Research Triangle Park

About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.

Apparatus and method for determining selection of touchable items on a computer touchscreen by an imprecise touch

Abstract: An apparatus and method of determining which touchable item depicted on a computer touchscreen to select for an imprecise touch, including the steps of identifying all potentially selected touchable items for the imprecise touch, calculating a probability of intended selection for each potentially selected touchable item, and selecting the potentially selected touchable item having the greatest calculated probability of intended selection. It will be seen that the identifying step includes determining which touchable items depicted on the computer touchscreen overlap with the imprecise touch. The probability calculating step is a function of a distance between a centerpoint of the imprecise touch and a centerpoint for each potentially selected touchable item and/or a function of an overlap area between the imprecise touch and each potentially selected touchable item. The selecting step further includes comparing the calculated probability of intended selection for each potentially selected touchable item and determining whether the potentially selected touchable item having the greatest calculated probability of intended selection is greater than the calculated probability of intended selection for the potentially selected touchable items by a predetermined amount.

In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates

Abstract: Because modulation of P-glycoprotein (Pgp) through inhibition or induction can lead to drug-drug interactions by altering intestinal, central nervous system, renal, or biliary efflux, it is anticipated that information regarding the potential interaction of drug candidates with Pgp will be a future regulatory expectation. Therefore, to be able to utilize in vitro Pgp inhibition findings to guide clinical drug interaction studies, the utility of five probe substrates (calcein-AM, colchicine, digoxin, prazosin, and vinblastine) was evaluated by inhibiting their Pgp-mediated transport across multidrug resistance-1-transfected Madin-Darby canine kidney cell type II monolayers with 20 diverse drugs having various degrees of Pgp interaction (e.g., efflux ratio, ATPase, and calcein-AM inhibition). Overall, the rank order of inhibition was generally similar with IC 50 values typically within 3- to 5-fold of each other. However, several notable differences in the IC 50 values were observed. Digoxin and prazosin were the most sensitive probes (e.g., lowest IC 50 values), followed by colchicine, vinblastine, and calcein-AM. Inclusion of other considerations such as a large dynamic range, commercially available radiolabel, and a clinically meaningful probe makes digoxin an attractive probe substrate. Therefore, it is recommended that digoxin be considered as the standard in vitro probe to investigate the inhibition profiles of new drug candidates. Furthermore, this study shows that it may not be necessary to generate IC 50 values with multiple probe substrates for Pgp as is currently done for cytochrome P450 3A4. Finally, a strategy integrating results from in vitro assays (efflux, inhibition, and ATPase) is provided to further guide clinical interaction studies.

Two-dimensional SEC/RPLC coupled to mass spectrometry for the analysis of peptides

Abstract: A two-dimensional liquid chromatography system is described here which uses size exclusion liquid chromatography (SEC) followed by reversed phase liquid chromatography (RPLC) to separate the mixture of peptides resulting from the enzymatic digestion of a protein. A novel LC/LC interface, using two RPLC columns in parallel rather than storage loops, joins the two chromatographic dimensions. This new interface design permits the use of conventional analytical diameter HPLC columns, 7.8 mm for SEC and 4.6 mm for RPLC, making construction and maintenance of this system very easy. The reversed phase chromatography utilizes 1.5 μm diameter, nonporous C-18 modified silica particles, which produce fast and efficient analyses. Following the high-resolution two-dimensional chromatographic separation, an electrospray mass spectrometer detects the peptide fragments. The mass spectrometer scans a 2000 m/z range to identify the analytes from their molecular weights. The analyses of tryptic digests of ovalbumin and seru...