No description available.

No description available.

No description available.

Abstract All-trans retinoic acid (ATRA) is a derivative of vitamin A. It is able to stimulate neutrophilic differentiation of normal progenitors and acute promyelocytic leukemia (APL) cells. Although ATRA-induced differentiation is not observed in any other acute myeloblastic leukemia (AML) subtypes, ATRA is known to be able to inhibit AML blast cell proliferation. The present in vitro study using AML cell lines representing subtypes other than APL focuses on the following questions: (1) Is the inhibitory effect of ATRA on AML cell growth related to apoptosis of cells? (2) Are the effects of ATRA dependent on two important regulators of apoptosis, p53 and Bcl-2? (3) Do mitochondria have any role in mediating the effects of ATRA? ATRA-induced apoptosis in AML cells was observed by morphology, DNA fragmentation, phosphatidylserine externalization, and poly(ADPribose)polymerase (PARP) cleavage. It was a slow event, manifested as DNA cleavage after 48 hours exposure and as morphological apoptosis after 72 hours exposure. The AML cells expressed constitutively p53 as determined by immunohistochemistry, Western blotting and flow cytometry. However, no mutation of TP53 was observed in exons 5 to 8 as analysed with a single strand conformation polymorphism technique. As the flow cytometer analysis showed, most of p53 was in a aberrant conformation, which was not changed into a wild type conformation by ATRA. Two of the cell lines were analysed more specifically in relation to Bcl-2 and mitochondral function: ATRA-induced apoptosis of the cell lines was associated with down-regulation of Bcl-2. Western blotting showed ATRA-induced apoptosis also to be related to the release of cytochrome c from mitochondria into cytosol, resulting in the activation of caspase-3, an apoptotic effector, which was manifested as a cleavage of its substrate PARP. The process was also accompanied by disruption of the mitochondrial membrane potential as determined fluoricytometrically. These results show that ATRA is able to induce apoptosis in AML cells other than APL, and ATRA-induced apoptosis in the AML cells studied is related to the down-regulation of Bcl-2 and the disruption of mitochondrial function, but is independent of the p53 pathway.

No description available.

Photosynthetic biofilms have much higher cell density than suspended cultures and when grown in a stacked waveguide configuration, can have orders of magnitude higher areal productivity. Evanescent and plasmonic growth of biofilm cultures have been demonstrated, solving issues with light penetration impeding growth, but thus far the technology has been limited to biofuel production applications. In this thesis, plasmonically excited cyanobacterial biofilms are used to produce electrical power in a photosynthetic-plasmonic-voltaic device. This approach uses red lasers to deliver light to cells via an optical waveguide through the generation of surface plasmons at the interface between a metal and dielectric, in this case a glass-gold-air interface. This gold film serves a dual purpose as a current collector for electrons generated at the cell surface. Experiments presented here demonstrate positive power output light response under both direct light and plasmonic excitation and produced equivalent power output of 6 uW/m2 under similar light power intensities.

Photosynthetic biofilms have much higher cell density than suspended cultures and when grown in a stacked waveguide configuration, can have orders of magnitude higher areal productivity. Evanescent and plasmonic growth of biofilm cultures have been demonstrated, solving issues with light penetration impeding growth, but thus far the technology has been limited to biofuel production applications. In this thesis, plasmonically excited cyanobacterial biofilms are used to produce electrical power in a photosynthetic-plasmonic-voltaic device. This approach uses red lasers to deliver light to cells via an optical waveguide through the generation of surface plasmons at the interface between a metal and dielectric, in this case a glass-gold-air interface. This gold film serves a dual purpose as a current collector for electrons generated at the cell surface. Experiments presented here demonstrate positive power output light response under both direct light and plasmonic excitation and produced equivalent power output of 6 uW/m2 under similar light power intensities.

A technique for designing and optimizing the next generation of smart process controllers has been developed in this dissertation. The literature review indicated that neural networks held the most promise for this application, yet fundamental limitations have prevented their introduction to commercial settings thus far. This fundamental limitation has been overcome through the enhancement of neural network theory. The approach taken in this research was to produce highly intelligent process control systems by accurately modeling the nervous structures of higher biological organisms. The mammalian cerebral cortex was selected as the primary model since it is the only computational element capable of interpreting and complex patterns that develop over time. However the choice of the mammalian cerebral cortex as the model introduced two new levels of network complexity. First, the cerebral cortex is a three dimensional structure with extremely complicated patterns of interconnectivity. Second, the structure of the cerebral cortex can only be realized when thousands or millions of neurons are integrated into a massive scale neural network. The neural networks developed in this research were designed around the Hebbian adaptation, the only training technique proven by the literature review to be applicable to massive scale networks. These design difficulties were resolved by not only modeling the cerebral cortex, but the process by which it develops and evolves in biological systems. To complete this model, an advanced genetic algorithm was produced, and a technique was developed to encode all functional and structural parameters that define the cerebral cortex into the artificial chromosome. The neural networks were designed by a cell growth simulation program that decoded the structural and functional information on the chromosome. The cell growth simulation program is capable of producing patterns of differentiation unique for any slight variations in the genetic parameters. These growth patterns are similar to patterns of cellular differentiation seen in biological systems. While the computational resources needed to implement a massive scale neural network are beyond that available in existing computer systems, the technique has produced output lists which fully define the interconnections and functional characteristic of the neurons, thereby laying the foundation for their future use in process control. / Ph. D.

No description available.

Recent studies have found that EPS8, a mediator of growth factor signaling to the cytoskeleton, may upregulate expression of the FoxM1B transcription factor and aurora A kinase, both of which have been linked to oncogenic activity. Cell lines transfected with EPS8 and FoxM1B, and appropriate controls, were generated and analyzed by MTT proliferation assays and flow cytometry for relative rates of cell proliferation as well as to determine the percentage of cells in different phases of the cell cycle. qRT-PCR and western blots confirmed higher levels of EPS8, FoxM1B and Aurora A kinase in the overexpressing cell lines. To investigate the role of PI3K-dependent signaling in EPS8-mediated upregulation of FoxM1B and its targets, studies were carried out usingLY294002, an inhibitor of PI3K. In cells overexpressing EPS8, treatment with LY294002resulted in decreased expression of FoxM1B and Aurora A kinase, indicating that PI3Ksignaling mediates EPS8-dependent upregulation of FoxM1B and Aurora A kinase. The study suggests that EPS8 deregulates cell growth by affecting the expression of common regulators of cell cycle progression, in part through PI3K, a known pro-oncogenic kinase.