An examination of strategic opportunities provided by the conference committee procedure in the U.S. Congress

Deference to committees in Congress has been a much studied phenomena for close to 100 years. This deference can be characterized as the unwillingness of a potentially winning coalition on the House floor to impose its will on a small minority, a standing committee. The congressional scholar is then faced with two problems: observing such deference to committees, and explaining it. Shepsle and Weingast have proposed the existence of an ex-post veto for standing committees as an explanation of committee deference. They claim that as conference reports in the House and Senate are considered under a rule that does not allow amendments, the conferees enjoy agenda-setting power. In this paper I describe a test of such a hypothesis (along with competing hypotheses regarding the effects of the conference procedure). A random-utility model is utilized to estimate legislators' ideal points on appropriations bills from 1973 through 1980. I prove two things: 1) that committee deference can not be said to be a result of the conference procedure; and moreover 2) that committee deference does not appear to exist at all.

Delivery of Targeted Nanoparticles Across the Blood-Brain Barrier Using a Detachable Targeting Ligand

Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.

To accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.

Transferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.

Next, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.

Finally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson’s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.