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Polymorphism Analysis of Antiviral Sensor Genes in Hcv Infections: Impact on Response to Therapy

Thesis Info

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Author

Iqbal, Muhammad Sarfaraz

Program

PhD

Institute

Government College University

City

Faisalabad

Province

Punjab

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Biotechnology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12736/1/Sarfaraz%20Iqbal%20%20%20%20PhD%20thesis%20GCUF%20%20%20Reg%202005%20gcuf%202743%20521.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726963222

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Hepatitis C virus (HCV) is a blood-borne virus and a principal source of liver cirrhosis, chronic hepatitis, and hepatocellular carcinoma (HCC). Approximately 180 million people, around 3% of the world’s population infected with HCV. Roughly, 10 million Pakistanis, representing 6% of the total population, are with HCV infection. Most HCV infections lead to chronic infections due to the failure of the immune response. Toll like Receptors (TLR) is a family of transmembrane proteins that expresses most of the immune cells and is the main component of innate immunity that perform an important role in the recognition of various types of pathogens. The major innate immune sensor TLRs (TLR2, 3, 4, 7, 8, and 9) and Retonicacid inducible like receptor (RLR) (MDA5) are important for viral nucleic acid detection and inducing antiviral reactions. Aberrant immune activation can be harmful to the host; Therefore, TLRs and RLR activities are strictly regulated by the immune system. In addition, an unbalanced inflammatory response to the host via a TRL or RRL based signaling pathway may be responsible for inflammation and autoimmune disease.” “In this studyTLR2, 3, 4, 7, 8, 9 and MDA5genes Polymorphism were analyzed to ensure that these genes may play a role in the failure of interferon therapy and HCV clearance. In TLR2 Polymorphisms, we analyzed SNP Arg677Trp and Arg753Gln. The polymorphisms of TLR3 we analyzed were SNP rs5743314 (G/C), rs78726532 (A/G) and rs3775290 (T/C). The TLR4 polymorphism, analyzed in our study was SNPrs4986790(C/T), TRL7 rs179009 (A/G), TLR8 rs3764879, TLR9 rs187084 (A/T), TLR9 rs5743836, MDA-5 rs1990760 (A/G).High resolution melting (HRM) curve method was applied to screen out the mutations.PCR was directed according to the protocols of Step OnePlus™ Real-Time PCR.Total 500 samples were collected (400 HCV patients and 100 healthy subjects). Out of 400 HCV patients, 323 were interferon responders and 77 were interferon nonresponders.TLR2 Arg677Gln, TLR3 rs3775290, TLR4 Asp299Gly, TLR7 rs179009 and TLR9 rs187084 shown significant association with HCV recurrence, while TLR2 Arg753Gln, TLR3 rs5743314 and rs78726532, TLR8 rs3764878, TLR9 rs5743836 and MDA5 rs1990760 did not show any association with HCV recurrence.” Our outcomes are inconsistent with the current positional data on the NCBI database. These genotypes may help to identify those patients at higher risk of developing complications during the first year of treatment. Outcomes of this study may have opened a door to set up prospectively planned randomized controlled trials (RCTs) that include TLRs genotype information while evaluating new and advanced treatments of HCV especially for patients infected with genotype 3.Finally, the outcomes of this study may result in a benefit for the patient when clinically use to improve the efficiency and immunogenicity of the current therapeutic regimens through combining therapy with alternate TLR agonists to overcome immune deficiencies induced by defective TLR signaling.
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حقوقِ انسانی کا اسلامی تصور

حقوق انسانی کا اسلامی تصور
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Politics of Confession: A Political Reading of Coetzee’s Disgrace

The use of religious models in political arena has been a vital tool in the hands of politicians in order to achieve secular objectives, unattainable otherwise. In current research several Confessional features are discussed, with particular emphasis on political confession where a religious practice (confession) is maneuvered to support political acrobats in South African post-apartheid politics. The research evaluates the authenticity of confessional model introduced in South African Truth and reconciliation commission (TRC); a post-apartheid political practice. Current research gauges the relationship of confession and forgiveness in South African context in the light of Coetzee’s Disgrace. The authenticity of contrition is discussed which is the pivotal element in this whole process. This paper evaluates TRC in reference to justice and the grant of amnesty to the violators of gross human rights, how justice is abrogated in order to bring reconciliation. The way TRC attached reconciliation to forgiveness was wrong in its very roots.

Analysis of Newtonian/Non-Newtonian Fluids by Lie Group Theoretic Methods

Analysis of Newtonian/Non-Newtonian Fluids by Lie Group Theoretic Methods The advent of efficient computation techniques has made it possible to solve nonlinear differential equations governing the fluid flow problems. Nevertheless, the possibility of obtaining exact or approximate analytical solutions is always preferred to understand the physics of fluid flow and to establish the reliability of both numerical and analytical results. This has always been an intellectual challenge for the mathematicians and engineers to find the analytical solutions of the nonlinear differential equations. Lie group analysis provides an analytic approach to find the solution of nonlinear problems and gives an insight for the possible exact and analytical solution techniques that may emerge as a consequence of this analysis. Further, Lie group analysis is a tool to simplify the problem systematically by applying the symmetries obtained through it. 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Chapter 2 contains some preliminaries, the basic equations of fluid flow and heat and mass transfer and general physical quantities that appear in the subsequent chapters. ixIn Chapter 3, we consider the Lie group analysis of mixed convection flow of Newtonian fluid with mass transfer over a stretching surface. We propose generalized forms of the wall stretching velocity, wall temperature and wall concentration and show the possibility of only two types of stretching velocities; namely the polynomial stretching and the exponential stretching. The similarity transformations are established and those available in the literature are extracted as special cases of our problem. Lie group analysis of non-Newtonian power-law fluid along a stretching surface is performed in Chapter 4. The application of infinitesimal generator on the generalized surface stretching conditions for non-Newtonian power-law fluid leads to the possibility of power-law and exponential stretching velocities. To author’s knowledge, exponential stretching in the flow of power-law fluid is not available in the literature. An exact analytical solution of the nonlinear similarity equation for new found exponential stretching is developed for shear thinning fluid with power-law index n = 1/2. Making use of the perturbation technique, analytical solutions are extended to a wider class of shear thinning fluids (0.1 ≤ n ≤ 0.9). The numerical solution for shear thinning fluid is also presented. An excellent agreement is found between the two solutions. The solution for the case of shear thickening fluid is obtained using the numerical technique namely; Keller box method. In Chapter 5, we investigate the flow and heat transfer of a non-Newtonian Powell- Eyring fluid over a stretching surface. Using Lie group analysis, the symmetries of the equations are found. The application of infinitesimal generator to the generalized boundary conditions leads us to the possibility of two types of surface condition that are in contrast to the findings in the last two chapters. Firstly, the surface is moving with constant velocity and surface temperature is either of exponential form or constant. Secondly, the surface is stretching with velocity proportional to x 1/3 (x is the distance along the plate) and the surface temperature is of power-law form. The latter case is discussed in this chapter and the similarity transformations are derived with help of the symmetries. The governing system of partial differential equations is transformed to a system of ordinary differential equations by using these similarity transformations. These equations are solved numerically using Keller box method. A xcomparison of the results thus obtained is made with the analytical and numerical solutions available in the literature and an excellent agreement is found. The effect of governing physical parameters on velocity and temperature profiles, skin friction and local Nusselt number is also analyzed and discussed. Chapter 6 is devoted to study the flow and heat transfer of Powell-Eyring fluid over a stretching surface in a parallel free stream. Geometry of the problem differs from the preceding problems, where the flow is caused solely by the stretching of the surface. The stretching velocity is proportional to x 1/3 and the free stream velocity is in terms of a generalized function. The governing equations are transformed to a system of nonlinear ordinary differential equations by using a special form of Lie group of transformations, namely scaling group of transformations. It is noted that self- similarity in the problem is possible only if free stream velocity is also proportional to x 1/3 . Numerical results are obtained by means of the Keller box method and the special cases of the problem are compared with the previous work giving good agreement. The effect of governing physical parameters on flow properties including their physical significance is also discussed. Steady three dimensional flow and heat transfer of viscous fluid on a rotating disk stretching in radial direction is investigated in Chapter 7. This problem is an extension of the traditional Von Karman flow problem to the configuration with stretchable rotating disk. Using Lie group theory the similarity transformations for nonlinear power-law stretching are derived. Exact analytical solutions are presented for pure stretching for stretching index n = 3. Numerical solutions, showing combined effects of stretching and rotation, are found using Keller box method. An excellent agreement is found between the two solutions for pure stretching problem. 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