Suchergebnisse

2017 Summer. ; Includes bibliographical references. ; Mammals, and in particular humans, are masterful at overcoming and adapting to extreme environments. Whether astronauts in low earth orbit aboard the International Space Station (ISS) or U.S. military veterans exposed to nuclear fallout from atomic weapons testing, humans can persist through a wide range of physical, psychological, and environmental stressors. The overall goal of the studies presented here was to evaluate the biological influences of extreme environments not commonly experienced by the general population. Whether spaceflight or exposure to nuclear fallout, results improve our understanding of short- and long-term effects of low gravity environments, exposure to ionizing radiation (IR) of mixed qualities, as well as low dose and low dose effects of IR. We explored these scenarios by evaluating biomarkers of stress, specifically telomere length dynamics, and biomarkers of DNA damage, specifically transmissible structural rearrangements. Telomeres are not only regarded as valuable biomarkers of aging and age-related degenerative pathologies like cardiovascular disease and cancer, and so are reflective of overall health status, they also serve as "hallmarks" of radiosensitivity. Stable chromosomal structural rearrangements (translocations and inversions) persist with time and so provide informative signatures of IR exposure as well. During the 1950's United States military personnel and weathermen, collectively known as the atomic veterans, were unintentionally exposed to nuclear fallout during atomic bomb testing following WWII. Here, directional Genomic Hybridization (dGH) for high-resolution detection of IR-induced chromosomal inversions and translocations was assessed as a more sensitive, quantitative retrospective biodosimetry approach. The influence of IR exposure on telomere length dynamics was also evaluated to determine the long-term influence of such exposures. Our results illustrate that even for nuclear events that occurred six decades in the past, evidence of exposure is still present. We find that although translocations and inversions are reliable biodosimeters independently, a combined approach provides a more sensitive measurement of past radiation exposure. We also report, for the first time, the influence of age and smoking on background inversion frequencies. Furthermore, telomere length was inversely related to IR dose, suggesting that a single acute exposure to nuclear fallout may lead to persistent long-term effects on overall health. Telomere length dynamics and structural rearrangements were also monitored longitudinally in monozygotic twin and unrelated astronauts. NASA astronauts are a unique group of individuals who experience an extreme environment that the human body is not adapted for. Little is known about the biological health effects of a low gravity environment with increased IR exposure including galactic cosmic rays (GCRs), solar particle events, and secondary neutrons. Not only do astronauts have shorter telomeres than age-/gender-matched controls at baseline (pre-flight), but a transient increase in telomere length during space flight was also observed. Results suggest this unexpected finding may be due to an upregulation of telomerase, the enzyme responsible for maintaining telomere length. Moreover, telomerase activity also increased post-flight in both twins, Scott and Mark Kelly. Although not spaceflight specific, this is the first report of telomerase upregulation in humans due to a psychologically traumatic event. A dose dependent increase in inversions, and to a lesser extent, translocations, as a consequence of IR exposure on the ISS was also seen in Scott Kelly. Collectively, the studies presented here demonstrate a profound influence of extreme environments, particularly those involving low dose IR, on human biological responses. Telomere length dynamics and chromosome aberration frequencies (e.g. translocations and inversions) provide insight into the long-term health effects and implications of spaceflight and exposure to nuclear events.

It has now been over 60 years since U.S. nuclear testing was conducted in the Pacific islands and Nevada, exposing military personnel to varying levels of ionizing radiation. Actual doses are not well-established, as film badges in the 1950s had many limitations. We sought a means of independently assessing dose for comparison with historical film badge records and dose reconstruction conducted in parallel. For the purpose of quantitative retrospective biodosimetry, peripheral blood samples from 12 exposed veterans and 12 age-matched (>80 years) veteran controls were collected and evaluated for radiation-induced chromosome damage utilizing directional genomic hybridization (dGH), a cytogenomics-based methodology that facilitates simultaneous detection of translocations and inversions. Standard calibration curves were constructed from six male volunteers in their mid-20s to reflect the age range of the veterans at time of exposure. Doses were estimated for each veteran using translocation and inversion rates independently; however, combining them by a weighted-average generally improved the accuracy of dose estimations. Various confounding factors were also evaluated for potential effects on chromosome aberration frequencies. Perhaps not surprisingly, smoking and age-associated increases in background frequencies of inversions were observed. Telomere length was also measured, and inverse relationships with both age and combined weighted dose estimates were observed. Interestingly, smokers in the non-exposed control veteran cohort displayed similar telomere lengths as those in the never-smoker exposed veteran group, suggesting that chronic smoking had as much effect on telomere length as a single exposure to radioactive fallout. Taken together, we find that our approach of combined chromosome aberration-based retrospective biodosimetry provided reliable dose estimation capability, particularly on a group average basis, for exposures above statistical detection limits.

"Monsanto Research Corporation a subsidiary of Monsanto Company"--Cover. ; "Issued: February 25, 1972." ; "MLM-1891; TID-4500 ; UC-4." ; Includes bibliographic references (page 22) ; Mound Laboratory, Miamisburg, Ohio, operated for United States Atomic Energy Commission, U.S. Government Contract no. ; Mode of access: Internet.

Phenomenology is the philosophy of our times. Through the entire twentieth century this philosophy unfolded and flourished, following stepwise the intrinsic logic and dynamism of its original project as proposed by its founder Edmund Husserl. Now its seminal ideas have been handed over to a new era. The worldwide contributors to this volume make it manifest that phenomenological inspiration knows no cultural barriers. It penetrates and invigorates not only philosophical disciplines but also most of the sectors of knowledge, transforming our way of seeing the world, our actions toward others, and our lives. Phenomenology's universal spread has, however, oftentimes diluted its original sense, even beyond recognition, and led to a weakening of its dynamics. There is at present an urgent need to retrieve the original understanding of phenomenology, to awaken its dormant forces and redirect them. This is the aim of the present book: resourcement and reinvigoration. It is meant to be not only a reference work but also a guide for research and study. To restore the authentic vision of phenomenology, we propose returning to its foundational source in Husserl's project of a `universal science', unpacking all its creative capacities. In the three parts of this work there are traced the stages of this philosophy's progressive uncovering of the grounding levels of reality: ideal structures, constitutive consciousness, the intersubjective lifeworld, and beyond. The key concepts and phases of Husserl's thought are here exfoliated. Then the thought of the movement's classical figures and of representative thinkers in succeeding generations is elucidated. Phenomenology's geographic spread is reviewed. We then proceed to the culminating work of this philosophy, to the phenomenological life engagements so vigorously advocated by Husserl, to the life-significant issues phenomenology addresses and to how it has enriched the human sciences. Lastly the phenomenological project's new horizons on the plane of life are limned, horizons with so powerful a draw that they may be said not to beckon but to summon. Here is the movement's vanguard. This collection has 71 entries. Each entry is followed by a relevant bibliography. There is a helpful Glossary of Terms and an Index of Names