The Growth of Online Retailing in India

Industrial experts have agreed that India’s small-scale industries are intensely competitive due to globalization, domestic economic liberalization, and digitization. The purpose of this quantitative correlational study was to evaluate the relationship between transaction costs, customer satisfaction, and customer trust in online shopping with the growth of online retailing in India. The theoretical foundation for this research study was the theory of planned behavior, and the unified theory of acceptance and the use of technology. The research questions examined India’s online retailing growth due to transaction costs, customer satisfaction, and customer trust. The study used a quantitative correlational research design. The data collected by the survey research method were analyzed with the software package IBM SPSS. The results indicated that customer satisfaction and transaction cost are significant predictors and can explain 59% (adjusted R2 = .589) of the variance in online retailing growth in India. The previous research had not empirically verified the relationship between transaction costs, customer satisfaction, and customer trust in online shopping with the growth of online retailing in India. The recommendation was to include environmental factors and to increase sample size in future research. Closing the gap may contribute to a positive social change by preparing small business owners to compete against online retail growth by understanding which factors affect the growth of online retail in India. With some online shopping support, small business owners can implement measures to retain and attract customers of specific demographic groups

New approaches for measuring fitness of Plasmodium falciparum mutations implicated in drug resistance

The repeated emergence of drug resistance in Plasmodium falciparum underscores the importance of understanding the genetic architecture of current resistance pathways, as well as any associated fitness costs. Why resistance emerges in particular regions of the world has been linked to particular genetic backgrounds that better tolerate resistance-associated polymorphisms; this is likely to play a key role in driving the epidemiology of drug resistance, however is infrequently studied at a large scale in a laboratory setting. The first results chapter establishes a barcoding approach for P. falciparum with the aim of tracking parasite growth in vitro. The strategy used was adapted for P. falciparum by using a pseudogene (PfRh3) as a safe harbour to insert unique molecular barcodes. These libraries of barcoded P. falciparum vectors were also used as a readout of transfection efficiency. The second chapter establishes a proof of principle for phenotyping by barcode sequencing, using a panel of barcoded parasites generated in different genetic backgrounds that comprise sufficient genetic diversity to pilot the method. These were grown in the presence and absence of antimalarial compounds, and growth phenotypes were measured in parallel using BarSeq. The third results chapter studies the contribution of mutations in Pfkelch13, a molecular marker of artemisinin resistance, to parasite fitness. Combining CRISPR/Cas9-based genome editing and high throughput sequencing, the impact of Pfkelch13 alleles on fitness in the context of particular strain backgrounds is revealed. In particular, the impact of genetic background in the emergence and spread of drug-resistant lineages (referred to as KEL1) in Southeast Asia carrying a Y580 Pfkelch13 allele. Overall, given the current pace of genome sequencing of pathogenic organisms such as P. falciparum, it will be important to increase the scale of experimental genetics, in order to tackle in real-time natural variation that might be under constant selection from drugs, thus anticipating the emergence of drug resistance in changing parasite populations. Through this work, tools were developed to facilitate parallel phenotyping by measuring in vitro growth using high-throughput sequencing. The work also develops novel approaches to address the importance of genetic background and a potential role for positive epistasis in a lineage responsible for the recent outbreak of drug-resistant malaria in Southeast Asia

Development of novel antibacterial agents through the design and synthesis of Aminoacyl tRNA Synthetase (AaRS) inhibitors

Antimicrobial resistance is a global public health issue which significantly threatens human life. There are approximately 50,000 deaths in the USA and Europe per year owing to antimicrobial resistance infections. This burden of resistance has increased resulting in an increase in morbidity and mortality in clinical and community setting. Thus, global collaborative action is needed for developing effective strategies to combat antimicrobial resistance. International and local approaches including antimicrobial surveillance, guidelines for treatment of bacterial infections, regulation of the availability of antibiotics, improving hand hygiene, understanding the mechanism of bacterial resistance and development of new antimicrobial agents have been advised. Aminoacyl tRNA synthetases are valuable targets for antibiotic development as they have a fundamental role at a cellular level during the translation process of the genetic code. Mupirocin (Bactroban ®) is an approved isoleucine tRNA synthetase inhibitor which is used for the treatment of methicillin resistant Staphylococcus aureus (MRSA). High and low level of mupirocin resistance has been demonstrated in most S. aureus isolates due to acquired plasmid-mediated mupA, which encodes a novel IleRS and mutation, respectively. Thus, the design of multitarget aminoacyl tRNA synthetases inhibitors could be an effective way to make significant reductions in the biological fitness of bacteria leading to a reduction in drug resistant microorganisms. Class IIb aminoacyl tRNA synthetases of which AspRS and AsnRS belong is a target of the project in Staphylococcus aureus and Enterococcus faecalis. A computational study of both enzymes in both microorganisms including homology modelling, validation techniques, molecular dynamics and docking of the natural substrates (aa-AMP) were used to be a platform for the design of dual site inhibitors containing a sulphamoyl linkage which mimic aa-AMP in both enzymes. Different series of AspRS/AsnRS inhibitors were designed to occupy both pockets of the target enzymes then synthesised after optimisation their synthetic routes. The minimum inhibitory concentration of compounds against a panel of microorganisms were evaluated compared with ciprofloxacin as the standard and one compound showed good inhibitory activity against Enterococcus faecalis (MIC = 2 μg/mL)