TARGETING SIGNAL(S) THAT MEDIATE LOCALIZATION OF [BETA]-GALACTOSIDE [ALPHA]2,6-SIALYLTRANSFERASE AND TGN38 TO THE GOLGI APPARATUS

Ph.DDOCTOR OF PHILOSOPH

Detecting macroeconomic phases in the Dow Jones Industrial Average time series

In this paper, we perform statistical segmentation and clustering analysis of the Dow Jones Industrial Average (DJI) time series between January 1997 and August 2008. Modeling the index movements and log-index movements as stationary Gaussian processes, we find a total of 116 and 119 statistically stationary segments respectively. These can then be grouped into between five and seven clusters, each representing a different macroeconomic phase. The macroeconomic phases are distinguished primarily by their volatilities. We find that the US economy, as measured by the DJI, spends most of its time in a low-volatility phase and a high-volatility phase. The former can be roughly associated with economic expansion, while the latter contains the economic contraction phase in the standard economic cycle. Both phases are interrupted by a moderate-volatility market correction phase, but extremely-high-volatility market crashes are found mostly within the high-volatility phase. From the temporal distribution of various phases, we see a high-volatility phase from mid-1998 to mid-2003, and another starting mid-2007 (the current global financial crisis).Published versio

Targeting the ‘Undruggable’ Driver Protein, KRAS, in Epithelial Cancers: Current Perspective

This review summarizes recent development in synthetic drugs and biologics targeting intracellular driver genes in epithelial cancers, focusing on KRAS, and provides a current perspective and potential leads for the field. Compared to biologics, small molecule inhibitors (SMIs) readily penetrate cells, thus being able to target intracellular proteins. However, SMIs frequently suffer from pleiotropic effects, off-target cytotoxicity and invariably elicit resistance. In contrast, biologics are much larger molecules limited by cellular entry, but if this is surmounted, they may have more specific effects and less therapy-induced resistance. Exciting breakthroughs in the past two years include engineering of non-covalent KRAS G12D-specific inhibitor, probody bispecific antibodies, drug–peptide conjugate as MHC-restricted neoantigen to prompt immune response by T-cells, and success in the adoptive cell therapy front in both breast and pancreatic cancers

Balloting ratio and degree of IPO underpricing.

This report examines the relationship between balloting ratio and degree of IPO underpricing. Using IPOs' data from 1995-2000, it provides for the first time that there is a significant relationship between balloting ratio and IPO underpricing

SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P

The sorting nexin (SNX) protein family is implicated in regulating membrane traffic, but the mechanism is still unknown. We show that SNX3 is associated with the early endosome through a novel motif (PX domain) capable of interaction with phosphatidylinositol-3-phosphate (PtdIns(3)P). Overexpression of SNX3 alters endosomal morphology and delays transport to the lysosome. Transport from the early to the recycling endosome is affected upon microinjection of SNX3 antibodies. Our results highlight a novel mechanism by which SNX proteins regulate traffic and uncover a novel class of effectors for PtdIns(3)P

Biochemical fractionation and characterization of proteins from Golgi- enriched membranes

Fractions enriched in Golgi membranes were prepared from rat liver by sucrose gradient ultracentrifugation. These enriched membranes were further subfractionated on the basis of their solubilities in EGTA, 150 mM sodium carbonate, pH 11.5, sodium deoxycholate, Triton X-100, or sodium dodecyl sulfate. This led to isolation of peripheral, luminal, and integral membrane proteins of the Golgi-enriched membranes. Luminal and membrane proteins were further purified by wheat germ agglutinin and concanavalin A lectin affinity chromatographies. Some proteins from these lectin columns were resolved by preparative gel electrophoresis and microsequenced. Subsequently, antibodies were produced for two proteins by immunization of either mice or rabbits. Immunofluorescence microscopy suggests that these proteins are confined to Golgi apparatus-like structures. The protocol described is well suited for the study of organelle structure and function.</p