6,211 research outputs found
Dr. Stephen W. Fox to James C. Furman
No full textA two page letter and envelope from Dr. Stephen W. Fox to James C. Furma
Dr. Stephen M. Fox to James C. Furman
No full textA two page letter and envelope from Dr. Stephen M. Fox to James C. Furma
Service-oriented models for audiovisual content storage
No full textWhat are the important topics to understand if involved with storage services to hold digital audiovisual content? This report takes a look at how content is created and moves into and out of storage; the storage service value networks and architectures found now and expected in the future; what sort of data transfer is expected to and from an audiovisual archive; what transfer protocols to use; and a summary of security and interface issues
Protein-ligand binding affinities from large-scale quantum mechanical simulations
No full textThe accurate prediction of protein-drug binding affinities is a major aim of computational drug optimisation and development. A quantitative measure of binding affinity is provided by the free energy of binding, and such calculations typically require extensive configurational sampling of entities such as proteins with thousands of atoms. Current binding free energy methods use force fields to perform the configurational sampling and to compute interaction energies. Due to the empirical nature of force fields and the neglect of electrons, electron polarisation and charge transfer are not accounted for explicitly. This can limit the accuracy with which interactions are calculated and consequently the free energies obtained. Ideally ab initio quantum chemistry approaches should be used as these explicitly include the electrons. However, conventional ab initio approaches are not suitable due to their prohibitively high computational cost and unfavourable scaling.In this thesis we use large-scale ab initio quantum chemistry calculations within the Density Functional Theory (DFT) method to address the above mentioned limitations of force fields. To obtain quantitative results with ab initio approaches it is important to converge the calculations with the size of the basis set. For this reason we have used the ONETEP program, which is capable of linear-scaling DFT with near-complete basis set accuracy.A well known binding free energy approach is the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA), which obtains free energies from evaluation of the energy of configurations in an implicit solvent model. We present the first application of a “QM-PBSA” approach to a protein-ligand system containing over 2600 atoms. In this QM-PBSA approach the energies of the configurations in vacuum are evaluated with ONETEP. The solvation energies were also obtained with ONETEP using a minimal parameter implicit solvent model within the self-consistent calculation. Large-scale DFT calculations were also applied within a more theoretically rigorous free energy approach which can, in principle, obtain the full entropic contributions to free energy change. The method performs a mutation from a molecular mechanical (MM) description to an quantum mechanical (QM) description of a system. As a result a QM correction is added to the relative binding free energy obtained from a thermodynamic integration calculation within the MM description.This approach was combined with an electrostatic embedding model within ONETEP and used to calculate the hydration energies of small molecules. As well as the computation of more accurate energies, large-scale DFT calculation compute the electron density of the entire system. Using electron density analysis approaches, such as the Hirshfeld density analysis, in combination with energy decomposition approaches, such as a second order perturbation estimate of natural bond orbital interactions, both qualitative and quantitative understandings can be gained into the contributions of particular chemical functional groups that define protein-ligand interactions. These two approaches where applied to study complexes of the Phosphodiesterase type 5 protein and used to rank ligand binding affinities that agree well with then experimentally observed trends
Review of Toward Other Worlds: Perspectives on John Milton, C. S. Lewis, Stephen King, Orson Scott Card, and Others
No full textWilliam Gentrup: Review of: Michael R. Collings, Toward Other Worlds: Perspectives on John Milton, C. S. Lewis, Stephen King, Orson Scott Card, and Others (Rockville, MD, 2010). 309 pages. $16.99. ISBN: 9781434457929.; .; . .; Suzanne Bray: .; David Llewellyn Dodds: .
Review of The Hidden Story of Narnia: A Book-by-Book Guide to C.S. Lewis\u27 Spiritual Themes
No full textStephen Yandell: Review of Will Vaus, The Hidden Story of Narnia: A Book-by-Book Guide to C. S. Lewis’ Spiritual Themes (Cheshire, Connecticut, 2010). ii + 135 pages. $19.97. ISBN 9781936294022
Review of Encyclopedia of Contemporary Christian Fiction: From C.S. Lewis to Left Behind
No full textStephen F. Hayes: Review of Nancy M. Tischler, Encyclopedia of Contemporary Christian Fiction: From C. S. Lewis to Left Behind (Santa Barbara, 2009). 352 pages. $96. ISBN 9780313345685
Memorandum from A. E. Demaray to E. C. Finney
No full textFour letters of correspondence about the purchase of Bright Angel Trail between A. E. Demaray, Acting Director of the Grand Canyon National Park; E. C. Finney, Department of the Interior First Assistant Secretary; Carl T. Hayden, Representative (AZ); and Stephen T. Mather, Director of the National Park Service
First principles-based calculations of free energy of binding: application to ligand binding in a self-assembling superstructure
No full textThe accurate prediction of ligand binding affinities to a protein remains a desirable goal of computational biochemistry. Many available methods use molecular mechanics (MM) to describe the system, however, MM force fields cannot fully describe the complex interactions involved in binding, specifically electron transfer and polarization. First principles approaches can fully account for these interactions, and with the development of linear-scaling first principles programs, it is now viable to apply first principles calculations to systems containing tens of thousands of atoms. In this paper, a quantum mechanical Poisson?Boltzmann surface area approach is applied to a model of a protein?ligand binding cavity, the “tennis ball” dimer. Results obtained from this approach demonstrate considerable improvement over conventional molecular mechanics Poisson?Boltzmann surface area due to the more accurate description of the interactions in the system. For the first principles calculations in this study, the linear-scaling density functional theory program ONETEP is used, allowing the approach to be applied to receptor?ligand complexes of pharmaceutical interest that typically include thousands of atoms.<br/
A molecular anchor for stabilizing triple-helical DNA
No full textMolecular modeling has been used to predict that 2,6-disubstituted amidoanthraquinones, and not the 1,4 series, should preferentially interact with and stabilize triple-stranded DNA structures over duplex DNA. This is due to marked differences in the nature of chromophore-base stacking and groove accessibility for the two series. A DNA footprinting method that monitors the extent of protection from DNase I cleavage on triplex formation has been used to examine the effects of a number of synthetic isomer compounds in the 1,4 and 2,6 series. The experimental results are in accord with the predicted behavior and confirm that the 1,4 series bind preferentially to double- rather than triple-stranded DNA, whereas the isomeric 2,6 derivatives markedly favor binding to triplex DNA.</p
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