The process of drug discovery is very slow and expensive. There is a need for reliable in silico methods; however the performance of these methods differs. This work presents a targeted study on how the drug discovery methods used in OpenEye’s tools ROCS, EON and FRED perform on targets with small ligands. It was examined if 12 compounds (markers) somewhat similar to AMP could be detected by ROCS in a random data set comprised of 1000 compounds. It was also examined if EON could find any electrostatic similarities between the queries and the markers. The performance of FRED with respect to re-generation of bound ligand modes was examined on ten different protein/ligand complexes from the Brookhaven Protein Data Bank. It was also examined if FRED is suitable as a screening tool since several other docking methods are used in such a way. Finally it was also examined if it was possible to reduce the time requirements of ROCS when running multiconformer queries by using a combination of single conformer queries coupled with multiconformer queries. The conclusions that could be drawn from this project were that FRED is not a good screening tool, but ROCS performs well as such. It was also found that the scoring functions are the weak spots of FRED. EON is probably very sensitive to the conformers used but can in some cases strengthen the results from ROCS. A novel and simple way to reduce the time complexity with multiconformer queries to ROCS was discovered and was shown to work well.

<p>The process of drug discovery is very slow and expensive. There is a need for reliable in silico methods; however the performance of these methods differs.</p><p>This work presents a targeted study on how the drug discovery methods used in OpenEye’s tools ROCS, EON and FRED perform on targets with small ligands. It was examined if 12 compounds (markers) somewhat similar to AMP could be detected by ROCS in a random data set comprised of 1000 compounds. It was also examined if EON could find any electrostatic similarities between the queries and the markers. The performance of FRED with respect to re-generation of bound ligand modes was examined on ten different protein/ligand complexes from the Brookhaven Protein Data Bank. It was also examined if FRED is suitable as a screening tool since several other docking methods are used in such a way. Finally it was also examined if it was possible to reduce the time requirements of ROCS when running multiconformer queries by using a combination of single conformer queries coupled with multiconformer queries.</p><p>The conclusions that could be drawn from this project were that FRED is not a good screening tool, but ROCS performs well as such. It was also found that the scoring functions are the weak spots of FRED. EON is probably very sensitive to the conformers used but can in some cases strengthen the results from ROCS. A novel and simple way to reduce the time complexity with multiconformer queries to ROCS was discovered and was shown to work well.</p>

It has long been the opinion of the writer that behind the great movements "which shape the lives of the multitudes, in the shadows of the public personalities which sponsor them, work quiet, unassuming men who really determine the course of our society. Uncompromised by the limelight, with little thought of great personal reward, these dedicated, prescient thinkers prepare the stage for posterity. [...]

No description available.

Zugl.: Mainz, Univ., Diss., 2006.

Thesis (D.M.A.)--University of Wisconsin--Madison, 1998. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 220-225).

El presente trabajo pretende analizar el alcance y relevancia que tiene la teoría de las representaciones mentales del filósofo norteamericano Fred Dretske para los desarrollos actuales en filosofía de la ciencia cognitiva. Como se verá su teoría contribuye al esclarecimiento de la naturaleza y funcionamiento de la mente y, de este modo, a la fundamentación de muchas de las presuposiciones sustantivas de la ciencia cognitiva contemporánea. Su aporte en este tópico dice relación con dos dimensiones de las representaciones mentales que están estrechamente relacionadas: (i) la individuación naturalista del contenido representacional sobre bases informacionales y (ii) la determinación del contenido intencional de una representación en virtud del control que esta ejerce sobre los mecanismos efectores de las respuestas de un organismo a estímulos determinados de su entorno. El tratamiento de (i) y (ii), no solamente tiene implicancias para las presuposiciones sustantivas de la ciencia cognitiva, sino que, además, esclarecen materias importantes relativas al aprendizaje como uno de los temas centrales de la ciencia cognitiva.

This master's thesis deals with domain registration and related registration systems administrators domains. The main focus is on domain registration via registrars, which is connected with an interface for the registrars registration systems. A part of the interface for the registrars is EPP communication protocol, which is in the project described in detail. Furthermore, there is an overview of freely available registration systems. After this overview, the work focuses more on the czech registration system FRED, specifically the section solving communication with the registrars. A part of is a little research conducted among the registrars aimed at their solving access to the registration system. To facilitate this approach, this work focuses on the implementation of the client library that shield programmers from the details of the communication protocol between the registrar and the registration system and provides an interface for easy implementation of client for the FRED system.

A new method for measuring the hardness-intensity correlation (HIC) present in gamma-ray bursts (GRB) is developed. This method is used to measure the HIC for 100 single-peak gamma-ray bursts, 17 with known redshifts. The HIC is thus shown to be a consequence of energy-dependent lag times between hard and soft photons. Parameters derived from time profile fits using a modified double sigmoidal function are used to calculate a new set of lag time parameters for bursts, and these parameters are analyzed statistically to look for correlations with intrinsic GRB properties. This analysis shows that GRB red shift is related to lag times between hard and soft photons and that, to within 65% accuracy, GRB redshift can be predicted by the equation: z = 2.49 - 0.131(dpeak) - 0.473(MADS_dpeak)+ 0.143(decay_lag)

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