Georgetown University

About: Georgetown University is a education organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 23377 authors who have published 43718 publications receiving 1748598 citations. The organization is also known as: GU & Georgetown.

Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex

Abstract: Using a sensitive histofluorescence staining method that allows for a quantitation of neuronal death, we compared the protective effects of gangliosides (a group of naturally occurring glycosphingolipids), phencyclidine (PCP), and MK-801 (dibenzocyclohepteneimine) on glutamate- and kainate-induced neuronal death in primary cultures of cortical and cerebellar neurons prepared from neonatal rats. PCP and MK-801 block neurotoxicity induced by glutamate doses 50 times higher than the LD50 (LD50 in Mg2+-free medium, 10 microM) but only partially block the kainate neurotoxicity (LD50 in presence of Mg2+, 100 microM). In contrast, pretreatment with gangliosides (GT1b greater than GD1b greater than GM1) results in complete and insurmountable protection against the neurotoxicity elicited by glutamate or kainate. In primary cultures of cerebellar granule cells gangliosides, unlike PCP and MK-801, fail to block glutamate-gated cationic currents and the glutamate-evoked increase of (i) inositol phospholipid hydrolysis (ii) c-fos mRNA content, and (iii) nuclear accumulation of c-fos protein. Protection of glutamate neurotoxicity by gangliosides does not require their presence in the incubation medium; however, it is proportional to the amount of glycosphingolipid accumulated in the neuronal membranes. The ganglioside concentration (30-60 microM) that blocks glutamate-elicited neuronal death also prevents glutamate- and kainate-induced protein kinase C translocation from cytosol to neuronal membranes.

Trials and Errors: Principle and Pragmatism in Strategies of International Justice

Abstract: Advocacy groups such as Human Rights Watch and Amnesty International have made a historic contribution to the cause of international human rights by publicizing the need to prevent mass atrocities such as war crimes, genocide, and widespread political killings and torture.1 However, a strategy that many such groups favor for achieving this goal—the prosecution of perpetrators of atrocities according to universal standards—risks causing more atrocities than it would prevent, because it pays insufacient attention to political realities.2 Recent international criminal tribunals have utterly failed to deter subsequent abuses in the former Yugoslavia and Central Africa. Because tribunals, including the International Criminal Court (ICC), have often been unable to gain the active cooperation of powerful actors in the United States and in countries where abuses occur, it is questionable whether this strategy will succeed in the long run unless it is implemented in a more pragmatic way. Trials and Errors

Optimal Design of Research Contests

Abstract: Procurement of an innovation often requires substantial effort by potential suppliers. Motivating effort may be difficult if the level of effort and quality of the resulting innovation are unverifiable, if innovators cannot benefit directly by marketing their innovations, and if the buyer cannot extract up-front payments from suppliers. We study the use of contests to procure an innovation in such an environment. An auction in which two suppliers are invited to innovate and then bid their prizes is optimal in a large class of contests. If contestants are asymmetric, it is optimal to handicap the most efficient one.