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Quest for antimicrobiol agent: from nanoparticle to computational biology (antimi crobial resistance element CFR as the target protein)
(2024) Shrestha, Pooja; Alina Shri Sapkota
Rapid emergence of superbugs at an unprecedented rate is posing great risk to human health. To address this issue, a diversified integrated approach of antibiotic development, scope of nanoparticles and in silico potentiators screening has been explored in this study. In this regard computation biology approach has been taken in consideration for identification of ligands that could be co-administered with the present-day PhLOPS antibiotics, especially chloramphenicol. The screening parameters ADMET was employed to screen ligands with drug-likeness. In addition, the ligand needed to be non-inhibitory to hMAT1A and Cyp450 3A4 due to their role in immunity and drug metabolism, hence molecular docking with these proteins were performed prior to final docking against the resistance element Cfr. The lead compound ZINC72320745 with inhibitory binding affinity against bacterial Cfr enzyme responsible for chloramphenicol clearance in bacteria has a furan scaffold that suggests the saprophytic nature of the Streptomyces sps. could be explored further with furfural supplementation in the media. However, in this research, tannic acid incorporated modified media was introduced to isolate robust Streptomyces, due to its polyphenolic stress inducing nature. Further, antimicrobials (antibiotic and biogenic nanoparticles) were synthesized and tested against standard pathogens after UV-Vis spectroscopy characterization of silver nanoparticles. The results showed the greater pathogen inhibition with silver nanoparticles than its secondary metabolite. Moreover, the FTIR analysis of the nanoparticle revealed presence of phenol, vinylic ether and imine or oxime group in extract, indicating responsible for its antimicrobial as well as reducing property. The isolate I53 has been found clade forming with Streptomyces rubiginosohelvolus strain 183DZ from the phylogenetic analysis suggesting relatedness. Keywords: Streptomycetes, antibiotics, Silver nanoparticle, Molecular docking, Cfr, RlmN, UV-Vis spectroscopy, FTIR
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Social accountability in lacal governance: Examining the practices in selected municipalities of Kailali, Nepal
(2026) Shahi, Min Bahadur; Binod Pokharel
v This dissertation critically examines social accountability mechanisms and deliberative decision-making practices within local governments in selected municipalities of Kailali District, Nepal. The research is positioned within the context of Nepal's decentralized local governance, which was established after the promulgation of the 2015 Constitution and the implementation of the Local Government Operation Act 201. Four local governments: Lamki Chuha Municipality, Bhajani Municipality, Joshipur Rural Municipality, and Bardagoriya Rural Municipality were selected based on purposive sampling method within Kailali District for detailed analysis. The primary objectives of this research are to assess the legal provisions, significance, and practical implementation of social accountability (SA) mechanisms, and to examine their role on local governance outcomes and the delivery of public services. Grounded in theoretical perspectives of accountability and deliberative democracy, the study adopts a pragmatic ontology with an explanatory sequential mixed-methods design, integrating quantitative surveys and qualitative interviews. The respondents in the survey comprised 42 elected representatives, 67 administrative staff, 402 service receiver citizens, and 20 key informants. The research evaluates key mechanisms such as public hearings, social audits, participatory planning, complaint management, and citizen charters, all of which are mandated to promote transparency, responsiveness, and inclusivity. Deliberative processes within local assemblies and executive bodies are also scrutinized. The triangulation of both quantitative and qualitative data facilitates a detailed analysis of the factors influencing SA practices in local governance. Findings reveal significant gaps between legal/institutional frameworks and actual implementation of SA mechanisms. Although the constitutional and legislative landscape strongly endorses social accountability, practical outcomes are undermined by limited citizen awareness, insufficient institutional capacity, political interference, and ethical concerns. Divergences in accountability perception between service providers and recipients, hierarchical leadership, and lack of stakeholder engagement further constrain the development of deliberative democratic culture. Executive and assembly meetings are often procedural rather than genuinely deliberative, with dominant party structures suppressing minority viewpoints and broader participation. The study highlights the critical role of SA mechanisms in fostering effective local governance and strengthening democratic practices. It addresses the persistent disconnect between the theoretical significance of deliberative governance and its pragmatic realization. Despite internal evaluations, including the Local Government Institutional Self-Assessment (LISA), which suggest satisfactory outcomes, thirdparty assessments highlight ongoing weaknesses in performance, although some gradual improvements in governance indicators can be observed. The research, therefore, emphasizes the necessity of integrating values such as transparency, the rule of law, participation, inclusiveness, efficiency, and sustainability with strong moral and ethical standards. The integration is pivotal for fostering accountability and achieving effective governance.In conclusion, strengthening SA and deliberative decision-making is imperative for enhancing local democracy and effective public service delivery in Nepal. The findings inform policymakers and practitioners on the critical need for capacity building, robust institutionalization of participatory governance, and the reinforcement of ethical and regulative mechanisms at the grassroots level.