooks, journal articles and popular books. His prodigious output across a wide range of subject areas is variably accepted today, with much of his geomorphological work being judged as misguided to varying degrees. His 'social science' publications - in the areas of race, migration, colonisation and economic development of Africa and Australia - espouse a viewpoint that is unacceptable in the twenty-first century. Nonetheless, that viewpoint sits squarely within the social and economic traditions of Gregory's era, and he was clearly a key 'Establishment' figure in natural and social sciences research in the first half of the twentieth century. The establishment of Geography in the University of Glasgow remains enduring testimony of J.W. Gregory's energy, dedication and foresight

    Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth

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    Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy

    CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

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    In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody–receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC

    Resilience and Alternative Stable States After Desert Wildfires

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    Improving models of community change is a fundamental goal in ecology and has renewed importance during global change and increasing human disturbance of the biosphere. Using the Mojave Desert (southwestern United States) as a model system, invaded by nonnative plants and subject to wildfire disturbances, we examined models of resilience, alternative stable states, and convergent-divergent trajectories for 36 yr of plant community change after 31 wildfires in communities dominated by the native shrubs Larrea tridentata or Coleogyne ramosissima. Perennial species richness on average was fully resilient within 23 yr after disturbance in both community types. Perennial cover was fully resilient within 25 yr in the Larrea community, but recovery was projected to require 52 yr in the Coleogyne community. Species composition shifts were persistent, and in the Coleogyne community, the projected compositional recovery time of 550 yr and increasing resembled a deflected trajectory toward potential alternative states. Disturbed sites contained a perennial species composition of predominately short-statured forbs, subshrubs, and grasses, contrasting with the larger-statured shrub and tree structure of undisturbed sites. Auxiliary data sets characterizing species recruitment, annual plants including nonnative grasses, biocrust communities, and soils showed persistent differences between disturbed and undisturbed sites consistent with positive feedbacks potentially contributing to alternative stable states. Resprouting produced limited resilience for the large shrubs L. tridentata and Yucca spp. important to population persistence but did not forestall long-term reduced abundance of the species. The nonnative annual grass Bromus rubens increased on disturbed sites over time, suggesting persistently abundant nonnative plant fuels and reburn potential. Biocrust cover on disturbed sites was half and species richness a third of amounts on undisturbed sites. Soil nitrogen was 30% greater on disturbed sites and no significant trend was evident for it to decline on even the oldest burns. Disturbed desert plant communities simultaneously supported all three models of resilience, alternative stable states, and convergent-divergent trajectories among community measures (e.g., species richness, composition), timeframes since disturbance, and spatial resolutions. Accommodating expression within ecosystems of multiple models, including those opposing each other, may help broaden theoretical models of ecosystem change

    Work-Unit Absenteeism: Effects of Satisfaction, Commitment, Labor Market Conditions, and Time

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    Prior research is limited in explaining absenteeism at the unit level and over time. We developed and tested a model of unit-level absenteeism using five waves of data collected over six years from 115 work units in a large state agency. Unit-level job satisfaction, organizational commitment, and local unemployment were modeled as time-varying predictors of absenteeism. Shared satisfaction and commitment interacted in predicting absenteeism but were not related to the rate of change in absenteeism over time. Unit-level satisfaction and commitment were more strongly related to absenteeism when units were located in areas with plentiful job alternatives

    Proactive and politically skilled professionals: What is the relationship with affective occupational commitment?

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    The aim of this study is to extend research on employee affective commitment in three ways: (1) instead of organizational commitment the focus is on occupational commitment; (2) the role of proactive personality on affective occupational commitment is examined; and (3) occupational satisfaction is examined as a mediator and political skills as moderator in the relationship between proactive personality and affective occupational commitment. Two connected studies, one in a hospital located in the private sector and one in a university located in the public sector, are carried out in Pakistan, drawing on a total sample of over 400 employees. The results show that proactive personality is positively related to affective occupational commitment, and that occupational satisfaction partly mediates the relationship between proactive personality and affective occupational commitment. No effect is found for a moderator effect of political skills in the relationship between proactive personality and affective occupational commitment. Political skills however moderate the relationship between proactive personality and affective organizational commitment

    Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages

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    International audienceMacrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the aetiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behaviour is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover and function. We demonstrat

    Physician Compensation from Salary and Quality of Diabetes Care

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    OBJECTIVE: To examine the association between physician-reported percent of total compensation from salary and quality of diabetes care. DESIGN: Cross-sectional analysis. PARTICIPANTS: Physicians (n = 1248) and their patients with diabetes mellitus (n = 4200) enrolled in 10 managed care plans. MEASUREMENTS: We examined the associations between physician-reported percent compensation from salary and processes of care including receipt of dilated eye exams and foot exams, advice to take aspirin, influenza immunizations, and assessments of glycemic control, proteinuria, and lipid profile, intermediate outcomes such as adequate control of hemoglobin A1c, lipid levels, and systolic blood pressure levels, and satisfaction with provider communication and perceived difficulty getting needed care. We used hierarchical logistic regression models to adjust for clustering at the health plan and physician levels, as well as for physician and patient covariates. We adjusted for plan as a fixed effect, meaning we estimated variation between physicians using the variance within a particular health plan only, to minimize confounding by other unmeasured health plan variables. RESULTS: In unadjusted analyses, patients of physicians who reported higher percent compensation from salary (>90%) were more likely to receive 5 of 7 diabetes process measures and more intensive lipid management and to have an HbA1c<8.0% than patients of physicians who reported lower percent compensation from salary (<10%). However, these associations did not persist after adjustment. CONCLUSIONS: Our findings suggest that salary, as opposed to fee-for-service compensation, is not independently associated with diabetes processes and intermediate outcomes
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