The Experience of Aging: A Reconstruction of the Meaning of Time's Passing within the Classical American Philosophical Tradition

The provocation for this dissertation is a brief contention: aging is not synonymous with disease. This contention is a corrective reaction to the pervasive sensibility that aging is a disease, and which therefore casts the character of time’s passing as a process of destruction. The upshot of this corrosive sensibility is that we are not aging well. Guided both by the belief that we can reconstruct the meaning of time’s passing and an ameliorative sensibility to heal human suffering, the dissertation offers an alternative, more fruitful understanding of aging in which the character of time changes from a process of destruction into one of creative individual genesis. This is how we should experience time as time passes. Living in this way is an achievement: It is the activity of ferreting out the best possible ways in which to live so that life is deep and robust with concatenated meaning. This philosophical diagnosis of aging is situated within two philosophical traditions—first, existentialism and, second and primarily, the pragmatism of classical American philosophers. The deceptively simple insights from existentialism at work in the dissertation are this: that we are ontologically free to choose our own persons and that our freedom resides in the ever-present possible. The next philosophical move that is made is the pragmatic turn: that, with a sense that there is always something better, we attend to how it is that we press into our possibilities by listening to and heeding experience so that we adapt and grow as individuals

Double conditional human embryonic kidney cell line based on FLP and ΦC31 mediated transgene integration

<p>Abstract</p> <p>Background</p> <p>FLP recombinase mediated integration into a pre-integrated FRT site is routinely used to generate highly reproducible stable transgenic cell lines. In this study, we broaden the system of site specific integration by introducing ΦC31 integrase mediated integration into attP sites.</p> <p>Results</p> <p>We generated a HEK293 host cell line with a single copy FRT as well as an attP site allowing site specific integration of two distinct transgenes. To achieve conditional control, we used the tetracycline and Shld1 inducible systems. By introducing fluorescent reporters we show that integration and induction of two transgenes are completely independent. We applied this new technique to investigate the effect of HNF4α on proliferation of HEK293 cells by introducing HNF4α into each integration site. We obtained in two independent cell lines highly reproducible results that prove the usefulness of this novel HEK-attP/FRT cell line.</p> <p>Conclusions</p> <p>In this study we have established and applied a HEK-attP/FRT cell line that allows site specific integration of two conditional transgenes using the FLP recombinase as well as the ΦC31 integrase.</p

Expression of Glucose Transporters in the Prelaminar Region of the Optic-Nerve Head of the Pig as Determined by Immunolabeling and Tissue Culture

Background: To develop the use of cultured tissue of the prelaminar optic nerve of the pig to explore possible alterations of the astrocyte-axon metabolic pathways in glaucoma, we map the distribution of the glucose transporters GLUT1 and GLUT3 in fresh and cultured tissue.Methods: We monitor cell survival in cultures of the prelaminar optic-nerve tissue, measuring necrosis and apoptosis markers biochemically as well as morphologically, and establish the presence of the glucose transporters GLUT1 and GLUT3. We map the distribution of these transporters with immunolabeling in histological sections of the optic nerve using confocal and electronic transmission microscopy.Results: We find that the main death type in prelaminar culture is apoptosis. Caspase 7 staining reveals an increment in apoptosis from day 1 to day 4 and a reduction from day 4 to day 8. Western blotting for GLUT1 shows stability with increased culture time. CLSM micrographs locate GLUT1 in the columnar astrocytes and in the area of axonal bundles. Anti-GLUT3 predominantly labels axonal bundles. TEM immunolabeling with colloidal gold displays a very specific distribution of GLUT-1 in the membranes of vascular endothelial cells and in periaxonal astrocyte expansions. The GLUT-3 isoform is observed with TEM only in axons in the axonal bundles.Conclusions: Tissue culture is suitable for apoptosis-induction experiments. The results suggest that glucose is transported to the axonal cleft intracytoplasmically and delivered to the cleft by GLUT1 transporters. As monocarboxylate transporters have been reported in the prelaminar region of the optic-nerve head, this area is likely to use both lactate and glucose as energy sources.This work was supported by a grant from the Consejería de Salud, Junta de Andalucia, Spain, Project PI-0655-2013

Converging or Diverging? A comparative analysis of contingent employment practice in Europe over a 10-year period

Tregaskis lead author. This output was selected as one of the 12 ‘Papers of Excellence’ shortlisted for the Academy of Management’s inaugural 2007 IHRM Scholarly Research Award.The file attached to this record is a post-peer-review, pre-copyedit version of an article published in the Journal of International Business Studies. The definitive publisher-authenticated version Tregaskis, O. and Brewster, C. (2006) Converging or diverging? A comparative analysis of trends in contingent employment practice in Europe over a decade. Journal of International Business Studies, 37 (1), pp. 111-126. is available online at: http://dx.doi.org/10.1057/palgrave.jibs.8400174This paper makes a unique contribution to the HRM convergence-divergence debate by examining whether organizations operating in Europe, over the 10-year time period preceding 2000, are converging in their adoption of contingent employment practice. The susceptibility of contingent employment practice to both convergent and divergent pressures acts as a useful analytical lens. Data are drawn from organizations operating in Germany, Spain, Sweden, the Netherlands and the UK in 1991 (2918 organizations), 1995 (2048 organizations) and 2000 (1555 organizations).The results suggest that convergence is limited by the institutional embeddedness of organizations