SYNTHESIS OF β-D-RIBOPYRANOSIDES DERIVATIVES FROM β-D-XYLOPYRANOSIDE

The aim of this thesis was to synthesize various β-D-ribopyranoside derivatives with different C-4 functional groups, using D-xylose as the starting material. The desired modifications were deoxygenation, fluorination, methylation and epimerization of the C-4 hydroxyl group. Methylation provided the best results with the final product being successfully synthesized. Deoxygenation was also achieved but the final de-protection step was not carried out. Epimerization was attempted using two different methods but without success, firstly probably due to the high energetic favorability of having the hydroxyl group in the equatorial position, and secondly due to harsh reaction conditions causing the cleavage of the hydroxyl group. Fluorination was not attempted.INTAG AV TRÄSOCKER SKA FÖREBYGGA CANCER Cancer är den näst största orsaken till död i industriländer idag. Det görs för tillfället oerhörda ekonomiska satsningar där bl.a. Cancerfonden delade ut 385 miljoner kronor för forskning inom området år 2016. Ett forskningsområde som fått mycket uppmärksamhet på senare tid är användandet av det trädbundna sockret, D-xylos (också kallat ’träsocker’), som en källa till anti-cancermedel. Sockret visar bra potential, mycket tack vare dess biologiska betydelse i däggdjur samt dess tillgänglighet i naturen. I detta projekt har olika modifieringar av sockret syntetiserats för att man eventuellt ska kunna undersöka dem för potentiella anti-cancer egenskaper. I cellen av däggdjur fungerar xylos som en länk mellan en proteinkärna och en kedja av andra kolhydrater i proteoglykaner (se figur 1). Proteoglykaner är essentiella för en lång rad av biologiska processer och dess uttryck är förknippat med varje steg av cancer utveckling, vilka inkluderar bl.a. tumörinflytande och tumörmetastas. Biosyntesen av proteoglykan initieras vanligen av att det interna enzymet xylostransferas tillför en xylos molekyl till proteinkärnan. Detta följs av att andra enzymer bygger på med ytterligare kolhydrater tills en kolhydratskedja bildas. Biosyntesen kan dock också ske genom att låta en aglykon-bärande xylos molekyl, en så kallad xylosid, penetrera cellmembranet vilket kommer att initiera byggandet av kolhydratskedjan (aglykonen fungerar som ersättare för protein kärnan). Kolhydraterna som sedan kommer att göra upp kedjan beror på strukturen av aglykonen och man har tidigare lyckats selektivt inhibera tumörväxt med 97 % i råttor genom att använda xylosiden XylNap. I detta examensarbete har syntesvägen för analoger av XylNap studerats. Modifikationerna har fokuserat på hydroxylgrupperna tillhörande C3 och C4 och har inkluderat epimerisering, deoxygenering och metylering. Den syntetiska processen har verifierats av TLC (Thin Layer Chromatography), NMR (Nuclear Magnetic Resonance) och HRMS (High Resolution Mass Spectrometry). Examensarbete har gett en bra insikt till hur det går till när man tar ett råmaterial och transformerar det till en substans för användning inom läkemedelsindustrin. Arbetet har också medfört en fördjupad kunskap av organisk kolhydrat syntes. Med en hel del lyckade modifikationer har genomförbarheten av forskningen också påvisats och med den omfattande tillgängligheten av xylos kommer intresset av forskningsområdet troligtvis bara fortsätta stiga

The self-controlled case series method: performance and design in studies of vaccine safety

The self-controlled case series method (SCCSM) is a novel study design to investigate associations between acute responses with transient point exposures (for example vaccination). The method provides an attractive alternative to cohort and case-control designs. The method is unusual in that it requires data only on individuals who experience a response (the ‘cases’). The method works as follows. Prior to the study a post-exposure risk period is defined, which corresponds to the period in which responses causally related to exposure are likely to occur. An observation period is also defined, and individuals with responses arising within this observation period are sampled. The data are then analysed using a Poisson model, conditional on the total number of events occurring for each individual. This conditioning ensures that including only cases does not bias the relative risk estimator. The self-controlled case series method has been used to good effect in many settings, particularly in investigating putative associations between adverse events and paediatric vaccines. However, so far only limited research has been undertaken on the statistical properties of the method in finite samples, and virtually no work has been undertaken on design issues. The method also needs to be extended in various directions, for example application in surveillance methods. This thesis provides detailed investigations of these topics. To this end, expressions for the asymptotic bias, variance and mean square error of the log-relative incidence are derived. Simulation studies taking account of age are carried out to study small and medium sample performance. Sample size formulae are obtained and validated via simulations, thus improving the design of self-controlled case series studies. The method is extended to applications in surveillance and simulation studies are conducted to evaluate this use of the method. The methods are illustrated using data on intussusception and oral polio vaccine

Spatial implications of foreign direct investment (FDI) on infrastructure delivery: A case of the City of Lusaka, Zambia

The is a strong belief that FDI offers possibilities towards a development that has eluded developing countries for decades. It has become a predominant feature in development policy. The influence towards this orientation to development emanates from geopolitical dynamisms that have revolutionized global production systems at the hands of globalization. Innovations in urban economic development strategies concentrate on integrating local economies into the global market through the provision of infrastructure as the operative of global capital inflows. It is argued, however, that to exploit the full benefits of FDI, not only should the country attract the appropriate kind of investment, but its investment policy should be consistent in its interaction and engagements with the overall country's development policy regimes. Appropriateness in this argument entails that, with infrastructure identified as the primary requirement for attracting FDI, it is not only a question of being able to link the provision of infrastructure to attract investment but understanding the social-technical nature of infrastructure and its overall spatial manifestation as a function of urban form and structure. It is the spatial character underlying urban production systems, which development strategies such as FDI need to appropriately understand because it is at that interface were FDI-economic growth argument translate into economic development. Using a formulated conceptual framework based on Socio-Technical Systems (STS) theorization, the study assessed the spatial impacts of the FDI on infrastructure in the City of Lusaka in Zambia. It identified key institutions at the fulcrum of investment promotion and spatial development planning with a focus on planning and provision of network infrastructure. It also reviewed the main policies and legislation driving the FDI-led development agenda. The findings point out that national government priorities at significantly focused on the provision of infrastructure, however, on a very selective and narrow perspective. Infrastructure provision priority is in what is termed as 'economic infrastructure' argued to be the missing element in attracting FDI. What was also discovered, which in a way explains how infrastructure provision is narrowly considered, is a fragmented institutional framework resulting from inadequate legislation. The inadequacies lack of recognition of the spatial embeddedness of investment in the legislation resulting in disconnection between investment strategies formulation and spatial development planning. The overarching conclusion from the study is that to actualize the benefits of FDI substantially, the framework of regimes at the core of advancing the development goal driven by infrastructure, needs to understand the socio-technical nature of network infrastructure. A purely economic consideration of infrastructure as was discovered in the study, significantly limits FDI's contributive value to development

Challenges Affecting the Implementation of Teaching Practice: The Case of the University of Zambia

For many years, the process of training a teacher has been extensively studied and discussed in the scientific and academic community worldwide. However, very few studies have been conducted on teaching practice in the developing world, which include Zambia. Teaching practice affords student teachers an opportunity to translate theory into practice in a real classroom situation. This study investigated challenges that the University of Zambia faces in implementing teaching practice in schools. In addition, the study probed teacher educators, supervising teachers and student teachers’ views on measures that can be taken to improve the implementation of teaching practice in schools. The theoretical framework for this qualitative study was the third generation activity theory. The sample was purposely selected and comprised eight teacher educators, 10 supervising teachers and 24 student teachers. Semi-structured interviews and focus group discussions were used to collect data.  The data were analysed thematically. The study established that the whole process of teaching practice faced many challenges such as lack of collaboration between teacher educators and supervising teachers and limited learning space resulting in inadequate learning and peer teaching time. Most of the study’s findings are consistent with findings of earlier studies. This study is significant as it attempts to reduce the knowledge gap that appears to stem from a paucity of research on teaching practice in Zambia. One major recommendation is that School of Education should be separated from other schools. Keywords:           Activity theory, Challenges, Teacher education, Teaching practice, Theory-practice divide. DOI: 10.7176/JEP/12-27-14 Publication date:September 30th 202

Gatekeeping through music: a case of the Patriotic Front in Zambia

What can music used by politicians during campaigns tell us about their behaviour, character and their rule? The article responds to this question by analysing political songs used by Patriotic Front (PF) in Zambia, before winning the 2011 elections and the subsequent elections. This article argues that music can be an important unacknowledged tool for understanding the behaviour of political leaders, and in this case, their gatekeeping behaviour that aims at sustaining the ruling party in power by undermining the opposition.Was kann uns die von Politikern im Wahlkampf verwendete Musik über ihr Verhalten, ihren Charakter und ihre Herrschaft verraten? Der Artikel beantwortet diese Frage durch die Analyse politischer Lieder, die von der Patriotischen Front in Sambia vor dem Wahlsieg 2011 und bei den folgenden Wahlen verwendet wurden. In diesem Artikel wird argumentiert, dass Musik ein wichtiges, unerkanntes Instrument sein kann, um das Verhalten von politischen Führern zu verstehen, und in diesem Fall ihr Gatekeeping-Verhalten, das die regierende Partei an der Macht halten möchte, indem es die Opposition untergräbt

Construction public client health and safety culture in Botswana : a pilot study.

This paper presents the preliminary findings of an exploratory pilot study into the health and safety culture of a public sector client in Botswana with a view to identifying aspects to be included in a larger broad-based national survey

Teaching of Earth Geometry at Secondary School in Zambia

The study explores the challenges associated with teaching Earth Geometry in secondary schools.  Selected secondary schools of Mufulira District in Zambia were the focus of the study and a total of 21 Teachers and 97 pupils formed the sample population to whom questionnaires were administered. In addition, a 5-point Likert scale formed part of the research instrument used to investigate the phenomenon. The collected data was analysed using SPSS which allowed for simple frequency counts, percentages, means and analysis of variance. To further understand the phenomenon under study, data collected from the pupils by way of interviews and document reviews was analyzed using the QDA miner 4.0 version software. It was established that pupils faced the following challenges: computation of the shortest distance between points on the same latitude, distinguishing between knots and kilometres per hour, and distinguishing great circles and small circles. Keywords: learners, teachers, earth geometry, latitudes, knots and kilometer, circle

Effectiveness of economic incentives on clients’ participation in health and safety programmes

The use of economic incentives to improve health and safety (H&S) performance in the construction industry in general has been investigated by various scholars. However, few studies have looked at the impact of economic incentives on construction clients, especially in the developing world. This paper reports findings on the feasibility of incentives to influence construction clients to perform on H&S. The investigation was conducted using a Delphi technique to determine the impact significance of economic incentives or disincentives on construction clients’ H&S performance. A panel of experts in construction H&S was assembled from most regions of the world. A three- round iterative Delphi study aimed at establishing consensus from the expert panel was then conducted. The study found that economic factors have critical impact significance on clients’ H&S performance, and that clients were ‘very likely’ to implement various H&S elements as a result of the economic incentives and or disincentives. There is little research on the use of incentives to influence construction clients’ H&S performance and the effectiveness of such incentives. This gap in literature, and the need for improvement in construction H&S performance, motivated the current study. Therefore it was necessary to investigate specifically the extent to which economic incentives could be used to influence construction clients to become involved in H&S programmes. Economic incentives are considered to be a proactive way of improving H&S performance among other key parties, such as employees in the construction industry. The paper reports on the findings from an analysis of the impact significance of economic incentives on clients. It underscores the point that economic incentives or disincentives for construction clients are necessary to encourage them to actively participate in H&S programmes, hence resulting in performance improvement