Doctor of Philosophy

dissertationN-methyl-D-aspartate receptors (NMDARs) are vital components of the mammalian nervous system that intimately contribute to excitatory neurotransmission. Learning, memory formation, synaptic plasticity, and many neurodegenerative diseases are linked with NMDARs. In order to study these processes, there is need for scientific tools that can be used to examine NMDARs. Cone snail venom is a mixture of neurotoxins with specific targets in the nervous system. Conantokins are a family of conotoxin that inhibit NMDARs and can select for different NMDAR subtypes. Therefore, understanding mechanisms of conantokin selectivity and using selective conantokins as tools to identify NMDAR subtypes in the brain are important advancements for neurobiology. In this dissertation, Chapters 2 and 3 describe structural studies of conantokin Bk-B (conBk-B) and of conantokin R/-B (conR/-B). These conantokins exhibited novel NMDAR subtype selectivities and were consequently of interest for structural characterization. The ultra-short conBk-B was found to adopt helical conformation similar to that observed in other conantokins. ConR/-B was found to be a kinked helix that is unique among structurally characterized conantokins. Comparison of conantokin structures, paired with mutational analysis, highlighted that residues 5, 6, 8, and 10 determine subtype selectivity in conantokins. Chapter 4 describes biochemical studies of NMDAR ligand-binding domain (LBD) proteins for the NR1-2b, NR2A, NR2B, and NR2C NMDAR subtypes. Limited proteolysis assays showed agonist binding, indicating LBD proteins were correctly folded. Additional experiments found no strong interactions between LBD proteins and conantokins. The results suggest that additional protein domains, heteromeric NMDARs, or neuronal membranes may be required for conantokin-NMDAR binding. In Chapter 5, conantokins are used to define the NMDAR subtypes in neurons from mouse cerebellum. Agonist challenge assays revealed diversity in cerebellar neurons, and conantokin R/-B was used to show NR2B NMDAR subtypes in cerebellar neurons of young mice. In older mice, a population of neurons with non-NR2B NMDARs was discovered. This dissertation demonstrates the first use of conantokins to define NMDAR subtypes in live neurons, provides a foundation for understanding neuronal diversity in the brain, and establishes NMDAR subtype composition in individual neurons of the developing cerebellum

Sub-Optimal Performance of Enterprise Resource Planning Systems in Non Governmental Organizations in Kenya: A Case Study of AMREF Kenya

The Non-Governmental Organizations play a key role in Kenya’s development. Many NGO’s have deployed Enterprise Resource Planning (ERP) systems in their management of the supply chain. There is a problem with Non-Governmental Organizations’ (NGO) ERP systems: they experience varying degrees of inefficiencies with the deployment and application of the e-procurement software.  This research had the overall objective of investigating the factors contributing to the sub-optimal performance in the ERP performance in the NGO’s in Kenya. The choice of AMREF is that it is one of the largest and oldest NGO’s in the medical sector in Kenya which recently implemented ERP systems. It is facing inefficiency issues with its ERP system. The research applied descriptive research design and used random sampling technique. The data collection was done with the aid of questionnaires. The key finding was that the Enterprise Resource Planning (ERP) training is wanting in terms of relevance and appropriateness.   The study recommends inter alia that training be made more involving by incorporating the stakeholders from other departments to participate in the training exercise other than to leave it to the supplies unit and the consultant.  It also recommends that the procurement procedures be enhanced in order to reduce on the number of signatories required and thus hasten the decision making process. Keywords: Enterprise Resource Planning, Non-Governmental Organizations, Sub-Optimal Performance

Border Security Management and State Security: a Case Study of Kenya and Somalia Border Relations (1991-2017)

The porous border of Kenya-Somalia has always been problematic to the Kenyan government, ever since the Somali government’s fall in 1991. This study was based along the Kenya-Somalia boundary in Mandera County. The study examined border security management and state security between Kenya-Somalia from 1991-2017. One specific objective guided it: To, identified cross-border security threats along with the Kenya-Somalia border. The study applied theories of structural realism and border security theory/ psychoanalytic theory.The study was guided by descriptive survey research design and experimental research designs. This research used several sampling strategies: convenience, systematic, snowball, random sampling, and purposive techniques. The researcher selected a sample size of 398 that comprised heads of families.Further, 85 critical informants of private and public responders were chosen from the two case studies. Primary information was gathered using FGDs, survey tools such as questionnaires and observations and interviews. On the other hand, secondary data is retrieved through relevant articles and publication content analysis. Descriptive and inferential statistics proved vital in analyzing preliminary information, while content analysis was utilized when analyzing qualitative data. Tables and figures presented the data analyzed. The study established that 70% of the respondents stated that terrorism was a critical security threat along the Kenya-Somalia border. The researcher was informed of a newly emerging strategy employed in terrorism, through which the beasts of burden( donkey) has made the war against terror more complex. The donkey, a domesticated animal, is used by man as a helper; however, the latest creative (mis) use of the beast of burden for terrorism has emerged as a critical concern to the security apparatus

EFFECT OF ENDOGENOUS PROTEASES ON GELATION OF RED TILE FISH SURIMI

Red tile fish Branchiostegus japonicus meat degrades easily. In market, the small- sized fish is traded at a low price. Additionally, the population of red tile fish in the sea around Japan has reduced. Therefore, for effective utilization of small-sized red tile fish, the effect of endogenous proteases on heat-induced gelation of red tile fish surimi was investigated in the research. Fish gels from red tile fish surimi were prepared at different temperatures between 30 – 90 oC. After heating, the samples were cooled in ice water and then mechanical properties and SDS-PAGE patterns were analyzed. Homogenates prepared from the surimi were mixed with protease inhibitor solutions. The mixtures were incubated in water bathes at 40 or 60 oC. After heating, peptide contents in the supernatant and autolytic protein patterns were determined by the Lowry method and SDS-PAGE respectively. The surimi didn’t form heat-induced gels at 30 - 80 oC and SDS–PAGE showed that proteolysis markedly occurred. Addition of 1, 10-phenanthroline, benzamidine or SBTI prevented proteolysis. These results suggest that red tile fish surimi had extremely low gel- forming ability due to endogenous metalloprotease and trypsin-like serine protease. Keywords: Fish products, Gelation, Protease inhibitor, Surimi

Border Security Challenges: a Case Study of Kenya and Somalia Border Relations (1991-2017)

The porous border of Kenya/ Somalia has always been problematic to the Kenyan government, ever since the Somali government's fall in 1991. This study was based along the Kenya- Somalia boundary in Mandera County. The study examined border security challenges between Kenya-Somalia from 1991 to 2017. One specific objective guided it: to discuss challenges to border security strategies along with Kenya- Somalia border. The study was guided by descriptive survey research design and experimental research designs. This research used several sampling strategies: convenience, systematic, snowball, random sampling, and purposive techniques. The researcher selected a sample size of 398 that comprised heads of families. Further, 85 critical informants of private and public responders were chosen from the two case studies. Primary information was gathered using FGDs, survey tools such as questionnaires and observations and interviews. On the other hand, secondary data was retrieved through relevant articles and publication content analysis. Descriptive and inferential statistics proved vital in analyzing preliminary information, while content analysis was utilized when analyzing qualitative data. Tables and figures present the data analyzed. The study established that 86 % of the respondents stated that regional politics, power politics and geopolitical conflicts were significant impediments to border management strategies. It was concluded that geopolitical disputes were the main challenge encountered in border management strategies. The study recommends that Kenya partner with like-minded stronger countries in Africa's horn, affected by the Somali problem like Ethiopia, and develop a common approach to learning from them on dealing with the border issue

Læring i Redningshelikoptertjenesten

Studien undersøker fenomenet læring i Luftforsvaret og har søkt å avdekke læringsprosesser og hva som påvirker disse i Redningshelikoptertjenesten (RHT). Læring er en vesentlig del av alle organisasjoners hverdag også i Luftforsvaret. Formålet med studien er skape organisatorisk forståelse og sette den i teoretisk kobling til læring og hva som påvirker denne. En slik forståelse kan være med på å bevisstgjøre hvilke prosesser som eksisterer og hva man eventuelt kan bli bedre på. Undersøkelsen har en kvalitativ tilnærming og et teoretisk utgangspunkt i David A. Garvin. Den tar utgangspunkt i RHT, herunder avdelingene 330 skvadronen og prosjektavdelingen Operativ Test & Evaluering (OT&E). Problemstillingen er delt i to. Del en søker å svare på hvordan RHT lærer. Del to beskriver hva som påvirker denne læringen. Problemstillingen operasjonaliseres gjennom Garvin sin teori om lærende organisasjon. Respondentene indentifiserer læringsprosesser ved RHT som støtter Garvin sine teoretiske linjer og kobler disse mot forhold som påvirker læringen. Hovedfunnene i studien peker på læring av egne erfaringer og historie og overføring av kunnskap som noen av styrkene i RHT, mens andre læringsprosesser som å lære av eksterne virksomheter ikke kommer like tydelig frem. OT&E skaper det systematiske og metodiske grunnlaget for læring slik Garvin legger til grunn. En slik ressurssetting som OT&E er et eksempel på, frigjør kapasitet til å drive læring i større grad enn det som er mulig for 330 skvadronen som må prioritere den daglige driften, søk og redning. Den siste delen av problemstillingen bringer frem empiri som viser til at RHT både innehar et støttende læringsmiljø og har en ledelse som støtter læring. Et støttende læringsmiljø kommer til uttrykk gjennom en toleranse for feil og uhell, tidsmessige og nøyaktige tilbakemeldinger og åpenhet for innspill. Ledelse som støtter læring forklares hovedsakelig gjennom å sette den rette stemningen, men også gjennom å skape muligheter for læring og å lede effektive diskusjoner. Enkelte læringsprosesser og forhold som virker positivt på læring kommer ikke like tydelig frem hos respondentene. Dette gjelder særlig prosesser som systematisk problemløsning, eksperimentering og aksept for ulikheter og mangfold. Til slutt oppleves Remedy som rapportering og risikostyringsverktøy som lite egnet for RHT, noe som i seg selv er bekymringsverdig

The Clinical Classification of Seizures among Children with Epilepsy Seen at The Moi Teaching and Referral Hospital in

Epilepsy continues to take its toll among children causing impaired physical, psychological and social functioning of those affected. The  annual rate of new cases of epilepsy is approximately 5-7 cases per 10,000 children from birth to age 15 years, and in any given year, about 5 of every 1,000 will have epilepsy. Classification of epileptic seizures relies on clinical phenomenology as well as electroencephalography (EEG), and accurate classification is important since it impacts on choice of medication as well as prognostication. This paper sought to describe the Clinical Classification of epilepsy in children seen at Moi Teaching and Referral Hospital, Eldoret. A cross sectional study was carried out between January 2011 and July 2011 in the general peadiatric wards and the paediatric outpatient clinic at the MTRH. The study subjects were all children aged one month to 14 years. Consecutive sampling of children who had clinical features consistent with epilepsy was done for in the recruitment of study subjects. Data was collected in a structured questionnaire and EEGs were recorded in the hospital’s EEG laboratory. Descriptive data was grouped in frequencies and mean and range was used to summate data. Association between factors was analysed by linear regression and Chi-square was used to analyse differences in epilepsy classification based on clinical features or EEG independently. From the study,  fifty-six children with epilepsy were enrolled into the study, 35(62.5 %) of whom were male and 21(37.5%) were female (M:F 1:0.6). The youngest age at onset of seizures recorded in the study was one month and the mean age was 4.2 years. Twenty-six patients (46.4%) had generalized tonic clonic seizures, nine (16.1%) had partial seizures, eight (14.3%) had mixed seizures, six children (10.7%) had absence seizures, six (10.7%) had tonic seizures and one (1.8%) had myoclonic seizures. The commonest seizure types in children seen at MTRH are generalized tonic-clonic and partial seizures. The generalized spike-and-wave patterns and focal spike-and-wave patterns were the commonest EEG patterns. However, EEG findings increased the proportion of children with partial (focal onset) seizures. Therefore, physicians should use both clinical phenomenology and EEG patterns in classifying patients with epilepsy so as to improve on treatment and follow-up. Keywords: Clinical Classification, Seizures, Epilepsy, Children, Referral Hospital, Keny

Challenges of setting up flow cytometry for diagnosis of leukemia and lymphoma at Moi Teaching and Referral Hospital, Eldoret, Kenya

The bone marrow (BM) is a complex tissue containing cells of multiple hematopoietic cell lineages in all stages of development. Flow cytometricimmunophenotyping evaluates the frequencies of the various leukocyte (sub) populations in BM and blood that then helps in the diagnosis of leukemia's. The aim of this study was to identify challenges of setting up an advanced diagnostic tool like flow cytometry in a resource strained country like Kenya. This is based on a 2 year experience of use of flow cytometry for diagnosis of leukemia, the challenges faced by both the pathologists and the technical team