This dissertation reports on the recent discovery that calix[4]pyrrole not only functions as an anion receptor, but also has the ability to act as an ion pair receptor. It was discovered that in the solid state large diffuse cations, such as Cs+ and imidazolium, will occupy the electron-rich cone-like cavity that is formed upon anion binding to the NH region of the calix[4]pyrrole core. Also discussed are efforts devoted to improving the anion binding ability of calixpyrroles and fine-tuning their inherent selectivity. This has been probed through a variety of structural modifications. One of the most attractive of the modification strategies currently being explored involves expansion of the central binding cavity by using higher order β-fluorinated calix[n]pyrroles; n = 5, 6, and 8. An advantage of β-fluorinated calix[4]pyrrole is that it shows enhanced anion binding affinities toward several anions compared to the parent calix[4]pyrrole. Fluorinated calixpyrroles have also shown an ability to extract anions from aqueous environments into organic media. An alternative strategy has been to attach “straps” resulting in bicyclic systems, which further define the binding cavity achieving higher affinity and anion selectivity. The binding interactions of calixpyrrole and it derivative have been quantified using analytical techniques, such as nuclear magnetic resonance spectroscopy and isothermal titration calorimetry. The results of these latter studies will be discussed herein. / text

Monitoring the limiting reactant concentration is a key question to maximize the productivity and to guarantee the safety of exothermic fed-batch processes. However in most applications, the concentration cannot be measured in real-time since suitable devices do not exist or are too expensive; the concentrations are then measured by off-line analyses. In this context monitoring the concentrations via software sensors, or state observer based estimators, is an attractive option. The presence of model uncertainties is a major limitation when applying state observers to real processes. More precisely, in fed-batch exothermic reactors the bad knowledge of both the reaction kinetics and the heat transfer may prevent the use of classical observers. In this study, we propose two different approaches to estimate the concentration of the limiting reactant in a class of single phase exothermic fed-batch reactors with uncertain kinetics and heat transfer. The first approach is based on a finite time converging observer that provides an estimate for the reaction rate via the reactor energy balance equation. The concentration is then computed from the reaction rate estimate via a material balance equation. The main contribution of this approach is the use of a finite time observer to limit the reconstruction error by guaranteeing a small convergence time interval for the reaction rate estimate. The second approach is based on an interval observer that provides two bounds for the concentration by considering uncertainties related to both the heat transfer and the reaction kinetics. The final estimate is then computed as the mean of the bounds. A systematic tuning procedure has been developed for each of both estimation techniques. Both estimators have then been tested and validated with real data coming from the production of different kinds of resins carried out in 10 tons reactors.

No description available.

ABSTRACT The magnitude of the AIDS epidemic is well documented. It has been shown that Africa constitutes about 70 % of people infected with HIV worldwide. Efforts to control the AIDS epidemic have focused heavily on studies pertaining to the biology, biochemistry and structural biology of HIV and on the interactions between HIV proteins and new drugs. One of the most challenging problems in AIDS therapy is that HIV develops drug-resistant variants rapidly. Extensive research has been dedicated to designing resistance-evading drugs for HIV-1 protease (predominantly subtype B), which is crucial for the maturation of viral, structural and enzymatic proteins. There are 10 subtypes of HIV-1 within the major group of the virus, with subtype C accounting for about 95 % of infections in South Africa. Since HIV-1 antiretroviral treatment has been developed and tested against the B subtype, which is prevalent in North America, Western Europe and Australia, an important question relates to the effectiveness of these drugs against the C subtype. At this point, however, little is known about inhibitor-resistant mutations in the subtype C. The study, therefore, looked at the two active site mutations (V82A and V82F/I84V) in the South African HIV-1 subtype C protease (C-SA) emerging from the viral population circulating in patients. These mutations are well-characterized within the framework of the subtype B and are known to cause cross-resistance to most of inhibitors currently in clinical use. Protein engineering techniques were used to generate the V82A and the V82F/I84V variants. Comparative studies with the wild-type HIV-1 C-SA protease were performed. The spectral properties of the V82A and the V82F/I84V variants indicated no changes in the secondary structure in the respective variant proteins. Tryptophan and tyrosine fluorescence indicated a major difference in the intensities at the emission maxima for all three proteins. The fluorescence intensity of the V82F/I84V variant, in particular, was significantly enhanced indicating the occurrence of tertiary structural changes at/near the flap region. Both mutations did not impact significantly upon catalytic function. Both variants also had the same Km values comparable to that of the wild-type enzyme. The catalytic efficiencies and the kinetic constants were lowered 3.6-fold for the V82A mutation and 6-fold for the V82F/I84V mutation relative to the wild-type C-SA protease. Inhibition studies were performed using four inhibitors in clinical use (saquinavir, ritonavir, indinavir and nelfinavir). For the V82A variant, IC50 and Ki values for saquinavir and nelfinavir iv were not affected, whilst those for ritonavir and indinavir were 5- and 9-fold higher than the wild-type C-SA protease, respectively. Against the V82F/I84V variant, however, the inhibition constants were drastically weaker and characterized by IC50 and Ki ratios ranging from 50 to 450. Isothermal titration calorimetry (ITC) was also used to determine the binding energetics of saquinavir, ritonavir, indinavir and nelfinavir to the wild-type C-SA, V82A and V82F/I84V HIV-1 protease. The V82A mutation lowered the Gibbs energy of binding for the respective four clinical inhibitors by 0.4 kcal/mol, 1.3 kcal/mol, 1.5 kcal/mol and 0.6 kcal/mol, respectively, relative to the wild-type C-SA HIV-1 protease. The affinity of V82A HIV-1 protease for saquinavir, ritonavir, indinavir and nelfinavir (Kd = 1.85 nM, 2.00 nM, 12.70 nM and 0.66 nM, respectively, at 25 °C) was in the range of 2- to 13-fold of magnitude weaker than that of the wild-type C-SA protein. The clinical inhibitors exhibited the highest binding affinity to both the wild-type and the V82A enzymes, but were extremely sensitive to the V82F/I84V mutation. The V82F/I84V mutant reduced the binding of saquinavir, ritonavir, indinavir and nelfinavir 117-, 1095-, 474- and 367- fold, respectively. A drop in Kd values obtained for the V82F/I84V in association with saquinavir, ritonavir, indinavir and nelfinavir was consistent with a decrease of between 2.8 - 4.2 kcal/mol in ΔG, which is equivalent to at least 2 to 3 orders of magnitude in binding affinity. Taken together, thermodynamic data indicated that the V82A and V82F/I84V active site mutations in the C-SA subtype lower the affinity of the first-generation inhibitors by making the binding entropy less positive (unfavorable) and making the enthalpy change slightly less favorable.

The formation, phase ordering, and evolution has been studied in lipid and liquid crystal (LC) colloidal aqueous mixtures as a function of LC concentration and thermal history. The lipid used was 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) while the liquid crystal was pentylcyanobiphenyl (5CB). POPC is a naturally occurring lipid in eukaryotic cell membranes and mimics many of the properties of human cell walls. 5CB is a polar liquid crystal that exhibits a thermodynamically stable orientationally ordered (nematic) state at room temperature. Colloidal dispersions were made at various 5CB and POPC concentrations in water and studied via optical microscopy (phase contrast, confocal, florescence, and cross-polarizing) to probe phase order and evolution as well as by calorimetry to study phase transformations. Very large vesicles (larger than 100 micrometers) were observed to form that appear to use the phase separated 5CB droplets as scaffolds. Also, there appears a unique promotion of dye (used to image the lipid bilayers) crystallization within liquid crystal domains well above room temperature.

This study presents the design, construction and testing of an Outdoor Gas Emission Sampling (OGES) System capable of gas sampling and calorimetry in outdoor conditions with wind. In large-scale, outdoor fire tests, wind-driven emission plumes present a challenge in heat release rate quantification because the emission plume rises upward at an angle. A new gas sampling system with a flexible hood design and smaller control volume has been designed and tested. Bulk flow rate, oxygen, carbon dioxide, and carbon monoxide concentrations are measured for heat release rate calculations. Two stages of experimentation are described. Experiments at intermediate-scale (indoor only) that were conducted to evaluate the performance of a smaller control volume for measurements, and large-scale (indoor and outdoor) experiments, to demonstrate feasibility in realistic field conditions as well as the new flexible hood design. Experiments show that the OGES system is capable of calculating the heat release rate of pool fires with an accuracy of 23% using oxygen consumption (OC) and carbon dioxide generation (CDG) methods. Further improvements of the OGES system for outdoor field deployment are also discussed.

Doctor of Philosophy(PhD) / Particle formation in RAFT-mediated emulsion polymerization has been studied using reaction calorimetry. By measuring the heat flow during controlled feed ab-initio emulsion polymerization in the presence of amphipathic RAFT agents, particle formation by self-assembly of these species could be observed. Two different monomer systems, i.e. styrene and n-butyl acrylate, and various degrees of hydrophobicity of the initial macro-RAFT agents have been studied and compared. The different macro-RAFT agents were synthesized by first forming a hydrophilic block of poly(acrylic acid) that would later on act as the electrosteric stabilizing group for the particles. Subsequently, different lengths of hydrophobic blocks were grown at the reactive end of the poly(acrylic acid) hydrophilic block via the RAFT-mediated controlled radical polymerization, either comprised of n-butyl acrylate or styrene. Two processes govern particle formation: adsorption of macro-RAFT agents onto growing particles and formation of new particles by initiation of micellar aggregates or by homogeneous nucleation. Competition between these processes could be observed when monomers with a relatively high (n-butyl acrylate) or low (styrene) propagation rate coefficient were used. A model describing particle formation has been developed and the results of model calculations are compared with experimental observations. Preliminary modeling results based on a set of reasonable physico-chemical parameters already showed good agreement with the experimental results. Most parameters used have been verified experimentally. The development of the molecular weight distribution of the macro-RAFT agents has been analyzed by different techniques. Quantification of the particle formation process by analytical techniques was difficult, but qualitative insights into the fundamental steps governing the nucleation process have been obtained. The amount of macro-RAFT agents initially involved in particle formation could be determined from the increase of molecular weight. The particle size distribution has been measured by capillary hydrodynamic fractionation, transmission electron microscopy and dynamic light scattering. From the data obtained from these particle-sizing techniques, the number of particles during the reaction could be monitored, leading to an accurate estimate for the particle formation time. Upon implementation of the experimental data obtained for the surface active macro-RAFT systems, the model demonstrated to be very sensitive towards the “headgroup” area of the macro-RAFT species. Three nucleation cases based on the initial surface activity of the macro-RAFT species in the aqueous phase are proposed to explain the deviations from the assumptions of the nucleation model. Even though the macro-RAFT species have a narrow molecular weight distribution, they are nevertheless made up of a distribution of block lengths of polystyrene upon a distribution of block lengths of poly(acrylic acid). The resulting differences in initial surface activity are the most probable reason for the observed differences between model calculations and experimental results for the nucleation time and particle size distribution of the final latex product. With the procedure described above, latexes have been synthesized without using conventional surfactants and the mechanisms involved in the particle formation for these systems have been elucidated. The results of this work enable production of latex systems with well defined molecular mass distributions and narrow particle size distributions. Furthermore, the technique based on the application of amphipathic RAFT agents is promising for the production of complex polymeric materials in emulsion polymerization on a technical scale.

Obesity is the most prevalent nutritional disorder in cats (Felis catus; Hoenig et al., 2011). High carbohydrate diets, prescribed for weight loss, may contribute to adiposity (Thiess et al., 2004). The effects of a high fat (HF; 30% fat, 10% carbohydrate), high carbohydrate (HC; 10% fat, 46% carbohydrate) and a moderate diet (15% fat, 30% carbohydrate) supplemented with a calorie restriction mimetic (mannoheptulose (MH); 8 mg/kg BW), fed to energy requirements, on feline metabolism and behaviour were investigated (n=20; 4 ± 2.5 kg). An 11 week acclimation procedure was designed to adapt cats to 24-hr restriction within a chamber used for indirect calorimetry. Stress indicative behaviour (Kessler and Turner, 1997) declined with repreated exposure to increasing lengths of restriction within chambers and on week 11 stress levels were low and consistent (P<0.05). Neither the HF nor HC diet impacted body weight (p>0.05); however, HF feeding caused an increase in body fat (0.75 kg (baseline) vs. 1 kg (86d)) after long-term feeding. Energy expenditure (EE) was not impacted by dietary fat/carbohydrate. Respiratory quotients (RQ) increased and decreased with exposure to the HC (fasted= 0.80 ± 0.008; fed= 0.87 ± 0.008), HF (fasted= 0.76 ± 0.008; fed= 0.78 ± 0.008) diet, respectively. Glucose to insulin (G:I) ratio increased with HF feeding; indicating improved insulin sensitivity. Physical activity, measured using accelerometers, declined with HF (-1.6 counts/hr) and HC (-2.8 counts/hr) feeding from baseline. T-maze performance decreased and increased with HF (-0.85 score/10) and HC (0.85 score/10) feeding from baseline (p<0.05). MH did not impact body weight or composition (p>0.05). Area under the curve for EE increased during the 15-22 hour post feeding with MH treatment (2370.3 (-MH) vs. 3292.0 (+MH) ± 0.0002). RQ and G:I were not impacted by MH (p>0.05). MH increased play motivation, measured using obstruction tests (p<0.05). Diets high in carbohydrate are not ideal for weight loss since they negatively impact insulin sensitivity and voluntary EE. Diets promoting elevated EE, activity and normal glucose/insulin profiles are ideal for weight control and MH offers a unique opportunity for use in weight loss regimes. / This work was funded by Procter and Gamble Co.

No description available.

Experiment 683, at Fermi National Accelerator Laboratory's Wide Band Photon Laboratory, is designed to study photon-hadron collisions at energies up to ~s = 27 GeV. The Wide Band Photon Lab currently the highest energy photon beam in the world. Several processes are to be studied. One such process in the quantum electrodynamic (QED) Compton effect. This paper is concerned with the design and construction of a small electromagnetic calorimeter (with embedded proportional wire chambers) to be used to aid in the study of the QED Compton effect. A theoretical description of the QED Compton effect is given. Basic principles of calorimetry, as it pertains to high energy physics, are discussed. Tests of the components used for construction of this device is discussed and results reviewed. The components include wavelength shifter, scintillator, photomultiplier tubes, and photomultiplier tube bases. Muon testing of this device is discussed also. / Department of Physics and Astronomy