Thioredoxin and Jab1 control estrogen- and antiestrogen-mediated progression of the cell cycle through p27 interactions

A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and protein-protein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

Phosphorus Availability and Salinity Control Productivity and Demography of the Seagrass Thalassia testudinum in Florida Bay

Biomass, net primary productivity (NPP), foliar elemental content, and demography of Thalassia testudinum were monitored in populations from five sites across Florida Bay beginning in January 2001. Sites were selected to take advantage of the spatial variability in phosphorus (P) availability and salinity climates across the bay. Aboveground biomass and NPP of T. testudinum were determined five to six times annually. Short-shoot demography, belowground biomass, and belowground NPP were assessed from a single destructive harvest at each site and short-shoot cohorts were estimated from leaf scar counts multiplied by site-specific leaf production rates. Biomass, relative growth rate (RGR), and overall NPP were positively correlated with P availability. Additionally, a positive correlation between P availability and the ratio of photosynthetic to non-photosynthetic biomass suggests that T. testudinum increases allocation to aboveground biomass as P availability increases. Population turnover increased with P availability, evident in positive correlations of recruitment and mortality rates with P availability. Departures from seasonally modeled estimates of RGR were found to be influenced by salinity, which depressed RGR when below 20 psu or above 40 psu. Freshwater management in the headwaters of Florida Bay will alter salinity and nutrient climates. It is becoming clear that such changes will affect T. testudinum, with likely feedbacks on ecosystem structure, function, and habitat quality.

Personality and job performance: The mediating roles of leader -member exchange quality and action control

The present investigation examined the relationships among personality (as conceptualized by the Big Five Factors), leader-member exchange (LMX) quality, action control, organizational citizenship behaviors (OCB), and overall job performance (OJP). Two mediator variables were proposed and tested in this study: LMX and Action Control. Two-hundred and seven currently employed regular elementary school classroom teachers provided data during the 2000–2001 academic school year. Teachers provided personality, LMX quality (member or subordinate perspective), action control, job tenure, and demographic data. Nine school administrators (i.e., Principals, Assistant Principals) were the source for supervisor ratings of OCB, OJP, and LMX quality (leader or supervisor perspective). In eight of the nine total schools, teachers completed questionnaires during an after-school teacher gathering; in the remaining school location questionnaires were dropped off, distributed to teachers, and re-collected two weeks later. Results indicated a significant relationship between the OCB scale and overall supervisory ratings of OJP. The relationship among the big five factors of personality and OJP did not reach statistical significance, nor did the relationships among personality and OCB. The data indicated that none of the teacher tenure variables (i.e., teacher, school, or time worked with principal tenure) moderated the personality-OCB relationship nor the personality-OJP relationship. Finally, a review of the correlations among the variables of interest precluded conducting a mediation between personality-performance by OCB, mediation of personality-OCB by action control, and mediation of personality-OCB by LMX. In conclusion, the data reveal that personality was not significantly correlated with supervisory ratings of OJP or significantly related to supervisory ratings of overall OCB. Moreover, LMX quality and action control did not mediate the relationships between Personality-OJP nor the Personality-OCB relationship. Significant relationships were found between disengagement and overall LMX quality and between Initiative and overall LMX quality (both LMX-Teacher perspectives) as well as between personality variables and both Disengagement and Initiative action control variables. Despite the limitations inherent in this study, these latter findings suggest “lessons” for teachers and school administrators alike. ^

Effect of Medical Advice for Diet on Diabetes Self-Management and Glycemic Control for Haitian and African Americans with Type 2 Diabetes

Adequate care of type 2 diabetes is reflected by the individual’s adherence to dietary guidance; yet, few patients are engaged in diabetes self-care at the recommended level, regardless of race/ethnicity. Few studies on the effect of dietary medical advice on diabetes self-management (DSM) and glycemic control have been conducted on Haitian and African American adults with type 2 diabetes. These relationships were assessed in total of 254 Blacks with type 2 diabetes (Haitian Americans = 129; African Americans = 125) recruited from Miami-Dade and Broward Counties, Florida by community outreach methods. Although dietary advice received was not significantly different between the two Black ethnicities, given advice “to follow a diet” as a predictor of “using food groups” was significant for Haitian Americans, but not for African Americans. Haitian Americans who were advised to follow a diet were approximately 3 times more likely to sometimes or often use food groups (or exchange lists) in planning meals. Less than optimal glycemic control (A1C > 7.2) was inversely related to DSM for African Americans; but the relationship was not significant for Haitian Americans. A one unit increase in DSM score decreased the odds ratio point estimate of having less than optimal glycemic control (A1C > 7.2%) by a factor of 0.94 in African Americans. These results suggest that medical advice for diet plans may not be communicated effectively for DSM for some races/ethnicities. Research aimed at uncovering the enablers and barriers of diet management specific to Black ethnicities with type 2 diabetes is recommended.

LPJ-LMfire simulations for Europe for the Last Glacial Maximum and preindustrial control, link to netCDF files

This data sets contains LPJ-LMfire dynamic global vegetation model output covering Europe and the Mediterranean for the Last Glacial Maximum (LGM; 21 ka) and for a preindustrial control simulation (20th century detrended climate). The netCDF data files are time averages of the final 30 years of the model simulation. Each netCDF file contains four or five variables: fractional cover of 9 plant functional types (PFTs; cover), total fractional coverage of trees (treecover), population density of hunter-gatherers (foragerPD; only for the "people" simulations), fraction of the gridcell burned on 30-year average (burnedf), and vegetation net primary productivity (NPP). The model spatial resolution is 0.5-degrees For the LGM simulations, LPJ-LMfire was driven by the PMIP3 suite of eight GCMs for which LGM climate simulations were available. Also provided in this archive is the result of an LPJ-LMfire run that was forced by the average climate of all GCMs (the "GCM-mean" files), and the average of each of the individual LPJ-LMfire runs over the eight LGM scenarios individually (the "LPJ-mean" files). The model simulations are provided that include the influence of human presence on the landscape (the "people" files), and in a "world without humans" scenario (the "natural" files). Finally this archive contains the preindustrial reference simulation with and without human influence ("PI_reference_people" and "PI_reference_nat", respectively). There are therefore 22 netCDF files in this archive: 8 each of LGM simulations with and without people (total 16) and the "GCM mean" simulation (2 files) and the "LPJ mean" aggregate (2 files), and finally the two preindustrial "control" simulations ("PI"), with and without humans (2 files). In addition to the LPJ-LMfire model output (netCDF files), this archive also contains a table of arboreal pollen percent calculated from pollen samples dated to the LGM at sites throughout (lgmAP.txt), and a table containing the location of archaeological sites dated to the LGM (LGM_archaeological_site_locations.txt).

Distributed Power balance and damping control for high power multiport LCL DC hub

This project is funded by European Research Council in FP7; grant no 259328, 2010 and EPSRC grant no EP/K006428/1, 2013.

Distributed Power balance and damping control for high power multiport LCL DC hub

This project is funded by European Research Council in FP7; grant no 259328, 2010 and EPSRC grant no EP/K006428/1, 2013.

Aspects of postural alignment and postural control relevant for the evaluation and the treatment of idiopathic scoliosis patients

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Glucolipotoxicity and the control of pancreatic ℓ-cell apoptosis

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Aspects of postural alignment and postural control relevant for the evaluation and the treatment of idiopathic scoliosis patients

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Glucolipotoxicity and the control of pancreatic ℓ-cell apoptosis

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Dealing with dark times : the changing forms and functions of humor in Mark Twain's later writings

Otto-von-Guericke-Universität Magdeburg, Fakultät für Verfahrens- und Systemtechnik, Dissertation, 2016

Investigations on the structural, optical and magnetic properties of nanostructured cerium oxide in pure and doped forms and its polymer nanocomposites

In recent years, nanoscience and nanotechnology has emerged as one of the most important and exciting frontier areas of research interest in almost all fields of science and technology. This technology provides the path of many breakthrough changes in the near future in many areas of advanced technological applications. Nanotechnology is an interdisciplinary area of research and development. The advent of nanotechnology in the modern times and the beginning of its systematic study can be thought of to have begun with a lecture by the famous physicist Richard Feynman. In 1960 he presented a visionary and prophetic lecture at the meeting of the American Physical Society entitled “there is plenty of room at the bottom” where he speculated on the possibility and potential of nanosized materials. Synthesis of nanomaterials and nanostructures are the essential aspects of nanotechnology. Studies on new physical properties and applications of nanomaterials are possible only when materials are made available with desired size, morphology, crystal structure and chemical composition. Cerium oxide (ceria) is one of the important functional materials with high mechanical strength, thermal stability, excellent optical properties, appreciable oxygen ion conductivity and oxygen storage capacity. Ceria finds a variety of applications in mechanical polishing of microelectronic devices, as catalysts for three-way automatic exhaust systems and as additives in ceramics and phosphors. The doped ceria usually has enhanced catalytic and electrical properties, which depend on a series of factors such as the particle size, the structural characteristics, morphology etc. Ceria based solid solutions have been widely identified as promising electrolytes for intermediate temperature solid oxide fuel cells (SOFC). The success of many promising device technologies depends on the suitable powder synthesis techniques. The challenge for introducing new nanopowder synthesis techniques is to preserve high material quality while attaining the desired composition. The method adopted should give reproducible powder properties, high yield and must be time and energy effective. The use of a variety of new materials in many technological applications has been realized through the use of thin films of these materials. Thus the development of any new material will have good application potential if it can be deposited in thin film form with the same properties. The advantageous properties of thin films include the possibility of tailoring the properties according to film thickness, small mass of the materials involved and high surface to volume ratio. The synthesis of polymer nanocomposites is an integral aspect of polymer nanotechnology. By inserting the nanometric inorganic compounds, the properties of polymers can be improved and this has a lot of applications depending upon the inorganic filler material present in the polymer.

Salicaceae Endophytes: Growth Promotion Potential in Rice (Oryza sativa L.) and Maize (Zea mays L.) and Bio-Control of Plant Pathogen

Thesis (Ph.D.)--University of Washington, 2016-08