Browsing by Subject "Recombination"

Now showing 1 - 7 of 7
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    Biological problem solving through computation
    (2023-06) Liu, Chaochih
    As sequencing becomes more and more affordable, data continues to grow exponentially, and dataset sizes utilized in biological studies continue to increase. There is an increasing importance for reproducible research, especially studies that rely heavily on computational analyses. Custom code written for study-specific goals that are well documented and hosted in source code repositories with version control can accelerate future studies with similar data processing or analysis steps. For example, updating the reference genome positions of old genotyping SNPs as new reference genome versions get released is just as important as handling the latest long-read sequencing technologies. In this dissertation, I present multiple computational solutions to address problems relevant to crop improvement. In Chapter 1 of this dissertation, I use whole-genome sequencing data from 11 barley lines derived from sodium azide mutagenesis to characterize the nature of mutations induced by sodium azide to understand the nature of variants that reduce fitness. In this work, careful variant filtering was performed to identify variants generated by the mutagen. In Chapter 2, I investigate 318 Wild Barley Diversity Collection accessions for evidence of introgression from 2,446 domesticated barley. Information on wild accessions showing crop-to-wild introgression can be used to make informed decisions on wild samples to include in downstream applications. Finally, in Chapter 3, I develop a reproducible computational workflow that automates the scoring of crossovers as a phenotype to provide a means to quickly evaluate the amount of crossover rate variation present in any biparental population. Output from the computational workflow can be used to address limitations imposed by linked selection in breeding populations. For all the chapters, all code used for data processing and analyses is stored in public GitHub repositories to speed up the advancement of future research built upon this work.
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    Electron transport and recombination in nanowire dye-sensitized solar cells.
    (2010-02) Enache-Pommer, Emil
    The dye-sensitized solar cell (DSSC) is a promising low cost photovoltaic device. A typical DSSC consists of a porous film made out of TiO2 nanoparticles, a monolayer of dye adsorbed on the TiO2 surface and a liquid electrolyte. The electrolyte fills the pores of the nanoparticle film forming a semiconductor-dye-electrolyte interface with large surface area. During illumination of the cell, the dye molecules inject electrons into the TiO2 nanoparticles. The injected electrons diffuse through the nanoparticle network by hopping from particle to particle until they are collected at a transparent conductive oxide (TCO) anode. Meanwhile, the charged dye molecules are reduced through an electrochemical reaction with a reductant in the electrolyte. The oxidized ionic species diffuse to the counter electrode and are reduced by electrons that have been collected at the anode and have traveled through the load to complete the circuit. Currently, dye-sensitized solar cells have reached efficiencies above 11 %, but further improvement is limited by electrons recombining with the electrolyte during their transport through the semiconductor nanoparticle network. Nanowire DSSCs have been recently introduced and have the potential to overcome the limitations of nanoparticle DSSCs, since the electron percolation through the nanoparticle network is replaced by a direct electron pathway from the point of injection to the TCO. Understanding the electron transport and recombination mechanisms in nanowire DSSCs is one of the key steps to improving DSSC efficiency. Towards this end polycrystalline TiO2, single-crystalline TiO2 and single crystalline ZnO nanowire DSSCs were fabricated and analyzed using current-voltage characteristics, optical measurements, and transient perturbation techniques such as intensity modulated photocurrent spectroscopy, photocurrent decay and open-circuit photovoltage decay. For single-crystal ZnO nanowire DSSCs, the measured electron transport time constants are independent of light intensity but change with nanowire length, seeding method and annealing time. Even if the measured transients are limited by the RC time constant of the solar cell, using the measured time constants as an upper limit for the actual electron transport time leads to the conclusion that the electron transport rate in ZnO nanowires is at least two orders of magnitude faster than the recombination rate. This indicates that the charge collection efficiency in ZnO nanowire DSSCs is nearly 100 %. These results show that films can be made out of 100 μm long ZnO nanowires while maintaining efficient charge collection. For DSSCs based on polycrystalline anatase TiO2 nanowires, the electron transport times show a power-law dependence on illumination intensity similar to that reported for TiO2 nanoparticle DSSCs. The magnitude of the electron transport times is also comparable to that of nanoparticle DSSCs, indicating that electron trapping and detrapping determine transport times for polycrystalline TiO2 nanowire DSSCs. Surprisingly, even for single-crystal rutile TiO2 nanowire DSSCs, the electron transport rate is on the order of the electron transport rate in nanoparticle-based DSSCs and not as fast as would be expected. Electron transport is slow and light intensity dependent indicating that trapping and detrapping, most likely in surface traps, still play an important role in electron transport even in single-crystal rutile TiO2 nanowires.
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    Energy Migration in Organic Thin Films—From Excitons to Polarons
    (2016-04) Mullenbach, Tyler
    The rise of organic photovoltaic devices (OPVs) and organic light-emitting devices has generated interest in the physics governing exciton and polaron dynamics in thin films. Energy transfer has been well studied in dilute solutions, but there are emergent properties in thin films and greater complications due to complex morphologies which must be better understood. Despite the intense interest in energy transport in thin films, experimental limitations have slowed discoveries. Here, a new perspective of OPV operation is presented where photovoltage, instead of photocurrent, plays the fundamental role. By exploiting this new vantage point the first method of measuring the diffusion length (LD) of dark (non-luminescent) excitons is developed, a novel photodetector is invented, and the ability to watch exciton arrival, in real-time, at the donor-acceptor heterojunction is presented. Using an enhanced understanding of exciton migration in thin films, paradigms for enhancing LD by molecular modifications are discovered, and the first exciton gate is experimentally and theoretically demonstrated. Generation of polarons from exciton dissociation represents a second phase of energy migration in OPVs that remains understudied. Current approaches are capable of measuring the rate of charge carrier recombination only at open-circuit. To enable a better understanding of polaron dynamics in thin films, two new approaches are presented which are capable of measuring both the charge carrier recombination and transit rates at any OPV operating voltage. These techniques pave the way for a more complete understanding of charge carrier kinetics in molecular thin films.
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    Identification and characterization of novel factors that influence minisatellite stability in stationary phase yeast cells
    (2012-11) Alver, Bonnie Maureen
    The eukaryotic genome is primarily comprised of non-coding regions of DNA consisting of several different types of repetitive elements. Minisatellites are a type of tandem repetitive element and are composed of repeat units that are 15-100bp in length. Rare altered alleles of minisatellites are associated with an increased risk of several different types of disease including cancer, diabetes, epilepsy and coronary artery disease. However, little is known about what factors prevent minisatellites from alternating and becoming potential pathogenic alleles. Our lab previously developed a color segregation assay to detect minisatellite instability in the yeast Saccharomyces cerevisiae. Using this assay, we discovered a unique color segregation phenotype known as `blebbing' which was shown to be indicative of minisatellite alterations that occurred in stationary phase yeast cells. Here, we perform a genome-wide screen known as the Synthetic Genetic Array (SGA) analysis to screen for mutants strains bearing different types of minisatellite alleles that produced a strong blebbing phenotype. Through our work, we identify over 100 candidate genes that regulate the stability of a minisatellite in stationary phase. Further characterization of specific subsets of these genes demonstrates that minisatellites are regulated by different factors depending upon the repeat unit composition and size. We also demonstrate the checkpoint and mismatch repair components are important for stationary phase minisatellite stability and that alterations occurring in mutant strains are mediated by mechanisms utilizing recombination. Together our work provides novel insight into the factors governing minisatellite stability in a unique population of non-dividing cells.
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    Identification and characterization of novel factors that influence minisatellite stability in stationary phase yeast cells
    (2012-11) Alver, Bonnie Maureen
    The eukaryotic genome is primarily comprised of non-coding regions of DNA consisting of several different types of repetitive elements. Minisatellites are a type of tandem repetitive element and are composed of repeat units that are 15-100bp in length. Rare altered alleles of minisatellites are associated with an increased risk of several different types of disease including cancer, diabetes, epilepsy and coronary artery disease. However, little is known about what factors prevent minisatellites from alternating and becoming potential pathogenic alleles. Our lab previously developed a color segregation assay to detect minisatellite instability in the yeast saccharomyces cerevisiae. Using this assay, we discovered a unique color segregation phenotype known as `blebbing' which was shown to be indicative of minisatellite alterations that occurred in stationary phase yeast cells. Here, we perform a genome-wide screen known as the Synthetic Genetic Array (SGA) analysis to screen for mutants strains bearing different types of minisatellite alleles that produced a strong blebbing phenotype. Through our work, we identify over 100 candidate genes that regulate the stability of a minisatellite in stationary phase. Further characterization of specific subsets of these genes demonstrates that minisatellites are regulated by different factors depending upon the repeat unit composition and size. We also demonstrate the checkpoint and mismatch repair components are important for stationary phase minisatellite stability and that alterations occurring in mutant strains are mediated by mechanisms utilizing recombination. Together our work provides novel insight into the factors governing minisatellite stability in a unique population of non-dividing cells.
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    Minisatellites in meiosis: crossover regulation and stability of repetitive DNA.
    (2012-04) LeClere, Andrea Ruth
    The minisatellite associated with the human HRAS1 proto-oncogene has an enhancer effect on HRAS1 expression. Rare minisatellite alleles have stronger enhancer activity and are frequently found in primary tumors of cancer patients. Rare alleles derive from a common allele that has undergone an alteration in length; alterations occur primarily during the process of meiotic recombination. Identifying factors that regulate minisatellite stability during meiosis is important to our understanding of the initiation and predisposition of minisatellite-associated human diseases. This is the focus of the Kirkpatrick lab using a minisatellite model system in yeast Saccharomyces cerevisiae where an HRAS1 minisatellite allele has been inserted into the promoter region upstream of the HIS4 locus on chromosome III. In this study, we identified CSM3, TOF1, and MRC1 as factors that contribute to meiotic minisatellite alterations. We also uncovered a novel recombination phenotype associated with the HRAS1 minisatellite in MSH4 and MSH5 mutants. Both of these projects have broader implications on our understanding of factors that regulate minisatellite alterations during meiosis. We present models based on our data and previously published research to explain the observed phenotypes.
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    Navigating the stages of innovation: a study of the U.S. biotechnology industry.
    (2010-07) Dahlin, Eric Carl
    My dissertation takes a broad view of innovation by investigating product success among U.S. biotechnology firms across various stages of innovation including product discovery, product development, and product success. Current explanations of biotechnology product success examine one or two stages of innovation and underscore the importance of strategic alliances. However, current explanations are incomplete. First, they fail to examine whether their explanations hold across the entire innovation process. Second, estimates suggest that up to 70% of strategic alliances fail to meet their objectives (Kale and Singh 2009) and product develop remains very costly despite the high incidence of alliances in the biotechnology industry. I propose that success across the stages of innovation is associated with the scope of learning that occurs within the firm, among strategic alliance partners, and from a focal firm's network. That is, product discovery is associated with learning within the firm, product development is associated with learning among strategic alliance partners, and product success is associated with learning from the firm's overall network. While entering strategic alliances to pool resources to defray the costs of innovation is likely a necessary condition for innovation success current research overlooks the role of product development strategies. In this study I examine product development strategies that influence the likelihood of innovation success including exploration, exploitation, and ambidexterity (i.e., the simultaneous pursuit of exploration and exploitation strategies). Moreover, findings from interviews with executives in biotechnology firms provide insight into the strategies firms use to develop new drugs and evaluate them at various stages of innovation. Results from regression models support the general proposition that success at different stages of innovation varies with the scope of learning. Learning at the organizational-level (firm age and absorptive capacity) is likely to increase success at the discovery stage. Alliance partnerships are sources of learning (research alliance and development alliances) that affect product development. Network-level learning (network centrality and network experience) influences sales growth, but only for smaller firms in my sample. I also find that ambidexterity product development strategies are statistically significant predictors of success at each stage of innovation.