Cystic fibrosis (CF) is a hereditary multi-organ disorder characterized by formation of thick, viscous mucus in the lungs, leading to decreased fluid clearance and significant bacterial colonization. The bacteria form colonies, called biofilms, that are attached to the mucosal surface and produce a protective polymeric matrix. The matrix helps the biofilms form stable structures in the lungs while also protecting the embedded bacterial colonies from the host defense system and antimicrobials. Pseudomonas aeruginosa are opportunistic bacteria that commonly infect CF airways in the biofilm form. Current antibiotic treatment regimens fail to completely eradicate these biofilms, leading to chronic, persistent infections that over time lead to patient death. Therefore, there is a need to investigate antibacterial strategies that would completely eradicate these infections at reasonable doses and improve quality of patients’ lives. In this thesis, two strategies are investigated to better eradicate bacterial colonies – (1) the use of nutrient dispersion compounds for increasing the susceptibility of biofilm bacteria to the co-administered antibiotics, and (2) PEGylation of antimicrobial peptides to increase peptide retention in the lung airways. Clinical strains of P. aeruginosa isolated from lungs of CF patients were used in this research to better mimic the greater robustness of clinical biofilms compared to biofilms of laboratory bacterial strains. Growth curve studies were carried out to characterize the growth patterns of the bacterial strains. Antibiotic susceptibility of the planktonic (free-flowing) bacteria was studied using the minimum inhibitory concentration (MIC) assay. A method to grow and characterize 1-day and 4-day old biofilms in the minimum biofilm eradication concentration (MBEC) assay apparatus was developed and characterized. The MBECs of combination formulations consisting of an antibiotic and a nutrient dispersion compound for different treatment durations were measured against biofilms of the clinical isolates using four commonly used antibiotics, and sodium citrate as the nutrient dispersion compound. The growth curve studies allowed for better understanding of the clinical isolates’ growth rates in vitro, which could play an important role on their susceptibility to antibiotics. All bacterial strains displayed susceptibility to tobramycin sulfate and ciprofloxacin hydrochloride. Uniform bacterial growth was observed for 1-day old biofilms of both clinical isolates across all pegs. Growing 4-day old biofilms using 100% MHB without refreshing the bacterial suspension over 4 days gave uniform biofilm bacterial growth across the pegs. Four-day old biofilms displayed greater biomass than 1-day old biofilms for 2 out of 3 bacterial strains. Combination formulations eradicated 1-day and 4-day old biofilms at lower antibiotic concentrations than the antibiotic alone, with further improvement in eradication after increasing the duration of treatment. Sodium citrate did not enhance the metabolic activity of the biofilm bacteria. The antimicrobial peptide CaLL was conjugated with different MW polyethylene glycol (PEG) molecules using disulfide and maleimide linkages, and the effect of PEGylation on its antibacterial activity against P. aeruginosa laboratory strain PAO1 was evaluated. PEGylation was observed to reduce bacterial growth inhibition by CaLL, with the disulfide-linked CaLL-PEG less efficacious than the maleimide-linked CaLL-PEG. Time-kill assays demonstrated the longer duration of action of PEGylated peptides compared to non-PEGylated peptides, probably due to prevention of enzymatic degradation of the peptide by the PEG molecule. This research will shed light on antibacterial strategies for complete and rapid eradication of bacterial biofilms, thereby reducing development of antibiotic resistance and prevent recurrence of infection, reducing progressive lung damage caused in people with CF, and improve their quality of life.

Atmospheric transport and dispersion modeling systems are often used in assessing human exposures to chemical hazards. Models validated through quantitative and qualitative evaluation can be applied to epidemiologic study. Here, we modeled the 2005 Graniteville, South Carolina, USA railcar release of chlorine using dense gas plume dispersion models including the Hazard Prediction and Assessment Capability (HPAC) and Areal Locations of Hazardous Atmospheres (ALOHA). The release volume (54,915 kg) and rate was estimated by an engineering analysis combining semi-quantitative observations and fundamental physical principles. The use of regional meteorological conditions was validated by statistically (correlation, mean bias, root mean square deviation) comparing 1,024 HPAC concentration and surface dosage point estimates generated by two source-location weather data sets. An improved HPAC model was then statistically (correlation, root mean square deviation) compared to the earlier HPAC model using up to 9,446 surface dosage sampling points paired in time and space. The older HPAC model consistently overpredicted compared to the newer, refined model. When compared to HPAC, the ALOHA model significantly overpredicted downwind, centerline concentrations (up to 55 times that of HPAC). The refined HPAC model was then evaluated against post-incident environmental indicators of exposure such as phytotoxicity, corrosion events, deposition benchmarks, casualty data and exposed animal health outcome. A further sub-analysis was performed by comparing observed dog health outcome-derived exposure estimations versus model-predicted exposure. This statistical sub-analysis showed good agreement between observed and estimated, particularly when a sub-cohort of indoor dogs was excluded to determine the impact of structural shielding. Although the model was favorably evaluated based on literature-established standards, further assessment should be performed before the model can be fully validated and applied in human epidemiologic study to estimate acute exposures. Language: English / 1 / Dev D. Jani

Lactose is the major carbohydrate in milk. The presence of lactose in whey constitutes a significant pollution problem for dairy factories. At the same time, there is an increasing market for high quality crystalline lactose. The main problem of lactose crystallisation, compared to sucrose, which is also a disaccharide, is that it is very slow, unpredictable and cannot easily be controlled. Compared to sucrose crystallisation, which has been extensively studied, lactose crystallisation lacks the fundamental research to identify the mechanisms of growth and effect of additives. An important difference from most other crystal growth systems is that ([alpha]-lactose hydrate crystals never grow from a pure environment; their growth environment always contains beta lactose. [alpha]-lactose monohydrate crystallises much more slowly because of the presence of [beta]- lactose in all solutions. Although there have been some studies on growth rates and the effect of additives, there has not been any reported work on the fundamentals of lactose crystallisation and the mechanisms that operate on the molecular level. The aim of this thesis is to gain a greater understanding at the fundamental processes, which occur at the molecular level during the crystallisation of lactose, in order to improve control at a macroscopic level. / The growth rates of the dominant crystallographic faces have been measured in situ, at three temperatures and over a wide range of supersaturation. The mean growth rates of faces were proportional to the power of between 2.5-3.1 of the relative supersaturation. The rate constants and the activation energies were calculated for four faces. The [alpha]-lactose monohydrate crystals grown in aqueous solutions exhibited growth rate dispersion. Crystals of similar size displayed almost 10 fold difference in the growth rate grown under identical conditions for all the faces. Growth rate dispersion increases with increasing growth rate and supersaturation for all the faces. The variance in the GRD for the (0 10) face is twice the variance of the GRD of the (110) and (100) faces and ten times higher than the (0 11) face at different supersaturations and temperatures. The influence of [beta]-lactose on the morphology of [alpha]-lactose monohydrate crystals has been investigated by crystallising [alpha]-lactose monohydrate from supersaturated DMSO ethanol solutions. The slowness of mutarotation in DMSO allowed preparation of saturated solutions with a fixed, chosen [beta]-lactose content. It was found that [beta]-lactose significantly influences the morphology of [alpha]- lactose monohydrate crystals grown from DMSO solution. At low concentrations of [beta]-lactose, the fastest growing face is the (011) face resulting in long thin prismatic crystals. At higher [beta]-lactose concentrations, the main growth occurs in the b direction and the (020) face becomes the fastest growing face (since the (011) face is blocked by [beta]-lactose), producing pyramid and tomahawk shaped crystals. / Molecular modeling was used to calculate morphologies of lactose crystals, thereby defining the surface energies of specific faces, and to calculate the energies of interactions between these faces and [beta]-lactose molecules. It was found that as the replacement energy of [beta]-lactose increased, the likelihood of [beta]-lactose to dock onto faces decreased and therefore the growth rate increased. The attachment energy of a new layer of [alpha]-lactose monohydrate to the faces containing [beta]-lactose was calculated for the (010) and (011) faces. For the (0 10) face, the attachment energy of a new layer was found to be lower than the attachment energy onto a pure lactose surface, meaning slower growth rates when [beta]-lactose was incorporated into the surface. For the (011) face, attachment energy calculations failed to predict the slower growth rates of this face in the presence of [beta]-lactose. AFM investigation of [alpha]-lactose monohydrate crystals produced very useful information about the surface characteristics of the different faces of the [alpha]-lactose monohydrate crystal. The growth of the (010) face of the crystal occurs by the lateral addition of growth layers. Steps are 2 nm high (unit cell height in the b direction) and emanate from double spirals, which usually occurred at the centre of the face. Double spirals rotate clockwise on the (010) face, while the direction of spirals is counterclockwise on the (010) face. A polygonised double spiral, showing anisotropy in the velocity of stepswas observed at the centre of the prism-shaped a-lactose monohydrate crystals grown in the presence of 5 and 10 % [beta]-lactose. / The mean spacing of the steps parallel to the (011) face is larger than those parallel to the (100) face, indicating higher growth rates of the (011 )face. The edge free energy of the (011) face is 6.6 times larger than the (100) face in the presence of 5% [beta]-lactose. Increase of [beta]-lactose content from 5% to 10 % decreases the edge free energy of the growth unit on a step parallel to the (011) face by 10 %. Tomahawk-shaped [alpha]-lactose monohydrate crystals produced from aqueous solutions where the [beta]-lactose content of the growth solution is about 60 % have shown clockwise double spirals as the source of unit cell high steps on the (010) face of the crystal. However , the spirals are more circular than polygonised, unlike the prism shaped crystals and the mean step spacing of the (011) face is less than the steps parallel to the (110) face, indicating the growth rate reducing effect of [beta]-lactose on the (011) face. The (100) face of the [alpha]-lactose monohydrate crystal grows by step advancement in relative supersaturations of up to 3.1. Steps are 0.8 nm high and parallel to the c rection. Above this supersaturation, rectangular shaped two-dimensional nuclei, 10 nm high, were observed. The (011) face of the crystal grown at low supersaturations (s= 2.1) displayed a very rough surface with no steps, covered by 4-10nm high and 100-200[micro]m wide formations. Triangular shaped macrosteps were observed when the crystal was grown in solutions with s=3.1. In situ AFM investigation of the (010) face (T = 20[degree]C and s = 1.18) has shown that growth occurs by lateral addition of growth units into steps emanated by double spirals. / The growth rate of the (010) face from in situ AFM growth experiments was calculated to be 1.25 gm/min. The growth rate of crystals grown in the in situ optical growth cell under identical conditions was 0.69 pm/min. The difference in growth rates can be attributed to the size difference of seed c stals used. The (010) face of a [alpha]-lactosemonohydrate crystal grown at 22.4 C and s=1.31 displayed triangular-shaped growth fronts parallel to the (011) face. The steps parallel to the (O11) face grow in a triangular shape, and spaces between triangles are filled by growth units until the end of the macrosteps is reached. No such formations were observed on steps parallel to the (110) face. Formation of macrosteps, 4-6 nm high, emanating from another spiral present on the surface was also observed on the (010) face of a crystal grown under these conditions.

This thesis presents an investigation into the behaviour of a laser beam of finite diameter in a plasma with respect to forces and optical properties, which lead to self-focusing of the beam. The transient setting of ponderomotive nonlinearity in a collisionless plasma has been studied, and consequently the self- focusing of the pulse, and the focusing of the plasma wave occurs. The description of a self-focusing mechanism of laser radiation in the plasma due to nonlinear forces acting on the plasma in the lateral direction, relative to the laser has been investigated in the non-relativistic regime. The behaviour of the laser beams in plasma, which is the domain of self-focusing at high or moderate intensity, is dominated by the nonlinear force. The investigation of self-focusing processes of laser beams in plasma result from the relativistic mass and energy dependency of the refractive index at high laser intensities. Here the relativistic effects are considered to evaluate the relativistic self-focusing lenghts for the neodymium glass radiation, at different plasma densities of various laser intensities. A sequence of code in C++ has been developed to explore in depth self-focusing over a wide range of parameters. The nonlinear plasma dielectric function to relativistic electron motion will be derived in the latter part of this thesis. From that, one can obtain the nonlinear refractive index of the plasma and estimate the importance of relativistic self-focusing as compared to ponderomotive non-relativistic self-focusing, at very high laser intensities. When the laser intensity is very high, pondermotive self-focusing will be dominant. But at some point, when the oscillating velocity of the plasma electron becomes very large, relativistic effects will also play a role in self-focusing. A numerical and theoretical study of the generation and propagation of oscillation in the semiclassical limit of the nonlinear paraxial equation is presented in this thesis. In a general setting of both dimension and nonlinearity, the essential differences between the 'defocusing' and 'focusing' cases hence is identified. Presented in this thesis are the nonlinearity and dispersion effects involved in the propagation of solitions which can be understood by using a numerical routines were implemented through the use of the mathematica program, and results give a very clear idea of this interesting phenomena / Doctor of Philosophy (PhD)

The disintegration of agglomerates of solid charge used in a nickel flash furnace has been investigated. The in-flight agglomerate size of solid charge with different characteristics has been measured using turbulent conditions similar to a full-scale flash furnace. Plant observations indicated that under certain conditions solid charge was able to pass through the furnace shaft unreacted. The motivation for this work was to improve the understanding and the modelling of a flash furnace. A review of the literature revealed that the disintegration of agglomerates of solid charge is very important to the performance of a flash furnace, however, there has been no detailed study of the factors governing the disintegration of in-flight agglomerates of solid charge.A laboratory-scale experimental rig was constructed to non-intrusively measure the in-flight agglomerate size distribution of solid charge and to visualise the powder injection process, while using turbulent conditions similar to a flash furnace. A high-speed video technique and a laser diffraction technique were used to measure the wide range of in-flight agglomerate sizes present during powder injection. A range of variables including the particle size, turbulence level, packing density, particle shape, solid concentration, and moisture content were investigated.

The disintegration of agglomerates of solid charge used in a nickel flash furnace has been investigated. The in-flight agglomerate size of solid charge with different characteristics has been measured using turbulent conditions similar to a full-scale flash furnace. Plant observations indicated that under certain conditions solid charge was able to pass through the furnace shaft unreacted. The motivation for this work was to improve the understanding and the modelling of a flash furnace. A review of the literature revealed that the disintegration of agglomerates of solid charge is very important to the performance of a flash furnace, however, there has been no detailed study of the factors governing the disintegration of in-flight agglomerates of solid charge.A laboratory-scale experimental rig was constructed to non-intrusively measure the in-flight agglomerate size distribution of solid charge and to visualise the powder injection process, while using turbulent conditions similar to a flash furnace. A high-speed video technique and a laser diffraction technique were used to measure the wide range of in-flight agglomerate sizes present during powder injection. A range of variables including the particle size, turbulence level, packing density, particle shape, solid concentration, and moisture content were investigated.

<p><p>Microstrip structures became very attractive with the development of cost-effective dielectric materials. Among several techniques suitable to the analysis of such structures, the discrete mode matching method (DMM) is a full-wave approach that allows a fast solution to Helmholz equation. Combined with a full-wave equivalent circuit, the DMM allows fast and accurate analysis of microstrips lines on multilayered substrates.</p><p> </p><p>The knowledge of properties like dispersion and electromagnetic fields is essential in the implementation of such transmission lines. For this objective a MATLAB computer code was developed based on the discrete mode matching method (DMM) to perform this analysis.</p><p> </p><p>The principal parameter for the analysis is the utilization of different dielectric profiles with the aim of a reduction in the dispersion in comparison with one-layer cylindrical microstrip line, showing a reduction of almost 50%. The analysis also includes current density distribution and electromagnetic fields representation. Finally, the data is compared with Ansoft HFSS to validate the results.</p></p> / The German Aerospace Center has rights over the thesis work

<p>Fiber-optic networks are an integral part of todays digital communication system. In these networks, distances of typically 400 km to 6000 km are linked together, and information is transfered at extremely high data rates. As the demands for capacity increases, finding new methods for cost effective long-haul transmission systems that can be used to increase the capacity becomes of high interest. In this work Orthogonal Frequency Division Multiplexing (OFDM), which is a standard digital modulation format in many wireless communication systems, for instance the IEEE 802.11n, is adapted to the optical domain and used for data transmission. The advantage of OFDM in the optical domain is that it transforms a high data rate stream into many simultaneously low bit rate streams that are efficiently frequency multiplexed. By doing so high spectral efficiency is achieved and many of the impairments encountered in high data rate transmissions are avoided. The disadvantage is however, that OFDM has inherently a high peak-to-average power ratio. As a result, OFDM suffers from nonlinearities occurring along the transmission line. The low nonlinear tolerance of OFDM in fiber optic applications restricts the feasible transmission distance. The goal of this work is to assess the suitability of OFDM in fiber-optic communications</p>

An interaction by exchange with the conditional mean (IECM) micromixing model is coupled to a three-dimensional single-particle Lagrangian stochastic (LS) model to estimate concentration fluctuations in plumes of a passive (i.e., non-buoyant), non-reactive (i.e., no chemistry) tracer dispersing from a variety of source configurations in four neutrally stratified flows: a horizontally-homogeneous wall shear layer flow; a horizontally-homogeneous representation of the Tombstone canopy flow; a three-dimensional inhomogeneous representation of the Tombstone canopy flow; and a three-dimensional inhomogeneous representation of the Mock Urban Setting Trials (MUST) canopy flow. The IECM micromixing model incorporates the combined effects of turbulent and molecular mixing on particle concentration. This allows the numerical estimation of all moments of the scalar concentration field, which is a significant advance over traditional LS models given that concentration fluctuations are a ubiquitous feature of a dispersing plume. The single-particle implementation of the LS-IECM model is based upon a previously reported implementation that used simultaneously computed particle trajectories to estimate the conditional mean concentration field [Cassiani, M. A., Franzese, P. A. and Giostra, U. A.: 2005, A PDF micromixing model of dispersion for atmospheric flow. Part I: development of model, application to homogeneous turbulence and to a neutral boundary layer, Atmospheric Environment 39, 1457-1469]. The model used in this thesis pre-calculates the conditional mean concentration field with an LS model for use with the IECM model, which runs as a separate simulation. The principal advantage of this single-particle approach is the performance increase on parallel computer architecture, which scales directly with the number of processors. The simulations presented in this thesis go beyond those performed with the previous model by considering three-dimensional inhomogeneous flows, as well as one-dimensional horizontally-homogeneous flows. The accuracy of the LS-IECM model was good for the flows with horizontal-homogeneity, and comparable to the results of previous simulations from older models. Rogue velocities in the simulations utilising inhomogeneous flow statistics resulted in acceptable to poor accuracy in these simulations. Suggestions for improvements to the model are made.

Microstrip structures became very attractive with the development of cost-effective dielectric materials. Among several techniques suitable to the analysis of such structures, the discrete mode matching method (DMM) is a full-wave approach that allows a fast solution to Helmholz equation. Combined with a full-wave equivalent circuit, the DMM allows fast and accurate analysis of microstrips lines on multilayered substrates.   The knowledge of properties like dispersion and electromagnetic fields is essential in the implementation of such transmission lines. For this objective a MATLAB computer code was developed based on the discrete mode matching method (DMM) to perform this analysis.   The principal parameter for the analysis is the utilization of different dielectric profiles with the aim of a reduction in the dispersion in comparison with one-layer cylindrical microstrip line, showing a reduction of almost 50%. The analysis also includes current density distribution and electromagnetic fields representation. Finally, the data is compared with Ansoft HFSS to validate the results. / The German Aerospace Center has rights over the thesis work