NMR Structural Investigation of Chlamydial Protein Complex and Lysine Glycomimetic for Drug Design

Research and design of drugs for treatment against microbial infections require the study of pathogenic proteins involved during infection and replication. Drugs can be designed to interfere with the interaction network of these pathogenic proteins and inhibit the infection process. Determination of the structure and ligands of the target proteins in microbes is essential for designing mechanistic-based drugs. Two Chlamydia proteins involved in host cell invasion were investigated in this study. The goal is to identify amino acids involved at the binding interface of Chlamydia chaperon proteins Scc1 and Scc4 by solution NMR spectroscopy. This information will give a lead in designing drugs that will interfere with Scc1:Scc4 binding, thus preventing Chlamydia invasion. Two new purification methods for isolating untagged Scc4 and the formation of mixed heterodimer complexes for NMR studies are described. The experimental NMR spectroscopy data was recorded and used to analyze the structural conformations of Scc4 when transitioning from homodimer to the heterodimer complex. Research presented in the second section is a novel structural modification method for therapeutic peptides through glycoalkylation. The modification is intended to improve the pharmacokinetic properties of lysine-containing peptide drugs, through half-life elongation and increased oral bioavailability. Specifically, the therapeutic tripeptide, Ac‑KPV-NH2, was modified with a sugar derivative. Although the effect of the modification could not be assessed through antimicrobial and anti-inflammatory tests, the glycoalkylated peptides are shown to be stable against pronase cleavage. The unmodified tripeptide was cleaved by pronase in less than 24 hours, indicating that the glycoalkylation confers proteolytic stability

Genetic diversity in pigeonpea [Cajanus cajan (L.) Millsp.] Landraces as revealed by simple sequence repeat markers

Genetic relationships among 88 pigeonpea accessions from a presumed centre of origin and diversity, India and a presumed secondary centre of diversity in East Africa were evaluated using six microsatellite markers. Forty-seven (47) alleles were detected in the populations studied, with a mean of eight alleles per locus. Populations were defined by region (India and East Africa) and sub-populations by country in the case of East Africa and State in the case of India. Substantial differentiation among regions was evident from Roger’s modified distance and Wright’s F statistic. Greatest genetic diversity in terms of number of alleles, number of rare alleles and Nei’s unbiased estimate of gene diversity (H) was found in India as opposed to East Africa. This supports the hypothesis that India is the centre of diversity and East Africa is a secondary centre of diversity. Within East Africa, germplasm from Tanzania had the highest diversity according to Nei’s unbiased estimate of gene diversity, followed byKenya and Uganda. Germplasm from Kenya and Tanzania were more closely related than that of Uganda according to Roger’s modified distance. Within India, results did not indicate a clear centre of diversity. Values of genetic distance indicated that genetic relationships followed geographicalproximity

Constitutionalizing secession as a mechanism for conflict avoidance

A Dissertation submitted in partial fulfillment of the requirements for the award of the degree of Bachelor of Laws (LL.B) at Strathmore UniversityThe right to secede is most often based on the right to self-determination as espoused in the United Nations Charter of 1945. The realization of this right can be either external or internal. External self-determination is often regarded as the last resort, where a people move to declare their own state. The internal aspect on the other hand regards practice of autonomy by a people within the boundaries of another state. The practice of self-determination by a people has been perceived as a major threat to the principle of territorial integrity of a state. It is this perception that has resulted in drawn out armed conflicts over seceding territories. It is based on this problem, the threat of violence in secessions to international peace and security, that there is need to generate a pacific solution. The best way this problem can be addressed is for governments to recognize that self-determination of peoples is an important right and to cater for it adequately by providing for it in the domestic constitution, so that self-determination becomes a constitutional right. Through the constitution, formal procedures of consultation can be outlined, the specific criteria that need to be met by a group claiming self-determination and a cogent negotiation process. Having studied countries that have constitutionalized secession, it is not always true that because of its legal recognition, secession has ceased to be a violent process. A peaceful secession only happens when the government recognizes the will of the people and accepts political divorce. It is not always that constitutional rights are adhered to. A peaceful secession fundamentally requires political will

Postmaterial Development : The Search for a New Asian Model

Conventional wisdom has it that the Asian "miracle" was fueled by a strictly defined set of "Asian values." On closer examination, those values turn out to be more Western than Asian. The "miracle," moreover, often achieved economic development at the expense of political underdevelopment and ecological destruction. The resulting "Asian model" eschewed a wide range of nonmaterial goals, such as communal integrity and environmental balance, which were deeply embedded in Asian traditions. It took the Asian Crash to puncture that model, casting doubt on the working assumptions of three decades of full-throttle economism. Before the Crash, democratic values were often dismissed - along with human rights, gender rights, and environmental protection - as luxuries to be deferred until after development was complete. Some iconoclasts, such as Amartya Sen, strongly refuted that modernist formula, but it was the Crash that provided the smoking gun to place postmaterialism on the Asian political map. The result is not only a more sustainable model of development, but a more inclusive view of Asian values. Key Words: Postmaterialim, Economism, Asian Values, Asian Model, Asian Cras

Implementing a regional integrated laboratory proficiency testing scheme for peripheral health facilities in East Africa

Introduction: Regular participation in external quality assessment (EQA) is critical for maintaining laboratory performance and is required for laboratory accreditation. Proficiency testing (PT) is effective for providing EQA, but available schemes rarely address the range of tests performed by peripheral laboratories in resource-limited settings. The East African Regional External Quality Assessment Scheme (EA-REQAS) was established in 2004 to address this need. Materials and methods: Surveys were distributed biannually comprising seven different panel materials and questions addressing laboratory, clinical and public health topics. Preserved materials were prepared using standard procedures and validated by accredited laboratories to establish target values. Survey materials were shipped by courier and results returned by paper copy, email or online. Immediate feedback reports included advice for addressing errors. Composite reports addressing participants’ performance were provided to national quality assurance offices. Results: Sixteen surveys were distributed between 2008 and 2015; enrolment increased from 195 to 560 facilities. Mean response rate remained static (56-59%), but overall number of participating facilities increased. Mean performance scores increased from 51% to 68% but remained below the accepted score of 80%; individual facilities achieving 80% or more increased from 0 to 25%. Facilities participating in 10 or more surveys performed better than facilities participating in 5 or less surveys. Conclusion: PT can be applied at peripheral level in resource-limited settings and identifies poorly performing areas. PT can also be used to assess performance of equipment and test kits as part of post-market surveillance. Smaller health facilities require additional support to address deficiencies

短期ジドブジン使用によるヒト免疫不全ウイルス母子感染予防の試み : ケニアの田舎において

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1603号, 学位授与年月日 : 平成15年6月30日, 学位授与大学 : 金沢大

A retrospective evaluation of proficiency testing, and rapid HIV test kits stock-outs among HTC facilities within Nairobi county

Background: Proficiency testing (PT) has been implemented as a form of External Quality Assurance (EQA) by the National HIV Reference Laboratory in Kenya since 2007 in order to monitor and improve on the quality of HIV testing and counselling HTC services.Objective: To compare concordance between National HIV Reference laboratory, and HIV testing and counseling (HTC) facilities.Design: A telephone survey was conducted to access consistencies in PT schemes. An independent EQA assessment questionnaire was developed and pretested on a randomly chosen sample of HTC facilities.Setting: HTC facilities selected from Client-initiated HTC and Provider initiated HTC facilities, within Nairobi County.Subjects: The HTC facilities were randomly selected (n = 45).Results: Inconsistencies and tremendous increase in non-participation in PT schemes. Gender χ² (5, N = 45) = 13.83; p= .017, experience using rapid test kits χ² (5, N =45) = 5.417; p = .020, and current facility ever participating in any PT scheme χ² (5, N = 45) = 15.38, p= .009, had significant effects in participation in PT schemes. Some facilities experienced test kits stock-outs most of the time (2.552 ≥ 3.777), while others sometimes (1.326 ≥ 2.551), t (43) =3.105; p= 0.003. However, there was no link between non participation in PT schemes and test kits stock-outs.Conclusion: The results generated by the study revealed inconsistencies in PT schemes and Test Kits stock-outs from 2012 up to May 2014. These findings will assist in the full adoption of HTC policy guidelines and ensure each and every HTC personnel participate in all PT quarters consistently. Challenges in forecasting, and quantification remains a major barrier to HTC supplies

Numerical simulation of heat recovery from asphalt pavement in Finnish climate conditions

A 3-dimensional mathematical model of asphalt pavement system was developed, based on the fundamental energy balance, to calculate temperatures beneath asphalt surface using hourly measured solar radiation, air temperature and wind velocity data. The modelling was conducted to predict the heat retention under the asphalt surface to seek an optimum position of pipe tubing to maximise the heat extraction considering the Nordic winter conditions for future infrastructure projects. The model results show good agreement with the experimental results conducted in a span of three months (June–Sept) notwithstanding the simplification of the model i.e. thermal properties unaffected by changing moisture content, perfect contact between different layers and homogeneous and isotropic thermal properties of materials (asphalt, sand and gravel). The findings indicated that the positioning of the heat extraction tubes under the asphalt layer will be dictated by the application. For heat extraction, pipes closer to the surface are ideal for maximal heat absorption during summer, however, in winter the outer temperature may effect properties the pipes. Parameters including pipe diameter, positioning of the pipes and flow rate were analysed. Temperature increase of up to 10 °C gain was observed for piping closer to the asphalt layer and 6 °C for pipes position at deeper from the asphalt layer. This model could be used in future to optimise critical variables for successful implementation of asphalt heating concepts.© 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Drug resistance mutations among antiretroviral-treated female sex workers in Nairobi, Kenya

Antiretroviral drug resistance remains an important and a growing challenge in HIV management as it almost always lead to treatment failure. Sex workers face persistent exposures to the different HIV-1 variants and in turn pose a risk of transmission to the general population and measuring drug resistance in this population may serve as a measure for the risk of transmission of these strains to drug naïve populations. The objective of this study was therefore to determine the pattern and prevalence of HIV-1 drug resistance mutations in a cohort of female sex workers in Nairobi, Kenya. Plasma from 60 female sex workers on antiretroviral treatment for over six months was analyzed by amplification and sequencing of the reverse transcriptase - pol region. Five samples (8.3%) showed antiretroviral resistance-associated mutations. One sample (1.7%) showed mutations conferring resistance only to the NNRTI class, 2 samples (3.3%) showed mutations conferring resistance only to the NRTI class while 2 samples (3.3%) showed mutations conferring resistance to both NRTI and NNRTI classes. Phylogenetic analysis revealed HIV-1 subtype A1 (96.7%) and HIV-1 subtype D (3.3%). The prevalence rate of 8.3% for reverse transcriptase-associated resistance mutations was observed. This is a lower rate than has been reported from studies among antiretroviral (ARV)-treated individuals in the country.Afr J Health Sci. 2013; 26:291-30