http://localhost/xmlui/handle/123456789/3878 2026-04-06T18:51:14Z http://localhost/xmlui/handle/123456789/6605 GENERATION AND FUNCTIONAL CHARACTERIZATION OF CHICKEN-BASED IgY POLYCLONAL ANTIBODIES AGAINST BLACK MAMBA (Dendroaspis polylepis) SNAKE VENOM Kpordze, Stephen Wilson The life-threatening medical issues associated with snakebites have been a public health concern for decades at the global level. The Black mamba, D. polylepis, is one of the many venomous snakes found in Kenya. According to the Kenyan Ministry of Health data, 15,000 snakebites occur annually. For snakebites, antivenom immunotherapy is still the preferred course of action and different antivenoms are needed to treat the venom of different snake species. Traditionally, antivenoms for treatment are produced from horse or sheep but have complicated and expensive production issues. Alternative production approaches, such as using immunoglobulin Y (IgY) antibodies derived from chicken egg yolks, may overcome disadvantages with traditional antivenom manufacturing techniques. In many tropical and subtropical nations such as Kenya, diagnosis of snakebite in the health facilities is imperative. For the purpose of determining which species caused the bite, it is critical to detect and measure snake venom in the blood of envenomed patients. The study presents the generation of IgY antibodies, and development of an enzyme-linked immunosorbent assay (ELISA) against D. polylepis. In this current study, D. polylepis specific IgY polyclonal antibodies were purified from the egg yolks of chickens immunized with D. polylepis venom. These antibodies were subsequently assessed for their in-vivo neutralizing capacity vis-à-vis commercial antivenoms, PANAF Premium and VINS. Additionally, the study sought to develop a sensitive ELISA prototype for detection of D. polylepis venom in Kenya using generated chicken-based IgY polyclonal antibodies. The IgY antibodies were purified by ammonium sulfate precipitation and affinity-chromatography, with quality and specificity determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ELISA. Furthermore, serum samples containing specific chicken-based IgY antibodies previously raised against D. polylepis venom toxins were used in the assay development. ELISA parameters were optimized, and developed assay assessed for applicability. The LD50 of D. polylepis was 0.54 mg/kg in chicks (via intramuscular route), and 0.34 mg/kg in mice (via intraperitoneal route), respectively. Pool of extracted IgY yielded 2.8 mg/mL concentration. Purified IgY under non-reducing and reducing conditions on SDS-PAGE xv exhibited a single-protein band of about 183 kDa and two bands (67 kDa and 25 kDa), respectively. The minimum-edematogenic dose was 0.05 µg. Anti-D. polylepis IgY antibodies and two antivenoms demonstrated the capacity to neutralize the toxic activities of D. polylepis venom. The median effective dose (ED50) for lethality neutralization were 41.36, 35.41 and 46.60 µL/3LD50, and for edema were 80±11.55, 60±18.26, 90±8.16 µL/6MED, respectively for IgY antibodies, VINS and PANAF antivenoms. There was no statistical differences among their neutralizing efficacies (P value = 0.320-0.859) The limit of detection (LoD) of the ELISA for neurotoxic venoms was 0.01 µg/mL. The developed assay identified venoms in blood of BALB/c mice and, distinguished D. polylepis venom from that of other snake species, as well as neurotoxic and cytotoxic venoms. This developed assay would be useful in helping physicians to diagnose and manage snakebite cases. The development of an effective IgY antibodies with higher titer represents a significant step towards antivenom production against D. polylepis. Diversity of the IgY antibodies development to capture other medically important snake venoms, molecularly characterize IgY, and development of venom detection kits with quick turnaround times based on liquid or lateral flow tests approach are recommend PhD in Molecular Biology and Biotechnology 2025-03-04T00:00:00Z http://localhost/xmlui/handle/123456789/6270 Bayesian and Frequentist Approaches for Flexible Parametric Hazard-Based Regression Models with Generalized Log-logistic Baseline Distribution: An Application to Right-Censored Oncology Data Sets Muse, Abdisalam Hassan n general, parametric hazard-based regression models can be motivated by allow ing baseline distribution parameters to be affected by covariates. Furthermore, it is common practice to link covariates to a single parameter of interest; this method will be called a single parameter hazard-based regression (SPHBR) models. The role of the additional (covariate independent) parameters in these SPHBR models is frequently little more than to provide the model with enough generality to adjust to data. A more flexible technique is to regress these additional distributional pa rameters on covariates as well; this is referred to as multi-parameter hazard-based regression (MPHBR) models. The development of MPHBR models in the context of Bayesian survival analysis with particular interest towards application to right censored oncology data is the main focus of this thesis. Chapter 2 of this thesis examines the fundamentals of survival analysis as well as the methodologies employed to achieve the study’s objective; these are common and can be ignored by readers with familiarity with the field. A flexible generalized log logistic distribution that can incorporate both monotone and non-monotone hazard rates is developed in chapter 3 and examined using both Bayesian and classical in ference methods. Using the baseline distribution proposed in chapter 3, chapter 4 presents a flexible parametric proportional hazard (PH) model. The tractability of the PH model is shown, and the implications of the method are discussed, including how to interpret covariate effects (via the hazard ratio), how to perform proportion ality assumption checks on regression coefficients, and how to use Bayesian model selection techniques. To show how versatile the accelerated failure time (AFT) model is, chapter 5 presents an alternative parametric hazard-based regression model to the one presented in chapter 4. The parametric hazard-based regression mod els proposed in chapters 4 and 5 might not be accurate if crossovers exist in the xxxv hazard or survival functions. The accelerated hazard (AH) model, a novel flexi ble hazard-based regression model that can take into account survival data with crossover survival curves, is proposed in Chapter 6 of this thesis as a solution to this issue. The parameters of the proposed AH model are estimated using Bayesian and frequentist approaches. The need to enable parametric hazard-based regression models—and really any parametric survival regression model—more interpretable motivates the presentation of a general class of parametric hazard-based regression models in Chapter 7. Covariate effects on the baseline hazard are straightforward to interpret due to the proposed general class. The class also has the benefit of allowing for both proportional and time-independent effects of some covariates on baseline hazard and non-proportional and time-dependent effects of other covariates in the same model, unlike PH, AFT, or AH. For estimating the model parameters, both the Bayesian and frequentist approaches are applied. In chapter 8, the Amoud Class, a novel class of survival regression models that includes all hazard-based and odds-based models as special cases and is more flexible in modelling survival data, is introduced. The main advantage of the class is that it can provide users with a quantitative tool for selecting which of the seven often employed methods for hazard-based and odds-based regression models is more appropriate for a certain set of data. For each of the models proposed in chapters 3, 4, 5, 6, and 7, several simulations are run using a variety of parameter settings and data generation sce narios in order to evaluate the efficacy of the model’s estimators. To demonstrate the adaptability of the proposed survival regression models, applications of right censored oncology data sets are explored. Finally, in Chapter 9, we conclude the thesis with a discussion and mention of some future works. PhD in Mathematics 2024-04-17T00:00:00Z http://localhost/xmlui/handle/123456789/5588 Optimization of Thermal Performance of Water in Glass Evacuated Tube Solar Heater Kyekyere, Ernest Solar water heaters provide a cost-e cient, unlimited, and environmentally friendly approach to hot water generation. Water in glass evacuated tube solar water heater (WG-ETSWH) is one of the commonly used solar water heaters (SWHs) available in the market. Despite its widespread use, WG-ETSWH has a low thermal performance and its installation cost is very high. As a result, hot water generation in homes and industries is highly dependent on electricity, fossil fuels, and traditional biomass despite the high solar potential in Africa. That has resulted in environmental pollution, various health problems and the high cost of conventional fuels. Several research studies have been conducted to help improve the performance of water in glass evacuated tube solar collectors (WG-ETSC). The performance of WG-ETSWH is dependent on the geographic location. Additionally, for collectors with identical parameters, tilt-type collectors absorb slightly more solar irradiation than horizontal-type collectors. The optimum thickness of the polyurethane insulation to reduce heat loss from the storage tank is 50 mm. However, the e ect of collector tube length, diameter and tilt angle on the performance of WG-ETSWH has not been fully studied. This research work is focused on optimizing the performance of WG-ETSWH for water heating applications using both experimental and numerical methods under the climatic conditions in Kenya. An experimental study on the performance of WG-ETSWH was conducted under the climatic conditions in Kenya. A CFD model was developed according to the speci cations of the experimental setup and its performance was then validated against the experimental data. The validated CFD model was then used to study the in uence of geometric variables such as the collector tilt angle, collector tube diameter and the collector tube length on the performance of the system. From the experimental study, the outlet temperature of the water in glass evacuated tube solar water heater was found to be ranged from 55 oC to 69 oC given an initial temperature of 25 oC for a whole day heat collection. The daily e ciency of the water in glass evacuated tube solar water heater under the climatic conditions in Kenya ranges from 58 % to 65 %. The collector tube length, diameter and tilt angle had a signi cant in uence on the xvii performance of WG-ETSWH. The optimum collector tube length, diameter and tilt angle were found to 2000 mm, 50 mm and 28 degrees respectively. The optimized design of the WG-ETSWH enhanced the outlet temperature of the water in the storage tank by 6.0 % and the average ow velocity of water in the system by 11.8 %. The results from this research will give insight into the design of improved products of water in glass evacuated tube solar water heater for the extraction of maximum heat energy from the sun. Master of Science in Mechanical Engineering 2021-07-12T00:00:00Z http://localhost/xmlui/handle/123456789/4942 MATHEMATICALMODELLINGOFANTHRAXANDLISTERIOSISCO-DYNAMICS WITH OPTIMAL CONTROL OSMAN, SHAIBU In this research, three mathematical models were developed to explain the transmission dynamics of zoonotic diseases that are bacteria related, specifically Listeriotic, Anthrax and their co-infection. Ordinary differential equations were used in the formulation of the Anthrax, Listeriosis and Anthrax-Listeriosisco-infection deterministic models. These deterministic models were formulated and analyzed qualitatively and quantitatively. A vaccination compartment with waning immunity was incorporated into the Anthrax model. The local and global stability analysis of equilibrium points were analyzed and found to be locally asymptotically stable whenever the basic reproductive number is less than one and unstable if the basic reproductive number is greater than one. The basic reproductive numbers were computed and used as the threshold parameter that governs the spread of Anthrax, Listeriosis and Anthrax-Listeriosis coinfection. Moreover, the extension of the Anthrax, Listeriosis and the co-infection models to optimal control theory seek to minimize the objective functional subject to some controls variables were determined. The resulting control problem was solved numerically in order to determine the most effective control measure in combating the Anthrax infections. It established that Anthrax and Listeriosis models exhibited multiple endemic equilibrium. Sensitivity analysis of the basic reproduction numbers of all the three models were determined. It was established that, increasing animal (livestock) recovery rate, would lead a decrease in the basic reproduction number. The qualitative analysis of optimal control of the Anthrax, Listeriosis and Anthrax-Listeriosis co-infection were performed and the necessary conditions for the optimality of Anthrax, Listeriosis and Anthrax-Listeriosisinfectionswereanalysed. The most effective control strategies of the Listeriosis model were the combination of treatment of infectious vectors and treatment of infectious humans, combination of prevention of susceptible humans and the treatment of infectious vectors. Anthrax-Listeriosis co-infection model analysis reveals that the disease free equilibrium was locally asymptotically stable whenever the reproduction number is less one. The co-infection model exhibited the phenomenon of backward bifurcation. Mathematically, it implies that the idea of the model been locally asymptotically stable whenever the reproduction number is less than unity and unstable otherwise is not a sufficient condition for disease eradication. The impact of Listeriosis on Anthrax infections reveals that Anthrax infections can be attributed to increased risk of Listeriosis butthereverseisnotthesame. However, optimal prevention and treatment of Anthrax and not keeping Listeriosis under control is not the best strategy for eradicating either of the disease. A Thesis submitted to Pan African University, Institute for Basic Sciences, Technology and Innovations in partial fulfillment of the requirement for the award of Doctor of Philosophy in Mathematics (Computational option) of the University. November, 2018. 2019-04-26T00:00:00Z