Abiotic stresses constitute a major category of stresses that negatively impact plant growth and development. It is important to understand how plants cope with environmental stresses and reprogram gene responses which in turn confers stress tolerance. Recent advances of genomic technologies have led to the generation of much genomic data for the model plant, Arabidopsis. To understand gene responses activated by specific external stress signals, these large-scale data sets need to be analyzed to generate new insight of gene functions in stress responses. This poses new computational challenges of mining gene associations and reconstructing regulatory interactions from large-scale data sets. In this dissertation, several computational tools were developed to address the challenges. In Chapter 2, ConSReg was developed to infer condition-specific regulatory interactions and prioritize transcription factors (TFs) that are likely to play condition specific regulatory roles. Comprehensive investigation was performed to optimize the performance of ConSReg and a systematic recovery of nitrogen response TFs was performed to evaluate ConSReg. In Chapter 3, CoReg was developed to infer co-regulation between genes, using only regulatory networks as input. CoReg was compared to other computational methods and the results showed that CoReg outperformed other methods. CoReg was further applied to identified modules in regulatory network generated from DAP-seq (DNA affinity purification sequencing). Using a large expression dataset generated under many abiotic stress treatments, many regulatory modules with common regulatory edges were found to be highly co-expressed, suggesting that target modules are structurally stable modules under abiotic stress conditions. In Chapter 4, exploratory analysis was performed to classify cell types for Arabidopsis root single cell RNA-seq data. This is a first step towards construction of a cell-type-specific regulatory network for Arabidopsis root cells, which is important for improving current understanding of stress response. / Doctor of Philosophy / Abiotic stresses constitute a major category of stresses that negatively impact plant growth and development. It is important to understand how plants cope with environmental stresses and reprogram gene responses which in turn confers stress tolerance to plants. Genomics technology has been used in past decade to generate gene expression data under different abiotic stresses for the model plant, Arabidopsis. Recent new genomic technologies, such as DAP-seq, have generated large scale regulatory maps that provide information regarding which gene has the potential to regulate other genes in the genome. However, this technology does not provide context specific interactions. It is unknown which transcription factor can regulate which gene under a specific abiotic stress condition. To address this challenge, several computational tools were developed to identify regulatory interactions and co-regulating genes for stress response. In addition, using single cell RNA-seq data generated from the model plant organism Arabidopsis, preliminary analysis was performed to build model that classifies Arabidopsis root cell types. This analysis is the first step towards the ultimate goal of constructing cell-typespecific regulatory network for Arabidopsis, which is important for improving current understanding of stress response in plants.

This study extends Regulatory Fit Theory (Higgins, 2000) to examine horizontal regulatory fit (Scholer & Higgins, 2010) in the context of performance feedback. Participants completed the Regulatory Focus Questionnaire (Higgins et al., 2001) to measure their chronic motivational orientation, then worked on an adapted version of an in-basket task (Holmes & Hauenstein, 2012) across two sessions. Hypotheses predicted that compared to instances of non-fit, conditions of regulatory fit between chronic and situational and motivational orientations (Promotion vs. Prevention) would have a significantly greater impact on the following three outcomes: 1) Variety and Frequency of Feedback Use, 2) Feedback Recall, and 3) Attitudes toward both Feedback and the In-basket Task. Overall results supported this assertion. Participants in condition of regulatory fit engaged in a significantly greater variety of behaviors and did so more frequently than those in non-fit conditions. Additionally, participants in regulatory fit conditions had stronger positive attitudes toward feedback than those in non-fit conditions. Counter to previous research, regulatory fit did not have significant impact on feedback recall in the current study, nor did regulatory fit have a significant impact on the attitudes toward in-basket task. / Master of Science

With the onset of large-scale gene expression profiling, many researchers have turned their attention toward biological process modeling and system identification. The abundance of data available, while inspiring, is also daunting to interpret. Following the initial work of Rangel et al., we propose a linear model for identifying the biological model behind the data and utilize a modification of the Expectation-Maximization algorithm for training it. With our model, we explore some commonly accepted assumptions concerning sampling, discretization, and state transformations. Also, we illuminate the model complexities and interpretation difficulties caused by unknown state transformations and propose some solutions for resolving these problems. Finally, we elucidate the advantages and limitations of our linear state-space model with simulated data from several nonlinear networks. / Master of Science

All companies are subject to some degree of regulatory oversight of their operations. Economics, finance, and government research demonstrate that operational regulatory oversight (for example, provided by the EPA or FDA) imposes financial and operating burdens on regulated firms. My study examines how auditors respond to their clients’ operational regulatory oversight with additional audit costs, as reflected in audit fees. I focus on operational regulatory oversight from six federal regulatory agencies with authority to regulate companies in any industry. I find that operational regulatory oversight intensity, measured by number of regulators, occurrences of regulator-specific disclosures, and regulatory fragmentation, is positively associated with audit fees. Cross-sectional tests show that operational oversight from “continuous” regulators (i.e., regulators that maintain routine oversight) significantly weakens the positive association between operational regulatory oversight and audit fees. Further analyses provide no evidence that the higher audit fees are accompanied by changes in auditor effort. Lastly, my results are robust to an audit fee change model and an alternative measure of regulatory fragmentation. / Business Administration/Accounting

No description available.

Financial services regulators are tasked with balancing the conflicting roles of empowering and policing their regulated communities. In order to be effective, agencies must be able to accomplish both tasks. This analysis examines several determinants of effectiveness among U.S. bank regulators. Using statistical and narrative analyses, it examines factors that have contributed to the regulatory effectiveness of the National Credit Union Administration, Office of the Comptroller of the Currency, and Office of Thrift Supervision. The study focused on the relationships between regulatory ability to prevent failures and influences including agency longevity, ability to manage complexity, appointee and staff qualities, mission stability, regulatory style, and resources. Agency longevity and resources had the greatest impact on effectiveness among the cases that were examined. Additionally, this study proposes a typology that suggests that more effective regulators are able to balance information from their regulated communities with a public interest orientation. This allows them to have current information regarding emerging regulatory issues but also to avoid becoming too reliant on their supervised institutions for information. / Ph. D.

One objective of the BCBS is to implement minimum supervisory capital standards in the banking sector. Basel I to Basel III attempted to maintain a minimum capital standard for credit risk, market risk and operational risk. Many loopholes were highlighted through years when political and economic disturbances occurred and caused volatility in the financial markets. This study analysed five major South African banks from 2002–2012 to determine the size of these disturbances on the regulatory capital levels. The empirical portion of this study comprised of statistical models to be applied to the quantitative observations of capital levels. These measurements served as the bases of comparison between the five banks. After the investigation it was evident that the capital levels of these five banks first decreased as the South African economy prevailed in a boom phase and banks were at ease. When the 2007–2009 financial crisis struck, the capital levels increased again in respect of the three risks. Global volatility surfaced as economic and political factors were introduced into the markets / MCom (Risk Management), North-West University, Vaal Triangle Campus, 2014

One objective of the BCBS is to implement minimum supervisory capital standards in the banking sector. Basel I to Basel III attempted to maintain a minimum capital standard for credit risk, market risk and operational risk. Many loopholes were highlighted through years when political and economic disturbances occurred and caused volatility in the financial markets. This study analysed five major South African banks from 2002–2012 to determine the size of these disturbances on the regulatory capital levels. The empirical portion of this study comprised of statistical models to be applied to the quantitative observations of capital levels. These measurements served as the bases of comparison between the five banks. After the investigation it was evident that the capital levels of these five banks first decreased as the South African economy prevailed in a boom phase and banks were at ease. When the 2007–2009 financial crisis struck, the capital levels increased again in respect of the three risks. Global volatility surfaced as economic and political factors were introduced into the markets / MCom (Risk Management), North-West University, Vaal Triangle Campus, 2014

Interferon regulatory factor 1 (IRF-1), the founding member of IRF family, is a nuclear transcription factor first described as a transcription factor that binds to the upstream region of interferon induced genes following viral infection. In addition, IRF-1 has been reported to be involved in cell growth regulation, induction of apoptosis, immune responses, post-transcriptional modification, and cell transformation by oncogenes. Thus, IRF-1 shows accumulative evidence supporting the theory that IRF-1 functions as a tumour suppressor. However, we still lack the knowledge in the regulation and function behind IRF-1 and many other tumour suppressors due to the lack of synthetic tools that can aid in understanding the mechanism of cancer biology. Here we described the creation of synthetic tools that can be applied to study the role of a transcription factor(s) in cancer biology. Firstly, we described the creation, using recombineering technology, of universal bacterial artificial chromosome (BAC) targeting vector. This targeting vector, carry a cre-conditioned STOP cassette that can be targeted at a desired specific area. The resulted targeting vector can aid the generation of mice models with a conditioned knock-in subtle mutation(s). The resulted cre-conditioned mice models are an essential tool for any outstanding research project in cancer biology. Secondly, we described the development of Flp-In System™ from Invitrogen; the system can ease the generation of isogenic stable mammalian expression cell lines. Using this system, we created two isogenic stable cell lines expressing wild-type IRF-1 and a mutant that abolish IRF-1 DNA binding ability (W11R). Both cell lines were investigated using microarray analysis revealing new IRF-1 target genes. We reported the up-regulation of expected standard interferon regulatory genes such as, interleukin-24 (IL-24) and interferon regulatory factor-2 binding protein-2 (IRF2BP2) and the up-regulation of standard apoptotic genes such as, early growth response-1 (EGR-1) and prostate transmembrane protein, androgen induced-1 (PMEPA1) confirming the role of IRF-1 as a tumour suppressor. However, we also reported the up-regulation of secreted phosphoprotein-1 (SPP1) and SH3 and PX domains-2A (SH3PXD2A) which are matricellular protein produced by cancer cells playing a role in cellular adhesion, invasion, tumour growth progression and metastasis. Thus, we proposed a new biological role of IRF-1 in cellular movement. Thirdly, we described the development of a synthetic stable reporter cell line which can report IRF-1 transcriptional activity; such reporter cell line can be used once large scale screening is needed. The created stable reporter cell line was used to screen a kinase inhibitor library which has revealed C3 as an IRF-1 modifier. The newly identified IRF-1 modifier regulates IRF-1 transcriptional activity by inhibiting platelet-derived growth factor receptor (PDGFR) and/or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase. Finally, we validated the synthetic Flp-In System™ by testing the system using a novel oncoprotein model. We have developed a stable cell line that overexpresses an oncoprotein named Anterior Gradient 2 (AGR-2). We have found that AGR-2 can attenuate IRF-1 protein levels dependent of p53. In addition, AGR-2 has been identified as a cellular survivor factor during unfolding protein response. In conclusion, this study descried the creation and the validation of synthetic tools: synthetic cassette for cre-conditioned mice creation, the Flp-In System™ for isogenic stable cell line creation, and IRF-1 reporter cell line for high throughput screening. All synthetic tools were validated and used to investigate IRF-1, a transcription factor that plays a role in cancer and immune system.

Societies have established various forms of governance to protect the natural environment from the adverse effects of human activity. While direct “command and control” regulation has achieved significant improvements in environmental protection, concerns for its efficiency have led governments to seek alternative approaches to achieve environmental policy objectives. Commentators describe a shift from “government” to “governance” as policy makers and regulators seek to harness wider social forces beyond government, while risk-based regulation is pursued to target constrained regulatory resources for maximum effect. However, robust evidence for the effectiveness of different forms of regulation is lacking. This thesis addresses this gap, providing an evidence base for instrument selection and a data-informed critique of regulatory reform practice. Research followed a case study strategy, gathering qualitative data through 58 in-depth semi-structured interviews, analysed using the NVIVO™ Computer Aided Qualitative Data Analysis System (CAQDAS), with senior policy makers at the Department for Environment, Food and Rural Affairs, England (Defra) and senior executives in businesses and trade associations in 5 UK sectors. (1) A new typology of regulatory instruments has been compiled, validated with sector experts, refined for policy end-users, and published as part of Defra’s guidance on instrument selection. (2) The critical case of instrument selection in practice at Defra has been examined for the first time, revealing factors affecting choice, the use of coregulation to develop evidence and the importance of retaining policy maker skills for new forms of regulation. (3) A multiple-case study of senior business representatives found five strongly preferred voluntary regulation, seven expressed significant doubts about its effectiveness, and 19 expressed no general preference. While voluntary approaches were valued for flexibility and lower burdens, direct regulation offered stability and a level playing field. They sought inter alia coherent, evidence based regulatory frameworks, delivered through positive regulatory relationships. This research progresses the better and smarter regulation debate on the use of alternatives to direct regulation and has already been used to inform policy making in practice.