Historical dissertations from or supervised by Lawrence Berkeley National Laboratory affiliated researchers.
Expression profiling offers a potential high-throughput phenotype screen for mutant mouse embryonic stem (ES) cells. We have assessed the ability of expression arrays to distinguish among heterozygous mutant ES cell lines and to accurately reflect the normal function of the mutated genes. Two ES cell lines hemizygous for overlapping regions of mouse chromosome 5 differed substantially from the wildtype parental and from each other. Expression differences included frequent downregulation of hemizygous genes and downstream effects on genes mapping to other chromosomes. Some genes were affected similarly in each deletion line, consistent with the overlap of the deletions. To determine whether such downstream effects reveal pathways impacted by a mutation, we examined ES cell lines heterozygous for mutations in either of two well-characterized genes. A heterozygous mutation in the cell cycle regulator, cyclin D kinase 4 (Cdk4), affected expression of many genes involved in cell growth and proliferation. A heterozygous mutation in the ATP binding cassette transporter family A, member 1 (Abca1) gene altered genes associated with lipid homeostasis, the cytoskeleton, and vesicle trafficking. Heterozygous Abca1 mutation had similar effects in liver, indicating that ES cell expression profile reflects changes in fundamental processes relevant to mutant gene function in multiple cell types.
Femtosecond angle resolved two photon photoemission spectroscopy is used to study the electronic structure and electron dynamics at interfaces. At interfaces of thiolates chemisorbed on Ag(111), the adsorbate molecular electronic orbitals are observed to be nondispersive at low coverages and become dispersive at higher coverages. This is attributed to a phase transition of the layer. The molecules initially adsorb with their chains parallel to the surface. As the coverage is increased, the molecules order into a layer with the chains standing up from the surface. This closer packing results in a larger overlap between neighboring molecular orbitals and a dispersive electronic state. The lack of a change in the n=1 image potential state electron lifetimes as a function of chain length indicate that the electrons reside in the layer. The n=2 and 3 image potential state electron lifetimes decrease as the chain length is increased. This is attributed to the repulsive potential of the alkyl chains pushing the electron density into the sulfur portion of the layer. At a layer of acetonitrile molecules adsrobed on Ag(111), the image potential state electrons interact strongly with the adsorbate molecular dipoles. The dipoles rotate to solvate the electron, resulting in a decrese of the observed photoemitted electron kinetic energy as a function of time delay between population and photoemission. This is attributed to a change in the local work function resulting from the reorganization of the adsorbate layer molecules. For two layers of acetonitrile adsorbed on the Ag(111) substrate, dynamic electron localization is also observed.
