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

A Cognitive Analysis of the Igbo Morpheme 'Na'

In the literature on Igbo grammar, the prevailing idea is that the function of the morpheme na depends on its structural position in a syntactic construction. Therefore, the structure of the clause determines the various meanings and functions assigned to na in Igbo grammar. This paper argues that na has one consistent function in Igbo, which is rather cohesive: it functions as a grounding element in all the positions it occurs in the syntax of the language. This grounding function is explored within the Cognitive Grammar framework which proposes the systematic analysis of language within the milieu of universal human cognitive abilities. For Cognitive Grammar, the meaning of a word is not independent of the common traditions (socio-cultural beliefs included) of the users of the language in which it occurs. The study concludes that na functions to ground; (1) subjects to their locations, (2) subjects to their source or goal, (3) the verb in the complement, and (4) a subject to a state or condition

Market impacts and global implications of U.S. shale development and hydraulic fracturing: an economic, engineering, and environmental perspective

Thesis (Ph.D.) University of Alaska Fairbanks, 2018The United States oil industry is experiencing a revolution because of significant oil production from tight oil plays since the mid-2000s. Advancements in horizontal well drilling and hydraulic fracturing are powering this new chapter in oil development. Increased oil production has brought billions of dollars of new revenue to oil companies involved in tight oil exploration and production, new jobs in the oil industry, and more tax revenue to oil regions around the U.S. However, tight oil resources do not only exist in the U.S. An understanding of the U.S. tight oil development experience could bring value to stakeholders within and outside the United States, and provide lessons and templates applicable in other tight oil regions. This research examines the U.S. tight oil experience and draws lessons for aspiring tight oil regions on the engineering, economic, and environmental fronts. On the economic front, I have examined an autoregressive distributed lag (ARDL) model on key oil industry macroeconomic data (West Texas Intermediate oil price, tight oil production, and rig count) from 2007 through 2016, and the impact of oil price on tight oil development for the Bakken, Eagle Ford, Niobrara, and Permian tight oil plays. The results show that oil companies in different plays react differently to oil price signals and do so in relation to oil field development characteristics. In addition, oil production and drilling intensity in the Eagle Ford play is found to be most responsive to oil price increases than the Permian, Bakken, or Niobrara oil plays. The Permian play was most resilient during the 2014 through 2016 oil price plunge. Oil production does not fall in response to a decrease in oil price, equally as it rises in response to oil price increase. Tight oil operators are quicker in bringing drilling rigs to service as prices rise than they take them away in response to falling oil prices, but do reduce drilling significantly in response to an oil price plunge. These results have significant ramifications for operators and assets in the respective oil plays or future plays with similar development characteristics. On the engineering front, I used petroleum engineering oil production forecasting Decline Curve Analysis techniques, the Drillinginfo Software, and historical development data of U.S. plays, to conduct oil production forecast for seven U.S. tight oil plays. Forecast results are shown to be comparable to forecasts by the Energy Information Administration (EIA). Building on previous EIA geologic studies on non-U.S. tight oil plays, and by selecting best analogues from within U.S. tight oil plays, I have completed an economic assessment and uncertainty analysis for 10 non-U.S. tight plays using a simple fiscal tax regime. The results indicate that the Eagle Ford play in Mexico, the Vaca Muerta play in Argentina, and the Qingshankou play in China rank highest among the plays studied. Of oil price, royalty rate, discount rate, well cost, extraction tax, and recovery factor parameters evaluated, results indicate that oil price and well cost are among the biggest drivers of profitability in these plays. On the environmental front, I conducted case studies on the busiest U.S. tight oil plays (Bakken and Eagle Ford) and examined the impact of tight oil development on the environment. Local solutions to environmental challenges alongside environmental regulations are discussed and presented as possible templates for other aspiring plays. Since securing freshwater sources alongside wastewater management emerge as major issues in tight oil development, a cost comparison is conducted for reused water disposal versus one-use water disposal options, for a hypothetical development. Results indicate that on a cost-per-well basis, the reduction in water disposal volume from subsurface frack flowback retention improves water reuse economics; the water reuse option is preferable to one-use water disposal for U.S. oil plays. This result points to potential cost savings for reused water disposal in regions such as the Bakken with few disposal wells

Health System Analysis of Diabetes and Diabetic Retinopathy Services in Nigeria – The Case of Akwa Ibom State

This research project, undertaken for a MPH dissertation investigated and analysed the situation of diabetes and diabetic retinopathy services and management systems in four (4) government hospitals in Akwa Ibom State Nigeria using the World Health Organisation (WHO) Tool for the Assessment of Diabetic Retinopathy and Diabetes Management Systems (TADDS). Part A is the research protocol, which explains the background and the key components of this research study. This is a cross sectional descriptive case study involving primary data collection. We conducted the case study using the WHO TADDS to survey health personnel involved in the management of diabetes mellitus (DM) and diabetic retinopathy (DR) in four (4) government hospitals in Akwa Ibom State. Concurrently, semi-structured interviews were conducted with key informants to investigate and analyse the situation of DM and DR services in Akwa Ibom State in Nigeria. Part B is a structured literature review of published articles, online reports, and summaries related to DR. It covers the review of scientific evidence (clinical overview) about the aetiology and prevention of DR and the known risk factors; the review of epidemiological evidence on DM and DR globally and in sub-Saharan Africa (SSA); and the review of the evidence on effectiveness and cost-effectiveness of public health and health system interventions for the prevention and management of DR. Part C is the journal-ready manuscript. In this part, the format of the journal Ophthalmic Epidemiology was used to present the research project and its main findings. Part D contains all the relevant appendices used during the research project

Evaluation of Extension Agents’ Communication Strategies in Promoting the New Rice for Africa Technology Among Rice Farmers in Ofada, Ogun State, Nigeria

This study focused on evaluating the effectiveness of extension agents’ communication strategies in promoting the New Rice for Africa Technology among farmers in Ofada, Ogun State, Nigeria. Hinged on the Diffusion of Innovations Theory, the study adopted the survey research design using structured questionnaire and focused group discussion sessions to elicit data from extension workers and rice farmers respectively. Findings from the study revealed that extension agents employed communication strategies such as one-to-one, group gatherings, radio jingles, short sms, and video demonstrations among others to promote NERICA among rice farmers in Ofada. It was also gathered that these communication strategies were effective in passing across required information however; the farmers prefer the one-to-one than the group gathering communication strategy which was more often used by the extension workers. This preference was premised on the inherent advantage of interactivity which the adoption of the one-to-one technique could provide. In the light of these findings, it was recommended that, more needed to be done by the extension agents and the government to ensure adoption of NERICA technology. With the right seedlings, good preservation techniques, and other backup supports such as availability of pesticides, herbicides and fertilizers, adopting NERICA technology would be easier for farmers. The study recommended use of the one-to-one communication strategy and periodic evaluation of the extension worker’s activities by government. Keywords: Communication; Communication Strategies; Agricultural Extension Agents, NERICA, Rice Farmers DOI: 10.7176/DCS/9-6-06 Publication date:June 30th 201

The morpho-syntactic coding of motion events in Igbò

The phenomenon of motion events is universal in human cognition and language. These events are coded in the verbal structure of human language. This work builds on the past study of Igbo motion verbs and seeks to investigate the interaction between morphology, syntax and semantics in the description of Igbo motion events. Igbo verbal morphosyntax codes four categories of motion events. The first category, which includes verbs like báá ‘enter’ and láá ‘go home / go to destination’, code the figure, path and ground in the motion event. The second category includes verbs like zọ̀ ‘transplant’ and kwá ‘push’ which code figure and ground in the motion event. The third category contains verbs like fé éfé ‘flying’ and gbé ígbé ‘crawling’ which code figure and manner in the event. The last category consists of verbs like ná áñà ‘wobble’ and sọ́ gọ̀nọ̀ gọ̀nọ̀ ‘stagger’ which code figure, manner and cause. The study concludes that motion events in Igbo are coded morphologically. This conclusion is foundational for further investigation of the core components of motion events in Igbo that is, path and manner. In other words, it is the groundwork of the contribution of Igbo to the study of the cross-linguistic phenomenon of motion events.L’expression du mouvement est un phénomène universel tant sur le plan cognitif que linguistique. Dans les langues humaines, c’est au niveau du verbe que le mouvement est généralement exprimé. Tout en prenant en compte les travaux déjà consacrés à l’étude des verbes de mouvement en ibo, la présente étude cherche à approfondir la question des interactions entre la morphologie, la syntaxe et la sémantique dans le domaine de l’expression du mouvement en ibo. D’un point de vue morphosyntaxique, en effet, la langue ibo distingue quatre types de verbes de mouvement. Le premier type, qui comprend des verbes tels que báá ‘entrer’ et láá ‘retourner chez soi / se rendre à une destination donnée’, exprime les éléments constituants du mouvement que sont la figure, la trajectoire et le fond. Le second type, auquel se rattachent des verbes tels que zọ̀ ‘repiquer’ et kwá ‘pousser’ permet l’expression des éléments figure et fond. Dans le troisième type, où l’on trouve par exemple les verbes fé éfé ‘voler (dans les airs)’ et gbé ígbé ‘marcher à quatre pattes’ ce sont la figure et la manière du mouvement qui sont exprimés. Enfin, le quatrième et dernier type regroupe des items tels que ñá àñà ‘trembl(ot)er’ et sọ́ gọ̀nọ̀ gọ̀nọ̀ ‘tituber’ qui expriment à la fois la figure, la manière et la cause du mouvement considéré. Les résultats de cette étude tendent à montrer que, en ibo, le mouvement est exprimé au niveau de la morphologie. Cette conclusion est un acquis fondamental en vue de futures recherches sur les deux plus importants éléments liés à la notion de mouvement en ibo, à savoir la trajectoire et la manière. Cette étude constitue aussi un travail pionnier en ce qui concerne la contribution de la langue ibo aux études consacrées à cet universel linguistique qu’est l’expression du mouvement

Who speaks for the poor? Poverty, Human Rights, Social Justice and Access to Media in Nigeria

Nigeria faces a major poverty crisis with more than half of the population living in extreme poverty. This conceptual paper delves into the critical issues surrounding the rights of the poor in Nigeria especially in regard their access to media, freedom of expression, and the broader implications for social justice and poverty alleviation. The central question explored in this study is whether the right to freedom of expression and the right to be heard by the poor are recognized and upheld within the Nigerian media landscape as a fundamental human right. Furthermore, this paper examines the extent to which the media has contributed to addressing poverty prevalence in Nigeria and the impactful ways in which this contribution has manifested. Relying on the analytical and critical methodology of study, the paper argues that access to information is a fundamental human right, and the poor, who face multifaceted inequalities, must have their rights protected. Doing so, the paper contends will enhance their capacity to escape poverty, since information and knowledge play pivotal roles in poverty reduction. Emphasis is laid on the importance of granting the poor adequate access to information through available and relevant media, to enable them make informed decisions and choices that can lead to their emancipation from poverty. Keywords: Human Rights, Media Access, Poverty Reduction, Social Justice, Freedom of Expression DOI: 10.7176/JPID/63-04 Publication date: April 30th 2024

The Law of Privacy: Appraising the Practice of Professional Journalism in a Democratic 21st Century Nigeria

The issue of the invasion of privacy in the practice of professional journalism is not a strange phenomenon to those following happenings in Nigeria. Although there is a law guarding against such practice, it appears journalists derive great pleasure from reporting matters that relate to individuals’ personal lives as long as such news is sensational. This paper attempts a synthesis of some of the principles that should inform the development and implementation of the right to individuals’ privacy in a democratic state like Nigeria. Since a chapter of the country’s constitution makes provision for guaranteed and protected rights to certain aspects of citizen’s personal lives, homes, correspondences and several other situations, the paper argues that there is no better time to take the implementation and enforcement of such rights to the next level as now.  The research relied on the analytical and critical methodology of study. It made several recommendations which includes the necessity for a re-appraisal of the current laws of Nigeria relating to citizen’s right to privacy viz-a-vis the duty of journalists to publish and reconcile the gaps where any in the legal regime of protection of persons’ privacy. Doing this, the paper concludes, will help significantly in upholding the dignity and integrity of human beings in Nigeria, thereby fostering the protection of fundamental human rights of citizens, and as well help in strengthening and deepening of our democratic values. Keywords: Fundamental Right to Privacy, Constitutional Right to Publish, and Liabilities in Defamatio

The effects of maternal dietary protein restriction during gestation in rats on postnatal growth of the body and internal organs of the offspring

Effects of maternal dietary protein restriction during gestation on postnatal growth of the body and internal organs of the offspring were  investigated using 32 pregnant rats randomly assigned to two groups (A and B). Pregnant rats in group A (control group) and group B (treatment group) received experimental diets containing 18 % and 8 % crude protein respectively, throughout the gestation period. Growth of the body and internal organs of the offspring of these rats was studied at various postnatal periods. The results showed that at the adult age of 84 days, the body weight and relative weights of the heart, liver, spleen, kidneys and testes were significantly (p<0.05) lower in rats in treatment B than the control. Histological findings revealed that the testes and kidneys were most adversely affected by prenatal protein restriction. Spermatids and spermatogenic cells were scanty in the seminiferous epithelium, while the renal cortex showed distorted and irregularly shaped renal corpuscles and shrunken glomeruli. These results suggest that maternal dietary protein restriction during pregnancy produced longterm adverse effects on postnatal growth and development of the body and internal organs of the offspring. This supports the idea that postnatal growth of adult  structures may be ‘programmed’ during the foetal stages of development. Keywords: Gestation in rats, Protein restriction, Postnatal growth, Foetal programming, Internal organ