Oxidative stress is transient and tissue-specific during cold acclimation of threespine sticklebacks

Thesis (M.S.) University of Alaska Fairbanks, 2010We sought to determine if oxidative stress occurs in liver, oxidative muscle or glycolytic muscle of threespine sticklebacks during cold acclimation. Fishes were held at 20°C for 12 wks and then acclimated to 8°C for 9 wks or held at 20°C for an additional 9 wks. Animals were harvested during the first four days of cold acclimation, and at wk 1, 4 and 9. Protein carbonyls were quantified as an indirect measure of the production of reactive oxygen species (ROS). The activity of superoxide dismutase (SOD), levels of SOD mRNA, and glutathione levels were quantified as indices of protection against ROS. All measurements were made in liver, glycolytic muscle and oxidative muscle. Protein carbonyl levels increased in livers of fishes after 1 wk at 8°C and decreased after wk 4. Total glutathione levels increased in livers on day 3 of cold acclimation and then decreased by wk 4. Measured at a common temperature, SOD activity increased early in all tissues and remained elevated throughout cold acclimation. Measured at the acclimation temperature, SOD activity increased only in oxidative muscle after 9 wks of cold acclimation. Together, these results indicate that oxidative stress is transient and tissue-specific during cold acclimation of fishes.1. Oxidative stress is transient and tissue-specific during cold acclimation of threespine sticklebacks -- 1.1. Summary -- 1.2. Introduction -- 1.3. Materials and methods -- 1.3.1. Animal care and experimental design -- 1.3.2. Protein carbonyl levels -- 1.3.3. Glutathione levels -- 1.3.4. Superoxide dismutase activity -- 1.3.5. RNA isolation -- 1.3.6. Quantitative real-time PCR -- 1.4. Statistical analysis -- 1.5. Results -- 1.5.1. Physical characteristics -- 1.5.2. Protein carbonylation -- 1.5.3. Glutathione content -- 1.5.4. Activity of superoxide dismutase -- 1.6. Discussion -- 1.6.1. Oxidative stress is tissue-specific -- 1.6.2. SOD activity increases in response to cold acclimation -- 1.6.3. Potential source of ROS during cold acclimation -- 1.6.4. ROS as signaling molecules -- 1.7. Conclusions -- 1.8. Acknowledgements -- 1.9. References -- Conclusions

Streaming Kernelization

Kernelization is a formalization of preprocessing for combinatorially hard problems. We modify the standard definition for kernelization, which allows any polynomial-time algorithm for the preprocessing, by requiring instead that the preprocessing runs in a streaming setting and uses $\mathcal{O}(poly(k)\log|x|)$ bits of memory on instances $(x,k)$. We obtain several results in this new setting, depending on the number of passes over the input that such a streaming kernelization is allowed to make. Edge Dominating Set turns out as an interesting example because it has no single-pass kernelization but two passes over the input suffice to match the bounds of the best standard kernelization

Underground nuclear power plant siting

This study is part of a larger evaluation of the problems associated with siting nuclear power plants in the next few decades. This evaluation is being undertaken by the Environmental Quality Laboratory of the California Institute of Technology in conjunction with The Aerospace Corporation and several other organizations. Current efforts are directed toward novel approaches to siting plants within the State of California. This report contains the results of efforts performed by The Aerospace Corporation to provide input information to the larger evaluation relative to underground siting of large central station nuclear power plants. Projections of electric power demand in California and the country as a whole suggest that a major increase in generating capacity will be required. The problem is complicated beyond that of a large but straightforward extension of capital investment by increased emphasis on environmental factors combined with the early stage of commercial application and regulation of nuclear power sources. Hydroelectric power generation is limited by the availability of suitable sites, and fossil fueled plants are constrained by the availability of high quality fuels and the adverse environmental and/or economic impact from the use of more plentiful fuels. A substantial increase in the number of nuclear power plants is now under way. This source of power is expected to provide the maj or portion of increased capacity. Other power sources such as geothermal and nuclear fusion are unlikely to satisfy the national needs due to technical problems and the lack of a comprehensive development program. There are several problems associated with meeting the projected power demand. Chief among these is the location of acceptable and economic plant sites. Indeed a sufficient number of sites may not be found unless changes occur in the procedures for selecting sites, the criteria for accepting sites, or the type of site required. Placement of a nuclear plant underground has been suggested as an alternative to present siting practices. It is postulated that the advantages of underground siting in some situations may more than compensate for added costs so that such facilities could be preferred even where surface sites are available. By virtue of greater safety, reduced surface area requirements, and improved aesthetics, underground sites might also be found where acceptable surface sites are not available. Four small European reactors have been constructed partially underground but plans for large size commercial plants have not progressed. Consequently, the features of underground power plant siting are not well understood. Gross physical features such as depth of burial, number and size of excavated galleries, equipment layout, and access or exit shafts/tunnels must be specified. Structural design features of the gallery liners, containment structure, foundations, and gallery interconnections must also be identified. Identification of the nuclear, electrical, and support equipment appropriate to underground operation is needed. Operational features must be defined for normal operations, refueling, and construction. Several magazine articles have been published addressing underground concepts. but adequate engineering data is not available to support an evaluation of the underground concept. There also remain several unresolved questions relative to the advantages of underground siting as well as the costs and other possible penalties associated with this novel approach to siting. These include the degree of increased safety through improved containment; the extent and value of isolation from falling objects, e. g. aircraft; the value of isolation from surface storms and tidal waves; the value of protection from vandalism or sabotage; the extent by which siting constraints are relieved through reduced population-distance requirements or aggravated by underground construction requirements; and the value to be placed upon the aesthetic differences of a less visible facility. The study described in this report has been directed toward some of these questions and uncertainties. Within the study an effort has been made to identify viable configurations and structural liners for typical light water reactor nuclear power plants. Three configurations are summarized in Section 3. A discussion of the underground gallery liner design and associated structural analyses is presented in Section 4. Also addressed in the study and discussed in Section 5 are some aspects of containment for underground plants. There it is suggested that the need for large separations between the plant and population centers may be significantly reduced, or perhaps eliminated. Section 6 contains a brief discussion of operational considerations for underground plants. The costs associated with excavation and lining of the underground galleries have been estimated in Section 7. These estimates include an assessment of variations implied by different seismic loading assumptions and differences in geologic media. It is shown that these costs are a small percentage of the total cost of comparable surface plants. Finally, the parameters characterizing an acceptable underground site are discussed in Section 8. Material is also included in the appendices pertaining to foreign underground plants, span limits of underground excavations, potential siting areas for underground plants in the State of California, pertinent data from the Underground Nuclear Test Program, and other supporting technical discussions

Sexual Harassment Among Medical Students: Prevalence, Prediction, and Correlated Outcomes

Background: Few studies are dedicated to understanding the extent and impact of sexual harassment among medical students. The aim of this study was to use behaviorally specific measures to examine prevalence of sexual harassment toward medical students. Associated mental health and academic impacts were also studied. Methods: A multisite survey was conducted at four medical schools. Sexual harassment was measured using the Sexual Experiences Questionnaire (SEQ), a valid and reliable instrument. Students were also surveyed about depressive and post-traumatic stress disorder (PTSD) symptoms and their level of academic engagement. We also assessed their perceptions of institutional response and whether they felt safe at their institution. Findings: The final sample included 524 medical students (response rate = 13%). Findings revealed that 36.6% reported sexual harassment by a faculty/ staff member and 38.5% reported harassment by a fellow student. The odds of harassment by faculty/staff, as well as peers, were significantly higher for women with an adjusted odds ratio (AOR) = 9.83, 95% confidence interval (CI) = [3.74, 25.80] and multiracial students with an AOR: 2.93, 95% CI: [1.16, 7.39]. Those who experienced sexual harassment were more likely to report academic disengagement and symptoms of depression and PTSD. Conclusion/Application to Practice: Sexual harassment in medical schools can potentially limit a student’s academic success and negatively impact their mental health. Supportive services and efforts to address peer and professional cultures that promote harassment are needed. Experiences of harassment require swift and competent responses by medical school leadership in collaboration with occupational and/or student health services to mitigate detrimental impacts and support medical students throughout their training.Institute on Domestic Violence and Sexual Assault (IDVSA

Transcranial magnetic stimulation in depression--lessons from the multicentre trials

Looking at novelties and advances in medicine in particular in the treatment of major depressive disorder no principally new antidepressant treatment strategy has been established in clinical routine in the last fifty years. However, regarding the considerable issue of treatment resistance in depression, new therapeutic strategies are urgently required. In this context, repetitive transcranial magnetic stimulation above the dorsolateral prefrontal cortex has been proposed as a potential new treatment option for depression; furthermore, in October 2008 a first rTMS-device (NeuroStar TMS Therapy System™) was approved by the FDA for the treatment of treatment resistant major refractory depression in adults. Yet, despite now nearly two decades of research in this field, no final answer concerning its validity for antidepressant treatment in the clinical practice is given. Numerous studies with small sample sizes and heterogeneous designs have been performed in this field yielding to different results. These were subjected to meta-analyses, assessing the antidepressant effect of rTMS, which are briefly summarized in this article. Further, multicentre-trials with larger numbers of patients were performed, which are presented and critically discussed here in more detail. This short review shall thus provide an overview of the current status of knowledge concerning rTMS in depression and it also provides some recommendations for future research in this field

Phases of methodological research in biostatistics—Building the evidence base for new methods

Although new biostatistical methods are published at a very high rate, many of these developments are not trustworthy enough to be adopted by the scientific community. We propose a framework to think about how a piece of methodological work contributes to the evidence base for a method. Similar to the well-known phases of clinical research in drug development, we propose to define four phases of methodological research. These four phases cover (I) proposing a new methodological idea while providing, for example, logical reasoning or proofs, (II) providing empirical evidence, first in a narrow target setting, then (III) in an extended range of settings and for various outcomes, accompanied by appropriate application examples, and (IV) investigations that establish a method as sufficiently well-understood to know when it is preferred over others and when it is not; that is, its pitfalls. We suggest basic definitions of the four phases to provoke thought and discussion rather than devising an unambiguous classification of studies into phases. Too many methodological developments finish before phase III/IV, but we give two examples with references. Our concept rebalances the emphasis to studies in phases III and IV, that is, carefully planned method comparison studies and studies that explore the empirical properties of existing methods in a wider range of problems