This thesis describes the use of a new technology, the Cytosensor® microphysiometer, in the in vitro evaluation of cytotoxic drugs, using the lymphoma cell line U-937 GTB and primary cultures of tumour cells from patients as model systems. The method was specifically applied to study the metabolic effects of the novel cyanoguanidine N-(6-(4-chlorophenoxy)hexyl)-N’-cyano-N’’-4-pyridylguanidine, CHS 828, currently in phase I/II clinical trials. The Cytosensor® measures metabolic effects as changes in the rate of extracellular acidification of cells exposed to a drug by perfusion. A number of standard cytotoxic drugs were found to produce typical and reproducible acidification response patterns during observation times up to 20 h. There seemed to be a relationship between a decrease in acidification and cytotoxicity, measured in the fluorometric microculture cytotoxicity assay (FMCA), after 20-24 h of continuous drug exposure. In U-937 cells, CHS 828 induced a cytotoxic effect characterised by a steep concentration-response relationship followed by a plateau. After 24 h of incubation the DNA and protein synthesis were turned off. CHS 828 was found to produce a rapid and prolonged increase in extracellular acidification and lactate production similar to that of the structurally related mitochondrial inhibitor m-iodobenzylguanidine (MIBG). The CHS 828 induced acidification was observed in cell lines as well as in cells from various tumour types from patients and probably originates from increased glycolytic flux. The effects may be secondary to block of oxidative phosphorylation in the mitochondria, but the relevance of the early acidification is not clear. CHS 828 seemed to induce a late, at approximately 15 h, inhibition of the glycolysis followed by loss of ATP and subsequent cell death. After exposure to MIBG the loss of ATP and cell death occurred earlier and in parallel. The effects of CHS 828 were not found to resemble those of the structurally related polyamine biosynthesis inhibitor methylglyoxal-bis(guanyl-hydrazone) (MGBG). Thus, CHS 828 may represent a new and, thus, interesting mode of cytotoxic action worthwhile for further development. In combinatory studies, a synergistic interaction was demonstrated between CHS 828 and the non-toxic drug amiloride. Additive-to-synergistic effects were also seen between CHS 828 and the bioreductive cytotoxic drug mitomycin C. In U-937 cells as well as in tumour cells from patients, CHS 828 demonstrated synergistic interactions in combination with melphalan and etoposide. It is concluded that measurement in the Cytosensor® microphysiometer of early cellular metabolic changes is a feasible and potentially valuable complement to more conventional methods used in the evaluation of anticancer agents.

The Fe-C-Cr-Mn-Ni-O system is of fundamental importance when describing the influence of oxygen on high alloyed steels. Both solid and liquid phases are of great interest: The solid phases regarding oxidation processes like the formation of oxide layers, inner oxidation, sintering processes and high temperature corrosion. The liquid phase is of interest concerning the interaction between steel and its slag in a metallurgical context. In this thesis the thermodynamic properties of this system is described using the Calphad technique. The main idea of the Calphad technique is to describe the Gibbs energy of all phases in the system as a function of temperature, pressure and composition using appropriate thermodynamic models. When thermodynamic descriptions of all phases taking part in the system are modelled and described in a database, the equilibrium state could be calculated with a software that minimizes the total Gibbs energy. Models within the compound energy formalism are used for all solution phases, among them the ionic two-sublattice liquid model, to describe both the metallic and oxide melts. All simple spinels (Cr3O4, FeCr2O4, Fe3O4, FeMn2O4, Mn3O4, MnCr2O4, NiCr2O4, NiFe2O4, NiMn2O4) within this system are described using a four-sublattice model. In this thesis several binary and ternary systems have been assessed or partly reassessed. The Fe-C-Cr-Mn-Ni-O database achieved can be used with an appropriate thermodynamic software to calculate thermodynamic properties, equilibrium states and phase diagrams. In general, the agreement between calculated and experimental values is good. / QC 20100723

This thesis investigates a technique to estimate the risk of the mean-variance (MV) portfolio optimization problem. We call this technique the Scaling technique. It provides a better estimator of the risk of the MV optimal portfolio. We obtain this result for a general estimator of the covariance matrix of the returns which includes the correlated sampling case as well as the independent sampling case and the exponentially weighted moving average case. This gave rise to the paper, [CMcS]. Our result concerning the Scaling technique relies on the moments of the inverse of compound Wishart matrices. This is an open problem in the theory of random matrices. We actually tackle a much more general setup, where we consider any random matrix provided that its distribution has an appropriate invariance property (orthogonal or unitary) under an appropriate action (by conjugation, or by a left-right action). Our approach is based on Weingarten calculus. As an interesting byproduct of our study - and as a preliminary to the solution of our problem of computing the moments of the inverse of a compound Wishart random matrix, we obtain explicit moment formulas for the pseudo-inverse of Ginibre random matrices. These results are also given in the paper, [CMS]. Using the moments of the inverse of compound Wishart matrices, we obtain asymptotically unbiased estimators of the risk and the weights of the MV portfolio. Finally, we have some numerical results which are part of our future work.

Solid phase microextraction (SPME), needle trap device (NTD), and membrane extraction with a sorbent interface (MESI) are solvent-free sample preparation techniques that were developed to perform the rapid routine analysis of organic compounds (VOCs) in various environmental matrices by integrating sampling, extraction, preconcentration and sample introduction procedures into one step. A portable ion mobility spectrometry (IMS) analyzer has some advantages, such as small size, light weight, operability under ambient pressure, air as carrier gas, and sensitivity, all of which make IMS suitable for on-site monitoring for low concentration of analytes. The aforementioned sampling and preconcentration techniques were coupled with a portable IMS analyzer, as well as a thermal desorption unit that can accommodate SPME, NTD and MESI, which was modified and combined with IMS for on-site monitoring of volatile organic compounds (VOCs) from human breath and plant emissions. Experimental results demonstrated that low detection limits were achievable for gaseous analytes, (25 ng/L for acetone (SPME-IMS), 43 ng/mL (NTD-IMS) and 2.3 ng/mL (MESI-IMS) for α-pinene). These three analytical systems were applied for on-site rapid determination of acetone in human breath and α-pinene from plant emissions respectively. The salient features of these systems that make them suitable for on-site monitoring of volatile organic compounds in different sources are: small size, simple operation, fast and/or on-line sampling, rapid analysis.

Solid phase microextraction (SPME), needle trap device (NTD), and membrane extraction with a sorbent interface (MESI) are solvent-free sample preparation techniques that were developed to perform the rapid routine analysis of organic compounds (VOCs) in various environmental matrices by integrating sampling, extraction, preconcentration and sample introduction procedures into one step. A portable ion mobility spectrometry (IMS) analyzer has some advantages, such as small size, light weight, operability under ambient pressure, air as carrier gas, and sensitivity, all of which make IMS suitable for on-site monitoring for low concentration of analytes. The aforementioned sampling and preconcentration techniques were coupled with a portable IMS analyzer, as well as a thermal desorption unit that can accommodate SPME, NTD and MESI, which was modified and combined with IMS for on-site monitoring of volatile organic compounds (VOCs) from human breath and plant emissions. Experimental results demonstrated that low detection limits were achievable for gaseous analytes, (25 ng/L for acetone (SPME-IMS), 43 ng/mL (NTD-IMS) and 2.3 ng/mL (MESI-IMS) for α-pinene). These three analytical systems were applied for on-site rapid determination of acetone in human breath and α-pinene from plant emissions respectively. The salient features of these systems that make them suitable for on-site monitoring of volatile organic compounds in different sources are: small size, simple operation, fast and/or on-line sampling, rapid analysis.

The development and application of portable LCD (Liquid crystal display) technology is the main trend on the market. The goal of this study is to fabricate a compound optical film, and we focus on the design and fabrication of a new type backlight module for side-LED (Light emitting diode) display. The optical efficiency can be improved via the compound optical film. The profile of optical film was determined using commercial optical software, FRED. The mold with multi aspect ratio and multi fill-factor microlens array by LIGA-like process (Lithographie galvanoformung abformung) was produced using THB-126N negative photoresist and AZ-4620 positive photoresist. The study presents many innovative processes, such as the homemade gray scale mask, and multi-step electroforming method, which both produces the microlens array with variable size and aspect ratio. In addition, the embedded micro-void caused light guide and diffusion under the quantitative control during the PDMS (Polydimethylsiloxane) optical film fabrication. The compound optical film with embedded micro-voids, multi aspect ratio and variable size microlens array can be fabricated quickly without substrate. Then the optical properties were analyzed by BM-7A to characterize the luminance, uniformity and optical efficiency.

Since Chu T¡¦ien-wen was sixteen years old, she has been an important role in Taiwan literature. Chu T¡¦ien-wen has been influence by her parents and Zhang Ai-ling in Chinese literature for a long time. In the chinese ritual music cultur, she was educated under Hu Lan-cheng and became an author in the style of Zhang Qiang Hu Diao. Therefor, Chu T¡¦ien-wen and her sister Chu T'ien-hsin published San San magazine. However, after been through Nativist Literature Controversy and Hu Lan-cheng's death, she became a screenwriter for the movie, directed by Hou Hsiao-hsien and became one of the important participant of New Movie Movement in Taiwan. To face the problems of cross-srait relations and the visitions for the relatives, leading Chu T'ien-wen walk out military dependents' village and walk out San San and Grand View Garden, the style has also changed from San San ¢w¢w a young girl¡¦s fantasies style through growth theme of military dependents' village style and turned into the metropolis mature style. After Hu Lan-cheng passed away, Chu T'ien-wen swore to accomplish his unfinished ¡§ Woman Theory ¡¨ . To pass down the Female Writing of Woman Theory of Civilization, she decided to use ¡§ the Splendors of Fin de Siècle ¡¨ Notes of a Desolate Man and Words of a Witch. Hu Lan-cheng used to describe Chu T'ien-wen as a Japanese witch, and praised of the youth and beauty of her literature of art, which gives an inspiration to Chu T'ien-wen and to start a journey for witch. In ¡§ the Splendors of Fin de Siècle ¡¨ , giving Chu T¡¦ien-wen an advice as witch who predicted that patriarchal society were devastated. And in Notes of a Desolate Man that a desolate man who had feminine soul to offer Japanese witching dance for god. In Words of a Witch as witching word to fly from time and death that become unique to Chu T'ien-wen¡¦s Witched Writings.

A novel analytical technique was developed where gaseous hydrogen selenide formed by sodium tetrahydroborate reduction is transported to and trapped on a resistively heated gold-coated W-coil atom trap for in situ preconcentration. The atom trap is held at 165 &ordm / C during the collection stage and is heated up to 675 &ordm / C for revolatilization / analyte species formed are transported to an externally heated quartz T-tube where the atomization takes place and the transient signal is obtained. For gold, a high volume gas liquid separator (HVGLS) was designed to improve the detection limit of Au down to the ng mL-1 levels. In this apparatus, analyte and reductant solutions are collected in a limited volume and volatile analyte species are formed. After separation of the volatile analyte species from liquid phase, the entire analyte vapor is sent to an atomizer. A W-coil trap was used to further decrease the detection limit. The enhancement factor for the characteristic concentration was found to be 10.7 when compared to HG-AAS performance without W-coil trap by using peak height values. Furthermore, the generation of analytically useful volatile form of Au has been studied. The flow injection generation was performed in a dedicated generator consisting of a special mixing apparatus and gas-liquid separator design. The on-line atomization in the quartz tube multiatomizer for atomic absorption (AAS) detection has been employed as the convenient atomization/detection mean. 198Au, 199Au radioactive indicator of high specific activity together with AAS measurements was used to track quantitatively the transfer of analyte in the course of generation and transport to the atomizer. In-situ trapping in GF for AAS was explored as an alternative to the on-line atomization. Transmission electron microscopy measurements proved the presence of Au nanoparticles of diameter of approximately 10 nm and smaller transported from the generator by the flow of carrier Ar. For silver, three types of GLS which are U-shaped, cylindrical and high volume gas liquid separators (HVGLS) were used to compare the sensitivities of these GLSs during Ag determination. The DL (3s) values were found as 29 ng mL-1, 0.4 ng mL-1 and 0.05 ng mL-1 for U-shaped GLS, cylindrical GLS with W-coil trap and HVGLS with W-coil trap, respectively. For indium, two types of GLS which are cylindrical and HVGLS with W-coil trap were used. The LOD and characteristic concentration were found as 148 and 317 ng mL-1 with cylindrical shape GLS. HVGLS with W-coil trap was used to improve sensitivity. In this case, LOD and characteristic concentration were found to be 0.46 and 0.98 ng mL-1, respectively. Moreover, to increase the reactivity between indium and reductant solutions, Ru(acac)3 catalyst was used. In this case, LOD and characteristic concentration were found to be 0.13 and 0.23 ng mL-1, respectively. In the case of using this catalyst, sensitivity was enhanced around 1378 fold with respect to cylindrical GLS.

The Au-Al bond is a commonly used interconection in IC package.The different composition for Au wire will change the different IMC growth. In this study, we will discuss the pure Au wire, and little Pd or Cu addition in Au wire reacted with Al pad for thermal aging, and we will give the models for these cases.

GaN-based light emitting diodes (LEDs) face several challenges if the technology is to make a significant impact on the solid state lighting market. The two most pressing of these challenges are cost and efficiency. The development of alternative substrate technologies shows promise toward addressing both of these challenges, as both GaN-based device technology and the associated metalorganic chemical vapor deposition (MOCVD) technology are already relatively mature. Zinc oxide (ZnO) and silicon (Si) are among the most promising alternative substrates for GaN epitaxy. This work focuses on the development of MOCVD growth processes to yield high quality GaN-based materials and devices on ZnO and Si. ZnO, because of its similar lattice constant and thermal expansion coefficient, is a promising substrate for growth of low defect-density GaN. The major hurdles for GaN growth on ZnO are the instability of ZnO in a hydrogen atmosphere and out-diffusion of zinc and oxygen from the substrate. A process was developed for the MOCVD growth of wurtzite GaN and InxGa1-xN on ZnO, and the structural and optical properties of these films were studied. High zinc and oxygen concentrations remained an issue, however, and the diffusion of zinc and oxygen into the subsequent GaN layer was studied more closely. Silicon is the most promising material for the development of an inexpensive, large-area substrate technology. The challenge in GaN growth on Si is the tensile strain induced by the lattice and thermal mismatch between GaN and Si. A thin atomic layer deposition (ALD)-grown Al2O3 interlayer was employed to relieve strain while also simplifying the growth process. While some strain was still observed, the oxide interlayer leads to an improvement in thin film quality and a reduction in both crack density and screw dislocation density in the GaN films. A comparison of GaN-based LEDs grown on sapphire and Al2O3/Si shows similar performance characteristics for both devices. IQE of the devices on silicon is ~32%, compared to ~37% on sapphire. These results show great promise toward an inexpensive, large-area, silicon-based substrate technology for MOCVD growth of GaN-based optoelectronic devices.