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This study investigates some of the basic aspects of conjugate, or coupled, heat transfer problems. The ultimate interest is in the improvement of an existing computational fluid dynamics (CFD) code by the inclusion of such a coupling capability. Many CFD codes in the past have treated the thermal boundary conditions of a bounding solid as the simple cases of either a surface across which there is no heat flux, or as a surface along which the temperature is a constant with respect to both space and time. These conditions are acceptable for some applications, but many real-world problems require a more-realistic treatment of the thermal wall condition. A thermal coupling may be accomplished by maintaining a continuous heat flux and temperature across the fluid-solid boundary. A heat flux is calculated on the fluid-side of the interface, and this is used as a boundary condition for a heat-conduction solver to calculate the temperature field within the solid and return an interface temperature to the fluid. This process is executed for each time-step iteration of the code, and, therefore, the temperature field of the solid and the fluid-solid interface temperature are allowed to evolve with time and space. A new heat-conduction solver is developed and coupled with an existing flow solver. For this reason, some of the study is devoted to the testing of the accuracy of the new heat-conduction solver on simple problems for which there exist analytical solutions. Additional coverage is devoted to the possibility of thermal communication between solid grid blocks. This is due to the fact that multiple grid blocking of the solid may be required for more complex geometries. For such cases, a similar procedure as that described for the fluid-solid interface is used to accomplish the solid-solid block-to-block communication. Relatively simple test cases of fluid-solid and solid-solid coupling are conducted; these cases are limited to two-dimensional grids. Other limitations include: the assumption of constant thermophysical properties for the solid, no consideration for thermal expansion of the solid, and no consideration for the radiation mode of heat transfer. The results indicate that the heat-conduction/flow solver shows potential.

[Rh(CO]2Cl]2 has been shown to catalyze sequential, mechanistically- distinct transformations in one pot. Tandem allylic alkylation/cycloisomerization sequences have been developed to access valuable, complex structures from relatively simple substrates. A methodology for the enantioselective conjugate addition of 2-heteroaryl nucleophiles to a variety of Michael acceptors has been developed. This method was used successfully in an ongoing approach to the synthesis of cortistatin A. 10 linear steps have been completed towards the synthesis of cortistatin A, including a highly regioselective propargylation to install a quaternary carbon and a diastereoselective intramolecular Diels-Alder reaction. / text

Six polyamine anthracene conjugates (Ants) were studied that take advantage of the polyamine transporter system (PTS) to target specific cancer. The structural features of the Ants involve planar aromatic anthracene that has highly cytotoxicity properties and a polyamine chain similar to natural polyamine, which is taken up by eukaryote cells expressing the PTS actively. Experimental data show that Ants with di-substituted polyamine chains have significantly higher DNA binding affinities than the mono-substituted anthracene conjugates. The high ionic conditions (~150 mM NaCl and 260 mM KCl) in the eukaryote cell nucleus extensively impair the apparent DNA binding of the Ants, but may further reinforce DNA structural stability. Combining the published cytotoxicity of the PTS data with the DNA interaction data reported here, the di-substituted polyamine anthracene conjugates have the highest potential to, after cellular uptake via PTS, bind to DNA.

The usual practice in any discussion of an inner-product space is to restrict the field over which the inner-product space is defined to the field of complex numbers. In defining the inner-product function, (x,y), a second function is needed; namely the conjugate function (x,y)* so that (x,y) ± (y,x)*. We will attempt to generalize this concept by investigating the existence of a conjugate function defined on fields other than the field of complex numbers and relate this function to an inner-product function defined on a linear space L over these fields.

The effect of a reinforcer on behavior is largely determined by the schedule in which it is implemented. One type of reinforcement schedule that has not been explored extensively is conjugate reinforcement. Previous researchers have used conjugate schedules to evaluate a reinforcer's effects on behavior and as an assessment tool. However, none have explored how to effectively engineer conjugate schedules in applied settings. The current study explores the effectiveness of conjugate reinforcement implemented by several interventionists across a variety of responses, reinforcers, and in a wide range of participants with autism. The results indicated that delivering social, audio/visual, and tangible stimuli in a conjugate schedule resulted in increased durations of various target responses (e.g. social skills, motor skills) and non-targeted measures (e.g., approach, social bids, speed) across participants. Considerations regarding reinforcer and response selection in implementing conjugate schedules in applied settings are provided.

Thesis advisor: James P. Morken / Described herein are methods for asymmetric allylation. Chapter 1 describes the scope of the Pd-catalyzed asymmetric diboration of prochiral allenes. The products of this process possess both a chiral allylboronate functional group and a vinylboronate moiety. The allylboronate functionality can subsequently be used for imine allylation, without isolation of the diboron intermediate, resulting in the formation of atypical allylation products through a tandem, one-pot sequence. Furthermore, enantioselection in the catalytic diboration and chirality transfer in the subsequent imine allylation are high; thus, non-racemic, protected homoallylic amines, and other derivatives, are produced in high enantiomeric excess. Chapter 2 describes the discovery and development of a transition-metal-catalyzed asymmetric conjugate allylation of allylboronate ester nucleophiles to activated enones. The scope, utility, and mechanistic aspects of this new reaction are discussed. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg 2017. / Background: Nasopharyngeal colonisation is a pre-requisite for developing bacterial respiratory and invasive disease. Immunisation of children with the pneumococcal conjugate vaccine (PCV) impacts upon colonising pneumococcal serotypes, which in turn could also affect the biome of the nasopharynx in relation to colonisation by other bacteria. Due to limitations in standard culture methods, the association between PCV-immunisation and bacterial carriage density is still unclear, including among HIV-infected children. In this study we aimed to evaluate the effect of infant vaccination with the 7-valent PCV (PCV7) on vaccine-serogroup colonisation in order to determine whether the increase in non-vaccine serotype (NVT) colonisation was due to unmasking of previously low density colonising serotypes or increase in acquisition of NVT. Also, we evaluated the association between PCV7 immunisation and HIV-infection on the prevalence density of nasopharyngeal colonisation by other common potentially pathogenic bacteria. Methods: A multiplex real-time qPCR assay was set up to detect 44 common pneumococcal serotypes and 5 bacterial pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes. All assays were optimised according to MIQE guidelines and their ability to detect multiple pneumococcal serotype/group and bacteria in archived nasopharyngeal swabs were evaluated. The multiplex qPCR assays were then used to evaluate vaccine-serotype, non-vaccine serotype and bacterial nasopharyngeal colonisation in achieved swabs of PCV7-vaccinated (at 6, 10 and 14 weeks of age) and PCV-unvaccinated African children at 9 and 15-16 months of age, prior to routine vaccination of children with PCV through the public immunisation program. In order to address the limitations of the qPCR assays, a nanofluidic real-time PCR assay was developed to simultaneously detect 53 pneumococcal serotypes, 6 serotypes of H. influenzae and 11 bacterial pathogens. Further, all assays were optimised and evaluated according to the MIQE guidelines and findings from Fluidigm and traditional qPCR assays were compared. Lastly, Fluidigm was used to evaluate the association of HIV-infection on the prevalence and density of nasopharyngeal colonisation at 9 and 16 months of age by common, potentially pathogenic bacteria including PCV7 pneumococcal serotypes, non-PCV7 serotypes, Haemophilus influenzae, non-typable Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pyogenes, Neisseria meningitidis, Neisseria lactamica, Bordetella pertussis, Bordetella parapertusis, Bordetella bronchiseptica and Bordetella holmesii in achieved nasophartngeal swabs collected from PCV7-vacciniated HIV-infected and HIV-uninfected children. Results: Molecular qPCR was more sensitive than culture in detecting multiple concurrent colonising pneumococcal serotypes as well as other common nasopharyngeal colonisers, with the majority of additional isolates detected by qPCR having a low carriage density (<104 CFU/ml). Further, qPCR identified a lower prevalence of PCV7-serotype colonisation among PCV7-vaccinated compared to PCV-unvaccinated children at 9 and 16 months of age [adjusted Odds Ratio (aOR): 0.37; 95% CI; 0.19-0.7 and 0.41; 95% CI; 0.26-0.63, respectively]; and an increase in NVT-serotype [aOR: 1.88; 95% CI; 1.02-3.48 and 2.2; 95% CI; 1.18-4.1] colonisation respectively. The increase in NVT carriage among PCV7-vaccinees was driven by serotype 19A, which increased by 53.4% (p=0.021) and 70.7% (p<0.001) at 9 and 16 months of age respectively. Further, 19A had a higher density of colonisation in PCV7-vaccinated groups compared to PCV-unvaccinated groups and was more likely to be identified as a primary than non-primary isolate in PCV7-vaccinated children alone. PCV immunisation was also associated with an increased prevalence of H. influenzae at 9 months (55.8% vs. 66.3%, p<0.001) and 16 months (72% vs. 62%, p=0.017) of age, while a temporary increase in the carriage prevalence of S. aureus was found in PCV7-vaccinated (18.9%) compared to PCV-unvaccinated children (11.1%, aOR 2.1; 95% CI 1.0-1.4; p=0.049) at 9 months of age only. The density of pneumococcus (4.68 vs. 4.28 CFU/ml; p=0.007), H. influenzae (3.86 vs. 4.34 CFU/ml; p=0.008), M. catarrhalis (2.98 vs. 3.52 CFU/ml; p<0.001) and S. aureus (3.06 vs. 4.02 CFU/ml; p=0.02) were also higher among PCV7-vaccinated compared to PCV-unvaccinated children at 9 months age, although this difference diminished with increasing age. There was excellent concordance between the qPCR and Fluidigm for carriage prevalence and density of the majority of assays, with Fluidigm identifying an additional 7 pneumococcal serotypes and 11 bacterial species above those detected by qPCR. Further, discordant results between the two PCR methods were strongly associated with a low carriage density (<102 CFU/ml). Using molecular Fluidigm, a lower carriage prevalence of overall pneumococci (58.6% vs. 69.9%; p=0.02), non-vaccine serotypes (27.8% vs. 40%; p=0.047) and H. influenzae (64.2% vs. 42.3%; p=0.01) was identified in HIV-infected children compared to HIV-uninfected children who were immunised with PCV7 at 9 months of age. No difference in the carriage prevalence of overall pneumococci was however found at 16 months of age (p=0.20), although the carriage prevalence of non-vaccine serotypes (50.9% vs. 60.4%; p=0.049) and H. influenzae (56% vs. 73.4%; p=0.02) was lower in HIV-infected children at 16 months of age. In addition, the density of overall pneumococcus was found to be higher in HIV-infected children (4.81 vs. 4.44 CFU/ml; p=0.014), despite the lower carriage prevalence at 9 months of age, which was driven by a higher density of vaccine serotypes/serogroups (4.21 vs. 3.72 CFU/ml; p=0.04). By 16 months of age, there was no difference in density of pneumococcal colonisation between the HIV-infected and HIV-uninfected children (p=0.89). No difference in the density of H. influenzae was found between HIV-infected and HIV-uninfected infants at 9 months of age (p=0.08); however, by 16 months of age, HIV-uninfected children had a higher density of overall H. influenzae colonisation (4.95 vs. 4.32 CFU/ml; p<0.001), which was largely due to the higher carriage density of NThinf in HIV-uninfected children (5.0 vs. 4.23 CFU/ml; p<0.001). Conclusion: Molecular qPCR assays were shown to be a promising alternative to WHO recommended culture in that multiple pneumococcal serotypes and other bacterial pathogens could be simultaneously detected as well as the bacterial load of each colonising bacteria quantified. The mechanism behind the vaccine effect was shown to be a combination of both serotype replacement and unmasking; however, the reduction in PCV7-serotype colonisation impacted on colonisation prevalence and density of other bacterial species of the nasopharynx and the clinical relevance of this needs further exploration in relation to mucosal and invasive disease outcomes, as well as for higher valence vaccines. While the higher carriage density of overall pneumococcus in HIV-infected children, despite the lower carriage prevalence might explain the higher invasive disease burden in HIV-infected compared to HIV-uninfected children even in the era of antiretroviral therapy treatment and PCV immunisation, future studies are required to provide clarity. Nevertheless, the findings from this thesis highlight the importance of continued surveillance of the circulation of pneumococcal serotypes as well as other bacterial pathogens especially in a population with a high burden of HIV-1 infection. / MT2017

The research presented herein is concerned with the exploration of rhodium-catalysed addition reactions with organoboranes encompassing the 1,4-addition enolate protonation to benzyl acrylate esters, and the synthesis of chiral organoboranes for use in the synthesis of natural products Hermitamides A and B. Chapter 1 introduces the area of rhodium-catalysed conjugate addition as a tool for asymmetric synthesis. An extensive discussion of this methodology is included and recent advances in the area will be highlighted. In addition to this some recently published alternatives to organoboranes are outlined and their use in rhodium-catalysed chemistry documented. Chapter 2 discusses the tandem process of rhodium-catalysed conjugate addition enolate protonation, a recently observed asymmetric development. By using a novel route to benzyl acrylic esters the synthesis of α,α′-dibenzyl esters is achieved in excellent yields and selectivity. This study highlights the fact that when dealing with 1,1-disubstituted activated alkenes it is more difficult to produce enantioselective results as the chirality is determined in the protonation step and not during insertion. Some insights into the mechanism are proposed based on the outcomes observed. Chapter 3 describes the total synthesis of Lyngbic Acid and related structures Hermitamides A and B. Synthesis of these natural products are achieved by synthesis of an enantiopure organoborane species and its subsequent coupling via rhodium catalysis. Some interesting insights into the addition of alkenyl organoborane species to unsubstituted 1,1-activated alkenes are detailed. Chapter 4 describes the synthesis and characterisation for the compounds discussed in the previous chapters.