Chronic diseases can often be managed by constantly delivering therapeutic amounts of drug for prolonged periods. A controlled release for extended duration would replace the need for multiple and frequent dosing. Local drug release would provide added benefit as a lower dose of drug at the target site will be needed as opposed to higher doses required by whole body administration. This would provide maximum efficacy with minimum side effects. Nonetheless, a problem with the known implantable drug delivery devices is that the delivery rate cannot be controlled, which leads to drug being released in an unpredictable pattern resulting in poor therapeutic management of patients. This dissertation is the result of development of an implantable drug delivery system that is capable of long-term zero order local release of drugs. The device can be optimized to deliver any pharmaceutical agent for any time period up to several years maintaining a controlled and desired rate. Initially significant efforts were dedicated to the characterization, biocompatibility, and loading capacity of nanoporous metal surfaces for controlled release of drugs. The physical characterization of the nanoporous wafers using Scanning electron microscropy (SEM) and atomic force microscopy techniques (AFM) yielded 3.55 x 10⁴ nm³ of pore volume / μm² of wafer surface. In vitro drug release study using 2 - octyl cyanoacrylate and methyl orange as the polymer-drug matrix was conducted and after 7 days, 88.1 ± 5.0 % drug was released. However, the initial goal to achieve zero order drug release rates for long periods of time was not achieved. The search for a better delivery system led to the design of a perforated microtube. The delivery system was designed and appropriate dimensions for the device size and hole size were estimated. Polyimide microtubes in different sizes (125-1000 μm) were used. Micro holes with dimensions ranging from 20-600 μm were fabricated on these tubes using photolithography, laser drilling, or manual drilling procedures. Small molecules such as crystal violet, prednisolone, and ethinyl estradiol were successfully loaded inside the tubes in powder or solution using manual filling or capillary filling methods. A drug loading of 0.05 – 5.40 mg was achieved depending on the tube size and the drug filling method used. The delivery system in different dimensions was characterized by performing in vitro release studies in phosphate buffered saline (pH 7.1-7.4) and in vitreous humor from the rabbit’s eye at 37.0 ± 1.0°C for up to four weeks. The number of holes was varied between 1 and 3. The tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE). Linear release rates with R²>0.9900 were obtained for all groups with CV and EE. Release rates of 7.8±2.5, 16.2±5.5, and 22.5±6.0 ng/day for CV and 30.1±5.8 ng/day for EE were obtained for small tubes (30 μm hole diameter; 125 μm tube diameter). For large tubes (362-542 μm hole diameter; 1000 μm tube diameter), a release rate of 10.8±4.1, 15.8±4.8 and 22.1±6.7 μg/day was observed in vitro in PBS and a release rate of 5.8±1.8 μg/day was observed ex vivo in vitreous humor. The delivery system was also evaluated for its ability to produce a biologically significant amounts in cells stably transfected with an estrogen receptor/luciferase construct (T47D-KBluc cells). These cells are engineered to produce a constant luminescent signal in proportion to drug exposure. The average luminescence of 1144.8±153.8 and 1219.9±127.7 RLU/day, (RLU = Relative Luminescence Units), yet again indicating the capability of the device for long-term zero order release. The polyimide device was characterized for biocompatibility. An automated goniometer was used to determine the contact angle for the device, which was found to be 63.7±3.7degreees indicating that it is hydrophilic and favors cell attachment. In addition, after 72 h incubation with mammalian cells (RAW 267.4), a high cell distribution was observed on the device’s surface. The polyimide tubes were also investigated for any signs of inflammation using inflammatory markers, TNF-α and IL-1β. No significant levels of either TNF-α or IL-1β were detected in polyimide device. The results indicated that polyimide tubes were biocompatible and did not produce an inflammatory response. / text

The chick chorio-allantoic membrane (CAM) contains a complex vascular network commonly used to study angiogenesis. The application of chemical factors and oxygen barrier films onto this tissue can easily influence the process of angiogenesis. In this study, oxygen barrier film patches (Krehalon, polyvinylidene chloride, 12 μm thick, O2 transmission rate = 2.19 cm3•ml/100 in2•day•atm) were applied to areas of the CAM. Holes were made in the film and alginate beads incubated in various chemical factors were placed in the holes. After 24 and 48 hours of exposure to the alginate beads, images were taken of the tissue using a stereomicroscope and then processed using ImageJ software (from the National Institue of Health (NIH)). The images were analyzed with the Fractal Analysis plugin of ImageJ (also from NIH) using four parameters. These parameters are the number of vessel segments, the number of vessel bifurcations, the total length of the vessels, and the complexity of the vascular network. From these parameters, the chemical factors can be identified as promoting angiogenesis (pro-angiogenic), inhibiting angiogenesis (anti-angiogenic), or having no effect on angiogenesis (not angiogenic). For the angiogenic beads, significant results were found in at least one of the four parameters. SNAP and H2O2 gave pro-angiogenic responses while Angiotensin II, Losartan, and Adenosine were anti-angiogenic. To test the effect of an oxygen barrier film patch on angiogenesis, images were taken of the tissue under the film patch (virtual holes) and holes exposed to atmospheric oxygen. Analysis of the virtual holes compared to the control holes gave significant results for several of the film patches. These film patches are distinguished by the chemical that was tested on each of the films. The virtual holes containing Angiotensin II, Losartan, Adenosine, and H2O2 gave pro-angiogenic results while SNAP and L-NAME virtual holes were anti-angiogenic. Thus, the chemical factors and the oxygen barrier film patches did have an effect on angiogenesis in the CAM.

Each of the studies conducted herein is related to best management practices for stormwater pollutant removal. This thesis is divided into two chapters. Chapter One details the development and functionality of a novel stormwater detention pond outlet, the solid state skimmer. The device is a perforated riser having no moving parts that is capable of draining detention ponds primarily from the topmost orifices. We found that such a device is capable of reducing effluent turbidity and sediment concentrations compared to a traditional riser outlet. Chapter Two describes a water quality monitoring study performed to show that a pervious concrete detention system can remove stormwater pollutants from parking lot runoff. The stormwater flowed across asphalt paving before infiltrating into the pervious concrete and an aggregate sub-base below. We sampled the runoff before it entered the pervious and after it passed through the detention system and found significant decreases in several pollutants.

In this study, the basic absorption and scattering characteristics of acoustic scatterers, specifically Schroeder Diffusers, are investigated. Schroeder Diffusers are one of the most widely used acoustic scatterers in which the scattering phenomenon is predictable due to the geometry of the diffuser, based on a particular mathematical sequence. It is shown that it is possible to increase the amount of absorption by modifying the diffuser structure by means of adding perforated panels into the wells or narrowing diffuser wells. In room acoustics applications, diffusers are conventionally mounted to a wall or ceiling assumed to be rigid enough such that sound wave cannot penetrate through. This thesis proposes a new modification on these diffusers where the diffuser is not backed by a rigid surface / it is hung over a space instead. To construct such a configuration, diffuser wells are terminated with micro-perforated panels (MPP). Inclusion of MPP introduces additional losses / hence, higher absorption can be achieved. However, the most significant absorption in this configuration is achieved below the first resonance frequency of the panel-air space system due to the existence of non-rigid backing. This thesis aims to model the absorption and scattering mechanisms enabled with the non-rigid backing by improving a previously introduced mathematical model.

Micro-perforated sound absorbers with sub-millimeter size holes can provide high absorption coefficients. Various types of micro-perforated absorbers are now available in literature for different applications. This thesis presents results of work on the development of an effective single layer micro-perforated sound absorber from the commercial composite material Parabeam with micro diameter holes drilled on one side. Parabeam is used as a structural material made from a fabric woven out of a E-glass yarn and consists of two decklayers bonded together by vertical piles in a sandwich structure with piles (thick fibers) woven into the decklayers. The thesis includes, the analytical model developed for prediction of absorption coefficients, finite element solution using commercial software MSC.ACTRAN and experimental results obtained from impedance tube measurements. Different absorption characteristics can be achieved by variations in hole diameter and hole spacing. Based on the developed models, an optimization is performed to obtain an efficient absorber configuration. It has been anticipated that several different and interesting applications can be deduced by combining structural and sound absorption properties of this new micro-perforated absorber along with conventional fibrous absorbers.

This work is primarily comprised of five self-contained papers. Three papers are applications oriented. A common element in the first three papers is that micro-perforated panels (MPP), the permeable membranes in diesel particulate filters, and a source impedance are all modeled as a transfer impedance. The first paper deals with enhancing the performance of micro-perforated panels by partitioning the backing cavity. Several different backing schemes are considered which enhance the performance without increasing the total volume of the MPP and backing. In the second paper, a finite element modeling approach is used to model diesel particulate filters below and above the plane wave cutoff frequency. The filter itself is modeled using a symmetric finite element model and results are compared to plane wave theory. After the transfer matrix of the filters is known, it is used in three-dimensional finite and boundary element models. The third paper is a tutorial that shows how a source impedance can be modeled using transfer impedance approaches in finite element analysis. The approach used is useful for better understanding the resonance effects caused by pipes upstream and downstream of the exhaust. The fourth paper examines the best practice for the two-load transmission loss measurement. This method was integral to obtaining the measurements for validating the diesel particulate filter models. The fifth paper proposes transmission and insertion loss metrics for multi-inlet mufflers. It is shown that the transmission loss depends on the amplitude and phase relationship between sources (at the inlets) whereas insertion loss depends on both the source strength and impedance for each inlet.

Perforated tubes in mufflers are generally modeled by the transfer impedance approach since modeling the actual geometry of the perforated tubes with holes is very expensive due to the enormity of the boundary elements required. With the development of the substructuring technique which greatly reduces the number of elements required detailed modeling of the perforated tubes has become possible. In this thesis mufflers with perforated tubes are analyzed by modeling the actual geometry and locations of holes on the perforated tubes. The Direct-mixed-body boundary element method with substructuring is used to model the mufflers. Mufflers of various geometry containing perforated tubes with holes of different sizes and porosity are tested. The results obtained from the analyses are compared with the empirical formula results and experimental results. A preliminary investigation on the detailed modeling of flow-through catalytic converters is also conducted.

Master of Science / Department of Mechanical and Nuclear Engineering / J. Kenneth Shultis / Perforated neutron detectors suffer the unfortunate effect that their efficiency is a strong function of the direction of neutron incidence. It is found, by Monte Carlo simulation of many perforation shapes, that sinusoidal-type perforations greatly reduce the variation of detector efficiency. Detectors with rod-type perforations are modeled using a hybrid transport method linking the MCNP transport code and a specialized ion-transport code to calculate the probability that a neutron is detected. Channel, chevron, and sinusoidal perforations are modeled using other customized transport codes. Detector efficiency calculations are performed for neutrons incident at various polar and azimuthal angles. It is discovered that the efficiency losses of the detectors result from the decreasing solid angle subtended by the detector from the source and streaming through the detector at specific azimuthal angles. Detectors achieving an efficiency in excess of 10% and having a relatively flat ± 1% angular dependence in all azimuthal angles and polar angles between 0 and 60 degrees are predicted. Efficiencies up to 25% are achievable at the loss of directional independence. In addition to minimizing the directional dependence of the perforated detectors, the feasibility of developing a neutron detector for deployment in cargo containers to locate nuclear weapon pits is investigated using the MCNP transport code. The detector considered is a 7-mm diameter, 6LiF, rod-perforated detector surrounded in a cylinder of polyethylene. The optimum thicknesses of surrounding polyethylene, to maximize the response of the detector, is determined to be 10 cm of radial, 5 cm of front, and 5 cm of back polyethylene for end-on neutron incidence. Such a detector is predicted to produce a count rate between 12 and 15 cpm from a nuclear-weapon pit composed of 90% 239Pu and 10% 240Pu at a distance of 3 m. Side incidence is also considered, and the optimum moderator dimensions are 8 cm of radial, 10 cm of front, and 10 cm of back polyethylene that produce approximately the same count rate.

Steel beams with web openings are frequently used in construction to achieve attractive, flexible and optimised design solutions. These beams are used to provide passages for building services, to reduce the overall construction height and to achieve long spans. However, the presence of the openings may lead to a substantial reduction in the load carrying capacity of the beam at both ambient and elevated temperatures and introduce additional failure modes including shear-moment interaction at the location of the openings causing the Vierendeel mechanism. Steel beams in practical construction are axially restrained and the presence of this axial restraint can drastically change the behaviour of the beams in comparison to those without axial restraint. One particular issue is premature buckling of the compressive tee-sections around the openings. The aim of this research is to investigate the effects of openings on axially restrained steel beams at elevated temperatures so as to develop an analytical method for design consideration. The analytical derivation will be based on the results of extensive numerical simulations. The research starts with the behaviour of steel beams with web openings under combined axial compression, bending moment and shear force at ambient temperature. The results show that buckling of the compressive tee-sections at the openings can reduce the plastic moment capacity of the openings; and an analytical method has been proposed to incorporate the influences of axial compression and tee-section buckling into the existing shear-moment design equations. The elevated temperature simulations show that axially restrained steel beams with web openings may enter catenary action at much lower temperatures than the commonly accepted critical failure temperatures calculated assuming no axial restraint and no tee-section buckling. Therefore, at the commonly accepted critical failure temperatures, many perforated steel beams exert tensile forces on the adjacent connections. It is important that the connections have the strength and deformation (rotation) capacity to enable catenary action to develop. The parametric study examines, in detail, how changing the different design parameters may affect the elevated temperature behaviour of perforated beams. The examined parameters including load ratio, level of axial restraint, cross-section temperature distribution profile, opening shape, opening size and opening position. Based on the results of the numerical parametric study, an analytical method has been derived to obtain the complete axial force-temperature relationship for axially restrained perforated steel beams. The key points of the analytical method include initial stiffness, point of initial failure under combined axial compression, bending moment and shear force, transition temperature at which the axial force on the beam changes from compression to tension and the magnitude of the tensile force resulting from the beams going into catenary action. Using the analytical method, it is possible to assess the maximum tensile force in the beam and the corresponding temperature so that the safety of the connections can be checked.

Numerické řešení matematických modelů popisujících chování materiálů s jemnou strukturou (kompozitní materiály, jemně perforované materiály, atp.) obvykle vyžaduje velký výpočetní výkon. Proto se při numerickém modelování původní materiál nahrazuje ekvivalentním materiálem homogenním. V této práci je k nalezení homogenizovaného materiálu použita dvojškálová konvergence založena na tzv. rozvinovacím operátoru (anglicky unfolding operator). Tento operátor poprvé použil J. Casado-Díaz. V disertační práci je operátor definován jiným způsobem, než jak uvádí původní autor. To dovoluje pro něj dokázat některé nové vlastnosti. Analogicky je definován operátor pro funkce definované na perforovaných oblastech a jsou dokázány jeho vlastnosti. Na závěr je rozvinovací operátor použit k nalezení homogenizovaného řešení speciální skupiny diferenciálních problémů s integrální okrajovou podmínkou. Odvozené homogenizované řešení je ilustrováno na numerických experimentech.