Rationale: Ventilation inhomogeneity (VI) may be an early sign of obstructive airway disease. The lung clearance index (LCI) has been suggested as a sensitive marker of VI, although it has not been well characterized in young children in health and in those with CF and asthma. Objective: To determine if LCI can detect VI in asymptomatic infants and preschool-age subjects with CF or wheeze/asthma compared to healthy controls. Methods: Sulphur hexafluoride (SF6) multiple breath washout (MBW) testing was completed in all subjects. Results: LCI was found to be dependent on age in a large healthy cohort. Accounting for age, LCI was significantly elevated in disease groups compared to healthy controls in early childhood, illustrating early presence of VI in wheezy infants and the progression of disease in CF. Furthermore, the effects of breathing pattern and the variability of MBW parameters showed positive associations with age and VI.

Before a new flight control system is released for flight, a huge number of simulations are evaluated to find weaknesses of the system. This process is called flight clearance. Flight clearance is a very important but time consuming process. There is a need of better flight clearance methods and one of the most promising methods is the use of optimization. In this thesis the flight clearance of a simulation model of JAS 39 Gripen is examined. Two flight clearance algorithms using two different optimization methods are evaluated and compared to each other and to a traditional flight clearance method. In this thesis the flight clearance process is separated into three cases: search for the worst flight condition, search for the worst manoeuvre and search for the worst flight condition including parameter uncertainties. For all cases the optimization algorithms find a more dangerous case than the traditional method. In the search for worst flight condition, both with and without uncertainties, the optimization algorithms are to prefer to the traditional method with respect to the clearance results and the number of objective function calls. The search for the worst manoeuvre is a much more complex problem. Even as the algorithms find more dangerous manoeuvres than the traditional method, it is not certain that they find the worst manoeuvres. If not other methods should be used the problem has to be rephrased. For example other optimization variables or a few linearizations of the optimization problem could reduce the complexity. The overall impression is that the need of information and problem characteristics define which method that is most suitable to use. The information required must be weighed against the cost of objective function calls. Compared to the traditional method, the optimization methods used in this thesis give extended information about the problems examined and are better to locate the worst case.

Flip-chip underfilling is a technology by which silica-filled epoxy resin is used to fill the micro-cavity between a silicon chip and a substrate, by dispensing the liquid encapsulant at elevated temperatures along the periphery of one or two sides of the chip and then allowing capillary action to draw the material into the gap. Since the chip, underfill material, and substrate solidify together as one unit, thermal stresses on solder joints during the temperature cycling (which are caused by a mismatch in the coefficients of thermal expansion between the silicon chip and the organic substrate) can be redistributed and transferred away from the fragile bump zone to a more strain-tolerant region. Modeling of the flow behaviour of a fluid in the underfill process is the key to this technology. One of the most important drawbacks in the existing models is inadequate treatment of non-Newtonian fluids in the underfill process in the development of both analytical models and numerical models. Another important drawback is the neglect of the presence of solder bumps in the existing analytical models. This thesis describes a study in which a proper viscosity constitutive equation, power-law model, is employed for describing the non-Newtonian fluid behaviour in flip-chip package. Based on this constitutive equation, two analytical models with closed-form solutions for predicting the fluid filling time and fluid flow front position with respect to time were derived. One model is for a setting with two parallel plates as an approximate to flip-chip package, while the other model is for a setting with two parallel plates within which an array of solder bumps are present. Furthermore, a numerical model using a general-purpose finite element package ANSYS was developed to predict the fluid flow map in two dimensions. The superiority of these models to the existing models (primarily those developed at Cornell University in 1997) is confirmed based on the results of the experiments conducted in this study. This thesis also presents a finding of the notion of critical clearance in the design of a flip-chip package through a careful simulation study using the models developed. The flip-chip package design should make the clearance between solder bumps larger than the critical clearance.

This paper aims to investigate the connection between clearance cairns and burial cairns. From this point of view I try to answer the questions why they are built in the same area and why these two different types of cairns are so similary constructed. Further I consider different theories about mounds of fire-cracked stones.

The present study was undertaken to evaluate the filtration efficiency of the bath sponge Spongia ceylonensis (Spongiidae) and fire sponge Tedania klausi (Tedaniidae) collected from Penghu. In the feeding experiements, live and algal powder of Tetraselmis chui (8-16£gm), Chaetoceros muelleri (6-9£gm), Isochrysis galbana (3-7£gm) and Nannochloropsis oculata (2-5£gm) were used to determine the clearance rate of sponges. Sponges S. ceylonensis and T. klausi showed selective feeding under various algal species, concentrations and conditions (live algae or powders). After 90 minutes, the clearance rate of T. klausi fed on N. oculata powder was 71 ml h-1 gDW-1 at algal concentration of 107 cells ml-1, but S. ceylonensis didn¡¦t feed at the same concentration. At 106 cells ml-1 concentrations, the clearance rate of S. ceylonensis fed on live I. galbana was 538 ml h-1 gDW-1 which was higher than T. klausi, i.e. 11 ml h-1 gDW-1. At 105 cells ml-1 concentrations, the clearance rate of T. klausi fed on live T. chui was 431 ml h-1 gDW-1 which was higher than S. ceylonensis, i.e. 23 ml h-1 gDW-1. At 104 cells ml-1 concentrations, S. ceylonensis fed on live T. chui with clearance rate 532 ml h-1 gDW-1, and T. klausi was 315 ml h-1 gDW-1. The results showed differential clearance rates of sponges depend on sponge species, algal species, concentrations and conditions (live or powder). In gerneral, sponge clearance rate is higher when feeds on live algae than algal powders. Although the filtration efficiency of algal powders is low, the advantage of low cost and high accessibility still make algal powder highly competitive in sponge aquaculture industry.

The environment of bivalve Sanguinolaria rostrata growth and reproduction is affected by temperature, salinity and algal concentration.The growth and fattening of the bivalves is closely associated with filter-feeding. Hence, the present work was to investigate the effect of temperature, salinity and algal concentration on the filter-feeding of the bivalves. The salinity ranging from 5 to 30 at the interval of 5 psu, four temperatures at 20¢X, 25¢X, 27¢X and 30¢J, and three algal concentrations of each Isochrysis galbana and each Chaetoceros gracilis, 104 , 105 and 106 cells/ml, were used. Algal concentration was measured each hour and each test run last for 6 hours. A peak appeared at the salinity of 20 psu in each clearance rate vs salinity curve and clearance rate decreased with increasing algal concentration; a peak also appeared at the salinity of either 15¡ã20 psu in the ingestion rate vs salinity curve; and ingestion rate and the amount of pseudofaeces increased with increasing algal concentration. Under the conditions of algal concentration 104 cells/ml and temperature range 20¢X~30¢J, a peak appeared at 25¢J in each clearance rate and each ingestion rate vs temperature curves, and the greatest peak of clearance rate was 1.13 l/h; and the amount of pseudofaeces was the greatest at 25¢J and 20 psu. The bivalves fed with Isochrysis galbana have greater clearance and ingestion rates but less amount of pseudofaeces, compared to those fed with Chaetoceros gracilis.

Rivets are widely used as a means of fastening in airframe construction industry. There are various types of riveted joints on an aircraft fuselage or on a helicopter body. Among the other types of fasteners riveted joints are preferred in such applications due to / their permanence after installation and their economical advantages. In a riveted joint, it is known that residual stresses are present as a result of the installation process. Furthermore, during the flight of an aircraft, the fuselage is loaded in one cycle and such cycles are repeated throughout the service life. As a result, the panels and the rivets are subjected to fatigue type loading. The integrity of the joint must be maintained against this combination of service loads and the residual stresses. Hence, the riveting process parameters which influence the residual stresses are utmost critical in terms of fatigue life of the hole body. In this study it is aimed to obtain an accurate numerical model of a single-lap riveted joint which is widely used in airframes. 2-D axisymmetrical and 3-D numerical models are generated using commercial finite element code ABAQUS/CAE and subsequent parametric studies are carried out on these models. The Results of both models are compared with those found in the literature. Clearance between hole and rivet shank is selected as the primary parameter to be inspected. The effects of hole clearance on the final residual stress field are examined on 2-D and 3D models. Furthermore, a through the thickness, crack on the inner panel which is initiated after installation is modeled. The crack is perpendicular to the direction of loading. It is placed to the residual tensile stress zone that surrounds the rivet hole. Hence, the effects of residual stresses are also taken into account. For a riveted joint subjected to fatigue loading, such a macroscopic crack could eventually form. In this thesis, stress intensity factors (SIF&rsquo / s) for this crack are calculated for various parameters such as clearance and crack length. These can be utilized in a subsequent fatigue crack growth analysis as the initial values or they can be used in a fracture analysis, to predict unstable crack growth due to overload (i.e. crack linking).

This thesis provides experimental static and dynamic results for four pairs of seals, including a pair of smooth seals and three pairs of centrally grooved seals. The grooved seals have groove depth to clearance ratios (Dg/C) of 5, 10, and 15. The radial clearance of each test seal is 0.0891 mm. Test conditions include three shaft rotational speeds from 4000 to 10000 rpm, three inlet oil pressures from 24 to 70 bars, and seal dimensionless eccentricities from 0 (centered) to 0.7. For each pair of test seals, dynamic results include stiffness and damping coefficients; static results include stator position, attitude angles, and seal leakage. Stiffness, damping, and leakage are compared among the seal pairs with various groove depths. Results show that all rotordynamic coefficients consistently decrease with increasing seal groove depths, and seal leakage remains constant through varying groove depths. Additionally, a comparison is made between experimental results of all test seals and XLLubeGT. XLLubeGT is a computer model developed at Texas A&M University, which uses a Reynolds equation + energy equation model to predict dynamic performance of a grooved seal. It operates on the assumption that the groove is large enough to create separate lands within the seal, creating a zero or negligible pressure perturbation across the seal. A comparison with XLLubeGT shows that even the seal with the largest groove depth tested is not deep enough to agree with XLLubeGT predictions.

Current methods to diagnose and treat cancer often involve expensive, time-consuming equipment and materials that may lead to unwanted side effects and may not even increase a patient’s chance of survival. Thus, for a while now, a large part of the research community has focused on developing improved methods to detect, diagnose, and treat cancer on the molecular scale. One of the most recently discovered methods of cancer therapy is targeted therapy. These targeted therapies have potential to provide a patient with a form of personalized medicine because these therapies are biological molecules that specifically target other molecules involved with a cancer’s growth. Past trials using these therapeutic molecules, however, have led to controversial results, where certain patients responded better than others to the therapy for unknown reasons. Elucidating the reason behind these mixed results can be accomplished using metal nanoparticle technologies which could provide a bright signal to monitor the path that these therapeutic molecules take in vivo as well as enhance the molecule’s efficacy. Literature has shown that presenting targeting molecules in a dense manner to their target will increase these molecules’ binding affinity. This concept has been explored here to increase binding affinity of therapeutic molecules by attaching these molecules in a dense manner on the surface of gold nanoparticles, and correlating this increased affinity with therapeutic efficacy. Additionally, gold nanoparticles provide an easy surface for molecules to be functionalized on and have shown to be effective imaging, x-ray, and photothermal therapy agents. A major roadblock to using these gold nanoparticles clinically is their non-degradability and thus potential to cause long-term negative side effects in vivo. A platform for developing biodegradable gold nanoparticles is also explored here to take advantage of the gold nanoparticles’ excellent imaging and drug delivery capabilities while still allowing them to be used safely in the long term. / text

Gold nanoparticles attain an intense focus in biomedical imaging applications due to their unique optical properties, facile conjugation with biomolecules, and biocompatibility. Although a considerable amount of work towards the development of gold nanoparticles has been completed, these promising contrast agents have not yet reached the clinic due to several challenges including efficient accumulation at the diseased site, sensitivity of detection in vivo, potential adverse effects, and clearance from the body. High signal-to-background ratio is required to enhance sensitivity of detection. Because near infrared (near-IR) light has the best tissue penetration, contrast agents designed to work in this range can significantly increase imaging sensitivity. Moreover, efficient targeting of the molecular biomarkers on diseased cells can decrease the required dosage, increase the site-specific accumulation, and enhance the imaging sensitivity. Molecular-specific contrast agents developed in this project use directional attachment of antibody molecules to the nanoparticle surface, enhancing the targeting efficacy. Additionally, cell-based delivery of diagnostic and therapeutic agents is gaining much interest due to the immune cells’ special access to the avascular, diseased regions. The contrast agents developed in this project enable detection of just a few cells per unit of imaging volume, enable multiplex imaging, and open up a possibility for tracking different cell populations with noninvasive photoacoustic and ultrasound imaging. Finally, the clearance of nanoparticles from the body dictates their clinical translation. The in vivo pharmacokinetics study along with the proposed in vitro model explored in this project will enable fast, reliable, and cost-efficient screening of promising agents and facilitate quick optimization of nanoparticles for their potential use in the clinic. / text