E2F-2 is a Retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyper-phosphorylation induces E2F transcriptional activator functions. E2F-2-loss causes reduced peripheral red blood cell (RBC) counts, without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout...
The striatum is a subcortical nucleus that regulates a number of complex activities ranging from voluntary action selection to the subconscious formation of habit. The coordination of these operations is mediated by the principle cells of the striatum, spiny projection neurons (SPNs). SPN activity is dictated by a confluence of...
The FDA approvals of afatinib and ibrutinib in 2013 led to a heightened interest in cysteine-reactive covalent inhibitors. However, there are few methods to discover new cysteine-reactive inhibitors for enzymes for which reversible binding scaffolds are not known. To this end, we rationally designed a chemical system to attach a...
Chronic pain is a prevalent and under-treated condition that remains a mystery to the medical system and a major social and economic problem. Unfortunately, there is no single treatment superior to others for relieving chronic pain. While recent scientific discoveries have provided us with functional and anatomical brain biomarkers of...
This dissertation develops and applies coupled marine sulfur and strontium cycle modeling to the highly dynamic Early Cretaceous demonstrating the value of increased model constraint from linkage of biogeochemical cycles with shared forcing factors. A foundation for this work is first provided by review of relevant geochemical, sedimentological, and paleontological...
Glaucoma is a neurodegenerative blinding disease associated with increased intraocular pressure, which is caused by an increased resistance to the outflow of aqueous humor. Although the cause for increased resistance remains unknown, it has been associated with a decreased density of pores in the cells of the inner wall endothelium...
Even though renal blood flow accounts for nearly a quarter of cardiac output, the renal medulla operates in an environment with a scant supply of oxygen. The reason for this apparent discrepancy is thought to be threefold. Blood flow to the outer medulla is less than 50% of that received...
Broadband networks are one of the most economically significant and fastest growing sectors of the Internet. Recent studies have shown that providing broadband Internet access is instrumental for social and economic development. Several governments, as well as the UN, have gone so far as to label broadband access a basic...
Tribological behaviors of lubricated interfaces are strongly affected by the interactions between mating surfaces and the rheological properties of the lubricant between them. This research aims to improve lubrication through two approaches: 1) designing surface textures for lubrication enhancement and adhesion reduction, and 2) developing lubricants of desired rheology.
Molecular...