Implementation and Optimization of an in vivo Photo-crosslinking Methodology to Define Direct Targets of Transcriptional Activators.

Protein-protein interactions are primarily used to accomplish many biological processes. Understanding protein-protein interactions, particularly, the direct interacting proteins and mechanism for interaction, is instrumental to offering therapeutic interventions for diseases they facilitate. For example in the transcription, many human diseases have strong correlations with alterations in gene expression. Thus, there is intense interest in the development of chemical agents to restore aberrant gene expression to normal levels. To properly define transcriptional activation and ultimately find therapies for diseases associated with altered transcription profiles, there needs to be an in-depth understanding of how transcriptional activators interact with their transcriptional machinery partners (coactivators). However, very few direct binding partners of transcriptional activators are known and structurally characterized, making the generation of tailored screens for inhibitors of activator−coactivator interactions challenging. To better understand activator−coactivator interactions, we probed for direct binding partners of activators in vivo, using an enhanced tRNA/tRNA synthetase pair, developed to site specifically incorporate the nonnatural amino acid pbenzoyl- L-phenylalanine (pBpa) into the amphipathic activators. Initially we started with the model prototypical yeast transcriptional activator, Gal4, and later expanded our studies to two other prototypical activators, Gcn4 and VP16. First, we used a powerful method, nonsense suppression, to incorporate pBpa, which has a crosslinking moiety, into Gal4. Using pBpa-containing constructs of Gal4 we carried out in vivo photo-crosslinking experiments in the yeast strain LS41. Crosslinked activator−coactivator complexes were immunoprecipitated and analyzed by Western blotting. Before identifying the binding partners of Gal4, we determined whether pBpa was readily incorporated into the Gal4 TAD and if these photo-crosslinkable constructs were transcriptionally active. Results showed that all Gal4Bpa constructs were permissive for the incorporation of pBpa, produced the full length protein and were transcriptionally functional. Our initial in vivo crosslinking experiments revealed a well-characterized binding partner of Gal4, the masking protein Gal80. Further, using in vivo photo-crosslinking again, we were able to capture other targets that engage in modest-affinity and/or transient interactions with transcriptional activators (Gal4, Gcn4 and VP16) including Med15, Taf12, Tra1 and Snf2. In the future, in vivo photo-crosslinking methodology can be used to define both tight and modest-affinity protein-protein interactions.Ph.D.Medicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91515/1/adaora_1.pd

The Effectiveness of Capital Budgeting Techniques in Evaluating Projects’ Profitability

This study was conducted to examine the effectiveness of capital budgeting techniques on the evaluation of projects’ profitability. To achieve this objective, research questions were raised, hypotheses were formulated and tested with the chi-square (X2) statistical test; and relevant literature was reviewed. The accessible population for this study was all the sixty-five (65) quoted companies in Rivers State with a sample size of fifty-six (56) companies. A simple random sampling technique was used to select members of the sample frame. The questionnaire, which was administered on the General Managers of the selected companies, was the major data collection instrument employed in this study. From the results of our analysis, the following findings were made: (i) the various capital budgeting techniques used in evaluating the profitability of a project are- pay-back, accounting rate of return, net present value, internal rare of returns, profitability index, and net terminal value (ii) the most significant factor influencing the choice of capital budgeting techniques is the wealth maximization factor, (iii) the capital budgeting technique lacks relevance in evaluating projects under conditions of risk and uncertainty, (vi) the most effective capital budgeting technique for evaluating the profitability of risk-free projects is the net present value (v) taxation has no significant effect on project evaluation. It was therefore recommended that in an environment of risk and uncertainty as we are today, the traditional capital budgeting techniques are not effective in evaluating the profitability of a project; therefore the risk-adjusted discount rate and the certainty equivalent techniques are to be adopted.Key words: Capital budgeting Techniques, Project Profitabilit

Model Development for Auto Spare Parts Inventory Control and Management

The immense dynamics and criticality of spare parts and the large revenues accrued, as essential motivating factors for providing control in manufacturing companies has never showed any sign of decrease. In fact, in the vast technological environment of today the complexities of Spare Parts Inventory Control enjoys more insights from analysts (in the Management Science, Information Technology and Industrial/Mechanical Engineering fields) as inventory policies get modeled to ensure customer satisfaction. In other words manual ways of handling inventory has failed to cope with factors like stochastic demands, better service levels, and shorter lead times and providing perfect heuristics for Inventory-related decision making. To this end, significant results for forecasting spare parts requirements can be achieved through the use of novel decision models. Besides the selling of vehicles, the spare parts of various models of heavy duty vehicles are stored and managed by the company. The management of these models which is complex was further complicated by the vast number of parts required in each model. In fact, more than 20,000 active parts needed to be controlled. The management of these parts can only be done with the aid of a computer; hence the spare parts complex has a computerized spare parts inventory database. Each of the parts that is supplied or replenished is continuously keyed into the computer and the inventory stock parameters are updated automatically. The company uses a software package for its inventory control. This is used to identify the part number of the spare parts. From the part number, the location of the spare parts in the stock room is identified. Key Words: Spare parts inventory, Information Technolog

Terms of trade instability and balance of payments adjustment in Nigeria: A simultaneous equation modelling

This paper employs simultaneous equation modeling to test the  hypothesis that impact of terms of trade instability has no significant  impact on Nigeria.s balance of payments position. Empirical evidence  reveals that BOP has negative relationship with terms of trade. This implies that for any 1percent instability (shock) in terms of trade, balance of  payment will be adversely affected by about 1.8 percent. Hence it becomes pertinent for policy makers to pursue policies that will stabilize terms of  trade. The study also invalidates the Marshal-learner condition. Hence,  caution should not be thrown to the wind in adopting the policy of  deliberately depreciating the naira especially because of the peculiarity of the country.s exports and imports. Indeed, evidence thus abound that it is not enough to increase exports rather the export basket should be  diversified. The negative association between inflation and BOP should be a source of worry to policy makers. It is therefore imperative for economy to address exchange control problems to the effect that the naira does not depreciate beneath a managed floor value.Key Words: Terms of trade instability, Balance of payments adjustment, Nigeri

Tax reforms and investment in Nigeria: an empirical examination

This study is informed by the quest to examine the investment implication of the series of tax reforms in Nigeria, particularly the tax reforms of 2003 and National tax policy of 2012. Annual time series data spanning the years (1981-2012) were utilized. Preliminary diagnostic test was conducted to examine whether the estimated model satisfies the OLS assumptions. The basic assumptions of the OLS were satisfied. The result of the estimated OLS model shows that tax reform as proxied by VAT and CIT, both positively and significantly stimulate investment in Nigeria. The study recommends that efforts should be made towards intensifying the tax reforms. Further, policies should be directed towards redressing multiple taxation and high company income tax as both have the tendency to adversely affect investment.Key words: Tax reform, Investment, Preliminary diagnostic test, National tax polic

Predisposing and bacteriological features of otitis media

Otitis media is an infectious condition that is more frequent in children. Its management is complex because the etiologies vary as the disease progresses. This study aimed to determine the predisposing factors and the bacterial etiology of otitis media. A total of 378 patients diagnosed with otitis media; comprised acute otitis media (29.4%), otitis media with effusion (32.3%) and chronic otitis media (38.4%). Bacteriological examination was done using aerobic and anaerobic culture methods. Children less than 5 years accounted for 46% of cases. Incidence was more in the rainy season (May-October). Unilateral infection which was more common (82%) was predominantly in the left ear (66.8%). Major predisposing factors to infection were age (19.8%), upper respiratory infection (14.8%), poor hygiene and unorthodox practices (14.8%), adenoid inflammation (8.5%) and trauma (6.1%). Streptococcus pneumoniae (38.1%), Moraxella catarrhalis (19.0%) and Staphylococcus aureus (16.7%) characterized AOM. A paradigm shift was observed in otitis media with effusion, with S. aureus (19.1%) and Bacteroides ureolyticus (14.9%) dominating the flora. Etiologies in chronic otitis media were largely mixed aerobic-anaerobic component of 68.3%; predominant flora being Pseudomonas aeruginosa (14.1%) and P. magnus (13.4%). The paradigm shift is instructive in deciding the line of antibiotic therapy to be instituted

Studies on the reproductive potential of homoplastic and heteroplastic pituitary hormones in Heterobranchus bidorsalis (Geoffroy Saint Hilaire, 1809)

Artificial induce breeding of gravid Heterobranchus bidorsalis was carried out using two hormonal materials – homoplastic and heteroplastic hormones. The study which involved 10 trials was carried out with 60 gravid female and 20 mature male. The broodfish used for the study were 18 months hatchery produced H. bidorsalis. The hormonal treatments led to the following results in terms of percentage weight loss (3.16 and 306%); fertilization rate (9522.77 ± 34813 and 8,857.93± 25557); and hatchability (9,18013± 34337 and 8,476.83 ± 34595) for homoplastic and heteroplastic hormones respectively. The mean numbers of dead eggs were 396.10± 19.15 forhomoplastic hormone injected catfish and 425.53 ± 17.09 for those injected heteroplastic hormone. Recorded deormed of larva were low (35.80 ± 1.11 and 34.27 ± 1.43) respectively for catfish injected homoplastic and heteroplastic hormones. Survival of hatchlings was high (99.61 and 9959 %) for gravid catfish inected homoplastic and heteroplastic hormones respectively. There was no significant difference (P < 005) in weight of pre and post female spawners. Although the two tested hormones investigated were effective inducers, homoplastic hormone is recommended as it recorded better results.Keywords: Homoplastic and Heteroplastic hormones, Induced spawning, Hatchability, Heterobranchus bidorsali