A Short and efficient syntheses of chiral 2, 2¡¦- bipyridine derivatives by Kröhnke reaction. The bipyridines allow well defined in self- assembly of double stranded helicates by coordinating with silver(¢¹).

Thesis (Ph.D.) - Simon Fraser University, 2004. / Theses (Dept. of Biological Sciences) / Simon Fraser University. Bibliography : leaves 134-154.

Little is known of trace metal concentrations and their possible role in the mortality of critically endangered Kemp??s ridley sea turtles (Lepidochelys kempii). Research described herein characterized concentrations of seven trace metals ?? Ag, Cd, Cr, Cu, Hg, Pb and Zn ?? in the blood and carapace tissue of captive Kemp??s ridleys for use in assessing levels of these metals in wild counterparts. Concentrations of same trace metals were characterized in post-pelagic through adult life stages of 127 wild Kemp??s ridleys captured from the Gulf of Mexico and southeast Atlantic during 2000 to 2002. Blood, carapace, liver, kidney, and muscle tissues from live and/or stranded Kemp??s ridleys were analyzed for the aforementioned trace metals via graphite furnace atomic absorption spectrophotometer and cold vapor atomic fluorescence techniques conducted under class-100 clean laboratory conditions. Similar trace metal assessments were conducted on blue crab (Callinectes sapidus) prey to determine the role of food as a possible uptake pathway in Kemp??s ridleys. Overall, trace metal levels in live, captive as well as wild ridleys were higher in carapace tissue than in blood. Carapace concentrations of Ag, Cr and Hg in Kemp??s ridleys across all post-pelagic life stages increased with increasing straight carapace length (SCL). Carapace tissue of wild ridleys exhibited higher Cr, Hg, and Pb levels than their blue crab prey, regardless of study area; whereas, crabs yielded higher Ag and Cu concentrations. Dead stranded ridleys yielded higher Ag, Cr, Hg, Pb, Zn levels in carapace tissue, whereas, their liver exhibited higher Cd and Cu levels. This finding suggests carapace tissue could serve as a suitable surrogate sample source for internal organs/tissues when monitoring exposure of live Kemp??s ridleys to certain metals. The fact that larger, stranded ridleys exhibited higher Ag, Cd, Hg, Pb and Zn levels than did their smaller, live analogs from Texas and Louisiana implies that these older ridleys had increased opportunities to accumulate higher metal concentrations in their carapace tissue than did their younger conspecifics. This trend suggests that carapace tissue has the potential to accumulate trace metals while blood-borne concentrations reflect only recent exposure to trace metals.

Thesis (Ph. D.) in Biochemistry and Molecular Biology--University of Maine, 2001. / Includes vita. Includes bibliographical references (leaves 71-83).

Thesis (Ph. D.)--Cornell University, May, 2008. / Vita. Includes bibliographical references (leaves 162-177).

Ship groundings are a low probability event, but can create severe environmental and financial consequences. The objective of this thesis is to provide knowledge and understanding of the grounded ship condition to salvors and ship owners so they can reduce the possible negative consequences of future ship groundings. There has been very little research on the motions of and loads on a grounded ship in waves. In this thesis, a model of the ground reaction forces due to the steady state motions of a grounded ship is developed. This model is derived from civil engineering applications but tailored to the stranded ship problem. The ground reaction sub-model is part of a ship motion model that predicts grounded ship motions and loads in waves. The model input specifies the static grounded equilibrium condition and static grounded forces. The model calculates steady state motions and loads around the equilibrium condition. This thesis describes a preliminary version of the full six degree of freedom model in which soil reactions are accounted for in two degrees of freedom, heave and pitch, assuming a rectangular shaped hull. Bottom types are categorized as sand, mud, coral and rock. The ship can be embedded or resting on the surface of the bottom. / Master of Science

DNA condensation is the process in which an anionic polymer in combination with condensing agents undergoes a drastic reduction in volume and collapses into ordered structures. Double-stranded DNA has a uniform helical secondary structure, whereas single-stranded DNA is complex and adopts numerous different conformations. Novel mixed-stranded DNA molecules, with defined regions of both single-stranded and double-stranded secondary structures attached to one another in the same molecule, were created in this body of work. Mixed-stranded DNA was designed to be intermediate between its parent secondary structures in order to discover if mixed-stranded DNA will find a balance in terms of condensation properties as well. Mixed-stranded DNA was found to condense into minimally aggregated, globular particles in the presence of low mM concentrations of divalent transition metals in aqueous solvent at room temperature, a property not observed for either pure dsDNA or ssDNA. A model is presented to describe how mixed-stranded DNA -Mn2+, -Ni2+, and -Cd2+ condensates with the observed properties are produced. Multivalent-induced condensation of mixed-stranded DNA is also characterized and found to involve an unusual rod-like morphology in order to accommodate the secondary structures condensing independent of one another at different concentrations of multivalent cations. The attachment of a ss region to an otherwise ds molecule was found to greatly influence condensation properties of the entire molecule.

Background: Genetic recombination is a driving force in genome evolution. Among viruses it has a dual role. For genomes with higher fitness, it maintains genome integrity in the face of high mutation rates. Conversely, for genomes with lower fitness, it provides immediate access to sequence space that cannot be reached by mutation alone. Understanding how recombination impacts the cohesion and dissolution of individual whole genomes within viral sequence space is poorly understood across double-stranded DNA bacteriophages (a.k.a phages) due to the challenges of obtaining appropriately scaled genomic datasets. Results: Here we explore the role of recombination in both maintaining and differentiating whole genomes of 142 wild double-stranded DNA marine cyanophages. Phylogenomic analysis across the 51 core genes revealed ten lineages, six of which were well represented. These phylogenomic lineages represent discrete genotypic populations based on comparisons of intra-and inter-lineage shared gene content, genome-wide average nucleotide identity, as well as detected gaps in the distribution of pairwise differences between genomes. McDonald-Kreitman selection tests identified putative niche-differentiating genes under positive selection that differed across the six well-represented genotypic populations and that may have driven initial divergence. Concurrent with patterns of recombination of discrete populations, recombination analyses of both genic and intergenic regions largely revealed decreased genetic exchange across individual genomes between relative to within populations. Conclusions: These findings suggest that discrete double-stranded DNA marine cyanophage populations occur in nature and are maintained by patterns of recombination akin to those observed in bacteria, archaea and in sexual eukaryotes.

Antibiotics are a foundation of modern medicine, helping to save millions of lives since their discovery in 1928. But the improper and excessive use of these drugs over the last few decades has led to an alarming increase in antimicrobial resistance; coupled with the recent decrease in antibiotic discovery, it is widely thought that we are approaching a post-antibiotic era. A less well-understood problem is that of drug tolerance. Even at high doses, antibiotics often cannot kill all the bacteria in an infection because of cells that are able to tolerate antibiotic treatment. Evidence points to drug-tolerant cells, also called persisters, to be a major cause of treatment failure and chronic and recurring infections It is imperative that we develop insight and methods to prevent the spread of antimicrobial resistance and combat antimicrobial tolerance. One key effort is characterizing bacterial responses to antibiotic drug treatment to generate a more comprehensive understanding of the factors that contribute to cell death and to elucidate potential targets for new therapies. Quinolones are an important class of antibiotics that target DNA replication. They bind to topoisomerase II and IV, leading to eventual DNA fragmentation and death. However, the precise mechanism by which they work is not well understood. Because they inhibit DNA replication, quinolones lead to up-regulation of the SOS response, which allows for increased mutagenesis and the potential for increased antimicrobial resistance, thus making quinolones an interesting class of antibiotics to study. Although quinolones are one of the most effective classes of antibiotics, there are many conditions in which they do not kill, such as in stationary-phase cultures. Understanding the mechanism behind quinolone killing, quinolone-induced mutagenesis and tolerance to quinolones is important to improve quinolone efficacy. Here I have presented my work on understanding quinolones: sensitivity, mutagenesis and tolerance. In understanding quinolone sensitivity, I focus on DNA repair and its involvement in quinolone-mediated death. I then probe the field of stress-induced mutagenesis by quinolones, uncovering phenotypes of dose-dependent mutagenesis that have previously been uncharacterized. Finally, I focus on drug tolerance and how density-dependent tolerance to quinolones can be reversed by up-regulating cellular respiration through the addition of a carbon source and electron acceptor. / 2018-11-02T00:00:00Z

Genome stability has great importance in maintaining cell viability and optimal functionality of cellular processes. Loss of genome stability can lead to cell death in the simplest organisms and to deregulation of the cell proliferation machinery in higher organisms, potentially causing cancer or morbid states. The Single Stranded DNA Binding (SSB) protein of Escherichia coli is an essential protein that binds and stabilises ssDNA stretches. Its role is particularly crucial during DNA replication, recombination and repair processes and it has therefore been predicted to play a prominent role in the maintenance of genome stability. The role of SSB in genome instability was investigated using an E. coli strain in which, the expression of the ssb gene was placed under the control of the arabinose promoter. The level of SSB protein present in the cell could therefore be tuned by varying the arabinose concentration in the medium. A wide characterisation of the behaviour of the strain at low SSB level was carried out. Viability and growth tests showed that a threshold level of protein is required to allow normal growth. Microscopy analyses were carried out to follow cell division, nucleoid morphology and SOS response activation. Cells grown at low SSB level, showed a phenotype consistent with impaired cell division and altered nucleoid morphology. The SOS response was activated at low SSB levels and cell elongation was detected. Lowering the arabinose concentration in solid medium allowed the selection of suppressor strains that could form colonies under the new conditions. Sequencing of the entire genome of one such suppressor strain was carried out revealing a possible candidate for the phenotype change. The stability of a 105bp and of a 246bp DNA imperfect palindromes and the stability of CAG·CTG trinucleotide repeat arrays, inserted in the E. coli chromosome, were investigated in correlation to the SSB cellular level. Lowering the SSB level in cells grown on solid medium, increased the instability of the 105bp palindrome presumably by increasing the number of slippage events. On the other hand, SSB overexpression did not have an effect on the stability of the 246bp palindrome. The stability of a leading strand (CAG)75 repeat array was highly increased by overexpressing SSB, while the same effect was not observed for a leading strand (CTG)137 repeat array. Furthermore, excess SSB caused a change in the deletion size distribution profile for the leading strand (CAG)75 strain, lowering the bias towards big deletions. This is consistent with SSB being able to preferentially impede the formation of big DNA hairpins. Also, SbcCD nuclease was shown to have an effect on the deletion size distribution profile of the leading strand (CTG)137 strain. The lack of SbcCD led to a slight reduction of the number of big deletions.