Browsing by Subject "Distribution"

Now showing 1 - 6 of 6
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    Data and code supporting: Simulations corroborate telegraph model predictions for the extension distributions of nanochannel confined DNA
    (2019-08-12) Bhandari, Aditya Bikram; Dorfman, Kevin D; dorfman@umn.edu; Dorfman, Kevin D; Dorfman
    Hairpins in the conformation of DNA confined in nanochannels close to their persistence length cause the distribution of their fractional extensions to be heavily left skewed. A recent theory rationalizes these skewed distributions using a correlated telegraph process, which can be solved exactly in the asymptotic limit of small but frequent hairpin formation. Pruned-enriched Rosenbluth method simulations of the fractional extension distribution for a channel-confined wormlike chain confirm the predictions of the telegraph model. Remarkably, the asymptotic result of the telegraph model remains robust well outside the asymptotic limit. As a result, the approximations in the theory required to map it to the polymer model and solve it in the asymptotic limit are not the source of discrepancies between the predictions of the telegraph model and experimental distributions of the extensions of DNA during genome mapping. The agreement between theory and simulations motivates future work to determine the source of the remaining discrepancies between the predictions of the telegraph model and experimental distributions of the extensions of DNA in nanochannels used for genome mapping.
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    Development of capillary electrophoretic-based techniques to analyze doxorubicin in tissues, cells and subcellular fractions.
    (2010-09) Wang, Yaohua
    Doxorubicin (DOX) is a widely used anti-cancer drug. It is hypothesized that the efficacy and toxicity of DOX is related to its distribution and metabolism. Capillary electrophoresis (CE) including its variants such as micellar electrokinetic chromatography (MEKC) is becoming a popular method in bioanalysis due to its high sensitivity and separation efficiency, small sample size requirements, simple sample preparation procedures, versatility in sampling and short separation times. The goal of this thesis is to take advantage of these features and develop CE-based methods to investigate the metabolism, subcellular distribution and localization of DOX in biological samples after DOX treatments. A direct sampling technique was developed to quantify DOX at or near the tumor site in hepatocellular carcinoma tissues after chemoembolization. This technique allows for sampling small volume of tissues (<10 picoliters) selectively from adjacent tumor and non-tumor regions with high spatial resolution (100 micrometers) and reproducibility. Using this technique coupled with MEKC-LIF (laser-induced fluorescence detection), DOX was detected and quantified, in both tumor and non-tumor regions in resected human livers. A MEKC method was developed to monitor the incorporation, transformation and subcellular metabolism of a DOX prodrug, N-L-leucyl-doxorubicin (LeuDOX), which is expected to have higher efficacy and lower toxicity. It successfully separated LeuDOX from DOX and its major metabolite, doxorubicinol (DOXol). The metabolism of LeuDOX in four subcellular fractions of human uterine sarcoma cells suggested that LeuDOX is mainly activated to DOX in the lysosome-enriched fraction which contains hydrolytic enzymes. Metabolism of DOX in isolated subcellular fractions from young and old rat livers was investigated by MEKC-LIF, suggesting that this technique is adequate to investigate the effect of aging on the metabolism of DOX at the subcellular level. The study showed that the young rat liver is more metabolic active than that of the old rat. In subcellular drug analysis, the purity of the subcellular fractions limits the determination of the subcellular localization of metabolites. Organelles with high purity and biological function are necessary to refine the understanding of DOX metabolism in a specific organelle type. An immunoisolation method based on the use of an antibody specific to a peroxisomal membrane protein was developed to isolate peroxisomes with low levels of contaminating mitochondria and lysosomes. The metabolism of DOX and a model compound, BODIPY fatty acid analog, showed possible peroxisomal biotransformation of these xenobiotics. The techniques and methodologies developed in the dissertation work would be the basis of future developments including assessing the function of new prodrugs at the cellular and subcellular levels, profiling subcellular specific metabolism and monitoring drug distribution and metabolism in tissue cross-sections. These measurements are necessary to understand the efficacy and toxicity of chemotherapy drug treatments in preclinical and clinical studies.
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    Distribution, migration chronology, and survival rates of Eastern Population sandhill cranes
    (2014-11) Fronczak, David Leonard
    The Eastern Population (EP) of greater sandhill cranes (Grus canadensis tabida; hereafter, cranes) is rapidly expanding in size and geographic range. The core of their breeding range is in Wisconsin, Michigan, and southern Ontario, Canada. Little information exists regarding the geographic extent of breeding, migration, and wintering ranges of EP cranes, or migration chronology and use of staging areas. In addition, there are no published estimates of survival rates for EP sandhill cranes. To address these information needs we trapped and deployed solar Global Positioning System (GPS) Platform Transmitting Terminals (PTTs) on 29 sandhill cranes from December 2009 through September 2011, primarily in known fall and winter concentration areas, to assess movements throughout the year. This thesis explores EP sandhill crane distribution during the breeding season and winter, migratory routes, and migration chronology (Chapter 1) and also estimates survival rates during the study period (Chapter 2). EP cranes settled on summer areas beginning mid-March in Minnesota (11%), Wisconsin (36%), Michigan (29%), and Ontario (21%). On average, PTT-tagged cranes arrived at their winter terminus beginning mid-December in Indiana (29%), Kentucky (11%), Tennessee (79%), Georgia (11%), and Florida (32%). Twenty-three marked cranes returned to their summer area's calculated mean center after a second spring migration. The average linear distance between individual estimated mean activity centers for a summer area was 1.34 km (range: 0.01 - 7.82 km). EP cranes used fall and spring migration routes similar to those previously documented. Annual survival rates (from October through September) were estimated at 0.921 (2010-2011; SE = 0.058) and 0.913 (2011-2012; SE = 0.087) using the known fates platform in Program MARK (Chapter 2).
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    Distribution, range connectivity, and trends of bear populations in Southeast Asia
    (2017-06) Scotson, Lorraine
    Sun bears and Asiatic black bears co-occur in Southeast Asia with wide areas of overlapping range. Both species are in decline, and are vulnerable to extinction due mainly to habitat loss and illegal hunting. Efforts to conserve bears in Southeast Asia are hampered by a lack of basic knowledge of distribution, population trends and habitat configuration. To advance the scientific understanding of sun bears and Asiatic back bears in this region I investigated fine and broad scale patterns of distribution. In Lao PDR, I gathered data on bear occurrence using bear sign transects walked in multiple forest blocks throughout the country. To model the country-wide relative abundance of bears and habitat quality, I related bear sign to environmental factors associated with bear occurrence. Within global sun bear range, I gathered camera trap records of sun bear detections from seven sun bear range countries. To generate quantitative measures of sun bear population trends, I related sun bear detection rates to tree cover and estimated related changes in country and global-level sun bear populations based on tree cover loss. To evaluate the global extent of sun bear range connectivity, I used the modelled relationship between sun bears and tree cover to create a habitat suitability index, and I identified areas of fractured range that have created unnatural subpopulations that are at risk from isolation. In Lao PDR, bears selected for areas of high elevation, rugged terrain, and areas of high tree density far from roads. My model-based estimates of sun bear global population trends predicted that over a 30-year period, sun bear populations in mainland southeast Asia have potentially declined by close to 20%, and insular sun bear populations have declined by ~50%. I identified seven potential sun bear subpopulations; two that are fully isolated with no potential for inter-subpopulation movement, and in the other five, inter and intra-subpopulation habitat fragmentation occurs in a continuum of severity. My findings advance the understanding of patterns in bear distribution and trends in southeast Asia, identify research priorities, and lay a framework for future monitoring efforts at country and region-level scales. I conclude with recommendations on how to better manage camera trap data for secondary research and sharing.
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    An ecological and evolutionary perspective on functional diversity in the genus Salix
    (2010-05) Savage, Jessica Anne
    Natural selection, along with biochemical and architectural constraints can limit the trait combinations expressed by plants, creating functional trade-offs across species. These trade-offs often play a critical role in limiting species distributions by preventing them from performing well under all environmental conditions. For this dissertation, I examined the role of functional trade-offs in limiting species distributions at two geographic scales, focusing on species in the genus Salix (the willows). First, I examined whether species exhibited niche differentiation across a local water availability gradient, and investigated the extent that plant function and functional similarity influence species distributions and patterns of co-occurrence. For this analysis, I examined species distributions in relation to physiological and functional data collected in the field and in a greenhouse common garden. I also estimated a phylogeny of the species to examine patterns of species phylogenetic community structure and trait evolution. Second, I examined whether there was evidence for a trade-off between freezing tolerance and growth that could explain species range limits. This analysis involved comparing species freezing tolerances and growth rates under different environmental conditions and determining the extent that these traits related to species distributions. Overall, I found evidence that functional trade-offs are important in determining species distributions both within local plant communities and across broader geographic distributions. On a local level, species exhibit niche differentiation across a water availability gradient, and this differentiation is driven by a functional trade-off between drought tolerance and relative growth rate. Traits related to species drought tolerance and recruitment strategies also demonstrate correlated evolution with species water availability niches. At a broader geographic scale, species demonstrate a trade-off between freezing tolerance and growth. This trade-off is primarily the result of species dependence on photoperiod cues for growth regulation. The strong correlation between species growth rates, their freezing tolerances, and their modeled geographic ranges suggests that this trade-off could influence their geographic distributions. This research demonstrates the importance of functional trade-offs in determining the distributions of species in an ecological and economically important genus. It also demonstrates the value of integrative research that draws on physiological, evolutionary and ecological methodology.
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    Phytoestrogen distribution and degradation in natural and engineered systems
    (2012-12) Fleischhacker, Nathan T.
    Phytoestrogens are plant-derived hormonally active compounds known to cause varied reproductive, immunosuppressive and behavioral effects in fish. Environmentally relevant concentrations of phytoestrogens have been identified in numerous industrial and wastewater effluents, but their presence in surface water has received little attention. Additionally, no work has been performed to assess the degradability of phytoestrogens in surface waters or to determine which microbial communities may be responsible for their degradation. Given the fundamental questions that exist regarding phytoestrogens in the environment, the objectives of this research were three-fold: 1) Determine the degradation capacity of genistein, a potent and common phytoestrogen species, in surface waters under a variety of environmental conditions, 2) Monitor the temporal and spatial fluctuations of 6 phytoestrogen species in wastewater-impacted and unimpacted surface waters, 3) Examine if genistein, like similarly structured steroidal estrogens, is capable of being degraded cometabolically by nitrifying organisms. Triplicate batch reactors with triplicate negative controls were used to investigate genistein degradation in both surface water and enriched nitrifying cultures. Grab samples were collected from impacted and unimpacted surface waters to identify temporal and spatial phytoestrogen patterns. Genistein degradation rates in surface water samples were found to vary significantly and depended on initial concentration, incubation temperature, season of water collection, and surface water source. Overall genistein degraded rapidly and variably, with the time to 50% degradation ranging from 15 to 70 hours. In reactors amended with 100 μg/L genistein, an enrichment period during which there was no or little degradation was followed by a period of rapid genistein degradation (zero-order), suggesting that genistein may be degraded intentionally as an energy source rather than incidentally via some cometabolic pathway. Experiments with nitrifying organisms indicated that genistein was not cometabolically degraded by nitrifying organisms, but it was degraded by organisms that were enriched under nitrifying conditions. Temporal and spatial studies detected several phytoestrogen species in surface waters at low nanogram per liter concentrations with no discernible temporal or spatial pattern. This research suggests that like genistein, phytoestrogens in general may be readily degraded in surface waters. It also suggests that phytoestrogens are not likely to cause widespread ecological harm, but caution should be taken as numerous compounds in this class exist and only a limited number of surface waters were sampled for phytoestrogen presence.