As obligatory intracellular parasites, viruses are in a constant battle with their host to establish infection. They can facilitate their propagation by modulating host immune or metabolic pathways. This modulation involves targeting various molecular factors such as microRNAs (miRNA), enzymes, or small molecules. Understanding how viruses alter the chemical makeup of a cell is crucial to identifying what pathways are being targeted, furthering our understanding of the virus life cycle, and may aid in identifying biomarkers of disease. Here, we examine host-virus interactions in the context of two viruses, hepatitis c virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First, the modulation of serine hydrolases by a pro-viral microRNA, miRNA-122, is investigated using activity-based protein profiling (ABPP). This study identifies a downstream target of miRNA-122 that is differentially activated during HCV infection which can be targeted pharmacologically to reduce HCV infectivity. Second, we apply similar techniques to identify serine hydrolase changes associated with SARS-CoV-2 infection. Results point towards enrichment of endocannabinoid metabolism which may offer an alternative therapeutic avenue for combating SARS-CoV-2 infection. Together, the work presented in this thesis provides avenues for further investigation into miRNA-122 interactions during HCV infection and endocannabinoid metabolism in SARS-CoV-2 infection.

This dissertation investigates two broad management accounting questions in the context of electric utility industry: How do regulators for electricity industry use the information generated from accounting systems to make pricing decisions? What are the economic consequences of these decisions? In Chapter 2, I review regulatory reforms and discuss existing issues of using DEA models for efficiency benchmarking in four aspects. Suggestions are given for improving the use of DEA models based on the review and discussion. In Chapter 3, I empirically investigate the effect of incentive regulation with DEA benchmarking on operational efficiency using a panel of electricity distribution firms in Brazil. In Chapter 4, I examine the effect of restructuring and retail competition on cost reduction using a sample of US investor-owned electric utilities. The effects of privatization, industrial restructuring, incentive regulation and benchmarking are effectively disentangled from one another using the research setting in Brazil and US electricity industry. In Chapter 5, I combine the idea of activity based costing and data envelopment analysis to further develop a detailed benchmarking model for incentive regulation. / Business Administration/Accounting

The serine hydrolase (SH) enzyme superfamily is one of the largest and most diverse enzyme classes in eukaryotes and prokaryotes. The most virulent human malaria parasite Plasmodium falciparum has over 40 predicted serine hydrolases (SH). Prior investigation on a few of these have suggested their critical role in parasite biology. The majority of the SHs in P. falciparum have not been functionally characterized. Investigation of these uncharacterized SHs will provide new insights into essential features of parasite metabolism and possibly lead to new antimalarial targets. In this study, we have employed activity-based protein profiling (ABPP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to functionally characterize SHs. In our effort to profile plasmodial SHs using ABPP, we have identified a human erythrocyte SH, acylpeptide hydrolase (APEH) in the developing parasites. This finding is the first report of internalization of host hydrolytic enzyme by the parasite. Treatment of parasites with an APEH specific triazole urea inhibitor, AA74-1, caused growth inhibition in parasites with poor potency in the first replication cycle, however, the potency dramatically increased in the second cycle. We show that this unique growth inhibition profile is due to the inability of AA74-1 to inhibit parasite-internalized APEH in vivo. These findings suggest that internalization of active APEH by the parasite is essential for parasite survival. Lipases catalyze the hydrolysis of ester bonds of lipid species such as neutral lipids and phospholipids. Although roles of lipases in propagation, as well as virulence in various organisms, have been acknowledged, in P. falciparum lipases remain understudied. We combined LC-MS/MS with the SH-directed ABPP to identify lipases of SH superfamily in P. falciparum. We have identified 16 plasmodial SHs with putative lipase activity. Bioinformatics analysis of our identified lipases is consistent with our findings. We have screened a panel of various classes of SH inhibitors in a competitive ABPP. A plasmodial putative lipase was potently and specifically inhibited by human monoacylglycerol lipase inhibitor. This inhibition profile suggests it as a monoacylglycerol lipase which plays a role in releasing fatty acids from neutral lipid. This finding shows that how inhibitor screening can aid in building hypotheses on biological roles of an enzyme. Altogether, in this dissertation, we have presented a robust strategy of identifying and functionally characterizing SHs in P. falciparum, which opens the door to the discovery of new biological processes. / Doctor of Philosophy / Malaria contributed to nearly a half a million deaths in 2017. The vast majority of malaria-related deaths are due to the parasite Plasmodium falciparum. This parasite resides inside human red blood cells (erythrocytes) and grows rapidly during a 48 hour cycle. There are over 40 serine hydrolase (SH) superfamily proteins in the parasite. Biological functions of the majority of SHs in the parasite remains unknown. Study on these SHs will provide new insights into parasite biology, and possibly present new antimalarial drug targets. We used chemical biology techniques to identify and functionally characterize parasite SHs. In one study, we show the parasite intenalized a human erythrocyte SH, acylpeptide hydrolase (APEH). We used an APEH-specific inhibitor to investigate the biological significance of internalized APEH in parasite biology. Treatment of the parasite with the inhibitor resulted in parasite growth inhibition suggesting internalization of APEH is essential for parasite survival. Lipases are enzymes that aid in break down of lipids and have shown to be crucial for growth and pathogenicity in various organisms. Lipases and lipid catabolism remain understudied in the malaria parasite. We used mass spectrometry in our approach to identify 16 lipases in asexual parasites. We have also shown that screening with highly specific inhibitors can help in predicting biological function of a particular enzyme. In summary, in this body of work, we have presented an approach of studying SHs in the malaria parasite, which will provide new insights into parasite biology.

The Water Trading Entity (WTE) is a subdivision of the Department of Water and Sanitation responsible for water infrastructure and resource management. Despite ABC implementation at the WTE, the water resource management charge remains high, raising concern. This study aimed to establish what influence ABC implementation has on this charge. Through semi-structured interviews, the study found that the steps and factors generally associated with successful ABC implementation are partially followed, but undefined duplicated activities exist, due to insufficient training and limited technology. The study found that ABC implementation has minimal influence on the increase of the charge. When deciding on the charge, factors such as capping play a role, therefore limiting ABC use. Further research on ABC implementation in government departments can be conducted to ascertain how they can adhere to policies without compromising the use of ABC and identify the skills and training needs for an effective ABC implementation / Management Accounting / M.A. (Accounting Sciences)

Abstracts in English, Xhosa and Afrikaans / The South African Social Security Agency (SASSA) is the mechanism that enables service delivery to alleviate poverty in South Africa through the payment of social grants as mandated by the Social Security Agency Act No. 9 of 2004. The rapid increase of social grant beneficiaries in the past decade, fuelled by social inequality, directly affects the administration cost associated with social grants. This study aimed to investigate the allocation of indirect costs related to the administrative elements that makes it possible for SASSA to pay social grants. Semi-structured interviews were conducted; the study concluded that ABC (activity-based costing) could be implemented as an alternative to the traditional costing (TC) method on a pilot project basis. The study also recommended a framework for SASSA to consider in laying the foundation to start the process of ABC implementation. Drawing from the research conducted, further studies on the implementation of ABC principles within the public sector could be pursued. / Ejensi ya Vuhlayiseki bya Vanhu ya Afrika Dzonga ku nga South African Social Security Agency (SASSA) i ndlela leyi endlaka leswaku mphakelo wa vukorhokeri wu koteka ku hunguta vusweti eAfrika Dzonga hikwalaho ka ku hakeriwa ka timalimpfuneto ta vanhu (social grants) tanihileswi swi pfumeleriweke hi Nawu wa Social Security Agency Act 9 wa 2004. Ku ndlandlamuka ka vavuyeriwa va malimpfuneto ya vanhu swi khumbha hi ku kongomisa tihakelo ta vulawuri leti fambelanaka na timalimpfuneto ta vanhu. Dyondzo leyi yi kongomisiwile eka ku lavisisa mphakelo wa tihakelo to ka ti nga kongomisi leti fambelanaka na swiyenge swa vulawuri leswi endlaka leswaku SASSA yi kota ku hakela timalimpfuneto ta vanhu. Ku endliwe ti-semi-structured interview. Dyondzo yi kumile leswo ti-activity-based costing (ABC) ti nga tirhisiwa hi ndlela yo cincana na maendlelo ya vupimahakelo bya ntolovelo eka projeke ya nkarhinyana. Dyondzo yi bumabumerile leswaku ku anakanyiwa rimba ro nyika mianakanyo yo sungula maendlelo yo tirhisa ABC. / Die “South African Social Security Agency” (SASSA) verlig armoede in Suid-Afrika deur ingevolge die “Social Security Agency Act” 9 van 2004 sosiale toelaes te betaal. Die aansienlike toename in die aantal begunstigdes het ʼn uitwerking op die administrasiekoste van sosiale toelaes. Hierdie studie ondersoek die toewysing van indirekte koste ten opsigte van die administratiewe elemente wat SASSA in staat stel om sosiale toelaes te betaal. Halfgestruktureerde onderhoude is gevoer. In hierdie studie word tot die gevolgtrekking gekom dat aktiwiteitsgebaseerde kosteberekening (ABK) as ʼn alternatief vir en as ʼn proefprojek die tradisionele kosteberamingsmetode geïmplementeer kan word. ʼn Raamwerk word aanbeveel wat as ʼn grondslag kan dien vir die implementering van ABK. / College of Accounting Sciences / M. Phil. (Accounting Sciences)

Measuring the success of Activity Based Costing (ABC) is part of a more general challenge of measuring the success of any major change in managerial methods. The past thirteen years have seen accelerated rates of change in the South African Post Office (SAPO). However little is known about `'Measuring the successful implementation of ABC in (SAPO)''. The objectives of this study is to research the perceptions of staff regarding the successful implementation of ABC, the benefits of ABC implementation and the conditions that affect the potential benefits from the successful implementation of ABC. This will allow organisations and provide them with relevant information that will enable them to make better decisions with regard to measuring the successful implementation of ABC. To achieve these objectives a questionnaire was prepared and handed out to the finance staff of the SAPO. They were asked to respond to the questionnaire on their experience and their perceptions on the implementation of ABC. 121 questionnaire were returned generating a 38% response rate. The findings in this study highlighted that top management fails in giving active support to the implementation of ABC and the technical factors were perceived as standing in the way of the successful implementation of ABC. These were training, the high cost of implementing ABC, the lack of software packages, the lack of data requirements and co-operation between departments. From the finding the recommendation was made were general strategies were suggested for the SAPO for measuring the successful implementation of ABC. / Business Management / M.Tech. (Business Administration)

Financail Accounting / D.Com. (Applied Accountancy)

諸多業界與管會研究者深深感覺因為經營及製造環境產生重大丕變，使得傳統成本管理系統已無法滿足企業經理人為提昇企業本身競爭力所需的資訊。因此，學者針對資訊的產生要素（原始資料及制度方法）加以探討及研究，結果發現以作業為基礎所建立的成本管理系統能明確指出企業資源耗用情況，此即近年來廣受重視的作業基礎成本及管理制度（Activity-Based Costing and Activity-Based Management，簡稱ABC及ABM）。 　　ABC及ABM已廣為討論及運用，惟大多以國外企業為主，我國企業正面臨轉型期，也逐漸重視此等成本管理新技術，但運用此等技術者多為外商企業，本土產業仍停留在觀念導入及模擬階段，故基於他山之石，可以攻錯之理念，本論文以個案研究的方式探討ABC及ABM於國內本土產業規劃、設計及實施之情況，俾供未來國內之學術及實務界人士推動ABC及ABM之參考。 　　本論文以五個構面為探討主題： 　　構面一、作業基礎成本及管理制度之發展（此屬理論部份）； 　　構面二、如何規劃及設計作業基礎成本及管理制度，並與實務相互比較； 　　構面三、實務上實施作業基礎成本及管理制度之步驟及程序； 　　構面四、組織文化、組織變革、及實施作業基礎成本及管理制度之相互關係； 　　構面五、活用作業基礎成本資訊。 　　經由實地個案研究所獲得之結論為： 　　一、實務上基於行業特性及企業本身需求之緣故，於規劃、設計、及實施作業基礎成本及管理制度時宜作適度的修正。 　　二、因目前個案公司之實際需求，故以作業時間為代理動因，俾計算作業或產品之真實成本。 　　三、作業基礎成本資訊與傳統制度成本資訊比較的結果顯示，相對而言，產品成本的高低估範圍從高估64%到低估616%，其中以低估的程度較大，然而，促使產品成本高低估的影響因素眾多，如印刷紙質、紙張磅數、印量、著墨量、印刷開式、印刷色數等，且各因素間亦相互影響，導致目前不易解釋根本原因。 　　四、運用資訊系統將作業基礎成本資訊加以整合並依所需表格化，可明確提供有關產品成本、作業成本、附加價值活動與無附加價值活動、及生產績效等有用之資訊，協助個案公司不同層級之主管了解公司資源使用的情況，俾於進行作業管理、企業策咯等活動時作為參考之依據。 　　五、由於個案公司的組織文化較能接受新觀念及管理技術，使得在沒有外部支援的情況下，由公司自行規劃、設計、及實施作業基礎成本及管理制度，筆者於研究末期親訪相關人員後，發現個案公司的企業文化稍有改變（如生產現場人員逐漸認為填寫工作報表為本身責任），而高階主管也愈趨重視攸關的管理技術之重要性，引發個案公司從事改善企業的活動等。

Strategic cost management is in its infancy. Researches and studies are still in an early exploratory stage and have not yet developed a consistent theory for strategic cost management. The thesis presents a comprehensive framework for strategic cost management. In particular the study attempts to contribute to filling the gap in the literature of strategic cost management. The suggested framework covers the concept, the objectives, the principles, the analysis fields & activities, the objects, the instruments and the key supports factors of strategic cost management to meet different challenges that the companies encounter from time to time and at different stages of development.

Made available in DSpace on 2010-04-20T20:15:09Z (GMT). No. of bitstreams: 0 Previous issue date: 1998-03-24T00:00:00Z / O trabalho apresenta uma evolução dos sistemas gerenciais de custos. Analisa as principais mudanças que estão ocorrendo no ambiente competitivo e seus reflexos na deterioração da qualidade das informações de custos dos sistemas gerenciais. Discute conceitos relacionados ao custeiobaseado em atividades (ABC) e à gestão-baseada em atividades (ABM), que podem constituir-se em instrumentos para melhoria dessas informações. Realiza ainda um estudo exploratório sobre o estágio de utilização desses conceitos em empresas situadas no Brasil, com base na experiência de empresas de consultoria que implementam esses projetos nos mais diversos setores da economia.