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باز آتے ہی نہیں لوگ دغا کرنے سے

باز آتے ہی نہیں لوگ دغا کرنے سے
رُکتا کب مَیں ہوں بھلا پھر بھی وفا کرنے سے

اس طرح ہاتھ مرے آئی بقا کی دولت
ذات میں تیری مجھے خود کو فنا کرنے سے

رنج مٹ جاتے ہیں دردوں کو شفا ملتی ہے
دور ہو جاتی بلائیں ہیں دعا کرنے سے

نہ کریں میرا بھلا یار بھلا نہ سوچیں
کوئی روکے نہ مجھے اُن کا بھلا کرنے سے

میری عادت ہی نہیں شکوے شکایت کرنا
دور رہتا ہوں میں تائبؔ جی گلہ کرنے سے

Probing Interpersonal Dynamics: A Thematic Analysis of Kamila Shamsie's 'Best of Friends'

This research scrutinizes Kamila Shamsie's novel, “Best of Friends”, authored in September 2022, employing a qualitative methodology and data analysis approach to discern major thematic elements. The study identifies five principal themes, encompassing ambivalence within friendships, societal norms and the suppression of desires, political and ethical decision-making, the construct of womanhood, and the motif of unhomeliness. This study applies Braun and Clarke's established six-phase thematic analysis framework (2006) to achieve its research objectives. The research expounds upon the interplay of these identified themes and their reverberations within the lives of the individuals central to the narrative, illuminating the intricacies that underpin the friendship between the main characters. Significantly, the analysis establishes a poignant connection between the novel's title, 'Best of Friends,' and the central theme of ambivalent friendships explored therein. This investigation not only advances comprehension of the thematic nuances within the novel but also underscores the depth and complexity of the issues it addresses. It serves as a foundational exploration, providing a springboard for future research on this recently published work and presenting a diverse array of narrative facets for scholarly inquiry.

Screening and Characterization of Potential Therapeutic Targets Against Hepatitis C Virus Hcv

HCV develops a chronic infection in humans, which ultimately leads to liver failure. Discovery of direct-acting antivirals (DAAs) has initiated the era of well tolerated medications. While these treatments are useful but still encounter certain limitations including drug resistance mutations, selective immune pressure and various side effects. Besides, no effective vaccine for the prevention of HCV infection is yet available. Therefore, for the development of efficient antiviral treatment, comprehensive knowledge of viral proteins characterization and pathogenesis is essential. The current study attempted to use integrated approaches to characterize the HCV major drug target proteins NS3/4A, NS5A and NS5B. Here, we provide a detailed analysis of the drug and immune driven variations among these viral proteins using systems virology and proposed a mechanistic insight highlighting the importance of these mutations on the therapeutic and immune response. In NS3/4A, DRMs such as A36V, Q80K, M175L, I132L, S138T, and R123T were observed in epitopes associated with HLAB*57, HLA-B*27, DRBl*ll04, and DRB1*0101 alleles. Within NS5A, DRMs such as L31M, Q30K/R, L28V, F28L, Q54H, and H58P were found in epitopes related to DRB1*0701, DRBl*ll04, HLA-A*68, and DRB1*0101 alleles. Similarly, DRMs including D168V, M423I, M419M, V494A, V499A, V138I, and I482T were frequently found in epitopes associated with DRB1*0101, DRB1*0701, HLA-B*57, HLAB*27, and DRB1*1104 alleles within NS5B. Among these alleles DRB1*0701, DQA*0201,DRBl*ll04, DRB1*0101, DRB*5701, DRB*5703, Cw*0102, DQBl*O301, HLA-B*57, HLA-A*03, HLA-A*68, and HLA B*27 are involved in HCV protection or clearance. Moreover, the efficacy of four prioritized drugs with no drug and immune driven variations, Danoprevir, Balaprivir, Narlaprevir, Samatasvir was compared with Sofosbuvir using in vitro analysis and highlight the significance of these drugs as more efficacious and potential therapeutic targets. This study also attempted to investigate the evolutionary conservation of these proteins (NS3/4A, NS5A and NS5B) via global consensus sequence profiling of all HCV genotypes (Thio et al.). This comprehensive analysis finds out many conserved drug targets and post translational modification sites (PTMs) that could be a target for the development of universal drug and vaccine. This study also aimed to propose a conserved pan genotypic multi-epitope vaccine by using structural modeling and epitope-epitope compatibility as a promising strategy to combat HCV infections, effectively. Multi-epitope vaccine construct was designed by using sixteen linear conserved epitopes, to induce better antigenic responses than a univalent subunit vaccine. Thus, surface-exposed, conserved and antigenic epitopes from the selected viral proteins were screened to design broad spectrum multi-epitope based subunit vaccines. While stable and substantial interactions were also observed with Toll-like receptor 3 and 8. This study showed that integrated lines offer various opportunities to amass the incomplete mystery of HCV biology in a meaningful way. It will increase our comprehension of how HCV roots liver diseases and how different hidden an unanticipated mechanism including immune driven variations could affect its therapeutic response. It also provides efficient screening stratagem to effectively extract worthwhile insights from multidimensional molecular datasets and helps in improving our understanding of the development of possible therapeutic targets against HCV
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