447 research outputs found
Perceptions of the rules of business behaviour in the competitive banking environment in Uganda
Business rules shape the behaviour of a business and guide the behaviour of employees when conducting business. Therefore, business rules explain what is allowed and not allowed. It is argued that all organisations have business rules and engage in some form of relationship whether through competition or cooperation with other companies. In today’s business environment, organisations are embedded in relationships with other actors in order to gain access to resources that are needed. Therefore, each organisation’s business rules define their strategies and actions. The type of business rule behaviour which is applied by organisations encourages them to grow by taking market share from rivals or creating new markets. The aim of this study was to determine the influence of the rules of business behaviour on perceptions of the competitive banking environment in Uganda and its potential impact on certain outcomes. In this study, a quantitative research approach was adopted, as the study sought to investigate the relationships between variables. This study collected data through the use of a structured self-administered survey questionnaire which was distributed to 233 branches of banks in Uganda, totaling 700 bank employees. The survey yielded 529 usable questionnaires which were analyzed, using several statistical analysis techniques. A hypothetical model and measuring instrument of perceptions of the rules of business behaviour in the competitive banking environment within Uganda was developed. Six null-hypotheses were subjected to statistical analysis. The influence of three independent variables, namely, confrontational business behaviour, co-operational business behaviour and typologies of competition on the intermediate variable, perceptions of the competitive banking environment in Uganda were tested. The impact of these variables on three independent outcome variables, namely, organisational performance and customer loyalty and retention were also tested The empirical findings revealed that the rules of business behaviour have a significant relationship with perceptions of the competitive banking environment in Uganda. These results showed that confrontational behaviour as a rule of business behaviour can be classified as being direct or indirect. The study further revealed that banks should consider competitors as co-partners and not only as aggressors, indicating that co-operational business behaviour is statistically significantly related to perceptions of the competitive business environment in Uganda. The three typologies of competition, namely, defy attack, defense and debase attack are also positively related to perceptions of the competitive business environment in Uganda. The empirical results of the study also indicated that perceptions of the competitive banking environment have a positive relationship with outcomes such as organisational performance, customer retention and customer loyalty. This study contributed to the literature and body of knowledge regarding the impact of rules of business behaviour in the competitive banking environment in Uganda. This study could also assist banks, employees and customers alike to understand the different rules of business behaviour that exist and what strategies banks can employ to improve their position in the market. This study could also be replicated by other banks in other developing countries so as to ensure successful competition and the cooperation of banks as they engage in their activities in the banking industry
Trends Shaping Education and Innovative Learning Environments: A Discourse Analysis of OECD CERI Projects
The Organization for Economic Co-operation and Development (OECD) was created in 1960 to advance economic expansion and world trade. Although it lacks a specific mandate for education, it has shaped national educational policy through the dissemination of ideas and transnational research. The Centre for Educational Research and Innovation (CERI), a branch of the OECD, was created in 1968. Its potential influence on the educational policy of nation states suggests a need to investigate its vision for K-12 education. The purpose of this research was to critically analyse two major projects undertaken by CERI: Trends Shaping Education and Innovative Learning Environments, with respect to the nature of their embedded political discourse, as well as their constructions of K-12 schooling, teachers, and learners. Additionally, it critically explored how the discourse of innovation, accountability, and governance shapes education in particular ways. Drawing from Fairclough’s methods of critical discourse analysis (CDA), as adapted by Grewal, it examined the ideological and discursive nature of the CERI projects. Texts were interpreted through a liberal theoretical framework. Findings suggest the CERI Projects frame a neoliberal vision for K-12 education focussed primarily on economic ends. Although the social dimension of education is recognized with respect to its need to foster equity, equality and social cohesion, its discourse is best characterized as a form of flanking and roll-out neoliberalism. Both Projects embrace a human capital approach to education and advance a neoliberal subjectivity in which learners are defined by their economic utility and are framed as future workers who are flexible, adaptable, resilient, responsible, innovative, entrepreneurial, and good problem solvers. The ILE Project’s promotion of networks and partnerships with other sectors and business reflects a transition away from government to governance as promoted by New Public Governance, which also reflects a neoliberal orientation. In both Projects, innovation, accountability, and governance are nominalizations that reinforce a neoliberal policy perspective of education.
The spatial genetic differentiation of the legume pod borer, Maruca vitrata F. (Lepidoptera: Crambidae) populations in West Africa
The legume pod borer, Maruca vitrata, is an endemic insect pest that causes significant yield loss to the cowpea crop in West Africa. The application of population genetic tools is important in the management of insect pests but such data on M. vitrata is lacking. We applied a set of six microsatellite markers to assess the population structure of M. vitrata collected at five sites from Burkina Faso, Niger and Nigeria. Observed polymorphisms ranged from one (marker 3393) to eight (marker 32008) alleles per locus. Observed and expected heterozygosities ranged from 0.0 to 0.8 and 0.0 to 0.6, respectively. Three of the loci in samples from Nigeria and Burkina Faso deviated significantly from Hardy-Weinberg Equilibrium (HWE), whereas no loci deviated significantly in samples from Niger. Analysis of molecular variance (AMOVA) indicated that 67.3% level of the genetic variation was within individuals compared to 17.3% among populations. A global estimate of FST=0.1 (ENA corrected FST=0.1) was significant (P≤0.05) and corroborated by pairwise FST values that were significant among all possible comparisons. A significant correlation was predicted between genetic divergence and geographic distance between subpopulations (R2=0.6, P=0.04), and cluster analysis by the program STRUCTURE predicted that co-ancestry of genotypes were indicative of three distinct populations. The spatial genetic variance among M. vitrata in West Africa may be due to limited gene flow, south-north seasonal movement pattern or other reproductive barriers. This information is important for the cultural, chemical and biological control strategies for managing M. vitrata
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Genomic, patterns of selection and differentiation in African populations and implications for mapping disease association
The main objective of this thesis is to gain a better understanding of genomic patterns of natural selection and population differentiation in Africa, where there is great genetic diversity, and of the implications for genetic mapping of complex diseases.
I began by studying two neighbouring villages in eastern Sudan that are of different ethnicity, Hausa and Masalit, and that appear to have different susceptibility to malaria and visceral leishmaniasis (VL). Specifically, I investigated patterns of linkage disequilibrium (LD) and haplotypic signals of positive selection in the 5q31 genomic region which contains immune genes that have been implicated in susceptibility to malaria and VL.
In my first analysis, by genotyping 34 single nucleotide polymorphisms (SNPs) in the 5q31 region, I did not find signals of selection or population differentiation between the Hausa and Masalit using available statistical methods. I conceived the idea that patterns of LD might provide a more sensitive test of population differentiation, and I developed an approach for this using permutation analysis. This method revealed differentiation between the Hausa, the Masalit and other African ethnic groups.
To better understand signals of selection, I next studied a region of the genome associated with a known malaria resistance factor, the haemoglobin S (HbS) variant of the HBB gene. By genotyping 26 SNPs in the region of the HBB gene, I observed a haplotype that extended in excess of 1 Mb, despite being at high frequency and spanning several recombinational hotspots. This long haplotype carried the HbS allele but, importantly, it could be readily detected without typing the HbS variant.
Building on this observation, I designed a new method to screen the whole genome for long haplotypes that might be signals of selection, and developed a software programme to implement this method. I validated this method using haplotypic data for the Yoruba generated by the HapMap project and complemented by additional SNP data that I generated on HapMap cell lines, and found that the HbS allele resides on a haplotype that extends to 1.2 Mb, and is at strikingly high frequency compared to other haplotypes of similar length on the same chromosome.
Next I applied this method to a large family-based association study of severe malaria in The Gambia, and identified several novel genomic regions with unusually long haplotypes of high frequency. These included a number of regions that may be associated with resistance to severe malaria, and which merit further investigation
Genetic characterization of nucleoside analogue transporters ABCC4 and ABCC5 gene loci
Ph.DDOCTOR OF PHILOSOPH
Human Cytomegalovirus Reprograms the Expression of Host Micro-RNAs whose Target Networks are Required for Viral Replication: A Dissertation
The parasitic nature of viruses requires that they adapt to their host environment in order to persist. Herpesviruses are among the largest and most genetically complex human viruses and they have evolved mechanisms that manipulate a variety of cellular pathways and processes required to replicate and persist within their hosts. Human cytomegalovirus (HCMV), a member of the β- herpesvirus sub-family, has the capacity to influence the expression of many host genes in an effort to create an optimal environment for infection. One mechanism utilized by HCMV to alter gene expression is the host RNA interference (RNAi) pathway. This is evidenced by a requirement of host factors to process viral micro-RNAs (miRNAs) and by the dynamic expression of host miRNAs during infection.
The work presented in this dissertation demonstrates that productive HCMV infection reprograms host miRNA expression in order to positively influence infection. I was able to identify a cohort of infection-associated host miRNAs whose change in expression during infection was highly significant. Using the enhancer-promoter sequences of this panel of host miRNAs, I statistically enriched for the presence of functional transcription factor binding sites that regulated the expression of two highly conserved clusters of host miRNAs: miR132/212 and miR143/145. Given that inhibiting their infection-associated change in expression during infection was detrimental to viral replication, it suggests that HCMV mechanistically influences the expression of these miRNA clusters. In order to determine the functional relevance of these miRNAs, I assembled a cohort of potential miRNA target genes using gene expression profiles from primary fibroblasts. By statistically enriching for miRNA recognition elements (MRE) in the respective 3’-UTR sequences, I generated a miRNA target network that includes thousands of host genes. I evaluated the efficacy of our novel miRNA target prediction algorithm by confirming the functionality of enriched MREs present in the 3’-UTR of KRas and by confirming anecdotal miRNA targets from published studies. Gene ontology terms enriched from infection-associated host miRNA target networks suggest that the utility of host miRNAs may extend to multiple host pathways that are required for viral replication. The targeting of multiple miRNAs to shared genes increased the statistical likelihood of target site enrichment. I propose that identifying cooperative miRNA networks is essential to establishing the functional relevance of miRNAs in any context. By combining contextual data on the relative miRNA/mRNA abundance with statistical MRE enrichments, one will be able to more accurately characterize the biological role of miRNAs
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Systematically Mapping the Epigenetic Context Dependence of Transcription Factor Binding
At the core of gene regulatory networks are transcription factors (TFs) that recognize specific DNA sequences and target distinct gene sets. Characterizing the DNA binding specificity of all TFs is a prerequisite for understanding global gene regulatory logic, which in recent years has resulted in the development of high-throughput methods that probe TF specificity in vitro and are now routinely used to inform or interpret in vivo studies. Despite the broad success of such methods, several challenges remain, two of which are addressed in this thesis.
Genomic DNA can harbor different epigenetic marks that have the potential to alter TF binding, the most prominent being CpG methylation. Given the vast number of modified CpGs in the human genome and an increasing body of literature suggesting a link between epigenetic changes and genome instability, or the onset of disease such as cancer, methods that can characterize the sensitivity of TFs to DNA methylation are needed to mechanistically interpret its impact on gene expression. We developed a high-throughput in vitro method (EpiSELEX-seq) that probes TF binding to unmodified and modified DNA sequences in competition, resulting in high-resolution maps of TF binding preferences. We found that methylation sensitivity can vary between TFs of the the same structural family and is dependent on the position of the 5mCpG within the TF binding site. The importance of our in vitro profiling of methylation sensitivity is demonstrated by the preference of human p53 tetramers for 5mCpGs within its binding site core. This previously unknown, stabilizing effect is also detectable in p53 ChIP-seq data when comparing methylated and unmethylated sites genome-wide.
A second impediment to predicting TF binding is our limited understanding of i) how cooperative participation of a TF in different complexes can alter their binding preference, and ii) how the detailed shape of DNA aids in creating a substrate for adaptive multi-TF binding. To address these questions in detail, we studied the in vitro binding preferences of three D. melanogaster homeodomain TFs: Homothorax (Hth), Extradenticle(Exd) and one of the eight Hox proteins. In vivo, Hth occurs in two splice forms: with (HthFL) and without (HthHM) the DNA binding domain (DBD). HthHM-Exd itself is a Hox cofactor that has been shown to induce latent sequence specificity upon complex formation with Hox proteins. There are three possible complexes that can be formed, all potentially having specific target genes: HthHM-Exd-Hox, HthFL-Exd-Hox, and HthFL-Exd. We characterized the in vitro binding preferences of each of these by developing new computational approaches to analyze high-throughput SELEX-seq data. We found distinct orientation and spacing preference for HthFL-Exd-Hox, alternative recognition modes that depend on the affinity class a sequence falls into, and a strong preference for a narrow DNA minor grove near Exd's N-terminal DBD. Strikingly, this shape readout is crucial to stabilize the HthHM-Exd-Hox complex in the absence of a Hth DBD and can thus be used to distinguish HthHM from HthFL isoform binding. Mutating the amino acids responsible for the shape readout by Exd and reinserting the engineered protein into the fly genome allowed us to classify in vivo binding sites based on ChIP-seq signal comparison between “shape-mutant” and wild-type Exd.
In summary, the research presented here has investigated TF binding preferences beyond sequence context by combining novel high-throughput experimental and computational methods. This interdisciplinary approach has enabled us to study binding preferences of TF complexes with respect to the epigenetic landscape of their cognate binding sites. Our novel mechanistic insights into DNA shape readout have provided a new avenue of exploiting guided protein engineering to probe how specific TFs interact with their co-factors in a cellular context, and how flanking genomic sequence helps determine which multi-TF complexes will form and which binding mode a complex adopts
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