Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.
Sullivan, David C; Lim, Carmay
2006-08-24
Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.
Kniss, Andreas; Schuetz, Denise; Kazemi, Sina; Pluska, Lukas; Spindler, Philipp E; Rogov, Vladimir V; Husnjak, Koraljka; Dikic, Ivan; Güntert, Peter; Sommer, Thomas; Prisner, Thomas F; Dötsch, Volker
2018-02-06
Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin code. In particular, processes that modify chain length will be affected by chain conformations as they require access to the elongation or cleavage sites. We investigated conformational distributions in the context of chain elongation and disassembly using pulsed electron-electron double resonance spectroscopy in combination with molecular modeling. Analysis of the conformational space of diubiquitin revealed conformational selection or remodeling as mechanisms for chain recognition during elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin increases the sampled conformational space, suggesting that a high intrinsic flexibility of K48-linked chains may contribute to efficient proteasomal degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Boundary conformal anomalies on hyperbolic spaces and Euclidean balls
NASA Astrophysics Data System (ADS)
Rodriguez-Gomez, Diego; Russo, Jorge G.
2017-12-01
We compute conformal anomalies for conformal field theories with free conformal scalars and massless spin 1/2 fields in hyperbolic space ℍ d and in the ball B^d , for 2≤d≤7. These spaces are related by a conformal transformation. In even dimensional spaces, the conformal anomalies on ℍ2 n and B^{2n} are shown to be identical. In odd dimensional spaces, the conformal anomaly on B^{2n+1} comes from a boundary contribution, which exactly coincides with that of ℍ2 n + 1 provided one identifies the UV short-distance cutoff on B^{2n+1} with the inverse large distance IR cutoff on ℍ2 n + 1, just as prescribed by the conformal map. As an application, we determine, for the first time, the conformal anomaly coefficients multiplying the Euler characteristic of the boundary for scalars and half-spin fields with various boundary conditions in d = 5 and d = 7.
Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution.
Kleinjung, J; Bayley, P; Fraternali, F
2000-03-31
A molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational 'leaps' to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques.
Guiding Conformation Space Search with an All-Atom Energy Potential
Brunette, TJ; Brock, Oliver
2009-01-01
The most significant impediment for protein structure prediction is the inadequacy of conformation space search. Conformation space is too large and the energy landscape too rugged for existing search methods to consistently find near-optimal minima. To alleviate this problem, we present model-based search, a novel conformation space search method. Model-based search uses highly accurate information obtained during search to build an approximate, partial model of the energy landscape. Model-based search aggregates information in the model as it progresses, and in turn uses this information to guide exploration towards regions most likely to contain a near-optimal minimum. We validate our method by predicting the structure of 32 proteins, ranging in length from 49 to 213 amino acids. Our results demonstrate that model-based search is more effective at finding low-energy conformations in high-dimensional conformation spaces than existing search methods. The reduction in energy translates into structure predictions of increased accuracy. PMID:18536015
Euclidean sections of protein conformation space and their implications in dimensionality reduction
Duan, Mojie; Li, Minghai; Han, Li; Huo, Shuanghong
2014-01-01
Dimensionality reduction is widely used in searching for the intrinsic reaction coordinates for protein conformational changes. We find the dimensionality–reduction methods using the pairwise root–mean–square deviation as the local distance metric face a challenge. We use Isomap as an example to illustrate the problem. We believe that there is an implied assumption for the dimensionality–reduction approaches that aim to preserve the geometric relations between the objects: both the original space and the reduced space have the same kind of geometry, such as Euclidean geometry vs. Euclidean geometry or spherical geometry vs. spherical geometry. When the protein free energy landscape is mapped onto a 2D plane or 3D space, the reduced space is Euclidean, thus the original space should also be Euclidean. For a protein with N atoms, its conformation space is a subset of the 3N-dimensional Euclidean space R3N. We formally define the protein conformation space as the quotient space of R3N by the equivalence relation of rigid motions. Whether the quotient space is Euclidean or not depends on how it is parameterized. When the pairwise root–mean–square deviation is employed as the local distance metric, implicit representations are used for the protein conformation space, leading to no direct correspondence to a Euclidean set. We have demonstrated that an explicit Euclidean-based representation of protein conformation space and the local distance metric associated to it improve the quality of dimensionality reduction in the tetra-peptide and β–hairpin systems. PMID:24913095
Conformal Yano-Killing Tensors for Space-times with Cosmological Constant
NASA Astrophysics Data System (ADS)
Czajka, P.; Jezierski, J.
We present a new method for constructing conformal Yano-Killing tensors in five-di\\-men\\-sio\\-nal Anti-de Sitter space-time. The found tensors are represented in two different coordinate systems. We also discuss, in terms of CYK tensors, global charges which are well defined for asymptotically (five-dimensional) Anti-de Sitter space-time. Additionally in Appendix we present our own derivation of conformal Killing one-forms in four-dimensional Anti-de Sitter space-time as an application of the Theorem presented in the paper.
Lu, Chao; Li, Xubin; Wu, Dongsheng; Zheng, Lianqing; Yang, Wei
2016-01-12
In aqueous solution, solute conformational transitions are governed by intimate interplays of the fluctuations of solute-solute, solute-water, and water-water interactions. To promote molecular fluctuations to enhance sampling of essential conformational changes, a common strategy is to construct an expanded Hamiltonian through a series of Hamiltonian perturbations and thereby broaden the distribution of certain interactions of focus. Due to a lack of active sampling of configuration response to Hamiltonian transitions, it is challenging for common expanded Hamiltonian methods to robustly explore solvent mediated rare conformational events. The orthogonal space sampling (OSS) scheme, as exemplified by the orthogonal space random walk and orthogonal space tempering methods, provides a general framework for synchronous acceleration of slow configuration responses. To more effectively sample conformational transitions in aqueous solution, in this work, we devised a generalized orthogonal space tempering (gOST) algorithm. Specifically, in the Hamiltonian perturbation part, a solvent-accessible-surface-area-dependent term is introduced to implicitly perturb near-solute water-water fluctuations; more importantly in the orthogonal space response part, the generalized force order parameter is generalized as a two-dimension order parameter set, in which essential solute-solvent and solute-solute components are separately treated. The gOST algorithm is evaluated through a molecular dynamics simulation study on the explicitly solvated deca-alanine (Ala10) peptide. On the basis of a fully automated sampling protocol, the gOST simulation enabled repetitive folding and unfolding of the solvated peptide within a single continuous trajectory and allowed for detailed constructions of Ala10 folding/unfolding free energy surfaces. The gOST result reveals that solvent cooperative fluctuations play a pivotal role in Ala10 folding/unfolding transitions. In addition, our assessment
Real-space visualization of conformation-independent oligothiophene electronic structure
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taber, Benjamen N.; Kislitsyn, Dmitry A.; Gervasi, Christian F.
2016-05-21
We present scanning tunneling microscopy and spectroscopy (STM/STS) investigations of the electronic structures of different alkyl-substituted oligothiophenes on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes adopted distinct straight and bent conformations. By combining STS maps with STM images, we visualize, in real space, particle-in-a-box-like oligothiophene molecular orbitals. We demonstrate that different planar conformers with significant geometrical distortions of oligothiophene backbones surprisingly exhibit very similar electronic structures, indicating a low degree of conformation-induced electronic disorder. The agreement of these results with gas-phase density functional theory calculations implies that the oligothiophene interaction with the Au(111) surface is generally insensitivemore » to molecular conformation.« less
Structural alphabets derived from attractors in conformational space
2010-01-01
Background The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis. Results A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness. Conclusions The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics. PMID:20170534
Conformal higher spin theory and twistor space actions
NASA Astrophysics Data System (ADS)
Hähnel, Philipp; McLoughlin, Tristan
2017-12-01
We consider the twistor description of conformal higher spin theories and give twistor space actions for the self-dual sector of theories with spin greater than two that produce the correct flat space-time spectrum. We identify a ghost-free subsector, analogous to the embedding of Einstein gravity with cosmological constant in Weyl gravity, which generates the unique spin-s three-point anti-MHV amplitude consistent with Poincaré invariance and helicity constraints. By including interactions between the infinite tower of higher-spin fields we give a geometric interpretation to the twistor equations of motion as the integrability condition for a holomorphic structure on an infinite jet bundle. Finally, we conjecture anti-self-dual interaction terms which give an implicit definition of a twistor action for the full conformal higher spin theory.
Hao, Xiaohu; Zhang, Guijun; Zhou, Xiaogen
2018-04-01
Computing conformations which are essential to associate structural and functional information with gene sequences, is challenging due to the high dimensionality and rugged energy surface of the protein conformational space. Consequently, the dimension of the protein conformational space should be reduced to a proper level, and an effective exploring algorithm should be proposed. In this paper, a plug-in method for guiding exploration in conformational feature space with Lipschitz underestimation (LUE) for ab-initio protein structure prediction is proposed. The conformational space is converted into ultrafast shape recognition (USR) feature space firstly. Based on the USR feature space, the conformational space can be further converted into Underestimation space according to Lipschitz estimation theory for guiding exploration. As a consequence of the use of underestimation model, the tight lower bound estimate information can be used for exploration guidance, the invalid sampling areas can be eliminated in advance, and the number of energy function evaluations can be reduced. The proposed method provides a novel technique to solve the exploring problem of protein conformational space. LUE is applied to differential evolution (DE) algorithm, and metropolis Monte Carlo(MMC) algorithm which is available in the Rosetta; When LUE is applied to DE and MMC, it will be screened by the underestimation method prior to energy calculation and selection. Further, LUE is compared with DE and MMC by testing on 15 small-to-medium structurally diverse proteins. Test results show that near-native protein structures with higher accuracy can be obtained more rapidly and efficiently with the use of LUE. Copyright © 2018 Elsevier Ltd. All rights reserved.
Dissecting the conformational determinants of chitosan and chitlac oligomers.
Esteban, Carmen; Donati, Ivan; Pantano, Sergio; Villegas, Myriam; Benegas, Julio; Paoletti, Sergio
2018-06-01
Chitosan and its highly hydrophilic 1-deoxy-lactit-1-yl derivative (Chitlac) are polysaccharides with increasing biomedical applications. Aimed to unravel their conformational properties we have performed a series of molecular dynamics simulations of Chitosan/Chitlac decamers, exploring different degrees of substitution (DS) of lactitol side chains. At low DS, two conformational regions with different populations are visited, while for DS ≥ 20% the oligomers remain mostly linear and only one main region of the glycosidic angles is sampled. These conformers are (locally) characterized by extended helical "propensities". Helical conformations 3 2 and 2 1, by far the most abundant, only develop in the main region. The accessible conformational space is clearly enlarged at high ionic strength, evidencing also a new region accessible to the glycosidic angles, with short and frequent interchange between regions. Simulations of neutral decamers share these features, pointing to a central role of electrostatic repulsion between charged moieties. These interactions seem to determine the conformational behavior of the chitosan backbone, with no evident influence of H-bond interactions. Finally, it is also shown that increasing temperature only slightly enlarges the available conformational space, but certainly without signs of a temperature-induced conformational transition. © 2018 Wiley Periodicals, Inc.
On the measure of conformal difference between Euclidean and Lobachevsky spaces
NASA Astrophysics Data System (ADS)
Zorich, Vladimir A.
2011-12-01
Euclidean space R^n and Lobachevsky space H^n are known to be not equivalent either conformally or quasiconformally. In this work we give exact asymptotics of the critical order of growth at infinity for the quasiconformality coefficient of a diffeomorphism f\\colon R^n\\to H^n for which such a mapping f is possible. We also consider the general case of immersions f\\colon M^n\\to N^n of conformally parabolic Riemannian manifolds. Bibliography: 17 titles.
Generative Topographic Mapping of Conformational Space.
Horvath, Dragos; Baskin, Igor; Marcou, Gilles; Varnek, Alexandre
2017-10-01
Herein, Generative Topographic Mapping (GTM) was challenged to produce planar projections of the high-dimensional conformational space of complex molecules (the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity to support property prediction models serves to objectively assess map quality (in terms of regression statistics). The properties to predict were total, non-bonded and contact energies, surface area and fingerprint darkness. Map building and selection was controlled by a previously introduced evolutionary strategy allowed to choose the best-suited conformational descriptors, options including classical terms and novel atom-centric autocorrellograms. The latter condensate interatomic distance patterns into descriptors of rather low dimensionality, yet precise enough to differentiate between close favorable contacts and atom clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map building and cross-validation of property regression models. The GTM build-up challenge reached robust three-fold cross-validated determination coefficients of Q 2 =0.7…0.8, for all modeled properties. Mapping of the full 2 M conformer set produced intuitive and information-rich property landscapes. Functional and folding subspaces appear as well-separated zones, even though RMSD with respect to the PDB structure was never used as a selection criterion of the maps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Conformal Nets II: Conformal Blocks
NASA Astrophysics Data System (ADS)
Bartels, Arthur; Douglas, Christopher L.; Henriques, André
2017-08-01
Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.
A probabilistic and continuous model of protein conformational space for template-free modeling.
Zhao, Feng; Peng, Jian; Debartolo, Joe; Freed, Karl F; Sosnick, Tobin R; Xu, Jinbo
2010-06-01
One of the major challenges with protein template-free modeling is an efficient sampling algorithm that can explore a huge conformation space quickly. The popular fragment assembly method constructs a conformation by stringing together short fragments extracted from the Protein Data Base (PDB). The discrete nature of this method may limit generated conformations to a subspace in which the native fold does not belong. Another worry is that a protein with really new fold may contain some fragments not in the PDB. This article presents a probabilistic model of protein conformational space to overcome the above two limitations. This probabilistic model employs directional statistics to model the distribution of backbone angles and 2(nd)-order Conditional Random Fields (CRFs) to describe sequence-angle relationship. Using this probabilistic model, we can sample protein conformations in a continuous space, as opposed to the widely used fragment assembly and lattice model methods that work in a discrete space. We show that when coupled with a simple energy function, this probabilistic method compares favorably with the fragment assembly method in the blind CASP8 evaluation, especially on alpha or small beta proteins. To our knowledge, this is the first probabilistic method that can search conformations in a continuous space and achieves favorable performance. Our method also generated three-dimensional (3D) models better than template-based methods for a couple of CASP8 hard targets. The method described in this article can also be applied to protein loop modeling, model refinement, and even RNA tertiary structure prediction.
Probing RNA Native Conformational Ensembles with Structural Constraints.
Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie
2016-05-01
Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.
Yamaguchi, Takumi; Sakae, Yoshitake; Zhang, Ying; Yamamoto, Sayoko; Okamoto, Yuko; Kato, Koichi
2014-10-06
Exploration of the conformational spaces of flexible biomacromolecules is essential for quantitatively understanding the energetics of their molecular recognition processes. We employed stable isotope- and lanthanide-assisted NMR approaches in conjunction with replica-exchange molecular dynamics (REMD) simulations to obtain atomic descriptions of the conformational dynamics of high-mannose-type oligosaccharides, which harbor intracellular glycoprotein-fate determinants in their triantennary structures. The experimentally validated REMD simulation provided quantitative views of the dynamic conformational ensembles of the complicated, branched oligosaccharides, and indicated significant expansion of the conformational space upon removal of a terminal mannose residue during the functional glycan-processing pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Conformal field theories and compact curves in moduli spaces
NASA Astrophysics Data System (ADS)
Donagi, Ron; Morrison, David R.
2018-05-01
We show that there are many compact subsets of the moduli space M g of Riemann surfaces of genus g that do not intersect any symmetry locus. This has interesting implications for N=2 supersymmetric conformal field theories in four dimensions.
29 CFR 1915.76 - Access to cargo spaces and confined spaces.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 29 Labor 7 2013-07-01 2013-07-01 false Access to cargo spaces and confined spaces. 1915.76 Section..., Ladders and Other Working Surfaces § 1915.76 Access to cargo spaces and confined spaces. The provisions of... this section applies to ship repairing only. (a) Cargo spaces. (1) There shall be at least one safe and...
29 CFR 1915.76 - Access to cargo spaces and confined spaces.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 29 Labor 7 2012-07-01 2012-07-01 false Access to cargo spaces and confined spaces. 1915.76 Section..., Ladders and Other Working Surfaces § 1915.76 Access to cargo spaces and confined spaces. The provisions of... this section applies to ship repairing only. (a) Cargo spaces. (1) There shall be at least one safe and...
29 CFR 1915.76 - Access to cargo spaces and confined spaces.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 29 Labor 7 2010-07-01 2010-07-01 false Access to cargo spaces and confined spaces. 1915.76 Section..., Ladders and Other Working Surfaces § 1915.76 Access to cargo spaces and confined spaces. The provisions of... this section applies to ship repairing only. (a) Cargo spaces. (1) There shall be at least one safe and...
29 CFR 1915.76 - Access to cargo spaces and confined spaces.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 29 Labor 7 2014-07-01 2014-07-01 false Access to cargo spaces and confined spaces. 1915.76 Section..., Ladders and Other Working Surfaces § 1915.76 Access to cargo spaces and confined spaces. The provisions of... this section applies to ship repairing only. (a) Cargo spaces. (1) There shall be at least one safe and...
29 CFR 1915.76 - Access to cargo spaces and confined spaces.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 29 Labor 7 2011-07-01 2011-07-01 false Access to cargo spaces and confined spaces. 1915.76 Section..., Ladders and Other Working Surfaces § 1915.76 Access to cargo spaces and confined spaces. The provisions of... this section applies to ship repairing only. (a) Cargo spaces. (1) There shall be at least one safe and...
Hao, Xiao-Hu; Zhang, Gui-Jun; Zhou, Xiao-Gen; Yu, Xu-Feng
2016-01-01
To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high-dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more
Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation.
Zlatanova, J; Leuba, S H; Yang, G; Bustamante, C; van Holde, K
1994-01-01
New studies on chromatin fiber morphology, using the technique of scanning force microscopy (SFM), have caused us to reexamine recent analysis of nuclease digestion of chromatin. Chicken erythrocyte chromatin fibers, glutaraldehyde-fixed at 0, 10, and 80 mM NaCl, were imaged with the help of SFM. The chromatin fibers possessed a loose three-dimensional 30-nm structure even in the absence of added salt. This structure slightly condensed upon addition of 10 mM NaCl, and highly compacted, irregularly segmented fibers were observed at 80 mM NaCl. This sheds new light upon our previously reported analysis of the kinetics of digestion by soluble and membrane-immobilized micrococcal nuclease [Leuba, S. H., Zlatanova, J. & van Holde, K. (1994) J. Mol. Biol. 235, 871-880]. While the low-ionic-strength fibers were readily digested, the highly compacted structure formed at 80 mM NaCl was refractory to nuclease attack, implying that the linkers were fully accessible in the low-ionic-strength conformation but not in the condensed fibers. We now find that cleavage of the linker DNA by a small molecule, methidiumpropyl-EDTA-Fe(II), proceeds for all types of conformations at similar rates. Thus, steric hindrance is responsible for the lack of accessibility to micrococcal nuclease in the condensed fiber. Taken in total the data suggest that reexamination of existing models of chromatin conformation is warranted. Images PMID:8202481
Pilot Non-Conformance to Alerting System Commands During Closely Spaced Parallel Approaches
NASA Technical Reports Server (NTRS)
Pritchett, Amy R.; Hansman, R. John
1997-01-01
Pilot non-conformance to alerting system commands has been noted in general and to a TCAS-like collision avoidance system in a previous experiment. This paper details two experiments studying collision avoidance during closely-spaced parallel approaches in instrument meteorological conditions (IMC), and specifically examining possible causal factors of, and design solutions to, pilot non-conformance.
ClustENM: ENM-Based Sampling of Essential Conformational Space at Full Atomic Resolution
Kurkcuoglu, Zeynep; Bahar, Ivet; Doruker, Pemra
2016-01-01
Accurate sampling of conformational space and, in particular, the transitions between functional substates has been a challenge in molecular dynamic (MD) simulations of large biomolecular systems. We developed an Elastic Network Model (ENM)-based computational method, ClustENM, for sampling large conformational changes of biomolecules with various sizes and oligomerization states. ClustENM is an iterative method that combines ENM with energy minimization and clustering steps. It is an unbiased technique, which requires only an initial structure as input, and no information about the target conformation. To test the performance of ClustENM, we applied it to six biomolecular systems: adenylate kinase (AK), calmodulin, p38 MAP kinase, HIV-1 reverse transcriptase (RT), triosephosphate isomerase (TIM), and the 70S ribosomal complex. The generated ensembles of conformers determined at atomic resolution show good agreement with experimental data (979 structures resolved by X-ray and/or NMR) and encompass the subspaces covered in independent MD simulations for TIM, p38, and RT. ClustENM emerges as a computationally efficient tool for characterizing the conformational space of large systems at atomic detail, in addition to generating a representative ensemble of conformers that can be advantageously used in simulating substrate/ligand-binding events. PMID:27494296
Safety Benefits of Access Spacing
DOT National Transportation Integrated Search
1997-01-01
The spacing of driveways and streets is an important element in roadway planning, design, and operation. Access points are the main source of accidents and congestion. Their location and spacing affects the safety and functional integrity of streets ...
Access to Space Interactive Design Web Site
NASA Technical Reports Server (NTRS)
Leon, John; Cutlip, William; Hametz, Mark
2000-01-01
The Access To Space (ATS) Group at NASA's Goddard Space Flight Center (GSFC) supports the science and technology community at GSFC by facilitating frequent and affordable opportunities for access to space. Through partnerships established with access mode suppliers, the ATS Group has developed an interactive Mission Design web site. The ATS web site provides both the information and the tools necessary to assist mission planners in selecting and planning their ride to space. This includes the evaluation of single payloads vs. ride-sharing opportunities to reduce the cost of access to space. Features of this site include the following: (1) Mission Database. Our mission database contains a listing of missions ranging from proposed missions to manifested. Missions can be entered by our user community through data input tools. Data is then accessed by users through various search engines: orbit parameters, ride-share opportunities, spacecraft parameters, other mission notes, launch vehicle, and contact information. (2) Launch Vehicle Toolboxes. The launch vehicle toolboxes provide the user a full range of information on vehicle classes and individual configurations. Topics include: general information, environments, performance, payload interface, available volume, and launch sites.
Conformational space annealing scheme in the inverse design of functional materials
NASA Astrophysics Data System (ADS)
Kim, Sunghyun; Lee, In-Ho; Lee, Jooyoung; Oh, Young Jun; Chang, Kee Joo
2015-03-01
Recently, the so-called inverse method has drawn much attention, in which specific electronic properties are initially assigned and target materials are subsequently searched. In this work, we develop a new scheme for the inverse design of functional materials, in which the conformational space annealing (CSA) algorithm for global optimization is combined with first-principles density functional calculations. To implement the CSA, we need a series of ingredients, (i) an objective function to minimize, (ii) a 'distance' measure between two conformations, (iii) a local enthalpy minimizer of a given conformation, (iv) ways to combine two parent conformations to generate a daughter one, (v) a special conformation update scheme, and (vi) an annealing method in the 'distance' parameter axis. We show the results of applications for searching for Si crystals with direct band gaps and the lowest-enthalpy phase of boron at a finite pressure and discuss the efficiency of the present scheme. This work is supported by the National Research Foundation of Korea (NRF) under Grant No. NRF-2005-0093845 and by Samsung Science and Technology Foundation under Grant No. SSTFBA1401-08.
Metadynamics in the conformational space nonlinearly dimensionally reduced by Isomap.
Spiwok, Vojtěch; Králová, Blanka
2011-12-14
Atomic motions in molecules are not linear. This infers that nonlinear dimensionality reduction methods can outperform linear ones in analysis of collective atomic motions. In addition, nonlinear collective motions can be used as potentially efficient guides for biased simulation techniques. Here we present a simulation with a bias potential acting in the directions of collective motions determined by a nonlinear dimensionality reduction method. Ad hoc generated conformations of trans,trans-1,2,4-trifluorocyclooctane were analyzed by Isomap method to map these 72-dimensional coordinates to three dimensions, as described by Brown and co-workers [J. Chem. Phys. 129, 064118 (2008)]. Metadynamics employing the three-dimensional embeddings as collective variables was applied to explore all relevant conformations of the studied system and to calculate its conformational free energy surface. The method sampled all relevant conformations (boat, boat-chair, and crown) and corresponding transition structures inaccessible by an unbiased simulation. This scheme allows to use essentially any parameter of the system as a collective variable in biased simulations. Moreover, the scheme we used for mapping out-of-sample conformations from the 72D to 3D space can be used as a general purpose mapping for dimensionality reduction, beyond the context of molecular modeling. © 2011 American Institute of Physics
Metadynamics in the conformational space nonlinearly dimensionally reduced by Isomap
NASA Astrophysics Data System (ADS)
Spiwok, Vojtěch; Králová, Blanka
2011-12-01
Atomic motions in molecules are not linear. This infers that nonlinear dimensionality reduction methods can outperform linear ones in analysis of collective atomic motions. In addition, nonlinear collective motions can be used as potentially efficient guides for biased simulation techniques. Here we present a simulation with a bias potential acting in the directions of collective motions determined by a nonlinear dimensionality reduction method. Ad hoc generated conformations of trans,trans-1,2,4-trifluorocyclooctane were analyzed by Isomap method to map these 72-dimensional coordinates to three dimensions, as described by Brown and co-workers [J. Chem. Phys. 129, 064118 (2008)]. Metadynamics employing the three-dimensional embeddings as collective variables was applied to explore all relevant conformations of the studied system and to calculate its conformational free energy surface. The method sampled all relevant conformations (boat, boat-chair, and crown) and corresponding transition structures inaccessible by an unbiased simulation. This scheme allows to use essentially any parameter of the system as a collective variable in biased simulations. Moreover, the scheme we used for mapping out-of-sample conformations from the 72D to 3D space can be used as a general purpose mapping for dimensionality reduction, beyond the context of molecular modeling.
2011-01-01
Background The performance of 3D-based virtual screening similarity functions is affected by the applied conformations of compounds. Therefore, the results of 3D approaches are often less robust than 2D approaches. The application of 3D methods on multiple conformer data sets normally reduces this weakness, but entails a significant computational overhead. Therefore, we developed a special conformational space encoding by means of Gaussian mixture models and a similarity function that operates on these models. The application of a model-based encoding allows an efficient comparison of the conformational space of compounds. Results Comparisons of our 4D flexible atom-pair approach with over 15 state-of-the-art 2D- and 3D-based virtual screening similarity functions on the 40 data sets of the Directory of Useful Decoys show a robust performance of our approach. Even 3D-based approaches that operate on multiple conformers yield inferior results. The 4D flexible atom-pair method achieves an averaged AUC value of 0.78 on the filtered Directory of Useful Decoys data sets. The best 2D- and 3D-based approaches of this study yield an AUC value of 0.74 and 0.72, respectively. As a result, the 4D flexible atom-pair approach achieves an average rank of 1.25 with respect to 15 other state-of-the-art similarity functions and four different evaluation metrics. Conclusions Our 4D method yields a robust performance on 40 pharmaceutically relevant targets. The conformational space encoding enables an efficient comparison of the conformational space. Therefore, the weakness of the 3D-based approaches on single conformations is circumvented. With over 100,000 similarity calculations on a single desktop CPU, the utilization of the 4D flexible atom-pair in real-world applications is feasible. PMID:21733172
NASA Astrophysics Data System (ADS)
Zhou, Peng; Chen, Xiang; Shang, Zhicai
2009-03-01
In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A*0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.
NASA Astrophysics Data System (ADS)
Carlotti, Marco; Kovalchuk, Andrii; Wächter, Tobias; Qiu, Xinkai; Zharnikov, Michael; Chiechi, Ryan C.
2016-12-01
Tunnelling currents through tunnelling junctions comprising molecules with cross-conjugation are markedly lower than for their linearly conjugated analogues. This effect has been shown experimentally and theoretically to arise from destructive quantum interference, which is understood to be an intrinsic, electronic property of molecules. Here we show experimental evidence of conformation-driven interference effects by examining through-space conjugation in which π-conjugated fragments are arranged face-on or edge-on in sufficiently close proximity to interact through space. Observing these effects in the latter requires trapping molecules in a non-equilibrium conformation closely resembling the X-ray crystal structure, which we accomplish using self-assembled monolayers to construct bottom-up, large-area tunnelling junctions. In contrast, interference effects are completely absent in zero-bias simulations on the equilibrium, gas-phase conformation, establishing through-space conjugation as both of fundamental interest and as a potential tool for tuning tunnelling charge-transport in large-area, solid-state molecular-electronic devices.
Towse, Clare-Louise; Akke, Mikael; Daggett, Valerie
2017-04-27
Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.
Conformational free energy modeling of druglike molecules by metadynamics in the WHIM space.
Spiwok, Vojtěch; Hlat-Glembová, Katarína; Tvaroška, Igor; Králová, Blanka
2012-03-26
Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformational change induced by its binding to the target. © 2012 American Chemical Society
Molecular Simulation Uncovers the Conformational Space of the λ Cro Dimer in Solution
Ahlstrom, Logan S.; Miyashita, Osamu
2011-01-01
The significant variation among solved structures of the λ Cro dimer suggests its flexibility. However, contacts in the crystal lattice could have stabilized a conformation which is unrepresentative of its dominant solution form. Here we report on the conformational space of the Cro dimer in solution using replica exchange molecular dynamics in explicit solvent. The simulated ensemble shows remarkable correlation with available x-ray structures. Network analysis and a free energy surface reveal the predominance of closed and semi-open dimers, with a modest barrier separating these two states. The fully open conformation lies higher in free energy, indicating that it requires stabilization by DNA or crystal contacts. Most NMR models are found to be unstable conformations in solution. Intersubunit salt bridging between Arg4 and Glu53 during simulation stabilizes closed conformations. Because a semi-open state is among the low-energy conformations sampled in simulation, we propose that Cro-DNA binding may not entail a large conformational change relative to the dominant dimer forms in solution. PMID:22098751
NASA Technical Reports Server (NTRS)
Rasky, Daniel J.
2004-01-01
The need for robust and reliable access from space is clearly demonstrated by the recent loss of the Space Shuttle Columbia; as well as the NASA s goals to get the Shuttle re-flying and extend its life, build new vehicles for space access, produce successful robotic landers and s a q k retrr? llisrions, and maximize the science content of ambitious outer planets missions that contain nuclear reactors which must be safe for re-entry after possible launch aborts. The technology lynch pin of access from space is hypersonic entry systems such the thermal protection system, along with navigation, guidance and control (NG&C). But it also extends to descent and landing systems such as parachutes, airbags and their control systems. Current space access technology maturation programs such as NASA s Next Generation Launch Technology (NGLT) program or the In-Space Propulsion (ISP) program focus on maturing laboratory demonstrated technologies for potential adoption by specific mission applications. A key requirement for these programs success is a suitable queue of innovative technologies and advanced concepts to mature, including mission concepts enabled by innovative, cross cutting technology advancements. When considering space access, propulsion often dominates the capability requirements, as well as the attention and resources. From the perspective of access from space some new cross cutting technology drivers come into view, along with some new capability opportunities. These include new miniature vehicles (micro, nano, and picosats), advanced automated systems (providing autonomous on-orbit inspection or landing site selection), and transformable aeroshells (to maximize capabilities and minimize weight). This paper provides an assessment of the technology drivers needed to meet future access from space mission requirements, along with the mission capabilities that can be envisioned from innovative, cross cutting access from space technology developments.
Hidden supersymmetry and quadratic deformations of the space-time conformal superalgebra
NASA Astrophysics Data System (ADS)
Yates, L. A.; Jarvis, P. D.
2018-04-01
We analyze the structure of the family of quadratic superalgebras, introduced in Jarvis et al (2011 J. Phys. A: Math. Theor. 44 235205), for the quadratic deformations of N = 1 space-time conformal supersymmetry. We characterize in particular the ‘zero-step’ modules for this case. In such modules, the odd generators vanish identically, and the quadratic superalgebra is realized on a single irreducible representation of the even subalgebra (which is a Lie algebra). In the case under study, the quadratic deformations of N = 1 space-time conformal supersymmetry, it is shown that each massless positive energy unitary irreducible representation (in the standard classification of Mack), forms such a zero-step module, for an appropriate parameter choice amongst the quadratic family (with vanishing central charge). For these massless particle multiplets therefore, quadratic supersymmetry is unbroken, in that the supersymmetry generators annihilate all physical states (including the vacuum state), while at the same time, superpartners do not exist.
Permuting input for more effective sampling of 3D conformer space
NASA Astrophysics Data System (ADS)
Carta, Giorgio; Onnis, Valeria; Knox, Andrew J. S.; Fayne, Darren; Lloyd, David G.
2006-03-01
SMILES strings and other classic 2D structural formats offer a convenient way to represent molecules as a simplistic connection table, with the inherent advantages of ease of handling and storage. In the context of virtual screening, chemical databases to be screened are often initially represented by canonicalised SMILES strings that can be filtered and pre-processed in a number of ways, resulting in molecules that occupy similar regions of chemical space to active compounds of a therapeutic target. A wide variety of software exists to convert molecules into SMILES format, namely, Mol2smi (Daylight Inc.), MOE (Chemical Computing Group) and Babel (Openeye Scientific Software). Depending on the algorithm employed, the atoms of a SMILES string defining a molecule can be ordered differently. Upon conversion to 3D coordinates they result in the production of ostensibly the same molecule. In this work we show how different permutations of a SMILES string can affect conformer generation, affecting reliability and repeatability of the results. Furthermore, we propose a novel procedure for the generation of conformers, taking advantage of the permutation of the input strings—both SMILES and other 2D formats, leading to more effective sampling of conformation space in output, and also implementing fingerprint and principal component analyses step to post process and visualise the results.
Marshall Space Flight Center's role in EASE/ACCESS mission management
NASA Technical Reports Server (NTRS)
Hawkins, Gerald W.
1987-01-01
The Marshall Space Flight Center (MSFC) Spacelab Payload Project Office was responsible for the mission management and development of several successful payloads. Two recent space construction experiments, the Experimental Assembly of Structures in Extravehicular Activity (EASE) and the Assembly Concept for Construction of Erectable Space Structures (ACCESS), were combined into a payload managed by the center. The Ease/ACCESS was flown aboard the Space Shuttle Mission 61-B. The EASE/ACCESS experiments were the first structures assembled in space, and the method used to manage this successful effort will be useful for future space construction missions. The MSFC mission management responsibilities for the EASE/ACCESS mission are addressed and how the lessons learned from the mission can be applied to future space construction projects are discussed.
46 CFR 111.01-7 - Accessibility and spacing.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 4 2012-10-01 2012-10-01 false Accessibility and spacing. 111.01-7 Section 111.01-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-7 Accessibility and spacing. (a) The design and arrangement of...
46 CFR 111.01-7 - Accessibility and spacing.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 4 2013-10-01 2013-10-01 false Accessibility and spacing. 111.01-7 Section 111.01-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-7 Accessibility and spacing. (a) The design and arrangement of...
Agniel, Rémy; Vendrely, Charlotte; Poulouin, Laurent; Bascetin, Rümeyza; Benachour, Hamanou; Gallet, Olivier; Leroy-Dudal, Johanne
2015-12-01
Fibronectin, a ≈ 450-kDa protein with 4-9% (w/w) glycosylation, is a key component of extracellular matrices and has a high conformational lability regarding its functions. However, the accessibility and the role of glycosylated moieties associated with the conformational changes of fibronectin are poorly understood. Using lectins as probes, we developed an approach comprising dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry to assess the accessibility of glycosylated moieties of fibronectin undergoing thermal-induced conformational changes. Among a set of 14 lectins, fibronectin mainly reacted with mannose-binding lectins, specifically concanavalin A. When temperature was raised from 25 to 50 °C, fibronectin underwent progressive unfolding, but the conformation of concanavalin A was unaffected. Dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry showed increased concanavalin A binding to fibronectin during progressive thermal-induced unfolding of the protein core. Such data suggest that mannosylated residues are progressively exposed as fibronectin unfolds. Because oligosaccharide moieties can be differently exposed to cells, and the cell's responses could be modified physiologically or pathologically, modulation of fibronectin sugar chains could be relevant to its biological functions. Thus, lectins might be useful tools to probe the glycosylation accessibility accompanying changes in protein core folding, for which a better understanding would be of value for biological and biomedical research. Copyright © 2015 John Wiley & Sons, Ltd.
Conformational analysis by intersection: CONAN.
Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve
2003-01-15
As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003
Pilot Non-Conformance to Alerting System Commands During Closely Spaced Parallel Approaches
NASA Technical Reports Server (NTRS)
Pritchett, Amy Ruth; Hansman, R. John; Corker, Kevin (Technical Monitor)
1997-01-01
Cockpit alerting systems monitor potentially hazardous situations, both inside and outside the aircraft. When a hazard is projected to occur, the alerting system displays alerts and/or command decisions to the pilot. However, pilots have been observed to not conform to alerting system commands by delaying their response or by not following the automatic commands exactly. This non-conformance to the automatic alerting system can reduce its benefit. Therefore, a need exists to understand the causes and effects of pilot non-conformance in order to develop automatic alerting systems whose commands the pilots are more likely to follow. These considerations were examined through flight simulator evaluations of the collision avoidance task during closely spaced parallel approaches. This task provided a useful case-study because the effects of non-conformance can be significant, given the time-critical nature of the task. A preliminary evaluation of alerting systems identified non-conformance in over 40% of the cases and a corresponding drop in collision avoidance performance. A follow-on experiment found subjects' alerting and maneuver selection criteria were consistent with different strategies than those used by automatic systems, indicating the pilot may potentially disagree with the alerting system if the pilot attempts to verify automatic alerts and commanded avoidance maneuvers. A final experiment found supporting automatic alerts with the explicit display of its underlying criteria resulted in more consistent subject reactions. In light of these experimental results, a general discussion of pilot non-conformance is provided. Contributing factors in pilot non-conformance include a lack of confidence in the automatic system and mismatches between the alerting system's commands and the pilots' own decisions based on the information available to them. The effects of non-conformance on system performance are discussed. Possible methods of reconciling mismatches are
Monitoring of the Conformational Space of Dipeptides by Generative Topographic Mapping.
Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre
2018-01-01
This work describes a procedure to build generative topographic maps (GTM) as 2D representation of the conformational space (CS) of dipeptides. GTMs with excellent propensities to support highly predictive landscapes of various conformational properties were reported for three dipeptides (AA, KE and KR). CS monitoring via GTMproceeds through the projection of conformer ensembles on the map, producing cumulated responsibility (CR) vectors characteristic of the CS areas covered by the ensemble. Overlap of the CS areas visited by two distinct simulations can be expressed by the Tanimoto coefficient Tc of the associated CRs. This idea was used to monitor the reproducibility of the stochastic evolutionary conformer generation process implemented in S4MPLE. It could be shown that conformers produced by <500 S4MPLE runs reproducibly cover the relevant CS zone at given setup of the driving force field. The propensity of a simulation to visit the native CS zone can thus be quantitatively estimated, as the Tc score with respect to the "native" CR, as defined by the ensemble of dipeptide geometries extracted from PDB proteins. It could be shown that low-energy CS regions were indeed found to fall within the native zone. The Tc overlap score behaved as a smooth function of force field parameters. This opens the perspective of a novel force field parameter tuning procedure, bound to simultaneously optimize the behavior of the in Silico simulations for every possible dipeptide. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Density functional theory study of the conformational space of an infinitely long polypeptide chain
NASA Astrophysics Data System (ADS)
Ireta, Joel; Scheffler, Matthias
2009-08-01
The backbone conformational space of infinitely long polyalanine is investigated with density-functional theory and mapping the potential energy surface in terms of (L, θ) cylindrical coordinates. A comparison of the obtained (L, θ) Ramachandran-like plot with results from an extended set of protein structures shows excellent conformity, with the exception of the polyproline II region. It is demonstrated the usefulness of infinitely long polypeptide models for investigating the influence of hydrogen bonding and its cooperative effect on the backbone conformations. The results imply that hydrogen bonding together with long-range electrostatics is the main actuator for most of the structures assumed by protein residues.
Entanglement entropy of black holes and anti-de Sitter space/conformal-field-theory correspondence.
Solodukhin, Sergey N
2006-11-17
A recent proposal by Ryu and Takayanagi for a holographic interpretation of entanglement entropy in conformal field theories dual to supergravity on anti-de Sitter space is generalized to include entanglement entropy of black holes living on the boundary of anti-de Sitter space. The generalized proposal is verified in boundary dimensions d=2 and d=4 for both the uv-divergent and uv-finite terms. In dimension d=4 an expansion of entanglement entropy in terms of size L of the subsystem outside the black hole is considered. A new term in the entropy of dual strongly coupled conformal-field theory, which universally grows as L(2)lnL and is proportional to the value of the obstruction tensor at the black hole horizon, is predicted.
NASA Astrophysics Data System (ADS)
Shallal, Muhannad A.; Jabbar, Hawraz N.; Ali, Khalid K.
2018-03-01
In this paper, we constructed a travelling wave solution for space-time fractional nonlinear partial differential equations by using the modified extended Tanh method with Riccati equation. The method is used to obtain analytic solutions for the space-time fractional Klein-Gordon and coupled conformable space-time fractional Boussinesq equations. The fractional complex transforms and the properties of modified Riemann-Liouville derivative have been used to convert these equations into nonlinear ordinary differential equations.
NASA Technical Reports Server (NTRS)
Wilson, Thomas L. (Editor); Wefel, John P. (Editor)
1999-01-01
In 1994 NASA Administrator selected the first high-energy particle physics experiment for the Space Station, the Alpha Magnetic Spectrometer (AMS), to place a magnetic spectrometer in Earth orbit and search for cosmic antimatter. A natural consequence of this decision was that NASA would begin to explore cost-effective ways through which the design and implementation of AMS might benefit other promising payload experiments. The first such experiment to come forward was Advanced Cosmic-Ray Composition Experiment for Space Station (ACCESS) in 1996. It was proposed as a new mission concept in space physics to attach a cosmic-ray experiment of weight, volume, and geometry similar to the AMS on the International Space Station (ISS), and replace the latter as its successor when the AMS is returned to Earth. This was to be an extension of NASA's suborbital balloon program, with balloon payloads serving as the precursor flights and heritage for ACCESS. The balloon programs have always been a cost-effective NASA resource since the particle physics instrumentation for balloon and space applications are directly related. The next step was to expand the process, pooling together expertise from various NASA centers and universities while opening up definition of the ACCESS science goals to the international community through the standard practice of peer review. This process is still ongoing, and the accommodation study presented here will discuss the baseline definition of ACCESS as we understand it today.
Protein Loop Structure Prediction Using Conformational Space Annealing.
Heo, Seungryong; Lee, Juyong; Joo, Keehyoung; Shin, Hang-Cheol; Lee, Jooyoung
2017-05-22
We have developed a protein loop structure prediction method by combining a new energy function, which we call E PLM (energy for protein loop modeling), with the conformational space annealing (CSA) global optimization algorithm. The energy function includes stereochemistry, dynamic fragment assembly, distance-scaled finite ideal gas reference (DFIRE), and generalized orientation- and distance-dependent terms. For the conformational search of loop structures, we used the CSA algorithm, which has been quite successful in dealing with various hard global optimization problems. We assessed the performance of E PLM with two widely used loop-decoy sets, Jacobson and RAPPER, and compared the results against the DFIRE potential. The accuracy of model selection from a pool of loop decoys as well as de novo loop modeling starting from randomly generated structures was examined separately. For the selection of a nativelike structure from a decoy set, E PLM was more accurate than DFIRE in the case of the Jacobson set and had similar accuracy in the case of the RAPPER set. In terms of sampling more nativelike loop structures, E PLM outperformed E DFIRE for both decoy sets. This new approach equipped with E PLM and CSA can serve as the state-of-the-art de novo loop modeling method.
Equivalence of emergent de Sitter spaces from conformal field theory
DOE Office of Scientific and Technical Information (OSTI.GOV)
Asplund, Curtis T.; Callebaut, Nele; Zukowski, Claire
Recently, two groups have made distinct proposals for a de Sitter space that is emergent from conformal field theory (CFT). The first proposal is that, for two-dimensional holographic CFTs, the kinematic space of geodesics on a space-like slice of the asymptotically anti-de Sitter bulk is two-dimensional de Sitter space (dS 2), with a metric that can be derived from the entanglement entropy of intervals in the CFT. In the second proposal, de Sitter dynamics emerges naturally from the first law of entanglement entropy for perturbations around the vacuum state of CFTs. We provide support for the equivalence of these twomore » emergent spacetimes in the vacuum case and beyond. In particular, we study the kinematic spaces of nontrivial solutions of 3d gravity, including the BTZ black string, BTZ black hole, and conical singularities. We argue that the resulting spaces are generically globally hyperbolic spacetimes that support dynamics given boundary conditions at future infinity. For the BTZ black string, corresponding to a thermal state of the CFT, we show that both prescriptions lead to an emergent hyperbolic patch of dS 2. As a result, we offer a general method for relating kinematic space and the auxiliary de Sitter space that is valid in the vacuum and thermal cases.« less
Equivalence of emergent de Sitter spaces from conformal field theory
Asplund, Curtis T.; Callebaut, Nele; Zukowski, Claire
2016-09-27
Recently, two groups have made distinct proposals for a de Sitter space that is emergent from conformal field theory (CFT). The first proposal is that, for two-dimensional holographic CFTs, the kinematic space of geodesics on a space-like slice of the asymptotically anti-de Sitter bulk is two-dimensional de Sitter space (dS 2), with a metric that can be derived from the entanglement entropy of intervals in the CFT. In the second proposal, de Sitter dynamics emerges naturally from the first law of entanglement entropy for perturbations around the vacuum state of CFTs. We provide support for the equivalence of these twomore » emergent spacetimes in the vacuum case and beyond. In particular, we study the kinematic spaces of nontrivial solutions of 3d gravity, including the BTZ black string, BTZ black hole, and conical singularities. We argue that the resulting spaces are generically globally hyperbolic spacetimes that support dynamics given boundary conditions at future infinity. For the BTZ black string, corresponding to a thermal state of the CFT, we show that both prescriptions lead to an emergent hyperbolic patch of dS 2. As a result, we offer a general method for relating kinematic space and the auxiliary de Sitter space that is valid in the vacuum and thermal cases.« less
NASA Astrophysics Data System (ADS)
Akhtar, S. S.; Hussain, T.; Bokhari, A. H.; Khan, F.
2018-04-01
We provide a complete classification of static plane symmetric space-times according to conformal Ricci collineations (CRCs) and conformal matter collineations (CMCs) in both the degenerate and nondegenerate cases. In the case of a nondegenerate Ricci tensor, we find a general form of the vector field generating CRCs in terms of unknown functions of t and x subject to some integrability conditions. We then solve the integrability conditions in different cases depending upon the nature of the Ricci tensor and conclude that the static plane symmetric space-times have a 7-, 10- or 15-dimensional Lie algebra of CRCs. Moreover, we find that these space-times admit an infinite number of CRCs if the Ricci tensor is degenerate. We use a similar procedure to study CMCs in the case of a degenerate or nondegenerate matter tensor. We obtain the exact form of some static plane symmetric space-time metrics that admit nontrivial CRCs and CMCs. Finally, we present some physical applications of our obtained results by considering a perfect fluid as a source of the energy-momentum tensor.
Global Trends in Space Access and Utilization
NASA Technical Reports Server (NTRS)
Rahman, Shamim A.; Keim, Nicholas S.; Zeender, Peter E.
2010-01-01
In the not-so-distant past, space access and air/space technology superiority were within the purview of the U.S. and former Soviet Union's respective space agencies, both vying for global leadership in space exploitation. In more recent years, with the emergence of the European Space Agency (ESA) member countries and Asian countries joining the family of space-faring nations, it is truer now more than ever that space access and utilization has become a truly global enterprise. In fact, according to the Space Report 2007, this enterprise is a $251-billion economy. It is possible to gauge the vitality of worldwide efforts from open sources in today's transparent, media-based society. In particular, print and web broadcasters regularly report and catalog global space activities for defense and civil purposes. For the purposes of this paper, a representative catalog of missions is used to illustrate the nature of the emerging "globalization." This paper highlights global trends in terms of not only the providers of space access, but also the end-users for the various recently accomplished missions. With well over 50 launches per year, in recent years, the launch-log reveals a surprising percentage of "cooperative or co-dependent missions" where different agencies, countries, and/or commercial entities are so engaged presumably to the benefit of all who participate. Statistics are cited and used to show that recently over d0% of the 50-plus missions involved multiple nations working collectively to deliver payloads to orbit. Observers, space policy professionals, and space agency leaders have eloquently proposed that it might require the combined resources and talents of multiple nations to advance human exploration goals beyond low earth orbit. This paper does not intend to offer new information with respect to whether international collaboration is necessary but to observe that, in continuing to monitor global trends, the results seem to support the thesis that a
An overview of the EASE/ACCESS space construction demonstration
NASA Technical Reports Server (NTRS)
Levin, George M.; Ross, Jerry L.; Spring, Sherwood C.
1988-01-01
Consideration is given to the development of the Experimental Assembly of Structures in EVA/Assembly Concept for Construction of Erectable Space Structures (EASE/ACCESS) space construction demonstration, which was performed during Space Shuttle mission 61-B. The mission equipment is described and illustrated and the EASE/ACCESS mission management structure is outlined. Simulations of the assembly and disassembly in the NASA neutral buoyancy simulators were used to test the mission plans. In addition, EVA training and crew performance for the mission are discussed.
Why Atens Enjoy Enhanced Accessibility for Human Space Flight
NASA Technical Reports Server (NTRS)
Barbee, Brent W.; Adamo, Daniel R.
2011-01-01
Near-Earth objects can be grouped into multiple orbit classifications, among them being the Aten group, whose members have orbits crossing Earth's with semi-major axes less than 1 astronomical unit. Atens comprise well under 10% of known near-Earth objects. This is in dramatic contrast to results from recent human space flight near-Earth object accessibility studies, where the most favorable known destinations are typically almost 50% Atens. Geocentric dynamics explain this enhanced Aten accessibility and lead to an understanding of where the most accessible near-Earth objects reside. Without a comprehensive space-based survey, however, highly accessible Atens will remain largely unknown.
The National Aerospace Initiative (NAI): Technologies For Responsive Space Access
NASA Technical Reports Server (NTRS)
Culbertson, Andrew; Bhat, Biliyar N.
2003-01-01
The Secretary of Defense has set new goals for the Department of Defense (DOD) to transform our nation's military forces. The Director for Defense Research and Engineering (DDR&E) has responded to this challenge by defining and sponsoring a transformational initiative in Science and Technology (S&T) - the National Aerospace Initiative (NAI) - which will have a fundamental impact on our nation's military capabilities and on the aerospace industry in general. The NAI is planned as a joint effort among the tri-services, DOD agencies and National Aeronautics and Space Administration (NASA). It is comprised of three major focus areas or pillars: 1) High Speed Hypersonics (HSH), 2) Space Access (SA), and 3) Space Technology (ST). This paper addresses the Space Access pillar. The NAI-SA team has employed a unique approach to identifying critical technologies and demonstrations for satisfying both military and civilian space access capabilities needed in the future. For planning and implementation purposes the NAI-SA is divided into five technology subsystem areas: Airframe, Propulsion, Flight Subsystems, Operations and Payloads. Detailed technology roadmaps were developed under each subsystem area using a time-phased, goal oriented approach that provides critical space access capabilities in a timely manner and involves subsystem ground and flight demonstrations. This S&T plan addresses near-term (2009), mid-term (2016), and long-term (2025) goals and objectives for space access. In addition, system engineering and integration approach was used to make sure that the plan addresses the requirements of the end users. This paper describes in some detail the technologies in NAI-Space Access pillar. Some areas of emphasis are: high temperature materials, thermal protection systems, long life, lightweight, highly efficient airframes, metallic and composite cryotanks, advanced liquid rocket engines, integrated vehicle health monitoring and management, highly operable systems and
IR-UV spectroscopy of jet-cooled 1-indanol: Restriction of the conformational space by hydration
NASA Astrophysics Data System (ADS)
Bouchet, Aude; Altnöder, Jonas; Broquier, Michel; Zehnacker, Anne
2014-11-01
The effect of hydration on a flexible amphiphilic molecule has been studied on the example of 1-hydroxyindan (1-indanol). Studies in jet-cooled conditions by means of resonance-enhanced two-photon ionization and IR-UV double resonance experiments show that the mono-hydrate 1-indanol(H2O) is formed in a dominant isomer, as well as the di-hydrate 1-indanol(H2O)2. 1-Indanol(H2O) favors a cooperative hydrogen bond pattern with -OH⋯O(H)-H⋯π topology, while 1-indanol(H2O)2 forms a cyclic hydrogen bond network with three OH⋯O interactions. The single conformation observed for the hydrates contrasts with the bare molecule which shows two dominant conformations, with the hydroxyl in axial or in equatorial position, respectively. Hydration therefore results in a restriction of the conformational space and conformational locking.
GOES-R Space Weather Data: Ensuring Access and Usability
NASA Astrophysics Data System (ADS)
Tilton, M.; Rowland, W. F.; Wilkinson, D. C.; Denig, W. F.; Darnel, J.; Kress, B. T.; Loto'aniu, P. T. M.; Machol, J. L.; Redmon, R. J.; Rodriguez, J. V.
2015-12-01
The upcoming Geostationary Operational Environmental Satellite series, GOES-R, will provide critical space weather data. These data are used to prevent communication outages, mitigate the damage solar weather causes to satellites and power grids, and reduce astronaut radiation exposure. The space weather instruments aboard GOES-R will deliver an operational dataset of unprecedented breadth. However, NOAA's National Centers for Environmental Information (NCEI)—the organization that provides access to archived GOES-R data—has faced several challenges in delivering this information to customers in usable form. For instance, the GOES-R ground system was contracted to develop higher-level products for terrestrial data but not space weather data. Variations in GOES-R data file formats and archive locations have also threatened to create an inconsistent user experience. This presentation will examine the ways in which NCEI is making GOES-R space weather data more accessible and actionable for customers. These efforts include NCEI's development of high-level data products to meet the requirements of NOAA's Space Weather Prediction Center—a role NCEI has not previously played. In addition, NCEI is creating a demonstration system to show how these products can be produced in real-time. The organization is also examining customer usage of the GOES-NOP data access system and using these access patterns to drive decisions about the GOES-R user interface.
Senate Hearing on Assured Access to Space
2014-07-16
General William Sherlton, Commander of the United States Air Force Space Command, answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
General William Sherlton, Commander of the United States Air Force Space Command, left; answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
General William Shelton, Commander of the United States Air Force Space Command, delivers his opening statement during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
NASA Technical Reports Server (NTRS)
1994-01-01
This report summarizes the results of a comprehensive NASA in-house study to identify and assess alternate approaches to access to space through the year 2030, and to select and recommend a preferred cause of action. The goals of the study were to identify the best vehicles and transportation architectures to make major reductions in the cost of space transportation (at least 50%), while at the same time increasing safety for flight crews by at least an order of magnitude. In addition, vehicle reliability was to exceed 0.98 percent, and, as important, the robustness, pad time, turnaround time, and other aspects of operability were to be vastly improved. This study examined three major optional architectures: (1) retain and upgrade the Space Shuttle and expendable launch vehicles; (2) develop new expendable vehicles using conventional technologies and transition from current vehicles beginning in 2005; and (3) develop new reusable vehicles using advanced technology, and transition from current vehicles beginning in 2008. The launch-needs, mission model utilized for for the study was based upon today's projection of civil, defense, and commercial mission payload requirements.
Towards conformal loop quantum gravity
NASA Astrophysics Data System (ADS)
H-T Wang, Charles
2006-03-01
A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.
Developing hybrid near-space technologies for affordable access to suborbital space
NASA Astrophysics Data System (ADS)
Badders, Brian David
High power rockets and high altitude balloons are two near-space technologies that could be combined in order to provide access to the mesosphere and, eventually, suborbital space. This "rockoon" technology has been used by several large budget space programs before being abandoned in favor of even more expensive, albeit more accurate, ground launch systems. With the increased development of nano-satellites and atmospheric sensors, combined with rising interest in global atmospheric data, there is an increase in desire for affordable access to extreme altitudes that does not necessarily require the precision of ground launches. Development of hybrid near-space technologies for access to over 200k ft. on a small budget brings many challenges within engineering, systems integration, cost analysis, market analysis, and business planning. This research includes the design and simulation testing of all the systems needed for a safe and reusable launch system, the cost analysis for initial production, the development of a business plan, and the development of a marketing plan. This project has both engineering and scientific significance in that it can prove the space readiness of new technologies, raise their technology readiness levels (TRLs), expedite the development process, and also provide new data to the scientific community. It also has the ability to stimulate university involvement in the aerospace industry and help to inspire the next generation of workers in the space sector. Previous development of high altitude balloon/high power rocket hybrid systems have been undertaken by government funded military programs or large aerospace corporations with varying degrees of success. However, there has yet to be a successful flight with this type of system which provides access to the upper mesosphere in a university setting. This project will aim to design and analyze a viable system while testing the engineering process under challenging budgetary constraints. The
46 CFR 111.01-7 - Accessibility and spacing.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 4 2010-10-01 2010-10-01 false Accessibility and spacing. 111.01-7 Section 111.01-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS... electric apparatus must afford accessibility to each part as needed to facilitate proper inspection...
46 CFR 111.01-7 - Accessibility and spacing.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 4 2014-10-01 2014-10-01 false Accessibility and spacing. 111.01-7 Section 111.01-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS... electric apparatus must afford accessibility to each part as needed to facilitate proper inspection...
46 CFR 111.01-7 - Accessibility and spacing.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 4 2011-10-01 2011-10-01 false Accessibility and spacing. 111.01-7 Section 111.01-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS... electric apparatus must afford accessibility to each part as needed to facilitate proper inspection...
Senate Hearing on Assured Access to Space
2014-07-16
General William Shelton, Commander of the United States Air Force Space Command, second from right, answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
The Implications of Lowering the Cost to Access Space on Airpower
2017-06-01
1 The Implications of Lowering the Cost to Access Space on Airpower Major Gabe Arrington School of Advanced Air and Space Studies...2017 DISTRIBUTION A: Approved for public release: distribution unlimited 2 Disclaimer Opinions, conclusions, and recommendations...implications that lowering the cost to access space will have on Airpower. The research conducted used predominantly qualitative research techniques to
Lee, Juyong; Lee, Jinhyuk; Sasaki, Takeshi N; Sasai, Masaki; Seok, Chaok; Lee, Jooyoung
2011-08-01
Ab initio protein structure prediction is a challenging problem that requires both an accurate energetic representation of a protein structure and an efficient conformational sampling method for successful protein modeling. In this article, we present an ab initio structure prediction method which combines a recently suggested novel way of fragment assembly, dynamic fragment assembly (DFA) and conformational space annealing (CSA) algorithm. In DFA, model structures are scored by continuous functions constructed based on short- and long-range structural restraint information from a fragment library. Here, DFA is represented by the full-atom model by CHARMM with the addition of the empirical potential of DFIRE. The relative contributions between various energy terms are optimized using linear programming. The conformational sampling was carried out with CSA algorithm, which can find low energy conformations more efficiently than simulated annealing used in the existing DFA study. The newly introduced DFA energy function and CSA sampling algorithm are implemented into CHARMM. Test results on 30 small single-domain proteins and 13 template-free modeling targets of the 8th Critical Assessment of protein Structure Prediction show that the current method provides comparable and complementary prediction results to existing top methods. Copyright © 2011 Wiley-Liss, Inc.
Watts, C R; Mezei, M; Murphy, R F; Lovas, S
2001-04-01
The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calculations, in agreement with previous experimental data, indicate that a conformation with a turn from residues 5 through 8 is preferred for GnRH in an aqueous environment. By contrast, a conformation with a helix from residues 2 through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy different regions of phase space and participate in weakly polar interactions different from those in GnRH. The unique conformational properties of lGnRH-III may account for its specific anti cancer activity.
Assessing equitable access to urban green space: the role of engineered water infrastructure.
Wendel, Heather E Wright; Downs, Joni A; Mihelcic, James R
2011-08-15
Urban green space and water features provide numerous social, environmental, and economic benefits, yet disparities often exist in their distribution and accessibility. This study examines the link between issues of environmental justice and urban water management to evaluate potential improvements in green space and surface water access through the revitalization of existing engineered water infrastructures, namely stormwater ponds. First, relative access to green space and water features were compared for residents of Tampa, Florida, and an inner-city community of Tampa (East Tampa). Although disparities were not found in overall accessibility between Tampa and East Tampa, inequalities were apparent when quality, diversity, and size of green spaces were considered. East Tampa residents had significantly less access to larger, more desirable spaces and water features. Second, this research explored approaches for improving accessibility to green space and natural water using three integrated stormwater management development scenarios. These scenarios highlighted the ability of enhanced water infrastructures to increase access equality at a variety of spatial scales. Ultimately, the "greening" of gray urban water infrastructures is advocated as a way to address environmental justice issues while also reconnecting residents with issues of urban water management.
Conformal superalgebras via tractor calculus
NASA Astrophysics Data System (ADS)
Lischewski, Andree
2015-01-01
We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.
REUSABLE PROPULSION ARCHITECTURE FOR SUSTAINABLE LOW-COST ACCESS TO SPACE
NASA Technical Reports Server (NTRS)
Bonometti, J. A.; Dankanich, J. W.; Frame, K. L.
2005-01-01
The primary obstacle to any space-based mission is, and has always been, the cost of access to space. Even with impressive efforts toward reusability, no system has come close to lowering the cost a significant amount. It is postulated here, that architectural innovation is necessary to make reusability feasible, not incremental subsystem changes. This paper shows two architectural approaches of reusability that merit further study investments. Both #inherently# have performance increases and cost advantages to make affordable access to space a near term reality. A rocket launched from a subsonic aircraft (specifically the Crossbow methodology) and a momentum exchange tether, reboosted by electrodynamics, offer possibilities of substantial reductions in the total transportation architecture mass - making access-to-space cost-effective. They also offer intangible benefits that reduce risk or offer large growth potential. The cost analysis indicates that approximately a 50% savings is obtained using today#s aerospace materials and practices.
Wang, Junmei; Hou, Tingjun
2012-01-01
It is of great interest in modern drug design to accurately calculate the free energies of protein-ligand or nucleic acid-ligand binding. MM-PBSA (Molecular Mechanics-Poisson Boltzmann Surface Area) and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) have gained popularity in this field. For both methods, the conformational entropy, which is usually calculated through normal mode analysis (NMA), is needed to calculate the absolute binding free energies. Unfortunately, NMA is computationally demanding and becomes a bottleneck of the MM-PB/GBSA-NMA methods. In this work, we have developed a fast approach to estimate the conformational entropy based upon solvent accessible surface area calculations. In our approach, the conformational entropy of a molecule, S, can be obtained by summing up the contributions of all atoms, no matter they are buried or exposed. Each atom has two types of surface areas, solvent accessible surface area (SAS) and buried SAS (BSAS). The two types of surface areas are weighted to estimate the contribution of an atom to S. Atoms having the same atom type share the same weight and a general parameter k is applied to balance the contributions of the two types of surface areas. This entropy model was parameterized using a large set of small molecules for which their conformational entropies were calculated at the B3LYP/6-31G* level taking the solvent effect into account. The weighted solvent accessible surface area (WSAS) model was extensively evaluated in three tests. For the convenience, TS, the product of temperature T and conformational entropy S, were calculated in those tests. T was always set to 298.15 K through the text. First of all, good correlations were achieved between WSAS TS and NMA TS for 44 protein or nucleic acid systems sampled with molecular dynamics simulations (10 snapshots were collected for post-entropy calculations): the mean correlation coefficient squares (R2) was 0.56. As to the 20 complexes, the TS changes
Liu, Xiaofeng; Bai, Fang; Ouyang, Sisheng; Wang, Xicheng; Li, Honglin; Jiang, Hualiang
2009-03-31
Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm. The conformational perturbation is subjected to evolutionary operation on the genome encoded with dihedral torsions. Various objectives are designated to render the generated Pareto optimal conformers to be energy-favoured as well as evenly scattered across the conformational space. An optional objective concerning the degree of molecular extension is added to achieve geometrically extended or compact conformations which have been observed to impact the molecular bioactivity (J Comput -Aided Mol Des 2002, 16: 105-112). Testing the performance of Cyndi against a test set consisting of 329 small molecules reveals an average minimum RMSD of 0.864 A to corresponding bioactive conformations, indicating Cyndi is highly competitive against other conformation generation methods. Meanwhile, the high-speed performance (0.49 +/- 0.18 seconds per molecule) renders Cyndi to be a practical toolkit for conformational database preparation and facilitates subsequent pharmacophore mapping or rigid docking. The copy of precompiled executable of Cyndi and the test set molecules in mol2 format are accessible in Additional file 1. On the basis of MOEA algorithm, we present a new, highly efficient conformation generation method, Cyndi, and report the results of validation and performance studies comparing with other four methods. The results reveal that Cyndi is capable of generating geometrically diverse conformers and outperforms other four multiple conformer generators in the case of
Stratospheric Balloon Platforms for Near Space Access
NASA Astrophysics Data System (ADS)
Dewey, R. G.
2012-12-01
For over five decades, high altitude aerospace balloon platforms have provided a unique vantage point for space and geophysical research by exposing scientific instrument packages and experiments to space-like conditions above 99% of Earth's atmosphere. Reaching altitudes in excess of 30 km for durations ranging from hours to weeks, high altitude balloons offer longer flight durations than both traditional sounding rockets and emerging suborbital reusable launch vehicles. For instruments and experiments requiring access to high altitudes, engineered balloon systems provide a timely, responsive, flexible, and cost-effective vehicle for reaching near space conditions. Moreover, high altitude balloon platforms serve as an early means of testing and validating hardware bound for suborbital or orbital space without imposing space vehicle qualifications and certification requirements on hardware in development. From float altitudes above 30 km visible obscuration of the sky is greatly reduced and telescopes and other sensors function in an orbit-like environment, but in 1g. Down-facing sensors can take long-exposure atmospheric measurements and images of Earth's surface from oblique and nadir perspectives. Payload support subsystems such as telemetry equipment and command, control, and communication (C3) interfaces can also be tested and operationally verified in this space-analog environment. For scientific payloads requiring over-flight of specific areas of interests, such as an active volcano or forest region, advanced mission planning software allows flight trajectories to be accurately modeled. Using both line-of-sight and satellite-based communication systems, payloads can be tracked and controlled throughout the entire mission duration. Under NASA's Flight Opportunities Program, NSC can provide a range of high altitude flight options to support space and geophysical research: High Altitude Shuttle System (HASS) - A balloon-borne semi-autonomous glider carries
Conformal Bootstrap in Mellin Space
NASA Astrophysics Data System (ADS)
Gopakumar, Rajesh; Kaviraj, Apratim; Sen, Kallol; Sinha, Aninda
2017-02-01
We propose a new approach towards analytically solving for the dynamical content of conformal field theories (CFTs) using the bootstrap philosophy. This combines the original bootstrap idea of Polyakov with the modern technology of the Mellin representation of CFT amplitudes. We employ exchange Witten diagrams with built-in crossing symmetry as our basic building blocks rather than the conventional conformal blocks in a particular channel. Demanding consistency with the operator product expansion (OPE) implies an infinite set of constraints on operator dimensions and OPE coefficients. We illustrate the power of this method in the ɛ expansion of the Wilson-Fisher fixed point by reproducing anomalous dimensions and, strikingly, obtaining OPE coefficients to higher orders in ɛ than currently available using other analytic techniques (including Feynman diagram calculations). Our results enable us to get a somewhat better agreement between certain observables in the 3D Ising model and the precise numerical values that have been recently obtained.
46 CFR 154.340 - Access to tanks and spaces in the cargo area.
Code of Federal Regulations, 2014 CFR
2014-10-01
... access from the weather deck to gas-safe spaces in the cargo area must be at least 2.4 m (7.9 ft.) above... 46 Shipping 5 2014-10-01 2014-10-01 false Access to tanks and spaces in the cargo area. 154.340... Equipment Ship Arrangements § 154.340 Access to tanks and spaces in the cargo area. (a) Each cargo tank must...
46 CFR 154.340 - Access to tanks and spaces in the cargo area.
Code of Federal Regulations, 2012 CFR
2012-10-01
... access from the weather deck to gas-safe spaces in the cargo area must be at least 2.4 m (7.9 ft.) above... 46 Shipping 5 2012-10-01 2012-10-01 false Access to tanks and spaces in the cargo area. 154.340... Equipment Ship Arrangements § 154.340 Access to tanks and spaces in the cargo area. (a) Each cargo tank must...
46 CFR 154.340 - Access to tanks and spaces in the cargo area.
Code of Federal Regulations, 2013 CFR
2013-10-01
... access from the weather deck to gas-safe spaces in the cargo area must be at least 2.4 m (7.9 ft.) above... 46 Shipping 5 2013-10-01 2013-10-01 false Access to tanks and spaces in the cargo area. 154.340... Equipment Ship Arrangements § 154.340 Access to tanks and spaces in the cargo area. (a) Each cargo tank must...
46 CFR 154.340 - Access to tanks and spaces in the cargo area.
Code of Federal Regulations, 2010 CFR
2010-10-01
... access from the weather deck to gas-safe spaces in the cargo area must be at least 2.4 m (7.9 ft.) above... 46 Shipping 5 2010-10-01 2010-10-01 false Access to tanks and spaces in the cargo area. 154.340... Equipment Ship Arrangements § 154.340 Access to tanks and spaces in the cargo area. (a) Each cargo tank must...
46 CFR 154.340 - Access to tanks and spaces in the cargo area.
Code of Federal Regulations, 2011 CFR
2011-10-01
... access from the weather deck to gas-safe spaces in the cargo area must be at least 2.4 m (7.9 ft.) above... 46 Shipping 5 2011-10-01 2011-10-01 false Access to tanks and spaces in the cargo area. 154.340... Equipment Ship Arrangements § 154.340 Access to tanks and spaces in the cargo area. (a) Each cargo tank must...
Senate Hearing on Assured Access to Space
2014-07-16
A general view of a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation regarding assured access to space on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC.
Conformal symmetries of Einstein's field equations and initial data
NASA Astrophysics Data System (ADS)
Sharma, Ramesh
2005-04-01
This paper examines the initial data for the evolution of the space-time solution of Einstein's equations admitting a conformal symmetry. Under certain conditions on the extrinsic curvature of the initial complete spacelike hypersurface and sectional curvature of the space-time with respect to sections containing the normal vector field, we have shown that the initial hypersurface is conformally diffeomorphic to a sphere or a flat space or a hyperbolic space or the product of an open real interval and a complete 2-manifold. It has been further shown that if the initial hypersurface is compact, then it is conformally diffeomorphic to a sphere. Finally, the conformal symmetries of a generalized Robertson-Walker space-time have been described.
46 CFR 153.217 - Access to enclosed spaces and dedicated ballast tanks.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Access to enclosed spaces and dedicated ballast tanks... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment General Vessel Requirements § 153.217 Access to enclosed spaces and dedicated ballast...
46 CFR 153.217 - Access to enclosed spaces and dedicated ballast tanks.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Access to enclosed spaces and dedicated ballast tanks... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment General Vessel Requirements § 153.217 Access to enclosed spaces and dedicated ballast...
46 CFR 153.217 - Access to enclosed spaces and dedicated ballast tanks.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Access to enclosed spaces and dedicated ballast tanks... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment General Vessel Requirements § 153.217 Access to enclosed spaces and dedicated ballast...
46 CFR 153.217 - Access to enclosed spaces and dedicated ballast tanks.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Access to enclosed spaces and dedicated ballast tanks... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment General Vessel Requirements § 153.217 Access to enclosed spaces and dedicated ballast...
46 CFR 153.217 - Access to enclosed spaces and dedicated ballast tanks.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Access to enclosed spaces and dedicated ballast tanks... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment General Vessel Requirements § 153.217 Access to enclosed spaces and dedicated ballast...
Advanced Cosmic Ray Composition Experiment for Space Station (ACCESS)
NASA Technical Reports Server (NTRS)
Wilson, Thomas L.; Wefel, John P.
1999-01-01
In 1994 the first high-energy particle physics experiment for the Space Station, the Alpha Magnetic Spectrometer (AMS), was selected by NASA's Administrator as a joint collaboration with the U.S. Department of Energy (DOE). The AMS program was chartered to place a magnetic spectrometer in Earth orbit and search for cosmic antimatter. A natural consequence of this decision was that NASA would begin to explore cost-effective ways through which the design and implementation of AMS might benefit other promising payload experiments which were evolving from the Office of Space Science. The first such experiment to come forward was ACCESS in 1996. It was proposed as a new mission concept in space physics to place a cosmic-ray experiment of weight, volume, and geometry similar to the AMS on the ISS, and replace the latter as its successor when the AMS is returned to Earth. This was to be an extension of NASA's sub-orbital balloon program, with balloon payloads serving as the precursor flights and heritage for ACCESS. The balloon programs have always been a cost-effective NASA resource since the particle physics instrumentation for balloon and space applications are directly related. The next step was to expand the process, pooling together expertise from various NASA centers and universities while opening up definition of the ACCESS science goals to the international community through the standard practice of peer-review. This process is still on-going and the Accommodation Study presented here will discuss the baseline definition of ACCESS as we understand it today. Further detail on the history, scope, and background of the study is provided in Appendix A.
Operator product expansion for conformal defects
NASA Astrophysics Data System (ADS)
Fukuda, Masayuki; Kobayashi, Nozomu; Nishioka, Tatsuma
2018-01-01
We study the operator product expansion (OPE) for scalar conformal defects of any codimension in CFT. The OPE for defects is decomposed into "defect OPE blocks", the irreducible representations of the conformal group, each of which packages the contribution from a primary operator and its descendants. We use the shadow formalism to deduce an integral representation of the defect OPE blocks. They are shown to obey a set of constraint equations that can be regarded as equations of motion for a scalar field propagating on the moduli space of the defects. By employing the Radon transform between the AdS space and the moduli space, we obtain a formula of constructing an AdS scalar field from the defect OPE block for a conformal defect of any codimension in a scalar representation of the conformal group, which turns out to be the Euclidean version of the HKLL formula. We also introduce a duality between conformal defects of different codimensions and prove the equivalence between the defect OPE block for codimension-two defects and the OPE block for a pair of local operators.
Senate Hearing on Assured Access to Space
2014-07-16
Sen. Ted Cruz, R-Texas, listens during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Multinational Experiment 7. Protecting Access to Space: Presentation to Senior Leaders
2013-07-08
Multinational Experiment 7: Outcome 3: Space Access Briefing to SLS 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...operations Consequence management Ship status during search & rescue Tele-medicine Broadband internet TV signal distribution Satellite radio Rural...military-usage • Significant economic & societal consequences Access to space at risk • Current approach unsustainable • Broad range of threats
Senate Hearing on Assured Access to Space
2014-07-16
Robert Lightfoot, NASA Associate Administrator, answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Sen. Ted Cruz, R-Texas, asks a question during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Sen. Mark Udall, D-CO, asks a question during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Iuzzolino, Luca; Reilly, Anthony M; McCabe, Patrick; Price, Sarah L
2017-10-10
Determining the range of conformations that a flexible pharmaceutical-like molecule could plausibly adopt in a crystal structure is a key to successful crystal structure prediction (CSP) studies. We aim to use conformational information from the crystal structures in the Cambridge Structural Database (CSD) to facilitate this task. The conformations produced by the CSD Conformer Generator are reduced in number by considering the underlying rotamer distributions, an analysis of changes in molecular shape, and a minimal number of molecular ab initio calculations. This method is tested for five pharmaceutical-like molecules where an extensive CSP study has already been performed. The CSD informatics-derived set of crystal structure searches generates almost all the low-energy crystal structures previously found, including all experimental structures. The workflow effectively combines information on individual torsion angles and then eliminates the combinations that are too high in energy to be found in the solid state, reducing the resources needed to cover the solid-state conformational space of a molecule. This provides insights into how the low-energy solid-state and isolated-molecule conformations are related to the properties of the individual flexible torsion angles.
Considerations on private human access to space from an institutional point of view
NASA Astrophysics Data System (ADS)
Hufenbach, Bernhard
2013-12-01
Private human access to space as discussed in this article addresses two market segments: suborbital flight and crew flights to Low Earth Orbit. The role of entrepreneurs, the technical complexity, the customers, the market conditions as well as the time to market in these two segments differ significantly. Space agencies take currently a very different approach towards private human access to space in both segments. Analysing the outcome of broader inter-agency deliberations on the future of human spaceflight and exploration, performed e.g. in the framework of the International Space Exploration Coordination Group, enables to derive some common general views on this topic. Various documents developed by inter-agency working groups recognise the general strategic importance for enabling private human access to space for ensuring a sustainable future of human spaceflight, although the specific definition of private human access and approaches vary. ESA has performed some reflections on this subject throughout the last 5 years. While it gained through these reflections a good understanding on the opportunities and implications resulting from the development of capabilities and markets for Private Human Access, limited concrete activities have been initiated in relation to this topic as of today.
Senate Hearing on Assured Access to Space
2014-07-16
Robert Lightfoot, NASA Associate Administrator, delivers his opening statement during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Robert Lightfoot, NASA Associate Administrator, third from left, answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
A Projective-to-Conformal Fefferman-Type Construction
NASA Astrophysics Data System (ADS)
Hammerl, Matthias; Sagerschnig, Katja; Šilhan, Josef; Taghavi-Chabert, Arman; Zádník, Vojtĕch
2017-10-01
We study a Fefferman-type construction based on the inclusion of Lie groups SL(n+1) into Spin(n+1,n+1). The construction associates a split-signature (n,n)-conformal spin structure to a projective structure of dimension n. We prove the existence of a canonical pure twistor spinor and a light-like conformal Killing field on the constructed conformal space. We obtain a complete characterisation of the constructed conformal spaces in terms of these solutions to overdetermined equations and an integrability condition on the Weyl curvature. The Fefferman-type construction presented here can be understood as an alternative approach to study a conformal version of classical Patterson-Walker metrics as discussed in recent works by Dunajski-Tod and by the authors. The present work therefore gives a complete exposition of conformal Patterson-Walker metrics from the viewpoint of parabolic geometry.
Senate Hearing on Assured Access to Space
2014-07-16
Howard Mitchell, Vice President of Program Assessments at The Aerospace Corporation, listens to opening statements during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Howard Mitchell, Vice President of Program Assessments at The Aerospace Corporation, delivers his opening statement during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Dr. Yool Kim, Senior Engineer at the Rand Corporation, delivers her opening statment during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Thickenings and conformal gravity
NASA Astrophysics Data System (ADS)
Lebrun, Claude
1991-07-01
A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M].
CASH 2021: commercial access and space habitation.
Aldrin, Andrew; Amara, Adam; Aris, Lodewijk; Baierl, Nida; Beatty, Patrick; Beaulieu, Catherine; Behnke, Torsten; Castegini, Roberta; Chauhan, Amitabh; Cojanis, Philip; Dayawansa, Pelawa; Diop, Marie; Eito, Kinya; Engle, Steve; Feretti, Stefano; Gassama, Hamet; Genova, Bojana; Goulding, Colin; Janjua, Jameel; Jansaeng, Thidarat; Jousset, Frederic; Kopik, Anatoly; Laurin, Catherine; Leggatt, Jason; Li, Hengnian; Mezzadri, Monica; Miura, Amane; Nolet, Simon; Ogami, Satoshi; Patry, Johanne; Patten, Laryssa; Payerne, Cyril; Peer, Guy; Prampolini, Marco; Rheaume, Caroline; Saary, Joan; Spehar, Daniela; Sufi, Atiya; Sun, Baosheng; Thompson, J Barry; Thomson, Ward; Trautner, Roland; Tursunmuratov, Murat; Venet, Vrata; Wilems, Elizabeth; Wilson, Helen; Wittwer, Karl; Wokke, Frank; Wu, Yansheng; Zhou, Shaobin; Zilioli, Ilaria
2002-01-01
Issues about commercialization of space have been a growing concern in the past decade for the space community. This paper focuses on the work from a team of 51 students attending the Summer Session Program of the International Space University in Bremen, Germany. CASH 2021 (Commercial Access and Space Habitation) documents a plan that identifies commercial opportunities for space utilization that will extend human presence in space, and will chart the way forward for the next 20 years. The group selected four commercial sectors that show the most promise for the future: tourism, entertainment, space system service, assembly and debris removal, and research and development/production. The content of this document presents the results of their research. Historical activities in each of the commercial sectors are reviewed along with the current market situation. To provide a coherent background for future commercialization possibilities a scenario has been developed. This scenario includes a postulated upon ideal future and includes social, political and economic factors that may affect the space industry over the timeline of the study. The study also presents a roadmap, within the limited optimistic scenario developed, for the successful commercialization of space leading to future human presence in space. A broad range of commercially viable opportunities, not only within the current limits of the International Space Station, but also among the many new developments that are expected by 2021 are discussed. c2002 International Astronautical Federation. Published by Elsevier Science Ltd. All rights reserved.
Astronaut Ross Approaches Assembly Concept for Construction of Erectable Space Structure (ACCESS)
NASA Technical Reports Server (NTRS)
1999-01-01
The crew assigned to the STS-61B mission included Bryan D. O'Conner, pilot; Brewster H. Shaw, commander; Charles D. Walker, payload specialist; mission specialists Jerry L. Ross, Mary L. Cleave, and Sherwood C. Spring; and Rodolpho Neri Vela, payload specialist. Launched aboard the Space Shuttle Atlantis November 28, 1985 at 7:29:00 pm (EST), the STS-61B mission's primary payload included three communications satellites: MORELOS-B (Mexico); AUSSAT-2 (Australia); and SATCOM KU-2 (RCA Americom). Two experiments were conducted to test assembling erectable structures in space: EASE (Experimental Assembly of Structures in Extravehicular Activity), and ACCESS (Assembly Concept for Construction of Erectable Space Structure). In a joint venture between NASA/Langley Research Center in Hampton, Virginia, and the Marshall Space Flight Center (MSFC), EASE and ACCESS were developed and demonstrated at MSFC's Neutral Buoyancy Simulator (NBS). In this STS-61B onboard photo, astronaut Ross, perched on the Manipulator Foot Restraint (MFR) approaches the erected ACCESS. The primary objective of these experiments was to test the structural assembly concepts for suitability as the framework for larger space structures and to identify ways to improve the productivity of space construction.
Hoffimann, Elaine; Barros, Henrique; Ribeiro, Ana Isabel
2017-08-15
Background : The provision of green spaces is an important health promotion strategy to encourage physical activity and to improve population health. Green space provision has to be based on the principle of equity. This study investigated the presence of socioeconomic inequalities in geographic accessibility and quality of green spaces across Porto neighbourhoods (Portugal). Methods : Accessibility was evaluated using a Geographic Information System and all the green spaces were audited using the Public Open Space Tool. Kendall's tau-b correlation coefficients and ordinal regression were used to test whether socioeconomic differences in green space quality and accessibility were statistically significant. Results : Although the majority of the neighbourhoods had an accessible green space, mean distance to green space increased with neighbourhood deprivation. Additionally, green spaces in the more deprived neighbourhoods presented significantly more safety concerns, signs of damage, lack of equipment to engage in active leisure activities, and had significantly less amenities such as seating, toilets, cafés, etc. Conclusions : Residents from low socioeconomic positions seem to suffer from a double jeopardy; they lack both individual and community resources. Our results have important planning implications and might contribute to understanding why deprived communities have lower physical activity levels and poorer health.
GOES-R Space Weather Data: Products and Data Access
NASA Astrophysics Data System (ADS)
Tilton, M.; Rowland, W. F.; Codrescu, S.; Denig, W. F.; Seaton, D. B.
2016-12-01
In November 2016 NOAA launched the first in the "R" series of Geostationary Operational Environmental Satellites (GOES-R). GOES-R continues a tradition of almost 40 years of continuous space and solar observations at geostationary orbit. Compared to its predecessors, the GOES-R satellite provides improved in situ measurements of charged particle and magnetic field environments. The satellite also offers enhanced remote sensing of the sun through ultraviolet (UV) imagery and X-ray/UV irradiance. After the spacecraft completes early-orbit checkout and calibration, GOES-R space weather data and derived products will be used for operations within NOAA's Space Weather Prediction Center and publicly released through the National Centers for Environmental Information (NCEI). This presentation will provide an overview of GOES-R space weather data ranging from direct measurements (L0 data) to higher level science (L2+) products developed by NCEI scientists. We will also present planned data access and distribution features. We emphasize our strategy to ensure data discoverability and accessibility, including our participation in NOAA's OneStop project and potential partnerships with NASA's Virtual Solar Observatory and projects like Helioviewer.
Conformal quantum mechanics and holography in noncommutative space-time
NASA Astrophysics Data System (ADS)
Gupta, Kumar S.; Harikumar, E.; Zuhair, N. S.
2017-09-01
We analyze the effects of noncommutativity in conformal quantum mechanics (CQM) using the κ-deformed space-time as a prototype. Up to the first order in the deformation parameter, the symmetry structure of the CQM algebra is preserved but the coupling in a canonical model of the CQM gets deformed. We show that the boundary conditions that ensure a unitary time evolution in the noncommutative CQM can break the scale invariance, leading to a quantum mechanical scaling anomaly. We calculate the scaling dimensions of the two and three point functions in the noncommutative CQM which are shown to be deformed. The AdS2 / CFT1 duality for the CQM suggests that the corresponding correlation functions in the holographic duals are modified. In addition, the Breitenlohner-Freedman bound also picks up a noncommutative correction. The strongly attractive regime of a canonical model of the CQM exhibit quantum instability. We show that the noncommutativity softens this singular behaviour and its implications for the corresponding holographic duals are discussed.
Senate Hearing on Assured Access to Space
2014-07-16
The Hon. Alan Estevez, Principle Deputy Under Secretary of Defense for Acquision, TEchnology, and Logitics, answers a question during testimony in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
Senate Hearing on Assured Access to Space
2014-07-16
Cristina Chaplain, Director of Acquisition and Sourcing Management at the Government Accountability Office, delivers her opening statement during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
CADB: Conformation Angles DataBase of proteins
Sheik, S. S.; Ananthalakshmi, P.; Bhargavi, G. Ramya; Sekar, K.
2003-01-01
Conformation Angles DataBase (CADB) provides an online resource to access data on conformation angles (both main-chain and side-chain) of protein structures in two data sets corresponding to 25% and 90% sequence identity between any two proteins, available in the Protein Data Bank. In addition, the database contains the necessary crystallographic parameters. The package has several flexible options and display facilities to visualize the main-chain and side-chain conformation angles for a particular amino acid residue. The package can also be used to study the interrelationship between the main-chain and side-chain conformation angles. A web based JAVA graphics interface has been deployed to display the user interested information on the client machine. The database is being updated at regular intervals and can be accessed over the World Wide Web interface at the following URL: http://144.16.71.148/cadb/. PMID:12520049
NASA Technical Reports Server (NTRS)
Willams, M. C.
1985-01-01
Assuring personnel and equipment are fully protected during the Space Shuttle launch and landing operations has been a primary concern of NASA and its associated contractors since the inception of the program. A key factor in support of this policy has been the area access safety training requirements for badging of employees assigned to work on Space Shuttle Launch and Facilities. This requirement was targeted for possible cost savings and the transition of physical on-site walkdowns to the use of television tapes has realized program cost savings while continuing to fully satisfy the area access safety training requirements.
NASA Astrophysics Data System (ADS)
Melandri, S.; Maris, A.; Merloni, A.
2011-06-01
Fluorine substitution in molecules is a common practice in bio-organic chemistry in order to modulate physicochemical properties and biological activity of molecules and an increasing number of drugs on the market contain fluorine, the presence of which is often of major importance to modify pharmacokinetics properties and molecular activity. The rationale for such a strategy is that fluorine is generally a stronger electron acceptor than the other halogen atoms and its size is intermediate between that of hydrogen and oxygen. We have studied two fluorinated analogs of 2-phenylethylamine (PEA), the prototype molecule for adrenergic neurotransmitters, namely: 4-Fluoro (4FPEA) and 2-Fluoro-2-phenylethylamine (2FPEA) by Molecular Beam Fourier Transform Microwave Spectroscopy in the frequency range 6-18 GHz and ab initio calculations at the MP2/6311++G** level. The aim is to obtain information on the spatial arrangement of the ethylamine side chain and the effects of fluorination on the energy landscape. The conformational space is dominated by low energy gauche conformations stabilized by weak interactions between the aminic hydrogens and the electron cloud of the benzene ring and anti conformations higher in energy. In 2FPEA the presence of the fluorine atom almost duplicate the number of possible conformation with respect to 4FPEA. We observed two conformers of 4FPEA and five conformers of 2FPEA which have been classified with the guide provided by accurate ab initio calculations. The identification of the conformational species was helped by the analysis of the quadrupole hyperfine pattern which is greatly influenced by the orientation of the amino group and acts as a fingerprint for each conformation. The orientation of the dipole moment within the principal axis frame and the order of stability of the different conformations are other independent pieces of evidence for the unambiguous assignment and identification of the conformers. The order of stability was
The ESPAS e-infrastructure: Access to data from near-Earth space
NASA Astrophysics Data System (ADS)
Belehaki, Anna; James, Sarah; Hapgood, Mike; Ventouras, Spiros; Galkin, Ivan; Lembesis, Antonis; Tsagouri, Ioanna; Charisi, Anna; Spogli, Luca; Berdermann, Jens; Häggström, Ingemar; ESPAS Consortium
2016-10-01
ESPAS, the ;near-Earth space data infrastructure for e-science; is a data e-infrastructure facilitating discovery and access to observations, ground-based and space borne, and to model predictions of the near-Earth space environment, a region extending from the Earth's atmosphere up to the outer radiation belts. ESPAS provides access to metadata and/or data from an extended network of data providers distributed globally. The interoperability of the heterogeneous data collections is achieved with the adoption and adaption of the ESPAS data model which is built entirely on ISO 19100 series geographic information standards. The ESPAS data portal manages a vocabulary of space physics keywords that can be used to narrow down data searches to observations of specific physical content. Such content-targeted search is an ESPAS innovation provided in addition to the commonly practiced data selection by time, location, and instrument. The article presents an overview of the architectural design of the ESPAS system, of its data model and ontology, and of interoperable services that allow the discovery, access and download of registered data. Emphasis is given to the standardization, and expandability concepts which represent also the main elements that support the building of long-term sustainability activities of the ESPAS e-infrastructure.
Multinational Experiment 7: Protecting Access to Space
2013-07-08
access to space cost to the design, engineering , production and operation of the spacecraft. They also have an impact on spacecraft mass, thermal...station and provide engineering support to receive data in the agreed format. Step 5 – Implementing interoperability. Once a framework has been...procedures or using alternative means (for example, high-altitude airships ). A7. The results support the view that better mitigation approaches need to
[Analysis on accessibility of urban park green space: the case study of Shenyang Tiexi District].
Lu, Ning; Li, Jun-Ying; Yan, Hong-Wei; Shi, Tuo; Li, Ying
2014-10-01
The accessibility of urban park green space is an important indicator to reflect how much the natural service supplied by parks could be enjoyed by citizens conveniently and fairly. This paper took Shenyang Tiexi District as an example to evaluate the accessibility of urban park green space based on QuickBird imagery and GIS software, with four modes of transportation, walking, non-motor vehicle, motor vehicle and public transport being considered. The research compared and analyzed the distribution of the accessible area and the accessible people of park green space. The result demonstrated that park green space in Shenyang Tiexi District was not enough and the distribution was not even. To be precise, the accessibility in southwest part and central part was relatively good, that in marginal sites was worse, and that in east part and north part was the worst. Furthermore, the accessibility based on different modes of transportation varied a lot. The accessibility of motor vehicle was the best, followed by non-motor vehicle and public transport, and walking was the worst. Most of the regions could be reached within 30 minutes by walking, 15 minutes by non-motor vehicle and public transport, and 10 minutes by motor vehicle. This paper had a realistic significance in terms of further, systematic research on the green space spatial pattern optimization.
SCit: web tools for protein side chain conformation analysis.
Gautier, R; Camproux, A-C; Tufféry, P
2004-07-01
SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.
SCit: web tools for protein side chain conformation analysis
Gautier, R.; Camproux, A.-C.; Tufféry, P.
2004-01-01
SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit. PMID:15215438
NASA Astrophysics Data System (ADS)
Bourget, Antoine; Troost, Jan
2018-04-01
We revisit the study of the multiplets of the conformal algebra in any dimension. The theory of highest weight representations is reviewed in the context of the Bernstein-Gelfand-Gelfand category of modules. The Kazhdan-Lusztig polynomials code the relation between the Verma modules and the irreducible modules in the category and are the key to the characters of the conformal multiplets (whether finite dimensional, infinite dimensional, unitary or non-unitary). We discuss the representation theory and review in full generality which representations are unitarizable. The mathematical theory that allows for both the general treatment of characters and the full analysis of unitarity is made accessible. A good understanding of the mathematics of conformal multiplets renders the treatment of all highest weight representations in any dimension uniform, and provides an overarching comprehension of case-by-case results. Unitary highest weight representations and their characters are classified and computed in terms of data associated to cosets of the Weyl group of the conformal algebra. An executive summary is provided, as well as look-up tables up to and including rank four.
Conformal invariants associated to a measure.
Chang, Sun-Yung A; Gursky, Matthew J; Yang, Paul
2006-02-21
In this note, we study some conformal invariants of a Riemannian manifold (M(n), g) equipped with a smooth measure m. In particular, we show that there is a natural definition of the Ricci and scalar curvatures associated to such a space, both of which are conformally invariant. We also adapt the methods of Fefferman and Graham [Fefferman, C. & Graham, C. R. (1985) Astérisque, Numero Hors Serie, 95-116] and Graham, Jenne, Mason, and Sparling [Graham, C. R., Jenne, R., Mason, L. J., & Sparling, G. A. J. (1992) J. London Math. Soc. 46, 557-565] to construct families of conformally covariant operators defined on these spaces. Certain variational problems in this setting are considered, including a generalization of the Einstein-Hilbert action.
Gluon amplitudes as 2 d conformal correlators
NASA Astrophysics Data System (ADS)
Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew
2017-10-01
Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.
Invariant classification of second-order conformally flat superintegrable systems
NASA Astrophysics Data System (ADS)
Capel, J. J.; Kress, J. M.
2014-12-01
In this paper we continue the work of Kalnins et al in classifying all second-order conformally-superintegrable (Laplace-type) systems over conformally flat spaces, using tools from algebraic geometry and classical invariant theory. The results obtained show, through Stäckel equivalence, that the list of known nondegenerate superintegrable systems over three-dimensional conformally flat spaces is complete. In particular, a seven-dimensional manifold is determined such that each point corresponds to a conformal class of superintegrable systems. This manifold is foliated by the nonlinear action of the conformal group in three dimensions. Two systems lie in the same conformal class if and only if they lie in the same leaf of the foliation. This foliation is explicitly described using algebraic varieties formed from representations of the conformal group. The proof of these results rely heavily on Gröbner basis calculations using the computer algebra software packages Maple and Singular.
2013-01-01
This study examines the association between objectively measured access to green space, frequency of green space use, physical activity, and the probability of being overweight or obese in the city of Bristol, England. Data from the Bristol Quality of Life in your Neighbourhood survey for 6,821 adults were combined with a comprehensive GIS database of neighbourhood and green space characteristics.. A range of green space accessibility measures were computed. Associations between accessibility and the odds of respondents achieving a recommended 30 minutes or more of moderate activity five times a week, or being overweight or obese, were examined using logistic regression. Results showed that the reported frequency of green space use declined with increasing distance. The study also found that respondents living closest to the type of green space classified as a Formal park were more likely to achieve the physical activity recommendation and less likely to be overweight or obese. The association with physical activity, but not with overweight or obesity, remained after adjustment for respondent characteristics, area deprivation, and a range of characteristics of the neighbourhood environment. The findings suggest that the provision of good access to green spaces in urban areas may help promote population physical activity. PMID:20060635
Senate Hearing on Assured Access to Space
2014-07-16
From left; Hon. Alan Estevez, Principle Deputy Under Secretary of Defense for Acquisition, Technology, and Logistics; General William Shelton, Commander of the United States Air Force Space Command; Robert Lightfoot, NASA Associate Administrator; Cristina Chaplain, Director of Acquisition and Sourcing Management at the Government Accountability Office; major General Howard Mitchell (USAF Ret.), Vice President for Program Assessments at The Aerospace Corporation; Daniel Dunbacher, Professor of Practice in the Department of Aeronautics and Aerospace Engineering at Purdue University; and Dr. Yool Kim, Senior Engineer at The Rand Corporation; are seen during a hearing in front of the Senate Subcommittee on Strategic Forces and Senate Committee on Commerce, Science, and Transportation on Wednesday, July 16, 2014, at the Hart Senate Office Building in Washington, DC. The Senate hearing focused on assured access to space.
The Virtual Space Physics Observatory: Quick Access to Data and Tools
NASA Technical Reports Server (NTRS)
Cornwell, Carl; Roberts, D. Aaron; McGuire, Robert E.
2006-01-01
The Virtual Space Physics Observatory (VSPO; see http://vspo.gsfc.nasa.gov) has grown to provide a way to find and access about 375 data products and services from over 100 spacecraft/observatories in space and solar physics. The datasets are mainly chosen to be the most requested, and include most of the publicly available data products from operating NASA Heliophysics spacecraft as well as from solar observatories measuring across the frequency spectrum. Service links include a "quick orbits" page that uses SSCWeb Web Services to provide a rapid answer to questions such as "What spacecraft were in orbit in July 1992?" and "Where were Geotail, Cluster, and Polar on 2 June 2001?" These queries are linked back to the data search page. The VSPO interface provides many ways of looking for data based on terms used in a registry of resources using the SPASE Data Model that will be the standard for Heliophysics Virtual Observatories. VSPO itself is accessible via an API that allows other applications to use it as a Web Service; this has been implemented in one instance using the ViSBARD visualization program. The VSPO will become part of the Space Physics Data Facility, and will continue to expand its access to data. A challenge for all VOs will be to provide uniform access to data at the variable level, and we will be addressing this question in a number of ways.
Protein Conformational Populations and Functionally Relevant Sub-states
DOE Office of Scientific and Technical Information (OSTI.GOV)
Agarwal, Pratul K; Burger, Virginia; Savol, Andrej
2013-01-01
Functioning proteins do not remain fixed in a unique structure, but instead they sample a range of conformations facilitated by motions within the protein. Even in the native state, a protein exists as a collection of interconverting conformations driven by thermodynamic fluctuations. Motions on the fast time scale allow a protein to sample conformations in the nearby area of its conformational landscape, while motions on slower time scales give it access to conformations in distal areas of the landscape. Emerging evidence indicates that protein landscapes contain conformational substates with dynamic and structural features that support the designated function of themore » protein. Nuclear magnetic resonance (NMR) experiments provide information about conformational ensembles of proteins. X-ray crystallography allows researchers to identify the most populated states along the landscape, and computational simulations give atom-level information about the conformational substates of different proteins. This ability to characterize and obtain quantitative information about the conformational substates and the populations of proteins within them is allowing researchers to better understand the relationship between protein structure and dynamics and the mechanisms of protein function. In this Account, we discuss recent developments and challenges in the characterization of functionally relevant conformational populations and substates of proteins. In some enzymes, the sampling of functionally relevant conformational substates is connected to promoting the overall mechanism of catalysis. For example, the conformational landscape of the enzyme dihydrofolate reductase has multiple substates, which facilitate the binding and the release of the cofactor and substrate and catalyze the hydride transfer. For the enzyme cyclophilin A, computational simulations reveal that the long time scale conformational fluctuations enable the enzyme to access conformational substates that
NASA Astrophysics Data System (ADS)
Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.
1989-06-01
The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.
Ross Works on the Assembly Concept for Construction of Erectable Space Structure (ACCESS) During
NASA Technical Reports Server (NTRS)
1985-01-01
The crew assigned to the STS-61B mission included Bryan D. O'Conner, pilot; Brewster H. Shaw, commander; Charles D. Walker, payload specialist; mission specialists Jerry L. Ross, Mary L. Cleave, and Sherwood C. Spring; and Rodolpho Neri Vela, payload specialist. Launched aboard the Space Shuttle Atlantis November 28, 1985 at 7:29:00 pm (EST), the STS-61B mission's primary payload included three communications satellites: MORELOS-B (Mexico); AUSSAT-2 (Australia); and SATCOM KU-2 (RCA Americom). Two experiments were conducted to test assembling erectable structures in space: EASE (Experimental Assembly of Structures in Extravehicular Activity), and ACCESS (Assembly Concept for Construction of Erectable Space Structure). In a joint venture between NASA/Langley Research Center in Hampton, Virginia, and the Marshall Space Flight Center (MSFC), EASE and ACCESS were developed and demonstrated at MSFC's Neutral Buoyancy Simulator (NBS). In this STS-61B onboard photo, astronaut Ross works on ACCESS high above the orbiter. The primary objective of these experiments was to test the structural assembly concepts for suitability as the framework for larger space structures and to identify ways to improve the productivity of space construction.
Rotationally resolved electronic spectroscopy study of the conformational space of 3-methoxyphenol
NASA Astrophysics Data System (ADS)
Wilke, Martin; Schneider, Michael; Wilke, Josefin; Ruiz-Santoyo, José Arturo; Campos-Amador, Jorge J.; González-Medina, M. Elena; Álvarez-Valtierra, Leonardo; Schmitt, Michael
2017-07-01
Conformational preferences are determined by (de-)stabilization effects like intramolecular hydrogen bonds or steric hindrance of adjacent substituents and thus, influence the stability and reactivity of the conformers. In the present contribution, we investigate the conformational landscape of 3-methoxyphenol using a combination of high resolution electronic spectroscopy and ab initio calculations. Three of the four possible conformational isomers were characterized in their electronic ground and lowest excited singlet states on the basis of their rotational constants and other molecular parameters. The absence of one conformer in molecular beam studies can be explained by its non-planar structure in the excited state, which leads to a vanishingly small Franck-Condon factor of the respective origin excitation.
Eikonalization of conformal blocks
Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; ...
2015-09-03
Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the t-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the 'eikonalization' of conformal blocks. We show that when an operator T appears in the OPE Ο(x)Ο(0), then the large spin Fock space states [TT···T] ℓ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an correlator build the classical 'T field' in the dual AdS description. In some limits the sum of all Fockmore » space exchanges can be represented as the exponential of a single T exchange in the 4-pt correlator of O. Our results should be useful for systematizing 1/ℓ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading log ℓ dependence of Fock space conformal block coefficients, and we directly compute the OPE coefficients of the simplest ‘triple-trace’ operators.« less
Molecular dynamics of conformation-specific dopamine transporter-inhibitor complexes.
Jean, Bernandie; Surratt, Christopher K; Madura, Jeffry D
2017-09-01
The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation. The 3β-aryltropane cocaine analogs LX10 and LX11, however, differ only in stereochemistry and share a preference for the outward-facing DAT, yet are reported to vary widely in abuse potential in an animal model. In search of the molecular basis for DAT conformation preference, complexes of cocaine, benztropine, LX10 or LX11 bound to each DAT conformation were subjected to 100ns of all-atom molecular dynamics simulation. Results were consistent with previous findings from cysteine accessibility assays used to assess an inhibitor's DAT conformation preference. The respective 2β- and 2α-substituted phenyltropanes of LX10 and LX11 interacted with hydrophobic regions of the DAT S1 binding site that were inaccessible to cocaine. Solvent accessibility measurements also revealed subtle differences in inhibitor positioning within a given DAT conformation. This work serves to advance our understanding of the conformational selectivity of DAT inhibitors and suggests that MD may be useful in antipsychostimulant therapeutic design. Copyright © 2017 Elsevier Inc. All rights reserved.
Krüger, Dennis M; Ahmed, Aqeel; Gohlke, Holger
2012-07-01
The NMSim web server implements a three-step approach for multiscale modeling of protein conformational changes. First, the protein structure is coarse-grained using the FIRST software. Second, a rigid cluster normal-mode analysis provides low-frequency normal modes. Third, these modes are used to extend the recently introduced idea of constrained geometric simulations by biasing backbone motions of the protein, whereas side chain motions are biased toward favorable rotamer states (NMSim). The generated structures are iteratively corrected regarding steric clashes and stereochemical constraint violations. The approach allows performing three simulation types: unbiased exploration of conformational space; pathway generation by a targeted simulation; and radius of gyration-guided simulation. On a data set of proteins with experimentally observed conformational changes, the NMSim approach has been shown to be a computationally efficient alternative to molecular dynamics simulations for conformational sampling of proteins. The generated conformations and pathways of conformational transitions can serve as input to docking approaches or more sophisticated sampling techniques. The web server output is a trajectory of generated conformations, Jmol representations of the coarse-graining and a subset of the trajectory and data plots of structural analyses. The NMSim webserver, accessible at http://www.nmsim.de, is free and open to all users with no login requirement.
The Space Shuttle: An Attempt at Low-Cost, Routine Access to Space
1990-09-01
thinking on new heavy-lift launch systems. The thesis objective is to show the Space Shuttle was an attempt at developing a routine, low-cost access to... development costs were those used to create a launch facility at Vandenburg Air Force Base. DOD agreed in 1971 not to develop any new launch vehicles...booster. • To reduce the design weight of the Shuttle so as not to decrease the 65,000 pound payload capability. * To develop a new thermal protection
Neighbourhood access to open spaces and the physical activity of residents: a national study.
Witten, Karen; Hiscock, Rosemary; Pearce, Jamie; Blakely, Tony
2008-09-01
Increasing population levels of physical activity is high on the health agenda in many countries. There is some evidence that neighbourhood access to public open space can increase physical activity by providing easier and more direct access to opportunities for exercise. This national study examines the relationship between travel time access to parks and beaches, BMI and physical activity in New Zealand neighbourhoods. Access to parks and beaches, measured in minutes taken by a car, was calculated for 38,350 neighbourhoods nationally using Geographic Information Systems. Multilevel regression analyses were used to establish the significance of access to these recreational amenities as a predictor of BMI, and levels of physical activity and sedentary behaviour in the 12,529 participants, living in 1178 neighbourhoods, of the New Zealand Health Survey 2002/3. Neighbourhood access to parks was not associated with BMI, sedentary behaviour or physical activity, after controlling for individual-level socio-economic variables, and neighbourhood-level deprivation and urban/rural status. There was some evidence of a relationship between beach access and BMI and physical activity in the expected direction. This study found little evidence of an association between locational access to open spaces and physical activity.
Aviation or space policy: New challenges for the insurance sector to private human access to space
NASA Astrophysics Data System (ADS)
van Oijhuizen Galhego Rosa, Ana Cristina
2013-12-01
The phenomenon of private human access to space has introduced a new set of problems in the insurance sector. Orbital and suborbital space transportation will surely be unique commercial services for this new market. Discussions are under way regarding space insurance, in order to establish whether this new market ought to be regulated by aviation or space law. Alongside new definitions, infrastructures, legal frameworks and liability insurances, the insurance sector has also been introducing a new approach. In this paper, I aim to analyse some of the possibilities of new premiums, capacities, and policies (under aviation or space insurance rules), as well as the new insurance products related to vehicles, passengers and third party liability. This paper claims that a change toward new insurance regimes is crucial, due to the current stage in development of space tourism and the urgency to adapt insurance rules to support future development in this area.
Pilot Non-Conformance to Alerting System Commands
NASA Technical Reports Server (NTRS)
Pritchett, Amy R.; Hansman, R. John
1997-01-01
Instances of pilot non-conformance to alerting system commands have been identified in previous studies. Pilot non-conformance changes the final behavior of the system, and therefore may reduce actual performance from that anticipated. A simulator study has examined pilot non-conformance, using the task of collision avoidance during closely spaced parallel approaches as a case study. Consonance between the display and the alerting system was found to significantly improve subject agreement with automatic alerts. Based on these results, a more general discussion of the factors involved in pilot conformance is given, and design guidelines for alerting systems are given.
NASA Astrophysics Data System (ADS)
Ververs, Patricia May
experimental findings. Attention was found to be more widely distributed in X-Y space when the pilots were flying with the conformal, tunnel-in-the-sky as compared to the partially conformal ILS (instrument landing system) symbology set. There was little evidence that the air-based navigation displays were supporting divided attention in three-dimensional space. The ground-based scene-linked (truly conformal) display indicated promising effects of dividing attention in depth without negative consequences to processing the near domain symbology. Event expectancy was found to modulate pilot performance in the detection of events both on the symbology and in the environment. The phenomenon known as cognitive tunneling is discussed as a possible cause of the inadequate response times in resolving the anomalous events.
High data rate modem simulation for the space station multiple-access communications system
NASA Technical Reports Server (NTRS)
Horan, Stephen
1987-01-01
The communications system for the space station will require a space based multiple access component to provide communications between the space based program elements and the station. A study was undertaken to investigate two of the concerns of this multiple access system, namely, the issues related to the frequency spectrum utilization and the possibilities for higher order (than QPSK) modulation schemes for use in possible modulators and demodulators (modems). As a result of the investigation, many key questions about the frequency spectrum utilization were raised. At this point, frequency spectrum utilization is seen as an area requiring further work. Simulations were conducted using a computer aided communications system design package to provide a straw man modem structure to be used for both QPSK and 8-PSK channels.
NASA Technical Reports Server (NTRS)
Haratunian, M.
1985-01-01
A system of access platforms and equipment within the space shuttle orbiter processing facility at Kennedy Space Center is described. The design challenges of the platforms, including clearance envelopes, load criteria, and movement, are discussed. Various applications of moveable platforms are considered.
Lungu, Claudiu N; Diudea, Mircea V
2018-01-01
Lipid II, a peptidoglycan, is a precursor in bacterial cell synthesis. It has both hydrophilic and lipophilic properties. The molecule translocates a bacterial membrane to deliver and incorporate "building blocks" from disaccharide-pentapeptide into the peptidoglican wall. Lipid II is a valid antibiotic target. A receptor binding pocket may be occupied by a ligand in various plausible conformations, among which only few ones are energetically related to a biological activity in the physiological efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its interaction with Teixobactin and other Lipid II ligands. In order to study computationally the complex between Lipid II and ligands, a docking study was first carried on. Docking site was retrieved form literature. After docking, 5 ligand conformations and further 5 complexes (denoted 00 to 04) for each molecule were taken into account. For each structure, conformational studies were performed. Statistical analysis, conformational analysis and molecular dynamics based clustering were used to predict the potency of these compounds. A score for potency prediction was developed. Appling lipid II classification according to Lipid II conformational energy, a conformation of Teixobactin proved to be energetically favorable, followed by Oritravicin, Dalbavycin, Telvanicin, Teicoplamin and Vancomycin, respectively. Scoring of molecules according to cluster band and PCA produced the same result. Molecules classified according to standard deviations showed Dalbavycin as the most favorable conformation, followed by Teicoplamin, Telvanicin, Teixobactin, Oritravicin and Vancomycin, respectively. Total score showing best energetic efficiency of complex formation shows Teixobactin to have the best conformation (a score of 15 points) followed by Dalbavycin (14 points), Oritravicin (12v points), Telvanicin (10 points), Teicoplamin (9 points), Vancomycin (3 points). Statistical analysis of
Transgender Adults' Access to College Bathrooms and Housing and the Relationship to Suicidality.
Seelman, Kristie L
2016-10-01
Transgender and gender non-conforming people frequently experience discrimination, harassment, and marginalization across college and university campuses (Bilodeau, 2007; Finger, 2010; Rankin et al., 2010; Seelman et al., 2012). The minority stress model (Meyer, 2007) posits that experiences of discrimination often negatively impact the psychological wellbeing of minority groups. However, few scholars have examined whether college institutional climate factors-such as being denied access to bathrooms or gender-appropriate campus housing-are significantly associated with detrimental psychological outcomes for transgender people. Using the National Transgender Discrimination Survey, this study analyzes whether being denied access to these spaces is associated with lifetime suicide attempts, after controlling for interpersonal victimization by students or teachers. Findings from sequential logistic regression (N = 2,316) indicate that denial of access to either space had a significant relationship to suicidality, even after controlling for interpersonal victimization. This article discusses implications for higher education professionals and researchers.
HL-20 structural design comparison - Conformal shell versus cylindrical crew compartment
NASA Technical Reports Server (NTRS)
Bush, Lance B.; Wahls, Deborah M.; Robinson, James C.
1993-01-01
Extensive studies have been performed at NASA Langley Research Center (LaRC) on personnel launch systems (PLS) concepts. The primary mission of a PLS is the transport of Space Station crew members from Earth to the Space Station and return. The NASA LaRC PLS studies have led to the design of a lifting body configuration named the HL-20. In this study, two different HL-20 structural configurations are evaluated. The two configurations are deemed the conformal shell and the cylindrical crew compartment. The configurations are based on two different concerns for maintenance and operations. One configuration allows for access to subsystems while on-orbit from the interior, while the other allows for easy access to the subsystems during ground maintenance and operations. For each concept, the total structural weight required to sustain the applied loads is quantified through a structural evaluation. Structural weight for both configurations is compared along with the particular attributes of each. Analyses of both configurations indicate no appreciable weight or load relief advantage of one concept over the other. Maintainability and operability, therefore become the primary discriminator, leading to a choice of a crew compartment configuration.
Raman Spectral Signatures as Conformational Probes of Biomolecules
NASA Astrophysics Data System (ADS)
Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana
2009-06-01
A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.
Raman Spectral Signatures as Conformational Probes of Biomolecules
NASA Astrophysics Data System (ADS)
Bar, Ilana; Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman
2009-03-01
A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.
Sharing Ideas: Making Earth and Space Science Accessible
NASA Astrophysics Data System (ADS)
Runyon, C. J.; Guimond, K.; Atkinson, C.
2005-12-01
There are nearly six million K-12 students with some form of disability in the U.S. and the majority of them are required to achieve the same academic levels as their non-impaired peers. Historically, students with disabilities have experienced difficulties in fully accessing and participating in middle school and high school science programs. With the passage of the No Child Left Behind (NCLB) Act and increasing focus on reading and math performance, many students with exceptional needs are now being taught science by mainstream science teachers, who have little to no training on how to work with students with exceptional needs. For the past 5 years, SERCH has engaged in organizing and hosting a series of Exceptional Space Science Materials for Exceptional Students Workshops (ENWS) focused on educating students with special needs about the space sciences. Each workshop has focused on a different aspect of formal and informal education and working with the various special needs. In all of these workshops, participants experience what a person or student with special needs might encounter when working through educational activities or exhibits by experiencing it first-hand. In addition to making many of NASA's education materials accessible for all learners, a top-ten list of "best practices" has been compiled by the professional educators as a result of our working together for five years and their formal and informal educational experiences.
Innovative Airbreathing Propulsion Concepts for Access to Space
NASA Technical Reports Server (NTRS)
Whitlow, Jr., Woodrow; Blech, Richard A.; Blankson, Isaiah M.
2001-01-01
This paper will present technologies and concepts for novel aeropropulsion systems. These technologies will enhance the safety of operations, reduce life cycle costs, and contribute to reduced costs of air travel and access to space. One of the goals of the NASA program is to reduce the carbon-dioxide emissions of aircraft engines. Engine concepts that use highly efficient fuel cell/electric drive technologies in hydrogen-fueled engines will be presented in the proposed paper. Carbon-dioxide emissions will be eliminated by replacing hydrocarbon fuel with hydrogen, and reduce NOx emissions through better combustion process control. A revolutionary exoskeletal engine concept, in which the engine drum is rotated, will be shown. This concept has the potential to allow a propulsion system that can be used for subsonic through hypersonic flight. Dual fan concepts that have ultra-high bypass ratios, low noise, and low drag will be presented. Flow-controlled turbofans and control-configured turbofans also will be discussed. To increase efficiency, a system of microengines distributed along lifting surfaces and on the fuselage is being investigated. This concept will be presented in the paper. Small propulsion systems for affordable, safe personal transportation vehicles will be discussed. These low-oil/oilless systems use technologies that enable significant cost and weight reductions. Pulse detonation engine-based hybrid-cycle and combined-cycle propulsion systems for aviation and space access will be presented.
A DTN-Based Multiple Access Fast Forward Service for the NASA Space Network
NASA Technical Reports Server (NTRS)
Israel, David; Davis, Faith; Marquart. Jane
2011-01-01
The NASA Space Network provides a demand access return link service capable of providing users a space link "on demand". An equivalent service in the forward link direction is not possible due to Tracking and Data Relay Spacecraft (TDRS) constraints. A Disruption Tolerant Networking (DTN)-based Multiple Access Fast Forward (MAFF) service has been proposed to provide a forward link to a user as soon as possible. Previous concept studies have identified a basic architecture and implementation approach. This paper reviews the user scenarios and benefits of an MAFF service and proposes an implementation approach based on the use of DTN protocols.
Promoting Environmental Justice Through Urban Green Space Access: A Synopsis
Viniece Jennings; Cassandra Johnson Gaither; Richard Schulterbrandt Gragg
2012-01-01
This article reviews literature on the connection between urban green space access and environmental justice. It discusses the dynamics of the relationship as it relates to factors such as environmental quality, land use, and environmental health disparities. Urban development stresses the landscape and may compromise environmental quality. Since some communities are...
Conformal and projective symmetries in Newtonian cosmology
NASA Astrophysics Data System (ADS)
Duval, C.; Gibbons, G. W.; Horváthy, P. A.
2017-02-01
Definitions of non-relativistic conformal transformations are considered both in the Newton-Cartan and in the Kaluza-Klein-type Eisenhart/Bargmann geometrical frameworks. The symmetry groups that come into play are exemplified by the cosmological, and also the Newton-Hooke solutions of Newton's gravitational field equations. It is shown, in particular, that the maximal symmetry group of the standard cosmological model is isomorphic to the 13-dimensional conformal-Newton-Cartan group whose conformal-Bargmann extension is explicitly worked out. Attention is drawn to the appearance of independent space and time dilations, in contrast with the Schrödinger group or the Conformal Galilei Algebra.
Protein Allostery and Conformational Dynamics.
Guo, Jingjing; Zhou, Huan-Xiang
2016-06-08
The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.
McQuoid, Julia; Jowsey, Tanisha; Talaulikar, Girish
2017-06-01
Stable routines are key to successful illness self-management for the growing number of people living with chronic illness around the world. Yet, the influence of chronically ill individuals' everyday contexts in supporting routines is poorly understood. This paper takes a space-time geographical approach to explore the everyday space-time contexts and routines of individuals with chronic kidney disease (CKD). We ask: what is the relationship between renal patients' space-time contexts and their ability to establish and maintain stable routines, and, what role does health service access play in this regard? We draw from a qualitative case study of 26 individuals with CKD in Australia. Data comprised self-reported two day participant diaries and semi-structured interviews. Thematic analysis of interview transcripts was guided by an inductive-deductive approach. We examined the embeddedness of routines within the space-time contexts of participants' everyday lives. We found that participants' everyday space-time contexts were highly complex, especially for those receiving dialysis and/or employed, making routines difficult to establish and vulnerable to disruption. Health service access helped shape participants' everyday space-time contexts, meaning that incidences of unpredictability in accessing health services set-off 'ripple effects' within participants' space-time contexts, disrupting routines and making everyday life negotiation more difficult. The ability to absorb ripple effects from unpredictable health services without disrupting routines varied by space-time context. Implications of these findings for the deployment of the concept of routine in health research, the framing of patient success in self-managing illness, and health services design are discussed. In conclusion, efforts to understand and support individuals in establishing and maintaining routines that support health and wellbeing can benefit from approaches that contextualise and de
McQuoid, Julia; Jowsey, Tanisha; Talaulikar, Girish
2017-01-01
Stable routines are key to successful illness self-management for the growing number of people living with chronic illness around the world. Yet, the influence of chronically ill individuals’ everyday contexts in supporting routines is poorly understood. This paper takes a space-time geographical approach to explore the everyday space-time contexts and routines of individuals with chronic kidney disease (CKD). We ask: what is the relationship between renal patients’ space-time contexts and their ability to establish and maintain stable routines, and, what role does health service access play in this regard? We draw from a qualitative case study of 26 individuals with CKD in Australia. Data comprised self-reported two day participant diaries and semi-structured interviews. Thematic analysis of interview transcripts was guided by an inductive-deductive approach. We examined the embeddedness of routines within the space-time contexts of participants’ everyday lives. We found that participants’ everyday space-time contexts were highly complex, especially for those receiving dialysis and/or employed, making routines difficult to establish and vulnerable to disruption. Health service access helped shape participants’ everyday space-time contexts, meaning that incidences of unpredictability in accessing health services set-off ‘ripple effects’ within participants’ space-time contexts, disrupting routines and making everyday life negotiation more difficult. The ability to absorb ripple effects from unpredictable health services without disrupting routines varied by space-time context. Implications of these findings for the deployment of the concept of routine in health research, the framing of patient success in self-managing illness, and health services design are discussed. In conclusion, efforts to understand and support individuals in establishing and maintaining routines that support health and wellbeing can benefit from approaches that contextualise
URSA MAIOR: a One Liter Nanosatellite Bus for Low Cost Access to Space
NASA Astrophysics Data System (ADS)
Santoni, F.
One of the main limitations in the access to space for developing countries is the economical effort typically required by space missions. Secondly, space activity is a field of very high technology, requiring technical skills, education and practice, at a level which is seldom reached by developing countries. Interventions aimed to facilitate access to space for developing countries should be focussed primarily on the missions allowing access to space at reasonable cost. Moreover, perhaps more importantly, they should emphasize conducting the mission design, construction, ground testing and operation in orbit as an open activity, accessible to developing countries personnel, in order to set up an education process, which is not just selling a product ready satellite. Universities could have a very important role in this activity. Many Universities around the world have designed, built and launched small satellites. Università di Roma "La Sapienza" set up a program for the construction of small satellites in an academic environment, involving directly the students in the design, construction, ground testing and operation in orbit. The first satellite built in the framework of this program, UNISAT, was successfully launched in September 2000. The second, UNISAT-2, initially scheduled for launch in 2001, has been delayed by the launch provider to late 2002. These two satellites, based on a modular design, emphasizing ease of construction and assembly, weight roughly 10 kg. The realization of these satellites was made possible within the regular financing given to university research programs, keeping down cost by the use of commercial off the shelf components instead of space rated ones. The microsatellite experience at Università di Roma "La Sapienza", is going further with the development of a new nanosatellite bus, URSA MAIOR (Università di Roma "la SApienza" Micro Autonomous Imager in ORbit), aiming at cutting down cost and possibly improving performance. The
Making Astronomy and Space Science Accessible to the Blind and Visually Impaired
NASA Astrophysics Data System (ADS)
Beck-Winchatz, B.; Hoette, V.; Grice, N.
2003-12-01
One of the biggest obstacles blind and visually impaired people face in science is the ubiquity of important graphical information, which is generally not made available in alternate formats accessible to them. Funded by NASA's Initiative to Develop Education through Astronomy and Space Science (IDEAS), we have recently formed a team of scientists and educators from universities, the SOFIA NASA mission, a science museum, an observatory, and schools for the blind. Our goal is to develop and test Braille/tactile space science activities that actively engage students from elementary grades through introductory college-level in space science. We will discuss effective strategies and low-cost technologies that can be used to make graphical information accessible. We will also demonstrate examples, such a thermal expansion graphics created from telescope images of the Moon and other celestial objects, a tactile planisphere, three-dimensional models of near-Earth asteroids and tactile diagrams of their orbits, and an infrared detector activity.
Pan, Lucy Yan; Salas-Solano, Oscar; Valliere-Douglass, John F
Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in C H 2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.
Probing the conformational dynamics of photosystem I in unconfined and confined spaces.
Das, Gaurav; Chattoraj, Shyamtanu; Nandi, Somen; Mondal, Prasenjit; Saha, Abhijit; Bhattacharyya, Kankan; Ghosh, Surajit
2017-12-20
The fluorescence dynamics of Photosystem I (PSI) in bulk water and inside a confined environment like a liposome have been investigated using time resolved confocal microscopy. In bulk water, PSI exhibits a major emission peak at ∼680 nm, while in the liposome it exhibits a markedly blue shifted emission maximum at ∼485 nm. This is indicative of conformational changes due to entrapment and emergence of a stressed conformation of PSI inside the liposome. The observed time constants for the fluorescence lifetime of PSI inside the liposome are significantly high as opposed to PSI in bulk water. More interestingly, the fluorescence intensity of PSI in bulk water exhibits strong fluctuations with many high intensity jumps and these are anti-correlated with the fluorescence lifetime of PSI. In contrast, inside the liposome, no such anti-correlated behaviour is observed. We further demonstrated that PSI exhibits at least two conformational states in bulk water, whereas a single conformation is observed inside the liposome, indicating the conformational rigidity and locking of the PSI complex inside a liposome.
NASA Astrophysics Data System (ADS)
Pankratz, C. K.; Baker, D. N.; Jaynes, A. N.; Elkington, S. R.; Baltzer, T.; Sanchez, F.
2017-12-01
Society's growing reliance on complex and highly interconnected technological systems makes us increasingly vulnerable to the effects of space weather events - maybe more than for any other natural hazard. An extreme solar storm today could conceivably impact hundreds of the more than 1400 operating Earth satellites. Such an extreme storm could cause collapse of the electrical grid on continental scales. The effects on navigation, communication, and remote sensing of our home planet could be devastating to our social functioning. Thus, it is imperative that the scientific community address the question of just how severe events might become. At least as importantly, it is crucial that policy makers and public safety officials be informed by the facts on what might happen during extreme conditions. This requires essentially real-time alerts, warnings, and also forecasts of severe space weather events, which in turn demands measurements, models, and associated data products to be available via the most effective data discovery and access methods possible. Similarly, advancement in the fundamental scientific understanding of space weather processes is also vital, requiring that researchers have convenient and effective access to a wide variety of data sets and models from multiple sources. The space weather research community, as with many scientific communities, must access data from dispersed and often uncoordinated data repositories to acquire the data necessary for the analysis and modeling efforts that advance our understanding of solar influences and space physics on the Earth's environment. The Laboratory for Atmospheric and Space Physics (LASP), as a leading institution in both producing data products and advancing the state of scientific understanding of space weather processes, is well positioned to address many of these issues. In this presentation, we will outline the motivating factors for effective space weather data access, summarize the various data
Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph
2017-01-01
Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.
Integrability conditions for Killing-Yano tensors and conformal Killing-Yano tensors
NASA Astrophysics Data System (ADS)
Batista, Carlos
2015-01-01
The integrability conditions for the existence of a conformal Killing-Yano tensor of arbitrary order are worked out in all dimensions and expressed in terms of the Weyl tensor. As a consequence, the integrability conditions for the existence of a Killing-Yano tensor are also obtained. By means of such conditions, it is shown that in certain Einstein spaces one can use a conformal Killing-Yano tensor of order p to generate a Killing-Yano tensor of order (p -1 ) . Finally, it is proved that in maximally symmetric spaces the covariant derivative of a Killing-Yano tensor is a closed conformal Killing-Yano tensor and that every conformal Killing-Yano tensor is uniquely decomposed as the sum of a Killing-Yano tensor and a closed conformal Killing-Yano tensor.
Measuring accessibility of sustainable transportation using space syntax in Bojonggede area
NASA Astrophysics Data System (ADS)
Suryawinata, B. A.; Mariana, Y.; Wijaksono, S.
2017-12-01
Changes in the physical structure of regional space as a result of the increase of planned and unplanned settlements in the Bojonggede area have an impact on the road network pattern system. Changes in road network patterns will have an impact on the permeability of the area. Permeability measures the extent to which road network patterns provide an option in traveling. If the permeability increases the travel distance decreases and the route of travel choice increases, permeability like this can create an easy access system and physically integrated. This study aims to identify the relationship of physical characteristics of residential area and road network pattern to the level of space permeability in Bojonggede area. By conducting this research can be a reference for the arrangement of circulation, accessibility, and land use in the vicinity of Bojonggede. This research uses quantitative method and space syntax method to see global integration and local integration on the region which become the parameter of permeability level. The results showed that the level of permeability globally and locally high in Bojonggede physical area is the physical characteristics of the area that has a grid pattern of road network grid.
Conformity and statistical tolerancing
NASA Astrophysics Data System (ADS)
Leblond, Laurent; Pillet, Maurice
2018-02-01
Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).
Minic, Djordje; Pleimling, Michel
2008-12-01
We point out that the recent discussion of nonrelativistic anti-de Sitter space and conformal field theory correspondence has a direct application in nonequilibrium statistical physics, a fact which has not been emphasized in the recent literature on the subject. In particular, we propose a duality between aging in systems far from equilibrium characterized by the dynamical exponent z=2 and gravity in a specific background. The key ingredient in our proposal is the recent geometric realization of the Schrödinger group. We also discuss the relevance of the proposed correspondence for the more general aging phenomena in systems where the value of the dynamical exponent is different from 2.
Inverse bootstrapping conformal field theories
NASA Astrophysics Data System (ADS)
Li, Wenliang
2018-01-01
We propose a novel approach to study conformal field theories (CFTs) in general dimensions. In the conformal bootstrap program, one usually searches for consistent CFT data that satisfy crossing symmetry. In the new method, we reverse the logic and interpret manifestly crossing-symmetric functions as generating functions of conformal data. Physical CFTs can be obtained by scanning the space of crossing-symmetric functions. By truncating the fusion rules, we are able to concentrate on the low-lying operators and derive some approximate relations for their conformal data. It turns out that the free scalar theory, the 2d minimal model CFTs, the ϕ 4 Wilson-Fisher CFT, the Lee-Yang CFTs and the Ising CFTs are consistent with the universal relations from the minimal fusion rule ϕ 1 × ϕ 1 = I + ϕ 2 + T , where ϕ 1 , ϕ 2 are scalar operators, I is the identity operator and T is the stress tensor.
Cerezo, Javier; Aranda, Daniel; Avila Ferrer, Francisco J; Prampolini, Giacomo; Mazzeo, Giuseppe; Longhi, Giovanna; Abbate, Sergio; Santoro, Fabrizio
2018-06-01
We extend a recently proposed mixed quantum/classical method for computing the vibronic electronic circular dichroism (ECD) spectrum of molecules with different conformers, to cases where more than one hindered rotation is present. The method generalizes the standard procedure, based on the simple Boltzmann average of the vibronic spectra of the stable conformers, and includes the contribution of structures that sample all the accessible conformational space. It is applied to the simulation of the ECD spectrum of (S)-2,2,2-trifluoroanthrylethanol, a molecule with easily interconvertible conformers, whose spectrum exhibits a pattern of alternating positive and negative vibronic peaks. Results are in very good agreement with experiment and show that spectra averaged over all the sampled conformational space can deviate significantly from the simple average of the contributions of the stable conformers. The present mixed quantum/classical method is able to capture the effect of the nonlinear dependence of the rotatory strength on the molecular structure and of the anharmonic couplings among the modes responsible for molecular flexibility. Despite its computational cost, the procedure is still affordable and promises to be useful in all cases where the ECD shape arises from a subtle balance between vibronic effects and conformational variety. © 2018 Wiley Periodicals, Inc.
Reversible ratchet effects for vortices in conformal pinning arrays
Reichhardt, Charles; Ray, Dipanjan; Reichhardt, Cynthia Jane Olson
2015-05-04
A conformal transformation of a uniform triangular pinning array produces a structure called a conformal crystal which preserves the sixfold ordering of the original lattice but contains a gradient in the pinning density. Here we use numerical simulations to show that vortices in type-II superconductors driven with an ac drive over gradient pinning arrays produce the most pronounced ratchet effect over a wide range of parameters for a conformal array, while square gradient or random gradient arrays with equivalent pinning densities give reduced ratchet effects. In the conformal array, the larger spacing of the pinning sites in the direction transversemore » to the ac drive permits easy funneling of interstitial vortices for one driving direction, producing the enhanced ratchet effect. In the square array, the transverse spacing between pinning sites is uniform, giving no asymmetry in the funneling of the vortices as the driving direction switches, while in the random array, there are numerous easy-flow channels present for either direction of drive. We find multiple ratchet reversals in the conformal arrays as a function of vortex density and ac amplitude, and correlate the features with a reversal in the vortex ordering, which is greater for motion in the ratchet direction. In conclusion, the enhanced conformal pinning ratchet effect can also be realized for colloidal particles moving over a conformal array, indicating the general usefulness of conformal structures for controlling the motion of particles.« less
Very special conformal field theories and their holographic duals
NASA Astrophysics Data System (ADS)
Nakayama, Yu
2018-03-01
Cohen and Glashow introduced the notion of very special relativity as viable space-time symmetry of elementary particle physics. As a natural generalization of their idea, we study the subgroup of the conformal group, dubbed very special conformal symmetry, which is an extension of the very special relativity. We classify all of them and construct field theory examples as well as holographic realization of the very special conformal field theories.
Renormalization, conformal ward identities and the origin of a conformal anomaly pole
NASA Astrophysics Data System (ADS)
Corianò, Claudio; Maglio, Matteo Maria
2018-06-01
We investigate the emergence of a conformal anomaly pole in conformal field theories in the case of the TJJ correlator. We show how it comes to be generated in dimensional renormalization, using a basis of 13 form factors (the F-basis), where only one of them requires renormalization (F13), extending previous studies. We then combine recent results on the structure of the non-perturbative solutions of the conformal Ward identities (CWI's) for the TJJ in momentum space, expressed in terms of a minimal set of 4 form factors (A-basis), with the properties of the F-basis, and show how the singular behaviour of the corresponding form factors in both basis can be related. The result proves the centrality of such massless effective interactions induced by the anomaly, which have recently found realization in solid state, in the theory of topological insulators and of Weyl semimetals. This pattern is confirmed in massless abelian and nonabelian theories (QED and QCD) investigated at one-loop.
Papaleo, Elena; Mereghetti, Paolo; Fantucci, Piercarlo; Grandori, Rita; De Gioia, Luca
2009-01-01
Several molecular dynamics (MD) simulations were used to sample conformations in the neighborhood of the native structure of holo-myoglobin (holo-Mb), collecting trajectories spanning 0.22 micros at 300 K. Principal component (PCA) and free-energy landscape (FEL) analyses, integrated by cluster analysis, which was performed considering the position and structures of the individual helices of the globin fold, were carried out. The coherence between the different structural clusters and the basins of the FEL, together with the convergence of parameters derived by PCA indicates that an accurate description of the Mb conformational space around the native state was achieved by multiple MD trajectories spanning at least 0.14 micros. The integration of FEL, PCA, and structural clustering was shown to be a very useful approach to gain an overall view of the conformational landscape accessible to a protein and to identify representative protein substates. This method could be also used to investigate the conformational and dynamical properties of Mb apo-, mutant, or delete versions, in which greater conformational variability is expected and, therefore identification of representative substates from the simulations is relevant to disclose structure-function relationship.
Tappura, K
2001-08-15
An adjustable-barrier dihedral angle potential was added as an extension to a novel, previously presented soft-core potential to study its contribution to the efficacy of the search of the conformational space in molecular dynamics. As opposed to the conventional soft-core potential functions, the leading principle in the design of the new soft-core potential, as well as of its extension, the soft-core and adjustable-barrier dihedral angle (SCADA) potential (referred as the SCADA potential), was to maintain the main equilibrium properties of the original force field. This qualifies the methods for a variety of a priori modeling problems without need for additional restraints typically required with the conventional soft-core potentials. In the present study, the different potential energy functions are applied to the problem of predicting loop conformations in proteins. Comparison of the performance of the soft-core and SCADA potential showed that the main hurdles for the efficient sampling of the conformational space of (loops in) proteins are related to the high-energy barriers caused by the Lennard-Jones and Coulombic energy terms, and not to the rotational barriers, although the conformational search can be further enhanced by lowering the rotational barriers of the dihedral angles. Finally, different evaluation methods were studied and a few promising criteria found to distinguish the near-native loop conformations from the wrong ones.
Boehm, Markus; Wu, Tong-Ying; Claussen, Holger; Lemmen, Christian
2008-04-24
Large collections of combinatorial libraries are an integral element in today's pharmaceutical industry. It is of great interest to perform similarity searches against all virtual compounds that are synthetically accessible by any such library. Here we describe the successful application of a new software tool CoLibri on 358 combinatorial libraries based on validated reaction protocols to create a single chemistry space containing over 10 (12) possible products. Similarity searching with FTrees-FS allows the systematic exploration of this space without the need to enumerate all product structures. The search result is a set of virtual hits which are synthetically accessible by one or more of the existing reaction protocols. Grouping these virtual hits by their synthetic protocols allows the rapid design and synthesis of multiple follow-up libraries. Such library ideas support hit-to-lead design efforts for tasks like follow-up from high-throughput screening hits or scaffold hopping from one hit to another attractive series.
Frank, Martin
2015-01-01
Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).
A note on φ-analytic conformal vector fields
NASA Astrophysics Data System (ADS)
Deshmukh, Sharief; Bin Turki, Nasser
2017-09-01
Taking clue from the analytic vector fields on a complex manifold, φ-analytic conformal vector fields are defined on a Riemannian manifold (Deshmukh and Al-Solamy in Colloq. Math. 112(1):157-161, 2008). In this paper, we use φ-analytic conformal vector fields to find new characterizations of the n-sphere Sn(c) and the Euclidean space (Rn,<,> ).
Conformational Heterogeneity of the HIV Envelope Glycan Shield.
Yang, Mingjun; Huang, Jing; Simon, Raphael; Wang, Lai-Xi; MacKerell, Alexander D
2017-06-30
To better understand the conformational properties of the glycan shield covering the surface of the HIV gp120/gp41 envelope (Env) trimer, and how the glycan shield impacts the accessibility of the underlying protein surface, we performed enhanced sampling molecular dynamics (MD) simulations of a model glycosylated HIV Env protein and related systems. Our simulation studies revealed a conformationally heterogeneous glycan shield with a network of glycan-glycan interactions more extensive than those observed to date. We found that partial preorganization of the glycans potentially favors binding by established broadly neutralizing antibodies; omission of several specific glycans could increase the accessibility of other glycans or regions of the protein surface to antibody or CD4 receptor binding; the number of glycans that can potentially interact with known antibodies is larger than that observed in experimental studies; and specific glycan conformations can maximize or minimize interactions with individual antibodies. More broadly, the enhanced sampling MD simulations described here provide a valuable tool to guide the engineering of specific Env glycoforms for HIV vaccine design.
Making Space Science and Exploration Accessible
NASA Astrophysics Data System (ADS)
Runyon, C. J.; Guimond, K. A.; Hurd, D.; Heinrich, G.
There are currently 28 million hard of hearing and deaf Americans, approximately 10 to 11 million blind and visually impaired people in North America, and more than 50 million Americans with disabilities, approximately half of whom are students. The majority of students with disabilities in the US are required to achieve the same academic levels as their non-impaired peers. Unfortunately, there are few specialized materials to help these exceptional students in the formal and informal settings. To assist educators in meeting their goals and engage the students, we are working with NASA product developers, scientists and education and outreach personnel in concert with teachers from exceptional classrooms to identify the types of materials they need and which mediums work best for the different student capabilities. Our goal is to make the wonders of space science and exploration accessible to all. As such, over the last four years we have been hosting interactive workshops, observing classroom settings, talking and working with professional educators, product developers, museum and science center personnel and parents to synthesize the most effective media and method for presenting earth and space science materials to audiences with exceptional needs. We will present a list of suggested best practices and example activities that can help engage and encourage a person with special needs to study the sciences, technology, engineering, and mathematics.
Conformational Entropy of Intrinsically Disordered Proteins from Amino Acid Triads
Baruah, Anupaul; Rani, Pooja; Biswas, Parbati
2015-01-01
This work quantitatively characterizes intrinsic disorder in proteins in terms of sequence composition and backbone conformational entropy. Analysis of the normalized relative composition of the amino acid triads highlights a distinct boundary between globular and disordered proteins. The conformational entropy is calculated from the dihedral angles of the middle amino acid in the amino acid triad for the conformational ensemble of the globular, partially and completely disordered proteins relative to the non-redundant database. Both Monte Carlo (MC) and Molecular Dynamics (MD) simulations are used to characterize the conformational ensemble of the representative proteins of each group. The results show that the globular proteins span approximately half of the allowed conformational states in the Ramachandran space, while the amino acid triads in disordered proteins sample the entire range of the allowed dihedral angle space following Flory’s isolated-pair hypothesis. Therefore, only the sequence information in terms of the relative amino acid triad composition may be sufficient to predict protein disorder and the backbone conformational entropy, even in the absence of well-defined structure. The predicted entropies are found to agree with those calculated using mutual information expansion and the histogram method. PMID:26138206
NASA Astrophysics Data System (ADS)
Gord, Joseph R.; Hewett, Daniel M.; Kubasik, Matthew A.; Zwier, Timothy S.
2015-06-01
2-Aminoisobutyric acid (Aib) is an achiral, α-amino acid having two equivalent methyl groups attached to C_α. Extended Aib oligomers are known to have a strong preference for the adoption of a 310-helical structure in the condensed phase. Here, we have taken a simplifying step and focused on the intrinsic folding propensities of Aib by looking at a series of capped Aib oligomers in the gas phase, free from the influence of solvent molecules and cooled in a supersonic expansion. Resonant two-photon ionization and IR-UV holeburning have been used to record single-conformation UV spectra using the Z-cap as the UV chromophore. Resonant ion-dip infrared (RIDIR) spectroscopy provides single-conformation IR spectra in the OH stretch and NH stretch regions. Data have been collected on a set of Z-(Aib)n-X oligomers with n = 1, 2, 4, 6 and X = -OH and -OMethyl. The impacts of these capping groups and differences in backbone length have been found to dramatically influence the conformational space accessed by the molecules studied here. Oligomers of n=4 have sufficient backbone length for a full turn of the 310-helix to be formed. Early interpretation of the data collected shows clear spectroscopic markers signaling the onset of 310-helix formation as well as evidence of structures incorporating C7 and C14 hydrogen bonded rings. Toniolo, C.; Bonora, G. M.; Barone, V.; Bavoso, A.; Benedetti, E.; Di Blasio, B.; Grimaldi, P.; Lelj, F.; Pavone, V.; Pedone, C., Conformation of Pleionomers of α-Aminoisobutyric Acid. Macromolecules 1985, 18, 895-902.
Debeck, Kora; Wood, Evan; Qi, Jiezhi; Fu, Eric; McArthur, Doug; Montaner, Julio; Kerr, Thomas
2012-01-01
Limited attention has been given to the potential role that the structure of housing available to people who are entrenched in street-based drug scenes may play in influencing the amount of time injection drug users (IDU) spend on public streets. We sought to examine the relationship between time spent socializing in Vancouver's drug scene and access to private space. Using multivariate logistic regression we evaluated factors associated with socializing (three+ hours each day) in Vancouver's open drug scene among a prospective cohort of IDU. We also assessed attitudes towards relocating socializing activities if greater access to private indoor space was provided. Among our sample of 1114 IDU, 43% fit our criteria for socializing in the open drug scene. In multivariate analysis, having limited access to private space was independently associated with socializing (adjusted odds ratio: 1.80, 95% confidence interval: 1.28-2.55). In further analysis, 65% of 'socializers' reported positive attitudes towards relocating socializing if they had greater access to private space. These findings suggest that providing IDU with greater access to private indoor space may reduce one component of drug-related street disorder. Low-threshold supportive housing based on the 'housing first' model that include safeguards to manage behaviors associated with illicit drug use appear to offer important opportunities to create the types of private spaces that could support a reduction in street disorder. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Anomalies, conformal manifolds, and spheres
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar
The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space $M$ is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail $N$ = (2; 2) and $N$ = (0; 2) supersymmetric theories in d = 2 and $N$ = 2 supersymmetric theories in d = 4. This reasoning leads tomore » new information about the conformal manifolds of these theories, for example, we show that the manifold is K ahler-Hodge and we further argue that it has vanishing K ahler class. For $N$ = (2; 2) theories in d = 2 and N = 2 theories in d = 4 we also show that the relation between the sphere partition function and the K ahler potential of $M$ follows immediately from the appropriate sigma models that we construct. Ultimately, along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.« less
Anomalies, conformal manifolds, and spheres
NASA Astrophysics Data System (ADS)
Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; Schwimmer, Adam; Seiberg, Nathan; Theisen, Stefan
2016-03-01
The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space {M} is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail {N}=(2,2) and {N}=(0,2) supersymmetric theories in d = 2 and {N}=2 supersymmetric theories in d = 4. This reasoning leads to new information about the conformal manifolds of these theories, for example, we show that the manifold is Kähler-Hodge and we further argue that it has vanishing Kähler class. For {N}=(2,2) theories in d = 2 and {N}=2 theories in d = 4 we also show that the relation between the sphere partition function and the Kähler potential of {M} follows immediately from the appropriate sigma models that we construct. Along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.
DeBeck, Kora; Wood, Evan; Qi, Jiezhi; Fu, Eric; McArthur, Doug; Montaner, Julio; Kerr, Thomas
2011-01-01
Background Limited attention has been given to the potential role that the structure of housing available to people who are entrenched in street-based drug scenes may play in influencing the amount of time injection drug users (IDU) spend on public streets. We sought to examine the relationship between time spent socializing in Vancouver's drug scene and access to private space. Methods Using multivariate logistic regression we evaluated factors associated with socializing (three+ hours each day) in Vancouver's open drug scene among a prospective cohort of IDU. We also assessed attitudes towards relocating socializing activities if greater access to private indoor space was provided. Results Among our sample of 1114 IDU, 43% fit our criteria for socializing in the open drug scene. In multivariate analysis, having limited access to private space was independently associated with socializing (adjusted odds ratio: 1.80, 95% confidence interval: 1.28 – 2.55). In further analysis, 65% of ‘socializers’ reported positive attitudes towards relocating socializing if they had greater access to private space. Conclusion These findings suggest that providing IDU with greater access to private indoor space may reduce one component of drug-related street disorder. Low-threshold supportive housing based on the ‘housing first’ model that include safeguards to manage behaviors associated with illicit drug use appear to offer important opportunities to create the types of private spaces that could support a reduction in street disorder. PMID:21764528
Anomalies, conformal manifolds, and spheres
Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; ...
2016-03-04
The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space $M$ is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail $N$ = (2; 2) and $N$ = (0; 2) supersymmetric theories in d = 2 and $N$ = 2 supersymmetric theories in d = 4. This reasoning leads tomore » new information about the conformal manifolds of these theories, for example, we show that the manifold is K ahler-Hodge and we further argue that it has vanishing K ahler class. For $N$ = (2; 2) theories in d = 2 and N = 2 theories in d = 4 we also show that the relation between the sphere partition function and the K ahler potential of $M$ follows immediately from the appropriate sigma models that we construct. Ultimately, along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.« less
Accessing protein conformational ensembles using room-temperature X-ray crystallography
Fraser, James S.; van den Bedem, Henry; Samelson, Avi J.; Lang, P. Therese; Holton, James M.; Echols, Nathaniel; Alber, Tom
2011-01-01
Modern protein crystal structures are based nearly exclusively on X-ray data collected at cryogenic temperatures (generally 100 K). The cooling process is thought to introduce little bias in the functional interpretation of structural results, because cryogenic temperatures minimally perturb the overall protein backbone fold. In contrast, here we show that flash cooling biases previously hidden structural ensembles in protein crystals. By analyzing available data for 30 different proteins using new computational tools for electron-density sampling, model refinement, and molecular packing analysis, we found that crystal cryocooling remodels the conformational distributions of more than 35% of side chains and eliminates packing defects necessary for functional motions. In the signaling switch protein, H-Ras, an allosteric network consistent with fluctuations detected in solution by NMR was uncovered in the room-temperature, but not the cryogenic, electron-density maps. These results expose a bias in structural databases toward smaller, overpacked, and unrealistically unique models. Monitoring room-temperature conformational ensembles by X-ray crystallography can reveal motions crucial for catalysis, ligand binding, and allosteric regulation. PMID:21918110
Conformal collineations and anisotropic fluids in general relativity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Duggal, K.L.; Sharma, R.
1986-10-01
Recently, Herrera et al. (L. Herrera, J. Jimenez, L. Leal, J. Ponce de Leon, M. Esculpi, and V. Galino, J. Math. Phys. 25, 3274 (1984)) studied the consequences of the existence of a one-parameter group of conformal motions for anisotropic matter. They concluded that for special conformal motions, the stiff equation of state (p = ..mu..) is singled out in a unique way, provided the generating conformal vector field is orthogonal to the four-velocity. In this paper, the same problem is studied by using conformal collineations (which include conformal motions as subgroups). It is shown that, for a special conformalmore » collineation, the stiff equation of state is not singled out. Non-Einstein Ricci-recurrent spaces are considered as physical models for the fluid matter.« less
Research on conformal dome of Karman-curve shape
NASA Astrophysics Data System (ADS)
Zhang, Yunqiang; Chang, Jun; Niu, Yajun
2018-01-01
Because the conformal optical technology can obviously improve the aerodynamic performance of the infrared guidance missile, it has been studied deeply in recent years. By comparing the performance of the missiles with conformal dome and conventional missiles, the advantages of the conformal optical technology are demonstrated in the maneuverability and stealth of the missile. At present, the study of conformal optical systems focuses on ellipsoid or quadratic curve types. But in actual use, the dome using these curves is not the best choice. In this paper, the influence of different shape of the dome on aerodynamic performance, aerodynamic heating, internal space volume and other properties is discussed. The result shows infrared optical system with conformal dome of Karman-curve shape has a good application prospect, is the future direction of development. Finally, the difficult problems of conformal dome of Karman-curve shape are discussed.
Access to green space, physical activity and mental health: a twin study.
Cohen-Cline, Hannah; Turkheimer, Eric; Duncan, Glen E
2015-06-01
Increasing global urbanisation has resulted in a greater proportion of the world's population becoming exposed to risk factors unique to urban areas, and understanding these effects on public health is essential. The aim of this study was to examine the association between access to green space and mental health among adult twin pairs. We used a multilevel random intercept model of same-sex twin pairs (4338 individuals) from the community-based University of Washington Twin Registry to analyse the association between access to green space, as measured by the Normalised Difference Vegetation Index and self-reported depression, stress, and anxiety. The main parameter of interest was the within-pair effect for identical (monozygotic, MZ) twins because it was not subject to confounding by genetic or shared childhood environment factors. Models were adjusted for income, physical activity, neighbourhood deprivation and population density. When treating twins as individuals and not as members of a twin pair, green space was significantly inversely associated with each mental health outcome. The association with depression remained significant in the within-pair MZ univariate and adjusted models; however, there was no within-pair MZ effect for stress or anxiety among the models adjusted for income and physical activity. These results suggest that greater access to green space is associated with less depression, but provide less evidence for effects on stress or anxiety. Understanding the mechanisms linking neighbourhood characteristics to mental health has important public health implications. Future studies should combine twin designs and longitudinal data to strengthen causal inference. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Network visualization of conformational sampling during molecular dynamics simulation.
Ahlstrom, Logan S; Baker, Joseph Lee; Ehrlich, Kent; Campbell, Zachary T; Patel, Sunita; Vorontsov, Ivan I; Tama, Florence; Miyashita, Osamu
2013-11-01
Effective data reduction methods are necessary for uncovering the inherent conformational relationships present in large molecular dynamics (MD) trajectories. Clustering algorithms provide a means to interpret the conformational sampling of molecules during simulation by grouping trajectory snapshots into a few subgroups, or clusters, but the relationships between the individual clusters may not be readily understood. Here we show that network analysis can be used to visualize the dominant conformational states explored during simulation as well as the connectivity between them, providing a more coherent description of conformational space than traditional clustering techniques alone. We compare the results of network visualization against 11 clustering algorithms and principal component conformer plots. Several MD simulations of proteins undergoing different conformational changes demonstrate the effectiveness of networks in reaching functional conclusions. Copyright © 2013 Elsevier Inc. All rights reserved.
Efficient solid rocket propulsion for access to space
NASA Astrophysics Data System (ADS)
Maggi, Filippo; Bandera, Alessio; Galfetti, Luciano; De Luca, Luigi T.; Jackson, Thomas L.
2010-06-01
Space launch activity is expected to grow in the next few years in order to follow the current trend of space exploitation for business purpose. Granting high specific thrust and volumetric specific impulse, and counting on decades of intense development, solid rocket propulsion is a good candidate for commercial access to space, even with common propellant formulations. Yet, some drawbacks such as low theoretical specific impulse, losses as well as safety issues, suggest more efficient propulsion systems, digging into the enhancement of consolidated techniques. Focusing the attention on delivered specific impulse, a consistent fraction of losses can be ascribed to the multiphase medium inside the nozzle which, in turn, is related to agglomeration; a reduction of agglomerate size is likely. The present paper proposes a model based on heterogeneity characterization capable of describing the agglomeration trend for a standard aluminized solid propellant formulation. Material microstructure is characterized through the use of two statistical descriptors (pair correlation function and near-contact particles) looking at the mean metal pocket size inside the bulk. Given the real formulation and density of a propellant, a packing code generates the material representative which is then statistically analyzed. Agglomerate predictions are successfully contrasted to experimental data at 5 bar for four different formulations.
Conformational Preferences of α-Substituted Proline Analogues
Flores-Ortega, Alejandra; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Casanovas, Jordi
2009-01-01
DFT calculations at the B3LYP/6-31+G(d,p) level have been used to investigate how the replacement of the α hydrogen by a more sterically demanding group affects the conformational preferences of proline. Specifically, the N-acetyl-N’-methylamide derivatives of L-proline, L-α-methylproline and L-α-phenylproline have been calculated, with both the cis/trans isomerism of the peptide bonds and the puckering of the pyrrolidine ring being considered. The effects of solvation have been evaluated using a Self Consistent Reaction Field model. As expected, tetrasubstitution at the α carbon destabilizes the conformers with one or more peptide bonds arranged in cis. The lowest energy minimum has been found to be identical for the three compounds investigated, but important differences are observed regarding other energetically accessible backbone conformations. The results obtained provide evidence that the distinct steric requirements of the substituent at Cα may play a significant role in modulating the conformational preferences of proline. PMID:18351745
Exploration of the relationship between topology and designability of conformations
NASA Astrophysics Data System (ADS)
Leelananda, Sumudu P.; Towfic, Fadi; Jernigan, Robert L.; Kloczkowski, Andrzej
2011-06-01
Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the relationship between protein sequence and the three-dimensional (3D) structure that the sequence folds into is an important problem in computational structural biology. Lattice models have been utilized in numerous studies to model protein folds and predict the designability of certain folds. In this study, all possible compact conformations within a set of two-dimensional and 3D lattice spaces are explored. Complementary interaction graphs are then generated for each conformation and are described using a set of graph features. The full HP sequence space for each lattice model is generated and contact energies are calculated by threading each sequence onto all the possible conformations. Unique conformation giving minimum energy is identified for each sequence and the number of sequences folding to each conformation (designability) is obtained. Machine learning algorithms are used to predict the designability of each conformation. We find that the highly designable structures can be distinguished from other non-designable conformations based on certain graphical geometric features of the interactions. This finding confirms the fact that the topology of a conformation is an important determinant of the extent of its designability and suggests that the interactions themselves are important for determining the designability.
Protonation-dependent conformational dynamics of the multidrug transporter EmrE
Dastvan, Reza; Mishra, Smriti; Meiler, Jens; Mchaourab, Hassane S.
2016-01-01
The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient. PMID:26787875
Conformal array design on arbitrary polygon surface with transformation optics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Deng, Li, E-mail: dengl@bupt.edu.cn; Hong, Weijun, E-mail: hongwj@bupt.edu.cn; Zhu, Jianfeng
2016-06-15
A transformation-optics based method to design a conformal antenna array on an arbitrary polygon surface is proposed and demonstrated in this paper. This conformal antenna array can be adjusted to behave equivalently as a uniformly spaced linear array by applying an appropriate transformation medium. An typical example of general arbitrary polygon conformal arrays, not limited to circular array, is presented, verifying the proposed approach. In summary, the novel arbitrary polygon surface conformal array can be utilized in array synthesis and beam-forming, maintaining all benefits of linear array.
Intrinsic Conformational Preferences of Cα,α-Dibenzylglycine
Casanovas, Jordi; Nussinov, Ruth; Alemán, Carlos
2009-01-01
The intrinsic conformational preferences of Cα,α-dibenzylglycine, a symmetric α,α-dialkylated amino acid bearing two benzyl substituents on the α-carbon atom, have been determined using quantum chemical calculations at the B3LYP/6-31+G(d,p) level. A total of 46 minimum energy conformations were found for the N-acetyl-N'-methylamide derivative, even though only 9 of them showed a relative energy lower than 5.0 kcal/mol. The latter involves C7, C5 and α' backbone conformations stabilized by intramolecular hydrogen bonds and/or N-H…π interactions. Calculation of the conformational free energies in different environments (gas-phase, carbon tetrachloride, chloroform, methanol and water solutions) indicates that four different minima (two C5 and two C7) are energetically accessible at room temperature in the gas-phase, while in methanol and aqueous solutions one such minimum (C5) becomes the only significant conformation. Comparison with results recently reported for Cα,α-diphenylglycine indicates that substitution of phenyl side groups by benzyl enhances the conformational flexibility leading to (i) a reduction of the strain of the peptide backbone; and (ii) alleviating the repulsive interactions between the π electron density of the phenyl groups and the lone pairs of the carbonyl oxygen atoms. PMID:18465898
Microscopic insights into the NMR relaxation based protein conformational entropy meter
Kasinath, Vignesh; Sharp, Kim A.; Wand, A. Joshua
2013-01-01
Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven pro! teins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side-chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion - the NMR-derived generalized order parameters - as a proxy from which to derive changes in protein conformational entropy. PMID:24007504
NASA Astrophysics Data System (ADS)
Yaşar, Elif; Yıldırım, Yakup; Yaşar, Emrullah
2018-06-01
This paper devotes to conformable fractional space-time perturbed Gerdjikov-Ivanov (GI) equation which appears in nonlinear fiber optics and photonic crystal fibers (PCF). We consider the model with full nonlinearity in order to give a generalized flavor. The sine-Gordon equation approach is carried out to model equation for retrieving the dark, bright, dark-bright, singular and combined singular optical solitons. The constraint conditions are also reported for guaranteeing the existence of these solitons. We also present some graphical simulations of the solutions for better understanding the physical phenomena of the behind the considered model.
Web Accessibility and Guidelines
NASA Astrophysics Data System (ADS)
Harper, Simon; Yesilada, Yeliz
Access to, and movement around, complex online environments, of which the World Wide Web (Web) is the most popular example, has long been considered an important and major issue in the Web design and usability field. The commonly used slang phrase ‘surfing the Web’ implies rapid and free access, pointing to its importance among designers and users alike. It has also been long established that this potentially complex and difficult access is further complicated, and becomes neither rapid nor free, if the user is disabled. There are millions of people who have disabilities that affect their use of the Web. Web accessibility aims to help these people to perceive, understand, navigate, and interact with, as well as contribute to, the Web, and thereby the society in general. This accessibility is, in part, facilitated by the Web Content Accessibility Guidelines (WCAG) currently moving from version one to two. These guidelines are intended to encourage designers to make sure their sites conform to specifications, and in that conformance enable the assistive technologies of disabled users to better interact with the page content. In this way, it was hoped that accessibility could be supported. While this is in part true, guidelines do not solve all problems and the new WCAG version two guidelines are surrounded by controversy and intrigue. This chapter aims to establish the published literature related to Web accessibility and Web accessibility guidelines, and discuss limitations of the current guidelines and future directions.
Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu
2015-01-01
Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation. PMID:26492886
Why Atens Enjoy Enhanced Accessibility For Human Space Flight
NASA Technical Reports Server (NTRS)
Barbee, Brent; Adamo, Daniel
2011-01-01
In the context of human space flight (HSF), the concept of near-Earth object (NEO) accessibility is highly subjective. Whether or not a particular NEO is accessible critically depends on mass, performance, and reliability of interplanetary HSF systems yet to be designed. Such systems would certainly include propulsion and crew life support with adequate shielding from both solar flares and galactic cosmic radiation. Equally critical architecture options are relevant to NEO accessibility. These options are also far from being determined and include the number of launches supporting an HSF mission, together with whether or not consumables are to be pre-emplaced at the destination. Until the unknowns of HSF to NEOs come into clearer focus, the notion of relative accessibility is of great utility. Imagine a group of NEOs, each with nearly equal HSF merit determined from their individual characteristics relating to crew safety, scientific return, resource utilization, and planetary defense. The more accessible members of this group are more likely to be explored first. A highly accessible NEO could conceivably be deferred in favor of a less accessible HSF destination because the latter is more accessible during a programmatically desirable launch compliant mission trajectory solutions detected in association with a specific NEO. The known NEO population is then surveyed to illustrate in which regions of heliocentric semi-major axis, eccentricity, and inclination (a, e, i) space NEOs with large n values are mapped. The (a, e, i) mapping is also formatted such that membership in each of four NEO orbit classifications, as defined below, is evident. Amors have orbits everywhere superior to (outside of) Earth's. An Amor is therefore defined to have perihelion between 1.017 astronomical units (AU) and the maximum NEO value of 1.3 AU. As of 0 hrs Universal Time on 1 January 2011 (UT epoch 2011.0), Amors numbered 2855 in the Jet Propulsion Laboratory (JPL) Small-Body Database
Noise kernels of stochastic gravity in conformally-flat spacetimes
NASA Astrophysics Data System (ADS)
Cho, H. T.; Hu, B. L.
2015-03-01
The central object in the theory of semiclassical stochastic gravity is the noise kernel, which is the symmetric two point correlation function of the stress-energy tensor. Using the corresponding Wightman functions in Minkowski, Einstein and open Einstein spaces, we construct the noise kernels of a conformally coupled scalar field in these spacetimes. From them we show that the noise kernels in conformally-flat spacetimes, including the Friedmann-Robertson-Walker universes, can be obtained in closed analytic forms by using a combination of conformal and coordinate transformations.
Swellix: a computational tool to explore RNA conformational space.
Sloat, Nathan; Liu, Jui-Wen; Schroeder, Susan J
2017-11-21
The sequence of nucleotides in an RNA determines the possible base pairs for an RNA fold and thus also determines the overall shape and function of an RNA. The Swellix program presented here combines a helix abstraction with a combinatorial approach to the RNA folding problem in order to compute all possible non-pseudoknotted RNA structures for RNA sequences. The Swellix program builds on the Crumple program and can include experimental constraints on global RNA structures such as the minimum number and lengths of helices from crystallography, cryoelectron microscopy, or in vivo crosslinking and chemical probing methods. The conceptual advance in Swellix is to count helices and generate all possible combinations of helices rather than counting and combining base pairs. Swellix bundles similar helices and includes improvements in memory use and efficient parallelization. Biological applications of Swellix are demonstrated by computing the reduction in conformational space and entropy due to naturally modified nucleotides in tRNA sequences and by motif searches in Human Endogenous Retroviral (HERV) RNA sequences. The Swellix motif search reveals occurrences of protein and drug binding motifs in the HERV RNA ensemble that do not occur in minimum free energy or centroid predicted structures. Swellix presents significant improvements over Crumple in terms of efficiency and memory use. The efficient parallelization of Swellix enables the computation of sequences as long as 418 nucleotides with sufficient experimental constraints. Thus, Swellix provides a practical alternative to free energy minimization tools when multiple structures, kinetically determined structures, or complex RNA-RNA and RNA-protein interactions are present in an RNA folding problem.
The Road from the NASA Access to Space Study to a Reusable Launch Vehicle
NASA Technical Reports Server (NTRS)
Powell, Richard W.; Cook, Stephen A.; Lockwood, Mary Kae
1998-01-01
NASA is cooperating with the aerospace industry to develop a space transportation system that provides reliable access-to-space at a much lower cost than is possible with today's launch vehicles. While this quest has been on-going for many years it received a major impetus when the U.S. Congress mandated as part of the 1993 NASA appropriations bill that: "In view of budget difficulties, present and future..., the National Aeronautics and Space Administration shall ... recommend improvements in space transportation." NASA, working with other organizations, including the Department of Transportation, and the Department of Defense identified three major transportation architecture options that were to be evaluated in the areas of reliability, operability and cost. These architectural options were: (1) retain and upgrade the Space Shuttle and the current expendable launch vehicles; (2) develop new expendable launch vehicles using conventional technologies and transition to these new vehicles beginning in 2005; and (3) develop new reusable vehicles using advanced technology, and transition to these vehicles beginning in 2008. The launch needs mission model was based on 1993 projections of civil, defense, and commercial payload requirements. This "Access to Space" study concluded that the option that provided the greatest potential for meeting the cost, operability, and reliability goals was a rocket-powered single-stage-to-orbit fully reusable launch vehicle (RLV) fleet designed with advanced technologies.
Probabilistic sampling of protein conformations: new hope for brute force?
Feldman, Howard J; Hogue, Christopher W V
2002-01-01
Protein structure prediction from sequence alone by "brute force" random methods is a computationally expensive problem. Estimates have suggested that it could take all the computers in the world longer than the age of the universe to compute the structure of a single 200-residue protein. Here we investigate the use of a faster version of our FOLDTRAJ probabilistic all-atom protein-structure-sampling algorithm. We have improved the method so that it is now over twenty times faster than originally reported, and capable of rapidly sampling conformational space without lattices. It uses geometrical constraints and a Leonard-Jones type potential for self-avoidance. We have also implemented a novel method to add secondary structure-prediction information to make protein-like amounts of secondary structure in sampled structures. In a set of 100,000 probabilistic conformers of 1VII, 1ENH, and 1PMC generated, the structures with smallest Calpha RMSD from native are 3.95, 5.12, and 5.95A, respectively. Expanding this test to a set of 17 distinct protein folds, we find that all-helical structures are "hit" by brute force more frequently than beta or mixed structures. For small helical proteins or very small non-helical ones, this approach should have a "hit" close enough to detect with a good scoring function in a pool of several million conformers. By fitting the distribution of RMSDs from the native state of each of the 17 sets of conformers to the extreme value distribution, we are able to estimate the size of conformational space for each. With a 0.5A RMSD cutoff, the number of conformers is roughly 2N where N is the number of residues in the protein. This is smaller than previous estimates, indicating an average of only two possible conformations per residue when sterics are accounted for. Our method reduces the effective number of conformations available at each residue by probabilistic bias, without requiring any particular discretization of residue conformational
Evidence for conformational capture mechanism for damage recognition by NER protein XPC/Rad4.
NASA Astrophysics Data System (ADS)
Chakraborty, Sagnik; Steinbach, Peter J.; Paul, Debamita; Min, Jung-Hyun; Ansari, Anjum
Altered flexibility of damaged DNA sites is considered to play an important role in damage recognition by DNA repair proteins. Characterizing lesion-induced DNA dynamics has remained a challenge. We have combined ps-resolved fluorescence lifetime measurements with cytosine analog FRET pair uniquely sensitive to local unwinding/twisting to analyze DNA conformational distributions. This innovative approach maps out with unprecedented sensitivity the alternative conformations accessible to a series of DNA constructs containing 3-base-pair mismatch, suitable model lesions for the DNA repair protein xeroderma pigmentosum C (XPC) complex. XPC initiates eukaryotic nucleotide excision repair by recognizing various DNA lesions primarily through DNA deformability. Structural studies show that Rad4 (yeast ortholog of XPC) unwinds DNA at the lesion site and flips out two nucleotide pairs. Our results elucidate a broad range of conformations accessible to mismatched DNA even in the absence of the protein. Notably, the most severely distorted conformations share remarkable resemblance to the deformed conformation seen in the crystal structure of the Rad4-bound ``recognition'' complex supporting for the first time a possible ``conformational capture'' mechanism for damage recognition by XPC/Rad4. NSF Univ of Illinois-Chicago.
Anti-de Sitter-space/conformal-field-theory Casimir energy for rotating black holes.
Gibbons, G W; Perry, M J; Pope, C N
2005-12-02
We show that, if one chooses the Einstein static universe as the metric on the conformal boundary of Kerr-anti-de Sitter spacetime, then the Casimir energy of the boundary conformal field theory can easily be determined. The result is independent of the rotation parameters, and the total boundary energy then straightforwardly obeys the first law of thermodynamics. Other choices for the metric on the conformal boundary will give different, more complicated, results. As an application, we calculate the Casimir energy for free self-dual tensor multiplets in six dimensions and compare it with that of the seven-dimensional supergravity dual. They differ by a factor of 5/4.
Karch, Andreas; Sully, James; Uhlemann, Christoph F.; ...
2017-08-10
We extend kinematic space to a simple scenario where the state is not fixed by conformal invariance: the vacuum of a conformal field theory with a boundary (bCFT). We identify the kinematic space associated with the boundary operator product expansion (bOPE) as a subspace of the full kinematic space. In addition, we establish representations of the corresponding bOPE blocks in a dual gravitational description. We show how the new kinematic dictionary and the dynamical data in bOPE allows one to reconstruct the bulk geometry. This is evidence that kinematic space may be a useful construction for understanding bulk physics beyondmore » just kinematics.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Karch, Andreas; Sully, James; Uhlemann, Christoph F.
We extend kinematic space to a simple scenario where the state is not fixed by conformal invariance: the vacuum of a conformal field theory with a boundary (bCFT). We identify the kinematic space associated with the boundary operator product expansion (bOPE) as a subspace of the full kinematic space. In addition, we establish representations of the corresponding bOPE blocks in a dual gravitational description. We show how the new kinematic dictionary and the dynamical data in bOPE allows one to reconstruct the bulk geometry. This is evidence that kinematic space may be a useful construction for understanding bulk physics beyondmore » just kinematics.« less
National Report Norway: Arctic Access to Space
NASA Astrophysics Data System (ADS)
Brekke, P.
2015-09-01
Norway has long traditions as a space nation, much due to our northern latitude. Our space science activities are concentrated into relatively few areas. This concentration is necessary due to limited resources, both in funding and personnel. The main scientific activities are within Solar-terrestrial physics and cosmology. The first field has been a priority since before the space age and is still the major priority. The usage of the ground infrastructure in Northern Norway and on Svalbard is essential in studying the middle and upper atmosphere and the interaction with the Sun. This includes the utilization of sounding rockets, both small and large, and ground based installations like radars, lidars and other optical instrumentation. The planned use of Svalbard as a launch site for large stratospheric balloons may allow the cosmology community access to our northern infrastructure. The solar physics community is also heavily involved in the HINODE and IRIS missions and Norway is supporting downlink of data via the Svalbard Station for these missions. The sounding rocket program is in close collaboration with many countries like Germany, USA, France, Canada and Japan. Two scientific sounding rocket programs are currently being pursued: The ICI series (from Svalbard) and MaxiDusty (from Andoya). A series of scientific publications have recently appeared from the ECOMA campaign a few years ago. A significant improvement of today's polar and ionospheric research infrastructure in Northern Norway and Svalbard has recently been put on the ESFRI roadmap for European research infrastructure through the 5105 and EISCAT 3D initiatives. The Norwegian government has recently decided to upgrade the VLBI facilities at Svalbard.
Focused conformational sampling in proteins
NASA Astrophysics Data System (ADS)
Bacci, Marco; Langini, Cassiano; Vymětal, Jiří; Caflisch, Amedeo; Vitalis, Andreas
2017-11-01
A detailed understanding of the conformational dynamics of biological molecules is difficult to obtain by experimental techniques due to resolution limitations in both time and space. Computer simulations avoid these in theory but are often too short to sample rare events reliably. Here we show that the progress index-guided sampling (PIGS) protocol can be used to enhance the sampling of rare events in selected parts of biomolecules without perturbing the remainder of the system. The method is very easy to use as it only requires as essential input a set of several features representing the parts of interest sufficiently. In this feature space, new states are discovered by spontaneous fluctuations alone and in unsupervised fashion. Because there are no energetic biases acting on phase space variables or projections thereof, the trajectories PIGS generates can be analyzed directly in the framework of transition networks. We demonstrate the possibility and usefulness of such focused explorations of biomolecules with two loops that are part of the binding sites of bromodomains, a family of epigenetic "reader" modules. This real-life application uncovers states that are structurally and kinetically far away from the initial crystallographic structures and are also metastable. Representative conformations are intended to be used in future high-throughput virtual screening campaigns.
Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin
NASA Astrophysics Data System (ADS)
Lermyte, Frederik; Łącki, Mateusz Krzysztof; Valkenborg, Dirk; Gambin, Anna; Sobott, Frank
2017-01-01
Owing to its versatility, electron transfer dissociation (ETD) has become one of the most commonly utilized fragmentation techniques in both native and non-native top-down mass spectrometry. However, several competing reactions—primarily different forms of charge reduction—occur under ETD conditions, as evidenced by the distorted isotope patterns usually observed. In this work, we analyze these isotope patterns to compare the stability of nondissociative electron transfer (ETnoD) products, specifically noncovalent c/ z fragment complexes, across a range of ubiquitin conformational states. Using ion mobility, we find that more extended states are more prone to fragment release. We obtain evidence that for a given charge state, populations of ubiquitin ions formed either directly by electrospray ionization or through collapse of more extended states upon charge reduction, span a similar range of collision cross-sections. Products of gas-phase collapse are, however, less stabilized towards unfolding than the native conformation, indicating that the ions retain a memory of previous conformational states. Furthermore, this collapse of charge-reduced ions is promoted if the ions are `preheated' using collisional activation, with possible implications for the kinetics of gas-phase compaction.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.
2008-07-08
B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reducesmore » the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.« less
NASA Technical Reports Server (NTRS)
Chassay, Charles
1987-01-01
The integration process of activities conducted at the NASA Lyndon B. Johnson Space Center (JSC) for the Experimental Assembly of Structures in Extravehicular activity (EASE)/Assembly Concept for Construction of Erectable Space Structures (ACCESS) payload is provided as a subset to the standard payload integration process used by the NASA Space Transportation System (STS) to fly payloads on the Space Shuttle. The EASE/ACCESS payload integration activities are chronologically reviewed beginning with the initiation of the flight manifesting and integration process. The development and documentation of the EASE/ACCESS integration requirements are also discussed along with the implementation of the mission integration activities and the engineering assessments supporting the flight integration process. In addition, the STS management support organizations, the payload safety process leading to the STS 61-B flight certification, and the overall EASE/ACCESS integration schedule are presented.
Enabling Dedicated, Affordable Space Access Through Aggressive Technology Maturation
NASA Technical Reports Server (NTRS)
Jones, Jonathan; Kibbey, Tim; Lampton, Pat; Brown, Thomas
2014-01-01
A recent explosion in nano-sat, small-sat, and university class payloads has been driven by low cost electronics and sensors, wide component availability, as well as low cost, miniature computational capability and open source code. Increasing numbers of these very small spacecraft are being launched as secondary payloads, dramatically decreasing costs, and allowing greater access to operations and experimentation using actual space flight systems. While manifesting as a secondary payload provides inexpensive rides to orbit, these arrangements also have certain limitations. Small, secondary payloads are typically included with very limited payload accommodations, supported on a non interference basis (to the prime payload), and are delivered to orbital conditions driven by the primary launch customer. Integration of propulsion systems or other hazardous capabilities will further complicate secondary launch arrangements, and accommodation requirements. The National Aeronautics and Space Administration's Marshall Space Flight Center has begun work on the development of small, low cost launch system concepts that could provide dedicated, affordable launch alternatives to small, risk tolerant university type payloads and spacecraft. These efforts include development of small propulsion systems and highly optimized structural efficiency, utilizing modern advanced manufacturing techniques. This paper outlines the plans and accomplishments of these efforts and investigates opportunities for truly revolutionary reductions in launch and operations costs. Both evolution of existing sounding rocket systems to orbital delivery, and the development of clean sheet, optimized small launch systems are addressed. A launch vehicle at the scale and price point which allows developers to take reasonable risks with new propulsion and avionics hardware solutions does not exist today. Establishing this service provides a ride through the proverbial "valley of death" that lies between
Quantum integrable systems from conformal blocks
NASA Astrophysics Data System (ADS)
Chen, Heng-Yu; Qualls, Joshua D.
2017-05-01
In this note, we extend the striking connections between quantum integrable systems and conformal blocks recently found in [M. Isachenkov and V. Schomerus, Phys. Rev. Lett. 117, 071602 (2016), 10.1103/PhysRevLett.117.071602] in several directions. First, we explicitly demonstrate that the action of the quartic conformal Casimir operator on general d-dimensional scalar conformal blocks can be expressed in terms of certain combinations of commuting integrals of motions of the two particle hyperbolic BC2 Calogero-Sutherland system. The permutation and reflection properties of the underlying Dunkl operators play crucial roles in establishing such a connection. Next, we show that the scalar superconformal blocks in superconformal field theories (SCFTs) with four and eight supercharges and suitable chirality constraints can also be identified with the eigenfunctions of the same Calogero-Sutherland system; this demonstrates the universality of such a connection. Finally, we observe that the so-called "seed" conformal blocks for constructing four point functions for operators with arbitrary space-time spins in four-dimensional CFTs can also be linearly expanded in terms of Calogero-Sutherland eigenfunctions.
Constrained proper sampling of conformations of transition state ensemble of protein folding
Lin, Ming; Zhang, Jian; Lu, Hsiao-Mei; Chen, Rong; Liang, Jie
2011-01-01
Characterizing the conformations of protein in the transition state ensemble (TSE) is important for studying protein folding. A promising approach pioneered by Vendruscolo [Nature (London) 409, 641 (2001)] to study TSE is to generate conformations that satisfy all constraints imposed by the experimentally measured ϕ values that provide information about the native likeness of the transition states. Faísca [J. Chem. Phys. 129, 095108 (2008)] generated conformations of TSE based on the criterion that, starting from a TS conformation, the probabilities of folding and unfolding are about equal through Markov Chain Monte Carlo (MCMC) simulations. In this study, we use the technique of constrained sequential Monte Carlo method [Lin , J. Chem. Phys. 129, 094101 (2008); Zhang Proteins 66, 61 (2007)] to generate TSE conformations of acylphosphatase of 98 residues that satisfy the ϕ-value constraints, as well as the criterion that each conformation has a folding probability of 0.5 by Monte Carlo simulations. We adopt a two stage process and first generate 5000 contact maps satisfying the ϕ-value constraints. Each contact map is then used to generate 1000 properly weighted conformations. After clustering similar conformations, we obtain a set of properly weighted samples of 4185 candidate clusters. Representative conformation of each of these cluster is then selected and 50 runs of Markov chain Monte Carlo (MCMC) simulation are carried using a regrowth move set. We then select a subset of 1501 conformations that have equal probabilities to fold and to unfold as the set of TSE. These 1501 samples characterize well the distribution of transition state ensemble conformations of acylphosphatase. Compared with previous studies, our approach can access much wider conformational space and can objectively generate conformations that satisfy the ϕ-value constraints and the criterion of 0.5 folding probability without bias. In contrast to previous studies, our results show that
Supergravitational conformal Galileons
NASA Astrophysics Data System (ADS)
Deen, Rehan; Ovrut, Burt
2017-08-01
The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and "bouncing" cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory, but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios
Homologous ligands accommodated by discrete conformations of a buried cavity
Merski, Matthew; Fischer, Marcus; Balius, Trent E.; Eidam, Oliv; Shoichet, Brian K.
2015-01-01
Conformational change in protein–ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design. PMID:25847998
Homologous ligands accommodated by discrete conformations of a buried cavity.
Merski, Matthew; Fischer, Marcus; Balius, Trent E; Eidam, Oliv; Shoichet, Brian K
2015-04-21
Conformational change in protein-ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design.
Ares Launch Vehicles Overview: Space Access Society
NASA Technical Reports Server (NTRS)
Cook, Steve
2007-01-01
America is returning to the Moon in preparation for the first human footprint on Mars, guided by the U.S. Vision for Space Exploration. This presentation will discuss NASA's mission, the reasons for returning to the Moon and going to Mars, and how NASA will accomplish that mission in ways that promote leadership in space and economic expansion on the new frontier. The primary goals of the Vision for Space Exploration are to finish the International Space Station, retire the Space Shuttle, and build the new spacecraft needed to return people to the Moon and go to Mars. The Vision commits NASA and the nation to an agenda of exploration that also includes robotic exploration and technology development, while building on lessons learned over 50 years of hard-won experience. NASA is building on common hardware, shared knowledge, and unique experience derived from the Apollo Saturn, Space Shuttle, and contemporary commercial launch vehicle programs. The journeys to the Moon and Mars will require a variety of vehicles, including the Ares I Crew Launch Vehicle, which transports the Orion Crew Exploration Vehicle, and the Ares V Cargo Launch Vehicle, which transports the Lunar Surface Access Module. The architecture for the lunar missions will use one launch to ferry the crew into orbit, where it will rendezvous with the Lunar Module in the Earth Departure Stage, which will then propel the combination into lunar orbit. The imperative to explore space with the combination of astronauts and robots will be the impetus for inventions such as solar power and water and waste recycling. This next chapter in NASA's history promises to write the next chapter in American history, as well. It will require this nation to provide the talent to develop tools, machines, materials, processes, technologies, and capabilities that can benefit nearly all aspects of life on Earth. Roles and responsibilities are shared between a nationwide Government and industry team. The Exploration Launch
Conformational and stereoelectronic investigation of tryptamine. An AIM/NBO study.
Lobayan, Rosana M; Pérez Schmit, María C; Jubert, Alicia H; Vitale, Arturo
2012-06-01
Due to the free radical scavenger properties of Tryptamine (TRA), as well as of others indole derivatives, it is in our interest to explore deeply the stereoelectronic aspects that would be relevant in their stabilization and antioxidant activity. In this work the conformational space of TRA was scanned using molecular dynamics complemented with functional density calculations at B3LYP/6-31 + G** level. Twenty one conformers of lowest energy were obtained, their electronic distributions were analyzed at a higher calculation level, thus improving the basis set (B3LYP/6-311++G**). A topological study based on Bader's theory ( atoms in molecules) and natural bond orbital (NBO) framework was performed. The study was enriched by a deep analysis of maps of molecular electrostatic potential (MEP) through a coordinated NBO/AIM analysis. The conformational preferences were explained by hyperconjugative interactions, which were revealed by NBO data. Because radical scavenging by indolic compounds is strongly modulated by their functional residues our study was related to similar analysis done previously on Indole and 1H-indole-3-acetic acid (IAA). Therefore, the conformational space of TRA was studied from a new perspective focusing on a deep analysis of the geometric and electronic properties of TRA conformers. The changes of the electronic distribution introduced by the substituent and the conformational flexibility of the side chain were addressed. The results reported contribute to the understanding of the structure, stability and reactivity of TRA and others indole derivatives.
Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro
2004-05-01
A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.
Accessing space: A catalogue of process, equipment and resources for commercial users
NASA Technical Reports Server (NTRS)
1988-01-01
This catalogue, produced by NASA's Office of Commercial Programs, provides a broad source of information for the commercial developer interested in the areas of microgravity research and remote sensing. Methods for accessing space for research are reviewed including the shuttle, expendable launch vehicles, suborbital sounding rockets, experimental aircraft, and drop towers and other ground-based facilities. Procedures for using these vehicles and facilities are described along with funding options to pay for their use. Experiment apparatus and carriers for microgravity research are also described. A separate directory of resources and services is also included which contains a listing of transportation products and services, a listing of businesses and industries which provide space-related services and products, and a listing of the NASA and CCDS (Center for the Commercial Development of Space) points of contact.
Backbone conformational preferences of an intrinsically disordered protein in solution.
Espinoza-Fonseca, L Michel; Ilizaliturri-Flores, Ian; Correa-Basurto, José
2012-06-01
We have performed a 4-μs molecular dynamics simulation to investigate the native conformational preferences of the intrinsically disordered kinase-inducible domain (KID) of the transcription factor CREB in solution. There is solid experimental evidence showing that KID does not possess a bound-like structure in solution; however, it has been proposed that coil-to-helix transitions upon binding to its binding partner (CBP) are template-driven. While these studies indicate that IDPs possess a bias towards the bound structure, they do not provide direct evidence on the time-dependent conformational preferences of IDPs in atomic detail. Our simulation captured intrinsic conformational characteristics of KID that are in good agreement with experimental data such as a very small percentage of helical structure in its segment α(B) and structural disorder in solution. We used dihedral principal component analysis dPCA to map the conformations of KID in the microsecond timescale. By using principal components as reaction coordinates, we further constructed dPCA-based free energy landscapes of KID. Analysis of the free energy landscapes showed that KID is best characterized as a conformational ensemble of rapidly interconverting conformations. Interestingly, we found that despite the conformational heterogeneity of the backbone and the absence of substantial secondary structure, KID does not randomly sample the conformational space in solution: analysis of the (Φ, Ψ) dihedral angles showed that several individual residues of KID possess a strong bias toward the helical region of the Ramachandran plot. We suggest that the intrinsic conformational preferences of KID provide a bias toward the folded state without having to populate bound-like conformations before binding. Furthermore, we argue that these conformational preferences do not represent actual structural constraints which drive binding through a single pathway, which allows for specific interactions with multiple
Clausen, Rudy; Ma, Buyong; Nussinov, Ruth; Shehu, Amarda
2015-01-01
An important goal in molecular biology is to understand functional changes upon single-point mutations in proteins. Doing so through a detailed characterization of structure spaces and underlying energy landscapes is desirable but continues to challenge methods based on Molecular Dynamics. In this paper we propose a novel algorithm, SIfTER, which is based instead on stochastic optimization to circumvent the computational challenge of exploring the breadth of a protein’s structure space. SIfTER is a data-driven evolutionary algorithm, leveraging experimentally-available structures of wildtype and variant sequences of a protein to define a reduced search space from where to efficiently draw samples corresponding to novel structures not directly observed in the wet laboratory. The main advantage of SIfTER is its ability to rapidly generate conformational ensembles, thus allowing mapping and juxtaposing landscapes of variant sequences and relating observed differences to functional changes. We apply SIfTER to variant sequences of the H-Ras catalytic domain, due to the prominent role of the Ras protein in signaling pathways that control cell proliferation, its well-studied conformational switching, and abundance of documented mutations in several human tumors. Many Ras mutations are oncogenic, but detailed energy landscapes have not been reported until now. Analysis of SIfTER-computed energy landscapes for the wildtype and two oncogenic variants, G12V and Q61L, suggests that these mutations cause constitutive activation through two different mechanisms. G12V directly affects binding specificity while leaving the energy landscape largely unchanged, whereas Q61L has pronounced, starker effects on the landscape. An implementation of SIfTER is made available at http://www.cs.gmu.edu/~ashehu/?q=OurTools. We believe SIfTER is useful to the community to answer the question of how sequence mutations affect the function of a protein, when there is an abundance of experimental
Zhu, Lizhe; Bolhuis, Peter G.; Vreede, Jocelyne
2013-01-01
The HAMP domain is a linker region in prokaryotic sensor proteins and relays input signals to the transmitter domain and vice versa. Functional as a dimer, the structure of HAMP shows a parallel coiled-coil motif comprising four helices. To date, it is unclear how HAMP can relay signals from one domain to another, although several models exist. In this work, we use molecular simulation to test the hypothesis that HAMP adopts different conformations, one of which represents an active, signal-relaying configuration, and another an inactive, resting state. We first performed molecular dynamics simulation on the prototype HAMP domain Af1503 from Archaeoglobus fulgidus. We explored its conformational space by taking the structure of the A291F mutant disabling HAMP activity as a starting point. These simulations revealed additional conformational states that differ in the tilt angles between the helices as well as the relative piston shifts of the helices relative to each other. By enhancing the sampling in a metadynamics set up, we investigated three mechanistic models for HAMP signal transduction. Our results indicate that HAMP can access additional conformational states characterized by piston motion. Furthermore, the piston motion of the N-terminal helix of one monomer is directly correlated with the opposite piston motion of the C-terminal helix of the other monomer. The change in piston motion is accompanied by a change in tilt angle between the monomers, thus revealing that HAMP exhibits a collective motion, i.e. a combination of changes in tilt angles and a piston-like displacement. Our results provide insights into the conformational changes that underlie the signaling mechanism involving HAMP. PMID:23468603
Enhanced conformational sampling using enveloping distribution sampling.
Lin, Zhixiong; van Gunsteren, Wilfred F
2013-10-14
To lessen the problem of insufficient conformational sampling in biomolecular simulations is still a major challenge in computational biochemistry. In this article, an application of the method of enveloping distribution sampling (EDS) is proposed that addresses this challenge and its sampling efficiency is demonstrated in simulations of a hexa-β-peptide whose conformational equilibrium encompasses two different helical folds, i.e., a right-handed 2.7(10∕12)-helix and a left-handed 3(14)-helix, separated by a high energy barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force field did not reach convergence of the free enthalpy difference between the two helices even after 500 ns of simulation time. The use of soft-core non-bonded interactions in the centre of the peptide did enhance the number of transitions between the helices, but at the same time led to neglect of relevant helical configurations. In the simulations of a two-state EDS reference Hamiltonian that envelops both the physical peptide and the soft-core peptide, sampling of the conformational space of the physical peptide ensures that physically relevant conformations can be visited, and sampling of the conformational space of the soft-core peptide helps to enhance the transitions between the two helices. The EDS simulations sampled many more transitions between the two helices and showed much faster convergence of the relative free enthalpy of the two helices compared with the standard MD simulations with only a slightly larger computational effort to determine optimized EDS parameters. Combined with various methods to smoothen the potential energy surface, the proposed EDS application will be a powerful technique to enhance the sampling efficiency in biomolecular simulations.
Prediction of conformationally dependent atomic multipole moments in carbohydrates
Cardamone, Salvatore
2015-01-01
The conformational flexibility of carbohydrates is challenging within the field of computational chemistry. This flexibility causes the electron density to change, which leads to fluctuating atomic multipole moments. Quantum Chemical Topology (QCT) allows for the partitioning of an “atom in a molecule,” thus localizing electron density to finite atomic domains, which permits the unambiguous evaluation of atomic multipole moments. By selecting an ensemble of physically realistic conformers of a chemical system, one evaluates the various multipole moments at defined points in configuration space. The subsequent implementation of the machine learning method kriging delivers the evaluation of an analytical function, which smoothly interpolates between these points. This allows for the prediction of atomic multipole moments at new points in conformational space, not trained for but within prediction range. In this work, we demonstrate that the carbohydrates erythrose and threose are amenable to the above methodology. We investigate how kriging models respond when the training ensemble incorporating multiple energy minima and their environment in conformational space. Additionally, we evaluate the gains in predictive capacity of our models as the size of the training ensemble increases. We believe this approach to be entirely novel within the field of carbohydrates. For a modest training set size of 600, more than 90% of the external test configurations have an error in the total (predicted) electrostatic energy (relative to ab initio) of maximum 1 kJ mol−1 for open chains and just over 90% an error of maximum 4 kJ mol−1 for rings. © 2015 Wiley Periodicals, Inc. PMID:26547500
Prediction of conformationally dependent atomic multipole moments in carbohydrates.
Cardamone, Salvatore; Popelier, Paul L A
2015-12-15
The conformational flexibility of carbohydrates is challenging within the field of computational chemistry. This flexibility causes the electron density to change, which leads to fluctuating atomic multipole moments. Quantum Chemical Topology (QCT) allows for the partitioning of an "atom in a molecule," thus localizing electron density to finite atomic domains, which permits the unambiguous evaluation of atomic multipole moments. By selecting an ensemble of physically realistic conformers of a chemical system, one evaluates the various multipole moments at defined points in configuration space. The subsequent implementation of the machine learning method kriging delivers the evaluation of an analytical function, which smoothly interpolates between these points. This allows for the prediction of atomic multipole moments at new points in conformational space, not trained for but within prediction range. In this work, we demonstrate that the carbohydrates erythrose and threose are amenable to the above methodology. We investigate how kriging models respond when the training ensemble incorporating multiple energy minima and their environment in conformational space. Additionally, we evaluate the gains in predictive capacity of our models as the size of the training ensemble increases. We believe this approach to be entirely novel within the field of carbohydrates. For a modest training set size of 600, more than 90% of the external test configurations have an error in the total (predicted) electrostatic energy (relative to ab initio) of maximum 1 kJ mol(-1) for open chains and just over 90% an error of maximum 4 kJ mol(-1) for rings. © 2015 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Hazboun, Jeffrey Shafiq
2014-10-01
Cartan geometry provides a rich formalism from which to look at various geometrically motivated extensions to general relativity. In this manuscript, we start by motivating reasons to extend the theory of general relativity. We then introduce the reader to our technique, called the quotient manifold method, for extending the geometry of spacetime. We will specifically look at the class of theories formed from the various quotients of the conformal group. Starting with the conformal symmetries of Euclidean space, we construct a manifold where time manifests as a part of the geometry. Though there is no matter present in the geome- try studied here, geometric terms analogous to dark energy and dark matter appear when we write down the Einstein tensor. Specifically, the quotient of the conformal group of Euclidean four-space by its Weyl subgroup results in a geometry possessing many of the properties of relativistic phase space, including both a natural symplectic form and nondegenerate Killing metric. We show the general solution possesses orthogonal Lagrangian submanifolds, with the induced metric and the spin connection on the submanifolds necessarily Lorentzian, despite the Euclidean starting point. By examining the structure equations of the biconformal space in an orthonormal frame adapted to its phase space properties, we also find two new tensor fields exist in this geometry, not present in Riemannian geometry. The first is a combination of the Weyl vector with the scale factor on the metric, and determines the time-like directions on the submanifolds. The second comes from the components of the spin connection, symmetric with respect to the new metric. Though this field comes from the spin connection, it transforms ho- mogeneously. Finally, we show in the absence of Cartan curvature or sources, the configuration space has geometric terms equivalent to a perfect fluid and a cosmological constant. We complete the analysis of this homogeneous space by
NASA Technical Reports Server (NTRS)
Lulla, Kamlesh
1994-01-01
There have been many significant improvements in the public access to the Space Shuttle Earth Observations Photography Database. New information is provided for the user community on the recently released videodisc of this database. Topics covered included the following: earlier attempts; our first laser videodisc in 1992; the new laser videodisc in 1994; and electronic database access.
Does Access to Green Space Impact the Mental Well-being of Children: A Systematic Review.
McCormick, Rachel
An increasing body of research is showing associations between green space and overall health. Children are spending more time indoors while pediatric mental and behavioral health problems are increasing. A systematic review of the literature was done to examine the association between access to green space and the mental well-being of children. Articles were limited to English language, ages 0-18 years, and publish date 2012-2017. The search yielded 341 articles in Ovid, 81 in Pub Med and 123 in Scopus. Articles that were not original research and that were not a pediatric population were excluded. Twelve articles fit the selection criteria. Twelve articles relating to green space and the mental well-being of children were reviewed. Three articles outside the date criteria were included as they are cited often in the literature as important early research on this topic. Access to green space was associated with improved mental well-being, overall health and cognitive development of children. It promotes attention restoration, memory, competence, supportive social groups, self-discipline, moderates stress, improves behaviors and symptoms of ADHD and was even associated with higher standardized test scores. Scientific evidence demonstrating the mental health benefits of access to nature for children can guide policy and urban planning, while nursing interventions and initiatives can enhance health by promoting outdoor play, educating patients and families, advocating for recess times and green environments at school as well as healing gardens in hospital settings. Copyright © 2017 Elsevier Inc. All rights reserved.
A surprising role for conformational entropy in protein function
Wand, A. Joshua; Moorman, Veronica R.; Harpole, Kyle W.
2014-01-01
Formation of high-affinity complexes is critical for the majority of enzymatic reactions involving proteins. The creation of the family of Michaelis and other intermediate complexes during catalysis clearly involves a complicated manifold of interactions that are diverse and complex. Indeed, computing the energetics of interactions between proteins and small molecule ligands using molecular structure alone remains a grand challenge. One of the most difficult contributions to the free energy of protein-ligand complexes to experimentally access is that due to changes in protein conformational entropy. Fortunately, recent advances in solution nuclear magnetic resonance (NMR) relaxation methods have enabled the use of measures-of-motion between conformational states of a protein as a proxy for conformational entropy. This review briefly summarizes the experimental approaches currently employed to characterize fast internal motion in proteins, how this information is used to gain insight into conformational entropy, what has been learned and what the future may hold for this emerging view of protein function. PMID:23478875
Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui
2014-10-21
The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N-H···O=C, type II by a strong O-H···N hydrogen bond, type III by weak N-H···O-H hydrogen bonds, and type IV by a C=O···H-C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O-H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm(-1), respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG undergoes facile
DOE Office of Scientific and Technical Information (OSTI.GOV)
Borba, Ana, E-mail: anaborba@ci.uc.pt; Fausto, Rui; Gómez-Zavaglia, Andrea
The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N–H···O=C, type II by a strong O–H···N hydrogen bond, type III by weak N–H···O–H hydrogen bonds, and type IV by a C=O···H–C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the casemore » of conformers of type II, where the strong intramolecular O–H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N{sub 2} matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm{sup −1}, respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix
Virtual Mission Operations of Remote Sensors With Rapid Access To and From Space
NASA Technical Reports Server (NTRS)
Ivancic, William D.; Stewart, Dave; Walke, Jon; Dikeman, Larry; Sage, Steven; Miller, Eric; Northam, James; Jackson, Chris; Taylor, John; Lynch, Scott;
2010-01-01
This paper describes network-centric operations, where a virtual mission operations center autonomously receives sensor triggers, and schedules space and ground assets using Internet-based technologies and service-oriented architectures. For proof-of-concept purposes, sensor triggers are received from the United States Geological Survey (USGS) to determine targets for space-based sensors. The Surrey Satellite Technology Limited (SSTL) Disaster Monitoring Constellation satellite, the United Kingdom Disaster Monitoring Constellation (UK-DMC), is used as the space-based sensor. The UK-DMC s availability is determined via machine-to-machine communications using SSTL s mission planning system. Access to/from the UK-DMC for tasking and sensor data is via SSTL s and Universal Space Network s (USN) ground assets. The availability and scheduling of USN s assets can also be performed autonomously via machine-to-machine communications. All communication, both on the ground and between ground and space, uses open Internet standards.
Nei, Y-w; Crampton, K T; Berden, G; Oomens, J; Rodgers, M T
2013-10-17
The IRMPD action spectra of the deprotonated forms of the four common RNA mononucleotides, adenosine-5'-monophosphate (A5'p), guanosine-5'-monophosphate (G5'p), cytidine-5'-monophosphate (C5'p), and uridine-5'-monophosphate (U5'p), are measured to probe their gas-phase structures. The IRMPD action spectra of all four deprotonated RNA mononucleotides exhibit distinct IR signatures in the frequency region investigated, 570-1900 cm(-1), that allows these deprotonated mononucleotides to be easily differentiated from one other. Comparison of the measured IRMPD action spectra to the linear IR spectra calculated at the B3LYP/6-31+G(d,p) level of theory finds that the most stable conformations of the deprotonated forms of A5'p, C5'p, and U5'p are accessed in the experiments, and these conformers adopt the C3' endo conformation of the ribose moiety and the anti conformation of the nucleobase. In the case of deprotonated G5'p, the most stable conformer is also accessed in the experiments. However, the ground-state conformer differs from the other three deprotonated RNA mononucleotides in that it adopts the syn rather than anti conformation for the nucleobase. Present results are compared to results previously obtained for the deprotonated forms of the four common DNA mononucleotides to examine the fundamental conformational differences between these species, and thus elucidate the effects of the 2'-hydroxyl group on their structure, stability, and fragmentation behavior.
Supergravitational conformal Galileons
DOE Office of Scientific and Technical Information (OSTI.GOV)
Deen, Rehan; Ovrut, Burt
The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and “bouncing” cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory,more » but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios« less
Supergravitational conformal Galileons
Deen, Rehan; Ovrut, Burt
2017-08-04
The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and “bouncing” cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory,more » but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios« less
Space Access for Small Satellites on the K-1
NASA Astrophysics Data System (ADS)
Faktor, L.
Affordable access to space remains a major obstacle to realizing the increasing potential of small satellites systems. On a per kilogram basis, small launch vehicles are simply too expensive for the budgets of many small satellite programs. Opportunities for rideshare with larger payloads on larger launch vehicles are still rare, given the complications associated with coordinating delivery schedules and deployment orbits. Existing contractual mechanisms are also often inadequate to facilitate the launch of multiple payload customers on the same flight. Kistler Aerospace Corporation is committed to lowering the price and enhancing the availability of space access for small satellite programs through the fully-reusable K-1 launch vehicle. Kistler has been working with a number of entities, including Astrium Ltd., AeroAstro, and NASA, to develop innovative approaches to small satellite missions. The K-1 has been selected by NASA as a Flight Demonstration Vehicle for the Space Launch Initiative. NASA has purchased the flight results during the first four K-1 launches on the performance of 13 advanced launch vehicle technologies embedded in the K-1 vehicle. On K-1 flights #2-#4, opportunities exist for small satellites to rideshare to low-earth orbit for a low-launch price. Kistler's flight demonstration contract with NASA also includes options to fly Add-on Technology Experiment flights. Opportunities exist for rideshare payloads on these flights as well. Both commercial and government customers may take advantage of the rideshare pricing. Kistler is investigating the feasibility of flying dedicated, multiple small payload missions. Such a mission would launch multiple small payloads from a single customer or small payloads from different customers. The orbit would be selected to be compatible with the requirements of as many small payload customers as possible, and make use of reusable hardware, standard interfaces (such as the existing MPAS) and verification plans
Maintaining and Enhancing Diversity of Sampled Protein Conformations in Robotics-Inspired Methods.
Abella, Jayvee R; Moll, Mark; Kavraki, Lydia E
2018-01-01
The ability to efficiently sample structurally diverse protein conformations allows one to gain a high-level view of a protein's energy landscape. Algorithms from robot motion planning have been used for conformational sampling, and several of these algorithms promote diversity by keeping track of "coverage" in conformational space based on the local sampling density. However, large proteins present special challenges. In particular, larger systems require running many concurrent instances of these algorithms, but these algorithms can quickly become memory intensive because they typically keep previously sampled conformations in memory to maintain coverage estimates. In addition, robotics-inspired algorithms depend on defining useful perturbation strategies for exploring the conformational space, which is a difficult task for large proteins because such systems are typically more constrained and exhibit complex motions. In this article, we introduce two methodologies for maintaining and enhancing diversity in robotics-inspired conformational sampling. The first method addresses algorithms based on coverage estimates and leverages the use of a low-dimensional projection to define a global coverage grid that maintains coverage across concurrent runs of sampling. The second method is an automatic definition of a perturbation strategy through readily available flexibility information derived from B-factors, secondary structure, and rigidity analysis. Our results show a significant increase in the diversity of the conformations sampled for proteins consisting of up to 500 residues when applied to a specific robotics-inspired algorithm for conformational sampling. The methodologies presented in this article may be vital components for the scalability of robotics-inspired approaches.
A new open-source Python-based Space Weather data access, visualization, and analysis toolkit
NASA Astrophysics Data System (ADS)
de Larquier, S.; Ribeiro, A.; Frissell, N. A.; Spaleta, J.; Kunduri, B.; Thomas, E. G.; Ruohoniemi, J.; Baker, J. B.
2013-12-01
Space weather research relies heavily on combining and comparing data from multiple observational platforms. Current frameworks exist to aggregate some of the data sources, most based on file downloads via web or ftp interfaces. Empirical models are mostly fortran based and lack interfaces with more useful scripting languages. In an effort to improve data and model access, the SuperDARN community has been developing a Python-based Space Science Data Visualization Toolkit (DaViTpy). At the center of this development was a redesign of how our data (from 30 years of SuperDARN radars) was made available. Several access solutions are now wrapped into one convenient Python interface which probes local directories, a new remote NoSQL database, and an FTP server to retrieve the requested data based on availability. Motivated by the efficiency of this interface and the inherent need for data from multiple instruments, we implemented similar modules for other space science datasets (POES, OMNI, Kp, AE...), and also included fundamental empirical models with Python interfaces to enhance data analysis (IRI, HWM, MSIS...). All these modules and more are gathered in a single convenient toolkit, which is collaboratively developed and distributed using Github and continues to grow. While still in its early stages, we expect this toolkit will facilitate multi-instrument space weather research and improve scientific productivity.
Galactic conformity measured in semi-analytic models
NASA Astrophysics Data System (ADS)
Lacerna, I.; Contreras, S.; González, R. E.; Padilla, N.; Gonzalez-Perez, V.
2018-03-01
We study the correlation between the specific star formation rate of central galaxies and neighbour galaxies, also known as `galactic conformity', out to 20 h^{-1} {Mpc} using three semi-analytic models (SAMs, one from L-GALAXIES and other two from GALFORM). The aim is to establish whether SAMs are able to show galactic conformity using different models and selection criteria. In all the models, when the selection of primary galaxies is based on an isolation criterion in real space, the mean fraction of quenched (Q) galaxies around Q primary galaxies is higher than that around star-forming primary galaxies of the same stellar mass. The overall signal of conformity decreases when we remove satellites selected as primary galaxies, but the effect is much stronger in GALFORM models compared with the L-GALAXIES model. We find this difference is partially explained by the fact that in GALFORM once a galaxy becomes a satellite remains as such, whereas satellites can become centrals at a later time in L-GALAXIES. The signal of conformity decreases down to 60 per cent in the L-GALAXIES model after removing central galaxies that were ejected from their host halo in the past. Galactic conformity is also influenced by primary galaxies at fixed stellar mass that reside in dark matter haloes of different masses. Finally, we explore a proxy of conformity between distinct haloes. In this case, the conformity is weak beyond ˜3 h^{-1} {Mpc} (<3 per cent in L-GALAXIES, <1-2 per cent in GALFORM models). Therefore, it seems difficult that conformity is directly related with a long-range effect.
Ethernet access network based on free-space optic deployment technology
NASA Astrophysics Data System (ADS)
Gebhart, Michael; Leitgeb, Erich; Birnbacher, Ulla; Schrotter, Peter
2004-06-01
The satisfaction of all communication needs from single households and business companies over a single access infrastructure is probably the most challenging topic in communications technology today. But even though the so-called "Last Mile Access Bottleneck" is well known since more than ten years and many distribution technologies have been tried out, the optimal solution has not yet been found and paying commercial access networks offering all service classes are still rare today. Conventional services like telephone, radio and TV, as well as new and emerging services like email, web browsing, online-gaming, video conferences, business data transfer or external data storage can all be transmitted over the well known and cost effective Ethernet networking protocol standard. Key requirements for the deployment technology driven by the different services are high data rates to the single customer, security, moderate deployment costs and good scalability to number and density of users, quick and flexible deployment without legal impediments and high availability, referring to the properties of optical and wireless communication. We demonstrate all elements of an Ethernet Access Network based on Free Space Optic distribution technology. Main physical parts are Central Office, Distribution Network and Customer Equipment. Transmission of different services, as well as configuration, service upgrades and remote control of the network are handled by networking features over one FSO connection. All parts of the network are proven, the latest commercially available technology. The set up is flexible and can be adapted to any more specific need if required.
Interplanetary space science data base and access/display tool on the NSSDC heliospheric CD-ROM
NASA Technical Reports Server (NTRS)
Papitashvili, N. E.; King, J. H.
1995-01-01
The National Space Science Data Center (NSSDC) has accumulated a rich archive of heliospheric, magnetospheric, and ionospheric data, as well as data from most other NASA-involved science disciplines. To facilitate access to and use of these data, NSSDC has begun to put selected data onto CD-ROM's. This paper describes one such CD-ROM, and the access and display software developed at NSSDC to support its use. The data on the CD-ROM consist primarily of hourly solar wind magnetic field and plasma data from many near-Earth spacecraft (OMNI) and deep space spacecraft (Voyagers, Pioneers, Helios, Pioneer Venus Orbiter). In addition, 5-minute resolution IMP-8 and ISEE-3 magnetic field and plasma data are also included. Data are stored in both ASCII and CDF formats.
Refinement of protein termini in template-based modeling using conformational space annealing.
Park, Hahnbeom; Ko, Junsu; Joo, Keehyoung; Lee, Julian; Seok, Chaok; Lee, Jooyoung
2011-09-01
The rapid increase in the number of experimentally determined protein structures in recent years enables us to obtain more reliable protein tertiary structure models than ever by template-based modeling. However, refinement of template-based models beyond the limit available from the best templates is still needed for understanding protein function in atomic detail. In this work, we develop a new method for protein terminus modeling that can be applied to refinement of models with unreliable terminus structures. The energy function for terminus modeling consists of both physics-based and knowledge-based potential terms with carefully optimized relative weights. Effective sampling of both the framework and terminus is performed using the conformational space annealing technique. This method has been tested on a set of termini derived from a nonredundant structure database and two sets of termini from the CASP8 targets. The performance of the terminus modeling method is significantly improved over our previous method that does not employ terminus refinement. It is also comparable or superior to the best server methods tested in CASP8. The success of the current approach suggests that similar strategy may be applied to other types of refinement problems such as loop modeling or secondary structure rearrangement. Copyright © 2011 Wiley-Liss, Inc.
Enzymatic Detoxication, Conformational Selection, and the Role of Molten Globule Active Sites*
Honaker, Matthew T.; Acchione, Mauro; Zhang, Wei; Mannervik, Bengt; Atkins, William M.
2013-01-01
The role of conformational ensembles in enzymatic reactions remains unclear. Discussion concerning “induced fit” versus “conformational selection” has, however, ignored detoxication enzymes, which exhibit catalytic promiscuity. These enzymes dominate drug metabolism and determine drug-drug interactions. The detoxication enzyme glutathione transferase A1–1 (GSTA1–1), exploits a molten globule-like active site to achieve remarkable catalytic promiscuity wherein the substrate-free conformational ensemble is broad with barrierless transitions between states. A quantitative index of catalytic promiscuity is used to compare engineered variants of GSTA1–1 and the catalytic promiscuity correlates strongly with characteristics of the thermodynamic partition function, for the substrate-free enzymes. Access to chemically disparate transition states is encoded by the substrate-free conformational ensemble. Pre-steady state catalytic data confirm an extension of the conformational selection model, wherein different substrates select different starting conformations. The kinetic liability of the conformational breadth is minimized by a smooth landscape. We propose that “local” molten globule behavior optimizes detoxication enzymes. PMID:23649628
Distinguishing Signatures of Multipathway Conformational Transitions
NASA Astrophysics Data System (ADS)
Pierse, Christopher A.; Dudko, Olga K.
2017-02-01
The folding and binding of biomolecules into functional conformations are thought to be commonly mediated by multiple pathways rather than a unique route. Yet even in experiments where one can "see" individual conformational transitions, their stochastic nature generally precludes one from determining whether the transitions occurred through one or multiple pathways. We establish model-free, observable signatures in the response of macromolecules to force that unambiguously identify multiple pathways—even when the pathways themselves cannot be resolved. The unified analytical description reveals that, through multiple pathways, the response of molecules to external forces can be shaped in diverse ways, resulting in a rich design space for a tailored biological function already at the single-molecule level.
Bootstrapping conformal field theories with the extremal functional method.
El-Showk, Sheer; Paulos, Miguel F
2013-12-13
The existence of a positive linear functional acting on the space of (differences between) conformal blocks has been shown to rule out regions in the parameter space of conformal field theories (CFTs). We argue that at the boundary of the allowed region the extremal functional contains, in principle, enough information to determine the dimensions and operator product expansion (OPE) coefficients of an infinite number of operators appearing in the correlator under analysis. Based on this idea we develop the extremal functional method (EFM), a numerical procedure for deriving the spectrum and OPE coefficients of CFTs lying on the boundary (of solution space). We test the EFM by using it to rederive the low lying spectrum and OPE coefficients of the two-dimensional Ising model based solely on the dimension of a single scalar quasiprimary--no Virasoro algebra required. Our work serves as a benchmark for applications to more interesting, less known CFTs in the near future.
Analysis of Potential Alternatives to Reduce NASA's Cost of Human Access to Space
NASA Technical Reports Server (NTRS)
1998-01-01
The purpose of this report is to analyze NASA's potential options for significantly reducing the cost of human access to space. The opinions expressed in this report are based on Hawthorne, Krauss & Associates' ("HKA") interaction with NASA and several of its key contractors over the past nine months. This report is not intended to be an exhaustive quantitative analysis of the various options available to NASA. Instead, its purpose is to outline key decision-related issues that the agency should consider prior to making a decision as to which option to pursue. This report attempts to bring a private-sector perspective to bear on the issue of reducing the cost of human access to space. HKA believes that the key to the NASA's success in reducing those costs over the long-term is the involvement of the private-sector incentives and disciplines--which is achieved only through the assumption of risk by the private sector, not through a traditional contractor relationship--is essential to achieve significant long-term cost reductions.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-05
... conformity assessment bodies meet the requirements to test for compliance to specified children's product... West Highway, Bethesda, MD 20814; telephone (301) 504-7923. For access to the docket to read background... conformity assessment body; Qualifications for acceptance by CPSC to test for compliance to specified...
Compactification on phase space
NASA Astrophysics Data System (ADS)
Lovelady, Benjamin; Wheeler, James
2016-03-01
A major challenge for string theory is to understand the dimensional reduction required for comparison with the standard model. We propose reducing the dimension of the compactification by interpreting some of the extra dimensions as the energy-momentum portion of a phase-space. Such models naturally arise as generalized quotients of the conformal group called biconformal spaces. By combining the standard Kaluza-Klein approach with such a conformal gauge theory, we may start from the conformal group of an n-dimensional Euclidean space to form a 2n-dimensional quotient manifold with symplectic structure. A pair of involutions leads naturally to two n-dimensional Lorentzian manifolds. For n = 5, this leaves only two extra dimensions, with a countable family of possible compactifications and an SO(5) Yang-Mills field on the fibers. Starting with n=6 leads to 4-dimensional compactification of the phase space. In the latter case, if the two dimensions each from spacetime and momentum space are compactified onto spheres, then there is an SU(2)xSU(2) (left-right symmetric electroweak) field between phase and configuration space and an SO(6) field on the fibers. Such a theory, with minor additional symmetry breaking, could contain all parts of the standard model.
CliniSpace: a multiperson 3D online immersive training environment accessible through a browser.
Dev, Parvati; Heinrichs, W LeRoy; Youngblood, Patricia
2011-01-01
Immersive online medical environments, with dynamic virtual patients, have been shown to be effective for scenario-based learning (1). However, ease of use and ease of access have been barriers to their use. We used feedback from prior evaluation of these projects to design and develop CliniSpace. To improve usability, we retained the richness of prior virtual environments but modified the user interface. To improve access, we used a Software-as-a-Service (SaaS) approach to present a richly immersive 3D environment within a web browser.
The relative isoperimetric inequality on a conformally parabolic manifold with boundary
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kesel'man, Vladimir M
2011-07-31
For an arbitrary noncompact n-dimensional Riemannian manifold with a boundary of conformally parabolic type it is proved that there exists a conformal change of metric such that a relative isoperimetric inequality of the same form as in the closed n-dimensional Euclidean half-space holds on the manifold with the new metric. This isoperimetric inequality is asymptotically sharp. Bibliography: 6 titles.
Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps
2011-01-01
Background Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from
PubChem3D: conformer ensemble accuracy
2013-01-01
Background PubChem is a free and publicly available resource containing substance descriptions and their associated biological activity information. PubChem3D is an extension to PubChem containing computationally-derived three-dimensional (3-D) structures of small molecules. All the tools and services that are a part of PubChem3D rely upon the quality of the 3-D conformer models. Construction of the conformer models currently available in PubChem3D involves a clustering stage to sample the conformational space spanned by the molecule. While this stage allows one to downsize the conformer models to more manageable size, it may result in a loss of the ability to reproduce experimentally determined “bioactive” conformations, for example, found for PDB ligands. This study examines the extent of this accuracy loss and considers its effect on the 3-D similarity analysis of molecules. Results The conformer models consisting of up to 100,000 conformers per compound were generated for 47,123 small molecules whose structures were experimentally determined, and the conformers in each conformer model were clustered to reduce the size of the conformer model to a maximum of 500 conformers per molecule. The accuracy of the conformer models before and after clustering was evaluated using five different measures: root-mean-square distance (RMSD), shape-optimized shape-Tanimoto (STST-opt) and combo-Tanimoto (ComboTST-opt), and color-optimized color-Tanimoto (CTCT-opt) and combo-Tanimoto (ComboTCT-opt). On average, the effect of clustering decreased the conformer model accuracy, increasing the conformer ensemble’s RMSD to the bioactive conformer (by 0.18 ± 0.12 Å), and decreasing the STST-opt, ComboTST-opt, CTCT-opt, and ComboTCT-opt scores (by 0.04 ± 0.03, 0.16 ± 0.09, 0.09 ± 0.05, and 0.15 ± 0.09, respectively). Conclusion This study shows the RMSD accuracy performance of the PubChem3D conformer models is operating as designed. In addition, the effect of PubChem3D
Makam, Pandeeswar; Gazit, Ehud
2018-05-21
Molecular self-assembly is a ubiquitous process in nature and central to bottom-up nanotechnology. In particular, the organization of peptide building blocks into ordered supramolecular structures has gained much interest due to the unique properties of the products, including biocompatibility, chemical and structural diversity, robustness and ease of large-scale synthesis. In addition, peptides, as short as dipeptides, contain all the molecular information needed to spontaneously form well-ordered structures at both the nano- and the micro-scale. Therefore, peptide supramolecular assembly has been effectively utilized to produce novel materials with tailored properties for various applications in the fields of material science, engineering, medicine, and biology. To further expand the conformational space of peptide assemblies in terms of structural and functional complexity, multicomponent (two or more) peptide supramolecular co-assembly has recently evolved as a promising extended approach, similar to the structural diversity of natural sequence-defined biopolymers (proteins) as well as of synthetic covalent co-polymers. The use of this methodology was recently demonstrated in various applications, such as nanostructure physical dimension control, the creation of non-canonical complex topologies, mechanical strength modulation, the design of light harvesting soft materials, fabrication of electrically conducting devices, induced fluorescence, enzymatic catalysis and tissue engineering. In light of these significant advancements in the field of peptide supramolecular co-assembly in the last few years, in this tutorial review, we provide an updated overview and future prospects of this emerging subject.
NASA Astrophysics Data System (ADS)
Joung, InSuk; Kim, Jong Yun; Gross, Steven P.; Joo, Keehyoung; Lee, Jooyoung
2018-02-01
Many problems in science and engineering can be formulated as optimization problems. One way to solve these problems is to develop tailored problem-specific approaches. As such development is challenging, an alternative is to develop good generally-applicable algorithms. Such algorithms are easy to apply, typically function robustly, and reduce development time. Here we provide a description for one such algorithm called Conformational Space Annealing (CSA) along with its python version, PyCSA. We previously applied it to many optimization problems including protein structure prediction and graph community detection. To demonstrate its utility, we have applied PyCSA to two continuous test functions, namely Ackley and Eggholder functions. In addition, in order to provide complete generality of PyCSA to any types of an objective function, we demonstrate the way PyCSA can be applied to a discrete objective function, namely a parameter optimization problem. Based on the benchmarking results of the three problems, the performance of CSA is shown to be better than or similar to the most popular optimization method, simulated annealing. For continuous objective functions, we found that, L-BFGS-B was the best performing local optimization method, while for a discrete objective function Nelder-Mead was the best. The current version of PyCSA can be run in parallel at the coarse grained level by calculating multiple independent local optimizations separately. The source code of PyCSA is available from http://lee.kias.re.kr.
Autotransporter structure reveals intra-barrel cleavage followed by conformational changes.
Barnard, Travis J; Dautin, Nathalie; Lukacik, Petra; Bernstein, Harris D; Buchanan, Susan K
2007-12-01
Autotransporters are virulence factors produced by Gram-negative bacteria. They consist of two domains, an N-terminal 'passenger' domain and a C-terminal beta-domain. beta-domains form beta-barrel structures in the outer membrane while passenger domains are translocated into the extracellular space. In some autotransporters, the two domains are separated by proteolytic cleavage. Using X-ray crystallography, we solved the 2.7-A structure of the post-cleavage state of the beta-domain of EspP, an autotransporter produced by Escherichia coli strain O157:H7. The structure consists of a 12-stranded beta-barrel with the passenger domain-beta-domain cleavage junction located inside the barrel pore, approximately midway between the extracellular and periplasmic surfaces of the outer membrane. The structure reveals an unprecedented intra-barrel cleavage mechanism and suggests that two conformational changes occur in the beta-domain after cleavage, one conferring increased stability on the beta-domain and another restricting access to the barrel pore.
Spherically symmetric conformal gravity and ''gravitational bubbles''
DOE Office of Scientific and Technical Information (OSTI.GOV)
Berezin, V.A.; Dokuchaev, V.I.; Eroshenko, Yu.N., E-mail: berezin@inr.ac.ru, E-mail: dokuchaev@inr.ac.ru, E-mail: eroshenko@inr.ac.ru
2016-01-01
The general structure of the spherically symmetric solutions in the Weyl conformal gravity is described. The corresponding Bach equations are derived for the special type of metrics, which can be considered as the representative of the general class. The complete set of the pure vacuum solutions is found. It consists of two classes. The first one contains the solutions with constant two-dimensional curvature scalar of our specific metrics, and the representatives are the famous Robertson-Walker metrics. One of them we called the ''gravitational bubbles'', which is compact and with zero Weyl tensor. Thus, we obtained the pure vacuum curved space-timesmore » (without any material sources, including the cosmological constant) what is absolutely impossible in General Relativity. Such a phenomenon makes it easier to create the universe from ''nothing''. The second class consists of the solutions with varying curvature scalar. We found its representative as the one-parameter family. It appears that it can be conformally covered by the thee-parameter Mannheim-Kazanas solution. We also investigated the general structure of the energy-momentum tensor in the spherical conformal gravity and constructed the vectorial equation that reveals clearly some features of non-vacuum solutions. Two of them are explicitly written, namely, the metrics à la Vaidya, and the electrovacuum space-time metrics.« less
Efficient conformational space exploration in ab initio protein folding simulation.
Ullah, Ahammed; Ahmed, Nasif; Pappu, Subrata Dey; Shatabda, Swakkhar; Ullah, A Z M Dayem; Rahman, M Sohel
2015-08-01
Ab initio protein folding simulation largely depends on knowledge-based energy functions that are derived from known protein structures using statistical methods. These knowledge-based energy functions provide us with a good approximation of real protein energetics. However, these energy functions are not very informative for search algorithms and fail to distinguish the types of amino acid interactions that contribute largely to the energy function from those that do not. As a result, search algorithms frequently get trapped into the local minima. On the other hand, the hydrophobic-polar (HP) model considers hydrophobic interactions only. The simplified nature of HP energy function makes it limited only to a low-resolution model. In this paper, we present a strategy to derive a non-uniform scaled version of the real 20×20 pairwise energy function. The non-uniform scaling helps tackle the difficulty faced by a real energy function, whereas the integration of 20×20 pairwise information overcomes the limitations faced by the HP energy function. Here, we have applied a derived energy function with a genetic algorithm on discrete lattices. On a standard set of benchmark protein sequences, our approach significantly outperforms the state-of-the-art methods for similar models. Our approach has been able to explore regions of the conformational space which all the previous methods have failed to explore. Effectiveness of the derived energy function is presented by showing qualitative differences and similarities of the sampled structures to the native structures. Number of objective function evaluation in a single run of the algorithm is used as a comparison metric to demonstrate efficiency.
47 CFR 68.324 - Supplier's Declaration of Conformity requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Conformity is designed to operate in conjunction with other equipment, the characteristics of which can... available to the general public on its company website. The information shall be accessible to the disabled community from the website. If the responsible party does not have a functional and reliable website, then...
47 CFR 68.324 - Supplier's Declaration of Conformity requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Conformity is designed to operate in conjunction with other equipment, the characteristics of which can... available to the general public on its company website. The information shall be accessible to the disabled community from the website. If the responsible party does not have a functional and reliable website, then...
47 CFR 68.324 - Supplier's Declaration of Conformity requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... Conformity is designed to operate in conjunction with other equipment, the characteristics of which can... available to the general public on its company website. The information shall be accessible to the disabled community from the website. If the responsible party does not have a functional and reliable website, then...
47 CFR 68.324 - Supplier's Declaration of Conformity requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... Conformity is designed to operate in conjunction with other equipment, the characteristics of which can... available to the general public on its company website. The information shall be accessible to the disabled community from the website. If the responsible party does not have a functional and reliable website, then...
47 CFR 68.324 - Supplier's Declaration of Conformity requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Conformity is designed to operate in conjunction with other equipment, the characteristics of which can... available to the general public on its company website. The information shall be accessible to the disabled community from the website. If the responsible party does not have a functional and reliable website, then...
New potentials for conformal mechanics
NASA Astrophysics Data System (ADS)
Papadopoulos, G.
2013-04-01
We find under some mild assumptions that the most general potential of one-dimensional conformal systems with time-independent couplings is expressed as V = V0 + V1, where V0 is a homogeneous function with respect to a homothetic motion in configuration space and V1 is determined from an equation with source a homothetic potential. Such systems admit at most an SL(2,{R}) conformal symmetry which, depending on the couplings, is embedded in {Diff}({R}) in three different ways. In one case, SL(2,{R}) is also embedded in Diff(S1). Examples of such models include those with potential V = αx2 + βx-2 for arbitrary couplings α and β, the Calogero models with harmonic oscillator couplings and nonlinear models with suitable metrics and potentials. In addition, we give the conditions on the couplings for a class of gauge theories to admit a SL(2,{R}) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries that include the isometries of AdS2 × S3 and AdS2 × S3 × S3 which arise as backgrounds in AdS2/CFT1.
LabVIEW Interface for PCI-SpaceWire Interface Card
NASA Technical Reports Server (NTRS)
Lux, James; Loya, Frank; Bachmann, Alex
2005-01-01
This software provides a LabView interface to the NT drivers for the PCISpaceWire card, which is a peripheral component interface (PCI) bus interface that conforms to the IEEE-1355/ SpaceWire standard. As SpaceWire grows in popularity, the ability to use SpaceWire links within LabVIEW will be important to electronic ground support equipment vendors. In addition, there is a need for a high-level LabVIEW interface to the low-level device- driver software supplied with the card. The LabVIEW virtual instrument (VI) provides graphical interfaces to support all (1) SpaceWire link functions, including message handling and routing; (2) monitoring as a passive tap using specialized hardware; and (3) low-level access to satellite mission-control subsystem functions. The software is supplied in a zip file that contains LabVIEW VI files, which provide various functions of the PCI-SpaceWire card, as well as higher-link-level functions. The VIs are suitably named according to the matching function names in the driver manual. A number of test programs also are provided to exercise various functions.
Ab initio conformational analysis of N-formyl ?-alanine amide including electron correlation
NASA Astrophysics Data System (ADS)
Yu, Ching-Hsing; Norman, Mya A.; Schäfer, Lothar; Ramek, Michael; Peeters, Anik; van Alsenoy, Christian
2001-06-01
The conformational properties of N-formyl L-alanine amide (ALA) were investigated using RMP2/6-311G∗∗ ab initio gradient geometry optimization. One hundred forty four structures of ALA were optimized at 30° grid points in its φ(N-C(α)), ψ(C(α)-C‧) conformational space. Using cubic spline functions, the grid structures were then used to construct analytical representations of complete surfaces, in φ,ψ-space, of bond lengths, bond angles, torsional sensitivity and electrostatic atomic charges. Analyses show that, in agreement with previous studies, the right-handed helical conformation, αR, is not a local energy minimum of the potential energy surface of ALA. Comparisons with protein crystallographic data show that the characteristic differences between geometrical trends in dipeptides and proteins, previously found for ab initio dipeptide structures obtained without electron correlation, are also found in the electron-correlated geometries. In contrast to generally accepted features of force fields used in empirical molecular modeling, partial atomic charges obtained by the CHELPG method are found to be not constant, but to vary significantly throughout the φ,ψ-space. By comparing RHF and MP2 structures, the effects of dispersion forces on ALA were studied, revealing molecular contractions for those conformations, in which small adjustments of torsional angles entail large changes in non-bonded distances.
Kim, Minkyoung; Choi, Seung-Hoon; Kim, Junhyoung; Choi, Kihang; Shin, Jae-Min; Kang, Sang-Kee; Choi, Yun-Jaie; Jung, Dong Hyun
2009-11-01
This study describes the application of a density-based algorithm to clustering small peptide conformations after a molecular dynamics simulation. We propose a clustering method for small peptide conformations that enables adjacent clusters to be separated more clearly on the basis of neighbor density. Neighbor density means the number of neighboring conformations, so if a conformation has too few neighboring conformations, then it is considered as noise or an outlier and is excluded from the list of cluster members. With this approach, we can easily identify clusters in which the members are densely crowded in the conformational space, and we can safely avoid misclustering individual clusters linked by noise or outliers. Consideration of neighbor density significantly improves the efficiency of clustering of small peptide conformations sampled from molecular dynamics simulations and can be used for predicting peptide structures.
NASA Technical Reports Server (NTRS)
Logsdon, John M. (Editor); Williamson, Ray A. (Editor); Launius, Roger D. (Editor); Acker, Russell J. (Editor); Garber, Stephen J. (Editor); Friedman, Jonathan L. (Editor)
1999-01-01
The documents selected for inclusion in this volume are presented in four major chapters, each covering a particular aspect of access to space and the manner in which it has developed over time. These chapters focus on the evolution toward the giant Saturn V rocket, the development of the Space Shuttle, space transportation commercialization, and future space transportation possibilities. Each chapter in this volume is introduced by an overview essay, prepared by individuals who are particularly well qualified to write on the topic. In the main, these essays are intended to introduce and complement the documents in the chapter and to place them, for the most part, in a chronological and substantive context. Each essay contains references to the documents in the chapter it introduces, and many also contain references to documents in other chapters of the collection. These introductory essays are the responsibility of their individual authors, and the views and conclusions contained therein do not necessarily represent the opinions of either George Washington University or NASA.
Derrer, Carmen; Wittek, Anke; Bamberg, Ernst; Carpaneto, Armando; Dreyer, Ingo; Geiger, Dietmar
2013-01-01
Proton-driven Suc transporters allow phloem cells of higher plants to accumulate Suc to more than 1 M, which is up to ∼1000-fold higher than in the surrounding extracellular space. The carrier protein can accomplish this task only because proton and Suc transport are tightly coupled. This study provides insights into this coupling by resolving the first step in the transport cycle of the Suc transporter SUT1 from maize (Zea mays). Voltage clamp fluorometry measurements combining electrophysiological techniques with fluorescence-based methods enable the visualization of conformational changes of SUT1 expressed in Xenopus laevis oocytes. Using the Suc derivate sucralose, binding of which hinders conformational changes of SUT1, the association of protons to the carrier could be dissected from transport-associated movements of the protein. These combined approaches enabled us to resolve the binding of protons to the carrier and its interrelationship with the alternating movement of the protein. The data indicate that the rate-limiting step of the reaction cycle is determined by the accessibility of the proton binding site. This, in turn, is determined by the conformational change of the SUT1 protein, alternately exposing the binding pockets to the inward and to the outward face of the membrane. PMID:23964025
Liu, Zhiwei; Ensing, Bernd; Moore, Preston B
2011-02-08
The free energy surfaces (FESs) of alanine dipeptide are studied to illustrate a new strategy to assess the performance of classical molecular mechanics force field on the full range of the (ϕ-ψ) conformational space. The FES is obtained from metadynamics simulations with five commonly used force fields and from ab initio density functional theory calculations in both gas phase and aqueous solution. The FESs obtained at the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d,p) level of theory are validated by comparison with previously reported MP2 and LMP2 results as well as with experimentally obtained probability distribution between the C5-β (or β-PPII) and αR states. A quantitative assessment is made for each force field in three conformational basins, LeRI (C5-β-C7eq), LeRII (β2-αR), and LeRIII(αL-C7ax-αD) as well as three transition-state regions linking the above conformational basins. The performance of each force field is evaluated in terms of the average free energy of each region in comparison with that of the ab initio results. We quantify how well a force field FES matches the ab initio FES through the calculation of the standard deviation of a free energy difference map between the two FESs. The results indicate that the performance varies largely from region to region or from force field to force field. Although not one force field is able to outperform all others in all conformational areas, the OPLSAA/L force field gives the best performance overall, followed by OPLSAA and AMBER03. For the three top performers, the average free energies differ from the corresponding ab initio values from within the error range (<0.4 kcal/mol) to ∼1.5 kcal/mol for the low-energy regions and up to ∼2.0 kcal/mol for the transition-state regions. The strategy presented and the results obtained here should be useful for improving the parametrization of force fields targeting both accuracy in the energies of conformers and the transition-state barriers.
Increased conformity offers diminishing returns for reducing total knee replacement wear.
Fregly, Benjamin J; Marquez-Barrientos, Carlos; Banks, Scott A; DesJardins, John D
2010-02-01
Wear remains a significant problem limiting the lifespan of total knee replacements (TKRs). Though increased conformity between TKR components has the potential to decrease wear, the optimal amount and planes of conformity have not been investigated. Furthermore, differing conformities in the medial and lateral compartments may provide designers the opportunity to address both wear and kinematic design goals simultaneously. This study used a computational model of a Stanmore knee simulator machine and a previously validated wear model to investigate this issue for simulated gait. TKR geometries with different amounts and planes of conformity on the medial and lateral sides were created and tested in two phases. The first phase utilized a wide range of sagittal and coronal conformity combinations to blanket a physically realistic design space. The second phase performed a focused investigation of the conformity conditions from the first phase to which predicted wear volume was sensitive. For the first phase, sagittal but not coronal conformity was found to have a significant effect on predicted wear volume. For the second phase, increased sagittal conformity was found to decrease predicted wear volume in a nonlinear fashion, with reductions gradually diminishing as conformity increased. These results suggest that TKR geometric design efforts aimed at minimizing wear should focus on sagittal rather than coronal conformity and that at least moderate sagittal conformity is desirable in both compartments.
Conformation and Aggregation of LKα14 Peptide in Bulk Water and at the Air/Water Interface.
Dalgicdir, Cahit; Sayar, Mehmet
2015-12-10
Historically, the protein folding problem has mainly been associated with understanding the relationship between amino acid sequence and structure. However, it is known that both the conformation of individual molecules and their aggregation strongly depend on the environmental conditions. Here, we study the aggregation behavior of the model peptide LKα14 (with amino acid sequence LKKLLKLLKKLLKL) in bulk water and at the air/water interface. We start by a quantitative analysis of the conformational space of a single LKα14 in bulk water. Next, in order to analyze the aggregation tendency of LKα14, by using the umbrella sampling technique we calculate the potential of mean force for pulling a single peptide from an n-molecule aggregate. In agreement with the experimental results, our calculations yield the optimal aggregate size as four. This equilibrium state is achieved by two opposing forces: Coulomb repulsion between the lysine side chains and the reduction of solvent accessible hydrophobic surface area upon aggregation. At the vacuum/water interface, however, even dimers of LKα14 become marginally stable, and any larger aggregate falls apart instantaneously. Our results indicate that even though the interface is highly influential in stabilizing the α-helix conformation for a single molecule, it significantly reduces the attraction between two LKα14 peptides, along with their aggregation tendency.
VanDersarl, Jules J.; Xu, Alexander M.; Melosh, Nicholas A.; Tayebi, Noureddine
2016-02-23
In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, embodiments of the present disclosure, in one aspect, relate to methods of making a structure including nanotubes, a structure including nanotubes, methods of delivering a fluid to a cell, methods of removing a fluid to a cell, methods of accessing intracellular space, and the like.
Space environment data storage and access: lessons learned and recommendations for the future
NASA Astrophysics Data System (ADS)
Evans, Hugh; Heynderickx, Daniel
2012-07-01
With the ever increasing volume of space environment data available at present and planned for the near future, the demands on data storage and access methods are increasing as well. In addition, continued access to historical, archived data remains crucial. On the basis of many years of experience, the authors identify the following issues as important for continued and efficient handling of datasets now and in the future: The huge data volumes currently or very soon avaiable from a number of space missions will limi direct Internet download access to even relatively short epoch ranges of data. Therefore, data providers should establish or extend standardised data (post-) processing services so that only data query results should be downloaded. Although a single standardised data format will in all likelihood remain utopia, data providers should at least include extensive metadata with their data products, according to established standards and practices (e.g. ISTP, SPASE). Standardisation of (sets of) metadata greatly facilitates data mining and querying. The use of SQL database storage should be considered instead of, or in parallel with, classic storage of data files. The use of SQL does away with having to handle file parsing and processing, while at the same time standard access protocols can be used to (remotely) connect to such data repositories. Many data holdings are still lacking in extensive descriptions of data provenance (e.g. instrument description), content and format. Unfortunately, detailed data information is usually rejected by scientific and technical journals. Re-processing of historical archived datasets into modern formats, making them easily available and usable, is urgently required, as knowledge is being lost. A global data directory has still not been achieved; policy makers should enforce stricter rules for "broadcasting" dataset information.
Random Access Frames (RAF): Alternative to Rack and Standoff for Deep Space Habitat Outfitting
NASA Technical Reports Server (NTRS)
Howe, A. Scott; Polit-Casillas, Raul
2014-01-01
A modular Random Access Frame (RAF) system is proposed as an alternative to the International Standard Payload Rack (ISPR) for internal module layout and outfitting in a Deep Space Habitat (DSH). The ISPR approach was designed to allow for efficient interchangeability of payload and experiments for the International Space Station (ISS) when frequent resupply missions were available (particularly the now-retired Space Shuttle). Though the standard interface approach to the ISPR system allowed integration of subsystems and hardware from a variety of sources and manufacturers, the heavy rack and standoff approach may not be appropriate when resupply or swap-out capabilities are not available, such as on deep space, long-duration missions. The lightweight RAF concept can allow a more dense packing of stowage and equipment, and may be easily broken down for repurposing or reuse. Several example layouts and workstations are presented.
ESPAS: the European e-science platform to access near-Earth space data (Invited)
NASA Astrophysics Data System (ADS)
Belehaki, A.; Hapgood, M. A.; Ritschel, B.; Manola, N.
2013-12-01
The aim of ESPAS platform is to integrate heterogeneous data from the earth's thermosphere, ionosphere, plasmasphere and magnetosphere. ESPAS supports the systematic exploration of multipoint measurements from the near-Earth space through homogenised access to multi-instrument data. It provides access to more than 40 datasets: Cluster, EISCAT, GIRO, DIAS, SWACI, CHAMP, SuperDARN, FPI, magnetometers INGV, SGO, DTU, IMAGE, TGO, IMAGE/RPI, ACE, SOHO, PROBA2, NOAA/POES, etc. The concept of extensibility to new data sets is an important element in the ESPAS architecture. Within the first year of the project, the main components of the system have been developed, namely, the data model, the XML schemas for metadata exchange format, the ontology, the wrapper installed at the data nodes so that the main platform harvest the metadata, the main platform built on the D-NET framework and the GUI with its designed workflows. The first working prototype supports the search for datasets among a selected number of databases (i.e., EDAM, DIAS, Cluster, SWACI data). The next immediate step would be the implementation of search for characteristics within the datasets. For the second release we are planning to deploy tools for conjunctions between ground-space and space-space and for coincidences. For the final phase of the project the ESPAS infrastructure will be extensively tested through the application of several use cases, designed to serve the needs of the wide interdisciplinary users and producers communities, such as the ionospheric, thermospheric, magnetospheric, space weather and space climate communities, the geophysics community, the space communications engineering, HF users, satellite operators, navigation and surveillance systems, and space agencies. The final ESPAS platform is expected to be delivered in 2015. The abstract is submitted on behalf of the ESPAS-FP7EU team (http://www.espas-fp7.eu): Mike Hapgood, Anna Belehaki, Spiros Ventouras, Natalia Manola, Antonis
Ryu, Shinsei; Takayanagi, Tadashi
2006-05-12
A holographic derivation of the entanglement entropy in quantum (conformal) field theories is proposed from anti-de Sitter/conformal field theory (AdS/CFT) correspondence. We argue that the entanglement entropy in d + 1 dimensional conformal field theories can be obtained from the area of d dimensional minimal surfaces in AdS(d+2), analogous to the Bekenstein-Hawking formula for black hole entropy. We show that our proposal agrees perfectly with the entanglement entropy in 2D CFT when applied to AdS(3). We also compare the entropy computed in AdS(5)XS(5) with that of the free N=4 super Yang-Mills theory.
Fast, clash-free RNA conformational morphing using molecular junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus
Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less
Fast, clash-free RNA conformational morphing using molecular junctions
Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus; ...
2017-03-13
Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less
Guo, Qingbin; Kang, Ji; Wu, Yan; Cui, Steve W; Hu, Xinzhong; Yada, Rickey Y
2015-12-10
The structure and conformation relationships of a heteropolysaccharide (GlcpA)Xylan in terms of various molecular weights, Xylp/GlcpA ratio and the distribution of GlcpA along xylan chain were investigated using computer modeling. The adiabatic contour maps of xylobiose, XylpXylp(GlcpA) and (GlcpA)XylpXylp(GlcpA) indicated that the insertion of the side group (GlcpA) influenced the accessible conformational space of xylobiose molecule. RIS-Metropolis Monte Carlo method indicated that insertion of GlcpA side chain induced a lowering effect of the calculated chain extension at low GlcpA:Xylp ratio (GlcpA:Xylp = 1:3). The chain, however, became extended when the ratio of GlcpA:Xylp above 2/3. It was also shown that the spatial extension of the polymer chains was dependent on the distribution of side chain: the random distribution demonstrated the most flexible structure compared to block and alternative distribution. The present studies provide a unique insight into the dependence of both side chain ratio and distribution on the stiffness and flexibility of various (GlcpA)Xylan molecules. Copyright © 2015. Published by Elsevier Ltd.
The Ligand Trans Influence Governs Conformation in Cobalamin-Dependent Methionine Synthase†
Fleischhacker, Angela S.; Matthews, Rowena G.
2008-01-01
Cobalamin-dependent methionine synthase (MetH) of Escherichia coli is a large, modular enzyme that uses a cobalamin prosthetic group as a donor or acceptor in three separate methyl transfer reactions. The prosthetic group alternates between methylcobalamin and cob(I)alamin during catalysis as homocysteine is converted to methionine using a methyl group derived from methyltetrahydrofolate. Occasional oxidation of cob(I)alamin to cob(II)alamin inactivates the enzyme. Reductive methylation with flavodoxin and adenosylmethionine returns the enzyme to an active methylcobalamin state. At different points during the reaction cycle, the coordination of the cobalt of the cobalamin changes. The imidazole side chain of His759 coordinates to cobalamin in a “His-on” state and dissociates to produce a “His-off” state. The His-off state has been associated with a conformation of MetH that is poised for reactivation of cobalamin by reductive methylation rather than catalysis. Our studies on cob(III)alamins bound to MetH, specifically aqua-, methyl-, and n-propylcobalamin, show a correlation between the accessibility of the reactivation conformation and the order of the established ligand trans influence. The trans influence also controls the affinity of MetH in the cob(III)alamin form for flavodoxin. Flavodoxin, which acts to shift the conformational equilibrium towards the reactivation conformation, binds less tightly to MetH when the cob(III)alamin has a strong trans ligand and therefore has less positive charge on cobalt. These results are compared to those for cob(II)alamin MetH, illustrating that access to the reactivation conformation is governed by the net charge on the cobalt as well as the trans influence in cob(III)alamins. PMID:17924667
Appendage mountable electronic devices conformable to surfaces
Rogers, John; Ying, Ming; Bonifas, Andrew; Lu, Nanshu
2017-01-24
Disclosed are appendage mountable electronic systems and related methods for covering and conforming to an appendage surface. A flexible or stretchable substrate has an inner surface for receiving an appendage, including an appendage having a curved surface, and an opposed outer surface that is accessible to external surfaces. A stretchable or flexible electronic device is supported by the substrate inner and/or outer surface, depending on the application of interest. The electronic device in combination with the substrate provides a net bending stiffness to facilitate conformal contact between the inner surface and a surface of the appendage provided within the enclosure. In an aspect, the system is capable of surface flipping without adversely impacting electronic device functionality, such as electronic devices comprising arrays of sensors, actuators, or both sensors and actuators.
Conformational flexibility and packing plausibility of repaglinide polymorphs
NASA Astrophysics Data System (ADS)
Rani, Dimpy; Goyal, Parnika; Chadha, Renu
2018-04-01
The present manuscript highlights the structural insight into the repaglinide polymorphs. The experimental screening for the possible crystal forms were carried out using various solvents, which generated three forms. The crystal structure of Form II and III was determined using PXRD pattern whereas structural analysis of Form I has already been reported. Form I, II and II was found to exist in P212121, PNA21 and P21/c space groups respectively. Conformational analysis was performed to account the conformational flexibility of RPG. The obtained conformers were further utilized to obtain the information about the crystal packing pattern of RPG polymorphs by polymorph prediction module. The lattice energy landscape, depicting the relationship between lattice energy and density of the polymorphs has been obtained for various possible polymorphs. The experimentally isolated polymorphs were successfully fitted into lattice energy landscape.
In silico Exploration of the Conformational Universe of GPCRs.
Rodríguez-Espigares, Ismael; Kaczor, Agnieszka A; Selent, Jana
2016-07-01
The structural plasticity of G protein coupled receptors (GPCRs) leads to a conformational universe going from inactive to active receptor states with several intermediate states. Many of them have not been captured yet and their role for GPCR activation is not well understood. The study of this conformational space and the transition dynamics between different receptor populations is a major challenge in molecular biophysics. The rational design of effector molecules that target such receptor populations allows fine-tuning receptor signalling with higher specificity to produce drugs with safer therapeutic profiles. In this minireview, we outline highly conserved receptor regions which are considered determinant for the establishment of distinct receptor states. We then discuss in-silico approaches such as dimensionality reduction methods and Markov State Models to explore the GPCR conformational universe and exploit the obtained conformations through structure-based drug design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Conformational Flexibility of Metazoan Fatty Acid Synthase Enables Catalysis
Brignole, Edward J.; Smith, Stuart; Asturias, Francisco J.
2008-01-01
The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers. While the 3D architecture of FAS has been mostly defined, it is unclear how reaction intermediates can transfer between distant catalytic domains. Using single-particle electron microscopy we have identified a near continuum of conformations consistent with remarkable flexibility of FAS. The distribution of conformations was influenced by the presence of substrates and altered by different catalytic mutations suggesting a direct correlation between conformation and specific enzymatic activities. 3D reconstructions were interpreted by docking high-resolution structures of individual domains and illustrate that the substrate loading and condensation domains dramatically swing and swivel to access substrates within either reaction chamber. Concomitant rearrangement of the β-carbon processing domains synchronizes acyl-chain reduction in one chamber with acyl-chain elongation in the other. PMID:19151726
Banner, David W; Gsell, Bernard; Benz, Jörg; Bertschinger, Julian; Burger, Dominique; Brack, Simon; Cuppuleri, Simon; Debulpaep, Maja; Gast, Alain; Grabulovski, Dragan; Hennig, Michael; Hilpert, Hans; Huber, Walter; Kuglstatter, Andreas; Kusznir, Eric; Laeremans, Toon; Matile, Hugues; Miscenic, Christian; Rufer, Arne C; Schlatter, Daniel; Steyaert, Jan; Stihle, Martine; Thoma, Ralf; Weber, Martin; Ruf, Armin
2013-06-01
The aspartic protease BACE2 is responsible for the shedding of the transmembrane protein Tmem27 from the surface of pancreatic β-cells, which leads to inactivation of the β-cell proliferating activity of Tmem27. This role of BACE2 in the control of β-cell maintenance suggests BACE2 as a drug target for diabetes. Inhibition of BACE2 has recently been shown to lead to improved control of glucose homeostasis and to increased insulin levels in insulin-resistant mice. BACE2 has 52% sequence identity to the well studied Alzheimer's disease target enzyme β-secretase (BACE1). High-resolution BACE2 structures would contribute significantly to the investigation of this enzyme as either a drug target or anti-target. Surface mutagenesis, BACE2-binding antibody Fab fragments, single-domain camelid antibody VHH fragments (Xaperones) and Fyn-kinase-derived SH3 domains (Fynomers) were used as crystallization helpers to obtain the first high-resolution structures of BACE2. Eight crystal structures in six different packing environments define an ensemble of low-energy conformations available to the enzyme. Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared.
Bentz, Erika N; Pomilio, Alicia B; Lobayan, Rosana M
2014-12-01
The extension of the study of the conformational space of the structure of (+)-catechin at the B3LYP/6-31G(d,p) level of theory is presented in this paper. (+)-Catechin belongs to the family of the flavan-3-ols, which is one of the five largest phenolic groups widely distributed in nature, and whose biological activity and pharmaceutical utility are related to the antioxidant activity due to their ability to scavenge free radicals. The effects of free rotation around all C-O bonds of the OH substituents at different rings are taken into account, obtaining as the most stable conformer, one that had not been previously reported. One hundred seven structures, and a study of the effects of charge delocalization and stereoelectronic effects at the B3LYP/6-311++G(d,p) level are reported by natural bond orbital analysis, streamlining the order of these structures. For further analysis of the structural and molecular properties of this compound in a biological environment, the calculation of polarizabilities, and the study of the electric dipole moment are performed considering the whole conformational space described. The results are analyzed in terms of accumulated knowledge for (4α → 6″, 2α → O → 1″)-phenylflavans and (+)-catechin in previous works, enriching the study of both types of structures, and taking into account the importance of considering the whole conformational space in modeling both the polarizability and the electric dipole moment, also proposing to define a descriptive subspace of only 16 conformers.
Conformational Asymmetry and Quasicrystal Approximants in Linear Diblock Copolymers
NASA Astrophysics Data System (ADS)
Schulze, Morgan W.; Lewis, Ronald M.; Lettow, James H.; Hickey, Robert J.; Gillard, Timothy M.; Hillmyer, Marc A.; Bates, Frank S.
2017-05-01
Small angle x-ray scattering experiments on three model low molar mass diblock copolymer systems containing minority polylactide and majority hydrocarbon blocks demonstrate that conformational asymmetry stabilizes the Frank-Kasper σ phase. Differences in block flexibility compete with space filling at constant density inducing the formation of polyhedral shaped particles that assemble into this low symmetry ordered state with local tetrahedral coordination. These results confirm predictions from self-consistent field theory that establish the origins of symmetry breaking in the ordering of block polymer melts subjected to compositional and conformational asymmetry.
Conformal structure of massless scalar amplitudes beyond tree level
NASA Astrophysics Data System (ADS)
Banerjee, Nabamita; Banerjee, Shamik; Bhatkar, Sayali Atul; Jain, Sachin
2018-04-01
We show that the one-loop on-shell four-point scattering amplitude of massless ϕ 4 scalar field theory in 4D Minkowski space time, when Mellin transformed to the Celestial sphere at infinity, transforms covariantly under the global conformal group (SL(2, ℂ)) on the sphere. The unitarity of the four-point scalar amplitudes is recast into this Mellin basis. We show that the same conformal structure also appears for the two-loop Mellin amplitude. Finally we comment on some universal structure for all loop four-point Mellin amplitudes specific to this theory.
Single-Molecule Studies of Hyaluronic Acid Conformation
NASA Astrophysics Data System (ADS)
Innes-Gold, Sarah; Berezney, John; Saleh, Omar
Hyaluronic acid (HA) is a charged linear polysaccharide abundant in extracellular spaces. Its solution conformation and mechanical properties help define the environment outside of cells, play key roles in cell motility and adhesion processes, and are of interest for the development of HA biomaterials. Intra-chain hydrogen bonds and electrostatic repulsion contribute to HAs physical structure, but the nature of this structure, as well as its dependence on solution electrostatics, are not well-understood. To address this problem, we have investigated HA conformation and mechanical properties under a range of solution conditions systematically designed to affect charge screening or hydrogen bonding. We used magnetic tweezers to apply biological-scale stretching forces to individual HA chains under varying solution conditions.
Construction of all N=4 conformal supergravities.
Butter, Daniel; Ciceri, Franz; de Wit, Bernard; Sahoo, Bindusar
2017-02-24
All N=4 conformal supergravities in four space-time dimensions are constructed. These are the only N=4 supergravity theories whose actions are invariant under off-shell supersymmetry. They are encoded in terms of a holomorphic function that is homogeneous of zeroth degree in scalar fields that parametrize an SU(1,1)/U(1) coset space. When this function equals a constant the Lagrangian is invariant under continuous SU(1,1) transformations. The construction of these higher-derivative invariants also opens the door to various applications for nonconformal theories.
Conformal manifolds: ODEs from OPEs
NASA Astrophysics Data System (ADS)
Behan, Connor
2018-03-01
The existence of an exactly marginal deformation in a conformal field theory is very special, but it is not well understood how this is reflected in the allowed dimensions and OPE coefficients of local operators. To shed light on this question, we compute perturbative corrections to several observables in an abstract CFT, starting with the beta function. This yields a sum rule that the theory must obey in order to be part of a conformal manifold. The set of constraints relating CFT data at different values of the coupling can in principle be written as a dynamical system that allows one to flow arbitrarily far. We begin the analysis of it by finding a simple form for the differential equations when the spacetime and theory space are both one-dimensional. A useful feature we can immediately observe is that our system makes it very difficult for level crossing to occur.
Express Payload Project - A new method for rapid access to Space Station Freedom
NASA Technical Reports Server (NTRS)
Uhran, Mark L.; Timm, Marc G.
1993-01-01
The deployment and permanent operation of Space Station Freedom will enable researchers to enter a new era in the 21st century, in which continuous on-orbit experimentation and observation become routine. In support of this objective, the Space Station Freedom Program Office has initiated the Express Payload Project. The fundamental project goal is to reduce the marginal cost associated with small payload development, integration, and operation. This is to be accomplished by developing small payload accommodations hardware and a new streamlined small payload integration process. Standardization of small payload interfaces, certification of small payload containers, and increased payload developer responsibility for mission success are key aspects of the Express Payload Project. As the project progresses, the principles will be applied to both pressurized payloads flown inside the station laboratories and unpressurized payloads attached to the station external structures. The increased access to space afforded by Space Station Freedom and the Express Payload Project has the potential to significantly expand the scope, magnitude, and success of future research in the microgravity environment.
Zheng, Lianqing; Chen, Mengen; Yang, Wei
2009-06-21
To overcome the pseudoergodicity problem, conformational sampling can be accelerated via generalized ensemble methods, e.g., through the realization of random walks along prechosen collective variables, such as spatial order parameters, energy scaling parameters, or even system temperatures or pressures, etc. As usually observed, in generalized ensemble simulations, hidden barriers are likely to exist in the space perpendicular to the collective variable direction and these residual free energy barriers could greatly abolish the sampling efficiency. This sampling issue is particularly severe when the collective variable is defined in a low-dimension subset of the target system; then the "Hamiltonian lagging" problem, which reveals the fact that necessary structural relaxation falls behind the move of the collective variable, may be likely to occur. To overcome this problem in equilibrium conformational sampling, we adopted the orthogonal space random walk (OSRW) strategy, which was originally developed in the context of free energy simulation [L. Zheng, M. Chen, and W. Yang, Proc. Natl. Acad. Sci. U.S.A. 105, 20227 (2008)]. Thereby, generalized ensemble simulations can simultaneously escape both the explicit barriers along the collective variable direction and the hidden barriers that are strongly coupled with the collective variable move. As demonstrated in our model studies, the present OSRW based generalized ensemble treatments show improved sampling capability over the corresponding classical generalized ensemble treatments.
Remote Memory Access Protocol Target Node Intellectual Property
NASA Technical Reports Server (NTRS)
Haddad, Omar
2013-01-01
The MagnetoSpheric Multiscale (MMS) mission had a requirement to use the Remote Memory Access Protocol (RMAP) over its SpaceWire network. At the time, no known intellectual property (IP) cores were available for purchase. Additionally, MMS preferred to implement the RMAP functionality with control over the low-level details of the design. For example, not all the RMAP standard functionality was needed, and it was desired to implement only the portions of the RMAP protocol that were needed. RMAP functionality had been previously implemented in commercial off-the-shelf (COTS) products, but the IP core was not available for purchase. The RMAP Target IP core is a VHDL (VHSIC Hardware Description Language description of a digital logic design suitable for implementation in an FPGA (field-programmable gate array) or ASIC (application-specific integrated circuit) that parses SpaceWire packets that conform to the RMAP standard. The RMAP packet protocol allows a network host to access and control a target device using address mapping. This capability allows SpaceWire devices to be managed in a standardized way that simplifies the hardware design of the device, as well as the development of the software that controls the device. The RMAP Target IP core has some features that are unique and not specified in the RMAP standard. One such feature is the ability to automatically abort transactions if the back-end logic does not respond to read/write requests within a predefined time. When a request times out, the RMAP Target IP core automatically retracts the request and returns a command response with an appropriate status in the response packet s header. Another such feature is the ability to control the SpaceWire node or router using RMAP transactions in the extended address range. This allows the SpaceWire network host to manage the SpaceWire network elements using RMAP packets, which reduces the number of protocols that the network host needs to support.
Conformal Cryogenic Tank Trade Study for Reusable Launch Vehicles
NASA Technical Reports Server (NTRS)
Rivers, H. Kevin
1999-01-01
Future reusable launch vehicles may be lifting bodies with non-circular cross section like the proposed Lockheed-Martin VentureStar(tm). Current designs for the cryogenic tanks of these vehicles are dual-lobed and quad-lobed tanks which are packaged more efficiently than circular tanks, but still have low packaging efficiencies with large gaps existing between the vehicle outer mold line and the outer surfaces of the tanks. In this study, tanks that conform to the outer mold line of a non-circular vehicle were investigated. Four structural concepts for conformal cryogenic tanks and a quad-lobed tank concept were optimized for minimum weight designs. The conformal tank concepts included a sandwich tank stiffened with axial tension webs, a sandwich tank stiffened with transverse tension webs, a sandwich tank stiffened with rings and tension ties, and a sandwich tank stiffened with orthogrid stiffeners and tension ties. For each concept, geometric parameters (such as ring frame spacing, the number and spacing of tension ties or webs, and tank corner radius) and internal pressure loads were varied and the structure was optimized using a finite-element-based optimization procedure. Theoretical volumetric weights were calculated by dividing the weight of the barrel section of the tank concept and its associated frames, webs and tension ties by the volume it circumscribes. This paper describes the four conformal tank concepts and the design assumptions utilized in their optimization. The conformal tank optimization results included theoretical weights, trends and comparisons between the concepts, are also presented, along with results from the optimization of a quad-lobed tank. Also, the effects of minimum gauge values and non-optimum weights on the weight of the optimized structure are described in this paper.
NASA Astrophysics Data System (ADS)
Favata', P.; Martineau, N.
2002-01-01
creating a revolutionary space-orbiting habitat dedicated to tourism. Up to now, such proposals have focused on two approaches. The first accounts for financial and technological constraints on space flight and living, and sacrifices creativity for practicality. The second is more utopic in nature and proposes projects, which are imaginative but unfeasible in the near future. This proposal is innovative because it considers the current obstacles to space tourism and utilizes existing technologies and infrastructures, but also includes the forethinking of futuristic commercial projects. Project Objectives: NASA claims that commercialization of space activities is so difficult that it will require decades more funding of so-called space-technology development. The benefits of this project show that this is not true. First, safety has been addressed because this proposal utilizes already space tested and assured technologies. Second, the project demonstrates potential for significant economic profit within the near future. Because we are using the least expensive technology available, we have limited start up costs. We forecast up to forty flights per year, with a potential capacity of eighty tourists. The design objectives focus on the proposal of a new approach to space tourism. These include: the expansion of the living space in the interiors, innovative and creative interior design, increased concern for the physiological and psychological comfort of tourists, and attention to entertainment possibilities. Project Content: The efficiency of the launch and configuration phase is one of the strengths of the proposed project. We propose the use of the Zenith 2 launcher, a large two-stage vehicle developed in the Soviet Union in the early 1980s, for the configuration of the orbiting platform. Following the Russian outfitting philosophy, once in orbit, the platform is already functional. The interior design is based on advanced lightweight inflatable technologies which
Second-order hydrodynamics and universality in non-conformal holographic fluids
NASA Astrophysics Data System (ADS)
Kleinert, Philipp; Probst, Jonas
2016-12-01
We study second-order hydrodynamic transport in strongly coupled non-conformal field theories with holographic gravity duals in asymptotically anti-de Sitter space. We first derive new Kubo formulae for five second-order transport coefficients in non-conformal fluids in (3 + 1) dimensions. We then apply them to holographic RG flows induced by scalar operators of dimension Δ = 3. For general background solutions of the dual bulk geometry, we find explicit expressions for the five transport coefficients at infinite coupling and show that a specific combination, tilde{H}=2η {τ}_{π }-2(κ -{κ}^{ast})-{λ}_2 , always vanishes. We prove analytically that the Haack-Yarom identity H = 2 ητ π - 4λ1 - λ2 = 0, which is known to be true for conformal holographic fluids at infinite coupling, also holds when taking into account leading non-conformal corrections. The numerical results we obtain for two specific families of RG flows suggest that H vanishes regardless of conformal symmetry. Our work provides further evidence that the Haack-Yarom identity H = 0 may be universally satisfied by strongly coupled fluids.
The Ares I Crew Launch Vehicle: Human Space Access for the Moon and Beyond
NASA Technical Reports Server (NTRS)
Cook, Stephen A.
2008-01-01
The National Aeronautics and Space Administration (NASA)'s Constellation Program is depending on the Ares Projects to deliver the crew launch capabilities needed to send human explorers to the Moon and beyond. The Ares Projects continue to make progress toward design, component testing, and early flight testing of the Ares I crew launch vehicle (Figure 1), the United States first new human-rated launch vehicle in over 25 years. Ares I will provide the core space launch capabilities the United States needs to continue providing crew and cargo access to the International Space Station (ISS), maintaining the U.S. pioneering tradition as a spacefaring nation, and enabling cooperative international ventures to the Moon and beyond. This paper will discuss programmatic, design, fabrication, and testing progress toward building this new launch vehicle.
Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120
Korkut, Anil; Hendrickson, Wayne A.
2012-01-01
HIV envelope glycoproteins undergo large-scale conformational changes as they interact with cellular receptors to cause the fusion of viral and cellular membranes that permits viral entry to infect targeted cells. Conformational dynamics in HIV gp120 are also important in masking conserved receptor epitopes from being detected for effective neutralization by the human immune system. Crystal structures of HIV gp120 and its complexes with receptors and antibody fragments provide high-resolution pictures of selected conformational states accessible to gp120. Here we describe systematic computational analyses of HIV gp120 plasticity in such complexes with CD4 binding fragments, CD4 mimetic proteins, and various antibody fragments. We used three computational approaches: an isotropic elastic network analysis of conformational plasticity, a full atomic normal mode analysis, and simulation of conformational transitions with our coarse-grained virtual atom molecular mechanics (VAMM) potential function. We observe collective sub-domain motions about hinge points that coordinate those motions, correlated local fluctuations at the interfacial cavity formed when gp120 binds to CD4, and concerted changes in structural elements that form at the CD4 interface during large-scale conformational transitions to the CD4-bound state from the deformed states of gp120 in certain antibody complexes. PMID:23300605
Bhella, David; Ralph, Adam; Yeo, Robert Paul
2004-07-02
Measles virus is a highly contagious virus that, despite the existence of an effective vaccine, is a major cause of illness and mortality worldwide. The virus has a negative-sense, single-stranded RNA genome that is encapsidated by the nucleocapsid protein (N) to form a helical ribonucleoprotein complex known as the nucleocapsid. This structure serves as the template for both transcription and replication. Paramyxovirus nucleocapsids are flexible structures, a trait that has hitherto hampered structural analysis even at low resolution. We have investigated the extent of this structural plasticity, using real-space methods to calculate three-dimensional reconstructions of recombinant nucleocapsids from cryo-negative stain transmission electron micrographs. Images of short sections of helix were sorted according to both pitch (the axial rise per turn) and twist (the number of subunits per turn). Our analysis indicates that there is extensive conformational flexibility within these structures, ranging in pitch from 50 Angstrom to 66 Angstrom, while twist varies from at least 13.04 to 13.44 with a greater number of helices comprising around 13.1 subunits per turn. We have also investigated the influence of the C terminus of N on helix conformation, analysing nucleocapsids after having removed this domain by trypsin digestion. We have found that this causes a marked change in both pitch and twist, such that the pitch becomes shorter, ranging from 46 Angstrom to 52 Angstrom, while more helices have a twist of approximately 13.3 subunits per turn. Our findings lead us to propose a mechanism whereby changes in conformation, influenced by interactions between viral or host proteins and the C terminus of N, might have a role in regulating the balance of transcription and replication during virus infection.
NASA Astrophysics Data System (ADS)
Abell, Paul; Barbee, B. W.; Mink, R. G.; Adamo, D. R.; Alberding, C. M.; Mazanek, D. D.; Johnson, L. N.; Yeomans, D. K.; Chodas, P. W.; Chamberlin, A. B.; Benner, L. A. M.; Drake, B. G.; Friedensen, V. P.
2012-10-01
Introduction: Much attention has recently been focused on human exploration of near-Earth asteroids (NEAs). Detailed planning for deep space exploration and identification of potential NEA targets for human space flight requires selecting objects from the growing list of known NEAs. NASA therefore initiated the Near-Earth Object Human Space Flight Accessible Target Study (NHATS), which uses dynamical trajectory performance constraints to identify potentially accessible NEAs. Accessibility Criteria: Future NASA human space flight capability is being defined while the Orion Multi-Purpose Crew Vehicle and Space Launch System are under development. Velocity change and mission duration are two of the most critical factors in any human spaceflight endeavor, so the most accessible NEAs tend to be those with orbits similar to Earth’s. To be classified as NHATS-compliant, a NEA must offer at least one round-trip trajectory solution satisfying purposely inclusive constraints, including total mission change in velocity ≤ 12 km/s, mission duration ≤ 450 days (with at least 8 days at the NEA), Earth departure between Jan 1, 2015 and Dec 31, 2040, Earth departure C3 ≤ 60 km2/s2, and Earth return atmospheric entry speed ≤ 12 km/s. Monitoring and Updates: The NHATS list of potentially accessible targets is continuously updated as NEAs are discovered and orbit solutions for known NEAs are improved. The current list of accessible NEAs identified as potentially viable for future human exploration under the NHATS criteria is available to the international community via a website maintained by NASA’s NEO Program Office (http://neo.jpl.nasa.gov/nhats/). This website also lists predicted optical and radar observing opportunities for each NHATS-compliant NEA to facilitate acquisition of follow-up observations. Conclusions: This list of NEAs will be useful for analyzing robotic mission opportunities, identifying optimal round trip human space flight trajectories, and
Dual of the Janus solution: An interface conformal field theory
NASA Astrophysics Data System (ADS)
Clark, A. B.; Freedman, D. Z.; Karch, A.; Schnabl, M.
2005-03-01
We propose and study a specific gauge theory dual of the smooth, nonsupersymmetric (and apparently stable) Janus solution of Type IIB supergravity found in Bak et al. [J. High Energy Phys., JHEPFG, 1029-8479 05 (2003) 072]. The dual field theory is N=4 SYM theory on two half-spaces separated by a planar interface with different coupling constants in each half-space. We assume that the position dependent coupling multiplies the operator L' which is the fourth descendent of the primary TrX{IXJ} and closely related to the N=4 Lagrangian density. At the classical level supersymmetry is broken explicitly, but SO(3,2) conformal symmetry is preserved. We use conformal perturbation theory to study various correlation functions to first and second order in the discontinuity of g2YM, confirming quantum level conformal symmetry. Certain quantities such as the vacuum expectation value
NASA Technical Reports Server (NTRS)
Trauger, John
2008-01-01
Topics include and overview, science objectives, study objectives, coronagraph types, metrics, ACCESS observatory, laboratory validations, and summary. Individual slides examine ACCESS engineering approach, ACCESS gamut of coronagraph types, coronagraph metrics, ACCESS Discovery Space, coronagraph optical layout, wavefront control on the "level playing field", deformable mirror development for HCIT, laboratory testbed demonstrations, high contract imaging with the HCIT, laboratory coronagraph contrast and stability, model validation and performance predictions, HCIT coronagraph optical layout, Lyot coronagraph on the HCIT, pupil mapping (PIAA), shaped pupils, and vortex phase mask experiments on the HCIT.
USDA-ARS?s Scientific Manuscript database
Free-access stalls allow sows to choose the protection of a stall or use of a shared group space. This study investigated the effect of group space width: 0.91 (SS), 2.13 (IS), and 3.05 (LS) m on the health, production, behavior, and welfare of gestating sows. At gestational day (GD) 35.4 ± 2.3, 21 ...
NASA Astrophysics Data System (ADS)
Bieler, Noah S.; Hünenberger, Philippe H.
2015-04-01
Estimating the relative stabilities of different conformational states of a (bio-)molecule using molecular dynamics simulations involves two challenging problems: the conceptual problem of how to define the states of interest and the technical problem of how to properly sample these states, along with achieving a sufficient number of interconversion transitions. In this study, the two issues are addressed in the context of a decaalanine peptide in water, by considering the 310-, α-, and π-helical states. The simulations rely on the ball-and-stick local-elevation umbrella-sampling (B&S-LEUS) method. In this scheme, the states are defined as hyperspheres (balls) in a (possibly high dimensional) collective-coordinate space and connected by hypercylinders (sticks) to ensure transitions. A new object, the pipe, is also introduced here to handle curvilinear pathways. Optimal sampling within the so-defined space is ensured by confinement and (one-dimensional) memory-based biasing potentials associated with the three different kinds of objects. The simulation results are then analysed in terms of free energies using reweighting, possibly relying on two distinct sets of collective coordinates for the state definition and analysis. The four possible choices considered for these sets are Cartesian coordinates, hydrogen-bond distances, backbone dihedral angles, or pairwise sums of successive backbone dihedral angles. The results concerning decaalanine underline that the concept of conformational state may be extremely ambiguous, and that its tentative absolute definition as a free-energy basin remains subordinated to the choice of a specific analysis space. For example, within the force-field employed and depending on the analysis coordinates selected, the 310-helical state may refer to weakly overlapping collections of conformations, differing by as much as 25 kJ mol-1 in terms of free energy. As another example, the π-helical state appears to correspond to a free
Bieler, Noah S; Hünenberger, Philippe H
2015-04-28
Estimating the relative stabilities of different conformational states of a (bio-)molecule using molecular dynamics simulations involves two challenging problems: the conceptual problem of how to define the states of interest and the technical problem of how to properly sample these states, along with achieving a sufficient number of interconversion transitions. In this study, the two issues are addressed in the context of a decaalanine peptide in water, by considering the 310-, α-, and π-helical states. The simulations rely on the ball-and-stick local-elevation umbrella-sampling (B&S-LEUS) method. In this scheme, the states are defined as hyperspheres (balls) in a (possibly high dimensional) collective-coordinate space and connected by hypercylinders (sticks) to ensure transitions. A new object, the pipe, is also introduced here to handle curvilinear pathways. Optimal sampling within the so-defined space is ensured by confinement and (one-dimensional) memory-based biasing potentials associated with the three different kinds of objects. The simulation results are then analysed in terms of free energies using reweighting, possibly relying on two distinct sets of collective coordinates for the state definition and analysis. The four possible choices considered for these sets are Cartesian coordinates, hydrogen-bond distances, backbone dihedral angles, or pairwise sums of successive backbone dihedral angles. The results concerning decaalanine underline that the concept of conformational state may be extremely ambiguous, and that its tentative absolute definition as a free-energy basin remains subordinated to the choice of a specific analysis space. For example, within the force-field employed and depending on the analysis coordinates selected, the 310-helical state may refer to weakly overlapping collections of conformations, differing by as much as 25 kJ mol(-1) in terms of free energy. As another example, the π-helical state appears to correspond to a free
Coarse-grained Simulations of Conformational Changes in Multidrug Resistance Transporters
NASA Astrophysics Data System (ADS)
Jewel, S. M. Yead; Dutta, Prashanta; Liu, Jin
2016-11-01
The overexpression of multidrug resistance (MDR) systems on the gram negative bacteria causes serious problems for treatment of bacterial infectious diseases. The system effectively pumps the antibiotic drugs out of the bacterial cells. During the pumping process one of the MDR components, AcrB undergoes a series of large-scale conformational changes which are responsible for drug recognition, binding and expelling. All-atom simulations are unable to capture those conformational changes because of computational cost. Here, we implement a hybrid coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid, to investigate the proton-dependent conformational changes of AcrB. The simulation results in early stage ( 100 ns) of proton-dependent conformational changes agree with all-atom simulations, validating the coarse-grained model. The coarse-grained force field allows us to explore the process in microsecond simulations. Starting from the crystal structures of Access(A)/Binding(B)/Extrusion(E) monomers in AcrB, we find that deprotonation of Asp407 and Asp408 in monomer E causes a series of large-scale conformational changes from ABE to AAA in absence of drug molecules, which is consistent with experimental findings. This work is supported by NIH Grant: 1R01GM122081-01.
Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations
NASA Astrophysics Data System (ADS)
Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng
2017-04-01
VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states.
Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations
Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng
2017-01-01
VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states. PMID:28425502
Structure-based conformational preferences of amino acids
Koehl, Patrice; Levitt, Michael
1999-01-01
Proteins can be very tolerant to amino acid substitution, even within their core. Understanding the factors responsible for this behavior is of critical importance for protein engineering and design. Mutations in proteins have been quantified in terms of the changes in stability they induce. For example, guest residues in specific secondary structures have been used as probes of conformational preferences of amino acids, yielding propensity scales. Predicting these amino acid propensities would be a good test of any new potential energy functions used to mimic protein stability. We have recently developed a protein design procedure that optimizes whole sequences for a given target conformation based on the knowledge of the template backbone and on a semiempirical potential energy function. This energy function is purely physical, including steric interactions based on a Lennard-Jones potential, electrostatics based on a Coulomb potential, and hydrophobicity in the form of an environment free energy based on accessible surface area and interatomic contact areas. Sequences designed by this procedure for 10 different proteins were analyzed to extract conformational preferences for amino acids. The resulting structure-based propensity scales show significant agreements with experimental propensity scale values, both for α-helices and β-sheets. These results indicate that amino acid conformational preferences are a natural consequence of the potential energy we use. This confirms the accuracy of our potential and indicates that such preferences should not be added as a design criterion. PMID:10535955
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brodsky, S
2003-11-19
Theoretical and phenomenological evidence is now accumulating that the QCD coupling becomes constant at small virtuality; i.e., {alpha}{sub s}(Q{sup 2}) develops an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. For example, the hadronic decays of the {tau} lepton can be used to determine the effective charge {alpha}{sub {tau}}(m{sub {tau}{prime}}{sup 2}) for a hypothetical {tau}-lepton with mass in the range 0 < m{sub {tau}{prime}} < m{sub {tau}}. The {tau} decay data at low mass scales indicates that the effective charge freezes at a value of s = m{sub {tau}{prime}}{sup 2} of order 1more » GeV{sup 2} with a magnitude {alpha}{sub {tau}} {approx} 0.9 {+-} 0.1. The near-constant behavior of effective couplings suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer and why there are no significant running coupling corrections to quark counting rules for exclusive processes. The AdS/CFT correspondence of large N{sub c} supergravity theory in higher-dimensional anti-de Sitter space with supersymmetric QCD in 4-dimensional space-time also has interesting implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for exclusive processes and light-front wavefunctions. The utility of light-front quantization and light-front Fock wavefunctions for analyzing nonperturbative QCD and representing the dynamics of QCD bound states is also discussed.« less
Plan-graph Based Heuristics for Conformant Probabilistic Planning
NASA Technical Reports Server (NTRS)
Ramakrishnan, Salesh; Pollack, Martha E.; Smith, David E.
2004-01-01
In this paper, we introduce plan-graph based heuristics to solve a variation of the conformant probabilistic planning (CPP) problem. In many real-world problems, it is the case that the sensors are unreliable or take too many resources to provide knowledge about the environment. These domains are better modeled as conformant planning problems. POMDP based techniques are currently the most successful approach for solving CPP but have the limitation of state- space explosion. Recent advances in deterministic and conformant planning have shown that plan-graphs can be used to enhance the performance significantly. We show that this enhancement can also be translated to CPP. We describe our process for developing the plan-graph heuristics and estimating the probability of a partial plan. We compare the performance of our planner PVHPOP when used with different heuristics. We also perform a comparison with a POMDP solver to show over a order of magnitude improvement in performance.
NASA Technical Reports Server (NTRS)
Beck, Robin A S.; Arnold, James O.; Gasch, Matthew J.; Stackpoole, Margaret M.; Prabhu, Dinesh K.; Szalai, Christine E.; Wercinski, Paul F.; Venkatapathy, Ethiraj
2013-01-01
The Office of Chief Technologist, NASA identified the need for research and technology development in part from NASAs Strategic Goal 3.3 of the NASA Strategic Plan to develop and demonstrate the critical technologies that will make NASAs exploration, science, and discovery missions more affordable and more capable. Furthermore, the Game Changing Development Program is a primary avenue to achieve the Agencys 2011 strategic goal to Create the innovative new space technologies for our exploration, science, and economic future. The National Research Council (NRC) Space Technology Roadmaps and Priorities report highlights six challenges and they are: Mass to Surface, Surface Access, Precision Landing, Surface Hazard Detection and Avoidance, Safety and Mission Assurance, and Affordability. In order for NASA to meet these challenges, the report recommends immediate focus on Rigid and Flexible Thermal Protection Systems. Rigid TPS systems such as Avcoat or SLA are honeycomb based and PICA is in the form of tiles. The honeycomb systems are manufactured using techniques that require filling of each (38 cell) by hand, and in a limited amount of time all of the cells must be filled and the heatshield must be cured. The tile systems such as PICA pose a different challenge as the low strain-to-failure and manufacturing size limitations require large number of small tiles with gap-fillers between the tiles. Recent investments in flexible ablative systems have given rise to the potential for conformal ablative TPS. A conformal TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials. The high strain-to-failure nature of the conformal ablative materials will allow integration of the TPS with the underlying aeroshell structure much easier and enable monolithic-like configuration and larger segments (or parts) to be used. By reducing the overall part count, the cost of installation (based on cost comparisons between blanket
Symmetric factorization of the conformation tensor in viscoelastic fluid models
NASA Astrophysics Data System (ADS)
Thomases, Becca; Balci, Nusret; Renardy, Michael; Doering, Charles
2010-11-01
The positive definite symmetric polymer conformation tensor possesses a unique symmetric square root that satisfies a closed evolution equation in the Oldroyd-B and FENE-P models of viscoelastic fluid flow. When expressed in terms of the velocity field and the symmetric square root of the conformation tensor, these models' equations of motion formally constitute an evolution in a Hilbert space with a total energy functional that defines a norm. Moreover, this formulation is easily implemented in direct numerical simulations resulting in significant practical advantages in terms of both accuracy and stability.
Free energy landscapes of peptides by enhanced conformational sampling.
Nakajima, N; Higo, J; Kidera, A; Nakamura, H
2000-02-11
The free energy landscapes of peptide conformations in water have been observed by the enhanced conformational sampling method, applying the selectively enhanced multicanonical molecular dynamics simulations. The conformations of the peptide dimers, -Gly-Gly-, -Gly-Ala-, -Gly-Ser-, -Ala-Gly-, -Asn-Gly-, -Pro-Gly-, -Pro-Ala-, and -Ala-Ala-, which were all blocked with N-terminal acetyl and C-terminal N-methyl groups, were individually sampled with the explicit TIP3P water molecules. From each simulation trajectory, we obtained the canonical ensemble at 300 K, from which the individual three-dimensional landscape was drawn by the potential of mean force using the three reaction coordinates: the backbone dihedral angle, psi, of the first amino acid, the backbone dihedral angle, phi, of the second amino acid, and the distance between the carbonyl oxygen of the N-terminal acetyl group and the C-terminal amide proton. The most stable state and several meta-stable states correspond to extended conformations and typical beta-turn conformations, and their free energy values were accounted for from the potentials of mean force at the states. In addition, the contributions from the intra-molecular energies of peptides and those from the hydration effects were analyzed. Consequently, the stable beta-turn conformations in the free energy landscape were consistent with the empirically preferred beta-turn types for each amino acid sequence. The thermodynamic values for the hydration effect were decomposed and they correlated well with the empirical values estimated from the solvent accessible surface area of each molecular conformation during the trajectories. The origin of the architecture of protein local fragments was analyzed from the viewpoint of the free energy and its decomposed factors. Copyright 2000 Academic Press.
An investigation into Ca-DNA conformation as a function of relative humidity
NASA Astrophysics Data System (ADS)
Smith, Megan Schwenker
Raman spectroscopy experiments on CaDNA free-standing, highly-ordered wet-spun films containing various concentrations of CaCl2 show that CaDNA does not adopt the A conformation and reveals a maximum of DNA in the B conformation at 80% relative humidity. Swelling experiments on these same films give information as to the intermolecular spacing between molecules. Finally, a proof of principle measurement of the activation enthalpy of guanosine is also given.
Solving the Nonlocality Riddle by Conformal Quantum Geometrodynamics
NASA Astrophysics Data System (ADS)
Santamato, Enrico; de Martini, Francesco
2012-01-01
Since the 1935 proposal by Einstein, Podolsky and Rosen the riddle of nonlocality, today demonstrated by the violation of Bell's inequalities within innumerable experiments, has been a cause of concern and confusion within the debate over the foundations of quantum mechanics. The present paper tackles the problem by a nonrelativistic approach based on conformal differential geometry applied to the solution of the dynamical problem of two entangled spin 1/2 particles. It is found that the quantum nonlocality may be understood on the basis of a conformal quantum geometrodynamics acting necessarily on the full "configuration space" of the entangled particles. At the end, the violation of the Bell inequalities is demonstrated without making recourse to the common nonlocality paradigm.
NASA Astrophysics Data System (ADS)
Fawkes, S.
This paper compares and contrasts the characteristics of the first space race, which ran from the late 1950s to the late 1990s, and the second space race that began with the successful space flight of SpaceShipOne in 2004. The first space race was between superpowers seeking to establish geo-political dominance in the Cold War. The second space race will be between competing companies seeking to establish low cost access to space for ordinary people. The first space race achieved its geo- political objectives but did not open up low cost access to space but rather restricted access to a select few, highly trained astronauts and cosmonauts. The second space race, driven by the size and growth of the travel and tourism industry, promises to open up access to space to millions of space tourists.
NASA Technical Reports Server (NTRS)
Roberts, Aaron
2005-01-01
New tools for data access and visualization promise to make the analysis of space plasma data both more efficient and more powerful, especially for answering questions about the global structure and dynamics of the Sun-Earth system. We will show how new existing tools (particularly the Virtual Space Physics Observatory-VSPO-and the Visual System for Browsing, Analysis and Retrieval of Data-ViSBARD; look for the acronyms in Google) already provide rapid access to such information as spacecraft orbits, browse plots, and detailed data, as well as visualizations that can quickly unite our view of multispacecraft observations. We will show movies illustrating multispacecraft observations of the solar wind and magnetosphere during a magnetic storm, and of simulations of 3 0-spacecraft observations derived from MHD simulations of the magnetosphere sampled along likely trajectories of the spacecraft for the MagCon mission. An important issue remaining to be solved is how best to integrate simulation data and services into the Virtual Observatory environment, and this talk will hopefully stimulate further discussion along these lines.
Helmling, Christina; Wacker, Anna; Wolfinger, Michael T; Hofacker, Ivo L; Hengesbach, Martin; Fürtig, Boris; Schwalbe, Harald
2017-02-22
Gene repression induced by the formation of transcriptional terminators represents a prime example for the coupling of RNA synthesis, folding, and regulation. In this context, mapping the changes in available conformational space of transcription intermediates during RNA synthesis is important to understand riboswitch function. A majority of riboswitches, an important class of small metabolite-sensing regulatory RNAs, act as transcriptional regulators, but the dependence of ligand binding and the subsequent allosteric conformational switch on mRNA transcript length has not yet been investigated. We show a strict fine-tuning of binding and sequence-dependent alterations of conformational space by structural analysis of all relevant transcription intermediates at single-nucleotide resolution for the I-A type 2'dG-sensing riboswitch from Mesoplasma florum by NMR spectroscopy. Our results provide a general framework to dissect the coupling of synthesis and folding essential for riboswitch function, revealing the importance of metastable states for RNA-based gene regulation.
Ariel, Federico; Latrasse, David; Mariappan, Kiruthiga Gayathri; Kim, Soon-Kap; Crespi, Martin; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cécile; Benhamed, Moussa
2016-01-01
Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns. PMID:27410265
Yu, Rongjun; Sun, Sai
2013-01-01
When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.
Conformation and structure of 3-methoxyphenyl-salicylaldimine
NASA Astrophysics Data System (ADS)
Elmali, A.; Kabak, M.; Elerman, Y.
1999-06-01
3-methoxyphenyl-salicylaldimine (C 14H 13NO 2) was studied by X-ray analysis and AM1 molecular orbital methods. It crystallises in the monoclinic space group P2 1/c with a=20.486(4) Å, b=4.7935(8) Å Å, c=12.310(5) Å, β=107.43(2)°, V=1153.3(6) Å 3, Z=4, D 0=1.309 g cm -3, Z=4, and μ(MoK α)=0.088 mm -1. The structure was solved by direct methods and refined to R=0.033 for 1635 reflections [ I<2(( I)]. The title molecule was nearly planar. There was a strong intramolecular hydrogen bond of distance 2.598(2) Å between the hydroxyl oxygen atom and imine nitrogen atom, the hydrogen atom essentially being bonded to the oxygen atom. Minimum energy conformations from AM1 were calculated as a function of the three torsion angles θ1(C8-N1-C7-C6), θ2(N1-C7-C6-C5), and θ3(C9-C8-N1-C7) varied every 10°. The theoretical calculations were carried out to compare with experimental results of the molecular conformations. The optimized geometry of the crystal structure corresponding to a non-planar conformation is the most stable conformation in all theoretical calculations.
Frustration-guided motion planning reveals conformational transitions in proteins
DOE Office of Scientific and Technical Information (OSTI.GOV)
Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here in this paper, we present a new, robotics-inspired motion planning procedure called dCCRRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eightmore » proteins determined in two conformations separated by, on average, 7.5Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. Additionally, we then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions.Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/.« less
Frustration-guided motion planning reveals conformational transitions in proteins.
Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; van den Bedem, Henry
2017-10-01
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25 Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/. © 2017 Wiley Periodicals, Inc.
Frustration-guided motion planning reveals conformational transitions in proteins
Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; ...
2017-07-12
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here in this paper, we present a new, robotics-inspired motion planning procedure called dCCRRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eightmore » proteins determined in two conformations separated by, on average, 7.5Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. Additionally, we then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions.Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/.« less
Buczek, Aneta; Siodłak, Dawid; Bujak, Maciej; Broda, Małgorzata A
2011-04-21
Two E isomers of α,β-dehydro-phenylalanine, Ac-(E)-ΔPhe-NHMe (1a) and Ac-(E)-ΔPhe-NMe(2) (2a), have been synthesized and their low temperature structures determined by single-crystal X-ray diffraction. A systematic theoretical analysis was performed on these molecules and their Z isomers (1b and 2b). The ϕ,ψ potential energy surfaces were calculated at the MP2/6-31+G(d,p) and B3LYP/6-31+G(d,p) levels in the gas phase and at the B3LYP/6-31+G(d,p) level in the chloroform and water solutions with the SCRF-PCM method. All minima were fully optimized by the MP2 and DFT methods, and their relative stabilities were analyzed in terms of π-conjugation, internal H-bonds, and dipole-dipole interactions between carbonyl groups. The results indicate that all the studied compounds can adopt the conformation H (ϕ, ψ ≈ ±40°, ∓120°) which is atypical for standard amino acids residues. A different arrangement of the side chain in the E and Z isomers causes them to have different conformational preferences. In the presence of a polar solvent both Z isomers of ΔPhe (1b and 2b) are found to adopt the 3(10)-helical conformation (left- and right-handed are equally likely). On the other hand, this conformation is not accessible or highly energetic for E isomers of ΔPhe (1a and 2a). Those isomers have an intrinsic inclination to have an extended conformation. The conformational space of the Z isomers is much more restricted than that of the E derivative both in the gas phase and in solution. In the gas phase the E isomers of ΔPhe have lower energies than the Z ones, but in the aqueous solution the energy order is reversed.
Khakinejad, Mahdiar; Kondalaji, Samaneh Ghassabi; Tafreshian, Amirmahdi; Valentine, Stephen J
2015-07-01
The per-residue, gas-phase hydrogen deuterium exchange (HDX) kinetics for individual amino acid residues on selected ion conformer types of the model peptide KKDDDDDIIKIIK have been examined using ion mobility spectrometry (IMS) and HDX-tandem mass spectrometry (MS/MS) techniques. The [M + 4H](4+) ions exhibit two major conformer types with collision cross sections of 418 Å(2) and 446 Å(2); the [M + 3H](3+) ions also yield two different conformer types having collision cross sections of 340 Å(2) and 367 Å(2). Kinetics plots of HDX for individual amino acid residues reveal fast- and slow-exchanging hydrogens. The contributions of each amino acid residue to the overall conformer type rate constant have been estimated. For this peptide, N- and C-terminal K residues exhibit the greatest contributions for all ion conformer types. Interior D and I residues show decreased contributions. Several charge state trends are observed. On average, the D residues of the [M + 3H](3+) ions show faster HDX rate contributions compared with [M + 4H](4+) ions. In contrast the interior I8 and I9 residues show increased accessibility to exchange for the more elongated [M + 4H](4+) ion conformer type. The contribution of each residue to the overall uptake rate showed a good correlation with a residue hydrogen accessibility score model calculated using a distance from charge site and initial incorporation site for nominal structures obtained from molecular dynamic simulations (MDS).
Man-made space debris - Does it restrict free access to space
NASA Technical Reports Server (NTRS)
Wolfe, M.; Chobotov, V.; Kessler, D.; Reynolds, R.
1981-01-01
Consideration is given to the hazards posed by existing and future man-made space debris to spacecraft operations. The components of the hazard are identified as those fragments resulting from spacecraft explosions and spent stages which can be tracked, those fragments which are too small to be tracked at their present distances, and future debris, which, if present trends in spacecraft design and operation continue, may lead to an unacceptably high probability of collision with operational spacecraft within a decade. It is argued that a coordinated effort must be undertaken by all space users to evaluate means of space debris control in order to allow for the future unrestricted use of near-earth space. A plan for immediate action to forestall the space debris problem by activities in the areas of education, debris monitoring and collection technology, space vehicle design, space operational procedures and practices and space policies and treaties is proposed.
PDB ligand conformational energies calculated quantum-mechanically.
Sitzmann, Markus; Weidlich, Iwona E; Filippov, Igor V; Liao, Chenzhong; Peach, Megan L; Ihlenfeldt, Wolf-Dietrich; Karki, Rajeshri G; Borodina, Yulia V; Cachau, Raul E; Nicklaus, Marc C
2012-03-26
We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6-311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies-the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer-significant energy values were found. The range of 0 to ~25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 Å. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R(free)-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient
Kuş, Nihal; Henriques, Marta Sofia; Paixão, José António; Lapinski, Leszek; Fausto, Rui
2014-09-25
The crystal structure of 3-quinolinecarboxaldehyde (3QC) has been solved, and the compound has been shown to crystallize in the space group P21/c (monoclinic) with a = 6.306(4), b = 18.551(11), c = 6.999(4) Å, β = 106.111(13)°, and Z = 4. The crystals were found to exhibit pseudomerohedral twinning with a twin law corresponding to a two-fold rotation around the monoclinic (100) reciprocal lattice axis (or [4 0 1] in direct space). Individual molecules adopt the syn conformation in the crystal, with the oxygen atom of the aldehyde substituent directed toward the same side of the ring nitrogen atom. In the gas phase, the compound exists in two nearly isoenergetic conformers (syn and anti), which could be successfully trapped in solid argon at 10 K, and their infrared spectra are registered and interpreted. Upon in situ irradiation of matrix-isolated 3QC with UV light (λ > 315 nm), significant reduction of the population of the less stable anti conformer was observed, while that of the conformational ground state (syn conformer) increased, indicating occurrence of the anti → syn isomerization. Upon irradiation at higher energy (λ > 235 nm), the syn → anti reverse photoreaction was observed. Interpretation of the structural, spectroscopic, and photochemical experimental data received support from quantum chemical theoretical results obtained at both DFT/B3LYP (including TD-DFT investigation of excited states) and MP2 levels, using the 6-311++G(d,p) basis set.
Characterizing protein conformations by correlation analysis of coarse-grained contact matrices.
Lindsay, Richard J; Siess, Jan; Lohry, David P; McGee, Trevor S; Ritchie, Jordan S; Johnson, Quentin R; Shen, Tongye
2018-01-14
We have developed a method to capture the essential conformational dynamics of folded biopolymers using statistical analysis of coarse-grained segment-segment contacts. Previously, the residue-residue contact analysis of simulation trajectories was successfully applied to the detection of conformational switching motions in biomolecular complexes. However, the application to large protein systems (larger than 1000 amino acid residues) is challenging using the description of residue contacts. Also, the residue-based method cannot be used to compare proteins with different sequences. To expand the scope of the method, we have tested several coarse-graining schemes that group a collection of consecutive residues into a segment. The definition of these segments may be derived from structural and sequence information, while the interaction strength of the coarse-grained segment-segment contacts is a function of the residue-residue contacts. We then perform covariance calculations on these coarse-grained contact matrices. We monitored how well the principal components of the contact matrices is preserved using various rendering functions. The new method was demonstrated to assist the reduction of the degrees of freedom for describing the conformation space, and it potentially allows for the analysis of a system that is approximately tenfold larger compared with the corresponding residue contact-based method. This method can also render a family of similar proteins into the same conformational space, and thus can be used to compare the structures of proteins with different sequences.
Characterizing protein conformations by correlation analysis of coarse-grained contact matrices
NASA Astrophysics Data System (ADS)
Lindsay, Richard J.; Siess, Jan; Lohry, David P.; McGee, Trevor S.; Ritchie, Jordan S.; Johnson, Quentin R.; Shen, Tongye
2018-01-01
We have developed a method to capture the essential conformational dynamics of folded biopolymers using statistical analysis of coarse-grained segment-segment contacts. Previously, the residue-residue contact analysis of simulation trajectories was successfully applied to the detection of conformational switching motions in biomolecular complexes. However, the application to large protein systems (larger than 1000 amino acid residues) is challenging using the description of residue contacts. Also, the residue-based method cannot be used to compare proteins with different sequences. To expand the scope of the method, we have tested several coarse-graining schemes that group a collection of consecutive residues into a segment. The definition of these segments may be derived from structural and sequence information, while the interaction strength of the coarse-grained segment-segment contacts is a function of the residue-residue contacts. We then perform covariance calculations on these coarse-grained contact matrices. We monitored how well the principal components of the contact matrices is preserved using various rendering functions. The new method was demonstrated to assist the reduction of the degrees of freedom for describing the conformation space, and it potentially allows for the analysis of a system that is approximately tenfold larger compared with the corresponding residue contact-based method. This method can also render a family of similar proteins into the same conformational space, and thus can be used to compare the structures of proteins with different sequences.
NASA Technical Reports Server (NTRS)
Carnahan, Richard S., Jr.; Corey, Stephen M.; Snow, John B.
1989-01-01
Applications of rapid prototyping and Artificial Intelligence techniques to problems associated with Space Station-era information management systems are described. In particular, the work is centered on issues related to: (1) intelligent man-machine interfaces applied to scientific data user support, and (2) the requirement that intelligent information management systems (IIMS) be able to efficiently process metadata updates concerning types of data handled. The advanced IIMS represents functional capabilities driven almost entirely by the needs of potential users. Space Station-era scientific data projected to be generated is likely to be significantly greater than data currently processed and analyzed. Information about scientific data must be presented clearly, concisely, and with support features to allow users at all levels of expertise efficient and cost-effective data access. Additionally, mechanisms for allowing more efficient IIMS metadata update processes must be addressed. The work reported covers the following IIMS design aspects: IIMS data and metadata modeling, including the automatic updating of IIMS-contained metadata, IIMS user-system interface considerations, including significant problems associated with remote access, user profiles, and on-line tutorial capabilities, and development of an IIMS query and browse facility, including the capability to deal with spatial information. A working prototype has been developed and is being enhanced.
NASA Astrophysics Data System (ADS)
Geary, E. E.; Barstow, D.
2001-12-01
Enhancing access to high quality science education resources for teachers, students, and the general public is a high priority for the earth and space science education communities. However, to significantly increase access to these resources and promote their effective use will require a coordinated effort between content developers, publishers, professional developers, policy makers, and users in both formal and informal education settings. Federal agencies, academic institutions, professional societies, informal science centers, the Digital Library for Earth System Education, and other National SMETE Digital Library Projects are anticipated to play key roles in this effort. As a first step to developing a coordinated, national strategy for developing and delivering high quality earth and space science education resources to students, teachers, and the general public, 65 science educators, scientists, teachers, administrators, policy makers, and business leaders met this June in Snowmass, Colorado to create "Earth and Space Science Education 2010: A Blueprint for Change". The Blueprint is a strategy document that will be used to guide Earth and space science education reform efforts in grades K-12 during the next decade. The Blueprint contains specific goals, recommendations, and strategies for coordinating action in the areas of: Teacher Preparation and Professional Development, Curriculum and Materials, Equity and Diversity, Assessment and Evaluation, Public Policy and Systemic Reform, Public and Informal Education, Partnerships and Collaborations, and Technology. If you develop, disseminate, or use exemplary earth and space science education resources, we invite you to review the Blueprint for Change, share it with your colleagues and local science educators, and join as we work to revolutionize earth and space science education in grades K-12.
A comparison of two conformal mapping techniques applied to an aerobrake body
NASA Technical Reports Server (NTRS)
Hommel, Mark J.
1987-01-01
Conformal mapping is a classical technique which has been utilized for solving problems in aerodynamics and hydrodynamics. Conformal mapping has been successfully applied in the construction of grids around airfoils, engine inlets and other aircraft configurations. Conformal mapping techniques were applied to an aerobrake body having an axis of symmetry. Two different approaches were utilized: (1) Karman-Trefftz transformation; and (2) Point Wise Schwarz Christoffel transformation. In both cases, the aerobrake body was mapped onto a near circle, and a grid was generated in the mapped plane. The mapped body and grid were then mapped back into physical space and the properties of the associated grids were examined. Advantages and disadvantages of both approaches are discussed.
NASA Technical Reports Server (NTRS)
Barbee, Brent W.; Mink, Ronald G.; Adamo, Daniel R.; Alberding, Cassandra M.
2011-01-01
Near-Earth Asteroids (NEAs) have been identified by the Administration as potential destinations for human explorers during the mid-2020s. Planning such ambitious missions requires selecting potentially accessible targets from the growing known population of 8,008 NEAs. NASA is therefore conducting the Near-Earth Object (NEO) Human Space Flight (HSF) Accessible Targets Study (NHATS), in which the trajectory opportunities to all known NEAs are being systematically evaluated with respect to a set of defined constraints. While the NHATS algorithms have identified hundreds of NEAs which satisfy purposely inclusive trajectory constraints, only a handful of them offer truly attractive mission opportunities in the time frame of greatest interest. In this paper we will describe the structure of the NHATS algorithms and the constraints utilized in the study, present current study results, and discuss various mission design considerations for future human space flight missions to NEAs.
Null conformal Killing-Yano tensors and Birkhoff theorem
NASA Astrophysics Data System (ADS)
Ferrando, Joan Josep; Sáez, Juan Antonio
2016-04-01
We study the space-times admitting a null conformal Killing-Yano tensor whose divergence defines a Killing vector. We analyze the similarities and differences with the recently studied non null case (Ferrando and Sáez in Gen Relativ Gravit 47:1911, 2015). The results by Barnes concerning the Birkhoff theorem for the case of null orbits are analyzed and generalized.
ConformRank: A conformity-based rank for finding top-k influential users
NASA Astrophysics Data System (ADS)
Wang, Qiyao; Jin, Yuehui; Cheng, Shiduan; Yang, Tan
2017-05-01
Finding influential users is a hot topic in social networks. For example, advertisers identify influential users to make a successful campaign. Retweeters forward messages from original users, who originally publish messages. This action is referred to as retweeting. Retweeting behaviors generate influence. Original users have influence on retweeters. Whether retweeters keep the same sentiment as original users is taken into consideration in this study. Influence is calculated based on conformity from emotional perspective after retweeting. A conformity-based algorithm, called ConformRank, is proposed to find top-k influential users, who make the most users keep the same sentiment after retweeting messages. Emotional conformity is introduced to denote how users conform to original users from the emotional perspective. Conforming weights are introduced to denote how two users keep the same sentiment after retweeting messages. Emotional conformity is applied for users and conforming weights are used for relations. Experiments were conducted on Sina Weibo. Experimental results show that users have larger influence when they publish positive messages.
Crossing symmetry in alpha space
NASA Astrophysics Data System (ADS)
Hogervorst, Matthijs; van Rees, Balt C.
2017-11-01
We initiate the study of the conformal bootstrap using Sturm-Liouville theory, specializing to four-point functions in one-dimensional CFTs. We do so by decomposing conformal correlators using a basis of eigenfunctions of the Casimir which are labeled by a complex number α. This leads to a systematic method for computing conformal block decompositions. Analyzing bootstrap equations in alpha space turns crossing symmetry into an eigenvalue problem for an integral operator K. The operator K is closely related to the Wilson transform, and some of its eigenfunctions can be found in closed form.
Shape dynamics and Mach's principles: Gravity from conformal geometrodynamics
NASA Astrophysics Data System (ADS)
Gryb, Sean
2012-04-01
In this PhD thesis, we develop a new approach to classical gravity starting from Mach's principles and the idea that the local shape of spatial configurations is fundamental. This new theory, "shape dynamics", is equivalent to general relativity but differs in an important respect: shape dynamics is a theory of dynamic conformal 3-geometry, not a theory of spacetime. Equivalence is achieved by trading foliation invariance for local conformal invariance (up to a global scale). After the trading, what is left is a gauge theory invariant under 3d diffeomorphisms and conformal transformations that preserve the volume of space. The local canonical constraints are linear and the constraint algebra closes with structure constants. Shape dynamics, thus, provides a novel new starting point for quantum gravity. The procedure for the trading of symmetries was inspired by a technique called "best matching". We explain best matching and its relation to Mach's principles. The key features of best matching are illustrated through finite dimensional toy models. A general picture is then established where relational theories are treated as gauge theories on configuration space. Shape dynamics is then constructed by applying best matching to conformal geometry. We then study shape dynamics in more detail by computing its Hamiltonian and Hamilton-Jacobi functional perturbatively. This thesis is intended as a pedagogical but complete introduction to shape dynamics and the Machian ideas that led to its discovery. The reader is encouraged to start with the introduction, which gives a conceptual outline and links to the relevant sections in the text for a more rigorous exposition. When full rigor is lacking, references to the literature are given. It is hoped that this thesis may provide a starting point for anyone interested in learning about shape dynamics.
Logarithmic conformal field theory: beyond an introduction
NASA Astrophysics Data System (ADS)
Creutzig, Thomas; Ridout, David
2013-12-01
This article aims to review a selection of central topics and examples in logarithmic conformal field theory. It begins with the remarkable observation of Cardy that the horizontal crossing probability of critical percolation may be computed analytically within the formalism of boundary conformal field theory. Cardy’s derivation relies on certain implicit assumptions which are shown to lead inexorably to indecomposable modules and logarithmic singularities in correlators. For this, a short introduction to the fusion algorithm of Nahm, Gaberdiel and Kausch is provided. While the percolation logarithmic conformal field theory is still not completely understood, there are several examples for which the formalism familiar from rational conformal field theory, including bulk partition functions, correlation functions, modular transformations, fusion rules and the Verlinde formula, has been successfully generalized. This is illustrated for three examples: the singlet model \\mathfrak {M} (1,2), related to the triplet model \\mathfrak {W} (1,2), symplectic fermions and the fermionic bc ghost system; the fractional level Wess-Zumino-Witten model based on \\widehat{\\mathfrak {sl}} \\left( 2 \\right) at k=-\\frac{1}{2}, related to the bosonic βγ ghost system; and the Wess-Zumino-Witten model for the Lie supergroup \\mathsf {GL} \\left( 1 {\\mid} 1 \\right), related to \\mathsf {SL} \\left( 2 {\\mid} 1 \\right) at k=-\\frac{1}{2} and 1, the Bershadsky-Polyakov algebra W_3^{(2)} and the Feigin-Semikhatov algebras W_n^{(2)}. These examples have been chosen because they represent the most accessible, and most useful, members of the three best-understood families of logarithmic conformal field theories. The logarithmic minimal models \\mathfrak {W} (q,p), the fractional level Wess-Zumino-Witten models, and the Wess-Zumino-Witten models on Lie supergroups (excluding \\mathsf {OSP} \\left( 1 {\\mid} 2n \\right)). In this review, the emphasis lies on the representation theory
Grouleff, Julie; Schiøtt, Birgit
2013-01-01
The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432
Using Local States To Drive the Sampling of Global Conformations in Proteins
2016-01-01
Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design. PMID:26808351
Using Local States To Drive the Sampling of Global Conformations in Proteins.
Pandini, Alessandro; Fornili, Arianna
2016-03-08
Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simulations. We find that (a) enhancing the sampling of native local states in both metadynamics and steered MD simulations allows the recovery of global folded states in small proteins; (b) folded states can still be recovered when the amount of information on the native local states is reduced by using a low-resolution version of the SA, where states are clustered into macrostates; and (c) sequences of SA states derived from collections of structural motifs can be used to sample alternative conformations of preselected protein regions. The present findings have potential impact on several applications, ranging from protein model refinement to protein folding and design.
Maglev Launch: Ultra-low Cost, Ultra-high Volume Access to Space for Cargo and Humans
NASA Astrophysics Data System (ADS)
Powell, James; Maise, George; Rather, John
2010-01-01
Despite decades of efforts to reduce rocket launch costs, improvements are marginal. Launch cost to LEO for cargo is ~$10,000 per kg of payload, and to higher orbit and beyond much greater. Human access to the ISS costs $20 million for a single passenger. Unless launch costs are greatly reduced, large scale commercial use and human exploration of the solar system will not occur. A new approach for ultra low cost access to space-Maglev Launch-magnetically accelerates levitated spacecraft to orbital speeds, 8 km/sec or more, in evacuated tunnels on the surface, using Maglev technology like that operating in Japan for high speed passenger transport. The cost of electric energy to reach orbital speed is less than $1 per kilogram of payload. Two Maglev launch systems are described, the Gen-1System for unmanned cargo craft to orbit and Gen-2, for large-scale access of human to space. Magnetically levitated and propelled Gen-1 cargo craft accelerate in a 100 kilometer long evacuated tunnel, entering the atmosphere at the tunnel exit, which is located in high altitude terrain (~5000 meters) through an electrically powered ``MHD Window'' that prevents outside air from flowing into the tunnel. The Gen-1 cargo craft then coasts upwards to space where a small rocket burn, ~0.5 km/sec establishes, the final orbit. The Gen-1 reference design launches a 40 ton, 2 meter diameter spacecraft with 35 tons of payload. At 12 launches per day, a single Gen-1 facility could launch 150,000 tons annually. Using present costs for tunneling, superconductors, cryogenic equipment, materials, etc., the projected construction cost for the Gen-1 facility is 20 billion dollars. Amortization cost, plus Spacecraft and O&M costs, total $43 per kg of payload. For polar orbit launches, sites exist in Alaska, Russia, and China. For equatorial orbit launches, sites exist in the Andes and Africa. With funding, the Gen-1 system could operate by 2020 AD. The Gen-2 system requires more advanced technology
C-metric solution for conformal gravity with a conformally coupled scalar field
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meng, Kun, E-mail: mengkun@tjpu.edu.cn; Zhao, Liu, E-mail: lzhao@nankai.edu.cn
The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformalmore » gauge choices on the structure of the spacetime.« less
Synthetic single domain antibodies for the conformational trapping of membrane proteins
Arnold, Fabian M; Stohler, Peter; Bocquet, Nicolas; Hug, Melanie N; Huber, Sylwia; Siegrist, Martin; Hetemann, Lisa; Gera, Jennifer; Gmür, Samira; Spies, Peter; Gygax, Daniel
2018-01-01
Mechanistic and structural studies of membrane proteins require their stabilization in specific conformations. Single domain antibodies are potent reagents for this purpose, but their generation relies on immunizations, which impedes selections in the presence of ligands typically needed to populate defined conformational states. To overcome this key limitation, we developed an in vitro selection platform based on synthetic single domain antibodies named sybodies. To target the limited hydrophilic surfaces of membrane proteins, we designed three sybody libraries that exhibit different shapes and moderate hydrophobicity of the randomized surface. A robust binder selection cascade combining ribosome and phage display enabled the generation of conformation-selective, high affinity sybodies against an ABC transporter and two previously intractable human SLC transporters, GlyT1 and ENT1. The platform does not require access to animal facilities and builds exclusively on commercially available reagents, thus enabling every lab to rapidly generate binders against challenging membrane proteins. PMID:29792401
Wu, Hui-Qun; Lv, Zheng-Min; Geng, Xing-Yun; Jiang, Kui; Tang, Le-Min; Zhou, Guo-Min; Dong, Jian-Cheng
2013-01-01
To address issues in interoperability between different fundus image systems, we proposed a web eye-picture archiving and communication system (PACS) framework in conformance with digital imaging and communication in medicine (DICOM) and health level 7 (HL7) protocol to realize fundus images and reports sharing and communication through internet. Firstly, a telemedicine-based eye care work flow was established based on integrating the healthcare enterprise (IHE) Eye Care technical framework. Then, a browser/server architecture eye-PACS system was established in conformance with the web access to DICOM persistent object (WADO) protocol, which contains three tiers. In any client system installed with web browser, clinicians could log in the eye-PACS to observe fundus images and reports. Multipurpose internet mail extensions (MIME) type of a structured report is saved as pdf/html with reference link to relevant fundus image using the WADO syntax could provide enough information for clinicians. Some functions provided by open-source Oviyam could be used to query, zoom, move, measure, view DICOM fundus images. Such web eye-PACS in compliance to WADO protocol could be used to store and communicate fundus images and reports, therefore is of great significance for teleophthalmology.
Ling, Sanliang; Gutowski, Maciej
2016-10-06
Computational results have been reported for 2'-deoxycytidine (dC), its gas phase isomers, tautomers, and their conformers, as well as for the crystalline phase. In addition to the neutral gas phase molecules, we have also considered associated radical anions and cations. The structural calculations were performed at the density functional and MP2 levels of theory. Vertical electron ionization energies and excess electron binding energies were determined using electron propagator theory. The α-anomer proved to be more stable by a fraction of kcal/mol than the biologically relevant canonical β-anomer. The conformational space of canonical dC has been systematically probed. dC in the crystalline phase or DNA structures favors canonical anti conformations. These structures were used in past computational studies to model gas phase characteristics of dC. Our findings indicate, however, that the gas phase dC favors syn conformations. It has repercussions for earlier interpretations of gas phase experimental results based on these computational results. The thermodynamic dominance of syn conformations results from the formation of an intramolecular O5'-H13···O2 hydrogen bond. The IR spectra of the most stable syn and anti canonical conformers differ markedly in the region of frequencies corresponding to NH/OH stretching modes. The MP2 value of deprotonation enthalpy of dC of 1411.7 kJ/mol is in very good agreement with the experimental value of 1409 ± 2.5 kJ/mol. The most stable valence anions are characterized by electron vertical detachment energies (VDE) in the 0.8-1.0 eV range, in good agreement with the experimental VDE of 0.87 eV. The barrier for the glycosidic bond cleavage is significant in the neutral canonical dC, 40.0 kcal/mol, and it is reduced to 22 and 16 kcal/mol for the anionic and cationic radicals of dC, respectively. The cleavage reaction is exothermic by 4 kcal/mol for dC - and endothermic by 7 and 9 kcal/mol for dC + and dC, respectively. We
Determining Serpin Conformational Distributions with Single Molecule Fluorescence
Mushero, Nicole; Gershenson, Anne
2012-01-01
Conformational plasticity is key to inhibitory serpin function, and this plasticity gives serpins relatively easy access to alternative, dysfunctional conformations. Thus, a given serpin population may contain both functional and dysfunctional proteins. Single molecule fluorescence (SMF), with its ability to interrogate one fluorescently labeled protein at a time, is a powerful method for elucidating conformational distributions and monitoring how these distributions change over time. SMF and related methods have been particularly valuable for characterizing serpin polymerization. Fluorescence correlation spectroscopy experiments have revealed a second lag phase during in vitro α1-antitrypsin polymerization associated with the formation of smaller oligomers that then condense to form longer polymers [Purkayastha, P., Klemke, J. W., Lavender, S., Oyola, R., Cooperman, B. S., and Gai, F. (2005). Alpha 1-antitrypsin polymerization: A fluorescence correlation spectroscopic study. Biochemistry 44, 2642–2649.]. SMF studies of in vitro neuroserpin polymerization have confirmed that a monomeric intermediate is required for polymer formation while providing a test of proposed polymerization mechanisms [Chiou, A., Hägglöf, P., Orte, A., Chen, A. Y., Dunne, P. D., Belorgey, D., Karlsson-Li, S., Lomas, D., and Klenerman, D. (2009)]. Probing neuroserpin polymerization and interaction with amyloid-beta peptides using single molecule fluorescence. Biophys. J. 97, 2306–2315.]. SMF has also been used to monitor protease–serpin interactions. Single pair Förster resonance energy transfer studies of covalent protease–serpin complexes suggest that the extent of protease structural disruption in the complex is protease dependent [Liu, L., Mushero, N., Hedstrom, L., and Gershenson, A. (2006). Conformational distributions of protease-serpin complexes: A partially translocated complex. Biochemistry 45, 10865–10872.]. SMF techniques are still evolving and the combination of
NASA Astrophysics Data System (ADS)
Yu, Garmay; A, Shvetsov; D, Karelov; D, Lebedev; A, Radulescu; M, Petukhov; V, Isaev-Ivanov
2012-02-01
Based on X-ray crystallographic data available at Protein Data Bank, we have built molecular dynamics (MD) models of homologous recombinases RecA from E. coli and D. radiodurans. Functional form of RecA enzyme, which is known to be a long helical filament, was approximated by a trimer, simulated in periodic water box. The MD trajectories were analyzed in terms of large-scale conformational motions that could be detectable by neutron and X-ray scattering techniques. The analysis revealed that large-scale RecA monomer dynamics can be described in terms of relative motions of 7 subdomains. Motion of C-terminal domain was the major contributor to the overall dynamics of protein. Principal component analysis (PCA) of the MD trajectories in the atom coordinate space showed that rotation of C-domain is correlated with the conformational changes in the central domain and N-terminal domain, that forms the monomer-monomer interface. Thus, even though C-terminal domain is relatively far from the interface, its orientation is correlated with large-scale filament conformation. PCA of the trajectories in the main chain dihedral angle coordinate space implicates a co-existence of a several different large-scale conformations of the modeled trimer. In order to clarify the relationship of independent domain orientation with large-scale filament conformation, we have performed analysis of independent domain motion and its implications on the filament geometry.
Residue solvent accessibilities in the unfolded polypeptide chain.
Zielenkiewicz, P; Saenger, W
1992-01-01
The difference of solvent accessibilities in the native and unfolded states of the protein is used as a measure of the hydrophobic contribution to the free energy of folding. We present a new approximation of amino acids solvent accessibilities in the unfolded state based on the 1-ns molecular dynamics simulation of Ala-X-Ala tripeptides at a temperature of 368 K. The standard accessibility values averaged from the molecular dynamics study are significantly lower from those previously obtained by considering only selected conformations of Ala-X-Ala tripeptides. PMID:1489908
Frauendiener, Jörg
2000-01-01
The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.
Frauendiener, Jörg
2004-01-01
The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.
Kumawat, Amit; Chakrabarty, Suman; Kulkarni, Kiran
2017-01-01
Ras superfamily of GTPases regulate myriad cellular processes through a conserved nucleotide (GTP/GDP) dependent switching mechanism. Unlike Ras family of GTPases, for the Rho GTPases, there is no clear evidence for the existence of “sub-states” such as state 1 & state 2 in the GTP bound form. To explore the nucleotide dependent conformational space of the Switch I loop and also to look for existence of state 1 like conformations in Rho GTPases, atomistic molecular dynamics and metadynamics simulations on RhoA were performed. These studies demonstrate that both the nucleotide-free state and the GDP bound “OFF” state have very similar conformations, whereas the GTP bound “ON” state has unique conformations with signatures of two intermediate states. The conformational free energy landscape for these systems suggests the presence of multiple intermediate states. Interestingly, the energetic penalty of exposing the non-polar residues in the GTP bound form is counter balanced by the favourable hydrogen bonded interactions between the γ-phosphate group of GTP with the highly conserved Tyr34 and Thr37 residues. These competing molecular interactions lead to a tuneable energy landscape of the Switch I conformation, which can undergo significant changes based on the local environment including changes upon binding to effectors. PMID:28374773
NASA Astrophysics Data System (ADS)
Kumawat, Amit; Chakrabarty, Suman; Kulkarni, Kiran
2017-04-01
Ras superfamily of GTPases regulate myriad cellular processes through a conserved nucleotide (GTP/GDP) dependent switching mechanism. Unlike Ras family of GTPases, for the Rho GTPases, there is no clear evidence for the existence of “sub-states” such as state 1 & state 2 in the GTP bound form. To explore the nucleotide dependent conformational space of the Switch I loop and also to look for existence of state 1 like conformations in Rho GTPases, atomistic molecular dynamics and metadynamics simulations on RhoA were performed. These studies demonstrate that both the nucleotide-free state and the GDP bound “OFF” state have very similar conformations, whereas the GTP bound “ON” state has unique conformations with signatures of two intermediate states. The conformational free energy landscape for these systems suggests the presence of multiple intermediate states. Interestingly, the energetic penalty of exposing the non-polar residues in the GTP bound form is counter balanced by the favourable hydrogen bonded interactions between the γ-phosphate group of GTP with the highly conserved Tyr34 and Thr37 residues. These competing molecular interactions lead to a tuneable energy landscape of the Switch I conformation, which can undergo significant changes based on the local environment including changes upon binding to effectors.
An improved reaction path optimization method using a chain of conformations
NASA Astrophysics Data System (ADS)
Asada, Toshio; Sawada, Nozomi; Nishikawa, Takuya; Koseki, Shiro
2018-05-01
The efficient fast path optimization (FPO) method is proposed to optimize the reaction paths on energy surfaces by using chains of conformations. No artificial spring force is used in the FPO method to ensure the equal spacing of adjacent conformations. The FPO method is applied to optimize the reaction path on two model potential surfaces. The use of this method enabled the optimization of the reaction paths with a drastically reduced number of optimization cycles for both potentials. It was also successfully utilized to define the MEP of the isomerization of the glycine molecule in water by FPO method.
NASA Astrophysics Data System (ADS)
Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex
2016-09-01
Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.
Conformal Ablative Thermal Protection System for Planetary and Human Exploration Missions
NASA Technical Reports Server (NTRS)
Beck, R.; Arnold, J.; Gasch, M.; Stackpole, M.; Wercinski, R.; Venkatapathy, E.; Fan, W.; Thornton, J; Szalai, C.
2012-01-01
interest. The entry environment is not always guaranteed with a direct entry, and improving the entry systems robustness to a variety of environmental conditions could aid in reaching more varied landing sites. The National Research Council (NRC) Space Technology Roadmaps and Priorities report highlights six challenges and they are: 1) Mass to Surface, 2) Surface Access, 3) Precision Landing, 4) Surface Hazard Detection and Avoidance, 5) Safety and Mission Assurance, and 6) Affordability. In order for NASA to meet these challenges, the report recommends immediate focus on Rigid and Flexible Thermal Protection Systems. Rigid TPS systems such as Avcoat or SLA are honeycomb based and PICA is in the form of tiles. The honeycomb systems is manufactured using techniques that require filling of each (3/8 cell) by hand and within a limited amount of time once the ablative compound is mixed, all of the cells have to be filled and the entire heat-shield has to be cured. The tile systems such as PICA pose a different challenge as the mechanical strength characteristic and the manufacturing limitations require large number of small tiles with gap-fillers between the tiles. Recent investments in flexible ablative systems have given rise to the potential for conformal ablative TPS> A conformal TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials.
NASA Astrophysics Data System (ADS)
Yamamoto, Takashi; Kimikawa, Yuichi
1992-10-01
The conformational motion of a polymethylene molecule constrained by a cylindrical potential is simulated up to 100 ps. The molecule consists of 60 CH2 groups and has variable bond lengths, bond angles, and dihedral angles. Our main concern here is the excitation and the dynamics of the conformational defects: kinks, jogs, etc. Under weaker constraint a number of gauche bonds are excited; they mostly form pairs such as gtḡ kinks or gtttḡ jogs. These conformational defects show no continuous drift in space. Instead they often annihilate and then recreate at different sites showing apparently random positional changes. The conformational defects produce characteristic strain fields around them. It seems that the conformational defects interact attractively through these strain fields. This is evidenced by remarkably correlated spatial distributions of the gauche bonds.
Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain.
Li, Qufei; Wanderling, Sherry; Sompornpisut, Pornthep; Perozo, Eduardo
2014-02-01
Voltage-gated ion channels respond to transmembrane electric fields through reorientations of the positively charged S4 helix within the voltage-sensing domain (VSD). Despite a wealth of structural and functional data, the details of this conformational change remain controversial. Recent electrophysiological evidence showed that equilibrium between the resting ('down') and activated ('up') conformations of the KvAP VSD from Aeropyrum pernix can be biased through reconstitution in lipids with or without phosphate groups. We investigated the structural transition between these functional states, using site-directed spin-labeling and EPR spectroscopic methods. Solvent accessibility and interhelical distance determinations suggest that KvAP gates through S4 movements involving an ∼3-Å upward tilt and simultaneous ∼2-Å axial shift. This motion leads to large accessibly changes in the intracellular water-filled crevice and supports a new model of gating that combines structural rearrangements and electric-field remodeling.
Convergence of quantum electrodynamics in a curved modification of Minkowski space.
Segal, I E; Zhou, Z
1994-01-01
The interaction and total hamiltonians for quantum electrodynamics, in the interaction representation, are entirely regular self-adjoint operators in Hilbert space, in the universal covering manifold M of the conformal compactification of Minkowski space Mo. (M is conformally equivalent to the Einstein universe E, in which Mo may be canonically imbedded.) In a fixed Lorentz frame this may be expressed as convergence in a spherical space with suitable periodic boundary conditions in time. The traditional relativistic theory is the formal limit of the present variant as the space curvature vanishes. PMID:11607455
Pope, D; Tisdall, R; Middleton, J; Verma, A; van Ameijden, E; Birt, C; Macherianakis, A; Bruce, N G
2018-02-01
Psychological distress (PD) (mental ill-health) has a frequency between 5 and 25% in urban populations, and there is mounting evidence that access to green space might reduce its occurrence. Evidence suggests that the quality of green space is as important as accessibility in promoting mental well-being. A pilot study for EURO-URHIS 2 allowed investigation of access to green space in relation to PD in a deprived urban population in the UK. An adult urban health indicator questionnaire, including the GHQ-12 and validated questions on access to and quality of green space, was sent to a stratified random sample of 1680 adults drawn from one general practice list in Sandwell, UK. Multivariable logistic regression was used to determine associations between attributes of green space and PD adjusting for age, sex and levels of deprivation. There were 578 (35%) completed responses. The reported prevalence of PD [n = 131 (22.7%)] was significantly greater than national England and Wales estimates. As well as accessibility (OR = 0.58; 95% CI = 0.35, 0.96) and sufficiency (OR = 0.12; 95% CI = 0.39, 0.89) of green spaces, having the ability to use them for relaxation and recreation were significantly associated with reduced PD [OR = 0.13 (0.42, 0.94) and OR = 0.11 (0.34, 0.80), respectively]. In addition, a dose-response relationship between number of positive green space attributes and PD was identified (P < 0.05). This population-based study in a deprived urban UK population demonstrates an association, and some dose-response relationship, between access to and quality of green spaces with reduced PD. The cross-sectional design and use of subjective measures limit interpretation of causality. More knowledge is needed on how UK planning affects green spaces and the potential mental health consequences. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
NASA Astrophysics Data System (ADS)
Slack, N. L.; Davidson, P.; Chibbaro, M. A.; Jeppesen, C.; Eiselt, P.; Warriner, H. E.; Schmidt, H.-W.; Pincus, P.; Safinya, C. R.
2001-10-01
Double-end-anchored poly-ethylene-glycol-surfactants (DEA-PEG-surfactants) induce the gelation of lyotropic lamellar Lα phases stabilized by undulation forces. The physical hydrogel (Lα,g) derives its viscoelasticity from the proliferation of defects at a mesoscopic level. The DEA-PEG-surfactants assume both looping and bridging conformations. The existence of novel bridging conformations is indicated by the coexistence of two lamellar phases and the limited swelling of the Lα and Lα,g phases. Modeling of the polymer decorated membranes demonstrates the existence of bridging and yields a rapidly decreasing density of bridging conformations with increasing interlayer spacing.
Quantum entanglement of local operators in conformal field theories.
Nozaki, Masahiro; Numasawa, Tokiro; Takayanagi, Tadashi
2014-03-21
We introduce a series of quantities which characterize a given local operator in any conformal field theory from the viewpoint of quantum entanglement. It is defined by the increased amount of (Rényi) entanglement entropy at late time for an excited state defined by acting the local operator on the vacuum. We consider a conformal field theory on an infinite space and take the subsystem in the definition of the entanglement entropy to be its half. We calculate these quantities for a free massless scalar field theory in two, four and six dimensions. We find that these results are interpreted in terms of quantum entanglement of a finite number of states, including Einstein-Podolsky-Rosen states. They agree with a heuristic picture of propagations of entangled particles.
Cotmore, S F; D'abramo, A M; Ticknor, C M; Tattersall, P
1999-02-01
Antisera were raised against peptides corresponding to the N-termini of capsid proteins VP1 and VP2 from the parvovirus minute virus of mice. Epitopes in the 142-amino-acid VP1-specific region were not accessible in the great majority of newly released viral particles, and sera directed against them failed to neutralize virus directly or deplete stocks of infectious virions. However, brief exposure to temperatures of 45 degreesC or more induced a conformational transition in a population of full virions, but not in empty viral particles, in which VP1-specific sequences became externally accessible. In contrast, the VP2 N-terminus was antibody-accessible in all full, but not empty, particles without prior treatment. An electrophoretic mobility shift assay, in which particles were heat-treated and/or preincubated with antibodies prior to electrophoresis, confirmed this pattern of epitope accessibility, showing that the heat-induced conformational transition produces a retarded form of virion that can be supershifted by incubation with VP1-specific sera. The proportion of virions undergoing transition increased with temperature, but at all temperatures up to 70 degreesC viral particles retained structure-specific antigenic determinants and remained essentially intact, without shedding individual polypeptide species or subunits. However, despite the apparent integrity of its protective coat, the genome became accessible to externally applied enzymes in an increasing proportion of virions through this temperature range, suggesting that the conformational transitions that expose VP1 likely also allow access to the genome. Heating particles to 80 degreesC or above finally induced disassembly to polypeptide monomers. Copyright 1999 Academic Press.
NASA Astrophysics Data System (ADS)
Cometta-Morini, Chiara; Loew, Gilda H.
1991-08-01
An extensive conformational search of the potent opioid analgesic, fentanyl, was performed using the semiempirical quantum mechanical method AM1 and the CHARMm potential energy function. A combination of two procedures was used to search the conformational space for fentanyl, which included nested dihedral scans, geometry optimization and molecular dynamics simulation at different temperatures. In addition, the effect of a continuum solvent environment was taken into account by use of appropriate values for the dielectric constant in the CHARMm computations. The results of the conformational search allowed the determination of the probable conformation of fentanyl in polar and nonpolar solvents and of three candidate conformers for its bioactive form.
Bedini, Annalida; Di Giacomo, Barbara; Gatti, Giuseppe; Spadoni, Gilberto
2005-08-01
Tetrahydrobenz[cd]indole, has been usually assumed to be a rigid scaffold of arylethylamines of pharmaceutical interest, such as melatonin and serotonin. A series of molecules containing this scaffold has been synthesized and their conformation in solution has been determined by 1H NMR. The values of the coupling constants show that the carbocycle fused with the indole ring is a mixture of the two conformers with substituent in equatorial or axial orientation. The molar fraction of the conformers appears to be sensibly affected by the bulkiness of the C-2 indole substituent. A pseudo-axial orientation of the C-3 alkylamido side chain is important for melatonin ligands to access the binding site and exhibit potent in vitro affinity, as illustrated for melatonin ligand 1 (pK(i)=9.32).
Conformational dependence of a protein kinase phosphate transfer reaction.
Henkelman, Graeme; LaBute, Montiago X; Tung, Chang-Shung; Fenimore, P W; McMahon, Benjamin H
2005-10-25
Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase are calculated by plane-wave density functional theory, starting from structures of proteins crystallized in both the reactant conformation (RC) and the transition-state conformation (TC). In TC, we calculate that the reactants and products are nearly isoenergetic with a 20-kJ/mol barrier, whereas phosphate transfer is unfavorable by 120 kJ/mol in the RC, with an even higher barrier. With the protein in TC, the motions involved in reaction are small, with only P(gamma) and the catalytic proton moving >0.5 A. Examination of the structures reveals that in the RC the active site cleft is not completely closed and there is insufficient space for the phosphorylated serine residue in the product state. Together, these observations imply that the phosphate transfer reaction occurs rapidly and reversibly in a particular conformation of the protein, and that the reaction can be gated by changes of a few tenths of an angstrom in the catalytic site.
Conformational Equilibria in Monomeric α-Synuclein at the Single-Molecule Level
Tessari, Isabella; Mammi, Stefano; Bergantino, Elisabetta; Musiani, Francesco; Brucale, Marco; Bubacco, Luigi; Samorì, Bruno
2008-01-01
Human α-Synuclein (αSyn) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to researchers attempting to decipher the molecular mechanisms of αSyn aggregation and formation of fibrils. Traditional bulk techniques used so far to solve this problem point to a direct correlation between αSyn's unique conformational properties and its propensity to aggregate, but these techniques can only provide ensemble-averaged information for monomers and oligomers alike. They therefore cannot characterize the full complexity of the conformational equilibria that trigger the aggregation process. We applied atomic force microscopy–based single-molecule mechanical unfolding methodology to study the conformational equilibrium of human wild-type and mutant αSyn. The conformational heterogeneity of monomeric αSyn was characterized at the single-molecule level. Three main classes of conformations, including disordered and “β-like” structures, were directly observed and quantified without any interference from oligomeric soluble forms. The relative abundance of the “β-like” structures significantly increased in different conditions promoting the aggregation of αSyn: the presence of Cu2+, the pathogenic A30P mutation, and high ionic strength. This methodology can explore the full conformational space of a protein at the single-molecule level, detecting even poorly populated conformers and measuring their distribution in a variety of biologically important conditions. To the best of our knowledge, we present for the first time evidence of a conformational equilibrium that controls the population of a specific class of monomeric αSyn conformers, positively correlated with conditions known to promote the formation of aggregates. A new tool is thus made
Sanchez Sorzano, Carlos Oscar; Alvarez-Cabrera, Ana Lucia; Kazemi, Mohsen; Carazo, Jose María; Jonić, Slavica
2016-04-26
Single-particle electron microscopy (EM) has been shown to be very powerful for studying structures and associated conformational changes of macromolecular complexes. In the context of analyzing conformational changes of complexes, distinct EM density maps obtained by image analysis and three-dimensional (3D) reconstruction are usually analyzed in 3D for interpretation of structural differences. However, graphic visualization of these differences based on a quantitative analysis of elastic transformations (deformations) among density maps has not been done yet due to a lack of appropriate methods. Here, we present an approach that allows such visualization. This approach is based on statistical analysis of distances among elastically aligned pairs of EM maps (one map is deformed to fit the other map), and results in visualizing EM maps as points in a lower-dimensional distance space. The distances among points in the new space can be analyzed in terms of clusters or trajectories of points related to potential conformational changes. The results of the method are shown with synthetic and experimental EM maps at different resolutions. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Witten diagrams revisited: the AdS geometry of conformal blocks
Hijano, Eliot; Kraus, Per; Perlmutter, Eric; ...
2016-01-25
Here, we develop a new method for decomposing blocks. The steps involved are elementary, requiring no explicit integration, and operate directly in position space. Central to this construction is an appealingly simple answer to the question: what object in AdS computes a conformal block? The answer is a "geodesic Witten diagram", which is essentially an ordinary exchange Witten diagram, except that the cubic vertices are not integrated over all of AdS, but only over bulk geodesics connecting the boundary operators. In particular, we also consider the case of four-point functions of scalar operators, and show how to easily reproduce existingmore » results for the relevant conformal blocks in arbitrary dimension.« less
Achieving Rigorous Accelerated Conformational Sampling in Explicit Solvent.
Doshi, Urmi; Hamelberg, Donald
2014-04-03
Molecular dynamics simulations can provide valuable atomistic insights into biomolecular function. However, the accuracy of molecular simulations on general-purpose computers depends on the time scale of the events of interest. Advanced simulation methods, such as accelerated molecular dynamics, have shown tremendous promise in sampling the conformational dynamics of biomolecules, where standard molecular dynamics simulations are nonergodic. Here we present a sampling method based on accelerated molecular dynamics in which rotatable dihedral angles and nonbonded interactions are boosted separately. This method (RaMD-db) is a different implementation of the dual-boost accelerated molecular dynamics, introduced earlier. The advantage is that this method speeds up sampling of the conformational space of biomolecules in explicit solvent, as the degrees of freedom most relevant for conformational transitions are accelerated. We tested RaMD-db on one of the most difficult sampling problems - protein folding. Starting from fully extended polypeptide chains, two fast folding α-helical proteins (Trpcage and the double mutant of C-terminal fragment of Villin headpiece) and a designed β-hairpin (Chignolin) were completely folded to their native structures in very short simulation time. Multiple folding/unfolding transitions could be observed in a single trajectory. Our results show that RaMD-db is a promisingly fast and efficient sampling method for conformational transitions in explicit solvent. RaMD-db thus opens new avenues for understanding biomolecular self-assembly and functional dynamics occurring on long time and length scales.
NASA Technical Reports Server (NTRS)
Murray, S.
1999-01-01
In this project, we worked with the University of California at Berkeley/Center for Extreme Ultraviolet Astrophysics and five science museums (the National Air and Space Museum, the Science Museum of Virginia, the Lawrence Hall of Science, the Exploratorium., and the New York Hall of Science) to formulate plans for computer-based laboratories located at these museums. These Science Learning Laboratories would be networked and provided with real Earth and space science observations, as well as appropriate lesson plans, that would allow the general public to directly access and manipulate the actual remote sensing data, much as a scientist would.
Mamidi, Ashalatha Sreshty; Surolia, Avadhesha
2015-01-01
Structural information over the entire course of binding interactions based on the analyses of energy landscapes is described, which provides a framework to understand the events involved during biomolecular recognition. Conformational dynamics of malectin's exquisite selectivity for diglucosylated N-glycan (Dig-N-glycan), a highly flexible oligosaccharide comprising of numerous dihedral torsion angles, are described as an example. For this purpose, a novel approach based on hierarchical sampling for acquiring metastable molecular conformations constituting low-energy minima for understanding the structural features involved in a biologic recognition is proposed. For this purpose, four variants of principal component analysis were employed recursively in both Cartesian space and dihedral angles space that are characterized by free energy landscapes to select the most stable conformational substates. Subsequently, k-means clustering algorithm was implemented for geometric separation of the major native state to acquire a final ensemble of metastable conformers. A comparison of malectin complexes was then performed to characterize their conformational properties. Analyses of stereochemical metrics and other concerted binding events revealed surface complementarity, cooperative and bidentate hydrogen bonds, water-mediated hydrogen bonds, carbohydrate-aromatic interactions including CH-π and stacking interactions involved in this recognition. Additionally, a striking structural transition from loop to β-strands in malectin CRD upon specific binding to Dig-N-glycan is observed. The interplay of the above-mentioned binding events in malectin and Dig-N-glycan supports an extended conformational selection model as the underlying binding mechanism.
Molt, Robert W; Bartlett, Rodney J; Watson, Thomas; Bazanté, Alexandre P
2012-12-13
We have identified the major conformers of CL-20 explosive, otherwise known as 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane, more formally known as 2,4,6,8,10,12-hexanitrohexaazatetracyclo[5.5.0.0]-dodecane, via Monte Carlo search in conformational space through molecular mechanics and subsequent quantum mechanical refinement using perturbation theory. Our search produced enough conformers to account for all of the various forms of CL-20 found in crystals. This suggests that our methodology will be useful in studying the conformational landscape of other nitramines. The energy levels of the conformers found are all within 0.25 eV of one another based on MBPT(2)/6-311G(d,p); consequently, without further refinement from a method such as coupled cluster theory, all conformers may reasonably be populated at STP in the gas phase. We also report the harmonic vibrational frequencies of conformers, including the implications on the mechanism of detonation. In particular, we establish that the weakest N-N nitramine of CL-20 is the cyclohexane equatorial nitramine. This preliminary mapping of the conformers of CL-20 makes it possible to study the mechanism of detonation of this explosive rigorously in future work.
Conformation and Dynamics of Human Urotensin II and Urotensin Related Peptide in Aqueous Solution.
Haensele, Elke; Mele, Nawel; Miljak, Marija; Read, Christopher M; Whitley, David C; Banting, Lee; Delépée, Carla; Sopkova-de Oliveira Santos, Jana; Lepailleur, Alban; Bureau, Ronan; Essex, Jonathan W; Clark, Timothy
2017-02-27
Conformation and dynamics of the vasoconstrictive peptides human urotensin II (UII) and urotensin related peptide (URP) have been investigated by both unrestrained and enhanced-sampling molecular-dynamics (MD) simulations and NMR spectroscopy. These peptides are natural ligands of the G-protein coupled urotensin II receptor (UTR) and have been linked to mammalian pathophysiology. UII and URP cannot be characterized by a single structure but exist as an equilibrium of two main classes of ring conformations, open and folded, with rapidly interchanging subtypes. The open states are characterized by turns of various types centered at K 8 Y 9 or F 6 W 7 predominantly with no or only sparsely populated transannular hydrogen bonds. The folded conformations show multiple turns stabilized by highly populated transannular hydrogen bonds comprising centers F 6 W 7 K 8 or W 7 K 8 Y 9 . Some of these conformations have not been characterized previously. The equilibrium populations that are experimentally difficult to access were estimated by replica-exchange MD simulations and validated by comparison of experimental NMR data with chemical shifts calculated with density-functional theory. UII exhibits approximately 72% open:28% folded conformations in aqueous solution. URP shows very similar ring conformations as UII but differs in an open:folded equilibrium shifted further toward open conformations (86:14) possibly arising from the absence of folded N-terminal tail-ring interaction. The results suggest that the different biological effects of UII and URP are not caused by differences in ring conformations but rather by different interactions with UTR.
New conformal mapping for adaptive resolving of the complex singularities of Stokes wave
Dyachenko, Sergey A.; A. Silantyev, Denis
2017-01-01
A new highly efficient method is developed for computation of travelling periodic waves (Stokes waves) on the free surface of deep water. A convergence of numerical approximation is determined by the complex singularities above the free surface for the analytical continuation of the travelling wave into the complex plane. An auxiliary conformal mapping is introduced which moves singularities away from the free surface thus dramatically speeding up numerical convergence by adapting the numerical grid for resolving singularities while being consistent with the fluid dynamics. The efficiency of that conformal mapping is demonstrated for the Stokes wave approaching the limiting Stokes wave (the wave of the greatest height) which significantly expands the family of numerically accessible solutions. It allows us to provide a detailed study of the oscillatory approach of these solutions to the limiting wave. Generalizations of the conformal mapping to resolve multiple singularities are also introduced. PMID:28690418
New conformal mapping for adaptive resolving of the complex singularities of Stokes wave.
Lushnikov, Pavel M; Dyachenko, Sergey A; A Silantyev, Denis
2017-06-01
A new highly efficient method is developed for computation of travelling periodic waves (Stokes waves) on the free surface of deep water. A convergence of numerical approximation is determined by the complex singularities above the free surface for the analytical continuation of the travelling wave into the complex plane. An auxiliary conformal mapping is introduced which moves singularities away from the free surface thus dramatically speeding up numerical convergence by adapting the numerical grid for resolving singularities while being consistent with the fluid dynamics. The efficiency of that conformal mapping is demonstrated for the Stokes wave approaching the limiting Stokes wave (the wave of the greatest height) which significantly expands the family of numerically accessible solutions. It allows us to provide a detailed study of the oscillatory approach of these solutions to the limiting wave. Generalizations of the conformal mapping to resolve multiple singularities are also introduced.
Jo, Sunhwan; Bahar, Ivet; Roux, Benoît
2014-01-01
Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results
Access management classification and spacing standards
DOT National Transportation Integrated Search
1996-08-23
The specific objectives of this background paper are:(1)Provide an overview of : the relationship between the functional integrity of the highway system and the : access management classification system, (2)Review and evaluate the current : Oregon De...
The Conformal Template and New Perspectives for Quantum Chromodynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brodsky, Stanley J.; /SLAC
2007-03-06
Conformal symmetry provides a systematic approximation to QCD in both its perturbative and nonperturbative domains. One can use the AdS/CFT correspondence between Anti-de Sitter space and conformal gauge theories to obtain an analytically tractable approximation to QCD in the regime where the QCD coupling is large and constant. For example, there is an exact correspondence between the fifth-dimensional coordinate of AdS space and a specific impact variable which measures the separation of the quark constituents within the hadron in ordinary space-time. This connection allows one to compute the analytic form of the frame-independent light-front wavefunctions of mesons and baryons, themore » fundamental entities which encode hadron properties and allow the computation of exclusive scattering amplitudes. One can also use conformal symmetry as a template for perturbative QCD predictions where the effects of the nonzero beta function can be systematically included in the scale of the QCD coupling. This leads to fixing of the renormalization scale and commensurate scale relations which relate observables without scale or scheme ambiguity. The results are consistent with the renormalization group and the analytic connection of QCD to Abelian theory at N{sub C} {yields} 0. I also discuss a number of novel phenomenological features of QCD. Initial- and .nal-state interactions from gluon-exchange, normally neglected in the parton model, have a profound effect in QCD hard-scattering reactions, leading to leading-twist single-spin asymmetries, diffractive deep inelastic scattering, di.ractive hard hadronic reactions, the breakdown of the Lam Tung relation in Drell-Yan reactions, and nuclear shadowing and non-universal antishadowing--leading-twist physics not incorporated in the light-front wavefunctions of the target computed in isolation. I also discuss tests of hidden color in nuclear wavefunctions, the use of diffraction to materialize the Fock states of a hadronic
Conformal completion of the standard model with a fourth generation
NASA Astrophysics Data System (ADS)
Ho, Chiu Man; Hung, Pham Q.; Kephart, Thomas W.
2012-06-01
We study dynamical electroweak symmetry breaking with a fourth generation within the Z n orbifolded AdS 5 ⊗ S 5 framework. A realistic Z 7 example is discussed. The initial theory reduces dynamically, due to the induced condensates, to a four-family trinification near a TeV-scale conformal fixed point where the gauge hierarchy problem does not exist. We predict new gauge bosons and bifundamental fermions and scalars accessible by the LHC.
Molecular mechanics approach for design and conformational studies of macrocyclic ligands
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: b.kanungo@gmail.com
2015-08-28
Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic andmore » random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.« less
NASA Astrophysics Data System (ADS)
Bagchi, Arjun; Grumiller, Daniel
2013-07-01
The holographic principle has a concrete realization in the Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence. If this principle is a true fact about quantum gravity then it must also hold beyond AdS/CFT. In this paper, we address specifically holographic field theory duals of gravitational theories in asymptotically flat spacetimes. We present some evidence of our recent conjecture that three-dimensional (3d) conformal Chern-Simons gravity (CSG) with flat space boundary conditions is dual to an extremal CFT.
Approaching Pharmacological Space: Events and Components.
Vistoli, Giulio; Pedretti, Alessandro; Mazzolari, Angelica; Testa, Bernard
2018-01-01
With a view to introducing the concept of pharmacological space and its potential applications in investigating and predicting the toxic mechanisms of xenobiotics, this opening chapter describes the logical relations between conformational behavior, physicochemical properties and binding spaces, which are seen as the three key elements composing the pharmacological space. While the concept of conformational space is routinely used to encode molecular flexibility, the concepts of property spaces and, particularly, of binding spaces are more innovative. Indeed, their descriptors can find fruitful applications (a) in describing the dynamic adaptability a given ligand experiences when inserted into a specific environment, and (b) in parameterizing the flexibility a ligand retains when bound to a biological target. Overall, these descriptors can conveniently account for the often disregarded entropic factors and as such they prove successful when inserted in ligand- or structure-based predictive models. Notably, and although binding space parameters can clearly be derived from MD simulations, the chapter will illustrate how docking calculations, despite their static nature, are able to evaluate ligand's flexibility by analyzing several poses for each ligand. Such an approach, which represents the founding core of the binding space concept, can find various applications in which the related descriptors show an impressive enhancing effect on the statistical performances of the resulting predictive models.
Experimental demonstration of conformal phased array antenna via transformation optics.
Lei, Juan; Yang, Juxing; Chen, Xi; Zhang, Zhiya; Fu, Guang; Hao, Yang
2018-02-28
Transformation Optics has been proven a versatile technique for designing novel electromagnetic devices and it has much wider applicability in many subject areas related to general wave equations. Among them, quasi-conformal transformation optics (QCTO) can be applied to minimize anisotropy of transformed media and has opened up the possibility to the design of broadband antennas with arbitrary geometries. In this work, a wide-angle scanning conformal phased array based on all-dielectric QCTO lens is designed and experimentally demonstrated. Excited by the same current distribution as such in a conventional planar array, the conformal system in presence of QCTO lens can preserve the same radiation characteristics of a planar array with wide-angle beam-scanning and low side lobe level (SLL). Laplace's equation subject to Dirichlet-Neumann boundary conditions is adopted to construct the mapping between the virtual and physical spaces. The isotropic lens with graded refractive index is realized by all-dielectric holey structure after an effective parameter approximation. The measurements of the fabricated system agree well with the simulated results, which demonstrate its excellent wide-angle beam scanning performance. Such demonstration paves the way to a robust but efficient array synthesis, as well as multi-beam and beam forming realization of conformal arrays via transformation optics.
NASA Astrophysics Data System (ADS)
Tarnowska, Monika; Liwo, Adam; Shenderovich, Mark D.; Liepiņa, Inta; Golbraikh, Alexander A.; Grzonka, Zbigniew; Tempczyk, Anna
1993-12-01
The effect of the substitution in position 1 on the low-energy conformations of the oxytocin/vasopressin 20-membered ring was investigated by means of molecular mechanics. Three representative substitutions were considered: β'-mercapto-β,β-dimethyl)propionic acid (Dmp), (β'-mercapto-β,β-cyclopentamethylene)propionic acid (Cpp), both forming strong antagonists, and (α,α-dimethyl-β-mercapto)propionic acid (α-Dmp), forming analogs of strongly reduced biological activity, with the β-mercaptopropionic (Mpa) residue taken as reference. Both ECEPP/2 (rigid valence geometry) and AMBER (flexible valence geometry) force fields were employed in the calculations. Three basic types of backbone conformations were taken into account which are distinguished by the type of β-turn at residues 3 and 4: β1/βIII, βII, and βI'/βIII', all types containing one or two intra-annular hydrogen bonds. The allowed (ring-closed) disulfide-bridge conformations were searched by an algorithm formulated in terms of scanning the disulfide-bridge torsional angle Cβ-S-S-Cβ. The ECEPP/2 and AMBER energies of the obtained conformations were found to be in reasonable agreement. Two of the low-energy conformers of the [Mpa1]-compound agreed very well with the cyclic part of the two conformers found in the crystal structure of [Mpa1]-oxytocin. An analysis of the effect of β-substitution on relative energies showed that the conformations with the N-C'-CH2-CH2 (ψ'1) and C'-CH2-CH2-S (ϰ'1) angles of the first residue around (-100°, 60°) and (100°, -60°) are not affected; this in most cases implies a left-handed disulfide bridge. In the case of α-substitution the allowed values of ψ'1 are close to ± 60°. This requirement, being in contradiction to the one concerning β-substitution, could explain the very low biological activity of the α-substituted analogs. The conformational preferences of substituted compounds can largely be explained by the analysis of local interactions
Alibay, Irfan; Burusco, Kepa K; Bruce, Neil J; Bryce, Richard A
2018-03-08
Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free-energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling, and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 μs trajectories; these simulations find a predominance of closed conformer and a range of low-occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the 4 C 1 form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 μs unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.
Visualization of SV2A conformations in situ by the use of Protein Tomography
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lynch, Berkley A.; Matagne, Alain; Braennstroem, Annika
2008-10-31
The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography{sup TM}. We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicatesmore » that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins.« less
Jo, Sunhwan; Lee, Hui Sun; Skolnick, Jeffrey; Im, Wonpil
2013-01-01
Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan's crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures.
Restricted N-glycan Conformational Space in the PDB and Its Implication in Glycan Structure Modeling
Jo, Sunhwan; Lee, Hui Sun; Skolnick, Jeffrey; Im, Wonpil
2013-01-01
Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan's crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures. PMID:23516343
Bentz, Emilie L; Goswami, Rajesh; Moloney, Mark G; Westaway, Susan M
2005-08-07
Bicyclic lactams derived from pyroglutamic acid provide a useful scaffold for synthesis of conformationally restricted analogues of lysine, ornithine and glutamine, as well as an Ala-Ala dipeptide analogue. Amino alcohol and carboxylic acid derivatives are accessible from a common intermediate. In this strategy, the bicyclic lactam system not only controls, but also facilitates the determination of the stereochemistry of the synthetic intermediates.
Access management for Kentucky.
DOT National Transportation Integrated Search
2004-02-01
The Access Management Manual published by the Transportation Research Board in 2003 defines access management as the "systematic control of the location, spacing, design, and operation of driveways, median openings, interchanges, and street connectio...
NASA's mobile satellite communications program; ground and space segment technologies
NASA Technical Reports Server (NTRS)
Naderi, F.; Weber, W. J.; Knouse, G. H.
1984-01-01
This paper describes the Mobile Satellite Communications Program of the United States National Aeronautics and Space Administration (NASA). The program's objectives are to facilitate the deployment of the first generation commercial mobile satellite by the private sector, and to technologically enable future generations by developing advanced and high risk ground and space segment technologies. These technologies are aimed at mitigating severe shortages of spectrum, orbital slot, and spacecraft EIRP which are expected to plague the high capacity mobile satellite systems of the future. After a brief introduction of the concept of mobile satellite systems and their expected evolution, this paper outlines the critical ground and space segment technologies. Next, the Mobile Satellite Experiment (MSAT-X) is described. MSAT-X is the framework through which NASA will develop advanced ground segment technologies. An approach is outlined for the development of conformal vehicle antennas, spectrum and power-efficient speech codecs, and modulation techniques for use in the non-linear faded channels and efficient multiple access schemes. Finally, the paper concludes with a description of the current and planned NASA activities aimed at developing complex large multibeam spacecraft antennas needed for future generation mobile satellite systems.
Application of geometric algebra for the description of polymer conformations.
Chys, Pieter
2008-03-14
In this paper a Clifford algebra-based method is applied to calculate polymer chain conformations. The approach enables the calculation of the position of an atom in space with the knowledge of the bond length (l), valence angle (theta), and rotation angle (phi) of each of the preceding bonds in the chain. Hence, the set of geometrical parameters {l(i),theta(i),phi(i)} yields all the position coordinates p(i) of the main chain atoms. Moreover, the method allows the calculation of side chain conformations and the computation of rotations of chain segments. With these features it is, in principle, possible to generate conformations of any type of chemical structure. This method is proposed as an alternative for the classical approach by matrix algebra. It is more straightforward and its final symbolic representation considerably simpler than that of matrix algebra. Approaches for realistic modeling by means of incorporation of energetic considerations can be combined with it. This article, however, is entirely focused at showing the suitable mathematical framework on which further developments and applications can be built.
Dubey, Ritesh; Desiraju, Gautam R.
2015-01-01
The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons. The crystal structures are characterized by distinctive O—H⋯N and O—H⋯O based synthons and are classified as nonporous, porous and helical. Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event. This space is the crystal structure landscape of the compound and is explored by fine-tuning the experimental conditions of crystallization. In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular ‘confusion’ that is inherent in a molecule like quercetin. The absence of concomitant polymorphism in this study highlights the selectivity in conformation and synthon choice from the virtual combinatorial library in solution. PMID:26175900
Cox, M B; Arjunan, P; Arora, S K
1990-08-01
X-ray, NMR and molecular mechanics studies on pentostatin (C11H16N4O4), a potent inhibitor of the enzyme adenosine deaminase, have been carried out to study the structure and conformation. The crystals belong to the monoclinic space group P21 with the cell dimensions of a = 4.960(1), b = 10.746(3), c = 11.279(4)A, beta = 101.18(2) degrees and Z = 2. The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.047 for 997 reflections. The trihydrodiazepine ring is nonplanar and adopts a distorted sofa conformation with C(7) deviated from the mean plane by 0.66A. The deoxyribose ring adopts a C3'-endo conformation, different from coformycin where the sugar has a C2'-endo conformation. The observed glycosidic torsion angle (chi = -119.5 degrees) is in the anti range. The conformation about the C(4')-C(5') bond is gauche+. The conformation of the molecule is compared with that of coformycin and 2-azacoformycin. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. The conformation of deoxyribose in solution is approximately 70% S and 30% N. Molecular mechanics studies were performed to obtain the energy minimized conformation, which is compared with X-ray and NMR results.
Dynamic Energy Landscapes of Riboswitches Help Interpret Conformational Rearrangements and Function
Quarta, Giulio; Sin, Ken; Schlick, Tamar
2012-01-01
Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant “downhill” pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the “new view” of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design. PMID:22359488
Conformal, Transparent Printed Antenna Developed for Communication and Navigation Systems
NASA Technical Reports Server (NTRS)
Lee, Richard Q.; Simons, Rainee N.
1999-01-01
Conformal, transparent printed antennas have advantages over conventional antennas in terms of space reuse and aesthetics. Because of their compactness and thin profile, these antennas can be mounted on video displays for efficient integration in communication systems such as palmtop computers, digital telephones, and flat-panel television displays. As an array of multiple elements, the antenna subsystem may save weight by reusing space (via vertical stacking) on photovoltaic arrays or on Earth-facing sensors. Also, the antenna could go unnoticed on automobile windshields or building windows, enabling satellite uplinks and downlinks or other emerging high-frequency communications.
Aspects of AdS/CFT: Conformal Deformations and the Goldstone Equivalence Theorem
NASA Astrophysics Data System (ADS)
Cantrell, Sean Andrew
The AdS/CFT correspondence provides a map from the states of theories situated in AdSd+1 to those in dual conformal theories in a d-dimensional space. The correspondence can be used to establish certain universal properties of some theories in one space by examining the behave of general objects in the other. In this thesis, we develop various formal aspects of AdS/CFT. Conformal deformations manifest in the AdS/CFT correspondence as boundary conditions on the AdS field. Heretofore, double-trace deformations have been the primary focus in this context. To better understand multitrace deformations, we revisit the relationship between the generating AdS partition function for a free bulk theory and the boundary CFT partition function subject to arbitrary conformal deformations. The procedure leads us to a formalism that constructs bulk fields from boundary operators. We independently replicate the holographic RG flow narrative to go on to interpret the brane used to regulate the AdS theory as a renormalization scale. The scale-dependence of the dilatation spectrum of a boundary theory in the presence of general deformations can be thus understood on the AdS side using this formalism. The Goldstone equivalence theorem allows one to relate scattering amplitudes of massive gauge fields to those of scalar fields in the limit of large scattering energies. We generalize this theorem under the framework of the AdS/CFT correspondence. First, we obtain an expression of the equivalence theorem in terms of correlation functions of creation and annihilation operators by using an AdS wave function approach to the AdS/CFT dictionary. It is shown that the divergence of the non-conserved conformal current dual to the bulk gauge field is approximately primary when computing correlators for theories in which the masses of all the exchanged particles are sufficiently large. The results are then generalized to higher spin fields. We then go on to generalize the theorem using conformal
Conformal expansions and renormalons
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rathsman, J.
2000-02-07
The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients.more » As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.« less
A random forest learning assisted "divide and conquer" approach for peptide conformation search.
Chen, Xin; Yang, Bing; Lin, Zijing
2018-06-11
Computational determination of peptide conformations is challenging as it is a problem of finding minima in a high-dimensional space. The "divide and conquer" approach is promising for reliably reducing the search space size. A random forest learning model is proposed here to expand the scope of applicability of the "divide and conquer" approach. A random forest classification algorithm is used to characterize the distributions of the backbone φ-ψ units ("words"). A random forest supervised learning model is developed to analyze the combinations of the φ-ψ units ("grammar"). It is found that amino acid residues may be grouped as equivalent "words", while the φ-ψ combinations in low-energy peptide conformations follow a distinct "grammar". The finding of equivalent words empowers the "divide and conquer" method with the flexibility of fragment substitution. The learnt grammar is used to improve the efficiency of the "divide and conquer" method by removing unfavorable φ-ψ combinations without the need of dedicated human effort. The machine learning assisted search method is illustrated by efficiently searching the conformations of GGG/AAA/GGGG/AAAA/GGGGG through assembling the structures of GFG/GFGG. Moreover, the computational cost of the new method is shown to increase rather slowly with the peptide length.
Accessible Near-Earth Objects (NEOs)
NASA Technical Reports Server (NTRS)
Barbee, Brent W.
2015-01-01
Near Earth Objects (NEOs) are asteroids and comets whose orbits are in close proximity to Earth's orbit; specifically, they have perihelia less than 1.3 astronomical units. NEOs particularly near Earth asteroids (NEAs) are identified as potential destinations for future human exploration missions. In this presentation I provide an overview of the current state of knowledge regarding the astrodynamical accessibility of NEAs according to NASA's Near Earth Object Human Space Flight Accessible Targets Study (NHATS). I also investigate the extremes of NEA accessibility using case studies and illuminate the fact that a space-based survey for NEOs is essential to expanding the set of known accessible NEAs for future human exploration missions.
14 CFR 1212.205 - Exceptions to individual's rights of access.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Exceptions to individual's rights of access. 1212.205 Section 1212.205 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PRIVACY ACT-NASA REGULATIONS Access to Records § 1212.205 Exceptions to individual's rights of access. (a) The...
14 CFR 1212.205 - Exceptions to individual's rights of access.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Exceptions to individual's rights of access. 1212.205 Section 1212.205 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PRIVACY ACT-NASA REGULATIONS Access to Records § 1212.205 Exceptions to individual's rights of access. (a) The...
Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai
2015-01-01
Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623
Ahmed, Aqeel; Rippmann, Friedrich; Barnickel, Gerhard; Gohlke, Holger
2011-07-25
A three-step approach for multiscale modeling of protein conformational changes is presented that incorporates information about preferred directions of protein motions into a geometric simulation algorithm. The first two steps are based on a rigid cluster normal-mode analysis (RCNMA). Low-frequency normal modes are used in the third step (NMSim) to extend the recently introduced idea of constrained geometric simulations of diffusive motions in proteins by biasing backbone motions of the protein, whereas side-chain motions are biased toward favorable rotamer states. The generated structures are iteratively corrected regarding steric clashes and stereochemical constraint violations. The approach allows performing three simulation types: unbiased exploration of conformational space; pathway generation by a targeted simulation; and radius of gyration-guided simulation. When applied to a data set of proteins with experimentally observed conformational changes, conformational variabilities are reproduced very well for 4 out of 5 proteins that show domain motions, with correlation coefficients r > 0.70 and as high as r = 0.92 in the case of adenylate kinase. In 7 out of 8 cases, NMSim simulations starting from unbound structures are able to sample conformations that are similar (root-mean-square deviation = 1.0-3.1 Å) to ligand bound conformations. An NMSim generated pathway of conformational change of adenylate kinase correctly describes the sequence of domain closing. The NMSim approach is a computationally efficient alternative to molecular dynamics simulations for conformational sampling of proteins. The generated conformations and pathways of conformational transitions can serve as input to docking approaches or as starting points for more sophisticated sampling techniques.
Comparison of molecular dynamics and superfamily spaces of protein domain deformation.
Velázquez-Muriel, Javier A; Rueda, Manuel; Cuesta, Isabel; Pascual-Montano, Alberto; Orozco, Modesto; Carazo, José-María
2009-02-17
It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space). Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases. Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pesin, Y.; Weiss, H.
1997-01-01
In this paper we establish the complete multifractal formalism for equilibrium measures for Holder continuous conformal expanding maps and expanding Markov Moran-like geometric constructions. Examples include Markov maps of an interval, beta transformations of an interval, rational maps with hyperbolic Julia sets, and conformal total endomorphisms. We also construct a Holder continuous homeomorphism of a compact metric space with an ergodic invariant measure of positive entropy for which the dimension spectrum is not convex, and hence the multifractal formalism fails.
Clegg, Jennifer M; Wen, Nicole J; Legare, Cristine H
2017-03-01
Cross-cultural comparisons provide critical insight into variation in reasoning about intelligence. In two studies, the authors used a novel methodology based on multivocal ethnography to assess the role of conformity in U.S. and Ni-Vanuatu adults' judgments of children's intelligence and, as a comparison trait, good behavior. In Study 1, there were cultural differences in the impact of conformity on U.S. and Ni-Vanuatu adults' judgments of children's intelligence and good behavior. When evaluating U.S. children only, U.S. adults were less likely to endorse high conformity children as intelligent, often citing creativity as a justification for their judgments. In contrast, Ni-Vanuatu adults were more likely to endorse Ni-Vanuatu high conformity children as intelligent. Ni-Vanuatu adults were also more likely to endorse high conformity children as well-behaved than U.S. adults. In Study 2, there were no effects of socioeconomic status on U.S. adults' evaluations of conformity. U.S. adults were less likely to endorse high conformity children as intelligent than Ni-Vanuatu adults. Taken together, the data demonstrate that beliefs about the relations between intelligence, conformity, and creativity vary within and across cultures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Neuwelt, Pat M; Kearns, Robin A; Browne, Annette J
2015-05-01
At the point of entry to the health care system sit general practice receptionists (GPRs), a seldom studied employment group. The place of the receptionist involves both a location within the internal geography of the clinic and a position within the primary care team. Receptionists literally 'receive' those who phone or enter the clinic, and are a critical influence in their transformation from a 'person' to a 'patient'. This process occurs in a particular space: the 'waiting room'. We explore the waiting room and its dynamics in terms of 'acceptability', an under-examined aspect of access to primary care. We ask 'How do GPRs see their role with regard to patients with complex health and social needs, in light of the spatio-temporal constraints of their working environments?' We engaged receptionists as participants to explore perceptions of their roles and their workspaces, deriving narrative data from three focus groups involving 14 GPRs from 11 practices in the Northland region of New Zealand. The study employed an adapted form of grounded theory. Our findings indicate that GPRs are on the edge of the practice team, yet carry a complex role at the frontline, in the waiting space. They are de facto managers of this space; however, they have limited agency within general practice settings, due to the constraints imposed upon them by physical and organisational structures. The agency of GPRs is most evident in their ability to shape the social dynamics of the waiting space, and to frame the health care experience as positive for people whose usual experience is marginalisation. We conclude that, if well supported, receptionists have the potential to positively influence health care acceptability, and patients' access to care. Copyright © 2014 Elsevier Ltd. All rights reserved.
A pH-dependent conformational ensemble mediates proton transport through the influenza A/M2 protein†
Polishchuk, Alexei L.; Lear, James D.; Ma, Chunlong; Lamb, Robert A.; Pinto, Lawrence H.; DeGrado, William F.
2010-01-01
The influenza A M2 protein exhibits inwardly rectifying, pH-activated proton transport that saturates at low pH. A comparison of high-resolution structures of the transmembrane domain at high and low pH suggests that pH-dependent conformational changes may facilitate proton conduction by alternately changing the accessibility of the N-terminal and C-terminal regions of the channel as a proton transits through the transmembrane domain. Here, we show that M2 functionally reconstituted in liposomes populates at least three different conformational states over a physiologically relevant pH range, with transition midpoints that are consistent with previously reported His37 pKas. We then develop and test two similar, quantitative mechanistic models of proton transport, where protonation shifts the equilibrium between structural states having different proton affinities and solvent accessibilities. The models account well for a collection of experimental data sets over a wide range of pHs and voltages and require only a small number of adjustable parameters to accurately describe the data. While the kinetic models do not require any specific conformation for the protein, they nevertheless are consistent with a large body of structural information based on high-resolution NMR and crystallographic structures, optical spectroscopy, and MD calculations. PMID:20968306
Identifying and correcting non-Markov states in peptide conformational dynamics
NASA Astrophysics Data System (ADS)
Nerukh, Dmitry; Jensen, Christian H.; Glen, Robert C.
2010-02-01
Conformational transitions in proteins define their biological activity and can be investigated in detail using the Markov state model. The fundamental assumption on the transitions between the states, their Markov property, is critical in this framework. We test this assumption by analyzing the transitions obtained directly from the dynamics of a molecular dynamics simulated peptide valine-proline-alanine-leucine and states defined phenomenologically using clustering in dihedral space. We find that the transitions are Markovian at the time scale of ≈50 ps and longer. However, at the time scale of 30-40 ps the dynamics loses its Markov property. Our methodology reveals the mechanism that leads to non-Markov behavior. It also provides a way of regrouping the conformations into new states that now possess the required Markov property of their dynamics.
NASA Technical Reports Server (NTRS)
Cohen, Marc M.; Bussolari, Steven
1987-01-01
Four concepts for on-orbit spacesuit donning, doffing, servicing, check-out, egress and ingress are presented. These are: the Space Transportation System (STS) Type (shuttle system enlarged), the Transit Airlock (Shuttle Airlock with suit servicing removed from the pump-down chamber), the Suitport (a rear-entry suit mates to a port in the airlock wall), and the Crewlock (a small, individual, conformal airlock). Each of these four concepts is compared through a series of seven steps representing a typical Extra Vehicular Activity (EVA) mission: (1) Predonning suit preparation; (2) Portable Life Support System (PLSS) preparation; (3) Suit Donning and Final Check; (4) Egress/Ingress; (5) Mid-EVA rest period; (6) Post-EVA Securing; (7) Non-Routine Maintenance. The different characteristics of each concept are articulated through this step-by-step approach. Recommendations concerning an approach for further evaluations of airlock geometry, anthropometrics, ergonomics, and functional efficiency are made. The key recommendation is that before any particular airlock can be designed, the full range of spacesuit servicing functions must be considered, including timelines that are most supportive of EVA human productivity.
Transforming community access to space science models
NASA Astrophysics Data System (ADS)
MacNeice, Peter; Hesse, Michael; Kuznetsova, Maria; Maddox, Marlo; Rastaetter, Lutz; Berrios, David; Pulkkinen, Antti
2012-04-01
Researching and forecasting the ever changing space environment (often referred to as space weather) and its influence on humans and their activities are model-intensive disciplines. This is true because the physical processes involved are complex, but, in contrast to terrestrial weather, the supporting observations are typically sparse. Models play a vital role in establishing a physically meaningful context for interpreting limited observations, testing theory, and producing both nowcasts and forecasts. For example, with accurate forecasting of hazardous space weather conditions, spacecraft operators can place sensitive systems in safe modes, and power utilities can protect critical network components from damage caused by large currents induced in transmission lines by geomagnetic storms.
Transforming Community Access to Space Science Models
NASA Technical Reports Server (NTRS)
MacNeice, Peter; Heese, Michael; Kunetsova, Maria; Maddox, Marlo; Rastaetter, Lutz; Berrios, David; Pulkkinen, Antti
2012-01-01
Researching and forecasting the ever changing space environment (often referred to as space weather) and its influence on humans and their activities are model-intensive disciplines. This is true because the physical processes involved are complex, but, in contrast to terrestrial weather, the supporting observations are typically sparse. Models play a vital role in establishing a physically meaningful context for interpreting limited observations, testing theory, and producing both nowcasts and forecasts. For example, with accurate forecasting of hazardous space weather conditions, spacecraft operators can place sensitive systems in safe modes, and power utilities can protect critical network components from damage caused by large currents induced in transmission lines by geomagnetic storms.
Nguyen, Phuong H
2007-05-15
Principal component analysis is a powerful method for projecting multidimensional conformational space of peptides or proteins onto lower dimensional subspaces in which the main conformations are present, making it easier to reveal the structures of molecules from e.g. molecular dynamics simulation trajectories. However, the identification of all conformational states is still difficult if the subspaces consist of more than two dimensions. This is mainly due to the fact that the principal components are not independent with each other, and states in the subspaces cannot be visualized. In this work, we propose a simple and fast scheme that allows one to obtain all conformational states in the subspaces. The basic idea is that instead of directly identifying the states in the subspace spanned by principal components, we first transform this subspace into another subspace formed by components that are independent of one other. These independent components are obtained from the principal components by employing the independent component analysis method. Because of independence between components, all states in this new subspace are defined as all possible combinations of the states obtained from each single independent component. This makes the conformational analysis much simpler. We test the performance of the method by analyzing the conformations of the glycine tripeptide and the alanine hexapeptide. The analyses show that our method is simple and quickly reveal all conformational states in the subspaces. The folding pathways between the identified states of the alanine hexapeptide are analyzed and discussed in some detail. 2007 Wiley-Liss, Inc.
Fabrication challenges associated with conformal optics
NASA Astrophysics Data System (ADS)
Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.
2001-09-01
A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.
Yang, Rong; Lee, Matthew C; Yan, Honggao; Duan, Yong
2005-07-01
Comparison of the crystallographic and NMR structures of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) suggests that the enzyme may undergo significant conformational change upon binding to its first substrate, ATP. Two of the three surface loops (loop 2 and loop 3) accounting for most of the conformational differences appear to be confined by crystal contacts, raising questions about the putative large-scale induced-fit conformational change of HPPK and the functional roles of the conserved side-chain residues on the loops. To investigate the loop dynamics in crystal-free environment, we carried out molecular dynamics and locally enhanced sampling simulations of the apo-enzyme and the HPPK.MgATP complex. Our simulations showed that the crystallographic B-factors underestimated the loop dynamics considerably. We found that the open-conformation of loop 3 in the binary complex is accessible to the apo-enzyme and is the favored conformation in solution phase. These results revise our previous view of HPPK-substrate interactions and the associated functional mechanism of conformational change. The lessons learned here offer valuable structural insights into the workings of HPPK and should be useful for structure-based drug design.
The Mission Accessibility of Near-Earth Asteroids
NASA Technical Reports Server (NTRS)
Barbee, Brent W.; Abell, P. A.; Adamo, D. R.; Mazanek, D. D.; Johnson, L. N.; Yeomans, D. K.; Chodas, P. W.; Chamberlin, A. B.; Benner, L. A. M.; Taylor, P.;
2015-01-01
The population of near-Earth asteroids (NEAs) that may be accessible for human space flight missions is defined by the Near-Earth Object Human Space Flight Accessible Targets Study (NHATS). The NHATS is an automated system designed to monitor the accessibility of, and particular mission opportunities offered by, the NEA population. This is analogous to systems that automatically monitor the impact risk posed to Earth by the NEA population. The NHATS system identifies NEAs that are potentially accessible for future round-trip human space flight missions and provides rapid notification to asteroid observers so that crucial follow-up observations can be obtained following discovery of accessible NEAs. The NHATS was developed in 2010 and was automated by early 2012. NHATS data are provided via an interactive web-site, and daily NHATS notification emails are transmitted to a mailing list; both resources are available to the public.
Otero, Toribio F
2017-01-18
In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.
Evaluating four-loop conformal Feynman integrals by D-dimensional differential equations
NASA Astrophysics Data System (ADS)
Eden, Burkhard; Smirnov, Vladimir A.
2016-10-01
We evaluate a four-loop conformal integral, i.e. an integral over four four-dimensional coordinates, by turning to its dimensionally regularized version and applying differential equations for the set of the corresponding 213 master integrals. To solve these linear differential equations we follow the strategy suggested by Henn and switch to a uniformly transcendental basis of master integrals. We find a solution to these equations up to weight eight in terms of multiple polylogarithms. Further, we present an analytical result for the given four-loop conformal integral considered in four-dimensional space-time in terms of single-valued harmonic polylogarithms. As a by-product, we obtain analytical results for all the other 212 master integrals within dimensional regularization, i.e. considered in D dimensions.
Fermion-scalar conformal blocks
Iliesiu, Luca; Kos, Filip; Poland, David; ...
2016-04-13
In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.
ERIC Educational Resources Information Center
Walling, Linda Lucas
1992-01-01
Summarizes federal legislation regarding equal access for students with disabilities and discusses environmental barriers to accessibility in the library media center. Solutions to these design problems are suggested in the following areas: material formats and space requirements; the physical setting, including furniture, floor coverings,…
NASA Astrophysics Data System (ADS)
Sarver, Ronald W.; Friedman, Alan R.; Thamann, Thomas J.
1997-10-01
The secondary structure of the bovine growth hormone releasing factor analog, [Ile 2, Ser 8,28, Ala 15, Leu 27, Hse 30] bGRF(1-30)-NH-Ethyl, acetate salt (U-90699F) was studied in solution by Fourier transform infrared and Raman spectroscopies. Spectroscopic studies revealed that concentrated aqueous solutions of U-90699F (100 mg ml -1) undergo a secondary structure transition from disordered coil/α-helix to intermolecular β-sheet. Disordered coil and α-helical structure were grouped together in the infrared and Raman studies since the amide I vibrations are close in frequency and overlap in assignments was possible. Before the conformational transition, the facile exchange of the peptide's amide hydrogens for deuterium indicated that the majority of amide hydrogens were readily accessible to solvent. The kinetics of the conformational transition coincided with an increase in solution viscosity and turbidity. An initiation phase preceded the conformational transition during which only minor spectral changes were observed by infrared spectroscopy. The initiation phase and reaction kinetics were consistent with a highly cooperative nucleation ultimately leading to a network of intermolecular β-sheet structure and gel formation. Increased temperature accelerated the conformational transition. The conformational transition was thermally irreversible but the β-sheet structure of aggregated or gelled peptide could be disrupted by dilution and agitation.
Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution.
Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M Eugenia; Molteni, Carla
2017-04-14
The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.
Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution
NASA Astrophysics Data System (ADS)
Comitani, Federico; Rossi, Kevin; Ceriotti, Michele; Sanz, M. Eugenia; Molteni, Carla
2017-04-01
The conformational free energy landscape of aspartic acid, a proteogenic amino acid involved in a wide variety of biological functions, was investigated as an example of the complexity that multiple rotatable bonds produce even in relatively simple molecules. To efficiently explore such a landscape, this molecule was studied in the neutral and zwitterionic forms, in the gas phase and in water solution, by means of molecular dynamics and the enhanced sampling method metadynamics with classical force-fields. Multi-dimensional free energy landscapes were reduced to bi-dimensional maps through the non-linear dimensionality reduction algorithm sketch-map to identify the energetically stable conformers and their interconnection paths. Quantum chemical calculations were then performed on the minimum free energy structures. Our procedure returned the low energy conformations observed experimentally in the gas phase with rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573 (2010)]. Moreover, it provided information on higher energy conformers not accessible to experiments and on the conformers in water. The comparison between different force-fields and quantum chemical data highlighted the importance of the underlying potential energy surface to accurately capture energy rankings. The combination of force-field based metadynamics, sketch-map analysis, and quantum chemical calculations was able to produce an exhaustive conformational exploration in a range of significant free energies that complements the experimental data. Similar protocols can be applied to larger peptides with complex conformational landscapes and would greatly benefit from the next generation of accurate force-fields.
NASA Astrophysics Data System (ADS)
Toal, Siobhan; Schweitzer-Stenner, Reinhard; Rybka, Karin; Schwalbe, Hardol
2013-03-01
In order to enable structural predictions of intrinsically disordered proteins (IDPs) the intrinsic conformational propensities of amino acids must be complimented by information on nearest-neighbor interactions. To explore the influence of nearest-neighbors on conformational distributions, we preformed a joint vibrational (Infrared, Vibrational Circular Dichroism (VCD), polarized Raman) and 2D-NMR study of selected GxyG host-guest peptides: GDyG, GSyG, GxLG, GxVG, where x/y ={A,K,LV}. D and S (L and V) were chosen at the x (y) position due to their observance to drastically change the distribution of alanine in xAy tripeptide sequences in truncated coil libraries. The conformationally sensitive amide' profiles of the respective spectra were analyzed in terms of a statistical ensemble described as a superposition of 2D-Gaussian functions in Ramachandran space representing sub-ensembles of pPII-, β-strand-, helical-, and turn-like conformations. Our analysis and simulation of the amide I' band profiles exploits excitonic coupling between the local amide I' vibrational modes in the tetra-peptides. The resulting distributions reveal that D and S, which themselves have high propensities for turn-structures, strongly affect the conformational distribution of their downstream neighbor. Taken together, our results indicate that Dx and Sx motifs might act as conformational randomizers in proteins, attenuating intrinsic propensities of neighboring residues. Overall, our results show that nearest neighbor interactions contribute significantly to the Gibbs energy landscape of disordered peptides and proteins.
OSI Conformance Testing for Bibliographic Applications.
ERIC Educational Resources Information Center
Arbez, Gilbert; Swain, Leigh
1990-01-01
Describes the development of Open Systems Interconnection (OSI) conformance testing sites, conformance testing tools, and conformance testing services. Discusses related topics such as interoperability testing, arbitration testing, and international harmonization of conformance testing. A glossary is included. (24 references) (SD)
PubChem3D: Conformer generation
2011-01-01
Background PubChem, an open archive for the biological activities of small molecules, provides search and analysis tools to assist users in locating desired information. Many of these tools focus on the notion of chemical structure similarity at some level. PubChem3D enables similarity of chemical structure 3-D conformers to augment the existing similarity of 2-D chemical structure graphs. It is also desirable to relate theoretical 3-D descriptions of chemical structures to experimental biological activity. As such, it is important to be assured that the theoretical conformer models can reproduce experimentally determined bioactive conformations. In the present study, we investigate the effects of three primary conformer generation parameters (the fragment sampling rate, the energy window size, and force field variant) upon the accuracy of theoretical conformer models, and determined optimal settings for PubChem3D conformer model generation and conformer sampling. Results Using the software package OMEGA from OpenEye Scientific Software, Inc., theoretical 3-D conformer models were generated for 25,972 small-molecule ligands, whose 3-D structures were experimentally determined. Different values for primary conformer generation parameters were systematically tested to find optimal settings. Employing a greater fragment sampling rate than the default did not improve the accuracy of the theoretical conformer model ensembles. An ever increasing energy window did increase the overall average accuracy, with rapid convergence observed at 10 kcal/mol and 15 kcal/mol for model building and torsion search, respectively; however, subsequent study showed that an energy threshold of 25 kcal/mol for torsion search resulted in slightly improved results for larger and more flexible structures. Exclusion of coulomb terms from the 94s variant of the Merck molecular force field (MMFF94s) in the torsion search stage gave more accurate conformer models at lower energy windows. Overall
Malešević, Miroslav; Schumann, Michael; Jahreis, Günther; Fischer, Gunter; Lücke, Christian
2012-09-24
Turns are secondary-structure elements that are omnipresent in natively folded polypeptide chains. A large variety of four-residue β-turns exist, which differ mainly in the backbone dihedral angle values of the two central residues i+1 and i+2. The βVI-type turns are of particular biological interest because the i+2 residue is always a proline in the cis conformation and might thus serve as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed cyclic hexapeptides containing two proline residues that predominantly adopt the cis conformation in aqueous solution. NMR data and MD calculations indicated that the cyclic peptide sequences c-(-DXaa-Ser-Pro-DXaa-Lys-Pro-) result in highly symmetric backbone structures when both prolines are in the cis conformation and the D-amino acids are either alanine or phenylalanine residues. Replacement of the serine residue either by phosphoserine or by tyrosine compromises this symmetry, but further increases the cis conformation content of both prolines. As a result, we obtained a cyclic hexapeptide that exists almost exclusively as the cis-Pro/cis-Pro conformer but shows no cis/trans interconversion even in the presence of the PPIase Pin1, apparently due to an energetically quite favorable but highly restricted conformational space. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Twistor Geometry of Null Foliations in Complex Euclidean Space
NASA Astrophysics Data System (ADS)
Taghavi-Chabert, Arman
2017-01-01
We give a detailed account of the geometric correspondence between a smooth complex projective quadric hypersurface Q^n of dimension n ≥ 3, and its twistor space PT, defined to be the space of all linear subspaces of maximal dimension of Q^n. Viewing complex Euclidean space CE^n as a dense open subset of Q^n, we show how local foliations tangent to certain integrable holomorphic totally null distributions of maximal rank on CE^n can be constructed in terms of complex submanifolds of PT. The construction is illustrated by means of two examples, one involving conformal Killing spinors, the other, conformal Killing-Yano 2-forms. We focus on the odd-dimensional case, and we treat the even-dimensional case only tangentially for comparison.
Impaired protein conformational landscapes as revealed in anomalous Arrhenius prefactors.
Nagel, Zachary D; Dong, Ming; Bahnson, Brian J; Klinman, Judith P
2011-06-28
A growing body of data supports a role for protein motion in enzyme catalysis. In particular, the ability of enzymes to sample catalytically relevant conformational substates has been invoked to model kinetic and spectroscopic data. However, direct experimental links between rapidly interconverting conformations and the chemical steps of catalysis remain rare. We report here on the kinetic analysis and characterization of the hydride transfer step catalyzed by a series of mutant thermophilic alcohol dehydrogenases (ht-ADH), presenting evidence for Arrhenius prefactor values that become enormously elevated above an expected value of approximately 10(13) s(-1) when the enzyme operates below its optimal temperature range. Restoration of normal Arrhenius behavior in the ht-ADH reaction occurs at elevated temperatures. A simple model, in which reduced temperature alters the ability of the ht-ADH variants to sample the catalytically relevant region of conformational space, can reproduce the available data. These findings indicate an impaired landscape that has been generated by the combined condition of reduced temperature and mutation at a single, active-site hydrophobic side chain. The broader implication is that optimal enzyme function requires the maintenance of a relatively smooth landscape that minimizes low energy traps.
Impaired protein conformational landscapes as revealed in anomalous Arrhenius prefactors
Nagel, Zachary D.; Dong, Ming; Bahnson, Brian J.; Klinman, Judith P.
2011-01-01
A growing body of data supports a role for protein motion in enzyme catalysis. In particular, the ability of enzymes to sample catalytically relevant conformational substates has been invoked to model kinetic and spectroscopic data. However, direct experimental links between rapidly interconverting conformations and the chemical steps of catalysis remain rare. We report here on the kinetic analysis and characterization of the hydride transfer step catalyzed by a series of mutant thermophilic alcohol dehydrogenases (ht-ADH), presenting evidence for Arrhenius prefactor values that become enormously elevated above an expected value of approximately 1013 s-1 when the enzyme operates below its optimal temperature range. Restoration of normal Arrhenius behavior in the ht-ADH reaction occurs at elevated temperatures. A simple model, in which reduced temperature alters the ability of the ht-ADH variants to sample the catalytically relevant region of conformational space, can reproduce the available data. These findings indicate an impaired landscape that has been generated by the combined condition of reduced temperature and mutation at a single, active-site hydrophobic side chain. The broader implication is that optimal enzyme function requires the maintenance of a relatively smooth landscape that minimizes low energy traps. PMID:21670258
Constraints on parity violating conformal field theories in d = 3
NASA Astrophysics Data System (ADS)
Chowdhury, Subham Dutta; David, Justin R.; Prakash, Shiroman
2017-11-01
We derive constraints on three-point functions involving the stress tensor, T, and a conserved U(1) current, j, in 2+1 dimensional conformal field theories that violate parity, using conformal collider bounds introduced by Hofman and Maldacena. Conformal invariance allows parity-odd tensor-structures for the 〈 T T T〉 and 〈 jjT〉 correlation functions which are unique to three space-time dimensions. Let the parameters which determine the 〈 T T T〉 correlation function be t 4 and α T , where α T is the parity-violating contribution. Similarly let the parameters which determine 〈 jjT〉 correlation function be a 2, and α J , where α J is the parity-violating contribution. We show that the parameters ( t 4, α T ) and (a2, α J ) are bounded to lie inside a disc at the origin of the t 4 - α T plane and the a 2 - α J plane respectively. We then show that large N Chern-Simons theories coupled to a fundamental fermion/boson lie on the circle which bounds these discs. The `t Hooft coupling determines the location of these theories on the boundary circles.
Vaddiraju, Sreeram; Cebeci, Hülya; Gleason, Karen K; Wardle, Brian L
2009-11-01
A novel method for the fabrication of carbon nanotube (CNT)-conducting polymer composites is demonstrated by conformally coating extremely high aspect ratio vertically aligned-CNT (A-CNT) arrays with conducting polymer via oxidative chemical vapor deposition (oCVD). A mechanical densification technique is employed that allows the spacing of the A-CNTs to be controlled, yielding a range of inter-CNT distances between 20 and 70 nm. Using this morphology control, oCVD is shown to conformally coat 8-nm-diameter CNTs having array heights up to 1 mm (an aspect ratio of 10(5)) at all inter-CNT spacings. Three phase CNT-conducting polymer nanocomposites are then fabricated by introducing an insulating epoxy via capillary-driven wetting. CNT morphology is maintained during processing, allowing quantification of direction-dependent (nonisotropic) composite properties. Electrical conductivity occurs primarily along the CNT axial direction, such that the conformal conducting polymer has little effect on the activation energy required for charge conduction. In contrast, the conducting polymer coating enhanced the conductivity in the radial direction by lowering the activation energy required for the creation of mobile charge carriers, in agreement with variable-range-hopping models. The fabrication strategy introduced here can be used to create many multifunctional materials and devices (e.g., direction-tailorable hydrophobic and highly conducting materials), including a new four-phase advanced fiber composite architecture.
New Skeletal-Space-Filling Models
ERIC Educational Resources Information Center
Clarke, Frank H.
1977-01-01
Describes plastic, skeletal molecular models that are color-coded and can illustrate both the conformation and overall shape of small molecules. They can also be converted to space-filling counterparts by the additions of color-coded polystyrene spheres. (MLH)
NASA Astrophysics Data System (ADS)
Calabrese, Camilla; Maris, Assimo; Evangelisti, Luca; Piras, Anna; Parravicini, Valentina; Melandri, Sonia
2018-02-01
Abstract We describe an experimental and quantum chemical study for the accurate determination of the conformational space of small molecular systems governed by intramolecular non-covalent interactions. The model systems investigated belong to the biological relevant aminoalcohol’s family, and include 2-aminophenylethanol, 2-methylaminophenylethanol, noradrenaline, adrenaline 2-aminoethanol and N-methyl-2-aminoethanol. For the latter molecule, the rotational spectrum in the 6-18 and 59.6-74.4 GHz ranges was recorded in the isolated conditions of a free jet expansion. Based on the analysis of the rotational spectra, two different conformational species and 11 isotopologues were observed and their spectroscopic constants, including 14N-nuclear hyperfine coupling constants and methyl internal rotation barriers, were determined. From the experimental data a structural determination was obtained, which was also used to benchmark accurate quantum chemical calculations on the whole conformational space. Atom in molecules and non-covalent interactions theories allowed the characterization of the position of the intramolecular non-covalent interactions and the energies involved, highlighting the subtle balance responsible of the stabilization of all the molecular systems.
IR low-temperature matrix, X-ray and ab initio study on L-isoserine conformations.
Dobrowolski, Jan Cz; Jamróz, Michał H; Kołos, Robert; Rode, Joanna E; Cyrański, Michał K; Sadlej, Joanna
2010-09-28
The IR low-temperature Ar and Kr matrix spectra of l-isoserine were registered for the first time and interpreted by means of the anharmonic DFT frequencies calculated at the B3LYP/aug-cc-pVTZ and B3LYP/aug-cc-pVDZ levels. 54 l-isoserine conformers were predicted to be stable at the B3LYP/aug-cc-pVDZ level. Population of the 8 most stable conformers was based on the QCISD/aug-cc-pVDZ energies, corrected for thermal anharmonic factors obtained at the B3LYP/aug-cc-pVDZ level. We found several conformers to be present in the measured matrices and conformer 1 to be dominating. Presence of the conformer 2 is well confirmed by the nu(C=O) band at 1790 cm(-1) and two bands at 1380 and 1350 cm(-1). Presence of the conformer 4 is quite well confirmed by the nu(C-O) bands at 1120 and 1095 cm(-1). Slightly weaker arguments are found for the observation of conformers 6 and 3. Calculations on 54 neutral and 5 zwitterionic conformers in water at the IEF-PCM/B3LYP/aug-cc-pVDZ level suggest that one neutral and one zwitterionic conformer co-exist in the aqueous environment. The crystal structure of l-isoserine was solved by X-ray diffraction analysis. The compound crystallizes without solvent in the chiral P2(1)2(1)2 space group. The asymmetric unit contains a single molecule. The molecule is in its zwitterionic form with the CH(2)-NH(3) side chain in the gauche conformation with respect to the hydroxyl group and in the anti conformation with respect to the carboxylate group. The structure of l-isoserine is dominated by a set of intermolecular hydrogen bonds. The strongest one appears between the OH and COOH groups of two neighbouring molecules: the O...H contact is of 1.66(2) A, which is amongst the shortest H-bonds of this kind observed in amino acid crystal structures.
Fake conformal symmetry in unimodular gravity
NASA Astrophysics Data System (ADS)
Oda, Ichiro
2016-08-01
We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.
2016-08-11
A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, departs from Oak Hill, Florida, and heads to NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.
2016-08-11
A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, passes through the entrance to NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.
Joint estimation of 2D-DOA and frequency based on space-time matrix and conformal array.
Wan, Liang-Tian; Liu, Lu-Tao; Si, Wei-Jian; Tian, Zuo-Xi
2013-01-01
Each element in the conformal array has a different pattern, which leads to the performance deterioration of the conventional high resolution direction-of-arrival (DOA) algorithms. In this paper, a joint frequency and two-dimension DOA (2D-DOA) estimation algorithm for conformal array are proposed. The delay correlation function is used to suppress noise. Both spatial and time sampling are utilized to construct the spatial-time matrix. The frequency and 2D-DOA estimation are accomplished based on parallel factor (PARAFAC) analysis without spectral peak searching and parameter pairing. The proposed algorithm needs only four guiding elements with precise positions to estimate frequency and 2D-DOA. Other instrumental elements can be arranged flexibly on the surface of the carrier. Simulation results demonstrate the effectiveness of the proposed algorithm.
Tavoulari, Sotiria; Forrest, Lucy R.; Rudnick, Gary
2010-01-01
Serotonin transporter (SERT) is the main target for widely used antidepressant agents. Several of these drugs, including imipramine, citalopram, sertraline, and fluoxetine (Prozac), bound more avidly to SERT in the presence of Cl–. In contrast, Cl– did not enhance cocaine or paroxetine binding. A Cl– binding site recently identified in SERT, and shown to be important for Cl– dependent transport, was also critical for the Cl– dependence of antidepressant affinity. Mutation of the residues contributing to this site eliminated the Cl–-mediated affinity increase for imipramine and fluoxetine. Analysis of ligand docking to a single state of SERT indicated only small differences in the energy of interaction between bound ligands and Cl–. These differences in interaction energy cannot account for the affinity differences observed for Cl– dependence. However, fluoxetine binding led to a conformational change, detected by cysteine accessibility experiments, that was qualitatively different from that induced by cocaine or other ligands. Given the known Cl– requirement for serotonin-induced conformational changes, we propose that Cl– binding facilitates conformational changes required for optimal binding of fluoxetine and other antidepressant drugs. PMID:19641126
Domain decomposition methods for nonconforming finite element spaces of Lagrange-type
NASA Technical Reports Server (NTRS)
Cowsar, Lawrence C.
1993-01-01
In this article, we consider the application of three popular domain decomposition methods to Lagrange-type nonconforming finite element discretizations of scalar, self-adjoint, second order elliptic equations. The additive Schwarz method of Dryja and Widlund, the vertex space method of Smith, and the balancing method of Mandel applied to nonconforming elements are shown to converge at a rate no worse than their applications to the standard conforming piecewise linear Galerkin discretization. Essentially, the theory for the nonconforming elements is inherited from the existing theory for the conforming elements with only modest modification by constructing an isomorphism between the nonconforming finite element space and a space of continuous piecewise linear functions.
Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji
2016-07-01
This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji
2016-01-01
This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins. Guest Editors: J.C. Gumbart and Sergei Noskov. PMID:26766517
Kusakiewicz-Dawid, Anna; Porada, Monika; Ochędzan-Siodłak, Wioletta; Broda, Małgorzata A; Bujak, Maciej; Siodłak, Dawid
2017-09-01
A series of model compounds containing 3-amino-1H-pyrazole-5-carboxylic acid residue with N-terminal amide/urethane and C-terminal amide/hydrazide/ester groups were investigated by using NMR, Fourier transform infrared, and single-crystal X-ray diffraction methods, additionally supported by theoretical calculations. The studies demonstrate that the most preferred is the extended conformation with torsion angles ϕ and ψ close to ±180°. The studied 1H-pyrazole with N-terminal amide/urethane and C-terminal amide/hydrazide groups solely adopts this energetically favored conformation confirming rigidity of that structural motif. However, when the C-terminal ester group is present, the second conformation with torsion angles ϕ and ψ close to ±180° and 0°, respectively, is accessible. The conformational equilibrium is observed in NMR and Fourier transform infrared studies in solution in polar environment as well as in the crystal structures of other related compounds. The observed conformational preferences are clearly related to the presence of intramolecular interactions formed within the studied residue. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
1985-11-30
The crew assigned to the STS-61B mission included Bryan D. O’Conner, pilot; Brewster H. Shaw, commander; Charles D. Walker, payload specialist; mission specialists Jerry L. Ross, Mary L. Cleave, and Sherwood C. Spring; and Rodolpho Neri Vela, payload specialist. Launched aboard the Space Shuttle Atlantis November 28, 1985 at 7:29:00 pm (EST), the STS-61B mission’s primary payload included three communications satellites: MORELOS-B (Mexico); AUSSAT-2 (Australia); and SATCOM KU-2 (RCA Americom). Two experiments were conducted to test assembling erectable structures in space: EASE (Experimental Assembly of Structures in Extravehicular Activity), and ACCESS (Assembly Concept for Construction of Erectable Space Structure). In a joint venture between NASA/Langley Research Center in Hampton, Virginia and the Marshall Space Flight Center (MSFC), EASE and ACCESS were developed and demonstrated at MSFC's Neutral Buoyancy Simulator (NBS). The primary objective of this experiment was to test the structural assembly concepts for suitability as the framework for larger space structures and to identify ways to improve the productivity of space construction. In this STS-61B onboard photo, astronaut Ross was working on the ACCESS experiment during an Extravehicular Activity (EVA).
1985-11-30
The crew assigned to the STS-61B mission included Bryan D. O’Conner, pilot; Brewster H. Shaw, commander; Charles D. Walker, payload specialist; mission specialists Jerry L. Ross, Mary L. Cleave, and Sherwood C. Spring; and Rodolpho Neri Vela, payload specialist. Launched aboard the Space Shuttle Atlantis November 28, 1985 at 7:29:00 pm (EST), the STS-61B mission’s primary payload included three communications satellites: MORELOS-B (Mexico); AUSSAT-2 (Australia); and SATCOM KU-2 (RCA Americom). Two experiments were conducted to test assembling erectable structures in space: EASE (Experimental Assembly of Structures in Extravehicular Activity), and ACCESS (Assembly Concept for Construction of Erectable Space Structure). In a joint venture between NASA/Langley Research Center in Hampton, Virginia and the Marshall Space Flight Center (MSFC), EASE and ACCESS were developed and demonstrated at MSFC's Neutral Buoyancy Simulator (NBS). In this STS-61B onboard photo astronaut Ross, located on the Manipulator Foot Restraint (MFR) over the cargo bay, erects ACCESS. The primary objective of this experiment was to test the structural assembly concepts for suitability as the framework for larger space structures and to identify ways to improve the productivity of space construction.
1985-11-30
The crew assigned to the STS-61B mission included Bryan D. O’Conner, pilot; Brewster H. Shaw, commander; Charles D. Walker, payload specialist; mission specialists Jerry L. Ross, Mary L. Cleave, and Sherwood C. Spring; and Rodolpho Neri Vela, payload specialist. Launched aboard the Space Shuttle Atlantis November 28, 1985 at 7:29:00 pm (EST), the STS-61B mission’s primary payload included three communications satellites: MORELOS-B (Mexico); AUSSAT-2 (Australia); and SATCOM KU-2 (RCA Americom). Two experiments were conducted to test assembling erectable structures in space: EASE (Experimental Assembly of Structures in Extravehicular Activity), and ACCESS (Assembly Concept for Construction of Erectable Space Structure). In a joint venture between NASA/Langley Research Center in Hampton, Virginia, and the Marshall Space Flight Center (MSFC), EASE and ACCESS were developed and demonstrated at MSFC's Neutral Buoyancy Simulator (NBS). In this STS-61B onboard photo, astronaut Ross works on ACCESS high above the orbiter. The primary objective of these experiments was to test the structural assembly concepts for suitability as the framework for larger space structures and to identify ways to improve the productivity of space construction.
Comparison of molecular dynamics and superfamily spaces of protein domain deformation
Velázquez-Muriel, Javier A; Rueda, Manuel; Cuesta, Isabel; Pascual-Montano, Alberto; Orozco, Modesto; Carazo, José-María
2009-01-01
Background It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space). Results Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases. Conclusion Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding. PMID:19220918
Conformational study and structure of N-(2,5-methylphenyl)salicylaldimine
NASA Astrophysics Data System (ADS)
Elmali, A.; Elerman, Y.; Zeyrek, C. T.
1998-02-01
N-(2,5-methylphenyl)salicylaldimine (C 15H 15NO) has been investigated by X-ray analysis and AM1 semi-empirical quantum mechanical method. The crystal is in the orthorhombic space group P2 12 12 1 with a = 6.839(1), b = 7.720(4), c = 23.183(3) Å, V = 1224.1(2) Å3, Z = 4, Dc = 1.222 g cm -3 and μ(Mo K α) = 0.076 mm -1. The title structure was solved by direct methods and refined to R = 0.0364 for 1489 reflections [ I > 2 σ( I)] by full-matrix anisotropic least-squares methods. The title compound is photochromic and the molecule is not planar. There is a strong intramolecular hydrogen bond of distance 2.604(2) Å between the hydroxyl oxygen atom and imine nitrogen atom, the hydrogen atom essentially being bonded to the oxygen atom. Minimum energy conformations from AM1 were calculated as a function of three torsion angles, θ1 (C8N1C7C6), θ2 (C9C8N1C7) and θ3 (N1C7C6C5), varied every 10°. The optimized geometry of the crystal structure corresponding to non-planar conformation is the most stable conformation in all calculations. The results strongly indicate that the minimum energy conformation is primarily determined by non-bonded hydrogen-hydrogen repulsions.
14 CFR 1203a.103 - Access to security areas.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Access to security areas. 1203a.103 Section 1203a.103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NASA SECURITY AREAS § 1203a.103 Access to security areas. (a) Only those NASA employees, NASA contractor employees, and...
14 CFR 1203a.103 - Access to security areas.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Access to security areas. 1203a.103 Section 1203a.103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NASA SECURITY AREAS § 1203a.103 Access to security areas. (a) Only those NASA employees, NASA contractor employees, and...
Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen
2015-01-01
Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630
Han, Dongmei; Försterling, F. Holger; Li, Xiaoyan; Deschamps, Jeffrey R.; Parrish, Damon; Cao, Hui; Rallapalli, Sundari; Clayton, Terry; Teng, Yun; Majumder, Samarpan; Sankar, Subramaniam; Roth, Bryan L.; Sieghart, Werner; Furtmuller, Roman; Rowlett, James; Weed, Mike R.; Cook, James M.
2013-01-01
The stable conformations of GABAA-benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for α5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors. PMID:18790643
Riera, Thomas V.; Zheng, Lianqing; Josephine, Helen R.; Min, Donghong; Yang, Wei; Hedstrom, Lizbeth
2011-01-01
Allosteric activators are generally believed to shift the equilibrium distribution of enzyme conformations to favor a catalytically productive structure; the kinetics of conformational exchange is seldom addressed. Several observations suggested that the usual allosteric mechanism might not apply to the activation of IMP dehydrogenase (IMPDH) by monovalent cations. Therefore we investigated the mechanism of K+ activation in IMPDH by delineating the kinetic mechanism in the absence of monovalent cations. Surprisingly, the K+-dependence of kcat derives from the rate of flap closure, which increases by ≥65-fold in the presence of K+. We performed both alchemical free energy simulations and potential of mean force calculations using the orthogonal space random walk strategy to computationally analyze how K+ accelerates this conformational change. The simulations recapitulate the preference of IMPDH for K+, validating the computational models. When K+ is replaced with a dummy ion, the residues of the K+ binding site relax into ordered secondary structure, creating a barrier to conformational exchange. K+ mobilizes these residues by providing alternate interactions for the main chain carbonyls. Potential of mean force calculations indicate that K+ changes the shape of the energy well, shrinking the reaction coordinate by shifting the closed conformation toward the open state. This work suggests that allosteric regulation can be under kinetic as well as thermodynamic control. PMID:21870820
2016-08-11
A heavy-lift transport truck, carrying the Crew Access Arm for Space Launch Complex 41, crosses the Haulover Canal Bridge on its way to the entrance of NASA’s Kennedy Space Center in Florida. The arm will be installed on the Complex 41 Crew Access Tower at Cape Canaveral Air Force Station. It will be used as a bridge by astronauts to board Boeing's CST-100 Starliner spacecraft as it stands on the launch pad atop a United Launch Alliance Atlas V rocket.
Spontaneous symmetry breaking, conformal anomaly and incompressible fluid turbulence
NASA Astrophysics Data System (ADS)
Oz, Yaron
2017-11-01
We propose an effective conformal field theory (CFT) description of steady state incompressible fluid turbulence at the inertial range of scales in any number of spatial dimensions. We derive a KPZ-type equation for the anomalous scaling of the longitudinal velocity structure functions and relate the intermittency parameter to the boundary Euler (A-type) conformal anomaly coefficient. The proposed theory consists of a mean field CFT that exhibits Kolmogorov linear scaling (K41 theory) coupled to a dilaton. The dilaton is a Nambu-Goldstone gapless mode that arises from a spontaneous breaking due to the energy flux of the separate scale and time symmetries of the inviscid Navier-Stokes equations to a K41 scaling with a dynamical exponent z=2/3 . The dilaton acts as a random measure that dresses the K41 theory and introduces intermittency. We discuss the two, three and large number of space dimensions cases and how entanglement entropy can be used to characterize the intermittency strength.
From a structural average to the conformational ensemble of a DNA bulge
Shi, Xuesong; Beauchamp, Kyle A.; Harbury, Pehr B.; Herschlag, Daniel
2014-01-01
Direct experimental measurements of conformational ensembles are critical for understanding macromolecular function, but traditional biophysical methods do not directly report the solution ensemble of a macromolecule. Small-angle X-ray scattering interferometry has the potential to overcome this limitation by providing the instantaneous distance distribution between pairs of gold-nanocrystal probes conjugated to a macromolecule in solution. Our X-ray interferometry experiments reveal an increasing bend angle of DNA duplexes with bulges of one, three, and five adenosine residues, consistent with previous FRET measurements, and further reveal an increasingly broad conformational ensemble with increasing bulge length. The distance distributions for the AAA bulge duplex (3A-DNA) with six different Au-Au pairs provide strong evidence against a simple elastic model in which fluctuations occur about a single conformational state. Instead, the measured distance distributions suggest a 3A-DNA ensemble with multiple conformational states predominantly across a region of conformational space with bend angles between 24 and 85 degrees and characteristic bend directions and helical twists and displacements. Additional X-ray interferometry experiments revealed perturbations to the ensemble from changes in ionic conditions and the bulge sequence, effects that can be understood in terms of electrostatic and stacking contributions to the ensemble and that demonstrate the sensitivity of X-ray interferometry. Combining X-ray interferometry ensemble data with molecular dynamics simulations gave atomic-level models of representative conformational states and of the molecular interactions that may shape the ensemble, and fluorescence measurements with 2-aminopurine-substituted 3A-DNA provided initial tests of these atomistic models. More generally, X-ray interferometry will provide powerful benchmarks for testing and developing computational methods. PMID:24706812
Big bounce, slow-roll inflation, and dark energy from conformal gravity
NASA Astrophysics Data System (ADS)
Gegenberg, Jack; Rahmati, Shohreh; Seahra, Sanjeev S.
2017-02-01
We examine the cosmological sector of a gauge theory of gravity based on the SO(4,2) conformal group of Minkowski space. We allow for conventional matter coupled to the spacetime metric as well as matter coupled to the field that gauges special conformal transformations. An effective vacuum energy appears as an integration constant, and this allows us to recover the late time acceleration of the Universe. Furthermore, gravitational fields sourced by ordinary cosmological matter (i.e. dust and radiation) are significantly weakened in the very early Universe, which has the effect of replacing the big bang with a big bounce. Finally, we find that this bounce is followed by a period of nearly exponential slow roll inflation that can last long enough to explain the large scale homogeneity of the cosmic microwave background.
NASA Astrophysics Data System (ADS)
Seredych, Mykola; Koscinski, Mikolaj; Sliwinska-Bartkowiak, Malgorzata; Bandosz, Teresa J.
2012-12-01
Composites of commercial graphene and nanoporous sodium-salt-polymer-derived carbons were prepared with 5 or 20 weight% graphene. The materials were characterized using the adsorption of nitrogen, SEM/EDX, thermal analysis, Raman spectroscopy and potentiometric titration. The samples' conductivity was also measured. The performance of the carbon composites in energy storage was linked to their porosity and electronic conductivity. The small pores (<0.7) were found as very active for double layer capacitance. It was demonstrated that when double layer capacitance is a predominant mechanism of charge storage, the degree of the pore space utilization for that storage can be increased by increasing the conductivity of the carbons. That active pore space utilization is defined as gravimetric capacitance per unit pore volume in pores smaller than 0.7 nm. Its magnitude is affected by conductivity of the carbon materials. The functional groups, besides pseudocapacitive contribution, increased the wettability and thus the degree of the pore space utilization. Graphene phase, owing to its conductivity, also took part in an insitu increase of the small pore accessibility and thus the capacitance of the composites via enhancing an electron transfer to small pores and thus imposing the reduction of groups blocking the pores for electrolyte ions.
Benchmarking Commercial Conformer Ensemble Generators.
Friedrich, Nils-Ole; de Bruyn Kops, Christina; Flachsenberg, Florian; Sommer, Kai; Rarey, Matthias; Kirchmair, Johannes
2017-11-27
We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, MOE Stochastic, MOE Conformation Import, and OMEGA) and one leading free algorithm, the distance geometry algorithm implemented in RDKit. The comparative study is based on a new version of the Platinum Diverse Dataset, a high-quality benchmarking dataset of 2859 protein-bound ligand conformations extracted from the PDB. Differences in the performance of commercial algorithms are much smaller than those observed for free algorithms in our previous study (J. Chem. Inf. 2017, 57, 529-539). For commercial algorithms, the median minimum root-mean-square deviations measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers are between 0.46 and 0.61 Å. Commercial conformer ensemble generators are characterized by their high robustness, with at least 99% of all input molecules successfully processed and few or even no substantial geometrical errors detectable in their output conformations. The RDKit distance geometry algorithm (with minimization enabled) appears to be a good free alternative since its performance is comparable to that of the midranked commercial algorithms. Based on a statistical analysis, we elaborate on which algorithms to use and how to parametrize them for best performance in different application scenarios.
On the effect of hydrostatic pressure on the conformational stability of globular proteins.
Graziano, Giuseppe
2015-12-01
The model developed for cold denaturation (Graziano, PCCP 2010, 12, 14245-14252) is extended to rationalize the dependence of protein conformational stability upon hydrostatic pressure, at room temperature. A pressure- volume work is associated with the process of cavity creation for the need to enlarge the liquid volume against hydrostatic pressure. This contribution destabilizes the native state that has a molecular volume slightly larger than the denatured state due to voids existing in the protein core. Therefore, there is a hydrostatic pressure value at which the pressure-volume contribution plus the conformational entropy loss of the polypeptide chain are able to overwhelm the stabilizing gain in translational entropy of water molecules, due to the decrease in water accessible surface area upon folding, causing denaturation. © 2015 Wiley Periodicals, Inc.
Innovative approach for low-cost quick-access small payload missions
NASA Astrophysics Data System (ADS)
Friis, Jan W., Jr.
2000-11-01
A significant part of the burgeoning commercial space industry is placing an unprecedented number of satellites into low earth orbit for a variety of new applications and services. By some estimates the commercial space industry now exceeds that of government space activities. Yet the two markets remain largely separate, with each deploying dedicated satellites and infrastructure for their respective missions. One commercial space firm, Final Analysis, has created a new program wherein either government, scientific or new technology payloads can be integrated on a commercial spacecraft on commercial satellites for a variety of mission scenarios at a fraction of the cost of a dedicated mission. NASA has recognized the advantage of this approach, and has awarded the Quick Ride program to provide frequent, low cost flight opportunities for small independent payloads aboard the Final Analysis constellation, and investigators are rapidly developing science programs that conform to the proposed payload accommodations envelope. Missions that were not feasible using dedicated launches are now receiving approval under the lower cost Quick Ride approach. Final Analysis has dedicated ten out of its thirty-eight satellites in support of the Quick Ride efforts. The benefit of this type of space access extend beyond NASA science programs. Commercial space firms can now gain valuable flight heritage for new technology and satellite product offerings. Further, emerging international space programs can now place a payload in orbit enabling the country to allocate its resources against the payload and mission requirements rather htan increased launch costs of a dedicated spacecraft. Finally, the low cost nature provides University-based research educational opportunities previously out of the reach of most space-related budgets. This paper will describe the motivation, benefits, technical features, and program costs of the Final Analysis secondary payload program. Payloads can be
Static models with conformal symmetry
NASA Astrophysics Data System (ADS)
Manjonjo, A. M.; Maharaj, S. D.; Moopanar, S.
2018-02-01
We study static spherically symmetric spacetimes with a spherical conformal symmetry and a nonstatic conformal factor associated with the conformal Killing field. With these assumptions we find an explicit relationship relating two metric components of the metric tensor field. This leads to the general solution of the Einstein field equations with a conformal symmetry in a static spherically symmetric spacetime. For perfect fluids we can find all metrics explicitly and show that the models always admit a barotropic equation of state. Contained within this class of spacetimes are the well known metrics of (interior) Schwarzschild, Tolman, Kuchowicz, Korkina and Orlyanskii, Patwardhan and Vaidya, and Buchdahl and Land. The isothermal metric of Saslaw et al also admits a conformal symmetry. For imperfect fluids an infinite family of exact solutions to the field equations can be generated.
49 CFR 38.23 - Mobility aid accessibility.
Code of Federal Regulations, 2012 CFR
2012-10-01
... in width. When the platform is at vehicle floor height with the inner barrier (if applicable) down or... accessible entrance as practicable and shall have a clear floor area of 30 inches by 48 inches. Such space shall adjoin, and may overlap, an access path. Not more than 6 inches of the required clear floor space...
49 CFR 38.23 - Mobility aid accessibility.
Code of Federal Regulations, 2014 CFR
2014-10-01
... in width. When the platform is at vehicle floor height with the inner barrier (if applicable) down or... accessible entrance as practicable and shall have a clear floor area of 30 inches by 48 inches. Such space shall adjoin, and may overlap, an access path. Not more than 6 inches of the required clear floor space...
Conformal and Nearly Conformal Theories at Large N
NASA Astrophysics Data System (ADS)
Tarnoplskiy, Grigory M.
In this thesis we present new results in conformal and nearly conformal field theories in various dimensions. In chapter two, we study different properties of the conformal Quantum Electrodynamics (QED) in continuous dimension d. At first we study conformal QED using large Nf methods, where Nf is the number of massless fermions. We compute its sphere free energy as a function of d, ignoring the terms of order 1/Nf and higher. For finite Nf we use the epsilon-expansion. Next we use a large Nf diagrammatic approach to calculate the leading corrections to CT, the coefficient of the two-point function of the stress-energy tensor, and CJ, the coefficient of the two-point function of the global symmetry current. We present explicit formulae as a function of d and check them versus the expectations in 2 and 4 - epsilon dimensions. In chapter three, we discuss vacuum stability in 1 + 1 dimensional conformal field theories with external background fields. We show that the vacuum decay rate is given by a non-local two-form. This two-form is a boundary term that must be added to the effective in/out Lagrangian. The two-form is expressed in terms of a Riemann-Hilbert decomposition for background gauge fields, and is given by its novel "functional'' version in the gravitational case. In chapter four, we explore Tensor models. Such models possess the large N limit dominated by the melon diagrams. The quantum mechanics of a real anti-commuting rank-3 tensor has a large N limit similar to the Sachdev-Ye-Kitaev (SYK) model. We also discuss the quantum mechanics of a complex 3-index anti-commuting tensor and argue that it is equivalent in the large N limit to a version of SYK model with complex fermions. Finally, we discuss models of a commuting tensor in dimension d. We study the spectrum of the large N quantum field theory of bosonic rank-3 tensors using the Schwinger-Dyson equations. We compare some of these results with the 4 - epsilon expansion, finding perfect agreement. We
Current state of web accessibility of Malaysian ministries websites
NASA Astrophysics Data System (ADS)
Ahmi, Aidi; Mohamad, Rosli
2016-08-01
Despite the fact that Malaysian public institutions have progressed considerably on website and portal usage, web accessibility has been reported as one of the issues deserves special attention. Consistent with the government moves to promote an effective use of web and portal, it is essential for the government institutions to ensure compliance with established standards and guidelines on web accessibility. This paper evaluates accessibility of 25 Malaysian ministries websites using automated tools i.e. WAVE and Achecker. Both tools are designed to objectively evaluate web accessibility in conformance with Web Content Accessibility Guidelines 2.0 (WCAG 2.0) and United States Rehabilitation Act 1973 (Section 508). The findings reported somewhat low compliance to web accessibility standard amongst the ministries. Further enhancement is needed in the aspect of input elements such as label and checkbox to be associated with text as well as image-related elements. This findings could be used as a mechanism for webmasters to locate and rectify errors pertaining to the web accessibility and to ensure equal access of the web information and services to all citizen.
Conformational Transitions and Convergence of Absolute Binding Free Energy Calculations
Lapelosa, Mauro; Gallicchio, Emilio; Levy, Ronald M.
2011-01-01
The Binding Energy Distribution Analysis Method (BEDAM) is employed to compute the standard binding free energies of a series of ligands to a FK506 binding protein (FKBP12) with implicit solvation. Binding free energy estimates are in reasonably good agreement with experimental affinities. The conformations of the complexes identified by the simulations are in good agreement with crystallographic data, which was not used to restrain ligand orientations. The BEDAM method is based on λ -hopping Hamiltonian parallel Replica Exchange (HREM) molecular dynamics conformational sampling, the OPLS-AA/AGBNP2 effective potential, and multi-state free energy estimators (MBAR). Achieving converged and accurate results depends on all of these elements of the calculation. Convergence of the binding free energy is tied to the level of convergence of binding energy distributions at critical intermediate states where bound and unbound states are at equilibrium, and where the rate of binding/unbinding conformational transitions is maximal. This finding mirrors similar observations in the context of order/disorder transitions as for example in protein folding. Insights concerning the physical mechanism of ligand binding and unbinding are obtained. Convergence for the largest FK506 ligand is achieved only after imposing strict conformational restraints, which however require accurate prior structural knowledge of the structure of the complex. The analytical AGBNP2 model is found to underestimate the magnitude of the hydrophobic driving force towards binding in these systems characterized by loosely packed protein-ligand binding interfaces. Rescoring of the binding energies using a numerical surface area model corrects this deficiency. This study illustrates the complex interplay between energy models, exploration of conformational space, and free energy estimators needed to obtain robust estimates from binding free energy calculations. PMID:22368530
Monochromatic plane-fronted waves in conformal gravity are pure gauge
NASA Astrophysics Data System (ADS)
Fabbri, Luca; Paranjape, M. B.
2011-05-01
We consider plane-fronted, monochromatic gravitational waves on a Minkowski background, in a conformally invariant theory of general relativity. By this we mean waves of the form: gμν=ημν+γμνF(k·x), where γμν is a constant polarization tensor, and kμ is a lightlike vector. We also assume the coordinate gauge condition |g|-1/4∂τ(|g|1/4gστ)=0 which is the conformal analog of the harmonic gauge condition gμνΓμνσ=-|g|-1/2∂τ(|g|1/2gστ)=0, where det[gμν]≡g. Requiring additionally the conformal gauge condition g=-1 surprisingly implies that the waves are both transverse and traceless. Although the ansatz for the metric is eminently reasonable when considering perturbative gravitational waves, we show that the metric is reducible to the metric of Minkowski space-time via a sequence of coordinate transformations which respect the gauge conditions, without any perturbative approximation that γμν be small. This implies that we have, in fact, exact plane-wave solutions; however, they are simply coordinate/conformal artifacts. As a consequence, they carry no energy. Our result does not imply that conformal gravity does not have gravitational wave phenomena. A different, more generalized ansatz for the deviation, taking into account the fourth-order nature of the field equation, which has the form gμν=ημν+Bμν(n·x)G(k·x), indeed yields waves which carry energy and momentum [P. D. Mannheim, Gen. Relativ. Gravit.GRGVA80001-7701 43, 703 (2010)10.1007/s10714-010-1088-z]. It is just surprising that transverse, traceless, plane-fronted gravitational waves, those that would be used in any standard, perturbative, quantum analysis of the theory, simply do not exist.
Shape Analysis of Planar Multiply-Connected Objects Using Conformal Welding.
Lok Ming Lui; Wei Zeng; Shing-Tung Yau; Xianfeng Gu
2014-07-01
Shape analysis is a central problem in the field of computer vision. In 2D shape analysis, classification and recognition of objects from their observed silhouettes are extremely crucial but difficult. It usually involves an efficient representation of 2D shape space with a metric, so that its mathematical structure can be used for further analysis. Although the study of 2D simply-connected shapes has been subject to a corpus of literatures, the analysis of multiply-connected shapes is comparatively less studied. In this work, we propose a representation for general 2D multiply-connected domains with arbitrary topologies using conformal welding. A metric can be defined on the proposed representation space, which gives a metric to measure dissimilarities between objects. The main idea is to map the exterior and interior of the domain conformally to unit disks and circle domains (unit disk with several inner disks removed), using holomorphic 1-forms. A set of diffeomorphisms of the unit circle S(1) can be obtained, which together with the conformal modules are used to define the shape signature. A shape distance between shape signatures can be defined to measure dissimilarities between shapes. We prove theoretically that the proposed shape signature uniquely determines the multiply-connected objects under suitable normalization. We also introduce a reconstruction algorithm to obtain shapes from their signatures. This completes our framework and allows us to move back and forth between shapes and signatures. With that, a morphing algorithm between shapes can be developed through the interpolation of the Beltrami coefficients associated with the signatures. Experiments have been carried out on shapes extracted from real images. Results demonstrate the efficacy of our proposed algorithm as a stable shape representation scheme.
Hossen, Abul; Westhues, Anne
2010-09-01
This study was an exploration of the experiences of 17 women, age 60 or more years, from Bangladesh. The women were asked about decision-making processes with respect to their access to health care and whether they perceived that there were differences based on age and sex in the way a household responds to an illness episode. The overall theme that characterized their experiences was "being in a socially excluded space." The themes that explained this perception of social exclusion included gender- and age-based social practices, gender- and class-based economic practices, religious beliefs that restricted the mobility of women, and social constructions of health and illness that led the women to avoid seeking health care. We conclude that the Bangladesh constitutional guarantee that disparities will be eliminated in access to health care between rich and poor, men and women, rural and urban residents, and younger and older citizens has not yet been realized.
NASA Astrophysics Data System (ADS)
Hosseini, Kamyar; Mayeli, Peyman; Bekir, Ahmet; Guner, Ozkan
2018-01-01
In this article, a special type of fractional differential equations (FDEs) named the density-dependent conformable fractional diffusion-reaction (DDCFDR) equation is studied. Aforementioned equation has a significant role in the modelling of some phenomena arising in the applied science. The well-organized methods, including the \\exp (-φ (\\varepsilon )) -expansion and modified Kudryashov methods are exerted to generate the exact solutions of this equation such that some of the solutions are new and have been reported for the first time. Results illustrate that both methods have a great performance in handling the DDCFDR equation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brodsky, S
2003-10-24
The effective QCD charge extracted from {tau} decay is remarkably constant at small momenta, implying the near-conformal behavior of hadronic interactions at small momentum transfer. The correspondence of large-N{sub c} supergravity theory in higher-dimensional anti-de Sitter spaces with gauge theory in physical space-time also has interesting implications for hadron phenomenology in the conformal limit, such as constituent counting rules for hard exclusive processes. The utility of light-front quantization and lightfront Fock wavefunctions for analyzing such phenomena and representing the dynamics of QCD bound states is reviewed. I also discuss the novel effects of initial- and final-state interactions in hard QCDmore » inclusive processes, including Bjorken-scaling single-spin asymmetries and the leading-twist diffractive and shadowing contributions to deep inelastic lepton-proton scattering.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance
2011-09-20
The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS-ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the {alpha}2 helix and in the conformation of the {alpha}3-{alpha}4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4-6.0). In contrast, at a highermore » pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS-ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS-ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less
The Building Game: From Enumerative Combinatorics to Conformational Diffusion
NASA Astrophysics Data System (ADS)
Johnson-Chyzhykov, Daniel; Menon, Govind
2016-08-01
We study a discrete attachment model for the self-assembly of polyhedra called the building game. We investigate two distinct aspects of the model: (i) enumerative combinatorics of the intermediate states and (ii) a notion of Brownian motion for the polyhedral linkage defined by each intermediate that we term conformational diffusion. The combinatorial configuration space of the model is computed for the Platonic, Archimedean, and Catalan solids of up to 30 faces, and several novel enumerative results are generated. These represent the most exhaustive computations of this nature to date. We further extend the building game to include geometric information. The combinatorial structure of each intermediate yields a systems of constraints specifying a polyhedral linkage and its moduli space. We use a random walk to simulate a reflected Brownian motion in each moduli space. Empirical statistics of the random walk may be used to define the rates of transition for a Markov process modeling the process of self-assembly.
Tamura, Koichi; Hayashi, Shigehiko
2015-07-14
Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.
Conformational selection in protein binding and function
Weikl, Thomas R; Paul, Fabian
2014-01-01
Protein binding and function often involves conformational changes. Advanced nuclear magnetic resonance (NMR) experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may “select” protein conformations for binding (or unbinding). In this review, we argue that this conformational selection requires transition times for ligand binding and unbinding that are small compared to the dwell times of proteins in different conformations, which is plausible for small ligand molecules. Such a separation of timescales leads to a decoupling and temporal ordering of binding/unbinding events and conformational changes. We propose that conformational-selection and induced-change processes (such as induced fit) are two sides of the same coin, because the temporal ordering is reversed in binding and unbinding direction. Conformational-selection processes can be characterized by a conformational excitation that occurs prior to a binding or unbinding event, while induced-change processes exhibit a characteristic conformational relaxation that occurs after a binding or unbinding event. We discuss how the ordering of events can be determined from relaxation rates and effective on- and off-rates determined in mixing experiments, and from the conformational exchange rates measured in advanced NMR or single-molecule fluorescence resonance energy transfer experiments. For larger ligand molecules such as peptides, conformational changes and binding events can be intricately coupled and exhibit aspects of conformational-selection and induced-change processes in both binding and unbinding direction. PMID:25155241
Sialyldisaccharide conformations: a molecular dynamics perspective
NASA Astrophysics Data System (ADS)
Selvin, Jeyasigamani F. A.; Priyadarzini, Thanu R. K.; Veluraja, Kasinadar
2012-04-01
Sialyldisaccharides are significant terminal components of glycoconjugates and their negative charge and conformation are extensively utilized in molecular recognition processes. The conformation and flexibility of four biologically important sialyldisaccharides [Neu5Acα(2-3)Gal, Neu5Acα(2-6)Gal, Neu5Acα(2-8)Neu5Ac and Neu5Acα(2-9)Neu5Ac] are studied using Molecular Dynamics simulations of 20 ns duration to deduce the conformational preferences of the sialyldisaccharides and the interactions which stabilize the conformations. This study clearly describes the possible conformational models of sialyldisaccharides deduced from 20 ns Molecular Dynamics simulations and our results confirm the role of water in the structural stabilization of sialyldisaccharides. An extensive analysis on the sialyldisaccharide structures available in PDB also confirms the conformational regions found by experiments are detected in MD simulations of 20 ns duration. The three dimensional structural coordinates for all the MD derived sialyldisaccharide conformations are deposited in the 3DSDSCAR database and these conformational models will be useful for glycobiologists and biotechnologists to understand the biological functions of sialic acid containing glycoconjugates.
Conformations of Substituted Ethanes.
ERIC Educational Resources Information Center
Kingsbury, Charles A.
1979-01-01
Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)
NASA Astrophysics Data System (ADS)
Csankó, K.; Forgo, P.; Boros, K.; Hohmann, J.; Sipos, P.; Pálinkó, I.
2013-07-01
Following a preliminary exploration of the conformational space by the PM3 and HF/6-31 G*ab initio methods the conformational characteristics of the scarcely available Z isomer of an α-pyridyl-substituted cinnamic acid dimer [Z-2(3‧-pyridyl)-3-phenylpropanoic acid] was studied by NMR spectroscopy (NOESY measurements) in DMSO(d6), methanol(d4) and chloroform(d1). Calculations predicted that full conjugation was overruled by steric interactions and the rotation of the pyridyl ring was not restricted. NOESY measurements verified indeed that in all three solvents the pyridyl group was virtually freely rotating, while some restriction applied for that of the phenyl group.
NASA Astrophysics Data System (ADS)
Schrogl, K.-U.; Summerer, L.
2016-12-01
This article provides a comprehensive look at climate engineering and space. Its starting point is that the States are failing to slow down global warming. The consequences for the environment and the economic and societal burden are uncontested. The priority to maintain the use of fossil resources might soon lead to the implementation of deliberate engineering measures to alter the climate instead of reducing the greenhouse gases. The article describes these currently discussed measures for such climate engineering. It will particularly analyse the expected contributions from space to these concepts. Based on this it evaluates the economic and political implications and finally tests the conformity of these concepts with space law.
Wadley, Leven M; Keating, Kevin S; Duarte, Carlos M; Pyle, Anna Marie
2007-09-28
Quantitatively describing RNA structure and conformational elements remains a formidable problem. Seven standard torsion angles and the sugar pucker are necessary to characterize the conformation of an RNA nucleotide completely. Progress has been made toward understanding the discrete nature of RNA structure, but classifying simple and ubiquitous structural elements such as helices and motifs remains a difficult task. One approach for describing RNA structure in a simple, mathematically consistent, and computationally accessible manner involves the invocation of two pseudotorsions, eta (C4'(n-1), P(n), C4'(n), P(n+1)) and theta (P(n), C4'(n), P(n+1), C4'(n+1)), which can be used to describe RNA conformation in much the same way that varphi and psi are used to describe backbone configuration of proteins. Here, we conduct an exploration and statistical evaluation of pseudotorsional space and of the Ramachandran-like eta-theta plot. We show that, through the rigorous quantitative analysis of the eta-theta plot, the pseudotorsional descriptors eta and theta, together with sugar pucker, are sufficient to describe RNA backbone conformation fully in most cases. These descriptors are also shown to contain considerable information about nucleotide base conformation, revealing a previously uncharacterized interplay between backbone and base orientation. A window function analysis is used to discern statistically relevant regions of density in the eta-theta scatter plot and then nucleotides in colocalized clusters in the eta-theta plane are shown to have similar 3-D structures through RMSD analysis of the RNA structural constituents. We find that major clusters in the eta-theta plot are few, underscoring the discrete nature of RNA backbone conformation. Like the Ramachandran plot, the eta-theta plot is a valuable system for conceptualizing biomolecular conformation, it is a useful tool for analyzing RNA tertiary structures, and it is a vital component of new approaches for
Shao, Qiang
2016-10-26
Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein. The open-to-closed transitions of three proteins, including nCaM, AdK, and HIV-1 PR, were investigated using NMA-ITS simulations. The three proteins have varied structural flexibilities and domain communications in their respective conformational changes. The transition state structure in the conformational change of nCaM and the associated free-energy barrier are in agreement with those measured in a standard explicit-solvent REMD simulation. The experimentally measured transition intermediate structures of the intrinsically flexible AdK are captured by the conformational transition pathway measured here. The dominant transition pathways between the closed and fully open states of HIV-1 PR are very similar to those observed in recent REMD simulations. Finally, the evaluated relaxation times of the conformational transitions of three proteins are roughly at the same level as reported experimental data. Therefore, the NMA-ITS method is applicable for a variety of cases, providing both qualitative and quantitative insights into the conformational changes associated with the real functions of proteins.
Conformable derivative approach to anomalous diffusion
NASA Astrophysics Data System (ADS)
Zhou, H. W.; Yang, S.; Zhang, S. Q.
2018-02-01
By using a new derivative with fractional order, referred to conformable derivative, an alternative representation of the diffusion equation is proposed to improve the modeling of anomalous diffusion. The analytical solutions of the conformable derivative model in terms of Gauss kernel and Error function are presented. The power law of the mean square displacement for the conformable diffusion model is studied invoking the time-dependent Gauss kernel. The parameters related to the conformable derivative model are determined by Levenberg-Marquardt method on the basis of the experimental data of chloride ions transportation in reinforced concrete. The data fitting results showed that the conformable derivative model agrees better with the experimental data than the normal diffusion equation. Furthermore, the potential application of the proposed conformable derivative model of water flow in low-permeability media is discussed.