DEVELOPMENT OF UNDER-COORDINATED METAL ORGANIC POLYMERIC MATERIALS FOR HIGH CAPACITY HYDROGEN PHYSISORPTION

Ph.DDOCTOR OF PHILOSOPH

Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs.

Knowledge of the within-host frequencies of resistance-associated amino acid variants (RAVs) is important to the identification of optimal drug combinations for the treatment of hepatitis C virus (HCV) infection. Multiple RAVs may exist in infected individuals, often below detection limits, at any resistance locus, defining the diversity of accessible resistance pathways. We developed a multiscale mathematical model to estimate the pre-treatment frequencies of the entire spectrum of mutants at chosen loci. Using a codon-level description of amino acids, we performed stochastic simulations of intracellular dynamics with every possible nucleotide variant as the infecting strain and estimated the relative infectivity of each variant and the resulting distribution of variants produced. We employed these quantities in a deterministic multi-strain model of extracellular dynamics and estimated mutant frequencies. Our predictions captured database frequencies of the RAV R155K, resistant to NS3/4A protease inhibitors, presenting a successful test of our formalism. We found that mutational pathway maps, interconnecting all viable mutants, and strong founder effects determined the mutant spectrum. The spectra were vastly different for HCV genotypes 1a and 1b, underlying their differential responses to drugs. Using a fitness landscape determined recently, we estimated that 13 amino acid variants, encoded by 44 codons, exist at the residue 93 of the NS5A protein, illustrating the massive diversity of accessible resistance pathways at specific loci. Accounting for this diversity, which our model enables, would help optimize drug combinations. Our model may be applied to describe the within-host evolution of other flaviviruses and inform vaccine design strategies

Melamine-terephthalaldehyde-lithium complex: A porous organic network based single ion electrolyte for lithium ion batteries

10.1039/c4ta06855fJournal of Materials Chemistry A395132-513

Tandem catalysis of amines using porous graphene oxide

10.1021/ja512470tJournal of the American Chemical Society1372685-69

Tandem Catalysis of Amines Using Porous Graphene Oxide

Porous graphene oxide can be used as a metal-free catalyst in the presence of air for oxidative coupling of primary amines. Herein, we explore a GO-catalyzed carbon–carbon or/and carbon–heteroatom bond formation strategy to functionalize primary amines in tandem to produce a series of valuable products, i.e., α-aminophosphonates, α-aminonitriles, and polycyclic heterocompounds. Furthermore, when decorated with nano-Pd, the Pd-coated porous graphene oxide can be used as a bifunctional catalyst for tandem oxidation and hydrogenation reactions in the <i>N</i>-alkylation of primary amines, achieving good to excellent yields under mild conditions