Doctor of Philosophy

dissertationThe research work presented in this dissertation describes tissue-specific functions of DNA methyltransferase 4 (an ortholog of the mammalian DNTM3B) during zebrafish hematopoiesis. Studies have implicated the involvement of DNA methylation in regulating hematopoiesis. Although DNA methylation by Dnmt1, Dnmt3a and Dnmt3b is required for HSC maintenance and self-renewal, the exact contributions of these enzymes in commitment of HSCs to different blood lineage precursors and terminal differentiation of these precursors into mature cells are not known. Answers to this idea are important as deregulations of DNMT1, DNMT3A and 3B are known to be involved in hematopoietic diseases. Thus, a better understanding of the contributions of DNMTs in regulating normal hematopoiesis will help in designing better drugs for treating hematopoietic diseases that arise due to aberrant methylation patterns. Chapter 1 is an introduction to DNA methylation and the enzymes, DNA methyltransferases that confer this methylation mark. This chapter summarizes literature from various model systems that allude to the requirement of DNA methyltransferases in a tissue-specific manner during normal development. Chapter 2 describes the utility of zebrafish as a model system to study DNA methylation. Also, I have characterized the embryonic expression patterns, iv morpholino knockdowns of DNA methyltransferases 4, 5, 6, 7, and 8 during zebrafish development. Chapter 3 discusses the epigenetic regulation of mature blood lineages by DNA methyltransferase dnmt4 in zebrafish. Here we show that dnmt4 is expressed in the hematopoietic compartment of zebrafish embryos. Transient knockdown of dnmt4 confers terminal differentiation defects of the erythroid and the myeloid cells. The data discussed in this chapter juxtapose dnmt4 morphants as an amenable model system to study the molecular pathways affected in (Immunodeficiency Centromere instability and Facial anomalies) ICF type-1 syndrome, which arises due to missense mutations in human DNMT3B. Chapter 4 describes the epistatic relationship of dnmt4 with the tumor suppressor gene apc in regulating zebrafish hematopoiesis. Chapter 5 presents the main conclusions of my dissertation work. I have described the implications of my findings and the future directions of this work

An Improved group acceptance sampling plan for weighted binomial on time truncated testing strategy: Inverse Rayleigh Distribution

This paper elucidate an Improved group acceptance sampling plan (IGASP) using weighted binomial, when the lifetime of the test items follows invers Rayleigh distribution. The optimum numbers of group are obtained for pre-defined parameters, acceptance number, quality levels, for different levels of consumer risk. The proposed plan compared with Naqvi and Bashir (2016). The results and comparison are discussed with the help of tables and figures. It observed that sometime proposed plan showed better results than existing plan, under the same parameter settings

Effect of Combined Hydroxyurea and Chelation Therapy in Reducing Serum Ferritin Level, Liver and Spleen Size in Transfusion Dependent Thalassaemia Major Patients.

Background: To compare hydroxyurea plus iron chelation therapy with iron chelation therapy alone in controlling iron overload in children with beta thalassaemia major. Methods: In this comparative study forty thalassaemia major, cases undergoing routine blood transfusion, were observed in iron chelation plus hydroxyurea group (n=20) and iron chelation therapy alone (n=20). The study outcome was measured in terms of impact of continuous blood transfusions on the size of liver ,spleen and Serum. Ferritin levels when compared among those given iron chelation therapy with hydroxyurea and those given iron chelation alone. Results: Mean age of patients was comparable among the two groups. Overall, males were slightly greater in proportion than females (52.5% versus 47.5%). The mean liver size, spleen size and ferritin levels were significantly low in hydroxyurea group compared to no hydroxyurea group (p-value, <0.001). Conclusion: Hydroxyurea plus iron chelation therapy is better than iron chelation therapy alone in controlling iron overload in terms of enlargement of liver, and also limiting iron stores

Sampling Plans for Generalized Pareto Distribution

In this paper, two sampling plans have been discussed, when the lifetime of the items follows the generalized Pareto distribution, Chain Sampling Plan (ChSP-1) and an improved group acceptance sampling plan (IGASP) using weighted binomial.The minimum number of sample size (n) and minimum number of groups (g) are obtained for two plans respectively. The plans are explain with the help of examples whereas the proposed plan compared with Aslam et al. (2010). The results and comparison are discussed with the help of tables and figure. It observed that sometime proposed plan Improved group acceptance sampling plan (IGASP) using weighted binomial, when the lifetime of the test items followsgeneralized Pareto distribution showed better results than existing plan, under the same parameter settings

SPC using size Biased Maxwell Distribution

This paper elucidates the control limits for size biased Maxwell distribution for different sample size(s) with fixed scale parameter. The performance of the control chart observed through the average run length (ARL). The propose control limits, size biased Maxwell (SBMW), compare with existing Maxwell Distribution with same parameter setting and found majority of times better in performance as compare to existing control chart

Quantile Function for Rayleigh and Scaled Half Logistic: Application in Missing Data

In this research paper quantile Functions for Scaled half logistic and Rayleigh distributions has been constructed. Data generated through the quantile Functions and then different limits for the full and missing data set have been developed with scale parameter. A number of such mean control limits could be constructed through purposed method but for analysis purpose few of them have discussed. The missing data limits broadened than the full data in each case, which was expected to be. The average run length (ARL) was also calculated for different sample sizes (50,100,150). The general decreasing behavior of ARL according to increasing shifts was observed that shows a worthy sign, for two distributions, as the probability of detecting an out of control signal increased due to decrease in ARL

An Analytical Study of Urdu Translation of Greek Tragedy “Medea”

“Medea” is ancient Greek tragic play written by Euripides which was produced in 431 BC for the first time. The play is about a serious social issue of remarriage of Men and the response of Women, resulting in parallel familial destructions about all around the world. The play reveals many universal themes like passion, rage, revenge, pride, intelligence, justice and unjust in a society. The play can be taken as the first work of feminism and Medea as a feminist heroine. Euripides deals with gender roles in a sophisticated manner as compared to any ancient Greek writer. His construction of the role of “Medea” is a unique blend of tradition and deviation. The play is translated in many languages and got worldwide recognition. Ahmed Aqeel Rubi translated the play into Urdu language. The translator gave a good chance to Urdu readers to get through the action practiced centuries back and exists ever beyond the geographical boundaries. In the article, Urdu translation of the play has been assessed and marked with the merits and demerits under different translation perspectives

An Improved Group Acceptance Sampling Plan for Weighted Binomial on Time Truncated Testing Strategy Using Multiple Testers: Exponential Distributed Lifetime

In this paper an improved group acceptance sampling plan using weighted binomial is developed when the lifetime of the test item follows exponential distribution. The optimal numbers of group are obtained for pre-specified parameters, acceptance number, quality levels, and number of tester per group at different level of consumer risk. The results are discussed with the help of example and figure. The proposed plan is compare with Anburajan and Ramaswamy (2015) and observed more efficient than the existing plan for Exponential Distribution

A preliminary study for establishing Perna viridis (Mollusca:Bivalvia) as a biological monitor for pollution in Karachi coastal water

Adverse effects of toxic substances on the environmental quality have become a subject of concern in recent years. Toxicity of heavy metals has never been in dispute and therefore their presence in our natural environment is undesirable. This study was undertaken to establish the capability of Perna viridis as a monitor for pollution in the Manora channel. Accumulation of Zinc, Copper, Iron and Manganese by marine mussels, sampled from Manora channel, was determined. Metal load varied markedly between individuals from the same populatin. This variability was partly accounted for systematic relationship between metal load and body weight and age. The distribution of metal between the major organs was considered, but the analysis of separate organs showed no advantage for their use as a biological monitor. comparison between Iron, Manganese, Copper and Zinc concentration in ambient sea water and in the mussel showed no clear correspondence. The results suggest that the mussel is capable of acting as a biological monitor, although may not be a good short term monitor of Iron, Manganese, Zinc and Copper. It may have potential as a long term and site comparison monitor for metals, once inherent variability is taken into accoun