Browsing by Subject "Imprinting"
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Item Analysis of Genomic Imprinting of UBE3A in Neurons(2015-05-05) Hillman, Paul RandolphAngelman syndrome (AS), chromosome 15q11-q13 duplication syndrome (Dup15q), and Prader-Willi syndrome (PWS) are neurodevelopmental disorders associated with dysregulated expression of imprinted genes located within the human 15q11-13 imprinted region. Angelman syndrome is caused by loss-of-function or loss-of-expression of the maternally inherited UBE3A allele; Dup15q syndrome is attributed to maternally inherited copy number gains of UBE3A; and, paternally inherited deletions of the SNORD116 cluster cause PWS. The UBE3A gene is imprinted in the brain with maternal-specific expression and biallelically expressed in all other cell types. The imprint is regulated by expression of the UBE3A antisense transcript (UBE3A-AS), which is expressed only in neurons and imprinted with paternal-specific expression. The UBE3A-AS represents the 3` end of a long polycistronic transcript that includes the SNORD116 and SNORD115 gene clusters. Thus, the genes causing AS, Dup15q, and PWS are transcriptionally linked; however, the functional significance of the neuron specific imprint is largely unknown. In this dissertation, it was hypothesized that imprinting of UBE3A evolved as a mechanism to negatively regulate UBE3A protein levels in neurons. This hypothesis was tested by examining allelic expression patterns and associated protein levels of the mouse 7c imprinted region, the orthologous region of human 15q11-q13. Analyses revealed that imprinted expression of Ube3a in the brain resulted in elevated RNA and protein levels compared to tissues where Ube3a was biallelically expressed. Likewise, Snord116, Snord115, and Ube3a-AS transcripts were highly expressed in the brain. The elevated Ube3a protein levels in the brain were due to increased maternal-allelic expression during neurogenesis concurrent with paternal-allelic suppression. Analysis of UBE3A expression in the opossum, a metatherian mammal lacking an orthologous imprinted region, showed that the UBE3A imprint did not evolve to negatively regulate UBE3A protein levels in the brain. Extensive alternative splicing of Ube3a-AS was detected in the brain, which generated at least two transcripts containing novel open reading frames. Novel Ube3a alternatively spliced transcripts were also identified in the brain. Collectively, these data reject the hypothesis that the UBE3A imprint evolved to negatively regulate UBE3A protein levels in the brain; instead, they suggest that the UBE3A imprint may allow co-expression of the UBE3A and SNORD gene cluster in neurons, which may also facilitate or regulate the expression of novel brain-specific UBE3A transcripts.Item Novel printing technologies for nanophotonic and nanoelectronic devices(2013-08) Lin, Xiaohui, active 21st century; Chen, Ray T.As optical interconnects make their paces to replace traditional electrical interconnects, implementing low cost optical components and hybrid optic-electronic systems are of great interest. In the research work described in this dissertation, we are making our efforts to develop several practical optical components using novel printing technologies including imprinting, ink-jet printing and a combination of both. Imprinting process using low cost electroplating mold is investigated and applied to the waveguide molding process, and it greatly reduces the surface roughness and thus the optical propagation loss. The imprinting process can be applied to photonic components from multi-mode waveguides with 50[mu]m critical dimension down to photonic crystal structures with 500nm hole diameter. Compared to traditional lithography process, imprinting process is featured by its great repeatability and high yield to define patterns on existing layers. Furthermore we still need an approach to deposit layers and that is the reason we integrate the ink-jet printing technology, another low-cost, low material consumption, environmental friendly process. Ink-jet printing process is capable of depositing a wide range of materials, including conductive layer, dielectric layer or other functional layers with defined patterns. Together with molding technology, we demonstrate three applications: proximity coupler, thermo-optic (TO) switch and electro-optic (EO) polymer modulator. The proximity coupler uses imprinted 50[mu]m waveguide with embedded mirrors and ink-jet printed micro-lenses to improve the board-to-board optical interconnects quality. The TO switch and EO modulator both utilize imprinting technology to define a core pattern in the cladding layer. Ink-jet printing is used to deposit the core layer for TO switch and the electrode layers for EO modulator. The fabricated TO switch operates at 1 kHz with less than 0.5ms switching time and the EO modulator shows V[pi][middle dot]L=5.68V[middle dot]cm. To the best of our knowledge, these are the first demonstrations of functional optical switches and modulators using printing method. To further enable the high rate fabrication of ink-jet printed photonic and electronic devices with multiple layers on flexible substrate, we develop a roll-to-roll ink-jet printing system, from hardware integration to software implementation. Machine vision aided real time automatic registration is achieved when printing multiple layers.