<p>There were 2.5 million people newly infected with HIV in 2007, clearly motivating the need for additional novel prevention methods. In response, topical vaginal antimicrobials, or microbicides, are being developed. These products aim to stop HIV transmission through local, vaginal delivery of antiviral compounds. To succeed, microbicides require a potent active compound within a well-engineered delivery vehicle.</p><p>A well-engineered delivery vehicle provides an antiviral compound with the greatest opportunity to interact with HIV and/or infected cells, thereby increasing overall microbicide effectiveness. The theoretical and experimental investigations within this dissertation are concerned with the study of HIV and active compound transport within microbicide delivery vehicles and with the mechanisms by which these transport processes can be affected to maximize viral neutralization. To initially investigate the factors contributing to microbicide effectiveness, a combined pharmacokinetic and pharmacodynamic model of HIV transport and neutralization within a microbicide product was created. Model results suggested that thin (~100µm) layers of microbicide product may protect against HIV infection. Model results also indicated that a specific and engineerable property of delivery vehicles - the ability to restrict viral transport - may increase the overall effectiveness of a microbicide. Two new experimental assays were developed to test the hypothesis that delivery vehicles can slow viral transport. First, a novel methodology was created to measure particle diffusion over length scales relevant to microbicide delivery (50-500µm). Results showed that current vehicles significantly restrict the transport of small molecules and proteins. The second assay was designed to test HIV transport in a biologically relevant, layered (fluid-microbicide-tissue) configuration of a microbicide product in vivo; infectious HIV was placed above a thin layer of a microbicide delivery vehicle. Assay results showed that HIV transport is significantly slowed by two different placebo gels. This experimental confirmation of viral restriction in hydrogels, combined with the theoretical finding that viral restriction increased microbicide effectiveness, strongly motivates the future development of new delivery vehicles that intentionally slow viral transport. These new experimental methodologies can also be used to screen and compare future delivery vehicles to produce optimal microbicide products.</p><p>Finally, a two-dimensional, computational finite-element vaginal model was created to evaluate the transport of drugs from an intravaginal ring. This model determined that while IVRs may be effective in the delivery of antiviral compound, their performance is influenced by the flow of vaginal fluid. The analysis also warns about the potential for local toxicity. </p><p>Well-engineered delivery vehicles are an essential component to microbicide performance because they maximize the opportunities for active compounds to interact with and neutralize HIV. The studies in this dissertation demonstrate that delivery vehicles have a significant effect on active compound and HIV transport. To create an effective microbicide, vehicle effects on transport processes must be well understood, purposefully engineered, and carefully optimized to ensure maximal interactions between antiviral compounds and virus. Directed engineering of delivery vehicles contribute to the foundation for microbicide success.</p> / Dissertation

<p>This dissertation explores strategies for reducing HIV-virion transport to mucosal surfaces to prevent HIV infection. Infection requires contact between HIV and an infectable cell, so any means of inhibiting this step could contribute to HIV prevention. Our goals were to quantify the effects of strategies that reduce transport of HIV virions and to evaluate them in the context of HIV prevention. We used fundamental transport theory to design two basic strategies: (1) modifying the effective radius of virions; and (2) modifying the native medium through which virions diffuse. We proposed to implement these strategies using (1) anti-HIV antibodies that would bind and aggregate virions and (2) topically-applied semi-solid gels that coat vaginal epithelial surfaces. </p> <p>We measured diffusion coefficients of HIV virions and HIV-like particles in the presence of antibodies and within semi-solid gels. In experiments with antibodies, we did not observe reductions in the diffusion coefficients. In experiments using particle tracking to measure the diffusion coefficients of virions in vaginal gels, we found that the diffusion coefficients in gels were approximately 10,000 times lower than those in water. </p> <p>We proceeded to evaluate the potential for semi-solid gels to prevent HIV transmission at mucosal surfaces. From previous experiments in our lab that characterized the topical deployment of vaginal gels <italic>in vivo</italic>, we know that vaginal gels form an uneven coating on the epithelium with gel layer thicknesses of the order of hundreds of microns. Thus, we determined whether semi-solid gels could function as physical barriers to HIV when deployed as thin, incomplete layers on the epithelium. </p> <p>We developed an experimental system to test the barrier functioning of thin gel layers. We applied thin gel layers to the porous membrane of a Transwell system, and added a solution of HIV to the top compartment. After incubation, samples were assayed for levels of HIV. We found that thin gel layers reduced levels of HIV in the bottom compartment compared to controls where no gel had been applied: There was a log reduction in levels of HIV in conditions where gel layers of approximately 150 &mu;m thickness had been applied to the membrane after 0-, 4-, and 8-hour incubation. Thus, it appears possible for gel layers of thicknesses found <italic>in vivo</italic> to function as physical barriers to HIV over biologically-relevant time scales. </p> <p>We studied how nonuniform deployment of semi-solid gels affects accumulation of virions in tissue using a mathematical model. We used transport theory to develop a model of HIV diffusing from semen, through gel layers where present, to tissue. Our findings suggest that comprehensive coating of over 80% of the tissue surface area and gel layer thicknesses over 100 &mu;m are crucial to the barrier functioning of topical gels. Under these conditions, the level of viral restriction makes a significant contribution to increasing the time required for virions to reach tissue. </p> <p>Overall, the work presented here applies transport theory in the context of HIV transmission and prevention. Results contribute to theoretical and experimental frameworks that can help understand events in HIV transmission and to design and evaluate new technologies for HIV prevention.</p> / Dissertation

Unmanned Underwater Vehicles (UUV) in open-seas are highly nonlinear with system motions. Because of the complex interaction of the body with environment it is difficult to control them efficiently. Linearization is applied to system in order to design controllers developed for linear systems. To overcome the effects of disturbances, a mathematical model which will compensate all disturbances and effects of linearization is required. In this study first a mathematical model is formed wherein the linear and nonlinear hydrodynamic coeffi- cients are calculated with strip theory. After the basic mathematical model is developed, it is simplified and decoupled into speed, steering and diving subsystems. Consequently PID (Proportional Derivative Integral), SMC (SlidingMode Control) and LQR (Linear Quadratic Regulator)/LQG (Linear Quadratic Gaussian) control methods can be applied on each subsystem to design controllers. Some of the system parameters can be estimated from state vector data based on measurements using the methods of linear sequential estimation and genetic algorithms. As for the final part of the study, an online obstacle avoidance algorithm which avoids local optimums using Boolean operators is presented. In addition a simple guidance algorithm is suggested for waypoint navigation. Due to the fact that ULISAR UUV is still on construction phase, we were unable to test our algorithms. But in the near future, we plan to study all these algorithms on the UUV ULISAR.

A comprehensive model, previously developed for a rectangular parallelepiped shaped 0.3 MWt circulating fluidized bed combustor (CFBC) fired with high calorific value coal burning in sand and validated against experimental data is adapted to cylindrical configuration and is extended to incorporate NOx formation and reduction reactions and pressure drops around cyclone, downcomer and loop seal. Its predictive accuracy is tested by applying it to the simulation of Middle East Technical University (METU) 150 kWt CFBC burning low calorific value indigenous lignite with high Volatile Matter/Fixed Carbon (VM/FC) ratio in its own ash and comparing its predictions with measurements. Favorable comparisons are obtained between the predicted and measured temperatures, pressure profiles and emissions of gaseous species. Results reveal that predictive accuracy in pressure profile strongly depends on the correlation utilized for entrainment in dilute zone and that accuracy in NO emission requires data on partitioning of coal nitrogen into char-N and volatile-N and is affected significantly by dilute zone oxygen content.

The flow of a liquid film over a rapidly rotating horizontal disk has many applications inmedical, industrial, and engineering fields. A specific example is the heat and mass transfer processes between expanded liquid and surrounded dense gas. Diferent wave regimes of a liquid film depend on a flow conditions such as the properties of a liquid, its initial speed,parameters of environment, etc. Therefore, experimental investigation of the film flow over a spinning disk is needed to both validate theoretical predictions and establish methods for fluid flow monitoring.This thesis presents novel video-based algorithms for detection and tracking wave structural data of the liquid film flowing over a spinning disk reactor. The algorithms are based on the spiral model of wave and the quasi-optimal method for estimation of a wave velocity as ill-posed problem. Their performance is compared with results predicted by the fluid dynamics based on the Navier-Stokes equations in the case of thin film.Using experimental video data, the developed models and algorithms allow investigators to estimate the characteristics of wave regimes such as wavelengths, inclination angles, and the radial and azimuthal velocity components of the fluid. The accuracy of estimated characteristics was analyzed. It was shown that average distance between consecutive two waves,their spiral shapes, and the radial velocities of waves confirm the theoretical results and predictions. In particular, computed wavelength is within 1% and a change of the inclination angles is within 2% of the predicted values.

A computational tool that uses an automated and reliable procedure for systematic generation of global phase equilibrium diagram (GPED) is developed for binary system using equation of state and its extension to the ternary system is discussed. The proposed algorithm can handle solid phase and also can predict all major six types of phase diagrams. The procedure enables automatic generation of GPED which incorporates calculations of all important landmarks such as critical endpoints, quadruple point (if any), critical line, liquid-liquid-vapor line (if any), solid-liquid-liquid line (if any) and solid-liquid-vapor line. The method is also capable of locating all azeotropic phenomena such as azeotropic endpoint, critical azeotrope, pure azeotropic point and azeotropic lines. Although, we demonstrated the methodology for cubic equation of state, the proposed strategy is completely general that doesn't require any knowledge about the type of phase diagram and can be applied to any pressure explicit equation of state model. Newton homotopy based global method has been applied for phase stability test and critical point calculations to ensure reliability. Having computed the binary phase diagrams, the methodology to generate global phase diagrams for ternary system is discussed that can locate all important thermodynamic landmarks such as tricritical point, quadruple critical endpoint, quadruple azeotropic endpoint, quintuple point and critical azeotropic endpoint. The procedure to trace ternary phenomena having two degree of freedom such as critical surface, solid-liquid-vapor surface and liquid-liquid-vapor surface has been discussed. Finally, applications of reliable global methods to solve the fluid-fluid phase equilibrium problem using SAFT equation for binary system and the solid-fluid phase equilibrium problem for binary and ternary systems have been demonstrated through representative computations.

Predictive models for diffusion-controlled particle dissolution are important for designing advanced and efficient solid products for controlled release applications. A computer-aided modeling framework was developed to derive the effective dissolution rates of multiple particles as the solid surface material eroded gradually into the surrounding liquid phase. The mathematical models were solved with numerical methods using the computational software MATLAB. Results from the models were imported into COMSOL Script to create three-dimensional plots of the particle size data as a function of time. The release model found for the monodispersed particles was manipulated to incorporate polydisperse solids, as these are found more frequently in chemical processes. The program was further developed to calculate the particle size as a function of time for particles encapsulated for use in controlled release. The parameters, such as radius size, coating material and encapsulation thickness, can be altered in the computer models to aid in the design of particles for different desired applications. Simulations produced conversion profiles and three-dimensional visualizations for the dissolution processes. Experiments for the dissolution of citric acid in water were performed using a reaction microcalorimeter to verify results found from the computer models.

Modern-day management of infectious diseases is critically linked to the use of mathematical models to understand and predict dynamics at many levels, from the mechanisms of pathogenesis to the patterns of population-wide transmission and evolution. This thesis describes the development and application of mathematical techniques for HIV infection and dynamics on social networks. Treatment of HIV infection has improved dramatically in the past few decades but is still limited by the development of drug resistance and the inability of current therapies to completely eradicate the virus from an individual. We begin with a synthesis of the important evolutionary principles governing the HIV epidemic, emphasizing the role of modeling. We then describe a modeling framework to study the emergence of drug-resistant HIV within a patient. Our model integrates laboratory data and patient behavior, with the goal of predicting outcomes of clinical trials. Current results demonstrate how pharmacologic properties of antiretroviral drugs affect selection for drug resistance, and can explain drug-class-specific resistance risks. Thirdly, we describe models for a new class of drugs that aim to eliminate cells with latent viral infection. We provide estimates for the required efficacy of these drugs and describe the potential challenges of future clinical trials. Finally, models and mechanisms for understanding viral dynamics are increasingly finding applications outside traditional virology. They can be used to study the dynamics of behaviors, to help predict and intervene in their spread. We describe techniques for applying infectious disease models to social contagion, drawing on techniques for network epidemiology. We use this framework to interpret data on the interpersonal spread of health-related behaviors.

A cell's ability to sense and respond to mechanical signals highlights the significance of physical forces in biology; however, to date most biomedical research has focused on genetics and biochemical signaling. We sought to further understand the physical mechanisms that guide the cellular migrations that occur in a number of biological processes, such as tissue development and regeneration, bacterial infections and cancer metastasis. We investigated the migration of single cells and determined whether the biomechanics of these cells could be used to elucidate multi-cellular mechanisms. We first studied Borrelia burgdorferi (Bb), the bacterium that causes Lyme disease. We created a mathematical model based on the mechanical interactions between the flagella and cell body that explained the rotation and undulation of the cell body that occurs as the bacterium swims. This model further predicts how the swimming dynamics could be affected by alterations in flagellar or cell wall stiffnesses. Fitting the model to experimental data allowed us to calculate the flagellar torque and drag for Bb, and showed that Treponema pallidum (Tp), the syphilis pathogen, is biomechanically similar to Bb. Next, we used experimentally-determined parameters of Bb's motility to develop a population-level model that accounts for the morphology and spreading of the "bulls-eye" rash that is typically the first indicator of Lyme disease. This work supported clinical findings on the efficacy of antibiotic treatment regimes. Finally, we investigated the dynamics of epithelial monolayers. We found that intracellular contractile stress is the primary driving force behind collective dynamics in epithelial layers, a result previously predicted from a biophysical model. Taken together, these findings identify the relevance of physics in cellular migration and a role of mechanical signaling in biomedical science.

Pagrindinė šio darbo užduotis yra statybos investicijų efektyvumo analizė taikant matematinio modeliavimo metodus. Darbą sudaro trys pagrindiniai skyriai. Apžvalginiame skyriuje atlikta įvairių pasaulio šalių mokslininkų investicijų efektyvumo nustatymo modelių analizė. Pateikti vieni naujausių mokslinėje literatūroje aptinkamų metodų, taikomų investicijoms skaičiuoti. Apžvelgti finansinių (klasikinių) investicijų efektyvumo vertinimo metodų trūkumai. Apibrėžtos pagrindinės matematinio modeliavimo sąvokos, taikymo sritys bei pagrindiniai matematinių modelių sudarymo principai. Antrasis skyrius skirtas investicinių projektų sudėties ir jų vertinimo principų apžvalgai. Apibrė��ta bendroji bei investicijų statyboje koncepcija, statybos investicinių projektų klasifikacija. Pateikta uždavinių, padedančių nustatyti statybos investicijų efektyvumą, klasifikacija bei statybos investicijų efektyvumo nustatymo etapai. Toliau gilinamasi į bendruosius investicinio projekto vertinimo principus, pateikiama schema, apibrėžianti investicinių projektų vertinimo eigą. Trečiojoje dalyje, pereinant prie statybos investicinių procesų analizės, pateikiama rinkos ir statistinių duomenų apžvalga, kadangi būtent šių duomenų pagrindu sudaromas matematinis modelis, nuo jų tikslumo priklauso galutiniai skaičiavimų rezultatai. Statistinių duomenų apdorojimo programa MINITABTM, regresinės analizės metodu, sudaromas matematinis modelis, nustatantis statybos investicinio proceso efektyvumą. Remiantis... [to full text] / The main task of this project is the analysis of the construction investment efficiency, by applying of mathematical modeling methods. The model is created in order to define the effectiveness of the construction investment process. According to the model, it was calculated the yield of the process and the risk zones.