Anti-apoptotic proteins and cholangiocarcinoma

Cholangiocarcinoma is refractory to treatment by chemotherapy and radiotherapy, which exert their effects on tumour cell growth mainly through the induction of apoptosis. The factors responsible for the poor response of this disease to the apoptosis inducing effect of chemotherapy and radiotherapy are unknown. Members of the Bcl-2 family of proteins play a central role as intracellular regulators of apoptosis. In vitro and in vivo studies have identified that in certain malignancies the expression by tumour cells of these mitochondrial targeting antiapoptotic proteins provide a survival advantage to these cells. The expression of these proteins by cancer cells may also reduce their response to cytotoxic therapy. The hypothesis of this thesis is that resistance to apoptosis may be one of the factors responsible for the poor response of cholangiocarcinoma to treatment, which may be a consequence of mitochondrial targeting antiapoptotic proteins. In the first section of the study, the expression of the antiapoptotic proteins Bcl-2, Mcl-l and BC1-XL was examined in 30 resected cases of cholangiocarcinoma, and 3 human cholangiocarcinoma cell lines using immunohistochemical and immunofluorescent techniques. In all the cholangiocarcinoma specimens examined, Mcl-l and BC1-XL proteins were co- expressed by the majority of the malignant cell population. Bcl-2 protein was not however detected in any of the specimens. This confirmed that antiapoptotic proteins are expressed by cholangiocarcinoma cells but provided no information on their biological effects. The second section analysed the kinetics of apoptosis in human cholangiocarcinoma cells after exposure to the therapeutic agents chemotherapy. X-ray and also UV irradiation to test the hypothesis that cholangiocarcinoma cells are resistant to cytotoxic therapy induced apoptosis. Human cholangiocarcinoma cell lines were incubated with various concentrations of chemotherapy drug or exposed to various doses of radiotherapy. The apoptotic responses were then monitored over a 96 hour period post treatment and then dose response graphs constucted. Cholangiocarcinoma cells were found to be resistant in vitro to chemotherapy and radiotherapy induced apoptosis. Finally, Pklll95 and diamide, drugs which target the mitochondria and functionally counteract antiapoptotic Bcl-2 proteins, were used to test the hypothesis that the inhibition of antiapoptotic proteins can increase the sensivity of cholangiocarcinoma cells to therapy. Experiments were carried out both in vitro and in vivo (xenografts on SCID/NOD mice). This study confirmed that in the presence of the Bcl-2 antagonists cholangiocarcinoma cell apoptosis was increased following chemotherapy and radiotherapy. This demonstrates for the first time an association between the expression of antiapoptotic proteins BC1-XL and Mcl-l and the susceptibility of cholangiocarcinoma cells to apoptosis. The work contained in this thesis demonstrates that human cholangiocarcinoma cells express the antiapoptotic proteins Mcl-l and BC1-XL and are resistant to chemotherapy and radiotherapy induced apoptosis. Antagonising the function of these proteins increases the sensitivity to both chemotherapy and radiotherapy in both cell cultures and an animal model. Inhibitors of the antiapoptotic proteins should be further investigated for their use in conjunction with conventional cytotoxic therapy for the treatment of CCA and may be of value in the treatment of other cancers

An integrated model for asset reliability, risk and production efficiency management in subsea oil and gas operations

PhD ThesisThe global demand for energy has been predicted to rise by 56% between 2010 and 2040 due to industrialization and population growth. This continuous rise in energy demand has consequently prompted oil and gas firms to shift activities from onshore oil fields to tougher terrains such as shallow, deep, ultra-deep and arctic fields. Operations in these domains often require deployment of unconventional subsea assets and technology. Subsea assets when installed offshore are super-bombarded by marine elements and human factors which increase the risk of failure. Whilst many risk standards, asset integrity and reliability analysis models have been suggested by many previous researchers, there is a gap on the capability of predictive reliability models to simultaneously address the impact of corrosion inducing elements such as temperature, pressure, pH corrosion on material wear-out and failure. There is also a gap in the methodology for evaluation of capital expenditure, human factor risk elements and use of historical data to evaluate risk. This thesis aims to contribute original knowledge to help improve production assurance by developing an integrated model which addresses pump-pipe capital expenditure, asset risk and reliability in subsea systems. The key contributions of this research is the development of a practical model which links four sub-models on reliability analysis, asset capital cost, event risk severity analysis and subsea risk management implementation. Firstly, an accelerated reliability analysis model was developed by incorporating a corrosion covariate stress on Weibull model of OREDA data. This was applied on a subsea compression system to predict failure times. A second methodology was developed by enhancing Hubbert oil production forecast model, and using nodal analysis for asset capital cost analysis of a pump-pipe system and optimal selection of best option based on physical parameters such as pipeline diameter, power needs, pressure drop and velocity of fluid. Thirdly, a risk evaluation method based on the mathematical determinant of historical event magnitude, frequency and influencing factors was developed for estimating the severity of risk in a system. Finally, a survey is conducted on subsea engineers and the results along with the previous models were developed into an integrated assurance model for ensuring asset reliability and risk management in subsea operations. A guide is provided for subsea asset management with due consideration to both technical and operational perspectives. The operational requirements of a subsea system can be measured, analysed and improved using the mix of mathematical, computational, stochastic and logical frameworks recommended in this work

The effects of menopause on the serum lipid profile of normal females of South East Nigeria

Dyslipidemia in menopause is a known feature in women, whether it leads to significant increase in the development of coronary heart disease (CHD) is still controversial, more so in our environment where little work has been done. The present study is aimed at comparing the level of total serum cholesterol, including its subunits in premenopausal with that of their postmenopausal counterparts. This is to enable us ascertain the relative risk of developing cardiovascular disease in postmenopausal women in our environment. One hundred and twenty six (126) apparently healthy, nonpregnant females (74 premenopausal and 52 postmenopausal) were recruited for the study. Serum total cholesterol and their subfractions- high-density lipoproteins (HDL), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and triglycerides (TG) were estimated using enzymatic and established mathematical methods. There was no significant difference in the total serum cholesterol and triglyceride between the two groups. There was however, a significant reduction of HDL and VLDL in the postmenopausal group (

Drivers of Audit Failure in Nigeria- Evidence from Cadbury (Nigeria) PLC.

This study is an investigation of audit failure factors in Nigeria’s corporate governance firmament. An explanatory case study approach was adopted for the study supplemented by archival data and newspaper reports. An explanation was sought for the findings of the regulatory authority that the auditor in this case was not only negligent and incompetent but also did not demonstrate sufficient Professional skepticism. One of our findings is the fact that the auditors may have stayed for too long on the job and had thus impaired their independence. Provision of non- accounting services to this particular audit client was also fingered as a cause of the audit failure. We recommend mandatory rotation of auditors and prohibition of provision of non- audit services to audit clients among others. One limitation, though, of our study is that it is a single case study and may not be generalised. KEY WORDS: Audit Failure, Cadbury (Nig.) Plc, Professional Skepticism, Negligence

Prediction of Bank Failure Using Camel and Market Information: Comparative Appraisal of Some Selected Banks in Nigeria.

This paper attempted to predict bank failure using CAMEL and stock market information. The study reviewed journal, seminal papers, articles, websites and banks’ annual financial statement. The study covered five accounting years between 2006 and 2010. Multiple discriminant model was used to predict bank failure and the status of Nigerian banks. It was discovered that almost all the banks used for the study had their Z score fall within bankruptcy region. An attempt was further made to thoroughly evaluate managerial quality because experience has shown that bank failure in Nigeria was largely due to managerial inefficiency . Managerial quality were evaluated using variable such as total loan to total deposit, interest expenses to total deposit and operating expenses to total deposit. We concluded that bank failure is as a result of  poor CAMEL rating as well as excessive risk taking and the end results are credit crunch, unemployment, illiquidity etc . we suggested that the only way to contain bank failure is by ensuring regular and transparent on site and off site examination by CBN and NDIC. Keywords: bank failure, CAMEL, stock market informatio

Fair Value Accounting and Loan Loss Provisioning- Early Evidence from Nigerian Banking Industry

The purpose of this study is to investigate the Loan Loss Provisioning under International Financial Reporting Standards (IFRS) and Nigerian Prudential Guidelines. The audited first time annual reports of four Nigerian banks were analysed.  Simple percentages and tables were used to determine the relationships between the figures thrown out by the two provisioning models. We found that prudential guidelines provisions were more aggressive and higher in all cases than IFRS provisions. In other words, the profit figures under prudential guideline model were more conservative than the corresponding figures under the IFRS model. The result of the study was based on 1 year 2012 audited first time IFRS accounts of 4 Nigerian banks and therefore cannot be generalised but regarded as rather indicative of the differences between the two models. The paper has practical implications for Nigerian regulatory authorities and in particular the CBN who may wish to retain its Loan Loss Provisioning Model or transmute to the IFRS model. This is about the first study on Nigerian banks on this subject matter post mandatory adoption of IFRS in 2012 and, has added to our knowledge of IFRS Loan Loss Provisioning compared to the Nigerian Prudential guideline model. Key Words: IFRS, Fair value, Prudential Guidelines, Loan Loss, Early Evidence

Environmental Cost Accounting and Cost Allocation (a Study of Selected Manufacturing Companies in Nigeria)

The major objective of this paper is to determine the extent to which Nigerian firms have embraced environmental cost accounting in cost allocation.  This research adopted a research survey and the main research instrument is the questionnaire. 105 Accountants from twenty-five (25) quoted manufacturing companies were the respondents for this research. The mean, standard deviation and simple percentages were used to analyze the questions while the ANOVA was used to statistically analyze the differences between means. Findings show that majority of the firms have not embraced environmental cost accounting, they still lump all indirect costs under overhead and use mostly, one absorption method which may not have any relationship with the indirect costs to apportion these costs into the product costs. The identified commonest method of overhead allocation basis is the material use. Although the treatments given to environmental costs were conventional in nature, significant differences exist among firms on the method of allocating environmental costs to products/processes. Environmental accounting can be said to be in embryonic stage in the manufacturing firms in Nigeria. This paper offers a valuable insight into the environmental cost accounting practices of Nigerian manufacturing firms. This paper will help firms to understand what environmental cost accounting is all about and how to embrace it. Keywords: Environmental accounting, Environmental cost accounting, environmental costs, conventional system

Reliability analysis and optimisation of subsea compression system facing operational covariate stresses

This paper proposes an enhanced Weibull-Corrosion Covariate model for reliability assessment of a system facing operational stresses. The newly developed model is applied to a Subsea Gas Compression System planned for offshore West Africa to predict its reliability index. System technical failure was modelled by developing a Weibull failure model incorporating a physically tested corrosion profile as stress in order to quantify the survival rate of the system under additional operational covariates including marine pH, temperature and pressure. Using Reliability Block Diagrams and enhanced Fusell-Vesely formulations, the whole system was systematically decomposed to sub-systems to analyse the criticality of each component and optimise them. Human reliability was addressed using an enhanced barrier weighting method. A rapid degradation curve is obtained on a subsea system relative to the base case subjected to a time-dependent corrosion stress factor. It reveals that subsea system components failed faster than their Mean time to failure specifications from Offshore Reliability Database as a result of cumulative marine stresses exertion. The case study demonstrated that the reliability of a subsea system can be systematically optimised by modelling the system under higher technical and organisational stresses, prioritising the critical sub-systems and making befitting provisions for redundancy and tolerances

Monetary Policy and Capital Market Performance: An Empirical Evidence from Nigerian Data

This study utilized time series data to determine the effect of monetary policy on the performance of Nigerian capital market. The study was motivated by the inconclusive debate on the real effect of monetary policy on capital market performance. Specifically, this study ascertained the effect of monetary policy rate and cash reserve ratio on the performance of Nigerian capital market surrogated by all share index. Secondary data for the period 1986 to 2016 were collected from the Nigerian Stock Exchange and Central Bank of Nigeria annual reports of various editions. The study applied the Ordinary Least Square (OLS) regression technique and causality analysis in which variations in all share index was regressed on monetary policy rate and cash reserve ratio. The analysis revealed that monetary policy tools have no significant effect on capital market performance. The monetary policy rate has negative significant relationship with capital market performance while cash reserve ratio positively relates with performance of the capital market. Considering the findings emanating from this study, the Central Bank of Nigeria should reduce the current double digit monetary policy to a single digit to attract investments in the capital market. Cash reserve ratio which is currently at 22.5% be lowered to the range: 10%-12% to cause an upsurge in money supply which will in turn improve capital market performance through upward movement in all share index

Effect of Liquidity on Performance of Deposit Money Banks

The study examines the effect of liquidity management on the performance of DMBs in Nigeria. The objective of the study is to determine the extent of relationship that exists between liquidity mechanism and DMBs performance in Nigeria from 2000 to 2015. The study employs Augmented Dickey Fuller Unit Root Test, OLS regression and Granger Causality. The result of the study revealed that liquidity mechanism is not significantly related to DMBs performance in the short run and long run. The granger result proves that liquidity mechanism hinder DMBs performance within the period under review in the study. Hence, the study recommends that DMBs should be given leverage of plugging back funds into investment to booster profitability while maintaining a level of liquidity ratio. Keywords: DMBs, Liquidity, Banks Performanc