Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.

PubMed

Metzger, Vincent T; Eun, Changsun; Kekenes-Huskey, Peter M; Huber, Gary; McCammon, J Andrew

2014-11-18

We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.

Metal active site elasticity linked to activation of homocysteine in methionine synthases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.

2008-04-02

Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry uponmore » binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.« less

'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

PubMed

Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

2014-04-09

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site.

PubMed

Jacewicz, Agata; Trzemecka, Anna; Guja, Kip E; Plochocka, Danuta; Yakubovskaya, Elena; Bebenek, Anna; Garcia-Diaz, Miguel

2013-01-01

Non-conserved amino acids that are far removed from the active site can sometimes have an unexpected effect on enzyme catalysis. We have investigated the effects of alanine replacement of residues distant from the active site of the replicative RB69 DNA polymerase, and identified a substitution in a weakly conserved palm residue (D714A), that renders the enzyme incapable of sustaining phage replication in vivo. D714, located several angstroms away from the active site, does not contact the DNA or the incoming dNTP, and our apoenzyme and ternary crystal structures of the Pol(D714A) mutant demonstrate that D714A does not affect the overall structure of the protein. The structures reveal a conformational change of several amino acid side chains, which cascade out from the site of the substitution towards the catalytic center, substantially perturbing the geometry of the active site. Consistent with these structural observations, the mutant has a significantly reduced k pol for correct incorporation. We propose that the observed structural changes underlie the severe polymerization defect and thus D714 is a remote, non-catalytic residue that is nevertheless critical for maintaining an optimal active site conformation. This represents a striking example of an action-at-a-distance interaction.

The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gopal, B.; Madan, Lalima L.; Betz, Stephen F.

2010-11-10

Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s),more » whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.« less

X-ray absorption spectroscopic studies of mononuclear non-heme iron enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westre, Tami E.

Fe-K-edge X-ray absorption spectroscopy (XAS) has been used to investigate the electronic and geometric structure of the iron active site in non-heme iron enzymes. A new theoretical extended X-ray absorption fine structure (EXAFS) analysis approach, called GNXAS, has been tested on data for iron model complexes to evaluate the utility and reliability of this new technique, especially with respect to the effects of multiple-scattering. In addition, a detailed analysis of the 1s→3d pre-edge feature has been developed as a tool for investigating the oxidation state, spin state, and geometry of iron sites. Edge and EXAFS analyses have then been appliedmore » to the study of non-heme iron enzyme active sites.« less

The influence of geometry and draught shields on the performance of passive samplers.

PubMed

Hofschreuder, P; van der Meulen, W; Heeres, P; Slanina, S

1999-04-01

Passive samplers provide an excellent opportunity to perform indicative measurements or establish a dense network of measuring sites. A drawback compared with conventional active measuring methods is the larger spread of results. This variation can, to a large extent, be attributed to the influence of temperature, sampler geometry and wind on sampling results. A proper design of sampler geometry and optimum choice of draught shield can reduce the influence of wind velocity on a badge type sampler to less than 10%. Wire mesh screens prove to be inadequate in damping turbulence. Filters give good results. Attention should be paid to the size and isolation value of the walls of the sampler to prevent thermal updrafts occurring within the sampler. Tube type samplers are less influenced by wind, provided that turbulence is prevented from influencing diffusion within the sampler.

Spin-orbit effects on the (119)Sn magnetic-shielding tensor in solids: a ZORA/DFT investigation.

PubMed

Alkan, Fahri; Holmes, Sean T; Iuliucci, Robbie J; Mueller, Karl T; Dybowski, Cecil

2016-07-28

Periodic-boundary and cluster calculations of the magnetic-shielding tensors of (119)Sn sites in various co-ordination and stereochemical environments are reported. The results indicate a significant difference between the predicted NMR chemical shifts for tin(ii) sites that exhibit stereochemically-active lone pairs and tin(iv) sites that do not have stereochemically-active lone pairs. The predicted magnetic shieldings determined either with the cluster model treated with the ZORA/Scalar Hamiltonian or with the GIPAW formalism are dependent on the oxidation state and the co-ordination geometry of the tin atom. The inclusion of relativistic effects at the spin-orbit level removes systematic differences in computed magnetic-shielding parameters between tin sites of differing stereochemistries, and brings computed NMR shielding parameters into significant agreement with experimentally-determined chemical-shift principal values. Slight improvement in agreement with experiment is noted in calculations using hybrid exchange-correlation functionals.

Activity loss by H46A mutation in Mycobacterium tuberculosis isocitrate lyase is due to decrease in structural plasticity and collective motions of the active site.

PubMed

Shukla, Rohit; Shukla, Harish; Tripathi, Timir

2018-01-01

Mycobacterium tuberculosis isocitrate lyase (MtbICL) is a crucial enzyme of the glyoxylate cycle and is a validated anti-tuberculosis drug target. Structurally distant, non-active site mutation (H46A) in MtbICL has been found to cause loss of enzyme activity. The aim of the present work was to explore the structural alterations induced by H46A mutation that caused the loss of enzyme activity. The structural and dynamic consequences of H46A mutation were studied using multiple computational methods such as docking, molecular dynamics simulation and residue interaction network analysis (RIN). Principal component analysis and cross correlation analysis revealed the difference in conformational flexibility and collective modes of motions between the wild-type and mutant enzyme, particularly in the active site region. RIN analysis revealed that the active site geometry was disturbed in the mutant enzyme. Thus, the dynamic perturbation of the active site led to enzyme transition from its active form to inactive form upon mutation. The computational analyses elucidated the mutant-specific conformational alterations, differential dominant motions, and anomalous residue level interactions that contributed to the abrogated function of mutant MtbICL. An understanding of interactions of mutant enzymes may help in modifying the existing drugs and designing improved drugs for successful control of tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA looping by FokI: the impact of synapse geometry on loop topology at varied site orientations

PubMed Central

Rusling, David A.; Laurens, Niels; Pernstich, Christian; Wuite, Gijs J. L.; Halford, Stephen E.

2012-01-01

Most restriction endonucleases, including FokI, interact with two copies of their recognition sequence before cutting DNA. On DNA with two sites they act in cis looping out the intervening DNA. While many restriction enzymes operate symmetrically at palindromic sites, FokI acts asymmetrically at a non-palindromic site. The directionality of its sequence means that two FokI sites can be bridged in either parallel or anti-parallel alignments. Here we show by biochemical and single-molecule biophysical methods that FokI aligns two recognition sites on separate DNA molecules in parallel and that the parallel arrangement holds for sites in the same DNA regardless of whether they are in inverted or repeated orientations. The parallel arrangement dictates the topology of the loop trapped between sites in cis: the loop from inverted sites has a simple 180° bend, while that with repeated sites has a convoluted 360° turn. The ability of FokI to act at asymmetric sites thus enabled us to identify the synapse geometry for sites in trans and in cis, which in turn revealed the relationship between synapse geometry and loop topology. PMID:22362745

The Cysteine Dioxygenase Homologue from Pseudomonas aeruginosa Is a 3-Mercaptopropionate Dioxygenase*

PubMed Central

Tchesnokov, Egor P.; Fellner, Matthias; Siakkou, Eleni; Kleffmann, Torsten; Martin, Lois W.; Aloi, Sekotilani; Lamont, Iain L.; Wilbanks, Sigurd M.; Jameson, Guy N. L.

2015-01-01

Thiol dioxygenation is the initial oxidation step that commits a thiol to important catabolic or biosynthetic pathways. The reaction is catalyzed by a family of specific non-heme mononuclear iron proteins each of which is reported to react efficiently with only one substrate. This family of enzymes includes cysteine dioxygenase, cysteamine dioxygenase, mercaptosuccinate dioxygenase, and 3-mercaptopropionate dioxygenase. Using sequence alignment to infer cysteine dioxygenase activity, a cysteine dioxygenase homologue from Pseudomonas aeruginosa (p3MDO) has been identified. Mass spectrometry of P. aeruginosa under standard growth conditions showed that p3MDO is expressed in low levels, suggesting that this metabolic pathway is available to the organism. Purified recombinant p3MDO is able to oxidize both cysteine and 3-mercaptopropionic acid in vitro, with a marked preference for 3-mercaptopropionic acid. We therefore describe this enzyme as a 3-mercaptopropionate dioxygenase. Mössbauer spectroscopy suggests that substrate binding to the ferrous iron is through the thiol but indicates that each substrate could adopt different coordination geometries. Crystallographic comparison with mammalian cysteine dioxygenase shows that the overall active site geometry is conserved but suggests that the different substrate specificity can be related to replacement of an arginine by a glutamine in the active site. PMID:26272617

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

3-D GPR data analysis for high-resolution imaging of shallow subsurface faults: the Mt Vettore case study (Central Apennines, Italy)

NASA Astrophysics Data System (ADS)

Ercoli, Maurizio; Pauselli, Cristina; Frigeri, Alessandro; Forte, Emanuele; Federico, Costanzo

2014-07-01

The activation of Late Quaternary faults in the Central Apennines (Italy) could generate earthquakes with magnitude of about 6.5, and the Monte Vettore fault system probably belongs to the same category of seismogenetic faults. Such structure has been defined `silent', because of its geological and geomorphological evidences of past activation, but the absence of historical records in the seismic catalogues to be associated with its activation. The `Piano di Castelluccio' intramountain basin, resulting from the Quaternary activity of normal faults, is characterized by a secondary fault strand highlighted by a NW-SE fault scarp: it has been already studied through palaeoseismological trenches, which highlighted evidences of Quaternary shallow faulting due to strong earthquakes, and through a 2-D ground penetrating radar (GPR) survey, showing the first geophysical signature of faulting for this site. Within the same place, a 3-D GPR volume over a 20 × 20 m area has been collected. The collection of radar echoes in three dimensions allows to map both the vertical and lateral continuity of shallow geometries of the fault zone (Fz), imaging features with high resolution, ranging from few metres to centimetres and therefore imaging also local variations at the microscale. Several geophysical markers of faulting, already highlighted on this site, have been taken as reference to plan the 3-D survey. In this paper, we provide the first 3-D subsurface imaging of an active shallow fault belonging to the Umbria-Marche Apennine highlighting the subsurface fault geometry and the stratigraphic sequence up to a depth of about 5 m. From our data, geophysical faulting signatures are clearly visible in three dimensions: diffraction hyperbolas, truncations of layers, local attenuated zones and varying dip of the layers have been detected within the Fz. The interpretation of the 3-D data set provided qualitative and quantitative geological information in addition to the fault location, like its geometry, boundaries and an estimation of the fault throw.

Streamflow characteristics related to channel geometry of streams in western United States

USGS Publications Warehouse

Hedman, E.R.; Osterkamp, W.R.

1982-01-01

Assessment of surface-mining and reclamation activities generally requires extensive hydrologic data. Adequate streamflow data from instrumented gaging stations rarely are available, and estimates of surface- water discharge based on rainfall-runoff models, drainage area, and basin characteristics sometimes have proven unreliable. Channel-geometry measurements offer an alternative method of quickly and inexpensively estimating stream-flow characteristics for ungaged streams. The method uses the empirical development of equations to yield a discharge value from channel-geometry and channel-material data. The equations are developed by collecting data at numerous streamflow-gaging sites and statistically relating those data to selected discharge characteristics. Mean annual runoff and flood discharges with selected recurrence intervals can be estimated for perennial, intermittent, and ephemeral streams. The equations were developed from data collected in the western one-half of the conterminous United States. The effect of the channel-material and runoff characteristics are accounted for with the equations.

Free-energy analysis of spin models on hyperbolic lattice geometries.

PubMed

Serina, Marcel; Genzor, Jozef; Lee, Yoju; Gendiar, Andrej

2016-04-01

We investigate relations between spatial properties of the free energy and the radius of Gaussian curvature of the underlying curved lattice geometries. For this purpose we derive recurrence relations for the analysis of the free energy normalized per lattice site of various multistate spin models in the thermal equilibrium on distinct non-Euclidean surface lattices of the infinite sizes. Whereas the free energy is calculated numerically by means of the corner transfer matrix renormalization group algorithm, the radius of curvature has an analytic expression. Two tasks are considered in this work. First, we search for such a lattice geometry, which minimizes the free energy per site. We conjecture that the only Euclidean flat geometry results in the minimal free energy per site regardless of the spin model. Second, the relations among the free energy, the radius of curvature, and the phase transition temperatures are analyzed. We found out that both the free energy and the phase transition temperature inherit the structure of the lattice geometry and asymptotically approach the profile of the Gaussian radius of curvature. This achievement opens new perspectives in the AdS-CFT correspondence theories.

Optimal Area Use in Orb Webs of the Spider Araneus diadematus

NASA Astrophysics Data System (ADS)

Krink, T.; Vollrath, F.

We studied the abilities of the garden cross spider Araneus diadematus regarding adaptation of web geometry to spatial constraints. Spiders reacted to a spatial reduction in their building site from a square-shaped frame to a slimmer, rectangular frame (side ratio 1 : 2) by maintaining overall web geometry while reducing the web area covered by the sticky capture spiral. However, when the frames were changed further to a rectangular side ratio of 1 : 3, the spiders changed specific web properties in such a way that a further reduction in the capture spiral area was prevented. Construction of the threads making up the web frame and the auxiliary spiral requires that the spider explores the spatial constraints of its building site. The geometry of both frame and auxiliary spiral threads in turn determine the geometry of the capture threads. Since in very narrow frames the spider adjusted the auxiliary to suit the subsequent capture spiral, we suggest that an initial spatial survey led to the final adaptation of overall web geometry to a web site.

Optimal area use in orb webs of the spider Araneus diadematus.

PubMed

Krink, T; Vollrath, F

2000-02-01

We studied the abilities of the garden cross spider Araneus diadematus regarding adaptation of web geometry to spatial constraints. Spiders reacted to a spatial reduction in their building site from a square-shaped frame to a slimmer, rectangular frame (side ratio 1 : 2) by maintaining overall web geometry while reducing the web area covered by the sticky capture spiral. However, when the frames were changed further to a rectangular side ratio of 1 : 3, the spiders changed specific web properties in such a way that a further reduction in the capture spiral area was prevented. Construction of the threads making up the web frame and the auxiliary spiral requires that the spider explores the spatial constraints of its building site. The geometry of both frame and auxiliary spiral threads in turn determine the geometry of the capture threads. Since in very narrow frames the spider adjusted the auxiliary to suit the subsequent capture spiral, we suggest that an initial spatial survey led to the final adaptation of overall web geometry to a web site.

Role of internal motions and molecular geometry on the NMR relaxation of hydrocarbons

NASA Astrophysics Data System (ADS)

Singer, P. M.; Asthagiri, D.; Chen, Z.; Valiya Parambathu, A.; Hirasaki, G. J.; Chapman, W. G.

2018-04-01

The role of internal motions and molecular geometry on 1H NMR relaxation rates in liquid-state hydrocarbons is investigated using MD (molecular dynamics) simulations of the autocorrelation functions for intramolecular and intermolecular 1H-1H dipole-dipole interactions. The effects of molecular geometry and internal motions on the functional form of the autocorrelation functions are studied by comparing symmetric molecules such as neopentane and benzene to corresponding straight-chain alkanes n-pentane and n-hexane, respectively. Comparison of rigid versus flexible molecules shows that internal motions cause the intramolecular and intermolecular correlation-times to get significantly shorter, and the corresponding relaxation rates to get significantly smaller, especially for longer-chain n-alkanes. Site-by-site simulations of 1H's across the chains indicate significant variations in correlation times and relaxation rates across the molecule, and comparison with measurements reveals insights into cross-relaxation effects. Furthermore, the simulations reveal new insights into the relative strength of intramolecular versus intermolecular relaxation as a function of internal motions, as a function of molecular geometry, and on a site-by-site basis across the chain.

SABER: A computational method for identifying active sites for new reactions

PubMed Central

Nosrati, Geoffrey R; Houk, K N

2012-01-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis.

PubMed

Saravanan, Kandasamy; Kalaiarasi, Chinnasamy; Kumaradhas, Poomani

2017-12-01

Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer's disease, as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution, and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE. Further, the charge density distribution and the electrostatic properties of curcumin molecule (lifted from the active site of rhAChE) were determined from the high level density functional theory (DFT) calculations coupled with the charge density analysis. On the other hand, the curcumin molecule was optimized (gas phase) using DFT method and further, the structure and charge density analysis were also carried out. On comparing the conformation, charge density distribution and the electrostatic potential of the active site form of curcumin with the corresponding gas phase form reveals that the above said properties are significantly altered when curcumin is present in the active site of rhAChE. The conformational stability and the interaction of curcumin in the active site are also studied using molecular dynamics simulation, which shows a large variation in the conformational geometry of curcumin as well as the intermolecular interactions.

Driving Protein Conformational Changes with Light: Photoinduced Structural Rearrangement in a Heterobimetallic Oxidase.

PubMed

Maugeri, Pearson T; Griese, Julia J; Branca, Rui M; Miller, Effie K; Smith, Zachary R; Eirich, Jürgen; Högbom, Martin; Shafaat, Hannah S

2018-01-31

The heterobimetallic R2lox protein binds both manganese and iron ions in a site-selective fashion and activates oxygen, ultimately performing C-H bond oxidation to generate a tyrosine-valine cross-link near the active site. In this work, we demonstrate that, following assembly, R2lox undergoes photoinduced changes to the active site geometry and metal coordination motif. Through spectroscopic, structural, and mass spectrometric characterization, the photoconverted species is found to consist of a tyrosinate-bound iron center following light-induced decarboxylation of a coordinating glutamate residue and cleavage of the tyrosine-valine cross-link. This process occurs with high quantum efficiencies (Φ = 3%) using violet and near-ultraviolet light, suggesting that the photodecarboxylation is initiated via ligand-to-metal charge transfer excitation. Site-directed mutagenesis and structural analysis suggest that the cross-linked tyrosine-162 is the coordinating residue. One primary product is observed following irradiation, indicating potential use of this class of proteins, which contains a putative substrate channel, for controlled photoinduced decarboxylation processes, with relevance for in vivo functionality of R2lox as well as application in environmental remediation.

Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.

PubMed

Calhoun, Jennifer R; Liu, Weixia; Spiegel, Katrin; Dal Peraro, Matteo; Klein, Michael L; Valentine, Kathleen G; Wand, A Joshua; DeGrado, William F

2008-02-01

We report the solution NMR structure of a designed dimetal-binding protein, di-Zn(II) DFsc, along with a secondary refinement step employing molecular dynamics techniques. Calculation of the initial NMR structural ensemble by standard methods led to distortions in the metal-ligand geometries at the active site. Unrestrained molecular dynamics using a nonbonded force field for the metal shell, followed by quantum mechanical/molecular mechanical dynamics of DFsc, were used to relax local frustrations at the dimetal site that were apparent in the initial NMR structure and provide a more realistic description of the structure. The MD model is consistent with NMR restraints, and in good agreement with the structural and functional properties expected for DF proteins. This work demonstrates that NMR structures of metalloproteins can be further refined using classical and first-principles molecular dynamics methods in the presence of explicit solvent to provide otherwise unavailable insight into the geometry of the metal center.

Constrained Geometry Organotitanium Catalysts Supported on Nanosized Silica for Ethylene (co)Polymerization.

PubMed

Li, Kuo-Tseng; Wu, Ling-Huey

2017-05-05

Supported olefin polymerization catalysts can prevent reactor-fouling problems and produce uniform polymer particles. Constrained geometry complexes (CGCs) have less sterically hindered active sites than bis-cyclopentadienyl metallocene catalysts. In the literature, micrometer-sized silica particles were used for supporting CGC catalysts, which might have strong mass transfer limitations. This study aims to improve the activity of supported CGC catalysts by using nanometer-sized silica. Ti[(C₅Me₄)SiMe₂(N t Bu)]Cl₂, a "constrained-geometry" titanium catalyst, was supported on MAO-treated silicas (nano-sized and micro-sized) by an impregnation method. Ethylene homo-polymerization and co-polymerization with 1-octene were carried out in a temperature range of 80-120 °C using toluene as the solvent. Catalysts prepared and polymers produced were characterized. For both catalysts and for both reactions, the maximum activities occurred at 100 °C, which is significantly higher than that (60 °C) reported before for supported bis-cyclopentadienyl metallocene catalysts containing zirconium, and is lower than that (≥140 °C) used for unsupported Ti[(C₅Me₄)SiMe₂(N t Bu)]Me₂ catalyst. Activities of nano-sized catalyst were 2.6 and 1.6 times those of micro-sized catalyst for homopolymerization and copolymerization, respectively. The former produced polymers with higher crystallinity and melting point than the latter. In addition, copolymer produced with nanosized catalyst contained more 1-octene than that produced with microsized catalyst.

Synthesis, crystal structure, superoxide scavenging activity, anticancer and docking studies of novel adamantyl nitroxide derivatives

NASA Astrophysics Data System (ADS)

Zhu, Xiao-he; Sun, Jin; Wang, Shan; Bu, Wei; Yao, Min-na; Gao, Kai; Song, Ying; Zhao, Jin-yi; Lu, Cheng-tao; Zhang, En-hu; Yang, Zhi-fu; Wen, Ai-dong

2016-03-01

A novel adamantyl nitroxide derivatives has been synthesized and characterized by IR, ESI-MS and elemental analysis. Quantum chemical calculations have also been performed to calculate the molecular geometry using density functional theory (B3LYP) with the 6-31G (d,p) basis set. The calculated results showed that the optimized geometry can well reproduce the crystal structure. The antioxidant and antiproliferative activity were evaluated by superoxide (NBT) and MTT assay. The adamantyl nitroxide derivatives exhibited stronger scavenging ability towards O2· - radicals when compared to Vitamin C, and demonstrated a remarked anticancer activity against all the tested cell lines, especially Bel-7404 cells with IC50 of 43.3 μM, compared to the positive control Sorafenib (IC50 = 92.0 μM). The results of molecular docking within EGFR using AutoDock confirmed that the titled compound favorably fitted into the ATP binding site of EGFR and would be a potential anticancer agent.

Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

PubMed

Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

2016-08-01

Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Identifying the Unique Properties of α-Bi 2Mo 3O 12 for the Activation of Propene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Licht, Rachel B.; Getsoian, Andrew; Bell, Alexis T.

In order to understand the remarkable activity of α-Bi 2Mo 3O 12 for selective oxidation and ammoxidation of propene, the propene activation ability of four molybdenum-based mixed metal oxides - Bi 2Mo 3O 12, PbMoO 4, Bi 2Pb 5Mo 8O 32, and MoO 3 - was investigated using density functional theory. Propene activation is considered to occur via abstraction of a hydrogen atom from the methyl group of physisorbed propene by lattice oxygen. For each material, the apparent activation energy was estimated by summing the heat of adsorption of propene, the C-H bond dissociation energy, and the hydrogen attachment energymore » (HAE) for hydrogen addition to lattice oxygen; this sum provides a lower bound for the apparent activation energy. It was found that two structural features of oxide surfaces are essential to achieve low activation barriers: under-coordinated surface cation sites enable strong propene adsorption, and suitable 5- or 6-coordinate geometries at molybdenum result in favorable HAEs. The impact of molybdenum coordination on HAE was elucidated by carrying out a molecular orbital analysis using a cluster model of the molybdate unit. This effort revealed that, in 5- and 6-coordinate molybdates, oxygen donor atoms trans to molybdenyl oxo atoms destabilize the molybdate prior to H addition but stabilize the molybdate after H addition, thereby providing an HAE ~15 kcal/mol more favorable than that on 4-coordinate molybdate oxo atoms. Bi 3+ cations in Bi 2Mo 3O 12 thus promote catalytic activity by providing both strong adsorption sites for propene and forcing molybdate into 5-coordinate geometries that lead to particularly favorable values of the HAE. (Graph Presented).« less

Identifying the Unique Properties of α-Bi 2Mo 3O 12 for the Activation of Propene

DOE PAGES

Licht, Rachel B.; Getsoian, Andrew; Bell, Alexis T.

2016-12-30

In order to understand the remarkable activity of α-Bi 2Mo 3O 12 for selective oxidation and ammoxidation of propene, the propene activation ability of four molybdenum-based mixed metal oxides - Bi 2Mo 3O 12, PbMoO 4, Bi 2Pb 5Mo 8O 32, and MoO 3 - was investigated using density functional theory. Propene activation is considered to occur via abstraction of a hydrogen atom from the methyl group of physisorbed propene by lattice oxygen. For each material, the apparent activation energy was estimated by summing the heat of adsorption of propene, the C-H bond dissociation energy, and the hydrogen attachment energymore » (HAE) for hydrogen addition to lattice oxygen; this sum provides a lower bound for the apparent activation energy. It was found that two structural features of oxide surfaces are essential to achieve low activation barriers: under-coordinated surface cation sites enable strong propene adsorption, and suitable 5- or 6-coordinate geometries at molybdenum result in favorable HAEs. The impact of molybdenum coordination on HAE was elucidated by carrying out a molecular orbital analysis using a cluster model of the molybdate unit. This effort revealed that, in 5- and 6-coordinate molybdates, oxygen donor atoms trans to molybdenyl oxo atoms destabilize the molybdate prior to H addition but stabilize the molybdate after H addition, thereby providing an HAE ~15 kcal/mol more favorable than that on 4-coordinate molybdate oxo atoms. Bi 3+ cations in Bi 2Mo 3O 12 thus promote catalytic activity by providing both strong adsorption sites for propene and forcing molybdate into 5-coordinate geometries that lead to particularly favorable values of the HAE. (Graph Presented).« less

New insights into the molecular characteristics behind the function of Renilla luciferase.

PubMed

Fanaei-Kahrani, Zahra; Ganjalikhany, Mohamad Reza; Rasa, Seyed Mohammad Mahdi; Emamzadeh, Rahman

2018-02-01

Renilla Luciferase (RLuc) is a blue light emitter protein which can be applied as a valuable tool in medical diagnosis. But due to lack of the crystal structure of RLuc-ligand complex, the functional motions and catalytic mechanism of this enzyme remain largely unknown. In the present study, the active site properties and the ligand-receptor interactions of the native RLuc and its red-shifted light emitting variant (Super RLuc 8) were investigated using molecular docking approach, molecular dynamics (MD) analysis, and MM-PBSA method. The detailed analysis of the main clusters led to identifying a lid-like structure and its functional motions. Furthermore, an induced-fit mechanism is proposed where ligand-binding induces conformational changes of the active site. Our findings give an insight into the deeper understanding of RLuc conformational changes during binding steps and ligand-receptor pattern. Moreover, our work broaden our understanding of how active site geometry is adjusted to support the catalytic activity and red-shifted light emission in Super RLuc 8. © 2017 Wiley Periodicals, Inc.

Effects of Vanadium Substitution on the Structure and Photocatalytic Behavior of ETS-10

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shough,A.; Doren, D.; Nash, M.

2007-01-01

A combination of experimental and computational methods has been used to investigate the effects of vanadium doping in ETS-10. Near edge X-ray absorption fine structure (NEXAFS) spectra reveal octahedrally coordinated V{sup IV} and V{sup V} species within V-doped ETS-10 materials, confirming substitution for Ti{sup IV} sites only. Computational models, using hybrid density functional theory/molecular mechanics (DFT/MM) methods, have been developed that contain varying concentrations of V{sup IV} and V{sup V} within the O-M-O (M = Ti, V) chain. Geometry optimizations indicate that V{sup V} substitution leads to larger changes in the local chain geometry than V{sup IV} substitution. Substitution energeticsmore » for V{sup IV} and V{sup V} in different sites have been calculated to determine preferred locations of the two species, suggesting that long chains of V{sup V} are not stable and demonstrating the need for both V{sup V} and V{sup IV} within V-substituted materials. Wavefunctions for systems with an electron added or removed are used to identify electron and hole trapping sites associated with the V{sup V} and V{sup IV} doping centers respectively. An increase in photocatalytic activity is predicted at low [V] due to improved charge separation. However photocatalytic activity is expected to decrease at high [V] due to increased carrier recombination. These results are consistent with recent experimental data.« less

Freeze-Quench Magnetic Circular Dichroism Spectroscopic Study of the "Very Rapid" Intermediate in Xanthine Oxidase.

PubMed

Jones, Robert M.; Inscore, Frank E.; Hille, Russ; Kirk, Martin L.

1999-11-01

Freeze-quench magnetic circular dichroism spectroscopy (MCD) has been used to trap and study the excited-state electronic structure of the Mo(V) active site in a xanthine oxidase intermediate generated with substoichiometric concentrations of the slow substrate 2-hydroxy-6-methylpurine. EPR spectroscopy has shown that the intermediate observed in the MCD experiment is the "very rapid" intermediate, which lies on the main catalytic pathway. The low-energy (< approximately 30 000 cm(-1)) C-term MCD of this intermediate is remarkably similar to that of the model compound LMoO(bdt) (L = hydrotris(3,5-dimethyl-1-pyrazolyl)borate; bdt = 1,2-benzenedithiolate), and the MCD bands have been assigned as dithiolate S(ip) --> Mo d(xy) and S(op) --> Mo d(xz,yz) LMCT transitions. These transitions result from a coordination geometry of the intermediate where the Mo=O bond is oriented cis to the ene-1,2-dithiolate of the pyranopterin. Since X-ray crystallography has indicated that a terminal sulfido ligand is oriented cis to the ene-1,2-dithiolate in oxidized xanthine oxidase related Desulfovibrio gigas aldehyde oxidoreductase, we have suggested that a conformational change occurs upon substrate binding. The substrate-mediated conformational change is extremely significant with respect to electron-transfer regeneration of the active site, as covalent interactions between the redox-active Mo d(xy) orbital and the S(ip) orbitals of the ene-1,2-dithiolate are maximized when the oxo ligand is oriented cis to the dithiolate plane. This underlies the importance of the ene-1,2-dithiolate portion of the pyranopterin in providing an efficient superexchange pathway for electron transfer. The results of this study indicate that electron-transfer regeneration of the active site may be gated by the orientation of the Mo=O bond relative to the ene-1,2-dithiolate chelate. Poor overlap between the Mo d(xy) orbital and the S(ip) orbitals of the dithiolate in the oxidized enzyme geometry may provide a means of preventing one-electron reduction of the active site, resulting in enzyme inhibition with respect to the two-electron oxidation of native substrates.

Electronic structure of the metal center in the Cd(2+), Zn(2+), and Cu(2+) substituted forms of KDO8P synthase: implications for catalysis.

PubMed

Kona, Fathima; Tao, Peng; Martin, Philip; Xu, Xingjue; Gatti, Domenico L

2009-04-28

Aquifex aeolicus 3-deoxy-d-manno-octulosonate 8-phosphate synthase (KDO8PS) is active with a variety of different divalent metal ions bound in the active site. The Cd(2+), Zn(2+), and Cu(2+) substituted enzymes display similar values of k(cat) and similar dependence of K(m)(PEP) and K(m)(A5P) on both substrate and product concentrations. However, the flux-control coefficients for some of the catalytically relevant reaction steps are different in the presence of Zn(2+) or Cu(2+), suggesting that the type of metal bound in the active site affects the behavior of the enzyme in vivo. The type of metal also affects the rate of product release in the crystal environment. For example, the crystal structure of the Cu(2+) enzyme incubated with phosphoenolpyruvate (PEP) and arabinose 5-phosphate (A5P) shows the formed product, 3-deoxy-d-manno-octulosonate 8-phosphate (KDO8P), still bound in the active site in its linear conformation. This observation completes our structural studies of the condensation reaction, which altogether have provided high-resolution structures for the reactants, the intermediate, and the product bound forms of KDO8PS. The crystal structures of the Cd(2+), Zn(2+), and Cu(2+) substituted enzymes show four residues (Cys-11, His-185, Glu-222, and Asp-233) and a water molecule as possible metal ligands. Combined quantum mechanics/molecular mechanics (QM/MM) geometry optimizations reveal that the metal centers have a delocalized electronic structure, and that their true geometry is square pyramidal for Cd(2+) and Zn(2+) and distorted octahedral or distorted tetrahedral for Cu(2+). These geometries are different from those obtained by QM optimization in the gas phase (tetrahedral for Cd(2+) and Zn(2+), distorted tetrahedral for Cu(2+)) and may represent conformations of the metal center that minimize the reorganization energy between the substrate-bound and product-bound states. The QM/MM calculations also show that when only PEP is bound to the enzyme the electronic structure of the metal center is optimized to prevent a wasteful reaction of PEP with water.

SABER: a computational method for identifying active sites for new reactions.

PubMed

Nosrati, Geoffrey R; Houk, K N

2012-05-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

The transition state for formation of the peptide bond in the ribosome

PubMed Central

Gindulyte, Asta; Bashan, Anat; Agmon, Ilana; Massa, Lou; Yonath, Ada; Karle, Jerome

2006-01-01

Using quantum mechanics and exploiting known crystallographic coordinates of tRNA substrate located in the ribosome peptidyl transferase center around the 2-fold axis, we have investigated the mechanism for peptide-bond formation. The calculation is based on a choice of 50 atoms assumed to be important in the mechanism. We used density functional theory to optimize the geometry and energy of the transition state (TS) for peptide-bond formation. The TS is formed simultaneously with the rotatory motion enabling the translocation of the A-site tRNA 3′ end into the P site, and we estimated the magnitude of rotation angle between the A-site starting position and the place at which the TS occurs. The calculated TS activation energy, Ea, is 35.5 kcal (1 kcal = 4.18 kJ)/mol, and the increase in hydrogen bonding between the rotating A-site tRNA and ribosome nucleotides as the TS forms appears to stabilize it to a value qualitatively estimated to be ≈18 kcal/mol. The optimized geometry corresponds to a structure in which the peptide bond is being formed as other bonds are being broken, in such a manner as to release the P-site tRNA so that it may exit as a free molecule and be replaced by the translocating A-site tRNA. At TS formation the 2′ OH group of the P-site tRNA A76 forms a hydrogen bond with the oxygen atom of the carboxyl group of the amino acid attached to the A-site tRNA, which may be indicative of its catalytic role, consistent with recent biochemical experiments. PMID:16938893

Gas-phase geometry optimization of biological molecules as a reasonable alternative to a continuum environment description: fact, myth, or fiction?

PubMed

Sousa, Sérgio Filipe; Fernandes, Pedro Alexandrino; Ramos, Maria João

2009-12-31

Gas-phase optimization of single biological molecules and of small active-site biological models has become a standard approach in first principles computational enzymology. The important role played by the surrounding environment (solvent, enzyme, both) is normally only accounted for through higher-level single point energy calculations performed using a polarizable continuum model (PCM) and an appropriate dielectric constant with the gas-phase-optimized geometries. In this study we analyze this widely used approximation, by comparing gas-phase-optimized geometries with geometries optimized with different PCM approaches (and considering different dielectric constants) for a representative data set of 20 very important biological molecules--the 20 natural amino acids. A total of 323 chemical bonds and 469 angles present in standard amino acid residues were evaluated. The results show that the use of gas-phase-optimized geometries can in fact be quite a reasonable alternative to the use of the more computationally intensive continuum optimizations, providing a good description of bond lengths and angles for typical biological molecules, even for charged amino acids, such as Asp, Glu, Lys, and Arg. This approximation is particularly successful if the protonation state of the biological molecule could be reasonably described in vacuum, a requirement that was already necessary in first principles computational enzymology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Midulla, Marco, E-mail: marco.midulla@chru-lille.fr; Moreno, Ramiro, E-mail: ramoroa@gmail.com; Negre-Salvayre, Anne, E-mail: anne.negre-salvayre@inserm.fr

PurposeAlthough the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implicationsMethodsCT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were comparedmore » for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described.ResultsSegmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0–3) in 11 (78 %).ConclusionModeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.« less

Analogy and Dynamic Geometry System Used to Introduce Three-Dimensional Geometry

ERIC Educational Resources Information Center

Mammana, M. F.; Micale, B.; Pennisi, M.

2012-01-01

We present a sequence of classroom activities on Euclidean geometry, both plane and space geometry, used to make three dimensional geometry more catchy and simple. The activity consists of a guided research activity that leads the students to discover unexpected properties of two apparently distant geometrical entities, quadrilaterals and…

Inhibition Kinetics and Emodin Cocrystal Structure of a Type II Polyketide Ketoreductase†,‡

PubMed Central

Korman, Tyler Paz; Tan, Yuhong; Wong, Justin; Luo, Rui; Tsai, Shiou-Chuan

2008-01-01

Type II polyketides are a class of natural products that include pharmaceutically important aromatic compounds such as the antibiotic tetracycline and antitumor compound doxorubicin. The type II polyketide synthase (PKS) is a complex consisting of 5–10 standalone domains homologous to fatty acid synthase (FAS). Polyketide ketoreductase (KR) provides regio- and stereochemical diversity during the reduction. How the type II polyketide KR specifically reduces only the C9 carbonyl group is not well understood. The cocrystal structures of actinorhodin polyketide ketoreductase (actKR) bound with NADPH or NADP+ and the inhibitor emodin were solved with the wild type and P94L mutant of actKR, revealing the first observation of a bent p-quinone in an enzyme active site. Molecular dynamics simulation help explain the origin of the bent geometry. Extensive screening for in vitro substrates shows that unlike FAS KR, the actKR prefers bicyclic substrates. Inhibition kinetics indicate that actKR follows an ordered Bi Bi mechanism. Together with docking simulations that identified a potential phosphopantetheine binding groove, the structural and functional studies reveal that the C9 specificity is a result of active site geometry and substrate ring constraints. The results lay the foundation for the design of novel aromatic polyketide natural products with different reduction patterns. PMID:18205400

Inhibition Kinetics And Emodin Cocrystal Structure of a Type II Polyketide Ketoreductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korman, T.P.; Tan, Y.-H.; Wong, J.

Type II polyketides are a class of natural products that include pharmaceutically important aromatic compounds such as the antibiotic tetracycline and antitumor compound doxorubicin. The type II polyketide synthase (PKS) is a complex consisting of 5-10 standalone domains homologous to fatty acid synthase (FAS). Polyketide ketoreductase (KR) provides regio- and stereochemical diversity during the reduction. How the type II polyketide KR specifically reduces only the C9 carbonyl group is not well understood. The cocrystal structures of actinorhodin polyketide ketoreductase (actKR) bound with NADPH or NADP{sup +} and the inhibitor emodin were solved with the wild type and P94L mutant ofmore » actKR, revealing the first observation of a bent p-quinone in an enzyme active site. Molecular dynamics simulation help explain the origin of the bent geometry. Extensive screening for in vitro substrates shows that unlike FAS KR, the actKR prefers bicyclic substrates. Inhibition kinetics indicate that actKR follows an ordered Bi Bi mechanism. Together with docking simulations that identified a potential phosphopantetheine binding groove, the structural and functional studies reveal that the C9 specificity is a result of active site geometry and substrate ring constraints. The results lay the foundation for the design of novel aromatic polyketide natural products with different reduction patterns.« less

Enrichment Activities for Geometry.

ERIC Educational Resources Information Center

Usiskin, Zalman

1983-01-01

Enrichment activities that teach about geometry as they instruct in geometry are given for some significant topics. The facets of geometry included are tessellations, round robin tournaments, geometric theorems on triangles, and connections between geometry and complex numbers. (MNS)

Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.

PubMed

Anderson, Michael; Schultz, Eric P; Martick, Monika; Scott, William G

2013-10-23

We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na(+) ion binding in the ribozyme's active site. At least two such Na(+) ions are observed. The first Na(+) ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na(+) ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na(+), but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na(+) directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank. Copyright © 2013 Elsevier Ltd. All rights reserved.

Four second-sphere residues of Thermus thermophilus SG0.5JP17-16 laccase tune the catalysis by hydrogen-bonding networks.

PubMed

Liu, Huiping; Zhu, Yanyun; Yang, Xiaorong; Lin, Ying

2018-05-01

The multicopper oxidases catalyze 1-electron oxidation of four substrate molecules and concomitantly 4-electron reduction of dioxygen to water. The substrate loses the electrons at the type 1 copper (T1 Cu) site of the enzyme, while the dioxygen is reduced to water at the trinuclear copper center. A highly conserved Glu residue, which is at the dioxygen-entering channel, shuttles the proton to break the O-O bond of dioxygen. At the water-leaving channel, an Asp residue was found to be important in the protonation mechanism. In this study, laccase from Thermus thermophilus SG0.5JP17-16 (lacTT) was investigated to address how four second-sphere residues E356, E456, D106, and D423 affect the activity of the enzyme. Kinetic data indicate that catalytic activities of the enzyme are altered by site-directed mutagenesis on four second-sphere residues. The structural model of lacTT was generated by homology modeling. Structural and spectral data indicate that the E356 residue is situated at the substrate-binding site, responsible for the binding of the substrate and the geometry of the T1 Cu site by hydrogen-bonding networks; the E456 residue, located at the dioxygen-entering channel, plays a critical role in stabilizing the structure of all active copper centers and shuttling the proton to the trinuclear copper cluster (TNC) for the reductive reaction of dioxygen; the D106 and D423 residues are at the water-leaving channel, and they are important for the essential geometry of the TNC and the release of the water molecules. Altogether, this study contributes to the further understanding of the basic mechanism involving the oxidation of the substrate, electron transfer, and the reduction of dioxygen in lacTT.

Hydraulic geometry and sediment data for the South Fork Salmon River, Idaho, 1985-86

USGS Publications Warehouse

Williams, Rhea P.; O'Dell, Ivalou; Megahan, Walter F.

1989-01-01

Hydraulic geometry, suspended-sediment, and bedload samples were collected at three sites in the upper reach of the South Fork Salmon River drainage basin from April 1985 to June 1986. Sites selected were South Fork Salmon River near Krassel Ranger Station, Buckhorn Creek, and North Fork Lick Creek. Results of the data collection are presented in this report.

Pyrovanadolysis: a Pyrophosphorolysis-like Reaction Mediated by Pyrovanadate MN2plus and DNA Polymerase of Bacteriophage T7

DOE Office of Scientific and Technical Information (OSTI.GOV)

B Akabayov; A Kulczyk; S Akabayov

2011-12-31

DNA polymerases catalyze the 3'-5'-pyrophosphorolysis of a DNA primer annealed to a DNA template in the presence of pyrophosphate (PP{sub i}). In this reversal of the polymerization reaction, deoxynucleotides in DNA are converted to deoxynucleoside 5'-triphosphates. Based on the charge, size, and geometry of the oxygen connecting the two phosphorus atoms of PP{sub i}, a variety of compounds was examined for their ability to carry out a reaction similar to pyrophosphorolysis. We describe a manganese-mediated pyrophosphorolysis-like activity using pyrovanadate (VV) catalyzed by the DNA polymerase of bacteriophage T7. We designate this reaction pyrovanadolysis. X-ray absorption spectroscopy reveals a shorter Mn-Vmore » distance of the polymerase-VV complex than the Mn-P distance of the polymerase-PP{sub i} complex. This structural arrangement at the active site accounts for the enzymatic activation by Mn-VV. We propose that the Mn{sup 2+}, larger than Mg{sup 2+}, fits the polymerase active site to mediate binding of VV into the active site of the polymerase. Our results may be the first documentation that vanadium can substitute for phosphorus in biological processes.« less

Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major.

PubMed

Vidal, Antonio E; Harkiolaki, Maria; Gallego, Claribel; Castillo-Acosta, Victor M; Ruiz-Pérez, Luis M; Wilson, Keith; González-Pacanowska, Dolores

2007-11-02

Apurinic/apyrimidinic endonucleases initiate the repair of abasic sites produced either spontaneously, from attack of bases by reactive oxygen species or as intermediates during base excision repair. The catalytic properties and crystal structure of Leishmania major apurinic/apyrimidinic endonuclease are described and compared with those of human APE1 and bacterial exonuclease III. The purified enzyme is shown to possess apurinic/apyrimidinic endonuclease activity of the same order as eukaryotic and prokaryotic counterparts and an equally robust 3'-phosphodiesterase activity. Consistent with this, expression of the L. major endonuclease confers resistance to both methyl methane sulphonate and H2O2 in Escherichia coli repair-deficient mutants while expression of the human homologue only reverts methyl methane sulphonate sensitivity. Structural analyses and modelling of the enzyme-DNA complex demonstrates a high degree of conservation to previously characterized homologues, although subtle differences in the active site geometry might account for the high 3'-phosphodiesterase activity. Our results confirm that the L. major's enzyme is a key element in mediating repair of apurinic/apyrimidinic sites and 3'-blocked termini and therefore must play an important role in the survival of kinetoplastid parasites after exposure to the highly oxidative environment within the host macrophage.

Predictability of dune activity in real dune fields under unidirectional wind regimes

NASA Astrophysics Data System (ADS)

Barchyn, Thomas E.; Hugenholtz, Chris H.

2015-02-01

We present an analysis of 10 dune fields to test a model-derived hypothesis of dune field activity. The hypothesis suggests that a quantifiable threshold exists for stabilization in unidirectional wind regimes: active dunes have slipface deposition rates that exceed the vegetation deposition tolerance, and stabilizing dunes have the opposite. We quantified aeolian sand flux, slipface geometry, and vegetation deposition tolerance to directly test the hypothesis at four dune fields (Bigstick, White Sands Stable, White Sands Active, and Cape Cod). We indirectly tested the hypothesis at six additional dune fields with limited vegetation data (Hanford, Año Nuevo, Skagen Odde, Salton Sea, Oceano Stable, and Oceano Active, "inverse calculation sites"). We used digital topographic data and estimates of aeolian sand flux to approximate the slipface deposition rates prior to stabilization. Results revealed a distinct, quantifiable, and consistent pattern despite diverse environmental conditions: the modal peak of prestabilization slipface deposition rates was 80% of the vegetation deposition tolerance at stabilized or stabilizing dune fields. Results from inverse calculation sites indicate deposition rates at stabilized sites were near a hypothesized maximum vegetation deposition tolerance (1 m a-1), and active sites had slipface deposition rates much higher. Overall, these results confirm the hypothesis and provide evidence of a globally applicable, simple, and previously unidentified predictor for the dynamics of vegetation cover in dune fields under unidirectional wind regimes.

Skeletal Geometry and Indices of Bone Strength in Artistic Gymnasts

PubMed Central

Dowthwaite, Jodi N.; Scerpella, Tamara A.

2010-01-01

This review addresses bone geometry and indices of skeletal strength associated with exposure to gymnastic loading during growth. A brief background characterizes artistic gymnastics as a mechanical loading model and outlines densitometric techniques, skeletal outcomes and challenges in assessment of skeletal adaptation. The literature on bone geometric adaptation to gymnastic loading is sparse and consists of results for disparate skeletal sites, maturity phases, gender compositions and assessment methods, complicating synthesis of an overriding view. Furthermore, most studies assess only females, with little information on males and adults. Nonetheless, gymnastic loading during growth appears to yield significant enlargement of total and cortical bone geometry (+10 to 30%) and elevation of trabecular density (+20%) in the forearm, yielding elevated indices of skeletal strength (+20 to +50%). Other sites exhibit more moderate geometric and densitometric adaptations (5 to 15%). Mode of adaptation appears to be site-specific; some sites demonstrate marked periosteal and endosteal expansion, whereas other sites exhibit negligible or moderate periosteal expansion coupled with endocortical contraction. Further research is necessary to address sex-, maturity- and bone tissue-specific adaptation, as well as maintenance of benefits beyond loading cessation. PMID:19949278

Diels-Alder active-template synthesis of rotaxanes and metal-ion-switchable molecular shuttles.

PubMed

Crowley, James D; Hänni, Kevin D; Leigh, David A; Slawin, Alexandra M Z

2010-04-14

A synthesis of [2]rotaxanes in which Zn(II) or Cu(II) Lewis acids catalyze a Diels-Alder cycloaddition to form the axle while simultaneously acting as the template for the assembly of the interlocked molecules is described. Coordination of the Lewis acid to a multidentate endotopic 2,6-di(methyleneoxymethyl)pyridyl- or bipyridine-containing macrocycle orients a chelated dienophile through the macrocycle cavity. Lewis acid activation of the double bond causes it to react with an incoming "stoppered" diene, affording the [2]rotaxane in up to 91% yield. Unusually for an active-template synthesis, the metal binding site "lives on" in these rotaxanes. This was exploited in the synthesis of a molecular shuttle containing two different ligating sites in which the position of the macrocycle could be switched by complexation with metal ions [Zn(II) and Pd(II)] with different preferred coordination geometries.

Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

PubMed Central

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier

2013-01-01

Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization. PMID:24115934

Ethene adsorption and dehydrogenation on clean and oxygen precovered Ni(111) studied by high resolution x-ray photoelectron spectroscopy

NASA Astrophysics Data System (ADS)

Lorenz, M. P. A.; Fuhrmann, T.; Streber, R.; Bayer, A.; Bebensee, F.; Gotterbarm, K.; Kinne, M.; Tränkenschuh, B.; Zhu, J. F.; Papp, C.; Denecke, R.; Steinrück, H.-P.

2010-07-01

The adsorption and thermal evolution of ethene (ethylene) on clean and oxygen precovered Ni(111) was investigated with high resolution x-ray photoelectron spectroscopy using synchrotron radiation at BESSY II. The high resolution spectra allow to unequivocally identify the local environment of individual carbon atoms. Upon adsorption at 110 K, ethene adsorbs in a geometry, where the two carbon atoms within the intact ethene molecule occupy nonequivalent sites, most likely hollow and on top; this new result unambiguously solves an old puzzle concerning the adsorption geometry of ethene on Ni(111). On the oxygen precovered surface a different adsorption geometry is found with both carbon atoms occupying equivalent hollow sites. Upon heating ethene on the clean surface, we can confirm the dehydrogenation to ethine (acetylene), which adsorbs in a geometry, where both carbon atoms occupy equivalent sites. On the oxygen precovered surface dehydrogenation of ethene is completely suppressed. For the identification of the adsorbed species and the quantitative analysis the vibrational fine structure of the x-ray photoelectron spectra was analyzed in detail.

Understanding the Geometry of Connected Fracture Flow with Multiperiod Oscillatory Hydraulic Tests.

PubMed

Sayler, Claire; Cardiff, Michael; Fort, Michael D

2018-03-01

An understanding of the spatial and hydraulic properties of fast preferential flow pathways in the subsurface is necessary in applications ranging from contaminant fate and transport modeling to design of energy extraction systems. One method for the characterization of fracture properties over interwellbore scales is Multiperiod Oscillatory Hydraulic (MOH) testing, in which the aquifer response to oscillatory pressure stimulations is observed. MOH tests were conducted on isolated intervals of wells in siliciclastic and carbonate aquifers in southern Wisconsin. The goal was to characterize the spatial properties of discrete fractures over interwellbore scales. MOH tests were conducted on two discrete fractured intervals intersecting two boreholes at one field site, and a nest of three piezometers at another field site. Fracture diffusivity estimates were obtained using analytical solutions that relate diffusivity to observed phase lag and amplitude decay. In addition, MOH tests were used to investigate the spatial extent of flow using different conceptual models of fracture geometry. Results indicated that fracture geometry at both field sites can be approximated by permeable two-dimensional fracture planes, oriented near-horizontally at one site, and near-vertically at the other. The technique used on MOH field data to characterize fracture geometry shows promise in revealing fracture network characteristics important to groundwater flow and transport. © 2017, National Ground Water Association.

In situ probing of the active site geometry of ultrathin nanowires for the oxygen reduction reaction

DOE PAGES

Liu, Haiqing; Wong, Stanislaus S.; An, Wei; ...

2015-09-24

To create truly effective electrocatalysts for the cathodic reaction governing proton exchange membrane fuel cells (PEMFC), namely the oxygen reduction reaction (ORR), necessitates an accurate and detailed structural understanding of these electrocatalysts, especially at the nanoscale, and to precisely correlate that structure with demonstrable performance enhancement. To address this key issue, we have combined and interwoven theoretical calculations with experimental, spectroscopic observations in order to acquire useful structural insights into the active site geometry with implications for designing optimized nanoscale electrocatalysts with rationally predicted properties. Specifically, we have probed ultrathin (~2 nm) core–shell Pt~Pd 9Au nanowires, which have been previouslymore » shown to be excellent candidates for ORR in terms of both activity and long-term stability, from the complementary perspectives of both DFT calculations and X-ray absorption spectroscopy (XAS). The combination and correlation of data from both experimental and theoretical studies has revealed for the first time that the catalytically active structure of our ternary nanowires can actually be ascribed to a PtAu~Pd configuration, comprising a PtAu binary shell and a pure inner Pd core. Moreover, we have plausibly attributed the resulting structure to a specific synthesis step, namely the Cu underpotential deposition (UPD) followed by galvanic replacement with Pt. Thus, the fundamental insights gained into the performance of our ultrathin nanowires from our demonstrated approach will likely guide future directed efforts aimed at broadly improving upon the durability and stability of nanoscale electrocatalysts in general.« less

Hydraulic-Geometry Relations for Rivers in Coastal and Central Maine

USGS Publications Warehouse

Dudley, Robert W.

2004-01-01

Hydraulic-geometry relations (curves) were derived for 15 sites on 12 rivers in coastal and central Maine on the basis of site-specific (at-a-station) hydraulic-geometry relations and hydraulic models. At-a-station hydraulic-geometry curves, expressed as well-established power functions, describe the relations between channel geometry, velocity, and flow at a given point on a river. The derived at-a-station hydraulic-geometry curves indicate that, on average, a given increase in flow at a given river cross section in the study area will be nearly equally conveyed by increases in velocity and channel cross-sectional area. Regional curves describing the bankfull streamflow and associated channel geometry as functions of drainage area were derived for use in stream-channel assessment and restoration projects specific to coastal and central Maine. Regional hydraulic-geometry curves were derived by combining hydraulic-geometry information for 15 river cross sections using bankfull flow as the common reference streamflow. The exponents of the derived regional hydraulic-geometry relations indicate that, in the downstream direction, most of the conveyance of increasing contribution of flow is accommodated by an increase in cross-sectional area?with about 50 percent of the increase in flow accommodated by an increase in channel width, and 32 percent by an increase in depth. The remaining 18 percent is accommodated by an increase in streamflow velocity. On an annual-peak-series basis, results of this study indicate that the occurrence of bankfull streamflow for rivers in Maine is more frequent than the 1.5-year streamflow. On a flow-duration basis, bankfull streamflow for rivers in coastal and central Maine is equaled or exceeded approximately 8.1 percent of the time on mean?or about 30 days a year. Bankfull streamflow is roughly three times that of the mean annual streamflow for the sites investigated in this study. Regional climate, snowmelt hydrology, and glacial geology may play important roles in dictating the magnitude and frequency of occurrence of bankfull streamflows observed for rivers in coastal and central Maine.

Teaching Activity-Based Taxicab Geometry

ERIC Educational Resources Information Center

Ada, Tuba

2013-01-01

This study aimed on the process of teaching taxicab geometry, a non-Euclidean geometry that is easy to understand and similar to Euclidean geometry with its axiomatic structure. In this regard, several teaching activities were designed such as measuring taxicab distance, defining a taxicab circle, finding a geometric locus in taxicab geometry, and…

On the dynamical nature of the active center in a single-site photocatalyst visualized by 4D ultrafast electron microscopy

PubMed Central

Yoo, Byung-Kuk; Su, Zixue; Thomas, John Meurig; Zewail, Ahmed H.

2016-01-01

Understanding the dynamical nature of the catalytic active site embedded in complex systems at the atomic level is critical to developing efficient photocatalytic materials. Here, we report, using 4D ultrafast electron microscopy, the spatiotemporal behaviors of titanium and oxygen in a titanosilicate catalytic material. The observed changes in Bragg diffraction intensity with time at the specific lattice planes, and with a tilted geometry, provide the relaxation pathway: the Ti4+=O2− double bond transformation to a Ti3+−O1− single bond via the individual atomic displacements of the titanium and the apical oxygen. The dilation of the double bond is up to 0.8 Å and occurs on the femtosecond time scale. These findings suggest the direct catalytic involvement of the Ti3+−O1− local structure, the significance of nonthermal processes at the reactive site, and the efficient photo-induced electron transfer that plays a pivotal role in many photocatalytic reactions. PMID:26729878

KatB, a cyanobacterial Mn-catalase with unique active site configuration: Implications for enzyme function.

PubMed

Bihani, Subhash C; Chakravarty, Dhiman; Ballal, Anand

2016-04-01

Manganese catalases (Mn-catalases), a class of H2O2 detoxifying proteins, are structurally and mechanistically distinct from the commonly occurring catalases, which contain heme. Active site of Mn-catalases can serve as template for the synthesis of catalase mimetics for therapeutic intervention in oxidative stress related disorders. However, unlike the heme catalases, structural aspects of Mn-catalases remain inadequately explored. The genome of the ancient cyanobacterium Anabaena PCC7120, shows the presence of two Mn-catalases, KatA and KatB. Here, we report the biochemical and structural characterization of KatB. The KatB protein (with a C-terminal his-tag) was over-expressed in Escherichia coli and purified by affinity chromatography. On the addition of Mn(2+) to the E. coli growth medium, a substantial increase in production of the soluble KatB protein was observed. The purified KatB protein was an efficient catalase, which was relatively insensitive to inhibition by azide. Crystal structure of KatB showed a hexameric assembly with four-helix bundle fold, characteristic of the Ferritin-like superfamily. With canonical Glu4His2 coordination geometry and two terminal water ligands, the KatB active site was distinctly different from that of other Mn-catalases. Interestingly, the KatB active site closely resembled the active sites of ruberythrin/bacterioferritin, bi-iron members of the Ferritin-like superfamily. The KatB crystal structure provided fundamental insights into the evolutionary relationship within the Ferritin-like superfamily and further showed that Mn-catalases can be sub-divided into two groups, each with a distinct active site configuration. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls

PubMed Central

Farr, Joshua N.; Chen, Zhao; Lisse, Jeffrey R.; Lohman, Timothy G.; Going, Scott B.

2010-01-01

Understanding the influence of total body fat mass (TBFM) on bone during the peri-pubertal years is critical for the development of future interventions aimed at improving bone strength and reducing fracture risk. Thus, we evaluated the relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and strength at metaphyseal and diaphyseal sites of the femur and tibia of young girls. Data from 396 girls aged 8–13 years from the “Jump-In: Building Better Bones” study were analyzed. Bone parameters were assessed using peripheral quantitative computed tomography (pQCT) at the 4% and 20% distal femur and 4% and 66% distal tibia of the non-dominant leg. Bone parameters at the 4% sites included trabecular vBMD, periosteal circumference, and bone strength index (BSI), while at the 20% femur and 66% tibia, parameters included cortical vBMD, periosteal circumference, and strength-strain index (SSI). Multiple linear regression analyses were used to assess associations between bone parameters and TBFM, controlling for muscle cross-sectional area (MCSA). Regression analyses were then repeated with maturity, bone length, physical activity, and ethnicity as additional covariates. Analysis of covariance (ANCOVA) was used to compare bone parameters among tertiles of TBFM. In regression models with TBFM and MCSA, associations between TBFM and bone parameters at all sites were not significant. TBFM explained very little variance in all bone parameters (0.2–2.3%). In contrast, MCSA was strongly related (p < 0.001) to all bone parameters, except cortical vBMD. The addition of maturity, bone length, physical activity, and ethnicity did not alter the relationship between TBFM and bone parameters. With bone parameters expressed relative to total body mass, ANCOVA showed that all outcomes were significantly (p < 0.001) greater in the lowest compared to the middle and highest tertiles of TBFM. Although TBFM is correlated with femur and tibia vBMD, periosteal circumference, and strength in young girls, this relationship is significantly attenuated after adjustment for MCSA. Nevertheless, girls with higher TBFM relative to body mass have markedly diminished vBMD, geometry, and bone strength at metaphyseal and diaphyseal sites of the femur and tibia. PMID:20060079

Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level

PubMed Central

Schvartzman, Mark; Palma, Matteo; Sable, Julia; Abramson, Justin; Hu, Xian; Sheetz, Michael P.; Wind, Shalom J.

2011-01-01

The ability to control the placement of individual molecules promises to enable a wide range of applications and is a key challenge in nanoscience and nanotechnology. Many biological interactions, in particular, are sensitive to the precise geometric arrangement of proteins. We have developed a technique which combines molecular-scale nanolithography with site-selective biochemistry to create biomimetic arrays of individual protein binding sites. The binding sites can be arranged in heterogeneous patterns of virtually any possible geometry with a nearly unlimited number of degrees of freedom. We have used these arrays to explore how the geometric organization of the extracellular matrix (ECM) binding ligand RGD (Arg-Gly-Asp) affects cell adhesion and spreading. Systematic variation of spacing, density and cluster size of individual integrin binding sites was used to elicit different cell behavior. Cell spreading assays on arrays of different geometric arrangements revealed a dramatic increase in spreading efficiency when at least 4 liganded sites were spaced within 60 nm or less, with no dependence on global density. This points to the existence of a minimal matrix adhesion unit for fibronectin defined in space and stoichiometry. Developing an understanding of the ECM geometries that activate specific cellular functional complexes is a critical step toward controlling cell behavior. Potential practical applications range from new therapeutic treatments to the rational design of tissue scaffolds that can optimize healing without scarring. More broadly, spatial control at the single-molecule level can elucidate factors controlling individual molecular interactions and can enable synthesis of new systems based on molecular-scale architectures. PMID:21319842

STEREO/Waves Education and Public Outreach

NASA Astrophysics Data System (ADS)

MacDowall, R. J.; Bougeret, J.; Bale, S. D.; Goetz, K.; Kaiser, M. L.

2005-05-01

We present the education and public outreach plan and activities of the STEREO Waves (aka SWAVES) investigation. SWAVES measures radio emissions from the solar corona, interplanetary medium, and terrestrial magnetosphere, as well as in situ waves in the solar wind. In addition to the web site components that display stereo/multi-spacecraft data in a graphical form and explain the science and instruments, we will focus on the following three areas of EPO: class-room demonstrations using models of the STEREO spacecraft with battery powered radio receivers (and speakers) to illustrate spacecraft radio direction finding, teacher developed and tested class-room activities using SWAVES solar radio observations to motivate geometry and trigonometry, and sound-based delivery of characteristic radio and plasma wave events from the SWAVES web site for accessibility and esthetic reasons. Examples of each element will be demonstrated.

Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase☆

PubMed Central

Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

2013-01-01

Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect. PMID:24251110

BOREAS TE-12 Incoming PAR Through the Forest Canopy Data

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Papagno, Andrea (Editor); Walter-Shea, Elizabeth A.; Mesarch, Mark A.

2000-01-01

The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-12 (Terrestrial Ecology) team collected photosynthetically active radiation (PAR) data sets in support of its efforts to characterize and interpret information on shoot geometry, leaf optical properties, leaf water potential, and leaf gas exchange. The data were collected at the Southern Study Area-Old Black Spruce (SSA-OBS) site from 04-Jul-1996 to 25-Jul-1996. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

UTSA-74: A MOF-74 Isomer with Two Accessible Binding Sites per Metal Center for Highly Selective Gas Separation.

PubMed

Luo, Feng; Yan, Changsheng; Dang, Lilong; Krishna, Rajamani; Zhou, Wei; Wu, Hui; Dong, Xinglong; Han, Yu; Hu, Tong-Liang; O'Keeffe, Michael; Wang, Lingling; Luo, Mingbiao; Lin, Rui-Biao; Chen, Banglin

2016-05-04

A new metal-organic framework Zn2(H2O)(dobdc)·0.5(H2O) (UTSA-74, H4dobdc = 2,5-dioxido-1,4-benzenedicarboxylic acid), Zn-MOF-74/CPO-27-Zn isomer, has been synthesized and structurally characterized. It has a novel four coordinated fgl topology with one-dimensional channels of about 8.0 Å. Unlike metal sites in the well-established MOF-74 with a rod-packing structure in which each of them is in a five coordinate square pyramidal coordination geometry, there are two different Zn(2+) sites within the binuclear secondary building units in UTSA-74 in which one of them (Zn1) is in a tetrahedral while another (Zn2) in an octahedral coordination geometry. After activation, the two axial water molecules on Zn2 sites can be removed, generating UTSA-74a with two accessible gas binding sites per Zn2 ion. Accordingly, UTSA-74a takes up a moderately high and comparable amount of acetylene (145 cm(3)/cm(3)) to Zn-MOF-74. Interestingly, the accessible Zn(2+) sites in UTSA-74a are bridged by carbon dioxide molecules instead of being terminally bound in Zn-MOF-74, so UTSA-74a adsorbs a much smaller amount of carbon dioxide (90 cm(3)/cm(3)) than Zn-MOF-74 (146 cm(3)/cm(3)) at room temperature and 1 bar, leading to a superior MOF material for highly selective C2H2/CO2 separation. X-ray crystal structures, gas sorption isotherms, molecular modeling, and simulated and experimental breakthroughs comprehensively support this result.

Near-IR MCD of the nonheme ferrous active site in naphthalene 1,2-dioxygenase: correlation to crystallography and structural insight into the mechanism of Rieske dioxygenases.

PubMed

Ohta, Takehiro; Chakrabarty, Sarmistha; Lipscomb, John D; Solomon, Edward I

2008-02-06

Near-IR MCD and variable temperature, variable field (VTVH) MCD have been applied to naphthalene 1,2-dioxygenase (NDO) to describe the coordination geometry and electronic structure of the mononuclear nonheme ferrous catalytic site in the resting and substrate-bound forms with the Rieske 2Fe2S cluster oxidized and reduced. The structural results are correlated with the crystallographic studies of NDO and other related Rieske nonheme iron oxygenases to develop molecular level insights into the structure/function correlation for this class of enzymes. The MCD data for resting NDO with the Rieske center oxidized indicate the presence of a six-coordinate high-spin ferrous site with a weak axial ligand which becomes more tightly coordinated when the Rieske center is reduced. Binding of naphthalene to resting NDO (Rieske oxidized and reduced) converts the six-coordinate sites into five-coordinate (5c) sites with elimination of a water ligand. In the Rieske oxidized form the 5c sites are square pyramidal but transform to a 1:2 mixture of trigonal bipyramial/square pyramidal sites when the Rieske center is reduced. Thus the geometric and electronic structure of the catalytic site in the presence of substrate can be significantly affected by the redox state of the Rieske center. The catalytic ferrous site is primed for the O2 reaction when substrate is bound in the active site in the presence of the reduced Rieske site. These structural changes ensure that two electrons and the substrate are present before the binding and activation of O2, which avoids the uncontrolled formation and release of reactive oxygen species.

Synaptic Efficacy as a Function of Ionotropic Receptor Distribution: A Computational Study

PubMed Central

Allam, Sushmita L.; Bouteiller, Jean-Marie C.; Hu, Eric Y.; Ambert, Nicolas; Greget, Renaud; Bischoff, Serge; Baudry, Michel; Berger, Theodore W.

2015-01-01

Glutamatergic synapses are the most prevalent functional elements of information processing in the brain. Changes in pre-synaptic activity and in the function of various post-synaptic elements contribute to generate a large variety of synaptic responses. Previous studies have explored postsynaptic factors responsible for regulating synaptic strength variations, but have given far less importance to synaptic geometry, and more specifically to the subcellular distribution of ionotropic receptors. We analyzed the functional effects resulting from changing the subsynaptic localization of ionotropic receptors by using a hippocampal synaptic computational framework. The present study was performed using the EONS (Elementary Objects of the Nervous System) synaptic modeling platform, which was specifically developed to explore the roles of subsynaptic elements as well as their interactions, and that of synaptic geometry. More specifically, we determined the effects of changing the localization of ionotropic receptors relative to the presynaptic glutamate release site, on synaptic efficacy and its variations following single pulse and paired-pulse stimulation protocols. The results indicate that changes in synaptic geometry do have consequences on synaptic efficacy and its dynamics. PMID:26480028

Synaptic Efficacy as a Function of Ionotropic Receptor Distribution: A Computational Study.

PubMed

Allam, Sushmita L; Bouteiller, Jean-Marie C; Hu, Eric Y; Ambert, Nicolas; Greget, Renaud; Bischoff, Serge; Baudry, Michel; Berger, Theodore W

2015-01-01

Glutamatergic synapses are the most prevalent functional elements of information processing in the brain. Changes in pre-synaptic activity and in the function of various post-synaptic elements contribute to generate a large variety of synaptic responses. Previous studies have explored postsynaptic factors responsible for regulating synaptic strength variations, but have given far less importance to synaptic geometry, and more specifically to the subcellular distribution of ionotropic receptors. We analyzed the functional effects resulting from changing the subsynaptic localization of ionotropic receptors by using a hippocampal synaptic computational framework. The present study was performed using the EONS (Elementary Objects of the Nervous System) synaptic modeling platform, which was specifically developed to explore the roles of subsynaptic elements as well as their interactions, and that of synaptic geometry. More specifically, we determined the effects of changing the localization of ionotropic receptors relative to the presynaptic glutamate release site, on synaptic efficacy and its variations following single pulse and paired-pulse stimulation protocols. The results indicate that changes in synaptic geometry do have consequences on synaptic efficacy and its dynamics.

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

PubMed

Astani, Elahe K; Heshmati, Emran; Chen, Chun-Jung; Hadipour, Nasser L

2016-07-01

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active Site Interaction: Study on Functionalized C60 Nanoparticles via in Vitro and in Silico Assays.

PubMed

Liu, Yanyan; Yan, Bing; Winkler, David A; Fu, Jianjie; Zhang, Aiqian

2017-06-07

Acetylcholinesterase (AChE) activity regulation by chemical agents or, potentially, nanomaterials is important for both toxicology and pharmacology. Competitive inhibition via direct catalytic active sites (CAS) binding or noncompetitive inhibition through interference with substrate and product entering and exiting has been recognized previously as an AChE-inhibition mechanism for bespoke nanomaterials. The competitive inhibition by peripheral anionic site (PAS) interaction without CAS binding remains unexplored. Here, we proposed and verified the occurrence of a presumed competitive inhibition of AChE without CAS binding for hydrophobically functionalized C 60 nanoparticles (NPs) by employing both experimental and computational methods. The kinetic inhibition analysis distinguished six competitive inhibitors, probably targeting the PAS, from the pristine and hydrophilically modified C 60 NPs. A simple quantitative nanostructure-activity relationship (QNAR) model relating the pocket accessible length of substituent to inhibition capacity was then established to reveal how the geometry of the surface group decides the NP difference in AChE inhibition. Molecular docking identified the PAS as the potential binding site interacting with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core covered the enzyme gorge as a lid through π-π stacking with Tyr72 and Trp286 in the PAS, while the hydrophobic ligands on the fullerene surface inserted into the AChE active site to provide further stability for the complexes. The modeling predicted that inhibition would be severely compromised by Tyr72 and Trp286 deletions, and the subsequent site-directed mutagenesis experiments proved this prediction. Our results demonstrate AChE competitive inhibition of NPs without CAS participation to gain further understanding of both the neurotoxicity and the curative effect of NPs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.

DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

Capturing Snapshots of APE1 Processing DNA Damage

PubMed Central

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

2015-01-01

DNA apurinic-apyrimidinic (AP) sites are prevalent non-coding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive due in part to limited structural information. We report multiple high-resolution human APE1:DNA structures that divulge novel features of the APE1 reaction, including the metal binding site, nucleophile, and arginine clamps that mediate product release. We also report APE1:DNA structures with a T:G mismatch 5′ to the AP-site, representing a clustered lesion occurring in methylated CpG dinucleotides. These reveal that APE1 molds the T:G mismatch into a unique Watson-Crick like geometry that distorts the active site reducing incision. These snapshots provide mechanistic clarity for APE1, while affording a rational framework to manipulate biological responses to DNA damage. PMID:26458045

Capturing snapshots of APE1 processing DNA damage

DOE PAGES

Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; ...

2015-10-12

DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

Detailed Geophysical Fault Characterization in Yucca Flat, Nevada Test Site, Nevada

USGS Publications Warehouse

Asch, Theodore H.; Sweetkind, Donald S.; Burton, Bethany L.; Wallin, Erin L.

2009-01-01

Yucca Flat is a topographic and structural basin in the northeastern part of the Nevada Test Site (NTS) in Nye County, Nevada. Between the years 1951 and 1992, 659 underground nuclear tests took place in Yucca Flat; most were conducted in large, vertical excavations that penetrated alluvium and the underlying Cenozoic volcanic rocks. Radioactive and other potential chemical contaminants at the NTS are the subject of a long-term program of investigation and remediation by the U.S. Department of Energy (DOE), National Nuclear Security Administration, Nevada Site Office, under its Environmental Restoration Program. As part of the program, the DOE seeks to assess the extent of contamination and to evaluate the potential risks to humans and the environment from byproducts of weapons testing. To accomplish this objective, the DOE Environmental Restoration Program is constructing and calibrating a ground-water flow model to predict hydrologic flow in Yucca Flat as part of an effort to quantify the subsurface hydrology of the Nevada Test Site. A necessary part of calibrating and evaluating a model of the flow system is an understanding of the location and characteristics of faults that may influence ground-water flow. In addition, knowledge of fault-zone architecture and physical properties is a fundamental component of the containment of the contamination from underground nuclear tests, should such testing ever resume at the Nevada Test Site. The goal of the present investigation is to develop a detailed understanding of the geometry and physical properties of fault zones in Yucca Flat. This study was designed to investigate faults in greater detail and to characterize fault geometry, the presence of fault splays, and the fault-zone width. Integrated geological and geophysical studies have been designed and implemented to work toward this goal. This report describes the geophysical surveys conducted near two drill holes in Yucca Flat, the data analyses performed, and the integrated interpretations developed from the suite of geophysical methodologies utilized in this investigation. Data collection for this activity started in the spring of 2005 and continued into 2006. A suite of electrical geophysical surveys were run in combination with ground magnetic surveys; these surveys resulted in high-resolution subsurface data that portray subsurface fault geometry at the two sites and have identified structures not readily apparent from surface geologic mapping, potential field geophysical data, or surface effects fracture maps.

Noninvasive imaging of three-dimensional cardiac activation sequence during pacing and ventricular tachycardia.

PubMed

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

2011-08-01

Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. This study sought to rigorously assess the imaging performance of a 3-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of 3D intracardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE)-induced ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in 13 healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computed tomography images were obtained to construct geometry models. The noninvasively imaged activation sequence correlated well with invasively measured counterpart, with a correlation coefficient of 0.72 ± 0.04, and a relative error of 0.30 ± 0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from the imaged site of initial activation to the pacing site or site of arrhythmias determined from intracardiac mapping was ∼5 mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. 3DCEI can noninvasively delineate important features of focal or multifocal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequences of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Noninvasive Imaging of Three-dimensional Cardiac Activation Sequence during Pacing and Ventricular Tachycardia

PubMed Central

Han, Chengzong; Pogwizd, Steven M.; Killingsworth, Cheryl R.; He, Bin

2011-01-01

Background Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. Objective This study aims to rigorously assess the imaging performance of a three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE) induced ventricular tachycardia (VT) in the rabbit heart. Methods Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computer tomography images were obtained to construct geometry model. Results The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72±0.04, and a relative error of 0.30±0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from imaged site of initial activation to pacing site or site of arrhythmias determined from intra-cardiac mapping was ~5mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. Conclusion 3-DCEI can non-invasively delineate important features of focal or multi-focal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequence of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. PMID:21397046

Spectroscopic and computational studies of cobalamin species with variable lower axial ligation: implications for the mechanism of Co-C bond activation by class I cobalamin-dependent isomerases.

PubMed

Conrad, Karen S; Jordan, Christopher D; Brown, Kenneth L; Brunold, Thomas C

2015-04-20

5'-deoxyadenosylcobalamin (coenzyme B12, AdoCbl) serves as the cofactor for several enzymes that play important roles in fermentation and catabolism. All of these enzymes initiate catalysis by promoting homolytic cleavage of the cofactor's Co-C bond in response to substrate binding to their active sites. Despite considerable research efforts, the role of the lower axial ligand in facilitating Co-C bond homolysis remains incompletely understood. In the present study, we characterized several derivatives of AdoCbl and its one-electron reduced form, Co(II)Cbl, by using electronic absorption and magnetic circular dichroism spectroscopies. To complement our experimental data, we performed computations on these species, as well as additional Co(II)Cbl analogues. The geometries of all species investigated were optimized using a quantum mechanics/molecular mechanics method, and the optimized geometries were used to compute absorption spectra with time-dependent density functional theory. Collectively, our results indicate that a reduction in the basicity of the lower axial ligand causes changes to the cofactor's electronic structure in the Co(II) state that replicate the effects seen upon binding of Co(II)Cbl to Class I isomerases, which replace the lower axial dimethylbenzimidazole ligand of AdoCbl with a protein-derived histidine (His) residue. Such a reduction of the basicity of the His ligand in the enzyme active site may be achieved through proton uptake by the catalytic triad of conserved residues, DXHXGXK, during Co-C bond homolysis.

Molecular dynamics explorations of active site structure in designed and evolved enzymes.

PubMed

Osuna, Sílvia; Jiménez-Osés, Gonzalo; Noey, Elizabeth L; Houk, K N

2015-04-21

This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter the structure and organization of enzyme active sites. As proposed by Pauling about 70 years ago and elaborated by many others since then, biocatalysis is efficient when functional groups in the active site of an enzyme are in optimal positions for transition state stabilization. Changes in mechanism and covalent interactions are often critical parts of enzyme catalysis. We describe our explorations of the dynamical preorganization of active sites using MD, studying the fluctuations between active and inactive conformations normally concealed to static crystallography. MD shows how the various arrangements of active site residues influence the free energy of the transition state and relates the populations of the catalytic conformational ensemble to the enzyme activity. This Account is organized around three case studies from our laboratory. We first describe the importance of dynamics in evaluating a series of computationally designed and experimentally evolved enzymes for the Kemp elimination, a popular subject in the enzyme design field. We find that the dynamics of the active site is influenced not only by the original sequence design and subsequent mutations but also by the nature of the ligand present in the active site. In the second example, we show how microsecond MD has been used to uncover the role of remote mutations in the active site dynamics and catalysis of a transesterase, LovD. This enzyme was evolved by Tang at UCLA and Codexis, Inc., and is a useful commercial catalyst for the production of the drug simvastatin. X-ray analysis of inactive and active mutants did not reveal differences in the active sites, but relatively long time scale MD in solution showed that the active site of the wild-type enzyme preorganizes only upon binding of the acyl carrier protein (ACP) that delivers the natural acyl group to the active site. In the absence of bound ACP, a noncatalytic arrangement of the catalytic triad is dominant. Unnatural truncated substrates are inactive because of the lack of protein-protein interactions provided by the ACP. Directed evolution is able to gradually restore the catalytic organization of the active site by motion of the protein backbone that alters the active site geometry. In the third case, we demonstrate the key role of MD in combination with crystallography to identify the origins of substrate-dependent stereoselectivities in a number of Codexis-engineered ketoreductases, one of which is used commercially for the production of the antibiotic sulopenem. Here, mutations alter the shape of the active site as well as the accessibility of water to different regions of it. Each of these examples reveals something different about how mutations can influence enzyme activity and shows that directed evolution, like natural evolution, can increase catalytic activity in a variety of remarkable and often subtle ways.

Implementation Plan for Flexible Automation in U.S. Shipyards

DTIC Science & Technology

1985-01-01

process steps, cramped work sites, interrupted geometries , irregular or novel shapes, and other factors that affect automatability. We also try to...held by 2 hands in awkward places. Interrupt geometry of plates and beams. Cannot predict outcome. Creates need to measure and recut. Automation, if...of standard. enough over time I every job. I Rearrange work.Redefine work units. Too many interruptions Time, space, geometry only a little work gets

Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

PubMed Central

Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

2011-01-01

Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

Replication infidelity via a mismatch with Watson–Crick geometry

PubMed Central

Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.

2011-01-01

In describing the DNA double helix, Watson and Crick suggested that “spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms.” Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson–Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base–base mismatch with Watson–Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson–Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson–Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G•T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA. PMID:21233421

Replication infidelity via a mismatch with Watson-Crick geometry.

PubMed

Bebenek, Katarzyna; Pedersen, Lars C; Kunkel, Thomas A

2011-02-01

In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA.

Molecular Basis of the Bohr Effect in Arthropod Hemocyanin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirota, S.; Kawahara, T; Beltramini, M

2008-01-01

Flash photolysis and K-edge x-ray absorption spectroscopy (XAS) were used to investigate the functional and structural effects of pH on the oxygen affinity of three homologous arthropod hemocyanins (Hcs). Flash photolysis measurements showed that the well-characterized pH dependence of oxygen affinity (Bohr effect) is attributable to changes in the oxygen binding rate constant, kon, rather than changes in koff. In parallel, coordination geometry of copper in Hc was evaluated as a function of pH by XAS. It was found that the geometry of copper in the oxygenated protein is unchanged at all pH values investigated, while significant changes were observedmore » for the deoxygenated protein as a function of pH. The interpretation of these changes was based on previously described correlations between spectral lineshape and coordination geometry obtained for model compounds of known structure A pH-dependent change in the geometry of cuprous copper in the active site of deoxyHc, from pseudotetrahedral toward trigonal was assigned from the observed intensity dependence of the 1s ? 4pz transition in x-ray absorption near edge structure (XANES) spectra. The structural alteration correlated well with increase in oxygen affinity at alkaline pH determined in flash photolysis experiments. These results suggest that the oxygen binding rate in deoxyHc depends on the coordination geometry of Cu(I) and suggest a structural origin for the Bohr effect in arthropod Hcs.« less

Platelet geometry sensing spatially regulates α-granule secretion to enable matrix self-deposition

PubMed Central

Sakurai, Yumiko; Fitch-Tewfik, Jennifer L.; Qiu, Yongzhi; Ahn, Byungwook; Myers, David R.; Tran, Reginald; Fay, Meredith E.; Ding, Lingmei; Spearman, Paul W.; Michelson, Alan D.; Flaumenhaft, Robert

2015-01-01

Although the biology of platelet adhesion on subendothelial matrix after vascular injury is well characterized, how the matrix biophysical properties affect platelet physiology is unknown. Here we demonstrate that geometric orientation of the matrix itself regulates platelet α-granule secretion, a key component of platelet activation. Using protein microcontact printing, we show that platelets spread beyond the geometric constraints of fibrinogen or collagen micropatterns with <5-µm features. Interestingly, α-granule exocytosis and deposition of the α-granule contents such as fibrinogen and fibronectin were primarily observed in those areas of platelet extension beyond the matrix protein micropatterns. This enables platelets to “self-deposit” additional matrix, provide more cellular membrane to extend spreading, and reinforce platelet-platelet connections. Mechanistically, this phenomenon is mediated by actin polymerization, Rac1 activation, and αIIbβ3 integrin redistribution and activation, and is attenuated in gray platelet syndrome platelets, which lack α-granules, and Wiskott-Aldrich syndrome platelets, which have cytoskeletal defects. Overall, these studies demonstrate how platelets transduce geometric cues of the underlying matrix geometry into intracellular signals to extend spreading, which endows platelets spatial flexibility when spreading onto small sites of exposed subendothelium. PMID:25964667

Radiation Protection Studies for Medical Particle Accelerators using Fluka Monte Carlo Code.

PubMed

Infantino, Angelo; Cicoria, Gianfranco; Lucconi, Giulia; Pancaldi, Davide; Vichi, Sara; Zagni, Federico; Mostacci, Domiziano; Marengo, Mario

2017-04-01

Radiation protection (RP) in the use of medical cyclotrons involves many aspects both in the routine use and for the decommissioning of a site. Guidelines for site planning and installation, as well as for RP assessment, are given in international documents; however, the latter typically offer analytic methods of calculation of shielding and materials activation, in approximate or idealised geometry set-ups. The availability of Monte Carlo (MC) codes with accurate up-to-date libraries for transport and interaction of neutrons and charged particles at energies below 250 MeV, together with the continuously increasing power of modern computers, makes the systematic use of simulations with realistic geometries possible, yielding equipment and site-specific evaluation of the source terms, shielding requirements and all quantities relevant to RP at the same time. In this work, the well-known FLUKA MC code was used to simulate different aspects of RP in the use of biomedical accelerators, particularly for the production of medical radioisotopes. In the context of the Young Professionals Award, held at the IRPA 14 conference, only a part of the complete work is presented. In particular, the simulation of the GE PETtrace cyclotron (16.5 MeV) installed at S. Orsola-Malpighi University Hospital evaluated the effective dose distribution around the equipment; the effective number of neutrons produced per incident proton and their spectral distribution; the activation of the structure of the cyclotron and the vault walls; the activation of the ambient air, in particular the production of 41Ar. The simulations were validated, in terms of physical and transport parameters to be used at the energy range of interest, through an extensive measurement campaign of the neutron environmental dose equivalent using a rem-counter and TLD dosemeters. The validated model was then used in the design and the licensing request of a new Positron Emission Tomography facility. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Accurate Monte Carlo modeling of cyclotrons for optimization of shielding and activation calculations in the biomedical field

NASA Astrophysics Data System (ADS)

Infantino, Angelo; Marengo, Mario; Baschetti, Serafina; Cicoria, Gianfranco; Longo Vaschetto, Vittorio; Lucconi, Giulia; Massucci, Piera; Vichi, Sara; Zagni, Federico; Mostacci, Domiziano

2015-11-01

Biomedical cyclotrons for production of Positron Emission Tomography (PET) radionuclides and radiotherapy with hadrons or ions are widely diffused and established in hospitals as well as in industrial facilities and research sites. Guidelines for site planning and installation, as well as for radiation protection assessment, are given in a number of international documents; however, these well-established guides typically offer analytic methods of calculation of both shielding and materials activation, in approximate or idealized geometry set up. The availability of Monte Carlo codes with accurate and up-to-date libraries for transport and interactions of neutrons and charged particles at energies below 250 MeV, together with the continuously increasing power of nowadays computers, makes systematic use of simulations with realistic geometries possible, yielding equipment and site specific evaluation of the source terms, shielding requirements and all quantities relevant to radiation protection. In this work, the well-known Monte Carlo code FLUKA was used to simulate two representative models of cyclotron for PET radionuclides production, including their targetry; and one type of proton therapy cyclotron including the energy selection system. Simulations yield estimates of various quantities of radiological interest, including the effective dose distribution around the equipment, the effective number of neutron produced per incident proton and the activation of target materials, the structure of the cyclotron, the energy degrader, the vault walls and the soil. The model was validated against experimental measurements and comparison with well-established reference data. Neutron ambient dose equivalent H*(10) was measured around a GE PETtrace cyclotron: an average ratio between experimental measurement and simulations of 0.99±0.07 was found. Saturation yield of 18F, produced by the well-known 18O(p,n)18F reaction, was calculated and compared with the IAEA recommended value: a ratio simulation to IAEA of 1.01±0.10 was found.

Simulation of radiofrequency ablation in real human anatomy.

PubMed

Zorbas, George; Samaras, Theodoros

2014-12-01

The objective of the current work was to simulate radiofrequency ablation treatment in computational models with realistic human anatomy, in order to investigate the effect of realistic geometry in the treatment outcome. The body sites considered in the study were liver, lung and kidney. One numerical model for each body site was obtained from Duke, member of the IT'IS Virtual Family. A spherical tumour was embedded in each model and a single electrode was inserted into the tumour. The same excitation voltage was used in all cases to underline the differences in the resulting temperature rise, due to different anatomy at each body site investigated. The same numerical calculations were performed for a two-compartment model of the tissue geometry, as well as with the use of an analytical approximation for a single tissue compartment. Radiofrequency ablation (RFA) therapy appears efficient for tumours in liver and lung, but less efficient in kidney. Moreover, the time evolution of temperature for a realistic geometry differs from that for a two-compartment model, but even more for an infinite homogenous tissue model. However, it appears that the most critical parameters of computational models for RFA treatment planning are tissue properties rather than tissue geometry. Computational simulations of realistic anatomy models show that the conventional technique of a single electrode inside the tumour volume requires a careful choice of both the excitation voltage and treatment time in order to achieve effective treatment, since the ablation zone differs considerably for various body sites.

Distribution, structure and temporal variability of hydrothermal outflow at a slow-spreading hydrothermal field from seafloor image mosaics.

NASA Astrophysics Data System (ADS)

Barreyre, Thibaut; Escartin, Javier; Cannat, Mathilde; Garcia, Rafael; Science Party, Momar'08; Science Party, Bathyluck'09

2010-05-01

The Lucky Strike hydrothermal site, located South of the Azores along the Mid-Atlantic Ridge, is one of the largest and best-known active hydrothermal fields along the ridge system. This site within the MoMAR area is also the target for the installation in 2010 of a pilot deep-sea observatory with direct telemetry to land, to be part of the European Seafloor Observatory Network (ESONET). The Lucky Strike hydrothermal site has seen extensive high-resolution, near-bottom geophysical surveys in 1996 (Lustre'96), 2006 (Momareto06), 2008 (MOMAR08) and 2009 (Bathyluck09). Vertically acquired black-and-white electronic still camera images have been projected and georeferenced to obtain 3 image mosaics covering the zone of active venting, extending ~ 700x800 m2, and with full image resolution (~10 mm pixels). These data allow us to study how hydrothermal outflow is structured, including the relationships between the zones of active high-temperature venting, areas of diffuse outflow, and the geological structure (nature of the substrate, faults and fissures, sediments, etc.). Hydrothermal outflow is systematically associated with bacterial mats that are easily identified in the imagery, allowing us to study temporal variability at two different scales. Over the 13-year period we can potentially track changes in both the geometry and intensity of hydrothermal activity throughout the system; our preliminary study of the Eiffel Tower, White Castle and Mt Segur indicate that activity has been sustained in recent times, with small changes in the detailed geometry of the diffuse outflow and its intensity. At longer times scales (hundreds to 1000 years?) imagery also shows evidence of areas of venting that are no longer active, often associated with the active structures. In combination with the high-resolution bathymetry, the imagery data thus allow us to characterize the shallow structure of hydrothermal outflow at depth, the structural and volcanic control, and ultimately quantify the heat flux associates with this hydrothermal outflow. Image mosaics are also key for the installation of instrumentation required by temporal studies, and for the infrastructure of the ESONET pilot seafloor observatory. This type of survey techniques and studies can also be extended to other areas of interest, such as hydrothermal fields, cold seeps, etc.

Spectroscopic Characterization of a Green Copper Site in a Single-Domain Cupredoxin

PubMed Central

Roger, Magali; Biaso, Frédéric; Castelle, Cindy J.; Bauzan, Marielle; Chaspoul, Florence; Lojou, Elisabeth; Sciara, Giuliano; Caffarri, Stefano; Giudici-Orticoni, Marie-Thérèse; Ilbert, Marianne

2014-01-01

Cupredoxins are widespread copper-binding proteins, mainly involved in electron transfer pathways. They display a typical rigid greek key motif consisting of an eight stranded β-sandwich. A fascinating feature of cupredoxins is the natural diversity of their copper center geometry. These geometry variations give rise to drastic changes in their color, such as blue, green, red or purple. Based on several spectroscopic and structural analyses, a connection between the geometry of their copper-binding site and their color has been proposed. However, little is known about the relationship between such diversity of copper center geometry in cupredoxins and possible implications for function. This has been difficult to assess, as only a few naturally occurring green and red copper sites have been described so far. We report herein the spectrocopic characterization of a novel kind of single domain cupredoxin of green color, involved in a respiratory pathway of the acidophilic organism Acidithiobacillus ferrooxidans. Biochemical and spectroscopic characterization coupled to bioinformatics analysis reveal the existence of some unusual features for this novel member of the green cupredoxin sub-family. This protein has the highest redox potential reported to date for a green-type cupredoxin. It has a constrained green copper site insensitive to pH or temperature variations. It is a green-type cupredoxin found for the first time in a respiratory pathway. These unique properties might be explained by a region of unknown function never found in other cupredoxins, and by an unusual length of the loop between the second and the fourth copper ligands. These discoveries will impact our knowledge on non-engineered green copper sites, whose involvement in respiratory chains seems more widespread than initially thought. PMID:24932914

Spectroscopic characterization of a green copper site in a single-domain cupredoxin.

PubMed

Roger, Magali; Biaso, Frédéric; Castelle, Cindy J; Bauzan, Marielle; Chaspoul, Florence; Lojou, Elisabeth; Sciara, Giuliano; Caffarri, Stefano; Giudici-Orticoni, Marie-Thérèse; Ilbert, Marianne

2014-01-01

Cupredoxins are widespread copper-binding proteins, mainly involved in electron transfer pathways. They display a typical rigid greek key motif consisting of an eight stranded β-sandwich. A fascinating feature of cupredoxins is the natural diversity of their copper center geometry. These geometry variations give rise to drastic changes in their color, such as blue, green, red or purple. Based on several spectroscopic and structural analyses, a connection between the geometry of their copper-binding site and their color has been proposed. However, little is known about the relationship between such diversity of copper center geometry in cupredoxins and possible implications for function. This has been difficult to assess, as only a few naturally occurring green and red copper sites have been described so far. We report herein the spectrocopic characterization of a novel kind of single domain cupredoxin of green color, involved in a respiratory pathway of the acidophilic organism Acidithiobacillus ferrooxidans. Biochemical and spectroscopic characterization coupled to bioinformatics analysis reveal the existence of some unusual features for this novel member of the green cupredoxin sub-family. This protein has the highest redox potential reported to date for a green-type cupredoxin. It has a constrained green copper site insensitive to pH or temperature variations. It is a green-type cupredoxin found for the first time in a respiratory pathway. These unique properties might be explained by a region of unknown function never found in other cupredoxins, and by an unusual length of the loop between the second and the fourth copper ligands. These discoveries will impact our knowledge on non-engineered green copper sites, whose involvement in respiratory chains seems more widespread than initially thought.

Non-thiolate ligation of nickel by nucleotide-free UreG of Klebsiella aerogenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin-Diaconescu, Vlad; Joseph, Crisjoe A.; Boer, Jodi L.

Nickel-dependent ureases are activated by a multiprotein complex that includes the GTPase UreG. Prior studies showed that nucleotide-free UreG from Klebsiella aerogenes is monomeric and binds one nickel or zinc ion with near-equivalent affinity using an undefined binding site, whereas nucleotide-free UreG from Helicobacter pylori selectively binds one zinc ion per dimer via a universally conserved Cys-Pro-His motif in each protomer. Iodoacetamide-treated K. aerogenes UreG was nearly unaffected in nickel binding compared to non-treated sample, suggesting the absence of thiolate ligands to the metal. X-ray absorption spectroscopy of nickel-bound UreG showed the metal possessed four-coordinate geometry with all O/N donormore » ligands including one imidazole, thus confirming the absence of thiolate ligation. The nickel site in Strep-tag II-modified protein possessed six-coordinate geometry, again with all O/N donor ligands, but now including two or three imidazoles. An identical site was noted for the Strep-tag II-modified H74A variant, substituted in the Cys-Pro-His motif, ruling out coordination by this His residue. These results are consistent with metal binding to both His6 and a His residue of the fusion peptide in Strep-tagged K. aerogenes UreG. We conclude that the nickel- and zinc-binding site in nucleotide-free K. aerogenes UreG is distinct from that of nucleotide-free H. pylori UreG and does not involve the Cys-Pro-His motif. Further, we show the Strep-tag II can perturb metal coordination of this protein.« less

Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

PubMed

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

Sulfated Low Molecular Weight Lignins, Allosteric Inhibitors of Coagulation Proteinases via the Heparin Binding Site, Significantly Alter the Active Site of Thrombin and Factor Xa Compared to Heparin

PubMed Central

Henry, Brian L.; Desai, Umesh R.

2014-01-01

Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. PMID:25242245

Sulfated low molecular weight lignins, allosteric inhibitors of coagulation proteinases via the heparin binding site, significantly alter the active site of thrombin and factor xa compared to heparin.

PubMed

Henry, Brian L; Desai, Umesh R

2014-11-01

Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

10 CFR 100.23 - Geologic and seismic siting criteria.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Earthquake Ground Motion, and to permit adequate engineering solutions to actual or potential geologic and..., earthquake recurrence rates, fault geometry and slip rates, site foundation material, and seismically induced... Earthquake Ground Motion for the site, the potential for surface tectonic and nontectonic deformations, the...

10 CFR 100.23 - Geologic and seismic siting criteria.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Earthquake Ground Motion, and to permit adequate engineering solutions to actual or potential geologic and..., earthquake recurrence rates, fault geometry and slip rates, site foundation material, and seismically induced... Earthquake Ground Motion for the site, the potential for surface tectonic and nontectonic deformations, the...

10 CFR 100.23 - Geologic and seismic siting criteria.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Earthquake Ground Motion, and to permit adequate engineering solutions to actual or potential geologic and..., earthquake recurrence rates, fault geometry and slip rates, site foundation material, and seismically induced... Earthquake Ground Motion for the site, the potential for surface tectonic and nontectonic deformations, the...

Effectiveness of Discovery Learning-Based Transformation Geometry Module

NASA Astrophysics Data System (ADS)

Febriana, R.; Haryono, Y.; Yusri, R.

2017-09-01

Development of transformation geometry module is conducted because the students got difficulties to understand the existing book. The purpose of the research was to find out the effectiveness of discovery learning-based transformation geometry module toward student’s activity. Model of the development was Plomp model consisting preliminary research, prototyping phase and assessment phase. The research was focused on assessment phase where it was to observe the designed product effectiveness. The instrument was observation sheet. The observed activities were visual activities, oral activities, listening activities, mental activities, emotional activities and motor activities. Based on the result of the research, it is found that visual activities, learning activities, writing activities, the student’s activity is in the criteria very effective. It can be concluded that the use of discovery learning-based transformation geometry module use can increase the positive student’s activity and decrease the negative activity.

Enthalpic Breakdown of Water Structure on Protein Active-Site Surfaces

PubMed Central

Haider, Kamran; Wickstrom, Lauren; Ramsey, Steven; Gilson, Michael K.; Kurtzman, Tom

2016-01-01

The principles underlying water reorganization around simple non-polar solutes are well understood and provide the framework for classical hydrophobic effect, whereby water molecules structure themselves around solutes so that they maintain favorable energetic contacts with both the solute and with other water molecules. However, for certain solute surface topographies, water molecules, due to their geometry and size, are unable to simultaneously maintain favorable energetic contacts with both the surface and neighboring water molecules. In this study, we analyze the solvation of ligand-binding sites for six structurally diverse proteins using hydration site analysis and measures of local water structure, in order to identify surfaces at which water molecules are unable to structure themselves in a way that maintains favorable enthalpy relative to bulk water. These surfaces are characterized by a high degree of enclosure, weak solute-water interactions, and surface constraints that induce unfavorable pair interactions between neighboring water molecules. Additionally, we find that the solvation of charged side-chains in an active site generally results in favorable enthalpy but can also lead to pair interactions between neighboring water molecules that are significantly unfavorable relative to bulk water. We find that frustrated local structure can occur not only in apolar and weakly polar pockets, where overall enthalpy tends to be unfavorable, but also in charged pockets, where overall water enthalpy tends to be favorable. The characterization of local water structure in these terms may prove useful for evaluating the displacement of water from diverse protein active-site environments. PMID:27169482

Probing the effect of the non-active-site mutation Y229W in New Delhi metallo-β-lactamase-1 by site-directed mutagenesis, kinetic studies, and molecular dynamics simulations.

PubMed

Chen, Jiao; Chen, Hui; Shi, Yun; Hu, Feng; Lao, Xingzhen; Gao, Xiangdong; Zheng, Heng; Yao, Wenbing

2013-01-01

New Delhi metallo-β-lactamase-1 (NDM-1) has attracted extensive attention for its high catalytic activities of hydrolyzing almost all β-lactam antibiotics. NDM-1 shows relatively higher similarity to subclass B1 metallo-β-lactamases (MβLs), but its residue at position 229 is identical to that of B2/B3 MβLs, which is a Tyr instead of a B1-MβL-conserved Trp. To elucidate the possible role of Y229 in the bioactivity of NDM-1, we performed mutagenesis study and molecular dynamics (MD) simulations. Although residue Y229 is spatially distant from the active site and not contacting directly with the substrate or zinc ions, the Y229W mutant was found to have higher kcat and Km values than those of wild-type NDM-1, resulting in 1 ∼ 7 fold increases in k(cat) /K(m) values against tested antibiotics. In addition, our MD simulations illustrated the enhanced flexibility of Loop 2 upon Y229W mutation, which could increase the kinetics of both substrate entrance (kon) and product egress (koff). The enhanced flexibility of Loop 2 might allow the enzyme to adjust the geometry of its active site to accommodate substrates with different structures, broadening its substrate spectrum. This study indicated the possible role of the residue at position 229 in the evolution of NDM-1.

Rural versus nonrural differences in BMC, volumetric BMD, and bone size: a population-based cross-sectional study.

PubMed

Specker, Bonny; Binkley, Teresa; Fahrenwald, Nancy

2004-12-01

Despite reports of lower fracture risk among rural versus urban populations, few studies have investigated rural versus urban differences in bone mineral content (BMC) and bone mineral density (BMD). Population differences in cross-sectional bone geometry and understanding lifestyle factors responsible for these differences may reveal insights into the reason for differences in fracture risk. We hypothesized that if lifestyle differences in bone mass, size, and geometry are a result of muscle strength, activity, or dietary differences, Hutterite and rural populations should have greater bone mass compared to nonrural populations. The study population consisted of 1189 individuals: 504 rural Hutterites (188 men), 349 rural individuals (>75% life farming, 184 men), and 336 nonrural individuals (never lived on farm, 134 men) aged 20 to 66 years. BMC, bone area, and areal BMD (aBMD) of the total body (TB), hip, femoral neck (FN), and spine by DXA; volumetric BMD (vBMD) and bone geometry at the 4% and 20% radius; polar stress strain index (pSSI), a measure of bone strength, at the 20% pQCT site; and strength, 7-day activity recall, and 24-h diet recall were collected and compared among groups. Hutterite women and men had greater grip strength compared to rural and nonrural populations (both, P <0.001). Rural women had greater activity versus Hutterite and nonrural (P <0.001), while both Hutterite and rural men had greater activity than nonrural (P <0.001). Hutterite and rural populations tended to have greater BMC and areal size than the nonrural population, while Hutterites had greater BMC and areal size than rural population at some (TB, FN for females only), but not all (proximal hip), sites. Cortical vBMD was inversely associated with periosteal circumference at the 20% radius in women (r=-0.25, P <0.001) and men (r=-0.28, P <0.001) and was higher in nonrural versus Hutterite and rural men. Hutterite and rural women and men had greater pSSI at the 20% radius compared to nonrural; inclusion of strength measurements explained population differences among women, but not men. Lifestyle differences did not explain population differences in BMC, aBMD, vBMD, or bone size.

Geophysics in Mejillones Basin, Chile: Dynamic analysis and associatedseismic hazard

NASA Astrophysics Data System (ADS)

Maringue, J. I.; Yanez, G. A.; Lira, E.; Podestá, L., Sr.; Figueroa, R.; Estay, N. P.; Saez, E.

2016-12-01

The active margin of South America has a high seismogenic potential. In particular, the Mejillones peninsula, located in northern Chile, represents a site of interest for seismic hazard due to 100-year seismic gap, the potentially large site effects, and the presence of the most important port in the region. We perform a dynamic analysis of the zone from a spatial and petrophysical model of the Mejillones Basin, to understand its behavior under realistic seismic scenarios. Geometry and petrophysics of the basin were obtained from an integrated modeling of geophysics observations (gravity, seismic and electromagnetic data) distributed mainly in Pampa Mejillones whose western edge is limited by Mejillones Fault, oriented north-south. This regional-scale normal fault shows a half-graben geometry which controls the development of the Mejillones basin eastwards. The gravimetric and magnetotelluric methods allow to define the geometry of the basin, through a cover/basement density contrast, and the transition zone from very low-moderate electrical resistivities, respectively. The seismic method complements the petrophysics in terms of the shear wave depth profile. The results show soil's thicknesses up to 700 meters on deeper zone, with steeper slopes to the west and lower slopes to the east, in agreement with the normal-fault-half-graben basin geometry. Along the N-S direction there are not great differences in basin depth, comprising an almost 2D problem. In terms of petrophysics, the sedimentary stratum is characterized by shear velocities between 300-700 m/s, extremely low electrical resistivities, below 1 ohm-m, and densities from 1.4 to 1.8 gr/cc. The numerical simulation of the seismic waves amplification gives values in the order of 0.8g, which implying large surface damages. The results demonstrate a potential risk in Mejillones bay to future events, therefore is very important to generate mitigations policies for infrastructure and human settlements.

Characterization of active-site residues of the NIa protease from tobacco vein mottling virus.

PubMed

Hwang, D C; Kim, D H; Lee, J S; Kang, B H; Han, J; Kim, W; Song, B D; Choi, K Y

2000-10-31

Nuclear inclusion a (NIa) protease of tobacco vein mottling virus is responsible for the processing of the viral polyprotein into functional proteins. In order to identify the active-site residues of the TVMV NIa protease, the putative active-site residues, His-46, Asp-81 and Cys-151, were mutated individually to generate H46R, H46A, D81E, D81N, C151S, and C151A, and their mutational effects on the proteolytic activities were examined. Proteolytic activity was completely abolished by the mutations of H46R, H46A, D81N, and C151A, suggesting that the three residues are crucial for catalysis. The mutation of D81E decreased kcat marginally by about 4.7-fold and increased Km by about 8-fold, suggesting that the aspartic acid at position 81 is important for substrate binding but can be substituted by glutamate without any significant decrease in catalysis. The replacement of Cys-151 by Ser to mimic the catalytic triad of chymotrypsin-like serine protease resulted in the drastic decrease in kcat by about 1,260-fold. This result might be due to the difference of the active-site geometry between the NIa protease and chymotrypsin. The protease exhibited a bell-shaped pH-dependent profile with a maximum activity approximately at pH 8.3 and with the abrupt changes at the respective pKa values of approximately 6.6 and 9.2, implying the involvement of a histidine residue in catalysis. Taken together, these results demonstrate that the three residues, His-46, Asp-81, and Cys-151, play a crucial role in catalysis of the TVMV NIa protease.

Construction of hexahedral finite element mesh capturing realistic geometries of a petroleum reserve

DOE PAGES

Park, Byoung Yoon; Roberts, Barry L.; Sobolik, Steven R.

2017-07-27

The three-dimensional finite element mesh capturing realistic geometries of the Bayou Choctaw site has been constructed using the sonar and seismic survey data obtained from the field. The mesh consists of hexahedral elements because the salt constitutive model is coded using hexahedral elements. Various ideas and techniques to construct finite element mesh capturing artificially and naturally formed geometries are provided. The techniques to reduce the number of elements as much as possible to save on computer run time while maintaining the computational accuracy is also introduced. The steps and methodologies could be applied to construct the meshes of Big Hill,more » Bryan Mound, and West Hackberry strategic petroleum reserve sites. The methodology could be applied to the complicated shape masses for various civil and geological structures.« less

Construction of hexahedral finite element mesh capturing realistic geometries of a petroleum reserve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Byoung Yoon; Roberts, Barry L.; Sobolik, Steven R.

The three-dimensional finite element mesh capturing realistic geometries of the Bayou Choctaw site has been constructed using the sonar and seismic survey data obtained from the field. The mesh consists of hexahedral elements because the salt constitutive model is coded using hexahedral elements. Various ideas and techniques to construct finite element mesh capturing artificially and naturally formed geometries are provided. The techniques to reduce the number of elements as much as possible to save on computer run time while maintaining the computational accuracy is also introduced. The steps and methodologies could be applied to construct the meshes of Big Hill,more » Bryan Mound, and West Hackberry strategic petroleum reserve sites. The methodology could be applied to the complicated shape masses for various civil and geological structures.« less

Sensor-Based Electromagnetic Navigation (Mediguide®): How Accurate Is It? A Phantom Model Study.

PubMed

Bourier, Felix; Reents, Tilko; Ammar-Busch, Sonia; Buiatti, Alessandra; Grebmer, Christian; Telishevska, Marta; Brkic, Amir; Semmler, Verena; Lennerz, Carsten; Kaess, Bernhard; Kottmaier, Marc; Kolb, Christof; Deisenhofer, Isabel; Hessling, Gabriele

2015-10-01

Data about localization reproducibility as well as spatial and visual accuracy of the new MediGuide® sensor-based electroanatomic navigation technology are scarce. We therefore sought to quantify these parameters based on phantom experiments. A realistic heart phantom was generated in a 3D-Printer. A CT scan was performed on the phantom. The phantom itself served as ground-truth reference to ensure exact and reproducible catheter placement. A MediGuide® catheter was repeatedly tagged at selected positions to assess accuracy of point localization. The catheter was also used to acquire a MediGuide®-scaled geometry in the EnSite Velocity® electroanatomic mapping system. The acquired geometries (MediGuide®-scaled and EnSite Velocity®-scaled) were compared to a CT segmentation of the phantom to quantify concordance. Distances between landmarks were measured in the EnSite Velocity®- and MediGuide®-scaled geometry and the CT dataset for Bland-Altman comparison. The visualization of virtual MediGuide® catheter tips was compared to their corresponding representation on fluoroscopic cine-loops. Point localization accuracy was 0.5 ± 0.3 mm for MediGuide® and 1.4 ± 0.7 mm for EnSite Velocity®. The 3D accuracy of the geometries was 1.1 ± 1.4 mm (MediGuide®-scaled) and 3.2 ± 1.6 mm (not MediGuide®-scaled). The offset between virtual MediGuide® catheter visualization and catheter representation on corresponding fluoroscopic cine-loops was 0.4 ± 0.1 mm. The MediGuide® system shows a very high level of accuracy regarding localization reproducibility as well as spatial and visual accuracy, which can be ascribed to the magnetic field localization technology. The observed offsets between the geometry visualization and the real phantom are below a clinically relevant threshold. © 2015 Wiley Periodicals, Inc.

In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels.

PubMed

Maïmoun, L; Coste, O; Mariano-Goulart, D; Galtier, F; Mura, T; Philibert, P; Briot, K; Paris, F; Sultan, C

2011-12-01

Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.

Crystallographic Analysis of Active Site Contributions to Regiospecificity in the Diiron Enzyme Toluene 4-Monooxygenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, Lucas J.; Acheson, Justin F.; McCoy, Jason G.

Crystal structures of toluene 4-monooxygenase hydroxylase in complex with reaction products and effector protein reveal active site interactions leading to regiospecificity. Complexes with phenolic products yield an asymmetric {mu}-phenoxo-bridged diiron center and a shift of diiron ligand E231 into a hydrogen bonding position with conserved T201. In contrast, complexes with inhibitors p-NH{sub 2}-benzoate and p-Br-benzoate showed a {mu}-1,1 coordination of carboxylate oxygen between the iron atoms and only a partial shift in the position of E231. Among active site residues, F176 trapped the aromatic ring of products against a surface of the active site cavity formed by G103, E104 andmore » A107, while F196 positioned the aromatic ring against this surface via a {pi}-stacking interaction. The proximity of G103 and F176 to the para substituent of the substrate aromatic ring and the structure of G103L T4moHD suggest how changes in regiospecificity arise from mutations at G103. Although effector protein binding produced significant shifts in the positions of residues along the outer portion of the active site (T201, N202, and Q228) and in some iron ligands (E231 and E197), surprisingly minor shifts (<1 {angstrom}) were produced in F176, F196, and other interior residues of the active site. Likewise, products bound to the diiron center in either the presence or absence of effector protein did not significantly shift the position of the interior residues, suggesting that positioning of the cognate substrates will not be strongly influenced by effector protein binding. Thus, changes in product distributions in the absence of the effector protein are proposed to arise from differences in rates of chemical steps of the reaction relative to motion of substrates within the active site channel of the uncomplexed, less efficient enzyme, while structural changes in diiron ligand geometry associated with cycling between diferrous and diferric states are discussed for their potential contribution to product release.« less

Characterization of Viscoelastic Materials Through an Active Mixer by Direct-Ink Writing

NASA Astrophysics Data System (ADS)

Drake, Eric

The goal of this thesis is two-fold: First, to determine mixing effectiveness of an active mixer attachment to a three-dimensional (3D) printer by characterizing actively-mixed, three-dimensionally printed silicone elastomers. Second, to understand mechanical properties of a printed lattice structure with varying geometry and composition. Ober et al defines mixing effectiveness as a measureable quantity characterized by two key variables: (i) a dimensionless impeller parameter (O ) that depends on mixer geometry as well as Peclet number (Pe) and (ii) a coefficient of variation (COV) that describes the mixer effectiveness based upon image intensity. The first objective utilizes tungsten tracer particles distributed throughout a batch of Dow Corning SE1700 (two parts silicone) - ink "A". Ink "B" is made from pure SE1700. Using the in-site active mixer, both ink "A" and "B" coalesce to form a hybrid ink just before extrusion. Two samples of varying mixer speeds and composition ratios are printed and analyzed by microcomputed tomography (MicroCT). A continuous stirred tank reactor (CSTR) model is applied to better understand mixing behavior. Results are then compared with computer models to verify the hypothesis. Data suggests good mixing for the sample with higher impeller speed. A Radial Distrubtion Function (RDF) macro is used to provide further qualitative analysis of mixing efficiency. The second objective of this thesis utilized three-dimensionally printed samples of varying geometry and composition to ascertain mechanical properties. Samples were printed using SE1700 provided by Lawrence Livermore National Laboratory with a face-centered tetragonal (FCT) structure. Hardness testing is conducted using a Shore OO durometer guided by a computer-controlled, three-axis translation stage to provide precise movements. Data is collected across an 'x-y' plane of the specimen. To explain the data, a simply supported beam model is applied to a single unit cell which yields basic structural behavior per cell. Characterizing the sample as a whole requires a more rigorous approach and non-trivial complexities due to varying geometries and compositions exist. The data demonstrates a uniform change in hardness as a function of position. Additionally, the data indicates periodicities in the lattice structure.

Geometric indices of bone strength are associated with physical activity and dietary calcium intake in healthy older women.

PubMed

Nurzenski, Michelle K; Briffa, N Kathryn; Price, Roger I; Khoo, Benjamin C C; Devine, Amanda; Beck, Thomas J; Prince, Richard L

2007-03-01

A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rautman, Christopher Arthur; Lord, Anna Snider

Downhole sonar surveys from the four active U.S. Strategic Petroleum Reserve sites have been modeled and used to generate a four-volume sonar atlas, showing the three-dimensional geometry of each cavern. This volume 3 focuses on the Bryan Mound SPR site, located in southeastern Texas. Volumes 1, 2, and 4, respectively, present images for the Bayou Choctaw SPR site, Louisiana, the Big Hill SPR site, Texas, and the West Hackberry SPR site, Louisiana. The atlas uses a consistent presentation format throughout. The basic geometric measurements provided by the down-cavern surveys have also been used to generate a number of geometric attributes,more » the values of which have been mapped onto the geometric form of each cavern using a color-shading scheme. The intent of the various geometrical attributes is to highlight deviations of the cavern shape from the idealized cylindrical form of a carefully leached underground storage cavern in salt. The atlas format does not allow interpretation of such geometric deviations and anomalies. However, significant geometric anomalies, not directly related to the leaching history of the cavern, may provide insight into the internal structure of the relevant salt dome.« less

Computational Study of the Adsorption of Dimethyl Methylphosphonate (DMMP) on the (010) Surface of Anatase TiO2 With and Without Faceting

DTIC Science & Technology

2009-12-05

surface area of anatase nanocrystals [6] and to be es- pecially active in photocatalysis [7]. Recent work by Dzwigaj et al. [8] has clearly shown that the...two-fold-coordinated (O2c) sites can also be involved in hydrogen bond (H-bond) formation. The effects, on the structure of the (100) and other...To reduce the computational cost , geometry optimization was done at the restricted Hartree Fock (RHF) level. This has previously been shown [36,37

Relationships among diet, physical activity, and dual plane dual-energy X-ray absorptiometry bone outcomes in pre-pubertalgirls.

PubMed

Ren, Jie; Brann, Lynn S; Bruening, Kay S; Scerpella, Tamara A; Dowthwaite, Jodi N

2017-12-01

In pre-pubertal girls, nutrient intakes and non-aquatic organized activity were evaluated as factors in vertebral body bone mass, structure, and strength. Activity, vitamin B 12 , and dietary fiber predicted bone outcomes most consistently. Exercise and vitamin B 12 appear beneficial, whereas high fiber intake appears to be adverse for vertebral body development. Childhood development sets the baseline for adult fracture risk. Most studies evaluate development using postero-anterior (PA) dual-energy X-ray absorptiometry (DXA) areal bone mineral density, bone mineral content, and bone mineral apparent density. In a prior analysis, we demonstrated that PA DXA reflects posterior element properties, rather than vertebral body fracture sites, such that loading is associated with subtle differences in vertebral body geometry, not 3D density. The current analysis is restricted to pre-pubertal girls, for a focused exploration of key nutrient intakes and physical activity as factors in dual plane indices of vertebral body geometry, density, and strength. This cross-sectional analysis used paired PA and supine lateral (LAT) lumbar spine DXA scans to assess "3D" vertebral body bone mineral apparent density (PALATBMAD), "3D" index of structural strength in axial compression (PALATIBS), and fracture risk index (PALATFRI). Diet data were collected using the Youth/Adolescent Questionnaire (YAQ, 1995); organized physical activity was recorded via calendar-based form. Pearson correlations and backward stepwise multiple linear regression analyzed associations among key nutrients, physical activity, and bone outcomes. After accounting for activity and key covariates, fiber, unsupplemented vitamin B 12 , zinc, carbohydrate, vitamin C, unsupplemented magnesium, and unsupplemented calcium intake explained significant variance for one or more bone outcomes (p < 0.05). After adjustment for influential key nutrients and covariates, activity exposure was associated with postero-anterior (PA) areal bone mineral density, PA bone mineral content, PA width, lateral (LAT) BMC, "3D" bone cross-sectional area (coronal plane), "3D" PALATIBS, and PALATFRI benefits (p < 0.05). Physical activity, fiber intake, and unsupplemented B 12 intake appear to influence vertebral body bone mass, density, geometry, and strength in well-nourished pre-pubertal girls; high fiber intakes may adversely affect childhood vertebral body growth.

Building Students' Understanding of Quadratic Equation Concept Using Naïve Geometry

ERIC Educational Resources Information Center

Fachrudin, Achmad Dhany; Putri, Ratu Ilma Indra; Darmawijoyo

2014-01-01

The purpose of this research is to know how Naïve Geometry method can support students' understanding about the concept of solving quadratic equations. In this article we will discuss one activities of the four activities we developed. This activity focused on how students linking the Naïve Geometry method with the solving of the quadratic…

13C ENDOR Spectroscopy of Lipoxygenase-Substrate Complexes Reveals the Structural Basis for C-H Activation by Tunneling.

PubMed

Horitani, Masaki; Offenbacher, Adam R; Carr, Cody A Marcus; Yu, Tao; Hoeke, Veronika; Cutsail, George E; Hammes-Schiffer, Sharon; Klinman, Judith P; Hoffman, Brian M

2017-02-08

In enzymatic C-H activation by hydrogen tunneling, reduced barrier width is important for efficient hydrogen wave function overlap during catalysis. For native enzymes displaying nonadiabatic tunneling, the dominant reactive hydrogen donor-acceptor distance (DAD) is typically ca. 2.7 Å, considerably shorter than normal van der Waals distances. Without a ground state substrate-bound structure for the prototypical nonadiabatic tunneling system, soybean lipoxygenase (SLO), it has remained unclear whether the requisite close tunneling distance occurs through an unusual ground state active site arrangement or by thermally sampling conformational substates. Herein, we introduce Mn 2+ as a spin-probe surrogate for the SLO Fe ion; X-ray diffraction shows Mn-SLO is structurally faithful to the native enzyme. 13 C ENDOR then reveals the locations of 13 C10 and reactive 13 C11 of linoleic acid relative to the metal; 1 H ENDOR and molecular dynamics simulations of the fully solvated SLO model using ENDOR-derived restraints give additional metrical information. The resulting three-dimensional representation of the SLO active site ground state contains a reactive (a) conformer with hydrogen DAD of ∼3.1 Å, approximately van der Waals contact, plus an inactive (b) conformer with even longer DAD, establishing that stochastic conformational sampling is required to achieve reactive tunneling geometries. Tunneling-impaired SLO variants show increased DADs and variations in substrate positioning and rigidity, confirming previous kinetic and theoretical predictions of such behavior. Overall, this investigation highlights the (i) predictive power of nonadiabatic quantum treatments of proton-coupled electron transfer in SLO and (ii) sensitivity of ENDOR probes to test, detect, and corroborate kinetically predicted trends in active site reactivity and to reveal unexpected features of active site architecture.

Analytical study of nano-scale logical operations

NASA Astrophysics Data System (ADS)

Patra, Moumita; Maiti, Santanu K.

2018-07-01

A complete analytical prescription is given to perform three basic (OR, AND, NOT) and two universal (NAND, NOR) logic gates at nano-scale level using simple tailor made geometries. Two different geometries, ring-like and chain-like, are taken into account where in each case the bridging conductor is coupled to a local atomic site through a dangling bond whose site energy can be controlled by means of external gate electrode. The main idea is that when injecting electron energy matches with site energy of local atomic site transmission probability drops exactly to zero, whereas the junction exhibits finite transmission for other energies. Utilizing this prescription we perform logical operations, and, we strongly believe that the proposed results can be verified in laboratory. Finally, we numerically compute two-terminal transmission probability considering general models and the numerical results match exactly well with our analytical findings.

Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

PubMed Central

Gottwald, E; Gottwald, M; Dhein, S

1998-01-01

Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. 

 Keywords: dispersion;  epicardial activation-recovery interval;  ischaemia PMID:9659194

Italian Case Studies Modelling Complex Earthquake Sources In PSHA

NASA Astrophysics Data System (ADS)

Gee, Robin; Peruzza, Laura; Pagani, Marco

2017-04-01

This study presents two examples of modelling complex seismic sources in Italy, done in the framework of regional probabilistic seismic hazard assessment (PSHA). The first case study is for an area centred around Collalto Stoccaggio, a natural gas storage facility in Northern Italy, located within a system of potentially seismogenic thrust faults in the Venetian Plain. The storage exploits a depleted natural gas reservoir located within an actively growing anticline, which is likely driven by the Montello Fault, the underlying blind thrust. This fault has been well identified by microseismic activity (M<2) detected by a local seismometric network installed in 2012 (http://rete-collalto.crs.inogs.it/). At this time, no correlation can be identified between the gas storage activity and local seismicity, so we proceed with a PSHA that considers only natural seismicity, where the rates of earthquakes are assumed to be time-independent. The source model consists of faults and distributed seismicity to consider earthquakes that cannot be associated to specific structures. All potentially active faults within 50 km of the site are considered, and are modelled as 3D listric surfaces, consistent with the proposed geometry of the Montello Fault. Slip rates are constrained using available geological, geophysical and seismological information. We explore the sensitivity of the hazard results to various parameters affected by epistemic uncertainty, such as ground motions prediction equations with different rupture-to-site distance metrics, fault geometry, and maximum magnitude. The second case is an innovative study, where we perform aftershock probabilistic seismic hazard assessment (APSHA) in Central Italy, following the Amatrice M6.1 earthquake of August 24th, 2016 (298 casualties) and the subsequent earthquakes of Oct 26th and 30th (M6.1 and M6.6 respectively, no deaths). The aftershock hazard is modelled using a fault source with complex geometry, based on literature data and field evidence associated with the August mainshock. Earthquake activity rates during the very first weeks after the deadly earthquake were used to calibrated an Omori-Utsu decay curve, and the magnitude distribution of aftershocks is assumed to follow a Gutenberg-Richter distribution. We apply uniform and non-uniform spatial distribution of the seismicity across the fault source, by modulating the rates as a decreasing function of distance from the mainshock. The hazard results are computed for short-exposure periods (1 month, before the occurrences of October earthquakes) and compared to the background hazard given by law (MPS04), and to observations at some reference sites. We also show the results of disaggregation computed for the city of Amatrice. Finally, we attempt to update the results in light of the new "main" events that occurred afterwards in the region. All source modeling and hazard calculations are performed using the OpenQuake engine. We discuss the novelties of these works, and the benefits and limitations of both analyses, particularly in such different contexts of seismic hazard.

X-ray absorption spectroscopic studies of the active sites of nickel- and copper-containing metalloproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Grace O.

1993-06-01

X-ray absorption spectroscopy (XAS) is a useful tool for obtaining structural and chemical information about the active sites of metalloproteins and metalloenzymes. Information may be obtained from both the edge region and the extended X-ray absorption fine structure (EXAFS) or post-edge region of the K-edge X-ray absorption spectrum of a metal center in a compound. The edge contains information about the valence electronic structure of the atom that absorbs the X-rays. It is possible in some systems to infer the redox state of the metal atom in question, as well as the geometry and nature of ligands connected to it,more » from the features in the edge in a straightforward manner. The EXAFS modulations, being produced by the backscattering of the ejected photoelectron from the atoms surrounding the metal atom, provide, when analyzed, information about the number and type of neighbouring atoms, and the distances at which they occur. In this thesis, analysis of both the edge and EXAFS regions has been used to gain information about the active sites of various metalloproteins. The metalloproteins studied were plastocyanin (Pc), laccase and nickel carbon monoxide dehydrogenase (Ni CODH). Studies of Cu(I)-imidazole compounds, related to the protein hemocyanin, are also reported here.« less

Theoretical Insights into Methane C–H Bond Activation on Alkaline Metal Oxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aljama, Hassan; Nørskov, Jens K.; Abild-Pedersen, Frank

Here, we investigate the role of alkaline metal oxides (AMO) (MgO, CaO, and SrO) in activating the C–H bond in methane. We also use Density Functional Theory (DFT) and microkinetic modeling to study the catalytic elementary steps in breaking the C–H bond in methane and creating the methyl radical, a precursor prior to creating C2 products. We also study the effects of surface geometry on the catalytic activity of AMO by examining terrace and step sites. We observe that the process of activating methane depends strongly on the structure of the AMO. When the AMO surface is doped with anmore » alkali metal, the transition state (TS) structure has a methyl radical-like behavior, where the methyl radical interacts weakly with the AMO surface. In this case, the TS energy scales with the hydrogen binding energy. On pure AMO, the TS interacts with AMO surface oxygen as well as the metal atom on the surface, and consequently the TS energy scales with the binding energy of hydrogen and methyl. We study the activity of AMO using a mean-field microkinetic model. The results indicate that terrace sites have similar catalytic activity, with the exception of MgO(100). Step sites bind hydrogen more strongly, making them more active, and this confirms previously reported experimental results. We map the catalytic activity of AMO using a volcano plot with two descriptors: the methyl and the hydrogen binding energies, with the latter being a more significant descriptor. The microkinetic model results suggest that C–H bond dissociation is not always the rate-limiting step. At weak hydrogen binding, the reaction is limited by C–H bond activation. At strong hydrogen binding, the reaction is limited due to poisoning of the active site. We found an increase in activity of AMO as the basicity increased. Finally, the developed microkinetic model allows screening for improved catalysts using simple calculations of the hydrogen binding energy.« less

Theoretical Insights into Methane C–H Bond Activation on Alkaline Metal Oxides

DOE PAGES

Aljama, Hassan; Nørskov, Jens K.; Abild-Pedersen, Frank

2017-07-17

Here, we investigate the role of alkaline metal oxides (AMO) (MgO, CaO, and SrO) in activating the C–H bond in methane. We also use Density Functional Theory (DFT) and microkinetic modeling to study the catalytic elementary steps in breaking the C–H bond in methane and creating the methyl radical, a precursor prior to creating C2 products. We also study the effects of surface geometry on the catalytic activity of AMO by examining terrace and step sites. We observe that the process of activating methane depends strongly on the structure of the AMO. When the AMO surface is doped with anmore » alkali metal, the transition state (TS) structure has a methyl radical-like behavior, where the methyl radical interacts weakly with the AMO surface. In this case, the TS energy scales with the hydrogen binding energy. On pure AMO, the TS interacts with AMO surface oxygen as well as the metal atom on the surface, and consequently the TS energy scales with the binding energy of hydrogen and methyl. We study the activity of AMO using a mean-field microkinetic model. The results indicate that terrace sites have similar catalytic activity, with the exception of MgO(100). Step sites bind hydrogen more strongly, making them more active, and this confirms previously reported experimental results. We map the catalytic activity of AMO using a volcano plot with two descriptors: the methyl and the hydrogen binding energies, with the latter being a more significant descriptor. The microkinetic model results suggest that C–H bond dissociation is not always the rate-limiting step. At weak hydrogen binding, the reaction is limited by C–H bond activation. At strong hydrogen binding, the reaction is limited due to poisoning of the active site. We found an increase in activity of AMO as the basicity increased. Finally, the developed microkinetic model allows screening for improved catalysts using simple calculations of the hydrogen binding energy.« less

Crystallographic comparison of manganese- and iron-dependent homoprotocatechuate 2,3-dioxygenases.

PubMed

Vetting, Matthew W; Wackett, Lawrence P; Que, Lawrence; Lipscomb, John D; Ohlendorf, Douglas H

2004-04-01

The X-ray crystal structures of homoprotocatechuate 2,3-dioxygenases isolated from Arthrobacter globiformis and Brevibacterium fuscum have been determined to high resolution. These enzymes exhibit 83% sequence identity, yet their activities depend on different transition metals, Mn2+ and Fe2+, respectively. The structures allow the origins of metal ion selectivity and aspects of the molecular mechanism to be examined in detail. The homotetrameric enzymes belong to the type I family of extradiol dioxygenases (vicinal oxygen chelate superfamily); each monomer has four betaalphabetabetabeta modules forming two structurally homologous N-terminal and C-terminal barrel-shaped domains. The active-site metal is located in the C-terminal barrel and is ligated by two equatorial ligands, H214NE1 and E267OE1; one axial ligand, H155NE1; and two to three water molecules. The first and second coordination spheres of these enzymes are virtually identical (root mean square difference over all atoms, 0.19 A), suggesting that the metal selectivity must be due to changes at a significant distance from the metal and/or changes that occur during folding. The substrate (2,3-dihydroxyphenylacetate [HPCA]) chelates the metal asymmetrically at sites trans to the two imidazole ligands and interacts with a unique, mobile C-terminal loop. The loop closes over the bound substrate, presumably to seal the active site as the oxygen activation process commences. An "open" coordination site trans to E267 is the likely binding site for O2. The geometry of the enzyme-substrate complexes suggests that if a transiently formed metal-superoxide complex attacks the substrate without dissociation from the metal, it must do so at the C-3 position. Second-sphere active-site residues that are positioned to interact with the HPCA and/or bound O2 during catalysis are identified and discussed in the context of current mechanistic hypotheses.

The effect of reservoir geometry, injection and production parameters and permeability structure on induced seismicity

NASA Astrophysics Data System (ADS)

Hosseini, S. M.; Goebel, T.; Aminzadeh, F.

2015-12-01

The recent increase in injection induced seismicity (IIS) in previously less seismically active regions highlighted a need for better mitigation strategies and physics-based models of induced seismicity. Previous models of pressure diffusion and fluid flow investigated the change in Coulomb stress as a result of induced pore-pressure perturbations (e.g. Zhang et al., 2013; Keranen et al., 2014; Hornbach et al., 2015; Segall and Lu, 2015). Here, we consider the additional effects of permeability structure, operational parameters and reservoir geometry. We numerically investigate the influence of net fluid injection volumes; linear, radial, and spherical reservoir geometry; as well as reservoir size. The latter can have a substantial effect on changes in Coulomb stress and subsequent induced seismicity. We report on results from two series of model runs, which explored pressure changes caused by wastewater disposal and water flooding. We observed that a typical water flooding operation that includes production wells and injectors has a lower probability of inducing seismicity. Our observations are in agreement with assessment by National Research Council report on induced seismicity (2012). We developed a third suite of models that investigate the effect of permeability structure on injection-induced seismicity. We examine two cases of wastewater disposal in proximity to active faults: 1) in Central Illinois Basin and 2) in central California. In both cases, we observed that the size of the reservoir, presence of faults, and permeability contrast relative to the host rock, strongly influences the pressure changes with distance and time. These pressure changes vary widely but can easily lead to fault instability and seismic activity at up to 10 km distance from the injection well. The results of this study may help to select safe injection sites and operational conditions in order to minimize injection induced seismicity hazard.

Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen

Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive because of uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for the treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligandmore » positioned in an adjacent pocket. With the geometry of the RPE65–substrate complex clarified, we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. Finally, these data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules.« less

Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

DOE PAGES

Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; ...

2015-04-20

Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive because of uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for the treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligandmore » positioned in an adjacent pocket. With the geometry of the RPE65–substrate complex clarified, we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. Finally, these data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules.« less

Catalytic mechanism of a retinoid isomerase essential for vertebrate vision

PubMed Central

Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; Li, Qingjiang; Shi, Wuxian; Sui, Xuewu; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

2015-01-01

Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase, RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive due to uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligand positioned in an adjacent pocket. With the geometry of the RPE65-substrate complex clarified we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. These data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules. PMID:25894083

Pharmacophore screening of the protein data bank for specific binding site chemistry.

PubMed

Campagna-Slater, Valérie; Arrowsmith, Andrew G; Zhao, Yong; Schapira, Matthieu

2010-03-22

A simple computational approach was developed to screen the Protein Data Bank (PDB) for putative pockets possessing a specific binding site chemistry and geometry. The method employs two commonly used 3D screening technologies, namely identification of cavities in protein structures and pharmacophore screening of chemical libraries. For each protein structure, a pocket finding algorithm is used to extract potential binding sites containing the correct types of residues, which are then stored in a large SDF-formatted virtual library; pharmacophore filters describing the desired binding site chemistry and geometry are then applied to screen this virtual library and identify pockets matching the specified structural chemistry. As an example, this approach was used to screen all human protein structures in the PDB and identify sites having chemistry similar to that of known methyl-lysine binding domains that recognize chromatin methylation marks. The selected genes include known readers of the histone code as well as novel binding pockets that may be involved in epigenetic signaling. Putative allosteric sites were identified on the structures of TP53BP1, L3MBTL3, CHEK1, KDM4A, and CREBBP.

Sonar atlas of caverns comprising the U.S. Strategic Petroleum Reserve. Volume 4, West Hackberry site, Louisiana.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rautman, Christopher Arthur; Lord, Anna Snider

2007-09-01

Downhole sonar surveys from the four active U.S. Strategic Petroleum Reserve sites have been modeled and used to generate a four-volume sonar atlas, showing the three-dimensional geometry of each cavern. This volume 4 focuses on the West Hackberry SPR site, located in southwestern Louisiana. Volumes 1, 2, and 3, respectively, present images for the Bayou Choctaw SPR site, Louisiana, the Big Hill SPR site, Texas, and the Bryan Mound SPR site, Texas. The atlas uses a consistent presentation format throughout. The basic geometric measurements provided by the down-cavern surveys have also been used to generate a number of geometric attributes,more » the values of which have been mapped onto the geometric form of each cavern using a color-shading scheme. The intent of the various geometrical attributes is to highlight deviations of the cavern shape from the idealized cylindrical form of a carefully leached underground storage cavern in salt. The atlas format does not allow interpretation of such geometric deviations and anomalies. However, significant geometric anomalies, not directly related to the leaching history of the cavern, may provide insight into the internal structure of the relevant salt dome.« less

Sonar atlas of caverns comprising the U.S. Strategic Petroleum Reserve. Volume 2, Big Hill Site, Texas.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rautman, Christopher Arthur; Lord, Anna Snider

2007-08-01

Downhole sonar surveys from the four active U.S. Strategic Petroleum Reserve sites have been modeled and used to generate a four-volume sonar atlas, showing the three-dimensional geometry of each cavern. This volume 2 focuses on the Big Hill SPR site, located in southeastern Texas. Volumes 1, 3, and 4, respectively, present images for the Bayou Choctaw SPR site, Louisiana, the Bryan Mound SPR site, Texas, and the West Hackberry SPR site, Louisiana. The atlas uses a consistent presentation format throughout. The basic geometric measurements provided by the down-cavern surveys have also been used to generate a number of geometric attributes,more » the values of which have been mapped onto the geometric form of each cavern using a color-shading scheme. The intent of the various geometrical attributes is to highlight deviations of the cavern shape from the idealized cylindrical form of a carefully leached underground storage cavern in salt. The atlas format does not allow interpretation of such geometric deviations and anomalies. However, significant geometric anomalies, not directly related to the leaching history of the cavern, may provide insight into the internal structure of the relevant salt dome.« less

Sonar atlas of caverns comprising the U.S. Strategic Petroleum Reserve. Volume 1, Bayou Choctaw site, Louisiana.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rautman, Christopher Arthur; Lord, Anna Snider

2007-10-01

Downhole sonar surveys from the four active U.S. Strategic Petroleum Reserve sites have been modeled and used to generate a four-volume sonar atlas, showing the three-dimensional geometry of each cavern. This volume 1 focuses on the Bayou Choctaw SPR site, located in southern Louisiana. Volumes 2, 3, and 4, respectively, present images for the Big Hill SPR site, Texas, the Bryan Mound SPR site, Texas, and the West Hackberry SPR site, Louisiana. The atlas uses a consistent presentation format throughout. The basic geometric measurements provided by the down-cavern surveys have also been used to generate a number of geometric attributes,more » the values of which have been mapped onto the geometric form of each cavern using a color-shading scheme. The intent of the various geometrical attributes is to highlight deviations of the cavern shape from the idealized cylindrical form of a carefully leached underground storage cavern in salt. The atlas format does not allow interpretation of such geometric deviations and anomalies. However, significant geometric anomalies, not directly related to the leaching history of the cavern, may provide insight into the internal structure of the relevant salt dome.« less

Electrical Advantages of Dendritic Spines

PubMed Central

Gulledge, Allan T.; Carnevale, Nicholas T.; Stuart, Greg J.

2012-01-01

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations. PMID:22532875

Biochemical profiling in silico--predicting substrate specificities of large enzyme families.

PubMed

Tyagi, Sadhna; Pleiss, Juergen

2006-06-25

A general high-throughput method for in silico biochemical profiling of enzyme families has been developed based on covalent docking of potential substrates into the binding sites of target enzymes. The method has been tested by systematically docking transition state--analogous intermediates of 12 substrates into the binding sites of 20 alpha/beta hydrolases from 15 homologous families. To evaluate the effect of side chain orientations to the docking results, 137 crystal structures were included in the analysis. A good substrate must fulfil two criteria: it must bind in a productive geometry with four hydrogen bonds between the substrate and the catalytic histidine and the oxyanion hole, and a high affinity of the enzyme-substrate complex as predicted by a high docking score. The modelling results in general reproduce experimental data on substrate specificity and stereoselectivity: the differences in substrate specificity of cholinesterases toward acetyl- and butyrylcholine, the changes of activity of lipases and esterases upon the size of the acid moieties, activity of lipases and esterases toward tertiary alcohols, and the stereopreference of lipases and esterases toward chiral secondary alcohols. Rigidity of the docking procedure was the major reason for false positive and false negative predictions, as the geometry of the complex and docking score may sensitively depend on the orientation of individual side chains. Therefore, appropriate structures have to be identified. In silico biochemical profiling provides a time efficient and cost saving protocol for virtual screening to identify the potential substrates of the members of large enzyme family from a library of molecules.

Understanding the HIV-1 protease reactivity with DFT: what do we gain from recent functionals?

PubMed

Garrec, J; Sautet, P; Fleurat-Lessard, P

2011-07-07

The modeling of HIV-1 plays a crucial role in the understanding of its reactivity and its interactions with specific drugs. In this work, we propose a medium sized model to test the ability of a variety of quantum chemistry approaches to provide reasonable geometric parameters and energetics for this system. Although our model is large enough to include the main polarizing groups of the active site, it is small enough to be used within full quantum studies up to the second order Møller-Plesset (MP2) level with extrapolations to coupled cluster CCSD(T) level. These high level calculations are used as reference to assess the ability of electronic structure methods (semiempirical and DFT) to provide accurate geometries and energies for the HIV-1 protease reaction. All semiempirical methods fail to describe the geometry of the protease active site. Within DFT, pure generalized gradient approximation (GGA) functionals have difficulty in reproducing the reaction energy and underestimate the barrier. Hybrid and/or meta GGA approaches do not yield a consistent improvement. The best results are obtained with hybrid GGA B3LYP or X3LYP and with hybrid meta GGA functionals with a fraction of exact exchange around 30-40%, such as M06, B1B95, or BMK functionals. On the basis of these results, we propose an accurate and computationally efficient strategy, employing quantum chemistry methods. This is applied here to study the protonation state of the reaction intermediate and could be easily used in further QM/MM studies.

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι.

PubMed

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F Peter

2016-09-30

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn 2+ than Mg 2+ The human germline R96G variant impairs both Mn 2+ -dependent and Mg 2+ -dependent activities of pol ι, whereas the Δ1-25 variant selectively enhances its Mg 2+ -dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1-445) proteins. The presence of Mn 2+ (0.15 mm) instead of Mg 2+ (2 mm) caused a 770-fold increase in efficiency (k pol /K d ,dCTP ) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in K d ,dCTP The R96G and Δ1-25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in k pol /K d ,dCTP for dCTP insertion opposite G with Mg 2+ when compared with wild type, substantially attenuated by substitution with Mn 2+ Crystal structures of pol ι ternary complexes, including the primer terminus 3'-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg 2+ or Mn 2+ , revealed that Mn 2+ achieves more optimal octahedral coordination geometry than Mg 2+ , with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι*

PubMed Central

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F. Peter

2016-01-01

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+. The human germline R96G variant impairs both Mn2+-dependent and Mg2+-dependent activities of pol ι, whereas the Δ1–25 variant selectively enhances its Mg2+-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1–445) proteins. The presence of Mn2+ (0.15 mm) instead of Mg2+ (2 mm) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP. The R96G and Δ1–25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared with wild type, substantially attenuated by substitution with Mn2+. Crystal structures of pol ι ternary complexes, including the primer terminus 3′-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. PMID:27555320

Structural Model for the Flip-Flop Action in Thiamin Pyrophosphate-Dependent Human Pyruvate Dehydrogenase

NASA Technical Reports Server (NTRS)

Ciszak, Ewa; Dominiak, Paulina

2003-01-01

The derivative of vitamin B1 thiamin pyrophosphate (TPP) is a cofactor of enzymes performing catalysis in pathways of energy production, including (i) decarboxylation of alpha-keto acids followed by (ii) transketolation. These enzymes have shown a common mechanism of TPP activation by imposing an active V-conformation of this coenzyme that brings the N4 atom of the aminopyrimidine ring to the distance required for the intramolecular C-H N hydrogen-bonding with the C2- atom of the thiazolium ring. The reactive C2 atom of TPP is the nucleophile that attacks the carbonyl carbon of different substrates used by the TPP-dependent enzymes. The structure of the heterotetrameric human pyruvate dehydrogenase (Elp) recently determined in our laboratory (1) revealed the association pattern of the subunits and the specifics of two chemically equivalent cofactor binding sites. Dynamic nonequivalence of these two cofactor sites directs the flip-flop action of this enzyme, depending upon which two active sites effect each other (2). The crystal structure derived from the holo-form of Elp provided the basis for the model of the flip-flop action of Elp in which different steps of the catalytic reaction are performed in each of the two cofactor sites at any given moment, where these steps are governed by the concerted shuttle-like motion of the subunits. It is further proposed that balancing a hydrogen-bond network and related cofactor geometry determine the continuity of catalytic events.

kmos: A lattice kinetic Monte Carlo framework

NASA Astrophysics Data System (ADS)

Hoffmann, Max J.; Matera, Sebastian; Reuter, Karsten

2014-07-01

Kinetic Monte Carlo (kMC) simulations have emerged as a key tool for microkinetic modeling in heterogeneous catalysis and other materials applications. Systems, where site-specificity of all elementary reactions allows a mapping onto a lattice of discrete active sites, can be addressed within the particularly efficient lattice kMC approach. To this end we describe the versatile kmos software package, which offers a most user-friendly implementation, execution, and evaluation of lattice kMC models of arbitrary complexity in one- to three-dimensional lattice systems, involving multiple active sites in periodic or aperiodic arrangements, as well as site-resolved pairwise and higher-order lateral interactions. Conceptually, kmos achieves a maximum runtime performance which is essentially independent of lattice size by generating code for the efficiency-determining local update of available events that is optimized for a defined kMC model. For this model definition and the control of all runtime and evaluation aspects kmos offers a high-level application programming interface. Usage proceeds interactively, via scripts, or a graphical user interface, which visualizes the model geometry, the lattice occupations and rates of selected elementary reactions, while allowing on-the-fly changes of simulation parameters. We demonstrate the performance and scaling of kmos with the application to kMC models for surface catalytic processes, where for given operation conditions (temperature and partial pressures of all reactants) central simulation outcomes are catalytic activity and selectivities, surface composition, and mechanistic insight into the occurrence of individual elementary processes in the reaction network.

Regional Curves of Bankfull Channel Geometry for Non-Urban Streams in the Piedmont Physiographic Province, Virginia

USGS Publications Warehouse

Lotspeich, R. Russell

2009-01-01

Natural-channel design involves constructing a stream channel with the dimensions, slope, and plan-view pattern that would be expected to transport water and sediment and yet maintain habitat and aesthetics consistent with unimpaired stream segments, or reaches. Regression relations for bankfull stream characteristics based on drainage area, referred to as 'regional curves,' are used in natural stream channel design to verify field determinations of bankfull discharge and stream channel characteristics. One-variable, ordinary least-squares regressions relating bankfull discharge, bankfull cross-sectional area, bankfull width, bankfull mean depth, and bankfull slope to drainage area were developed on the basis of data collected at 17 streamflow-gaging stations in rural areas with less than 20 percent urban land cover within the basin area (non-urban areas) of the Piedmont Physiographic Province in Virginia. These regional curves can be used to estimate the bankfull discharge and bankfull channel geometry when the drainage area of a watershed is known. Data collected included bankfull cross-sectional geometry, flood-plain geometry, and longitudinal profile data. In addition, particle-size distributions of streambed material were determined, and data on basin characteristics were compiled for each reach. Field data were analyzed to determine bankfull cross-sectional area, bankfull width, bankfull mean depth, bankfull discharge, bankfull channel slope, and D50 and D84 particle sizes at each site. The bankfull geometry from the 17 sites surveyed during this study represents the average of two riffle cross sections for each site. Regional curves developed for the 17 sites had coefficient of determination (R2) values of 0.950 for bankfull cross-sectional area, 0.913 for bankfull width, 0.915 for bankfull mean depth, 0.949 for bankfull discharge, and 0.497 for bankfull channel slope. The regional curves represent conditions for streams with defined channels and bankfull features in the Piedmont Physiographic Province in Virginia with drainage areas ranging from 0.29 to 111 square miles. All sites included in the development of the regional curves were located on streams with current or historical U.S. Geological Survey streamflow-gaging stations. These curves can be used to verify bankfull features identified in the field and bankfull stage for ungaged streams in non-urban areas.

Whispering gallery mode resonators for rapid label-free biosensing in small volume droplets.

PubMed

Wildgen, Sarah M; Dunn, Robert C

2015-03-23

Rapid biosensing requires fast mass transport of the analyte to the surface of the sensing element. To optimize analysis times, both mass transport in solution and the geometry and size of the sensing element need to be considered. Small dielectric spheres, tens of microns in diameter, can act as label-free biosensors using whispering gallery mode (WGM) resonances. WGM resonances are sensitive to the effective refractive index, which changes upon analyte binding to recognition sites on functionalized resonators. The spherical geometry and tens of microns diameter of these resonators provides an efficient target for sensing while their compact size enables detection in limited volumes. Here, we explore conditions leading to rapid analyte detection using WGM resonators as label-free sensors in 10 μL sample droplets. Droplet evaporation leads to potentially useful convective mixing, but also limits the time over which analysis can be completed. We show that active droplet mixing combined with initial binding rate measurements is required for accurate nanomolar protein quantification within the first minute following injection.

Computational insights into crystal plane dependence of thermal activity of anion (C and N)-substituted titania.

PubMed

V, Sai Phani Kumar; Arya, Rahul; Deshpande, Parag A

2017-11-29

Geometry optimizations of anion (C and N) doped anatase TiO 2 were carried out by using DFT+U calculations. Various anion vacancy sites were examined to study the synergistic effects of anion doping accompanied with anion vacancy formation on lattice oxygen activation. Two non-identical crystal planes (0 0 1) and (1 0 0) were chosen for C and N substitutions. Energetically favoured N-vacancy pairs were identified on TiO 2 surfaces. Substitution of N along with anion vacancies at various sites was energetically more favoured than that of C-doping in bulk TiO 2 while the energies were comparable for surface substitutions. Bond length distributions due to the formation of differential bonds were determined. Net oxygen activation and accompanying reversible oxygen exchange capacities were compared for TiO 2-2x C x and TiO 2-3x N 2x . Substitution of C in the surface exposed (1 0 0) plane of TiO 2 resulted in 47.6% and 23.8% of bond elongation and compression, respectively, resulting in 23.8% of net oxygen activation which was higher when compared to N substitution in the (1 0 0) plane of TiO 2 resulting in a net oxygen activation of 17%.

Bone geometry in young male and female football players: a peripheral quantitative computed tomography (pQCT) study.

PubMed

Lozano-Berges, Gabriel; Matute-Llorente, Ángel; Gómez-Bruton, Alejandro; González-Agüero, Alex; Vicente-Rodríguez, Germán; Casajús, José A

2018-05-08

The present study shows that football practice during growth may improve bone geometry in male and female football players. However, only females had better bone strength in comparison with controls. The aim of this study was to compare bone geometry in adolescent football players and controls. A total of 107 football players (71 males/36 females; mean age 12.7 ± 0.6/12.7 ± 0.6 years) and 42 controls (20 males/22 females; mean age 13.1 ± 1.4/12.7 ± 1.3 years) participated in this study. Total and trabecular volumetric bone mineral content (Tt.BMC/Tb.BMC), cross-sectional area (Tt.Ar/Tb.Ar), and bone strength index (BSI) were measured at 4% site of the non-dominant tibia by peripheral quantitative computed tomography (pQCT). Moreover, Tt.BMC, cortical BMC (Ct.BMC), Tt.Ar, cortical Ar (Ct.Ar), cortical thickness (Ct.Th), periosteal circumference (PC), endosteal circumference (EC), fracture load in X-axis, and polar strength strain index (SSIp) were measured at 38% site of the tibia. Multivariate analyses of covariance were used to compare bone pQCT variables between football players and controls using the tibia length and maturity offset as covariates. Female football players demonstrated 13.8-16.4% higher BSI, Ct.Th, fracture load in X-axis, and SSIp than controls (p < .0036). Males showed no significant differences in bone strength when compared to controls (p > .0036). In relation to bone mineral content and area, male football players showed 8.8% higher Tt.Ar and Tb.Ar at the 4% site of the tibia when compared to controls; whereas 13.8-15.8% higher Tt.BMC, Ct.BMC, and Ct.Ar at the 38% site of the tibia were found in female football players than controls (p < .0036). In this study, female adolescent football players presented better bone geometry and strength values than controls. In contrast, only bone geometry was higher in male football players than controls.

Origins of the brain networks for advanced mathematics in expert mathematicians

PubMed Central

Amalric, Marie; Dehaene, Stanislas

2016-01-01

The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit. PMID:27071124

Origins of the brain networks for advanced mathematics in expert mathematicians.

PubMed

Amalric, Marie; Dehaene, Stanislas

2016-05-03

The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit.

Isolated oxygen defects in 3C- and 4H-SiC: A theoretical study

NASA Astrophysics Data System (ADS)

Gali, A.; Heringer, D.; Deák, P.; Hajnal, Z.; Frauenheim, Th.; Devaty, R. P.; Choyke, W. J.

2002-09-01

Ab initio calculations in the local-density approximation have been carried out in SiC to determine the possible configurations of the isolated oxygen impurity. Equilibrium geometry and occupation levels were calculated. Substitutional oxygen in 3C-SiC is a relatively shallow effective mass like double donor on the carbon site (OC) and a hyperdeep double donor on the Si site (OSi). In 4H-SiC OC is still a double donor but with a more localized electron state. In 3C-SiC OC is substantially more stable under any condition than OSi or interstitial oxygen (Oi). In 4H-SiC OC is also the most stable one except for heavy n-type doping. We propose that OC is at the core of the electrically active oxygen-related defect family found by deep level transient spectroscopy in 4H-SiC. The consequences of the site preference of oxygen on the SiC/SiO2 interface are discussed.

Principles for designing proteins with cavities formed by curved β sheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheetmore » curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.« less

Effect of stretching on the ballistic conductance of Au nanocontacts in presence of CO: A density functional study

NASA Astrophysics Data System (ADS)

Sclauzero, Gabriele; Dal Corso, Andrea; Smogunov, Alexander

2012-04-01

CO adsorption on an Au monatomic chain is studied within density functional theory in nanocontact geometries as a function of the contact stretching. We compare the bridge and atop adsorption sites of CO, finding that the bridge site is energetically favored at all strains studied here. Atop adsorption gives rise to an almost complete suppression of the ballistic conductance of the nanocontact, while adsorption at the bridge site results in a conductance value close to 0.6G0, in agreement with previous experimental data. We show that only the bridge site can qualitatively account for the evolution of the conductance as a function of the contact stretching observed in the experimental conductance traces. The numerical discrepancy between the theoretical and experimental conductance slopes is rationalized through a simple model for the elastic response of the metallic leads. We also verify that our conductance values are not affected by the specific choice of the nanocontact geometry by comparing two different atomistic models for the tips.

Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the canine heart.

PubMed

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

2012-01-01

Single-beat imaging of myocardial activation promises to aid in both cardiovascular research and clinical medicine. In the present study we validate a three-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of simultaneous 3D intracardiac mapping to assess its capability to localize endocardial and epicardial initiation sites and image global activation sequences during pacing and ventricular tachycardia (VT) in the canine heart. Body surface potentials were measured simultaneously with bipolar electrical recordings in a closed-chest condition in healthy canines. Computed tomography images were obtained after the mapping study to construct realistic geometry models. Data analysis was performed on paced rhythms and VTs induced by norepinephrine (NE). The noninvasively reconstructed activation sequence was in good agreement with the simultaneous measurements from 3D cardiac mapping with a correlation coefficient of 0.74 ± 0.06, a relative error of 0.29 ± 0.05, and a root mean square error of 9 ± 3 ms averaged over 460 paced beats and 96 ectopic beats including premature ventricular complexes, couplets, and nonsustained monomorphic VTs and polymorphic VTs. Endocardial and epicardial origins of paced beats were successfully predicted in 72% and 86% of cases, respectively, during left ventricular pacing. The NE-induced ectopic beats initiated in the subendocardium by a focal mechanism. Sites of initial activation were estimated to be ∼7 mm from the measured initiation sites for both the paced beats and ectopic beats. For the polymorphic VTs, beat-to-beat dynamic shifts of initiation site and activation pattern were characterized by the reconstruction. The present results suggest that 3DCEI can noninvasively image the 3D activation sequence and localize the origin of activation of paced beats and NE-induced VTs in the canine heart with good accuracy. This 3DCEI technique offers the potential to aid interventional therapeutic procedures for treating ventricular arrhythmias arising from epicardial or endocardial sites and to noninvasively assess the mechanisms of these arrhythmias.

Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the canine heart

PubMed Central

Han, Chengzong; Pogwizd, Steven M.; Killingsworth, Cheryl R.

2012-01-01

Single-beat imaging of myocardial activation promises to aid in both cardiovascular research and clinical medicine. In the present study we validate a three-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of simultaneous 3D intracardiac mapping to assess its capability to localize endocardial and epicardial initiation sites and image global activation sequences during pacing and ventricular tachycardia (VT) in the canine heart. Body surface potentials were measured simultaneously with bipolar electrical recordings in a closed-chest condition in healthy canines. Computed tomography images were obtained after the mapping study to construct realistic geometry models. Data analysis was performed on paced rhythms and VTs induced by norepinephrine (NE). The noninvasively reconstructed activation sequence was in good agreement with the simultaneous measurements from 3D cardiac mapping with a correlation coefficient of 0.74 ± 0.06, a relative error of 0.29 ± 0.05, and a root mean square error of 9 ± 3 ms averaged over 460 paced beats and 96 ectopic beats including premature ventricular complexes, couplets, and nonsustained monomorphic VTs and polymorphic VTs. Endocardial and epicardial origins of paced beats were successfully predicted in 72% and 86% of cases, respectively, during left ventricular pacing. The NE-induced ectopic beats initiated in the subendocardium by a focal mechanism. Sites of initial activation were estimated to be ∼7 mm from the measured initiation sites for both the paced beats and ectopic beats. For the polymorphic VTs, beat-to-beat dynamic shifts of initiation site and activation pattern were characterized by the reconstruction. The present results suggest that 3DCEI can noninvasively image the 3D activation sequence and localize the origin of activation of paced beats and NE-induced VTs in the canine heart with good accuracy. This 3DCEI technique offers the potential to aid interventional therapeutic procedures for treating ventricular arrhythmias arising from epicardial or endocardial sites and to noninvasively assess the mechanisms of these arrhythmias. PMID:21984548

Converting Transaldolase into Aldolase through Swapping of the Multifunctional Acid-Base Catalyst: Common and Divergent Catalytic Principles in F6P Aldolase and Transaldolase.

PubMed

Sautner, Viktor; Friedrich, Mascha Miriam; Lehwess-Litzmann, Anja; Tittmann, Kai

2015-07-28

Transaldolase (TAL) and fructose-6-phosphate aldolase (FSA) both belong to the class I aldolase family and share a high degree of structural similarity and sequence identity. The molecular basis of the different reaction specificities (transferase vs aldolase) has remained enigmatic. A notable difference between the active sites is the presence of either a TAL-specific Glu (Gln in FSA) or a FSA-specific Tyr (Phe in TAL). Both residues seem to have analoguous multifunctional catalytic roles but are positioned at different faces of the substrate locale. We have engineered a TAL double variant (Glu to Gln and Phe to Tyr) with an active site resembling that of FSA. This variant indeed exhibits aldolase activity as its main activity with a catalytic efficiency even larger than that of authentic FSA, while TAL activity is greatly impaired. Structural analysis of this variant in complex with the dihydroxyacetone Schiff base formed upon substrate cleavage identifies the introduced Tyr (genuine in FSA) to catalyze protonation of the central carbanion-enamine intermediate as a key determinant of the aldolase reaction. Our studies pinpoint that the Glu in TAL and the Tyr in FSA, although located at different positions at the active site, similarly act as bona fide acid-base catalysts in numerous catalytic steps, including substrate binding, dehydration of the carbinolamine, and substrate cleavage. We propose that the different spatial positions of the multifunctional Glu in TAL and of the corresponding multifunctional Tyr in FSA relative to the substrate locale are critically controlling reaction specificity through either unfavorable (TAL) or favorable (FSA) geometry of proton transfer onto the common carbanion-enamine intermediate. The presence of both potential acid-base residues, Glu and Tyr, in the active site of TAL has deleterious effects on substrate binding and cleavage, most likely resulting from a differently organized H-bonding network. Large-scale motions of the protein associated with opening and closing of the active site that seem to bear relevance for catalysis are observed as covalent intermediates are exclusively observed in the "closed" conformation of the active site. Pre-steady-state kinetics are used to monitor catalytic processes and structural transitions and to refine the kinetic framework of TAL catalysis.

Creating Dynamic Learning Environment to Enhance Students’ Engagement in Learning Geometry

NASA Astrophysics Data System (ADS)

Sariyasa

2017-04-01

Learning geometry gives many benefits to students. It strengthens the development of deductive thinking and reasoning; it also provides an opportunity to improve visualisation and spatial ability. Some studies, however, have pointed out the difficulties that students encountered when learning geometry. A preliminary study by the author in Bali revealed that one of the main problems was teachers’ difficulties in delivering geometry instruction. It was partly due to the lack of appropriate instructional media. Coupling with dynamic geometry software, dynamic learning environments is a promising solution to this problem. Employing GeoGebra software supported by the well-designed instructional process may result in more meaningful learning, and consequently, students are motivated to engage in the learning process more deeply and actively. In this paper, we provide some examples of GeoGebra-aided learning activities that allow students to interactively explore and investigate geometry concepts and the properties of geometry objects. Thus, it is expected that such learning environment will enhance students’ internalisation process of geometry concepts.

Endpoint-based parallel data processing with non-blocking collective instructions in a parallel active messaging interface of a parallel computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Archer, Charles J; Blocksome, Michael A; Cernohous, Bob R

Methods, apparatuses, and computer program products for endpoint-based parallel data processing with non-blocking collective instructions in a parallel active messaging interface (`PAMI`) of a parallel computer are provided. Embodiments include establishing by a parallel application a data communications geometry, the geometry specifying a set of endpoints that are used in collective operations of the PAMI, including associating with the geometry a list of collective algorithms valid for use with the endpoints of the geometry. Embodiments also include registering in each endpoint in the geometry a dispatch callback function for a collective operation and executing without blocking, through a single onemore » of the endpoints in the geometry, an instruction for the collective operation.« less

The Impact of Challenging Geometry and Measurement Units on the Achievement of Grade 2 Students

ERIC Educational Resources Information Center

Gavin, M. Katherine; Casa, Tutita M.; Adelson, Jill L.; Firmender, Janine M.

2013-01-01

The primary goal of Project M[superscript 2] was to develop and field-test challenging geometry and measurement units for all K-2 students. This article reports on the achievement results for students in Grade 2 at 12 urban and suburban sites in 4 states using the Iowa Tests of Basic Skills (ITBS) mathematics concepts subtest and an open-response…

Estimation of ICBM (Intercontinental Ballistic Missile) Performance Parameters

DTIC Science & Technology

1985-12-01

Formulation . . . . . 42 Staging Event Detection . . . . . . 43 Staging Estimator for Two State System . 46 * Staging Time and Vehicle Parameter...6 4. Land Based Sensor Coordinate System . . . . 10 5. Radar Site Geometry . . . . . . . . . 1 6. Observation Geometry . . . . . . . . . 12 7...Ve dm mi + dmi+d Figure 3. Rocket Thrust of fuel, the equation of motion of the rocket can be devel--S oped. This is a closed system of particles

The Impact of Advanced Geometry and Measurement Curriculum Units on the Mathematics Achievement of First-Grade Students

ERIC Educational Resources Information Center

Gavin, M. Katherine; Casa, Tutita M.; Firmender, Janine M.; Carroll, Susan R.

2013-01-01

The goal of Project M2 was to develop and field-test challenging geometry and measurement units for K-2 students. The units were developed using recommendations from gifted, mathematics, and early childhood education. This article reports on achievement results for students in Grade 1 at 12 diverse sites in four states using the Iowa Tests of…

Monoatomic and dimer Mn adsorption on the Au(111) surface from first principles

NASA Astrophysics Data System (ADS)

Muñoz, Francisco; Romero, Aldo H.; Mejía-López, Jose; Morán-López, J. L.

2011-05-01

A theoretical study based on the density functional theory of the adsorption of Mn monomers and dimers on a Au-(111) surface is presented. As necessary preliminary steps, the bulk and clean surface electronic structure are calculated, which agree well with previous reports. Then, the electronic structure of the Mn adatom, chemisorbed on four different surface geometries, is analyzed. It is found that the most stable geometry is when the Mn atom is chemisorbed on threefold coordinated sites. Using this geometry for a single adatom a second Mn atom is chemisorbed and the most stable dimer geometrical structure is calculated. The lowest-energy configuration corresponds to the molecule lying parallel to the surface, adsorbed on two topological equivalent threefold coordinated sites. It is also found that the lowest-energy magnetic configuration corresponds to the antiferromagnetic arrangement with individual magnetic moments of 4.64μB. Finally, it is concluded that the dimer is not stable and should fragment at the surface.

Ground-state geometries and stability of impurity doped clusters: LinBe and LinMg (n=1-12)

NASA Astrophysics Data System (ADS)

Deshpande, M.; Dhavale, A.; Zope, R. R.; Chacko, S.; Kanhere, D. G.

2000-12-01

We have investigated the ground-state geometries of LinBe and LinMg (n=1-12) clusters using ab initio molecular dynamics. These divalent impurities Be and Mg induce different geometries and follow a different growth path for n>5. LinMg clusters are significantly different from the host geometries while LinBe clusters can be approximately viewed as Be occupying an interstitial site in the host. Our results indicate that Be gets trapped inside the Li cage, while Mg remains on the surface of the cluster. Mg-induced geometries become three-dimensional earlier at n=4 as compared to the Be system. In spite of a distinct arrangement of atoms in both cases the character of the wave functions in the d manifold is remarkably similar. In both cases an eight valence electron system has been found to be the most stable, in conformity with the spherical jellium model.

The Copper Active Site of CBM33 Polysaccharide Oxygenases

PubMed Central

2013-01-01

The capacity of metal-dependent fungal and bacterial polysaccharide oxygenases, termed GH61 and CBM33, respectively, to potentiate the enzymatic degradation of cellulose opens new possibilities for the conversion of recalcitrant biomass to biofuels. GH61s have already been shown to be unique metalloenzymes containing an active site with a mononuclear copper ion coordinated by two histidines, one of which is an unusual τ-N-methylated N-terminal histidine. We now report the structural and spectroscopic characterization of the corresponding copper CBM33 enzymes. CBM33 binds copper with high affinity at a mononuclear site, significantly stabilizing the enzyme. X-band EPR spectroscopy of Cu(II)-CBM33 shows a mononuclear type 2 copper site with the copper ion in a distorted axial coordination sphere, into which azide will coordinate as evidenced by the concomitant formation of a new absorption band in the UV/vis spectrum at 390 nm. The enzyme’s three-dimensional structure contains copper, which has been photoreduced to Cu(I) by the incident X-rays, confirmed by X-ray absorption/fluorescence studies of both aqueous solution and intact crystals of Cu-CBM33. The single copper(I) ion is ligated in a T-shaped configuration by three nitrogen atoms from two histidine side chains and the amino terminus, similar to the endogenous copper coordination geometry found in fungal GH61. PMID:23540833

Absorbed photosynthetically active radiation of steppe vegetation and sun-view geometry effects on APAR estimates

NASA Technical Reports Server (NTRS)

Walter-Shea, E. A.; Blad, B. L.; Mesarch, M. A.; Hays, C. J.; Deering, D. W.; Eck, T. F.

1992-01-01

Instantaneous fractions of absorbed photosynthetically active radiation (APAR) were measured at the Streletskaya Steppe Reserve in conjunction with canopy bidirectional-reflected radiation measured at solar zenith angles ranging between 37 and 74 deg during the Kursk experiment (KUREX-91). APAR values were higher for KUREX-91 than those for the first ISLSCP field experiment (FIFE-89) and the amount of APAR of a canopy was a function of solar zenith angle, decreasing as solar zenith angle increased at the resrve. Differences in absorption are attributed to leaf area index (LAI) and leaf angle distribution and subsequently transmitted radiation interactions. LAIs were considerably higher at the reserve than those at the FIFE site. Leaf angle distributions of the reserve approach a uniform distribution while distributions at the FIFE site more closely approximate erectophile distributions. Reflected photosynthetically active radiation (PAR) components at KUREX-91 and FIFE-89 were similar in magnitude and in their response to solar zenith angle. Transmitted PAR increased with increasing solar zenith angle at KUREX-91 and decreased with increasing solar zenith angle at FIFE-89. Transmitted PAR at FIFE-89 was considerably larger than those at KUREX-91.

Dynamics of the active site loops in catalyzing aminoacylation reaction in seryl and histidyl tRNA synthetases.

PubMed

Dutta, Saheb; Kundu, Soumya; Saha, Amrita; Nandi, Nilashis

2018-03-01

Aminoacylation reaction is the first step of protein biosynthesis. The catalytic reorganization at the active site of aminoacyl tRNA synthetases (aaRSs) is driven by the loop motions. There remain lacunae of understanding concerning the catalytic loop dynamics in aaRSs. We analyzed the functional loop dynamics in seryl tRNA synthetase from Methanopyrus kandleri ( mk SerRS) and histidyl tRNA synthetases from Thermus thermophilus ( tt HisRS), respectively, using molecular dynamics. Results confirm that the motif 2 loop and other active site loops are flexible spots within the catalytic domain. Catalytic residues of the loops form a network of interaction with the substrates to form a reactive state. The loops undergo transitions between closed state and open state and the relaxation of the constituent residues occurs in femtosecond to nanosecond time scale. Order parameters are higher for constituent catalytic residues which form a specific network of interaction with the substrates to form a reactive state compared to the Gly residues within the loop. The development of interaction is supported from mutation studies where the catalytic domain with mutated loop exhibits unfavorable binding energy with the substrates. During the open-close motion of the loops, the catalytic residues make relaxation by ultrafast librational motion as well as fast diffusive motion and subsequently relax rather slowly via slower diffusive motion. The Gly residues act as a hinge to facilitate the loop closing and opening by their faster relaxation behavior. The role of bound water is analyzed by comparing implicit solvent-based and explicit solvent-based simulations. Loops fail to form catalytically competent geometry in absence of water. The present result, for the first time reveals the nature of the active site loop dynamics in aaRS and their influence on catalysis.

Cooperative binding modes of Cu(II) in prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Chisnell, Robin; Lu, Wenchang; Bernholc, Jerry

2007-03-01

The misfolding of the prion protein, PrP, is responsible for a group of neurodegenerative diseases including mad cow disease and Creutzfeldt-Jakob disease. It is known that the PrP can efficiently bind copper ions; four high-affinity binding sites located in the octarepeat region of PrP are now well known. Recent experiments suggest that at low copper concentrations new binding modes, in which one copper ion is shared between two or more binding sites, are possible. Using our hybrid Thomas-Fermi/DFT computational scheme, which is well suited for simulations of biomolecules in solution, we investigate the geometries and energetics of two, three and four binding sites cooperatively binding one copper ion. These geometries are then used as inputs for classical molecular dynamics simulations. We find that copper binding affects the secondary structure of the PrP and that it stabilizes the unstructured (unfolded) part of the protein.

Preservice Mathematics Teachers' Perceptions of Using a Web 2.0 Technology as a Supportive Teaching-Learning Tool in a College Euclidean Geometry Course

ERIC Educational Resources Information Center

Hossain, Md. Mokter

2012-01-01

This mixed methods study examined preservice secondary mathematics teachers' perceptions of a blogging activity used as a supportive teaching-learning tool in a college Euclidean Geometry course. The effect of a 12-week blogging activity that was a standard component of a college Euclidean Geometry course offered for preservice secondary…

An improved FIB sample preparation technique for site-specific plan-view specimens: A new cutting geometry.

PubMed

Li, Chen; Habler, Gerlinde; Baldwin, Lisa C; Abart, Rainer

2018-01-01

Focused ion beam (FIB) sample preparation technique in plan-view geometry allows direct correlations of the atomic structure study via transmission electron microscopy with micrometer-scale property measurements. However, one main technical difficulty is that a large amount of material must be removed underneath the specimen. Furthermore, directly monitoring the milling process is difficult unless very large material volumes surrounding the TEM specimen site are removed. In this paper, a new cutting geometry is introduced for FIB lift-out sample preparation with plan-view geometry. Firstly, an "isolated" cuboid shaped specimen is cut out, leaving a "bridge" connecting it with the bulk material. Subsequently the two long sides of the "isolated" cuboid are wedged, forming a triangular prism shape. A micromanipulator needle is used for in-situ transfer of the specimen to a FIB TEM grid, which has been mounted parallel with the specimen surface using a simple custom-made sample slit. Finally, the grid is transferred to the standard FIB grid holder for final thinning with standard procedures. This new cutting geometry provides clear viewing angles for monitoring the milling process, which solves the difficulty of judging whether the specimen has been entirely detached from the bulk material, with the least possible damage to the surrounding materials. With an improved success rate and efficiency, this plan-view FIB lift-out specimen preparation technique should have a wide application for material science. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Searching for the IRA "disappeared": ground-penetrating radar investigation of a churchyard burial site, Northern Ireland.

PubMed

Ruffell, Alastair

2005-11-01

A search for the body of a victim of terrorist abduction and murder was made in a graveyard on the periphery of a major conurbation in Northern Ireland. The area is politically sensitive and the case of high profile. This required non-invasive, completely non-destructive and rapid assessment of the scene. A MALA RAMAC ground-penetrating radar system was used to achieve these objectives. Unprocessed and processed 400 MHz data show the presence of a collapse feature above and around a known 1970s burial with no similar collapse above the suspect location. In the saturated, clay-rich sediments of the site, 200 MHz data offered no advantage over 400 MHz data. Unprocessed 100 MHz data shows a series of multiples in the known burial with no similar features in the suspect location. Processed 100 MHz lines defined the shape of the collapse around the known burial to 2 m depth, together with the geometry of the platform (1 m depth) the gravedigger used in the 1970s to construct the site. In addition, processed 100 MHz data showed both the dielectric contrast in and internal reflection geometry of the soil imported above the known grave. Thus the sequence, geometry, difference in infill and infill direction of the grave was reconstructed 30 years after burial. The suspect site showed no evidence of shallow or deep inhumation. Subsequently, the missing person's body was found some distance from this site, vindicating the results and interpretation from ground-penetrating radar. The acquisition, processing, collapse feature and sequence stratigraphic interpretation of the known burial and empty (suspect) burial site may be useful proxies for other, similar investigations. GPR was used to evaluate this site within 3 h of the survey commencing, using unprocessed data. An additional day of processing established that the suspect body did not reside here, which was counter to police and community intelligence.

Brain activity associated with translation from a visual to a symbolic representation in algebra and geometry.

PubMed

Leikin, Mark; Waisman, Ilana; Shaul, Shelley; Leikin, Roza

2014-03-01

This paper presents a small part of a larger interdisciplinary study that investigates brain activity (using event related potential methodology) of male adolescents when solving mathematical problems of different types. The study design links mathematics education research with neurocognitive studies. In this paper we performed a comparative analysis of brain activity associated with the translation from visual to symbolic representations of mathematical objects in algebra and geometry. Algebraic tasks require translation from graphical to symbolic representation of a function, whereas tasks in geometry require translation from a drawing of a geometric figure to a symbolic representation of its property. The findings demonstrate that electrical activity associated with the performance of geometrical tasks is stronger than that associated with solving algebraic tasks. Additionally, we found different scalp topography of the brain activity associated with algebraic and geometric tasks. Based on these results, we argue that problem solving in algebra and geometry is associated with different patterns of brain activity.

Development of optically pumped DBR-free semiconductor disk lasers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yang, Zhou; Albrecht, Alexander R.; Cederberg, Jeffrey G.; Sheik-Bahae, Mansoor

2017-03-01

Semiconductor disk lasers (SDLs) are attractive for applications requiring good beam quality, wavelength versatility, and high output powers. Typical SDLs utilize the active mirror geometry, where a semiconductor DBR is integrated with the active region by growth or post-growth bonding. This imposes restrictions for the SDL design, like material system choice, thermal management, and effective gain bandwidth. In DBR-free geometry, these restrictions can be alleviated. An integrated gain model predicts DBR-free geometry with twice the gain bandwidth of typical SDLs, which has been experimentally verified with active regions near 1 μm and 1.15 μm. The lift-off and bonding technique enables the integration of semiconductor active regions with arbitrary high quality substrates, allowing novel monolithic geometries. Bonding an active region onto a straight side of a commercial fused silica right angle prism, and attaching a high reflectivity mirror onto the hypotenuse side, with quasi CW pumping at 780 nm, lasing operation was achieved at 1037 nm with 0.2 mW average power at 1.6 mW average pump power. Laser dynamics show that thermal lens generation in the active region bottlenecks the laser efficiency. Investigations on total internal reflection based monolithic ring cavities are ongoing. These geometries would allow the intracavity integration of 2D materials or other passive absorbers, which could be relevant for stable mode locking. Unlike typical monolithic microchip SDLs, with the evanescent wave coupling technique, these monolithic geometries allow variable coupling efficiency.

Tunable multiple emissions in manganese-concentrated sulfide through simultaneous tailoring of Mn-site coordination and Mn-Mn pair geometry

NASA Astrophysics Data System (ADS)

Chen, Zitao; Song, Enhai; Ye, Shi; Zhang, Qinyuan

2017-12-01

In contrast to generally single-band visible emission feature from Mn2+, simultaneous visible (VIS) and near-infrared (NIR) multiple emissions are demonstrated in Mn2+ concentrated sulfide (MnS) by only involving a single crystallographic site. Upon varying the Mn2+-site coordination and/or Mn-Mn pairs geometry in different structural MnS, the multiple emissions from divalent manganese can be easily tuned from 575 to 720 nm (VIS) or from 880 to 900 or 1380 nm (NIR), respectively. The excitation spectroscopy and the luminescent decay, together with crystal structural analyses, are employed to investigate the electronic transition and the excited state dynamics of these Mn2+ concentrated systems. It is found that the VIS and NIR emissions can be ascribed to the isolated Mn2+ ion and exchange coupled Mn-Mn pair center, respectively. The effect of crystal field and bridging geometry, as well as temperature on the exchange coupled Mn2+ pairs NIR emissive center, is also investigated in detail. This work not only provides keen insights into the de-excitation pathway of Mn2+-concentrated material, but also offers the possibilities of designing a novel NIR emitting source for various photonic applications.

Activation mechanism of a noncanonical RNA-dependent RNA polymerase.

PubMed

Garriga, Damià; Navarro, Aitor; Querol-Audí, Jordi; Abaitua, Fernando; Rodríguez, José F; Verdaguer, Núria

2007-12-18

Two lineages of viral RNA-dependent RNA polymerases (RDRPs) differing in the organization (canonical vs. noncanonical) of the palm subdomain have been identified. Phylogenetic analyses indicate that both lineages diverged at a very early stage of the evolution of the enzyme [Gorbalenya AE, Pringle FM, Zeddam JL, Luke BT, Cameron CE, Kalmakoff J, Hanzlik TN, Gordon KH, Ward VK (2002) J Mol Biol 324:47-62]. Here, we report the x-ray structure of a noncanonical birnaviral RDRP, named VP1, in its free form, bound to Mg(2+) ions, and bound to a peptide representing the polymerase-binding motif of the regulatory viral protein VP3. The structure of VP1 reveals that the noncanonical connectivity of the palm subdomain maintains the geometry of the catalytic residues found in canonical polymerases but results in a partial blocking of the active site cavity. The VP1-VP3 peptide complex shows a mode of polymerase activation in which VP3 binding promotes a conformational change that removes the steric blockade of the VP1 active site, facilitating the accommodation of the template and incoming nucleotides for catalysis. The striking structural similarities between birnavirus (dsRNA) and the positive-stranded RNA picornavirus and calicivirus RDRPs provide evidence supporting the existence of functional and evolutionary relationships between these two virus groups.

Teachers' Scaffolding of Students' Learning of Geometry While Using a Dynamic Geometry Program

ERIC Educational Resources Information Center

Dove, Anthony; Hollenbrands, Karen

2014-01-01

This study examined the scaffolds that three high school mathematics teachers provided to their geometry students as they used technology to explore geometric ideas. Teachers often used structured activities using a dynamic geometry program and provided significant emotive feedback while students worked through the tasks. This provided…

Molecular design of two sterol 14α-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole

NASA Astrophysics Data System (ADS)

Rupp, Bernd; Raub, Stephan; Marian, Christel; Höltje, Hans-Dieter

2005-03-01

Sterol 14α-demethylase (CYP51) is one of the known major targets for azole antifungals. Therapeutic side effects of these antifungals are based on interactions of the azoles with the human analogue enzyme. This study describes for the first time a comparison of a human CYP51 (HU-CYP51) homology model with a homology model of the fungal CYP51 of Candida albicans (CA-CYP51). Both models are constructed by using the crystal structure of Mycobacterium tuberculosis MT-CYP51 (PDB code: 1EA1). The binding mode of the azole ketoconazole is investigated in molecular dynamics simulations with the GROMACS force field. The usage of special parameters for the iron azole complex binding is necessary to obtain the correct complex geometry in the active site of the enzyme models. Based on the dynamics simulations it is possible to explain the enantioselectivity of the human enzyme and also to predict the binding mode of the isomers of ketoconazole in the active site of the fungal model.

Human topoisomerase I poisoning: docking protoberberines into a structure-based binding site model

NASA Astrophysics Data System (ADS)

Kettmann, Viktor; Košt'álová, Daniela; Höltje, Hans-Dieter

2004-12-01

Using the X-ray crystal structure of the human topoisomerase I (top1) - DNA cleavable complex and the Sybyl software package, we have developed a general model for the ternary cleavable complex formed with four protoberberine alkaloids differing in the substitution on the terminal phenyl rings and covering a broad range of the top1-poisoning activities. This model has the drug intercalated with its planar chromophore between the -1 and +1 base pairs flanking the cleavage site, with the nonplanar portion pointing into the minor groove. The ternary complexes were geometry-optimized and relative interaction energies, computed by using the Tripos force field, were found to rank in correct order the biological potency of the compounds; in addition, the model is also consistent with the top1-poisoning inactivity of berberine, a major prototype of the protoberberine alkaloids. The model might serve as a rational basis for elaboration of the most active compound as a lead structure, in order to develop more potent top1 poisons as next generation anti-cancer drugs.

Quantum chemical modeling of enzymatic reactions: the case of histone lysine methyltransferase.

PubMed

Georgieva, Polina; Himo, Fahmi

2010-06-01

Quantum chemical cluster models of enzyme active sites are today an important and powerful tool in the study of various aspects of enzymatic reactivity. This methodology has been applied to a wide spectrum of reactions and many important mechanistic problems have been solved. Herein, we report a systematic study of the reaction mechanism of the histone lysine methyltransferase (HKMT) SET7/9 enzyme, which catalyzes the methylation of the N-terminal histone tail of the chromatin structure. In this study, HKMT SET7/9 serves as a representative case to examine the modeling approach for the important class of methyl transfer enzymes. Active site models of different sizes are used to evaluate the methodology. In particular, the dependence of the calculated energies on the model size, the influence of the dielectric medium, and the particular choice of the dielectric constant are discussed. In addition, we examine the validity of some technical aspects, such as geometry optimization in solvent or with a large basis set, and the use of different density functional methods. Copyright 2010 Wiley Periodicals, Inc.

Design and analysis of an intelligent controller for active geometry suspension systems

NASA Astrophysics Data System (ADS)

Goodarzi, Avesta; Oloomi, Ehsan; Esmailzadeh, Ebrahim

2011-02-01

An active geometry suspension (AGS) system is a device to optimise suspension-related factors such as toe angle and roll centre height by controlling vehicle's suspension geometry. The suspension geometry could be changed through control of suspension mounting point's position. In this paper, analysis and control of an AGS system is addressed. First, the effects of suspension geometry change on roll centre height and toe angle are studied. Then, based on an analytical approach, the improvement of the vehicle's stability and handling due to the control of suspension geometry is investigated. In the next section, an eight-degree-of-freedom handling model of a sport utility vehicle equipped with an AGS system is introduced. Finally, a self-tuning proportional-integral controller has been designed, using the fuzzy control theory, to control the actuator that changes the geometry of the suspension system. The simulation results show that an AGS system can improve the handling and stability of the vehicle.

Variability of acute extracellular action potential measurements with multisite silicon probes

PubMed Central

Scott, Kimberly M.; Du, Jiangang; Lester, Henry A.; Masmanidis, Sotiris C.

2012-01-01

Device miniaturization technologies have led to significant advances in sensors for extracellular measurements of electrical activity in the brain. Multisite, silicon-based probes containing implantable electrode arrays afford greater coverage of neuronal activity than single electrodes and therefore potentially offer a more complete view of how neuronal ensembles encode information. However, scaling up the number of sites is not sufficient to ensure capture of multiple neurons, as action potential signals from extracellular electrodes may vary due to numerous factors. In order to understand the large-scale recording capabilities and potential limitations of multisite probes, it is important to quantify this variability, and to determine whether certain key device parameters influence the recordings. Here we investigate the effect of four parameters, namely, electrode surface, width of the structural support shafts, shaft number, and position of the recording site relative to the shaft tip. This study employs acutely implanted silicon probes containing up to 64 recording sites, whose performance is evaluated by the metrics of noise, spike amplitude, and spike detection probability. On average, we find no significant effect of device geometry on spike amplitude and detection probability but we find significant differences among individual experiments, with the likelihood of detecting spikes varying by a factor of approximately three across trials. PMID:22971352

2D-QSAR study of fullerene nanostructure derivatives as potent HIV-1 protease inhibitors

NASA Astrophysics Data System (ADS)

Barzegar, Abolfazl; Jafari Mousavi, Somaye; Hamidi, Hossein; Sadeghi, Mehdi

2017-09-01

The protease of human immunodeficiency virus1 (HIV-PR) is an essential enzyme for antiviral treatments. Carbon nanostructures of fullerene derivatives, have nanoscale dimension with a diameter comparable to the diameter of the active site of HIV-PR which would in turn inhibit HIV. In this research, two dimensional quantitative structure-activity relationships (2D-QSAR) of fullerene derivatives against HIV-PR activity were employed as a powerful tool for elucidation the relationships between structure and experimental observations. QSAR study of 49 fullerene derivatives was performed by employing stepwise-MLR, GAPLS-MLR, and PCA-MLR models for variable (descriptor) selection and model construction. QSAR models were obtained with higher ability to predict the activity of the fullerene derivatives against HIV-PR by a correlation coefficient (R2training) of 0.942, 0.89, and 0.87 as well as R2test values of 0.791, 0.67and 0.674 for stepwise-MLR, GAPLS-MLR, and PCA -MLR models, respectively. Leave-one-out cross-validated correlation coefficient (R2CV) and Y-randomization methods confirmed the models robustness. The descriptors indicated that the HIV-PR inhibition depends on the van der Waals volumes, polarizability, bond order between two atoms and electronegativities of fullerenes derivatives. 2D-QSAR simulation without needing receptor's active site geometry, resulted in useful descriptors mainly denoting ;C60 backbone-functional groups; and ;C60 functional groups; properties. Both properties in fullerene refer to the ligand fitness and improvement van der Waals interactions with HIV-PR active site. Therefore, the QSAR models can be used in the search for novel HIV-PR inhibitors based on fullerene derivatives.

Development and application of hydraulic geometry equations for tidal channel restoration in Atlantic Canada

NASA Astrophysics Data System (ADS)

Graham, J.; van Proosdij, D.; Bowron, T.

2017-12-01

Tidal wetlands play a key role in our environment, particularly in the face of climate change and rising sea levels. Successful restoration of these coastal habitats requires a good understanding of the hydrology and morphology of the site. In Atlantic Canada, restoration design must consider significant variation in tidal range (1 to 16 m), sediment supply (50-70,000 mg/L) and winter conditions. In 2012 ground surveys, aerial photos and digital terrain data were used to conduct a morphometric analysis of representative tidal channels and to establish regional hydraulic geometry relationships to aid in restoration design. Channel morphology was strongly related to freshwater discharge and channel order while drainage density, channel length, and sinuosity were related to site history and maturity. Five years after the initial study, two restored salt marshes have been analyzed to assess the validity of the equations. At both marshes, tidal channels were excavated and erosion/accretion tracked for five years following restoration. Channels were found to experience rapid erosion in the first 2 years following restoration but to stabilize with dimensions on par with those predicted. Furthermore, both sites rapidly developed hybrid creek networks beyond the primary excavated channels when allowed to self design. The methodology has been used to design tidal channels for 2 additional sites. Although these sites have not been restored at present, hydrodynamic modeling supported channel dimension predictions, with acceptable in-channel velocities and flood extents simulated in the model. The authors conclude that the use of regional hydraulic geometry equations have been effective in salt marsh restoration design in Atlantic Canada, particularly when used in conjunction with other techniques such as hydrodynamic modeling and analysis of historic conditions.

The effect of micro-ECoG substrate footprint on the meningeal tissue response

NASA Astrophysics Data System (ADS)

Schendel, Amelia A.; Nonte, Michael W.; Vokoun, Corinne; Richner, Thomas J.; Brodnick, Sarah K.; Atry, Farid; Frye, Seth; Bostrom, Paige; Pashaie, Ramin; Thongpang, Sanitta; Eliceiri, Kevin W.; Williams, Justin C.

2014-08-01

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Teaching Using Cabri--With a Little Help from Prepared Files.

ERIC Educational Resources Information Center

Mackrell, Kate

2002-01-01

Describes lessons with year 7 and year 9 classes that used the ATM Active Geometry package. Presents the main activities and how to use prepared files in the geometry package for mathematics instruction. (KHR)

Experimental and density functional theory studies on benzalkonium ibuprofenate, a double active pharmaceutical ingredient.

PubMed

Safna Hussan, K P; Thayyil, M Shahin; Rajan, Vijisha K; Muraleedharan, K

2018-02-01

Molecular aspects of a double active pharmaceutical ingredient in ionic liquid form, benzalkonium ibuprofenate (BaIb), were studied using density functional theory (DFT/B3LYP/6-31+G (d, p)). A detailed discussion on optimized geometry, energy, heat and the enthalpy of BaIb was carried out. The computed vibrational results agree well with the experimental results. The stability and biological activity were compared to the parent drugs on the basis of global descriptive parameters. The electrophilic and nucleophilic sites were pointed out in the MESP structures well evidently. NBO analysis was also done to predict the relative aromaticity, delocalization effects and the contribution towards stabilization energy of the title compound. The information about non-covalent, non-ionic weak interaction between the cation and anion was obtained from the list of Mulliken charges and NBO analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structure-activity relations of 2-(methylthio)benzimidazole by FTIR, FT-Raman, NMR, DFT and conceptual DFT methods.

PubMed

Arjunan, V; Raj, Arushma; Ravindran, P; Mohan, S

2014-01-24

The vibrational fundamental modes of 2-(methylthio)benzimidazole (2MTBI) have been analysed by combining FTIR, FT-Raman and quantum chemical calculations. The structural parameters of the compound are determined from the optimised geometry by B3LYP with 6-31G(∗∗), 6-311++G(∗∗) and cc-pVTZ basis sets and giving energies, harmonic vibrational frequencies, depolarisation ratios, IR intensities and Raman activities. (1)H and (13)C NMR spectra have been analysed and (1)H and (13)C nuclear magnetic resonance chemical shifts are calculated using the gauge independent atomic orbital (GIAO) method. The structure-activity relationship of the compound is also investigated by conceptual DFT methods. The chemical reactivity and site selectivity of the molecule has been determined with the help of global and local reactivity descriptors. Copyright © 2013 Elsevier B.V. All rights reserved.

Structure, reactivity, and electronic properties of V-doped Co clusters

NASA Astrophysics Data System (ADS)

Datta, Soumendu; Kabir, Mukul; Saha-Dasgupta, Tanusri; Mookerjee, Abhijit

2009-08-01

Structures and physicochemical properties of V-doped Co13 clusters have been studied in detail using density-functional-theory-based first-principles method. We have found anomalous variation in stability of the doped clusters with increasing V concentration, which has been nicely demonstrated in terms of energetics and electronic properties of the clusters. Our study explains the nonmonotonic variation in reactivity of Co13-mVm clusters toward H2 molecules as reported experimentally [Nonose , J. Phys. Chem. 94, 2744 (1990)]. Moreover, it provides useful insight into the cluster geometry and chemically active sites on the cluster surface, which can help to design better catalytic processes.

Micro-reaction chamber electrodes for neural stimulation and recording.

PubMed

Shanmugasundaram, Balaji; Gluckman, Bruce J

2011-01-01

Biocompatible electrodes with smaller geometric area are preferred to improve the selectivity of the neural recording and stimulation applications. We introduce the concept of a micro-reaction chamber (μRC) in which a volume within the electrode back plane is used to confine and sequester the electrochemical reactions used for charge passage. The URC electrode design helps decrease impedance and improves the charge storage capacity without altering the geometry of the active site. Here we demonstrate that μRC electrodes fabricated from 50 μm diameter microwire have significantly improved charge storage capacity and lowered impedance at physiologically relevant frequencies in phosphate buffered saline solution compared with other designs.

Developing the Concept of a Parabola in Taxicab Geometry

ERIC Educational Resources Information Center

Ada, Tuba; Kurtulus, Aytaç; Yanik, H. Bahadir

2015-01-01

The aim of this study was to observe the development process of the concept of a parabola in Taxicab geometry. The study was carried out in two stages. First, some activities related to Euclidean geometry and Taxicab geometry were designed based on concept development and real-life applications, and they were administered to a ninth-grade student.…

Technology in Spherical Geometry Investigations: Reflections on Spontaneous Use and Motivation

ERIC Educational Resources Information Center

Sinclair, Margaret

2010-01-01

Students in a graduate geometry class used items such as paper, ribbon, plastic spheres, cardboard tubes, and markers to carry out investigations in spherical geometry. The hands-on activities helped students develop a new appreciation of geometry as a study of shape and space; however, the difficulty of subduing wayward elastics and drawing lines…

A computational study of CH 4 storage in porous framework materials with metalated linkers: connecting the atomistic character of CH 4 binding sites to usable capacity

DOE PAGES

Tsivion, Ehud; Mason, Jarad A.; Gonzalez, Miguel. I.; ...

2016-03-29

In order to store natural gas (NG) inexpensively at adequate densities for use as a fuel in the transportation sector, new porous materials are being developed. Our work uses computational methods to explore strategies for improving the usable methane storage capacity of adsorbents, including metal-organic frameworks (MOFs), that feature open-metal sites incorporated into their structure by postsynthetic modification. The adsorption of CH 4 on several open-metal sites is studied by calculating geometries and adsorption energies and analyzing the relevant interaction factors. Approximate site-specific adsorption isotherms are obtained, and the open-metal site contribution to the overall CH 4 usable capacity ismore » evaluated. It is found that sufficient ionic character is required, as exemplified by the strong CH 4 affinities of 2,2'-bipyridine-CaCl 2 and Mg, Ca-catecholate. In addition, it is found that the capacity of a single metal site depends not only on its affinity but also on its geometry, where trigonal or "bent" low-coordinate exposed sites can accommodate three or four methane molecules, as exemplified by Ca-decorated nitrilotriacetic acid. The effect of residual solvent molecules at the open-metal site is also explored, with some positive conclusions. Not only can residual solvent stabilize the open-metal site, surprisingly, solvent molecules do not necessarily reduce CH 4 affinity, but can contribute to increased usable capacity by modifying adsorption interactions.« less

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study

PubMed Central

Severino, Marco; Rastelli, Claudio; Bernardi, Sara; Caruso, Silvia; Galli, Massimo; Lamazza, Luca; Di Paolo, Carlo

2017-01-01

Background The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. Material and Methods 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. Results The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. Conclusions In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized. Key words:Implant primary stability, resonance frequency analysis, implant site preparation. PMID:28160577

Automatic Generation of CFD-Ready Surface Triangulations from CAD Geometry

NASA Technical Reports Server (NTRS)

Aftosmis, M. J.; Delanaye, M.; Haimes, R.; Nixon, David (Technical Monitor)

1998-01-01

This paper presents an approach for the generation of closed manifold surface triangulations from CAD geometry. CAD parts and assemblies are used in their native format, without translation, and a part's native geometry engine is accessed through a modeler-independent application programming interface (API). In seeking a robust and fully automated procedure, the algorithm is based on a new physical space manifold triangulation technique which was developed to avoid robustness issues associated with poorly conditioned mappings. In addition, this approach avoids the usual ambiguities associated with floating-point predicate evaluation on constructed coordinate geometry in a mapped space, The technique is incremental, so that each new site improves the triangulation by some well defined quality measure. Sites are inserted using a variety of priority queues to ensure that new insertions will address the worst triangles first, As a result of this strategy, the algorithm will return its 'best' mesh for a given (prespecified) number of sites. Alternatively, the algorithm may be allowed to terminate naturally after achieving a prespecified measure of mesh quality. The resulting triangulations are 'CFD-ready' in that: (1) Edges match the underlying part model to within a specified tolerance. (2) Triangles on disjoint surfaces in close proximity have matching length-scales. (3) The algorithm produces a triangulation such that no angle is less than a given angle bound, alpha, or greater than Pi - 2alpha This result also sets bounds on the maximum vertex degree, triangle aspect-ratio and maximum stretching rate for the triangulation. In addition to tile output triangulations for a variety of CAD parts, tile discussion presents related theoretical results which assert the existence of such all angle bound, and demonstrate that maximum bounds of between 25 deg and 30 deg may be achieved in practice.

Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package.

PubMed

Borbulevych, Oleg Y; Plumley, Joshua A; Martin, Roger I; Merz, Kenneth M; Westerhoff, Lance M

2014-05-01

Macromolecular crystallographic refinement relies on sometimes dubious stereochemical restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule and any covalently bound ligand(s). The ligand stereochemical restraint file (CIF) requires a priori understanding of the ligand geometry within the active site, and creation of the CIF is often an error-prone process owing to the great variety of potential ligand chemistry and structure. Stereochemical restraints have been replaced with more robust functionals through the integration of the linear-scaling, semiempirical quantum-mechanics (SE-QM) program DivCon with the PHENIX X-ray refinement engine. The PHENIX/DivCon package has been thoroughly validated on a population of 50 protein-ligand Protein Data Bank (PDB) structures with a range of resolutions and chemistry. The PDB structures used for the validation were originally refined utilizing various refinement packages and were published within the past five years. PHENIX/DivCon does not utilize CIF(s), link restraints and other parameters for refinement and hence it does not make as many a priori assumptions about the model. Across the entire population, the method results in reasonable ligand geometries and low ligand strains, even when the original refinement exhibited difficulties, indicating that PHENIX/DivCon is applicable to both single-structure and high-throughput crystallography.

Mapping the fine structure of cortical activity with different micro-ECoG electrode array geometries

NASA Astrophysics Data System (ADS)

Wang, Xi; Gkogkidis, C. Alexis; Iljina, Olga; Fiederer, Lukas D. J.; Henle, Christian; Mader, Irina; Kaminsky, Jan; Stieglitz, Thomas; Gierthmuehlen, Mortimer; Ball, Tonio

2017-10-01

Objective. Innovations in micro-electrocorticography (µECoG) electrode array manufacturing now allow for intricate designs with smaller contact diameters and/or pitch (i.e. inter-contact distance) down to the sub-mm range. The aims of the present study were: (i) to investigate whether frequency ranges up to 400 Hz can be reproducibly observed in µECoG recordings and (ii) to examine how differences in topographical substructure between these frequency bands and electrode array geometries can be quantified. We also investigated, for the first time, the influence of blood vessels on signal properties and assessed the influence of cortical vasculature on topographic mapping. Approach. The present study employed two µECoG electrode arrays with different contact diameters and inter-contact distances, which were used to characterize neural activity from the somatosensory cortex of minipigs in a broad frequency range up to 400 Hz. The analysed neural data were recorded in acute experiments under anaesthesia during peripheral electrical stimulation. Main results. We observed that µECoG recordings reliably revealed multi-focal cortical somatosensory response patterns, in which response peaks were often less than 1 cm apart and would thus not have been resolvable with conventional ECoG. The response patterns differed by stimulation site and intensity, they were distinct for different frequency bands, and the results of functional mapping proved independent of cortical vascular. Our analysis of different frequency bands exhibited differences in the number of activation peaks in topographical substructures. Notably, signal strength and signal-to-noise ratios differed between the two electrode arrays, possibly due to their different sensitivity for variations in spatial patterns and signal strengths. Significance. Our findings that the geometry of µECoG electrode arrays can strongly influence their recording performance can help to make informed decisions that maybe important in number of clinical contexts, including high-resolution brain mapping, advanced epilepsy diagnostics or brain-machine interfacing.

The molecular architecture of human N-acetylgalactosamine kinase.

PubMed

Thoden, James B; Holden, Hazel M

2005-09-23

Galactokinase plays a key role in normal galactose metabolism by catalyzing the conversion of alpha-d-galactose to galactose 1-phosphate. Within recent years, the three-dimensional structures of human galactokinase and two bacterial forms of the enzyme have been determined. Originally, the gene encoding galactokinase in humans was mapped to chromosome 17. An additional gene, encoding a protein with sequence similarity to galactokinase, was subsequently mapped to chromosome 15. Recent reports have shown that this second gene (GALK2) encodes an enzyme with greater activity against GalNAc than galactose. This enzyme, GalNAc kinase, has been implicated in a salvage pathway for the reutilization of free GalNAc derived from the degradation of complex carbohydrates. Here we report the first structural analysis of a GalNAc kinase. The structure of the human enzyme was solved in the presence of MnAMPPNP and GalNAc or MgATP and GalNAc (which resulted in bound products in the active site). The enzyme displays a distinctly bilobal appearance with its active site wedged between the two domains. The N-terminal region is dominated by a seven-stranded mixed beta-sheet, whereas the C-terminal motif contains two layers of anti-parallel beta-sheet. The overall topology displayed by GalNAc kinase places it into the GHMP superfamily of enzymes, which generally function as small molecule kinases. From this investigation, the geometry of the GalNAc kinase active site before and after catalysis has been revealed, and the determinants of substrate specificity have been defined on a molecular level.

Increased density and periosteal expansion of the tibia in young adult men following short-term arduous training.

PubMed

Izard, Rachel M; Fraser, William D; Negus, Charles; Sale, Craig; Greeves, Julie P

2016-07-01

Few human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading. Tibial bone density and geometry were measured in 90 British Army male recruits (ages 21±3years, height: 1.78±0.06m, body mass: 73.9±9.8kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P<0.05). Bone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial-anterior and anterior-posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P<0.01). In vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Innovative Field Methods for Characterizing the Hydraulic Properties of a Complex Fractured Rock Aquifer (Ploemeur, Brittany)

NASA Astrophysics Data System (ADS)

Bour, O.; Le Borgne, T.; Longuevergne, L.; Lavenant, N.; Jimenez-Martinez, J.; De Dreuzy, J. R.; Schuite, J.; Boudin, F.; Labasque, T.; Aquilina, L.

2014-12-01

Characterizing the hydraulic properties of heterogeneous and complex aquifers often requires field scale investigations at multiple space and time scales to better constrain hydraulic property estimates. Here, we present and discuss results from the site of Ploemeur (Brittany, France) where complementary hydrological and geophysical approaches have been combined to characterize the hydrogeological functioning of this highly fractured crystalline rock aquifer. In particular, we show how cross-borehole flowmeter tests, pumping tests and frequency domain analysis of groundwater levels allow quantifying the hydraulic properties of the aquifer at different scales. In complement, we used groundwater temperature as an excellent tracer for characterizing groundwater flow. At the site scale, measurements of ground surface deformation through long-base tiltmeters provide robust estimates of aquifer storage and allow identifying the active structures where groundwater pressure changes occur, including those acting during recharge process. Finally, a numerical model of the site that combines hydraulic data and groundwater ages confirms the geometry of this complex aquifer and the consistency of the different datasets. The Ploemeur site, which has been used for water supply at a rate of about 106 m3 per year since 1991, belongs to the French network of hydrogeological sites H+ and is currently used for monitoring groundwater changes and testing innovative field methods.

Site characterization and construction of a controlled shallow test site in central Mexico for archaeological and engineering applications

NASA Astrophysics Data System (ADS)

Rosado-Fuentes, A.; Arango-Galvan, C.; Arciniega-Ceballos, A.; Hernández-Quintero, J. E.; Mendo-Perez, G.

2017-12-01

A controlled shallow test site (CSTS) has been constructed at the UNAM Geomagnetic Observatory in Teoloyucan, central Mexico. The objective of the CSTS is to have a controlled place to test new developments and arrays that can be used for archaeological and engineering exploration, as well as to calibrate instruments, train students and for future research. The CSTS was built far enough not to influence the geomagnetic sensors and not be affected by noise sources. Special attention was given to the distribution and geometry of buried materials as well as the instruments used. Before the CSTS was built, a combination of near-surface, non-invasive geophysical techniques was performed to characterize the area of 20 by 32 meters. The methods include magnetometry, electromagnetic induction, ground penetrating radar (GPR), electrical resistivity tomography (ERT) and seismic refraction tomography (SRT). The GPR, SRT and ERT results show relatively flat interfaces. In general, the vertical gradient of the total magnetic field and the electric conductivity have very small variations, showing only one strong magnetic dipole associated to a shallow anomaly. These results indicate that the area is ideal for the construction of the test site. The CSTS consists on buried structures made with different materials and geometries (cubes, cylinders and tubes) commonly used as construction materials in Mexico since Pre-Hispanic times. These materials include concrete, reinforced concrete, wood, brick, adobe, basalt, tezontle and also empty space for controlling responses. The CSTS is versatile enough to be reshaped considering new geometries or materials and to conduct further investigations.

Whispering Gallery Mode Resonators for Rapid Label-Free Biosensing in Small Volume Droplets

PubMed Central

Wildgen, Sarah M.; Dunn, Robert C.

2015-01-01

Rapid biosensing requires fast mass transport of the analyte to the surface of the sensing element. To optimize analysis times, both mass transport in solution and the geometry and size of the sensing element need to be considered. Small dielectric spheres, tens of microns in diameter, can act as label-free biosensors using whispering gallery mode (WGM) resonances. WGM resonances are sensitive to the effective refractive index, which changes upon analyte binding to recognition sites on functionalized resonators. The spherical geometry and tens of microns diameter of these resonators provides an efficient target for sensing while their compact size enables detection in limited volumes. Here, we explore conditions leading to rapid analyte detection using WGM resonators as label-free sensors in 10 μL sample droplets. Droplet evaporation leads to potentially useful convective mixing, but also limits the time over which analysis can be completed. We show that active droplet mixing combined with initial binding rate measurements is required for accurate nanomolar protein quantification within the first minute following injection. PMID:25806835

Computational Insights into an Enzyme-Catalyzed [4+2] Cycloaddition

PubMed Central

2017-01-01

The enzyme SpnF, involved in the biosynthesis of spinosyn A, catalyzes a formal [4+2] cycloaddition of a 22-membered macrolactone, which may proceed as a concerted [4+2] Diels–Alder reaction or a stepwise [6+4] cycloaddition followed by a Cope rearrangement. Quantum mechanics/molecular mechanics (QM/MM) calculations combined with free energy simulations show that the Diels–Alder pathway is favored in the enzyme environment. OM2/CHARMM free energy simulations for the SpnF-catalyzed reaction predict a free energy barrier of 22 kcal/mol for the concerted Diels–Alder process and provide no evidence of a competitive stepwise pathway. Compared with the gas phase, the enzyme lowers the Diels–Alder barrier significantly, consistent with experimental observations. Inspection of the optimized geometries indicates that the enzyme may prearrange the substrate within the active site to accelerate the [4+2] cycloaddition and impede the [6+4] cycloaddition through interactions with active-site residues. Judging from partial charge analysis, we find that the hydrogen bond between the Thr196 residue of SpnF and the substrate C15 carbonyl group contributes to the enhancement of the rate of the Diels–Alder reaction. QM/MM simulations show that the substrate can easily adopt a reactive conformation in the active site of SpnF because interconversion between the C5–C6 s-trans and s-cis conformers is facile. Our QM/MM study suggests that the enzyme SpnF does behave as a Diels-Alderase. PMID:29131960

Site-specific, adult bone benefits attributed to loading during youth: A preliminary longitudinal analysis.

PubMed

Scerpella, Tamara A; Bernardoni, Brittney; Wang, Sijian; Rathouz, Paul J; Li, Quefeng; Dowthwaite, Jodi N

2016-04-01

We examined site-specific bone development in relation to childhood and adolescent artistic gymnastics exposure, comparing up to 10years of prospectively acquired longitudinal data in 44 subjects, including 31 non-gymnasts (NON) and 13 gymnasts (GYM) who participated in gymnastics from pre-menarche to ≥1.9years post-menarche. Subjects underwent annual regional and whole-body DXA scans; indices of bone geometry and strength were calculated. Anthropometrics, physical activity, and maturity were assessed annually, coincident with DXA scans. Non-linear mixed effect models centered growth in bone outcomes at menarche and adjusted for menarcheal age, height, and non-bone fat-free mass to evaluate GYM-NON differences. A POST-QUIT variable assessed the withdrawal effect of quitting gymnastics. Curves for bone area, mass (BMC), and strength indices were higher in GYM than NON at both distal radius metaphysis and diaphysis (p<0.0001). At the femoral neck, greater GYM BMC (p<0.01), narrower GYM endosteal diameter (p<0.02), and similar periosteal width (p=0.09) yielded GYM advantages in narrow neck cortical thickness and buckling ratio (both p<0.001; lower BR indicates lower fracture risk). Lumbar spine and sub-head BMC were greater in GYM than NON (p<0.036). Following gymnastics cessation, GYM slopes increased for distal radius diaphysis parameters (p≤0.01) and for narrow neck BR (p=0.02). At the distal radius metaphysis, GYM BMC and compressive strength slopes decreased, as did slopes for lumbar spine BMC, femoral neck BMC, and narrow neck cortical thickness (p<0.02). In conclusion, advantages in bone mass, geometry, and strength at multiple skeletal sites were noted across growth and into young adulthood in girls who participated in gymnastics loading to at least 1.9years post-menarche. Following gymnastics cessation, advantages at cortical bone sites improved or stabilized, while advantages at corticocancellous sites stabilized or diminished. Additional longitudinal observation is necessary to determine whether residual loading benefits enhance lifelong skeletal strength. Copyright © 2016 Elsevier Inc. All rights reserved.

Do solar decimetric spikes originate in coronal X-ray sources?

NASA Astrophysics Data System (ADS)

Battaglia, M.; Benz, A. O.

2009-06-01

Context: In the standard solar flare scenario, a large number of particles are accelerated in the corona. Nonthermal electrons emit both X-rays and radio waves. Thus, correlated signatures of the acceleration process are predicted at both wavelengths, coinciding either close to the footpoints of a magnetic loop or near the coronal X-ray source. Aims: We attempt to study the spatial connection between coronal X-ray emission and decimetric radio spikes to determine the site and geometry of the acceleration process. Methods: The positions of radio-spike sources and coronal X-ray sources are determined and analyzed in a well-observed limb event. Radio spikes are identified in observations from the Phoenix-2 spectrometer. Data from the Nançay radioheliograph are used to determine the position of the radio spikes. RHESSI images in soft and hard X-ray wavelengths are used to determine the X-ray flare geometry. Those observations are complemented by images from GOES/SXI. Results: We find that the radio emission originates at altitudes much higher than the coronal X-ray source, having an offset from the coronal X-ray source amounting to 90´´ and to 113´´ and 131´´ from the two footpoints, averaged over time and frequency. Conclusions: Decimetric spikes do not originate from coronal X-ray flare sources contrary to previous expectations. However, the observations suggest a causal link between the coronal X-ray source, related to the major energy release site, and simultaneous activity in the higher corona.

Development of a Computerized Penetrometer System for Hazardous Waste Site Soils Investigations

DTIC Science & Technology

1988-08-30

soil to prevent contaminant movement . o To preserve the standard electric cone geometry, i.e., 600 point, 1.4-in. (3.56-cm) OD, 1.54-in. 2 (9.9-cm2...considerable soil movements without cracking or rupturing. The second objective was to preserve the ASTM standard electric cone exterior geometry so as to...electrokinesis, and telluric current phenomena. Of these, the electrochemical and electrokinesis phenomena typically produce the largest voltage magnitude (on

Theoretical NMR and conformational analysis of solvated oximes for organophosphates-inhibited acetylcholinesterase reactivation

NASA Astrophysics Data System (ADS)

da Silva, Jorge Alberto Valle; Modesto-Costa, Lucas; de Koning, Martijn C.; Borges, Itamar; França, Tanos Celmar Costa

2018-01-01

In this work, quaternary and non-quaternary oximes designed to bind at the peripheral site of acetylcholinesterase previously inhibited by organophosphates were investigated theoretically. Some of those oximes have a large number of degrees of freedom, thus requiring an accurate method to obtain molecular geometries. For this reason, the density functional theory (DFT) was employed to refine their molecular geometries after conformational analysis and to compare their 1H and 13C nuclear magnetic resonance (NMR) theoretical signals in gas-phase and in solvent. A good agreement with experimental data was achieved and the same theoretical approach was employed to obtain the geometries in water environment for further studies.

A global optimization algorithm for protein surface alignment

PubMed Central

2010-01-01

Background A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved. Results In this paper we propose a new method for local structural alignment of protein surfaces based on continuous global optimization techniques. Given the three-dimensional structures of two proteins, the method finds the isometric transformation (rotation plus translation) that best superimposes active regions of two structures. We draw our inspiration from the well-known Iterative Closest Point (ICP) method for three-dimensional (3D) shapes registration. Our main contribution is in the adoption of a controlled random search as a more efficient global optimization approach along with a new dissimilarity measure. The reported computational experience and comparison show viability of the proposed approach. Conclusions Our method performs well to detect similarity in binding sites when this in fact exists. In the future we plan to do a more comprehensive evaluation of the method by considering large datasets of non-redundant proteins and applying a clustering technique to the results of all comparisons to classify binding sites. PMID:20920230

Peripubertal female athletes in high-impact sports show improved bone mass acquisition and bone geometry.

PubMed

Maïmoun, Laurent; Coste, Olivier; Philibert, Pascal; Briot, Karine; Mura, Thibault; Galtier, Florence; Mariano-Goulart, Denis; Paris, Françoise; Sultan, Charles

2013-08-01

Intensive physical training may have a sport-dependent effect on bone mass acquisition. This cross-sectional study evaluated bone mass acquisition in girls practicing sports that put different mechanical loads on bone. Eighty girls from 10.7 to 18.0 years old (mean 13.83 ± 1.97) were recruited: 20 artistic gymnasts (AG; high-impact activity), 20 rhythmic gymnasts (RG; medium-impact activity), 20 swimmers (SW, no-impact activity), and 20 age-matched controls (CON; leisure physical activity <3h/wk). Areal bone mineral density (aBMD) was determined using DEXA. Hip structural analysis applied at the femur evaluated cross-sectional area (CSA, cm(2)), section modulus (Z, cm(3)), and buckling ratio. Bone turnover markers and OPG/RANKL levels were analyzed. AG had higher aBMD than SW and CON at all bone sites and higher values than RG in the lumbar spine and radius. RG had higher aBMD than SW and CON only in the femoral region. CSA and mean cortical thickness were significantly higher and the buckling ratio was significantly lower in both gymnast groups compared with SW and CON. In RG only, endocortical diameter and width were reduced, while Z was only increased in AG compared with SW and CON. Reduced bone remodeling was observed in RG compared with AG only when groups were subdivided according to menarcheal status. All groups showed similar OPG concentrations, while RANKL concentrations increased with age and were decreased in SW. High-impact activity clearly had a favorable effect on aBMD and bone geometry during the growth period, although the bone health benefits seem to be more marked after menarche. Copyright © 2013 Elsevier Inc. All rights reserved.

The growth of geological structures by repeated earthquakes: 2, Field examples of continental dip-slip faults

USGS Publications Warehouse

Stein, R.S.; King, G.C.P.; Rundle, J.B.

1988-01-01

A strong test of our understanding of the earthquake cycle is the ability to reproduce extant faultbounded geological structures, such as basins and ranges, which are built by repeated cycles of deformation. Three examples are considered for which the structure and fault geometry are well known: the White Wolf reverse fault in California, site of the 1952 Kern County M=7.3 earthquake, the Lost River normal fault in Idaho, site of the 1983 Borah Peak M=7.0 earthquake, and the Cricket Mountain normal fault in Utah, site of Quaternary slip events. Basin stratigraphy and seismic reflection records are used to profile the structure, and coseismic deformation measured by leveling surveys is used to estimate the fault geometry. To reproduce these structures, we add the deformation associated with the earthquake cycle (the coseismic slip and postseismic relaxation) to the flexure caused by the observed sediment load, treating the crust as a thin elastic plate overlying a fluid substrate. -from Authors

Three-Dimensional Digital Documentation of Heritage Sites Using Terrestrial Laser Scanning and Unmanned Aerial Vehicle Photogrammetry

NASA Astrophysics Data System (ADS)

Jo, Y. H.; Kim, J. Y.

2017-08-01

Three-dimensional digital documentation is an important technique for the maintenance and monitoring of cultural heritage sites. This study focuses on the three-dimensional digital documentation of the Magoksa Temple, Republic of Korea, using a combination of terrestrial laser scanning and unmanned aerial vehicle (UAV) photogrammetry. Terrestrial laser scanning mostly acquired the vertical geometry of the buildings. In addition, the digital orthoimage produced by UAV photogrammetry had higher horizontal data acquisition rate than that produced by terrestrial laser scanning. Thus, the scanning and UAV photogrammetry were merged by matching 20 corresponding points and an absolute coordinate system was established using seven ground control points. The final, complete threedimensional shape had perfect horizontal and vertical geometries. This study demonstrates the potential of integrating terrestrial laser scanning and UAV photogrammetry for three-dimensional digital documentation. This new technique is expected to contribute to the three-dimensional digital documentation and spatial analysis of cultural heritage sites.

Modeling study on the cleavage step of the self-splicing reaction in group I introns

NASA Technical Reports Server (NTRS)

Setlik, R. F.; Garduno-Juarez, R.; Manchester, J. I.; Shibata, M.; Ornstein, R. L.; Rein, R.

1993-01-01

A three-dimensional model of the Tetrahymena thermophila group I intron is used to further explore the catalytic mechanism of the transphosphorylation reaction of the cleavage step. Based on the coordinates of the catalytic core model proposed by Michel and Westhof (Michel, F., Westhof, E. J. Mol. Biol. 216, 585-610 (1990)), we first converted their ligation step model into a model of the cleavage step by the substitution of several bases and the removal of helix P9. Next, an attempt to place a trigonal bipyramidal transition state model in the active site revealed that this modified model for the cleavage step could not accommodate the transition state due to insufficient space. A lowering of P1 helix relative to surrounding helices provided the additional space required. Simultaneously, it provided a better starting geometry to model the molecular contacts proposed by Pyle et al. (Pyle, A. M., Murphy, F. L., Cech, T. R. Nature 358, 123-128. (1992)), based on mutational studies involving the J8/7 segment. Two hydrated Mg2+ complexes were placed in the active site of the ribozyme model, using the crystal structure of the functionally similar Klenow fragment (Beese, L.S., Steitz, T.A. EMBO J. 10, 25-33 (1991)) as a guide. The presence of two metal ions in the active site of the intron differs from previous models, which incorporate one metal ion in the catalytic site to fulfill the postulated roles of Mg2+ in catalysis. The reaction profile is simulated based on a trigonal bipyramidal transition state, and the role of the hydrated Mg2+ complexes in catalysis is further explored using molecular orbital calculations.

Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme

NASA Astrophysics Data System (ADS)

Patwardhan, Anjali A.

The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific with C-4' H abstraction resulting in characteristic base propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate. Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo . Our studies with complex ions like cobalt hexaammine and fac-triamminetriaquochromium(III) establish outer sphere interactions of Mg2+ with the hammerhead in the catalytic site. There are two sets of sites, one structural and one catalytic. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Byoung Yoon; Roberts, Barry L.

The three-dimensional finite element mesh capturing realistic geometries of Bayou Choctaw site has been constructed using the sonar and seismic survey data obtained from the field. The mesh is consisting of hexahedral elements because the salt constitutive model is coded using hexahedral elements. Various ideas and techniques to construct finite element mesh capturing artificially and naturally formed geometries are provided. The techniques to reduce the number of elements as much as possible to save on computer run time with maintaining the computational accuracy is also introduced. The steps and methodologies could be applied to construct the meshes of Big Hill,more » Bryan Mound, and West Hackberry strategic petroleum reserve sites. The methodology could be applied to the complicated shape masses for not only various civil and geological structures but also biological applications such as artificial limbs.« less

Lys314 is a nucleophile in non-classical reactions of orotidine-5'-monophosphate decarboxylase.

PubMed

Heinrich, Daniel; Diederichsen, Ulf; Rudolph, Markus Georg

2009-07-06

Orotidine-5'-monophosphate decarboxylase (OMPD) catalyzes the decarboxylation of orotidine-5'-monophosphate (OMP) to uridine-5'-monophosphate (UMP) in an extremely proficient manner. The reaction does not require any cofactors and proceeds by an unknown mechanism. In addition to decarboxylation, OMPD is able to catalyze other reactions. We show that several C6-substituted UMP derivatives undergo hydrolysis or substitution reactions that depend on a lysine residue (Lys314) in the OMPD active site. 6-Cyano-UMP is converted to UMP, and UMP derivatives with good leaving groups inhibit OMPD by a suicide mechanism in which Lys314 covalently binds to the substrate. These non-classical reactivities of human OMPD were characterized by cocrystallization and freeze-trapping experiments with wild-type OMPD and two active-site mutants by using substrate and inhibitor nucleotides. The structures show that the C6-substituents are not coplanar with the pyrimidine ring. The extent of this substrate distortion is a function of the substituent geometry. Structure-based mechanisms for the reaction of 6-substituted UMP derivatives are extracted in accordance with results from mutagenesis, mass spectrometry, and OMPD enzyme activity. The Lys314-based mechanisms explain the chemodiversity of OMPD, and offer a strategy to design mechanism-based inhibitors that could be used for antineoplastic purposes for example.

Equations for estimating bankfull channel geometry and discharge for streams in Massachusetts

USGS Publications Warehouse

Bent, Gardner C.; Waite, Andrew M.

2013-01-01

Regression equations were developed for estimating bankfull geometry—width, mean depth, cross-sectional area—and discharge for streams in Massachusetts. The equations provide water-resource and conservation managers with methods for estimating bankfull characteristics at specific stream sites in Massachusetts. This information can be used for the adminstration of the Commonwealth of Massachusetts Rivers Protection Act of 1996, which establishes a protected riverfront area extending from the mean annual high-water line corresponding to the elevation of bankfull discharge along each side of a perennial stream. Additionally, information on bankfull channel geometry and discharge are important to Federal, State, and local government agencies and private organizations involved in stream assessment and restoration projects. Regression equations are based on data from stream surveys at 33 sites (32 streamgages and 1 crest-stage gage operated by the U.S. Geological Survey) in and near Massachusetts. Drainage areas of the 33 sites ranged from 0.60 to 329 square miles (mi2). At 27 of the 33 sites, field data were collected and analyses were done to determine bankfull channel geometry and discharge as part of the present study. For 6 of the 33 sites, data on bankfull channel geometry and discharge were compiled from other studies done by the U.S. Geological Survey, Natural Resources Conservation Service of the U.S. Department of Agriculture, and the Vermont Department of Environmental Conservation. Similar techniques were used for field data collection and analysis for bankfull channel geometry and discharge at all 33 sites. Recurrence intervals of the bankfull discharge, which represent the frequency with which a stream fills its channel, averaged 1.53 years (median value 1.34 years) at the 33 sites. Simple regression equations were developed for bankfull width, mean depth, cross-sectional area, and discharge using drainage area, which is the most significant explanatory variable in estimating these bankfull characteristics. The use of drainage area as an explanatory variable is also the most commonly published method for estimating these bankfull characteristics. Regional curves (graphic plots) of bankfull channel geometry and discharge by drainage area are presented. The regional curves are based on the simple regression equations and can be used to estimate bankfull characteristics from drainage area. Multiple regression analysis, which includes basin characteristics in addition to drainage area, also was used to develop equations. Variability in bankfull width, mean depth, cross-sectional area, and discharge was more fully explained by the multiple regression equations that include mean-basin slope and drainage area than was explained by equations based on drainage area alone. The Massachusetts regional curves and equations developed in this study are similar, in terms of values of slopes and intercepts, to those developed for other parts of the northeastern United States. Limitations associated with site selection and development of the equations resulted in some constraints for the application of equations and regional curves presented in this report. The curves and equations are applicable to stream sites that have (1) less than about 25 percent of their drainage basin area occupied by urban land use (commercial, industrial, transportation, and high-density residential), (2) little to no streamflow regulation, especially from flood-control structures, (3) drainage basin areas greater than 0.60 mi2 and less than 329 mi2, and (4) a mean basin slope greater than 2.2 percent and less than 23.9 percent. The equations may not be applicable where streams flow through extensive wetlands. The equations also may not apply in areas of Cape Cod and the Islands and the area of southeastern Massachusetts close to Cape Cod with extensive areas of coarse-grained glacial deposits where none of the study sites are located. Regardless of the setting, the regression equations are not intended for use as the sole method of estimating bankfull characteristics; however, they may supplement field identification of the bankfull channel when used in conjunction with field verified bankfull indicators, flood-frequency analysis, or other supporting evidence.

The Structures of the C185S and C185A Mutants of Sulfite Oxidase Reveal Rearrangement of the Active Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, James A.; Wilson, Heather L.; Pushie, M. Jake

Sulfite oxidase (SO) catalyzes the physiologically critical conversion of sulfite to sulfate. Enzymatic activity is dependent on the presence of the metal molybdenum complexed with a pyranopterin-dithiolene cofactor termed molybdopterin. Comparison of the amino acid sequences of SOs from a variety of sources has identified a single conserved Cys residue essential for catalytic activity. The crystal structure of chicken liver sulfite oxidase indicated that this residue, Cys185 in chicken SO, coordinates the Mo atom in the active site. To improve our understanding of the role of this residue in the catalytic mechanism of sulfite oxidase, serine and alanine variants atmore » position 185 of recombinant chicken SO were generated. Spectroscopic and kinetic studies indicate that neither variant is capable of sulfite oxidation. The crystal structure of the C185S variant was determined to 1.9 {angstrom} resolution and to 2.4 {angstrom} resolution in the presence of sulfite, and the C185A variant to 2.8 {angstrom} resolution. The structures of the C185S and C185A variants revealed that neither the Ser or Ala side chains appeared to closely interact with the Mo atom and that a third oxo group replaced the usual cysteine sulfur ligand at the Mo center, confirming earlier extended X-ray absorption fine structure spectroscopy (EXAFS) work on the human C207S mutant. An unexpected result was that in the C185S variant, in the absence of sulfite, the active site residue Tyr322 became disordered as did the loop region flanking it. In the C185S variant crystallized in the presence of sulfite, the Tyr322 residue relocalized to the active site. The C185A variant structure also indicated the presence of a third oxygen ligand; however, Tyr322 remained in the active site. EXAFS studies of the Mo coordination environment indicate the Mo atom is in the oxidized Mo{sup VI} state in both the C185S and C185A variants of chicken SO and show the expected trioxodithiolene active site. Density functional theory calculations of the trioxo form of the cofactor reasonably reproducd the Mo=O distances of the complex; however, the calculated Mo-S distances were slightly longer than either crystallographic or EXAFS measurements. Taken together, these results indicate that the active sites of the C185S and C185A variants are essentially catalytically inactive, the crystal structures of C185S and C185A variants contain a fully oxidized, trioxo form of the cofactor, and Tyr322 can undergo a conformational change that is relevant to the reaction mechanism. Additional DFT calculations demonstrated that such methods can reasonably reproduce the geometry and bond lengths of the active site.« less

DJ-1 Is a Copper Chaperone Acting on SOD1 Activation*

PubMed Central

Girotto, Stefania; Cendron, Laura; Bisaglia, Marco; Tessari, Isabella; Mammi, Stefano; Zanotti, Giuseppe; Bubacco, Luigi

2014-01-01

Lack of oxidative stress control is a common and often prime feature observed in many neurodegenerative diseases. Both DJ-1 and SOD1, proteins involved in familial Parkinson disease and amyotrophic lateral sclerosis, respectively, play a protective role against oxidative stress. Impaired activity and modified expression of both proteins have been observed in different neurodegenerative diseases. A potential cooperative action of DJ-1 and SOD1 in the same oxidative stress response pathway may be suggested based on a copper-mediated interaction between the two proteins reported here. To investigate the mechanisms underlying the antioxidative function of DJ-1 in relation to SOD1 activity, we investigated the ability of DJ-1 to bind copper ions. We structurally characterized a novel copper binding site involving Cys-106, and we investigated, using different techniques, the kinetics of DJ-1 binding to copper ions. The copper transfer between the two proteins was also examined using both fluorescence spectroscopy and specific biochemical assays for SOD1 activity. The structural and functional analysis of the novel DJ-1 copper binding site led us to identify a putative role for DJ-1 as a copper chaperone. Alteration of the coordination geometry of the copper ion in DJ-1 may be correlated to the physiological role of the protein, to a potential failure in metal transfer to SOD1, and to successive implications in neurodegenerative etiopathogenesis. PMID:24567322

From Circle to Hyperbola in Taxicab Geometry

ERIC Educational Resources Information Center

Berger, Ruth I.

2015-01-01

This "Activity for Students" article presents a taxicab geometry problem that engages students in plotting points and observing surprising shapes and underlining reasons for the appearance of figures when working with street grids. With this activity, teachers can provide an extra challenge by writing additional problems introducing a…

Engaging in Problem Posing Activities in a Dynamic Geometry Setting and the Development of Prospective Teachers' Mathematical Knowledge

ERIC Educational Resources Information Center

Lavy, Ilana; Shriki, Atara

2010-01-01

In the present study we explore changes in perceptions of our class of prospective mathematics teachers (PTs) regarding their mathematical knowledge. The PTs engaged in problem posing activities in geometry, using the "What If Not?" (WIN) strategy, as part of their work on computerized inquiry-based activities. Data received from the PTs'…

Sex differences in parameters of bone strength in new recruits: beyond bone density.

PubMed

Evans, Rachel K; Negus, Charles; Antczak, Amanda J; Yanovich, Ran; Israeli, Eran; Moran, Daniel S

2008-11-01

Stress fracture (SF) injuries in new recruits have long been attributed to low bone mineral density (BMD). Low areal BMD assessed using two-dimensional dual-energy x-ray absorptiometry imaging, however, reflects structural density and is affected by smaller measures of bone geometry. Recent studies support a relationship between bone size and SF and indicate that slender bones are more susceptible to damage under identical loading conditions. Peripheral quantitative computed tomography (pQCT) is a three-dimensional imaging tool that provides measures of tissue density and geometry parameters of the tibia, a common site of SF. To evaluate sex differences in parameters of volumetric BMD (vBMD), geometry, and strength of the tibia in new recruits using a novel pQCT image analysis procedure. pQCT images were obtained from 128 healthy men and women (20 male, 108 female, aged 18-21 yr) entering a 4-month gender-integrated combat training program in the Israeli Defense Forces. Tibial scans taken at sites 4% (trabecular bone), 38%, and 66% (cortical bone) from the distal end plate were analyzed using MATLAB to assess whole-bone and regional parameters. Measures included vBMD, geometry (diameter, area, cortical thickness, and canal radius), and strength (moments of inertia and bone strength and slenderness indices). With the exception of normalized canal radius, which did not differ between sexes, all measures of bone geometry (P < 0.0001) and strength (P < 0.0001 to P = 0.07) were greater in men. Women exhibited 2.7% to 3.0% greater cortical vBMD than men, whereas trabecular vBMD was 8.4% lower in women (P < 0.001). These differences remained significant after adjusting for body size. Sex differences in bone geometry and mineralization of the tibia may contribute to a decreased ability to withstand the demands imposed by novel, repetitive exercise in untrained individuals entering recruit training.

Dynamic Geometry as a Context for Exploring Conjectures

ERIC Educational Resources Information Center

Wares, Arsalan

2018-01-01

The purpose of this paper is to provide examples of "non-traditional" proof-related activities that can explored in a dynamic geometry environment by university and high school students of mathematics. These propositions were encountered in the dynamic geometry environment. The author believes that teachers can ask their students to…

Sex differences and growth-related adaptations in bone microarchitecture, geometry, density and strength from childhood to early adulthood: a mixed longitudinal HR-pQCT study

PubMed Central

Gabel, Leigh; Macdonald, Heather M.; McKay, Heather A.

2016-01-01

Sex differences in bone strength and fracture risk are well-documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density and geometry that accompany gains in bone strength. Thus, our objectives are to 1) describe growth related adaptations in bone microarchitecture, geometry, density and strength at the distal tibia and radius in boys and girls; 2) compare differences in adaptations in bone microarchitecture, geometry, density and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9–20y at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity; APHV) and fit a mixed effects model to these longitudinal data. Importantly, boys demonstrated 28–63% greater estimated bone strength across 12 years of longitudinal growth. Boys demonstrated 28–80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls’ values were 2% greater than boys’. Boys demonstrated 13–48% greater cortical and total bone area across growth. Load-to-strength ratio was 26–27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys’ superior bone size and strength compared with girls may confer them a protective advantage. However, boys’ consistently more porous cortices may contribute to boys’ higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. PMID:27556581

Galileo photometry of Apollo landing sites

NASA Technical Reports Server (NTRS)

Helfenstein, P.; Veverka, J.; Head, James W.; Pieters, C.; Pratt, S.; Mustard, J.; Klaasen, K.; Neukum, G.; Hoffmann, H.; Jaumann, R.

1993-01-01

As of December 1992, the Galileo spacecraft performed its second and final flyby (EM2), of the Earth-Moon system, during which it acquired Solid State Imaging (SSI) camera images of the lunar surface suitable for photometric analysis using Hapke's, photometric model. These images, together with those from the first flyby (EM1) in December 1989, provide observations of all of the Apollo landing sites over a wide range of photometric geometries and at eight broadband filter wavelengths ranging from 0.41 micron to 0.99 micron. We have completed a preliminary photometric analysis of Apollo landing sites visible in EM1 images and developed a new strategy for a more complete analysis of the combined EM1 and EM2 data sets in conjunction with telescopic observations and spectrogoniometric measurements of returned lunar samples. No existing single data set, whether from spacecraft flyby, telescopic observation, or laboratory analysis of returned samples, describes completely the light scattering behavior of a particular location on the Moon at all angles of incidence (i), emission (e), and phase angles (a). Earthbased telescopic observations of particular lunar sites provide good coverage of incidence nad phase angles, but their range in emission angle is limited to only a few degrees because of the Moon's synchronous rotation. Spacecraft flyby observations from Galileo are now available for specific lunar features at many photometric geometries unobtainable from Earth; however, this data set lacks coverage at very small phase angles (a less than 13 deg) important for distinguishing the well-known 'opposition effect'. Spectrogoniometric measurements from returned lunar samples can provide photometric coverage at almost any geometry; however, mechanical properties of prepared particulate laboratory samples, such as particle compaction and macroscopic roughness, likely differ from those on the lunar surface. In this study, we have developed methods for the simultaneous analysis of all three types of data: we combine Galileo and telescopic observations to obtain the most complete coverage with photometric geometry, and use spectrogoniometric observations of lunar soils to help distinguish the photometric effects of macroscopic roughness from those caused by particle phase function behavior (i.e., the directional scattering properties of regolith particles).

Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases.

PubMed

Cahn, Jackson K B; Brinkmann-Chen, Sabine; Spatzal, Thomas; Wiig, Jared A; Buller, Andrew R; Einsle, Oliver; Hu, Yilin; Ribbe, Markus W; Arnold, Frances H

2015-06-15

Although most sequenced members of the industrially important ketol-acid reductoisomerase (KARI) family are class I enzymes, structural studies to date have focused primarily on the class II KARIs, which arose through domain duplication. In the present study, we present five new crystal structures of class I KARIs. These include the first structure of a KARI with a six-residue β2αB (cofactor specificity determining) loop and an NADPH phosphate-binding geometry distinct from that of the seven- and 12-residue loops. We also present the first structures of naturally occurring KARIs that utilize NADH as cofactor. These results show insertions in the specificity loops that confounded previous attempts to classify them according to loop length. Lastly, we explore the conformational changes that occur in class I KARIs upon binding of cofactor and metal ions. The class I KARI structures indicate that the active sites close upon binding NAD(P)H, similar to what is observed in the class II KARIs of rice and spinach and different from the opening of the active site observed in the class II KARI of Escherichia coli. This conformational change involves a decrease in the bending of the helix that runs between the domains and a rearrangement of the nicotinamide-binding site. © The Authors Journal Compilation © 2015 Biochemical Society.

Structural elements of the signal propagation pathway in squid rhodopsin and bovine rhodopsin.

PubMed

Sugihara, Minoru; Fujibuchi, Wataru; Suwa, Makiko

2011-05-19

Squid and bovine rhodopsins are G-protein coupled receptors (GPCRs) that activate Gq- and Gt-type G-proteins, respectively. To understand the structural elements of the signal propagation pathway, we performed molecular dynamics (MD) simulations of squid and bovine rhodopsins plus a detailed sequence analysis of class A GPCRs. The computations indicate that although the geometry of the retinal is similar in bovine and squid rhodopsins, the important interhelical hydrogen bond networks are different. In squid rhodopsin, an extended hydrogen bond network that spans ∼13 Å to Tyr315 on the cytoplasmic site is present regardless of the protonation state of Asp80. In contrast, the extended hydrogen bond network is interrupted at Tyr306 in bovine rhodopsin. Those differences in the hydrogen bond network may play significant functional roles in the signal propagation from the retinal binding site to the cytoplasmic site, including transmembrane helix (TM) 6 to which the G-protein binds. The MD calculations demonstrate that the elongated conformation of TM6 in squid rhodopsin is stabilized by salt bridges formed with helix (H) 9. Together with the interhelical hydrogen bonds, the salt bridges between TM6 and H9 stabilize the protein conformation of squid rhodopsin and may hinder the occurrence of large conformational changes that are observed upon activation of bovine rhodopsin. © 2011 American Chemical Society

Micro-Reaction Chamber Electrodes for Neural Stimulation and Recording

PubMed Central

Shanmugasundaram, Balaji; Gluckman, Bruce J.

2012-01-01

Biocompatible electrodes with smaller geometric area are preferred to improve the selectivity of the neural recording and stimulation applications. We introduce the concept of a micro-reaction chamber (µRC) in which a volume within the electrode back plane is used to confine and sequester the electrochemical reactions used for charge passage. The µRC electrode design helps decrease impedance and improves the charge storage capacity without altering the geometry of the active site. Here we demonstrate that µRC electrodes fabricated from 50 µm diameter microwire have significantly improved charge storage capacity and lowered impedance at physiologically relevant frequencies in phosphate buffered saline solution compared with other designs. PMID:22254394

Hayward Fault rate constraints at Berkeley: Evaluation of the 335-meter Strawberry Creek offset

NASA Astrophysics Data System (ADS)

Williams, P. L.

2007-12-01

At UC Berkeley the active channel of Strawberry Creek is offset 335 meters by the Hayward fault and two abandoned channels of Strawberry Creek are laterally offset 580 and 730 meters. These relationships record the displacement of the northern Hayward fault at Berkeley over a period of tens of millennia. The Strawberry Creek site has a similar geometry to the central San Andreas fault's Wallace Creek site, which arguably provides the best geological evidence of "millennial" fault kinematics in California (Sieh and Jahns, 1984). Slip rate determinations are an essential component of overall hazard evaluation for the Hayward fault, and this site is ripe to disclose a long-term form of this parameter, to contrast with geodetic and other geological rate evidence. Large offsets at the site may lower uncertainty in the rate equation relative to younger sites, as the affect of stream abandonment age, generally the greatest source of rate uncertainty, is greatly reduced. This is helpful here because it more-than-offsets uncertainties resulting from piercing projections to the fault. Strawberry Creek and its ancestral channels suggest west-side-up vertical deformation across the Hayward fault at this location. The development of the vertical deformation parameter will complement ongoing geodetic measurements, particularly InSAR, and motivate testing of other geological constraints. Up-to-the-west motion across the Hayward fault at Berkeley has important implications for the partitioning of strain and kinematics of the northern Hayward fault, and may explain anomalous up-on-the-west landforms elsewhere along the fault. For example, geological features of the western Berkeley Hills are consistent with rapid and recent uplift to the west of the fault. On the basis of a preliminary analysis of the offset channels of Strawberry Creek, up-to-the-west uplift is about 0.5mm/yr across the Hayward fault at Berkeley. If this is in fact the long-term rate, the 150 m height of the Hills to the northwest of the Strawberry Creek site was produced during the past about 300,000 years by a significant dip- slip (thrust) component of Hayward fault motion. Rapid and recent uplift of some portions of the East Bay Hills has important implications for fault geometries and slope stability, and should strongly influence the investigation fault hazards in areas that are more complexly deformed.

Ab initio study of the structural properties of ascorbic acid (vitamin C)

NASA Astrophysics Data System (ADS)

Allen, Reeshemah N.; Shukla, M. K.; Reed, Demarcio; Leszczynski, Jerzy

Geometries of the neutral and ionic tautomeric species of ascorbic acid were optimized at the density functional theory (DFT) level using the B3LYP functional. The radical species were evaluated using the unrestricted B3LYP method. Single-point energy calculations were also performed using the Møller-Plesset (MP2) and unrestricted MP2 (UMP2) methods for the closed-shell and open-shell systems, respectively. The effects of aqueous solution were evaluated using the conducting polarized continuum model (CPCM) and polarized continuum model (PCM). The geometries of most stable radicals in the respective groups were also optimized in the water solution using the CPCM model at the UB3LYP level. All calculation were performed using the 6-311++G(d,p) basis set. The nature of stationary points on the gas phase potential energy surfaces (PESs) was evaluated using vibrational frequency calculations; all geometries characterize local minima. The species obtained by the deprotonation of the O3 site is the most stable monoanion of ascorbic acid. For the radical species, the structure obtained by the dehydrogenation of the O3 site is the most stable monoradical. Among the radical anions, the species obtained by the deprotonation of the O3 site and subsequent dehydrogenation of the O2 site is the most stable in the gas phase and in an aqueous medium. The computed isotropic hyperfine coupling constants of this species were found to be in good agreement with the experimental data. Our investigation also supports the earlier findings that the oxidized species of ascorbic acid in water solution by the OH? radical is radical anion of the AAO?3O-2 form. The spin densities and molecular electrostatic potentials are also discussed.

Reusable High Aspect Ratio 3-D Nickel Shadow Mask

PubMed Central

Shandhi, M.M.H.; Leber, M.; Hogan, A.; Warren, D.J.; Bhandari, R.; Negi, S.

2017-01-01

Shadow Mask technology has been used over the years for resistless patterning and to pattern on unconventional surfaces, fragile substrate and biomaterial. In this work, we are presenting a novel method to fabricate high aspect ratio (15:1) three-dimensional (3D) Nickel (Ni) shadow mask with vertical pattern length and width of 1.2 mm and 40 μm respectively. The Ni shadow mask is 1.5 mm tall and 100 μm wide at the base. The aspect ratio of the shadow mask is 15. Ni shadow mask is mechanically robust and hence easy to handle. It is also reusable and used to pattern the sidewalls of unconventional and complex 3D geometries such as microneedles or neural electrodes (such as the Utah array). The standard Utah array has 100 active sites at the tip of the shaft. Using the proposed high aspect ratio Ni shadow mask, the Utah array can accommodate 300 active sites, 200 of which will be along and around the shaft. The robust Ni shadow mask is fabricated using laser patterning and electroplating techniques. The use of Ni 3D shadow mask will lower the fabrication cost, complexity and time for patterning out-of-plane structures. PMID:29056835

Theoretical study on the mechanism of a ring-opening reaction of oxirane by the active-site aspartic dyad of HIV-1 protease.

PubMed

Kóna, Juraj

2008-01-21

Two possible mechanisms of the irreversible inhibition of HIV-1 protease by epoxide inhibitors are investigated on an enzymatic model using ab initio (MP2) and density functional theory (DFT) methods (B3LYP, MPW1K and M05-2X). The calculations predict the inhibition as a general acid-catalyzed nucleophilic substitution reaction proceeding by a concerted SN2 mechanism with a reaction barrier of ca. 15-21 kcal mol(-1). The irreversible nature of the inhibition is characterized by a large negative reaction energy of ca. -17-(-24) kcal mol(-1). A mechanism with a direct proton transfer from an aspartic acid residue of the active site onto the epoxide ring has been shown to be preferred compared to one with the proton transfer from the acid catalyst facilitated by a bridging catalytic water molecule. Based on the geometry of the transition state, structural data important for the design of irreversible epoxide inhibitors of HIV-1 protease were defined. Here we also briefly discuss differences between the epoxide ring-opening reaction in HIV-1 protease and epoxide hydrolase, and the accuracy of the DFT method used.

Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.

PubMed

Sakkal, Leon A; Rajkowski, Kyle Z; Armen, Roger S

2017-06-05

Following insights from recent crystal structures of the muscarinic acetylcholine receptor, binding modes of Positive Allosteric Modulators (PAMs) were predicted under the assumption that PAMs should bind to the extracellular surface of the active state. A series of well-characterized PAMs for adenosine (A 1 R, A 2A R, A 3 R) and muscarinic acetylcholine (M 1 R, M 5 R) receptors were modeled using both rigid and flexible receptor CHARMM-based molecular docking. Studies of adenosine receptors investigated the molecular basis of the probe-dependence of PAM activity by modeling in complex with specific agonist radioligands. Consensus binding modes map common pharmacophore features of several chemical series to specific binding interactions. These models provide a rationalization of how PAM binding slows agonist radioligand dissociation kinetics. M 1 R PAMs were predicted to bind in the analogous M 2 R PAM LY2119620 binding site. The M 5 R NAM (ML-375) was predicted to bind in the PAM (ML-380) binding site with a unique induced-fit receptor conformation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Design and reactivity of Ni-complexes using pentadentate neutral-polypyridyl ligands: Possible mimics of NiSOD.

PubMed

Snider, Victoria G; Farquhar, Erik R; Allen, Mark; Abu-Spetani, Ayah; Mukherjee, Anusree

2017-10-01

Superoxide plays a key role in cell signaling, but can be cytotoxic within cells unless well regulated by enzymes known as superoxide dismutases (SOD). Nickel superoxide dismutase (NiSOD) catalyzes the disproportion of the harmful superoxide radical into hydrogen peroxide and dioxygen. NiSOD has a unique active site structure that plays an important role in tuning the potential of the nickel center to function as an effective catalyst for superoxide dismutation with diffusion controlled rates. The synthesis of structural and functional analogues of NiSOD provides a route to better understand the role of the nickel active site in superoxide dismutation. In this work, the synthesis of a series of nickel complexes supported by nitrogen rich pentadentate ligands is reported. The complexes have been characterized through absorption spectroscopy, mass spectrometry, and elemental analysis. X-ray absorption spectroscopy was employed to establish the oxidation state and the coordination geometry around the metal center. The reactivity of these complexes toward KO 2 was evaluated to elucidate the role of the coordination sphere in controlling superoxide dismutation reactivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Nature of local magma storage zones and geometry of conduit systems below balsatic eruption sites - Pu'u 'O'o, Kilauea East Rift, Hawaii, example

NASA Technical Reports Server (NTRS)

Wilson, Lionel; Head, James W., III

1988-01-01

The fluid dynamics of the well-documented eruptive episodes at Pu'u 'O'o, Kilauea are used to investigate quantitatively the size and shape of the shallow conduit system beneath the vent. The possible geometry of this region is considered. The dynamics of the eruptive episodes is used to place restrictions on the size and shape of the region and thermal calculations are used to show that the geometry is consistent with the region being the fluid residue of the partially cooled, major preepisode 1 dike. The Pu'u 'O'o example is used to illustrate some general properties of shallow magma storage zones.

Circular electrode geometry metal-semiconductor-metal photodetectors

NASA Technical Reports Server (NTRS)

Mcaddo, James A. (Inventor); Towe, Elias (Inventor); Bishop, William L. (Inventor); Wang, Liang-Guo (Inventor)

1994-01-01

The invention comprises a high speed, metal-semiconductor-metal photodetector which comprises a pair of generally circular, electrically conductive electrodes formed on an optically active semiconductor layer. Various embodiments of the invention include a spiral, intercoiled electrode geometry and an electrode geometry comprised of substantially circular, concentric electrodes which are interposed. These electrode geometries result in photodetectors with lower capacitances, dark currents and lower inductance which reduces the ringing seen in the optical pulse response.

Catalyst Architecture for Stable Single Atom Dispersion Enables Site-Specific Spectroscopic and Reactivity Measurements of CO Adsorbed to Pt Atoms, Oxidized Pt Clusters, and Metallic Pt Clusters on TiO2.

PubMed

DeRita, Leo; Dai, Sheng; Lopez-Zepeda, Kimberly; Pham, Nicholas; Graham, George W; Pan, Xiaoqing; Christopher, Phillip

2017-10-11

Oxide-supported precious metal nanoparticles are widely used industrial catalysts. Due to expense and rarity, developing synthetic protocols that reduce precious metal nanoparticle size and stabilize dispersed species is essential. Supported atomically dispersed, single precious metal atoms represent the most efficient metal utilization geometry, although debate regarding the catalytic activity of supported single precious atom species has arisen from difficulty in synthesizing homogeneous and stable single atom dispersions, and a lack of site-specific characterization approaches. We propose a catalyst architecture and characterization approach to overcome these limitations, by depositing ∼1 precious metal atom per support particle and characterizing structures by correlating scanning transmission electron microscopy imaging and CO probe molecule infrared spectroscopy. This is demonstrated for Pt supported on anatase TiO 2 . In these structures, isolated Pt atoms, Pt iso , remain stable through various conditions, and spectroscopic evidence suggests Pt iso species exist in homogeneous local environments. Comparing Pt iso to ∼1 nm preoxidized (Pt ox ) and prereduced (Pt metal ) Pt clusters on TiO 2 , we identify unique spectroscopic signatures of CO bound to each site and find CO adsorption energy is ordered: Pt iso ≪ Pt metal < Pt ox . Pt iso species exhibited a 2-fold greater turnover frequency for CO oxidation than 1 nm Pt metal clusters but share an identical reaction mechanism. We propose the active catalytic sites are cationic interfacial Pt atoms bonded to TiO 2 and that Pt iso exhibits optimal reactivity because every atom is exposed for catalysis and forms an interfacial site with TiO 2 . This approach should be generally useful for studying the behavior of supported precious metal atoms.

Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borbulevych, Oleg Y.; Plumley, Joshua A.; Martin, Roger I.

2014-05-01

Semiempirical quantum-chemical X-ray macromolecular refinement using the program DivCon integrated with PHENIX is described. Macromolecular crystallographic refinement relies on sometimes dubious stereochemical restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule and any covalently bound ligand(s). The ligand stereochemical restraint file (CIF) requires a priori understanding of the ligand geometry within the active site, and creation of the CIF is often an error-prone process owing to the great variety of potential ligand chemistry and structure. Stereochemical restraints have been replaced with more robust functionals through the integration of the linear-scaling, semiempirical quantum-mechanics (SE-QM)more » program DivCon with the PHENIX X-ray refinement engine. The PHENIX/DivCon package has been thoroughly validated on a population of 50 protein–ligand Protein Data Bank (PDB) structures with a range of resolutions and chemistry. The PDB structures used for the validation were originally refined utilizing various refinement packages and were published within the past five years. PHENIX/DivCon does not utilize CIF(s), link restraints and other parameters for refinement and hence it does not make as many a priori assumptions about the model. Across the entire population, the method results in reasonable ligand geometries and low ligand strains, even when the original refinement exhibited difficulties, indicating that PHENIX/DivCon is applicable to both single-structure and high-throughput crystallography.« less

Testing inhomogeneous solvation theory in structure-based ligand discovery.

PubMed

Balius, Trent E; Fischer, Marcus; Stein, Reed M; Adler, Thomas B; Nguyen, Crystal N; Cruz, Anthony; Gilson, Michael K; Kurtzman, Tom; Shoichet, Brian K

2017-08-15

Binding-site water is often displaced upon ligand recognition, but is commonly neglected in structure-based ligand discovery. Inhomogeneous solvation theory (IST) has become popular for treating this effect, but it has not been tested in controlled experiments at atomic resolution. To do so, we turned to a grid-based version of this method, GIST, readily implemented in molecular docking. Whereas the term only improves docking modestly in retrospective ligand enrichment, it could be added without disrupting performance. We thus turned to prospective docking of large libraries to investigate GIST's impact on ligand discovery, geometry, and water structure in a model cavity site well-suited to exploring these terms. Although top-ranked docked molecules with and without the GIST term often overlapped, many ligands were meaningfully prioritized or deprioritized; some of these were selected for testing. Experimentally, 13/14 molecules prioritized by GIST did bind, whereas none of the molecules that it deprioritized were observed to bind. Nine crystal complexes were determined. In six, the ligand geometry corresponded to that predicted by GIST, for one of these the pose without the GIST term was wrong, and three crystallographic poses differed from both predictions. Notably, in one structure, an ordered water molecule with a high GIST displacement penalty was observed to stay in place. Inclusion of this water-displacement term can substantially improve the hit rates and ligand geometries from docking screens, although the magnitude of its effects can be small and its impact in drug binding sites merits further controlled studies.

Dynamic geometry as a context for exploring conjectures

NASA Astrophysics Data System (ADS)

Wares, Arsalan

2018-01-01

The purpose of this paper is to provide examples of 'non-traditional' proof-related activities that can explored in a dynamic geometry environment by university and high school students of mathematics. These propositions were encountered in the dynamic geometry environment. The author believes that teachers can ask their students to construct proofs for these propositions.

A single mutation in the castor Delta9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry.

PubMed

Guy, Jodie E; Abreu, Isabel A; Moche, Martin; Lindqvist, Ylva; Whittle, Edward; Shanklin, John

2006-11-14

Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of the castor desaturase with that of a peroxidase, rubrerythrin, shows remarkable conservation of both identity and geometry of residues surrounding the diiron center, with the exception of residue 199. Position 199 is occupied by a threonine in the castor desaturase, but the equivalent position in rubrerythrin contains a glutamic acid. We previously hypothesized that a carboxylate in this location facilitates oxidase chemistry in rubrerythrin by the close apposition of a residue capable of facilitating proton transfer to the activated oxygen (in a hydrophobic cavity adjacent to the diiron center based on the crystal structure of the oxygen-binding mimic azide). Here we report that desaturase mutant T199D binds substrate but its desaturase activity decreases by approximately 2 x 10(3)-fold. However, it shows a >31-fold increase in peroxide-dependent oxidase activity with respect to WT desaturase, as monitored by single-turnover stopped-flow spectrometry. A 2.65-A crystal structure of T199D reveals active-site geometry remarkably similar to that of rubrerythrin, consistent with its enhanced function as an oxidase enzyme. That a single amino acid substitution can switch reactivity from desaturation to oxidation provides experimental support for the hypothesis that the desaturase evolved from an ancestral oxidase enzyme.

A single mutation in the castor Δ9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry

PubMed Central

Guy, Jodie E.; Abreu, Isabel A.; Moche, Martin; Lindqvist, Ylva; Whittle, Edward; Shanklin, John

2006-01-01

Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of the castor desaturase with that of a peroxidase, rubrerythrin, shows remarkable conservation of both identity and geometry of residues surrounding the diiron center, with the exception of residue 199. Position 199 is occupied by a threonine in the castor desaturase, but the equivalent position in rubrerythrin contains a glutamic acid. We previously hypothesized that a carboxylate in this location facilitates oxidase chemistry in rubrerythrin by the close apposition of a residue capable of facilitating proton transfer to the activated oxygen (in a hydrophobic cavity adjacent to the diiron center based on the crystal structure of the oxygen-binding mimic azide). Here we report that desaturase mutant T199D binds substrate but its desaturase activity decreases by ≈2 × 103-fold. However, it shows a >31-fold increase in peroxide-dependent oxidase activity with respect to WT desaturase, as monitored by single-turnover stopped-flow spectrometry. A 2.65-Å crystal structure of T199D reveals active-site geometry remarkably similar to that of rubrerythrin, consistent with its enhanced function as an oxidase enzyme. That a single amino acid substitution can switch reactivity from desaturation to oxidation provides experimental support for the hypothesis that the desaturase evolved from an ancestral oxidase enzyme. PMID:17088542

Reactivity of dinuclear copper(II) complexes towards melanoma cells: Correlation with its stability, tyrosinase mimicking and nuclease activity.

PubMed

Nunes, Cléia Justino; Borges, Beatriz Essenfelder; Nakao, Lia Sumie; Peyroux, Eugénie; Hardré, Renaud; Faure, Bruno; Réglier, Marius; Giorgi, Michel; Prieto, Marcela Bach; Oliveira, Carla Columbano; Da Costa Ferreira, Ana M

2015-08-01

In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species was very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Moreover, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational study of the electronic structure and magnetic properties of the Ni-C state in [NiFe] hydrogenases including the second coordination sphere.

PubMed

Kampa, Mario; Lubitz, Wolfgang; van Gastel, Maurice; Neese, Frank

2012-12-01

[NiFe] hydrogenases catalyze the reversible formation of H(2). The [NiFe] heterobimetallic active site is rich in redox states. Here, we investigate the key catalytic state Ni-C of Desulfovibrio vulgaris Miyazaki F hydrogenase using a cluster model that includes the truncated amino acids of the entire second coordination sphere of the enzyme. The optimized geometries, computed g tensors, hyperfine coupling constants, and IR stretching frequencies all agree well with experimental values. For the hydride in the bridging position, only a single minimum on the potential energy surface is found, indicating that the hydride bridges and binds to both nickel and iron. The influence of the second coordination sphere on the electronic structure is investigated by comparing results from the large cluster models with truncated models. The largest interactions of the second coordination sphere with the active site concern the hydrogen bonds with the cyanide ligands, which modulate the bond between iron and these ligands. Secondly, the electronic structure of the active site is found to be sensitive to the protonation state of His88. This residue forms a hydrogen bond with the spin-carrying sulfur atom of Cys549, which in turn tunes the spin density at the nickel and coordinating sulfur atoms. In addition, the unequal distribution of spin density over the equatorial cysteine residues results from different orientations of the cysteine side chains, which are kept in their particular orientation by the secondary structure of the protein.

Phe71 in Type III Trypanosomal Protein Arginine Methyltransferase 7 (TbPRMT7) Restricts the Enzyme to Monomethylation.

PubMed

Cáceres, Tamar B; Thakur, Abhishek; Price, Owen M; Ippolito, Nicole; Li, Jun; Qu, Jun; Acevedo, Orlando; Hevel, Joan M

2018-02-27

Protein arginine methyltransferase 7 (PRMT7) is unique within the PRMT family as it is the only isoform known to exclusively make monomethylarginine (MMA). Given its role in epigenetics, the mechanistic basis for the strict monomethylation activity is under investigation. It is thought that PRMT7 enzymes are unable to add a second methyl group because of steric hindrance in the active site that restricts them to monomethylation. To test this, we probed the active site of trypanosomal PRMT7 (TbPRMT7) using accelerated molecular dynamics, site-directed mutagenesis, kinetic, binding, and product analyses. Both the dynamics simulations and experimental results show that the mutation of Phe71 to Ile converts the enzyme from a type III methyltransferase into a mixed type I/II, that is, an enzyme that can now perform dimethylation. In contrast, the serine and alanine mutants of Phe71 preserve the type III behavior of the native enzyme. These results are inconsistent with a sterics-only model to explain product specificity. Instead, molecular dynamics simulations of these variants bound to peptides show hydrogen bonding between would-be substrates and Glu172 of TbPRMT7. Only in the case of the Phe71 to Ile mutation is this interaction between MMA and the enzyme maintained, and the geometry for optimal S N 2 methyl transfer is obtained. The results of these studies highlight the benefit of combined computational and experimental methods in providing a better understanding for how product specificity is dictated by PRMTs.

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.

PubMed

Elinder, Fredrik; Liin, Sara I

2017-01-01

Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (Na V ), potassium (K V ), calcium (Ca V ), and proton (H V ) channels, as well as calcium-activated potassium (K Ca ), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1 : The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2 : The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3 : The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4 : The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5 : The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels.

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels

PubMed Central

Elinder, Fredrik; Liin, Sara I.

2017-01-01

Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1: The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2: The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3: The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4: The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5: The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels. PMID:28220076

Individually addressable vertically aligned carbon nanofiber-based electrochemical probes

NASA Astrophysics Data System (ADS)

Guillorn, M. A.; McKnight, T. E.; Melechko, A.; Merkulov, V. I.; Britt, P. F.; Austin, D. W.; Lowndes, D. H.; Simpson, M. L.

2002-03-01

In this paper we present the fabrication and initial testing results of high aspect ratio vertically aligned carbon nanofiber (VACNF)-based electrochemical probes. Electron beam lithography was used to define the catalytic growth sites of the VACNFs. Following catalyst deposition, VACNF were grown using a plasma enhanced chemical vapor deposition process. Photolithography was performed to realize interconnect structures. These probes were passivated with a thin layer of SiO2, which was then removed from the tips of the VACNF, rendering them electrochemically active. We have investigated the functionality of completed devices using cyclic voltammetry (CV) of ruthenium hexammine trichloride, a highly reversible, outer sphere redox system. The faradaic current obtained during CV potential sweeps shows clear oxidation and reduction peaks at magnitudes that correspond well with the geometry of these nanoscale electrochemical probes. Due to the size and the site-specific directed synthesis of the VACNFs, these probes are ideally suited for characterizing electrochemical phenomena with an unprecedented degree of spatial resolution.

Visualizing the Reaction Cycle in an Iron(II)- and 2-(Oxo)-glutarate-Dependent Hydroxylase.

PubMed

Mitchell, Andrew J; Dunham, Noah P; Martinie, Ryan J; Bergman, Jonathan A; Pollock, Christopher J; Hu, Kai; Allen, Benjamin D; Chang, Wei-Chen; Silakov, Alexey; Bollinger, J Martin; Krebs, Carsten; Boal, Amie K

2017-10-04

Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon by iron(IV)-oxo (ferryl) complexes. Control of the relative orientation of the substrate C-H and ferryl Fe-O bonds, primarily by direction of the oxo group into one of two cis-related coordination sites (termed inline and offline), may be generally important for control of the reaction outcome. Neither the ferryl complexes nor their fleeting precursors have been crystallographically characterized, hindering direct experimental validation of the offline hypothesis and elucidation of the means by which the protein might dictate an alternative oxo position. Comparison of high-resolution X-ray crystal structures of the substrate complex, an Fe(II)-peroxysuccinate ferryl precursor, and a vanadium(IV)-oxo mimic of the ferryl intermediate in the l-arginine 3-hydroxylase, VioC, reveals coordinated motions of active site residues that appear to control the intermediate geometries to determine reaction outcome.

Measuring the effects of pore-pressure changes on seismic amplitude using crosswell continuous active-source seismic monitoring (CASSM)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchesini, Pierpaolo; Daley, Thomas; Ajo-Franklin, Jonathan

Monitoring of time-varying reservoir properties, such as the state of stress, is a primary goal of geophysical investigations, including for geological sequestration of CO 2, enhanced hydrocarbon recovery (EOR), and other subsurface engineering activities. In this work, we used Continuous Active-Source Seismic Monitoring (CASSM), with cross-well geometry, to measure variation in seismic coda amplitude, as a consequence of effective stress change (in the form of changes in pore fluid pressure). To our knowledge, the presented results are the first in-situ example of such crosswell measurement at reservoir scale and in field conditions. Data compliment the findings of our previous workmore » which investigated the relationship between pore fluid pressure and seismic velocity (velocity-stress sensitivity) using the CASSM system at the same field site (Marchesini et al., 2017, in review). We find that P-wave coda amplitude decreases with decreasing pore pressure (increasing effective stress).« less

On the behavior of Bronsted-Evans-Polanyi Relations for Transition Metal Oxides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vojvodic, Aleksandra

2011-08-22

Versatile Broensted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strongmore » intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a 'cyclic' behavior in the transition state characteristics upon change of the active transition metal of the oxide.« less

Ab initio ONIOM-molecular dynamics (MD) study on the deamination reaction by cytidine deaminase.

PubMed

Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

2007-08-23

We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase by calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket of the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determining step is the release of the NH3 molecule.

Tilt and strain deformation induced by hydrologically active natural fractures: application to the tiltmeters installed in Sainte-Croix-aux-Mines observatory (France)

NASA Astrophysics Data System (ADS)

Longuevergne, Laurent; Florsch, Nicolas; Boudin, Frédéric; Oudin, Ludovic; Camerlynck, Christian

2009-08-01

We investigate the deformation induced by water pressure variations in hydrologically active natural fractures, and recorded by tiltmeters and strainmeters. The deformation associated with a single fracture is derived using finite-element modelling (FEM). A range in fracture geometries is explored, first to highlight the sensitivity of each geometrical parameter to the deformation, and secondly to allow transfer to observation sites. Water level variations in the fracture are then derived from a hydrological model, driven by observed rainfall, and calibrated on fracture water flow measurements. The modelling results are explicitly applied to constrain the local hydrological contribution to observations with the 100-m-long hydrostatic tiltmeter installed at Sainte-Croix-aux-Mines (France). Our study shows that well-founded physical modelling of local hydrological effect allows a substantial correction of records in observatories.

Evaluating the potential for halogen bonding in ketosteroid isomerase’s oxyanion hole using unnatural amino acid mutagenesis

PubMed Central

Kraut, Daniel A; Churchil, Michael J; Dawson, Phillip E

2009-01-01

There has recently been an increasing interest in controlling macromolecular conformations and interactions through halogen bonding. Halogen bonds are favorable electrostatic interactions between polarized, electropositive chlorine, bromine or iodine atoms and electronegative atoms such as oxygen or nitrogen. These interactions have been likened to hydrogen bonds both in terms of their favored acceptor molecules, their geometries, and their energetics. We asked whether a halogen bond could replace a hydrogen bond in the oxyanion hole of ketosteroid isomerase, using semi-synthetic enzyme containing para-halogenated phenylalanine derivatives to replace the tyrosine hydrogen bond donor. Formation of a halogen bond to the oxyanion in the transition state would be expected to rescue the effects of mutation to phenylalanine, but all of the halogenated enzymes were comparable in activity to the phenylalanine mutant. We conclude that, at least in this active site, a halogen bond cannot functionally replace a hydrogen bond. PMID:19260691

Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism

PubMed Central

Dahms, Sven O.; Arciniega, Marcelino; Steinmetzer, Torsten; Huber, Robert; Than, Manuel E.

2016-01-01

Proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. An unbalanced activity of these enzymes is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Novel protein crystallographic structures of the prototypical PC family member furin in different functional states were determined to 1.8–2.0 Å. These, together with biochemical data and modeling by molecular dynamics calculations, suggest essential elements underlying its unusually high substrate specificity. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the “off state,” incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active “on state” seen in inhibitor-bound furin; and the respective (iii) calcium-free and (iv) calcium-bound forms. The transition from the off to the on state is triggered by ligand binding at subsites S1 to S4 and appears to underlie the preferential recognition of the four-residue sequence motif of furin. The molecular dynamics simulations of the four structural states reflect the experimental observations in general and provide approximations of the respective stabilities. Ligation by calcium at the PC-specific binding site II influences the active-site geometry and determines the rotamer state of the oxyanion hole-forming Asn295, and thus adds a second level of the activity modulation of furin. The described crystal forms and the observations of different defined functional states may foster the development of new tools and strategies for pharmacological intervention targeting furin. PMID:27647913

The role of chloride in the mechanism of O(2) activation at the mononuclear nonheme Fe(II) center of the halogenase HctB.

PubMed

Pratter, Sarah M; Light, Kenneth M; Solomon, Edward I; Straganz, Grit D

2014-07-02

Mononuclear nonheme Fe(II) (MNH) and α-ketoglutarate (α-KG) dependent halogenases activate O2 to perform oxidative halogenations of activated and nonactivated carbon centers. While the mechanism of halide incorporation into a substrate has been investigated, the mechanism by which halogenases prevent oxidations in the absence of chloride is still obscure. Here, we characterize the impact of chloride on the metal center coordination and reactivity of the fatty acyl-halogenase HctB. Stopped-flow kinetic studies show that the oxidative transformation of the Fe(II)-α-KG-enzyme complex is >200-fold accelerated by saturating concentrations of chloride in both the absence and presence of a covalently bound substrate. By contrast, the presence of substrate, which generally brings about O2 activation at enzymatic MNH centers, only has an ∼10-fold effect in the absence of chloride. Circular dichroism (CD) and magnetic CD (MCD) studies demonstrate that chloride binding triggers changes in the metal center ligation: chloride binding induces the proper binding of the substrate as shown by variable-temperature, variable-field (VTVH) MCD studies of non-α-KG-containing forms and the conversion from six-coordinate (6C) to 5C/6C mixtures when α-KG is bound. In the presence of substrate, a site with square pyramidal five-coordinate (5C) geometry is observed, which is required for O2 activation at enzymatic MNH centers. In the absence of substrate an unusual trigonal bipyramidal site is formed, which accounts for the observed slow, uncoupled reactivity. Molecular dynamics simulations suggest that the binding of chloride to the metal center of HctB leads to a conformational change in the enzyme that makes the active site more accessible to the substrate and thus facilitates the formation of the catalytically competent enzyme-substrate complex. Results are discussed in relation to other MNH dependent halogenases.

Debris flow occurrence and sediment persistence, Upper Colorado River Valley, CO

USGS Publications Warehouse

Grimsley, Kyle J; Rathburn, Sara L.; Friedman, Jonathan M.; Mangano, Joseph F.

2016-01-01

Debris flow magnitudes and frequencies are compared across the Upper Colorado River valley to assess influences on debris flow occurrence and to evaluate valley geometry effects on sediment persistence. Dendrochronology, field mapping, and aerial photographic analysis are used to evaluate whether a 19th century earthen, water-conveyance ditch has altered the regime of debris flow occurrence in the Colorado River headwaters. Identifying any shifts in disturbance processes or changes in magnitudes and frequencies of occurrence is fundamental to establishing the historical range of variability (HRV) at the site. We found no substantial difference in frequency of debris flows cataloged at eleven sites of deposition between the east (8) and west (11) sides of the Colorado River valley over the last century, but four of the five largest debris flows originated on the west side of the valley in association with the earthen ditch, while the fifth is on a steep hillslope of hydrothermally altered rock on the east side. These results suggest that the ditch has altered the regime of debris flow activity in the Colorado River headwaters as compared to HRV by increasing the frequency of debris flows large enough to reach the Colorado River valley. Valley confinement is a dominant control on response to debris flows, influencing volumes of aggradation and persistence of debris flow deposits. Large, frequent debris flows, exceeding HRV, create persistent effects due to valley geometry and geomorphic setting conducive to sediment storage that are easily delineated by valley confinement ratios which are useful to land managers.

Debris Flow Occurrence and Sediment Persistence, Upper Colorado River Valley, CO

NASA Astrophysics Data System (ADS)

Grimsley, K. J.; Rathburn, S. L.; Friedman, J. M.; Mangano, J. F.

2016-07-01

Debris flow magnitudes and frequencies are compared across the Upper Colorado River valley to assess influences on debris flow occurrence and to evaluate valley geometry effects on sediment persistence. Dendrochronology, field mapping, and aerial photographic analysis are used to evaluate whether a 19th century earthen, water-conveyance ditch has altered the regime of debris flow occurrence in the Colorado River headwaters. Identifying any shifts in disturbance processes or changes in magnitudes and frequencies of occurrence is fundamental to establishing the historical range of variability (HRV) at the site. We found no substantial difference in frequency of debris flows cataloged at eleven sites of deposition between the east (8) and west (11) sides of the Colorado River valley over the last century, but four of the five largest debris flows originated on the west side of the valley in association with the earthen ditch, while the fifth is on a steep hillslope of hydrothermally altered rock on the east side. These results suggest that the ditch has altered the regime of debris flow activity in the Colorado River headwaters as compared to HRV by increasing the frequency of debris flows large enough to reach the Colorado River valley. Valley confinement is a dominant control on response to debris flows, influencing volumes of aggradation and persistence of debris flow deposits. Large, frequent debris flows, exceeding HRV, create persistent effects due to valley geometry and geomorphic setting conducive to sediment storage that are easily delineated by valley confinement ratios which are useful to land managers.

Debris Flow Occurrence and Sediment Persistence, Upper Colorado River Valley, CO.

PubMed

Grimsley, K J; Rathburn, S L; Friedman, J M; Mangano, J F

2016-07-01

Debris flow magnitudes and frequencies are compared across the Upper Colorado River valley to assess influences on debris flow occurrence and to evaluate valley geometry effects on sediment persistence. Dendrochronology, field mapping, and aerial photographic analysis are used to evaluate whether a 19th century earthen, water-conveyance ditch has altered the regime of debris flow occurrence in the Colorado River headwaters. Identifying any shifts in disturbance processes or changes in magnitudes and frequencies of occurrence is fundamental to establishing the historical range of variability (HRV) at the site. We found no substantial difference in frequency of debris flows cataloged at eleven sites of deposition between the east (8) and west (11) sides of the Colorado River valley over the last century, but four of the five largest debris flows originated on the west side of the valley in association with the earthen ditch, while the fifth is on a steep hillslope of hydrothermally altered rock on the east side. These results suggest that the ditch has altered the regime of debris flow activity in the Colorado River headwaters as compared to HRV by increasing the frequency of debris flows large enough to reach the Colorado River valley. Valley confinement is a dominant control on response to debris flows, influencing volumes of aggradation and persistence of debris flow deposits. Large, frequent debris flows, exceeding HRV, create persistent effects due to valley geometry and geomorphic setting conducive to sediment storage that are easily delineated by valley confinement ratios which are useful to land managers.

Guided discovery of the nine-point circle theorem and its proof

NASA Astrophysics Data System (ADS)

Buchbinder, Orly

2018-01-01

The nine-point circle theorem is one of the most beautiful and surprising theorems in Euclidean geometry. It establishes an existence of a circle passing through nine points, all of which are related to a single triangle. This paper describes a set of instructional activities that can help students discover the nine-point circle theorem through investigation in a dynamic geometry environment, and consequently prove it using a method of guided discovery. The paper concludes with a variety of suggestions for the ways in which the whole set of activities can be implemented in geometry classrooms.

Potential flood hazards and hydraulic characteristics of distributary-flow areas in Maricopa County, Arizona

USGS Publications Warehouse

Hjalmarson, H.W.

1994-01-01

Flood hazards of distributary-flow areas in Maricopa County, Arizona, can be distinguished on the basis of morphological features. Five distributary-flow areas represent the range of flood-hazard degree in the study area. Descriptive factors, including the presence of desert varnish and the absence of saguaro cactus, are more useful than traditional hydraulic-based methods in defining hazards. The width, depth, and velocity exponents of the hydraulic-geometry relations at the primary diffluences of the sites are similar to theoretical exponents for streams with cohesive bank material and the average exponents of stream channels in other areas in the United States. Because of the unexplained scatter of the values of the exponent of channel width, however, the use of average hydraulic-geometry relations is con- sidered inappropriate for characterizing flood hazards for specific distributary-flow in Maricopa County. No evidence has been found that supports the use of stochastic modeling of flows or flood hazards of many distributary-flow areas. The surface of many distributary-flow areas is stable with many distributary channels eroded in the calcreted surface material. Many distributary- flow areas do not appear to be actively aggrading today, and the paths of flow are not changing.

Pinpointing the base of the AGN jets through general relativistic X-ray reverberation studies

NASA Astrophysics Data System (ADS)

Emmanoulopoulos, D.

2015-03-01

Many theoretical models of Active Galactic Nuclei (AGN) predict that the X-ray corona, lying above the black hole, constitutes the base of the X-ray jet. Thus, by studying the exact geometry of the close black hole environment, we can pinpoint the launching site of the jet. Detection of negative X-ray reverberation time delays (i.e. soft band X-ray variations lagging behind the corresponding hard band X-ray variations) can yield significant information about the geometrical properties of the AGN, such as the location of the X-ray source, as well as the physical properties of the the black hole, such as its mass and spin. In the frame-work of the lamp-post geometry, I present the first systematic X-ray time-lag modelling results of an ensemble of 12 AGN, using a fully general relativistic (GR) ray tracing approach for the estimation of the systems' response functions. By combing these state-of-the art GR response models with statistically innovative fitting routines, I derive the geometrical layout of the close BH environment for each source, unveiling the position of the AGN jet-base.

Mechanism of conformational coupling in SecA: Key role of hydrogen-bonding networks and water interactions.

PubMed

Milenkovic, Stefan; Bondar, Ana-Nicoleta

2016-02-01

SecA uses the energy yielded by the binding and hydrolysis of adenosine triphosphate (ATP) to push secretory pre-proteins across the plasma membrane in bacteria. Hydrolysis of ATP occurs at the nucleotide-binding site, which contains the conserved carboxylate groups of the DEAD-box helicases. Although crystal structures provide valuable snapshots of SecA along its reaction cycle, the mechanism that ensures conformational coupling between the nucleotide-binding site and the other domains of SecA remains unclear. The observation that SecA contains numerous hydrogen-bonding groups raises important questions about the role of hydrogen-bonding networks and hydrogen-bond dynamics in long-distance conformational couplings. To address these questions, we explored the molecular dynamics of SecA from three different organisms, with and without bound nucleotide, in water. By computing two-dimensional hydrogen-bonding maps we identify networks of hydrogen bonds that connect the nucleotide-binding site to remote regions of the protein, and sites in the protein that respond to specific perturbations. We find that the nucleotide-binding site of ADP-bound SecA has a preferred geometry whereby the first two carboxylates of the DEAD motif bridge via hydrogen-bonding water. Simulations of a mutant with perturbed ATP hydrolysis highlight the water-bridged geometry as a key structural element of the reaction path. Copyright © 2015. Published by Elsevier B.V.

Combined VSWIR/TIR Products Overview: Issues and Examples

NASA Technical Reports Server (NTRS)

Knox, Robert G.

2010-01-01

The presentation provides a summary of VSWIR data collected at 19-day intervals for most areas. TIR data was collected both day and night on a 5-day cycle (more frequently at higher latitudes), the TIR swath is four times as wide as VSWIR, and the 5-day orbit repeat is approximate. Topics include nested swath geometry for reference point design and coverage simulations for sample FLUXNET tower sites. Other points examined include variation in latitude for revisit frequency, overpass times, and TIR overlap geometry and timing between VSWIR data collections.

Tearing Plastic: A Laboratory Exercise on Fractals and Hyperbolic Geometry

ERIC Educational Resources Information Center

Taylor, Ron; Timberlake, Todd

2007-01-01

In this article we describe a hands-on activity for a liberal arts mathematics course that focuses on the beauty and unity of mathematics. The purpose of the activity is to tie together several topics in the context of a "real-world" situation. These topics include: fractals, non-Euclidean geometry, symmetry, and Platonic solids. This activity…

The Use of Molecular Modeling as "Pseudoexperimental" Data for Teaching VSEPR as a Hands-On General Chemistry Activity

ERIC Educational Resources Information Center

Martin, Christopher B.; Vandehoef, Crissie; Cook, Allison

2015-01-01

A hands-on activity appropriate for first-semester general chemistry students is presented that combines traditional VSEPR methods of predicting molecular geometries with introductory use of molecular modeling. Students analyze a series of previously calculated output files consisting of several molecules each in various geometries. Each structure…

Geometry-dependent viscosity reduction in sheared active fluids

NASA Astrophysics Data System (ADS)

Słomka, Jonasz; Dunkel, Jörn

2017-04-01

We investigate flow pattern formation and viscosity reduction mechanisms in active fluids by studying a generalized Navier-Stokes model that captures the experimentally observed bulk vortex dynamics in microbial suspensions. We present exact analytical solutions including stress-free vortex lattices and introduce a computational framework that allows the efficient treatment of higher-order shear boundary conditions. Large-scale parameter scans identify the conditions for spontaneous flow symmetry breaking, geometry-dependent viscosity reduction, and negative-viscosity states amenable to energy harvesting in confined suspensions. The theory uses only generic assumptions about the symmetries and long-wavelength structure of active stress tensors, suggesting that inviscid phases may be achievable in a broad class of nonequilibrium fluids by tuning confinement geometry and pattern scale selection.

The Computational Fluid Dynamics Rupture Challenge 2013—Phase I: prediction of rupture status in intracranial aneurysms.

PubMed

Janiga, G; Berg, P; Sugiyama, S; Kono, K; Steinman, D A

2015-03-01

Rupture risk assessment for intracranial aneurysms remains challenging, and risk factors, including wall shear stress, are discussed controversially. The primary purpose of the presented challenge was to determine how consistently aneurysm rupture status and rupture site could be identified on the basis of computational fluid dynamics. Two geometrically similar MCA aneurysms were selected, 1 ruptured, 1 unruptured. Participating computational fluid dynamics groups were blinded as to which case was ruptured. Participants were provided with digitally segmented lumen geometries and, for this phase of the challenge, were free to choose their own flow rates, blood rheologies, and so forth. Participants were asked to report which case had ruptured and the likely site of rupture. In parallel, lumen geometries were provided to a group of neurosurgeons for their predictions of rupture status and site. Of 26 participating computational fluid dynamics groups, 21 (81%) correctly identified the ruptured case. Although the known rupture site was associated with low and oscillatory wall shear stress, most groups identified other sites, some of which also experienced low and oscillatory shear. Of the 43 participating neurosurgeons, 39 (91%) identified the ruptured case. None correctly identified the rupture site. Geometric or hemodynamic considerations favor identification of rupture status; however, retrospective identification of the rupture site remains a challenge for both engineers and clinicians. A more precise understanding of the hemodynamic factors involved in aneurysm wall pathology is likely required for computational fluid dynamics to add value to current clinical decision-making regarding rupture risk. © 2015 by American Journal of Neuroradiology.

Effects of solutes on dislocation nucleation from grain boundaries

DOE PAGES

Borovikov, Valery; Mendelev, Mikhail I.; King, Alexander H.

2016-12-27

When grain sizes are reduced to the nanoscale, grain boundaries (GB) become the dominant sources of the dislocations that enable plastic deformation. Here, we present the first molecular dynamics (MD) study of the effect of substitutional solutes on the dislocation nucleation process from GBs during uniaxial tensile deformation. A simple bi-crystal geometry is utilized in which the nucleation and propagation of dislocations away from a GB is the only active mechanism of plastic deformation. Solutes with atomic radii both larger and smaller than the solvent atomic radius were considered. Although the segregation sites are different for the two cases, bothmore » produce increases in the stress required to nucleate a dislocation. MD simulations at room temperature revealed that this increase in the nucleation stress is associated with changes of the GB structure at the emission site caused by dislocation emission, leading to increases in the heats of segregation of the solute atoms, which cannot diffuse to lower-energy sites on the timescale of the nucleation event. These results contribute directly to understanding the strength of nanocrystalline materials, and suggest suitable directions for nanocrystalline alloy design leading toward structural applications.« less

Prediction of Viking lander camera image quality

NASA Technical Reports Server (NTRS)

Huck, F. O.; Burcher, E. E.; Jobson, D. J.; Wall, S. D.

1976-01-01

Formulations are presented that permit prediction of image quality as a function of camera performance, surface radiance properties, and lighting and viewing geometry. Predictions made for a wide range of surface radiance properties reveal that image quality depends strongly on proper camera dynamic range command and on favorable lighting and viewing geometry. Proper camera dynamic range commands depend mostly on the surface albedo that will be encountered. Favorable lighting and viewing geometries depend mostly on lander orientation with respect to the diurnal sun path over the landing site, and tend to be independent of surface albedo and illumination scattering function. Side lighting with low sun elevation angles (10 to 30 deg) is generally favorable for imaging spatial details and slopes, whereas high sun elevation angles are favorable for measuring spectral reflectances.

Minimizing pulling geometry errors in atomic force microscope single molecule force spectroscopy.

PubMed

Rivera, Monica; Lee, Whasil; Ke, Changhong; Marszalek, Piotr E; Cole, Daniel G; Clark, Robert L

2008-10-01

In atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS), it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Recent studies, however, have indicated that the pulling geometry errors can drastically alter the measured force-extension relationship of molecules. Here we describe a software-based alignment method that repositions the cantilever such that it is located directly above the molecule's substrate attachment site. By aligning the applied force with the measurement axis, the molecule is no longer undergoing combined loading, and the full force can be measured by the cantilever. Simulations and experimental results verify the ability of the alignment program to minimize pulling geometry errors in AFM-SMFS studies.

Microseismic and deformation imaging of hydraulic fracture growth and geometry in the C sand interval, GRI/DOE M-Site project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warpinski, N.R.; Uhl, J.E.; Engler, B.P.

Six hydraulic-fracture injections into a fluvial sandstone at a depth of 4300 ft were monitored with multi-level tri-axial seismic receivers in two wells and an inclinometer array in one well, resulting in maps of the growth and final geometry of each fracture injection. These diagnostic images show the progression of height and length growth with fluid volume, rate and viscosity. Complexities associated with shut downs and high treatment pressures can be observed. Validation of the seismic geometry was made with the inclinometers and diagnostic procedures in an intersecting well. Fracture information related to deformation, such as fracture closure pressure, residualmore » widths, and final prop distribution, were obtained from the inclinometer data.« less

Diffusion of a Concentrated Lattice Gas in a Regular Comb Structure

NASA Astrophysics Data System (ADS)

Garcia, Paul; Wentworth, Christopher

2008-10-01

Understanding diffusion in constrained geometries is of interest in a variety of contexts as varied as mass transport in disordered solids, such as a percolation cluster, or intercellular transport of water molecules in biological tissue. In this investigation we explore diffusion in a very simple constrained geometry: a comb-like structure involving a one-dimensional backbone of lattice sites with regularly spaced teeth of fixed length. The model considered assumes a fixed concentration of diffusing particles can hop to nearest-neighbor sites only, and they do not interact with each other except that double occupancy is not allowed. The system is simulated using a Monte Carlo simulation procedure. The mean-square displacement of a tagged particle is calculated from the simulation as a function of time. The simulation shows normal diffusive behavior after a period of anomalous diffusion that increases as the tooth size increases.

Satellite-Based Investigations of the Transition from an Oceanic to Continental Transform Margin

NASA Technical Reports Server (NTRS)

Miller, M. Meghan

1998-01-01

Detailed characterization of neotectonics evolution of the Valle de San Felipe and Arroyo Grande regions in northern Baja California. Reoccupied GEOMEX GPS sites, and occupied a regional GPS (Global Positioning System) network. The Baja California peninsula in Mexico offers a unique setting for studying the kinematic evolution of a complex, active strike-slip/rift plate boundary. We are currently conducting remote sensing, geologic, and geodetic studies of this boundary. The combined data sets will yield instantaneous and time integrated views of its evolution. This proposal solicits renewed funding from NASA to support remote sensing and geologic studies. During the late Cenozoic, Baja California has been the locus of changing fault geometry that has accommodated components of the relative motion between the North America and Pacific plates. Contemporary slip between the two plates occurs in a broad zone that encompasses much of southern California and the Baja California Peninsula. The transfer of slip across this zone in southern California is relatively well understood. South of the border, the geometry and role of specific faults and structural provinces in transferring plate margin deformation across the peninsula is enigmatic. Results We use Landsat Thematic Mapper imagery of the Baja California Peninsula to identify recent and active faults, and then conduct field studies that characterize the temporal and spatial structural evolution of the plate margin. These data address questions concerning the neotectonic development of the Gulf of California, the Baja California Peninsula, and their role in evolution of the post-Miocene Pacific - North American plate boundary. Moreover, these studies provide constraints on the geometry of active faults, allowing more exact understanding of the results of ongoing NASA-supported geodetic experiments. In addition, anticipated publication of the TM scenes will provide a widely available geological data base for relatively little-known peninsula California. Achievements include development of an ArcInfo data base of Landsat and SPOT imagery, detailed field studies of Neogene structures in northeastern Baja California, and new constraint on Pacific - North America plate motion at Baja California latitudes. These results are reported in maps, manuscripts and data products which are published or near completion.

Methods for estimating streamflow at mountain fronts in southern New Mexico

USGS Publications Warehouse

Waltemeyer, S.D.

1994-01-01

The infiltration of streamflow is potential recharge to alluvial-basin aquifers at or near mountain fronts in southern New Mexico. Data for 13 streamflow-gaging stations were used to determine a relation between mean annual stream- flow and basin and climatic conditions. Regression analysis was used to develop an equation that can be used to estimate mean annual streamflow on the basis of drainage areas and mean annual precipi- tation. The average standard error of estimate for this equation is 46 percent. Regression analysis also was used to develop an equation to estimate mean annual streamflow on the basis of active- channel width. Measurements of the width of active channels were determined for 6 of the 13 gaging stations. The average standard error of estimate for this relation is 29 percent. Stream- flow estimates made using a regression equation based on channel geometry are considered more reliable than estimates made from an equation based on regional relations of basin and climatic conditions. The sample size used to develop these relations was small, however, and the reported standard error of estimate may not represent that of the entire population. Active-channel-width measurements were made at 23 ungaged sites along the Rio Grande upstream from Elephant Butte Reservoir. Data for additional sites would be needed for a more comprehensive assessment of mean annual streamflow in southern New Mexico.

Rational Design of N- S- Fe- Doped Nanoporous Carbon Catalysts from Covalent Triazine Framework for High Efficient ORR.

PubMed

Zhu, Yuanzhi; Chen, Xifan; Liu, Jing; Zhang, Junfeng; Xu, Danyun; Peng, Wenchao; Li, Yang; Zhang, Guoliang; Zhang, Fengbao; Fan, Xiaobin

2018-05-15

Porous organic polymers (POFs) are promising precursors for developing high performance transition metal-nitrogen-carbon (M-N/C) catalysts towards ORR. But the rational design of POFs precursors remain a great challenge, because of the elusive structural association between the sacrificial POFs and the final M-N/C catalysts. Based on covalent triazine frameworks (CTFs), we developed a series of sulfur-doped Fe-N/C catalysts by selecting six different aromatic nitriles as building blocks. A new mixed solvent of molten FeCl3 and S was used for CTF polymerization, which benefit the formation of Fe-Nx site and make the subsequent pyrolysis process more convenient. Comprehensive study on these CTF-derived catalysts shows their ORR activities are not directly dependent on the theoretical N/C ratio of the building block, but closely correlated to the ratios of the nitrile group to benzene ring (Nnitrile/Nbenzene) and geometries of the building blocks. The high ratios of the Nnitrile/Nbenzene are crucial for ORR activity of the final catalysts due to the formation of more N-doped microporous and Fe-Nx sites in pyrolysis possess. The optimized catalyst shows high ORR performances in acid and superior ORR activity to the Pt/C catalysts under alkaline conditions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Probing catalytic rate enhancement during intramembrane proteolysis.

PubMed

Arutyunova, Elena; Smithers, Cameron C; Corradi, Valentina; Espiritu, Adam C; Young, Howard S; Tieleman, D Peter; Lemieux, M Joanne

2016-09-01

Rhomboids are ubiquitous intramembrane serine proteases involved in various signaling pathways. While the high-resolution structures of the Escherichia coli rhomboid GlpG with various inhibitors revealed an active site comprised of a serine-histidine dyad and an extensive oxyanion hole, the molecular details of rhomboid catalysis were unclear because substrates are unknown for most of the family members. Here we used the only known physiological pair of AarA rhomboid with its psTatA substrate to decipher the contribution of catalytically important residues to the reaction rate enhancement. An MD-refined homology model of AarA was used to identify residues important for catalysis. We demonstrated that the AarA active site geometry is strict and intolerant to alterations. We probed the roles of H83 and N87 oxyanion hole residues and determined that substitution of H83 either abolished AarA activity or reduced the transition state stabilization energy (ΔΔG‡) by 3.1 kcal/mol; substitution of N87 decreased ΔΔG‡ by 1.6-3.9 kcal/mol. Substitution M154, a residue conserved in most rhomboids that stabilizes the catalytic general base, to tyrosine, provided insight into the mechanism of nucleophile generation for the catalytic dyad. This study provides a quantitative evaluation of the role of several residues important for hydrolytic efficiency and oxyanion stabilization during intramembrane proteolysis.

Dinosaurs, Dinosaur Eggs, and Probability.

ERIC Educational Resources Information Center

Teppo, Anne R.; Hodgson, Ted

2001-01-01

Outlines several recommendations for teaching probability in the secondary school. Offers an activity that employs simulation by hand and using a programmable calculator in which geometry, analytical geometry, and discrete mathematics are explored. (KHR)

De novo design, synthesis and characterisation of MP3, a new catalytic four-helix bundle hemeprotein.

PubMed

Faiella, Marina; Maglio, Ornella; Nastri, Flavia; Lombardi, Angela; Lista, Liliana; Hagen, Wilfred R; Pavone, Vincenzo

2012-12-07

A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the excellent structural properties of four-helix bundle protein scaffolds with the activity of natural peroxidases, was synthesised and characterised. This new hemeprotein model was developed by covalently linking the deuteroporphyrin to two peptide chains of different compositions to obtain an asymmetric helix-loop-helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant distal site that is able to accommodate exogenous ligands or substrates; and 3) an Arg residue in the distal site that should assist in hydrogen peroxide activation to give an HRP-like catalytic process. MP3 was synthesised and characterised as its iron complex. CD measurements revealed the high helix-forming propensity of the peptide, confirming the appropriateness of the model procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)-MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the possibility of mimicking the functional features of natural enzymes. The synergistic application of de novo design methods, synthetic procedures, and spectroscopic characterisation, described herein, demonstrates a method by which to implement and optimise catalytic activity for an enzyme mimetic. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

True 3D kinematic analysis for slope instability assessment in the Siq of Petra (Jordan), from high resolution TLS

NASA Astrophysics Data System (ADS)

Gigli, Giovanni; Margottini, Claudio; Spizzichino, Daniele; Ruther, Heinz; Casagli, Nicola

2016-04-01

Most classifications of mass movements in rock slopes use relatively simple, idealized geometries for the basal sliding surface, like planar sliding, wedge sliding, toppling or columnar failures. For small volumes, the real sliding surface can be often well described by such simple geometries. Extended and complex rock surfaces, however, can exhibit a large number of mass movements, also showing various kind of kinematisms. As a consequence, the real situation in large rock surfaces with a complicate geometry is generally very complex and a site depending analysis, such as fieldwork and compass, cannot be comprehensive of the real situation. Since the outstanding development of terrestrial laser scanner (TLS) in recent years, rock slopes can now be investigated and mapped through high resolution point clouds, reaching the resolution of few mm's and accuracy less than a cm in most advanced instruments, even from remote surveying. The availability of slope surface digital data can offer a unique chance to determine potential kinematisms in a wide distributed area for all the investigated geomorphological processes. More in detail the proposed method is based on the definition of least squares fitting planes on clusters of points extracted by moving a sampling cube on the point cloud. If the associated standard deviation is below a defined threshold, the cluster is considered valid. By applying geometric criteria it is possible to join all the clusters lying on the same surface; in this way discontinuity planes can be reconstructed, rock mass geometrical properties are calculated and, finally, potential kinematisms established. The Siq of Petra (Jordan), is a 1.2 km naturally formed gorge, with an irregular horizontal shape and a complex vertical slope, that represents the main entrance to Nabatean archaeological site. In the Siq, discontinuities of various type (bedding, joints, faults), mainly related to geomorphological evolution of the slope, lateral stress released, stratigraphic setting and tectonic activity can be recognized. As a consequence, rock-falls have been occurring, even recently, with unstable rock mass volumes ranging from 0.1 m3 up to over some hundreds m3. Slope instability, acceleration of crack deformation and consequent increasing of rock-fall hazard conditions, could threaten the safety of tourist as well as the integrity of the heritage. 3D surface model coming from Terrestrial Laser Scanner acquisitions was developed almost all over the site of Petra, including the Siq. Comprehensively, a point cloud of five billion points was generated making the site of Petra likely the largest scanned archaeological site in the word. As far as the Siq, the scanner was positioned on the path floor at intervals of not more than 10 meters from each station. The total number of scans in the Siq was 220 with an average point cloud interval of approximately 3 cm. Subsequently, for the definition of the main rockfall source areas, a spatial kinematic analysis for the whole Siq has been performed, by using discontinuity orientation data extracted from the point cloud by means of the software Diana. Orientation, number of sets, spacing/frequency, persistence, block size and scale dependent roughness was obtained combining fieldwork and automatic analysis. This kind of analysis is able to establish where a particular instability mechanism is kinematically feasible, given the geometry of the slope, the orientation of discontinuities and shear strength of the rock. The final outcome of this project was a detail landslide kinematic index map, reporting main potential instability mechanisms for a given area. The kinematic index was finally calibrated for each instability mechanism (plane failure; wedge failure; block toppling; flexural toppling) surveyed in the site. The latter is including the collapse occurred in May 2015, likely not producing any victim, in a sector clearly identified by the susceptibility maps produced by the analysis.

Bio-important antipyrine derived Schiff bases and their transition metal complexes: Synthesis, spectroscopic characterization, antimicrobial, anthelmintic and DNA cleavage investigation

NASA Astrophysics Data System (ADS)

Manjunath, M.; Kulkarni, Ajaykumar D.; Bagihalli, Gangadhar B.; Malladi, Shridhar; Patil, Sangamesh A.

2017-01-01

Spectroscopic (IR, NMR, UV-vis, ESR, ESI-mass), magnetic and TGA studies suggests octahedral geometry for all the CoII, NiII and CuII complexes of the Schiff bases, derived from 4-aminoantipyrine and 8-formyl-7-Hydroxy-4-methylcoumarin/5-formyl-6-hydroxycoumarin, coordinated through ONO donor sites. Antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi), antifungal (Aspergillus niger, Aspergillus flavus and Cladosporium) and DNA cleavage properties of the metal complexes are investigated. The results suggested that some of the synthesized compounds are potential antimicrobials. The synthesized compounds tested for their anthelmintic activities and it was found that CoII and NiII complexes exhibited good anthelmintic properties.

Finite Element Estimation of Protein-Ligand Association Rates with Post-Encounter Effects: Applications to Calcium binding in Troponin C and SERCA

PubMed Central

Kekenes-Huskey, P. M.; Gillette, A.; Hake, J.; McCammon, J. A.

2012-01-01

We introduce a computational pipeline and suite of software tools for the approximation of diffusion-limited binding based on a recently developed theoretical framework. Our approach handles molecular geometries generated from high-resolution structural data and can account for active sites buried within the protein or behind gating mechanisms. Using tools from the FEniCS library and the APBS solver, we implement a numerical code for our method and study two Ca2+-binding proteins: Troponin C and the Sarcoplasmic Reticulum Ca2+ ATPase (SERCA). We find that a combination of diffusional encounter and internal ‘buried channel’ descriptions provide superior descriptions of association rates, improving estimates by orders of magnitude. PMID:23293662

Finite Element Estimation of Protein-Ligand Association Rates with Post-Encounter Effects: Applications to Calcium binding in Troponin C and SERCA.

PubMed

Kekenes-Huskey, P M; Gillette, A; Hake, J; McCammon, J A

2012-10-31

We introduce a computational pipeline and suite of software tools for the approximation of diffusion-limited binding based on a recently developed theoretical framework. Our approach handles molecular geometries generated from high-resolution structural data and can account for active sites buried within the protein or behind gating mechanisms. Using tools from the FEniCS library and the APBS solver, we implement a numerical code for our method and study two Ca(2+)-binding proteins: Troponin C and the Sarcoplasmic Reticulum Ca(2+) ATPase (SERCA). We find that a combination of diffusional encounter and internal 'buried channel' descriptions provide superior descriptions of association rates, improving estimates by orders of magnitude.

Finite-element estimation of protein-ligand association rates with post-encounter effects: applications to calcium binding in troponin C and SERCA

NASA Astrophysics Data System (ADS)

Kekenes-Huskey, P. M.; Gillette, A.; Hake, J.; McCammon, J. A.

2012-01-01

We introduce a computational pipeline and suite of software tools for the approximation of diffusion-limited binding based on a recently developed theoretical framework. Our approach handles molecular geometries generated from high-resolution structural data and can account for active sites buried within the protein or behind gating mechanisms. Using tools from the FEniCS library and the APBS solver, we implement a numerical code for our method and study two Ca2+-binding proteins: troponin C and the sarcoplasmic reticulum Ca2+ ATPase. We find that a combination of diffusional encounter and internal ‘buried channel’ descriptions provides superior descriptions of association rates, improving estimates by orders of magnitude.

Slab1.0: A three-dimensional model of global subduction zone geometries

NASA Astrophysics Data System (ADS)

Hayes, Gavin P.; Wald, David J.; Johnson, Rebecca L.

2012-01-01

We describe and present a new model of global subduction zone geometries, called Slab1.0. An extension of previous efforts to constrain the two-dimensional non-planar geometry of subduction zones around the focus of large earthquakes, Slab1.0 describes the detailed, non-planar, three-dimensional geometry of approximately 85% of subduction zones worldwide. While the model focuses on the detailed form of each slab from their trenches through the seismogenic zone, where it combines data sets from active source and passive seismology, it also continues to the limits of their seismic extent in the upper-mid mantle, providing a uniform approach to the definition of the entire seismically active slab geometry. Examples are shown for two well-constrained global locations; models for many other regions are available and can be freely downloaded in several formats from our new Slab1.0 website, http://on.doi.gov/d9ARbS. We describe improvements in our two-dimensional geometry constraint inversion, including the use of `average' active source seismic data profiles in the shallow trench regions where data are otherwise lacking, derived from the interpolation between other active source seismic data along-strike in the same subduction zone. We include several analyses of the uncertainty and robustness of our three-dimensional interpolation methods. In addition, we use the filtered, subduction-related earthquake data sets compiled to build Slab1.0 in a reassessment of previous analyses of the deep limit of the thrust interface seismogenic zone for all subduction zones included in our global model thus far, concluding that the width of these seismogenic zones is on average 30% larger than previous studies have suggested.

Study of Chemistry and Structure-Property Relationship on Tunable Plasmonic Nanostructures

NASA Astrophysics Data System (ADS)

Jing, Hao

In this dissertation, the rational design and controllable fabrication of an array of novel plasmonic nanostructures with geometrically tunable optical properties are demonstrated, including metal-semiconductor hybrid hetero-nanoparticles, bimetallic noble metal nanoparticles and hollow nanostructures (nanobox and nanocage). Firstly, I have developed a robust wet chemistry approach to the geometry control of Ag-Cu2O core-shell nanoparticles through epitaxial growth of Cu2O nanoshells on the surfaces of various Ag nanostructures, such as quasi-spherical nanoparticles, nanocubes, and nanocuboids. Precise control over the core and the shell geometries enables me to develop detailed, quantitative understanding of how the Cu2O nanoshells introduce interesting modifications to the resonance frequencies and the extinction spectral line shapes of multiple plasmon modes of the Ag cores. Secondly, I present a detailed and systematic study of the controlled overgrowth of Pd on Au nanorods. The overgrowth of Pd nanoshells with fine-controlled dimensions and architectures on single-crystalline Au nanorods through seed-mediated growth protocol in the presence of various surfactants is investigated. Thirdly, I have demonstrated that creation of high-index facets on subwavelength metallic nanoparticles provides a unique approach to the integration of desired plasmonic and catalytic properties on the same nanoparticle. Through site-selective surface etching of metallic nanocuboids whose surfaces are dominated by low-index facets, I have controllably fabricated nanorice and nanodumbbell particles, which exhibit drastically enhanced catalytic activities arising from the catalytically active high index facets abundant on the particle surfaces. And the nanorice and nanodumbbell particles also possess appealing tunable plasmonic properties that allow us to gain quantitative insights into nanoparticle-catalyzed reactions with unprecedented sensitivity and detail through time-resolved plasmon-enhanced spectroscopic measurements, such as surface-enhanced Raman scattering (SERS). Last but not least, I have demonstrated that the capability of geometry control over Ag-Pd bimetallic hollow nanostructures through nanoscale galvanic replacement can be greatly enhanced by the use of appropriate mild reducing agents, such as ascorbic acid and formaldehyde. With the aid of mild reducing agents, we have been able to fine-tailor the compositions, interior architectures, and surface morphologies of Ag-Pd bimetallic hollow nanoparticles with increased structural complexity through surface ligand-free galvanic replacement processes at room temperature. This reducing agent-mediated galvanic replacement provides a unique way of achieving both enhanced optical tunability and optimized catalytic activities through deliberate control over the geometries of complex Ag-Pd bimetallic nanoparticles.

Elastic Geometry and Storyknifing: A Yup'ik Eskimo Example.

ERIC Educational Resources Information Center

Lipka, Jerry; Wildfeuer, Sandra; Wahlberg, Nastasia; George, Mary; Ezran, Dafna R.

2001-01-01

Introduces elastic geometry, or topology, into the elementary classroom through the study of connecting the intuitive, visual, and spatial components of storyknifing as well as other everyday and ethnomathematical activities. (ASK)

Mechanochemical Association Reaction of Interfacial Molecules Driven by Shear.

PubMed

Khajeh, Arash; He, Xin; Yeon, Jejoon; Kim, Seong H; Martini, Ashlie

2018-05-29

Shear-driven chemical reaction mechanisms are poorly understood because the relevant reactions are often hidden between two solid surfaces moving in relative motion. Here, this phenomenon is explored by characterizing shear-induced polymerization reactions that occur during vapor phase lubrication of α-pinene between sliding hydroxylated and dehydroxylated silica surfaces, complemented by reactive molecular dynamics simulations. The results suggest that oxidative chemisorption of the α-pinene molecules at reactive surface sites, which transfers oxygen atoms from the surface to the adsorbate molecule, is the critical activation step. Such activation takes place more readily on the dehydroxylated surface. During this activation, the most strained part of the α-pinene molecules undergoes a partial distortion from its equilibrium geometry, which appears to be related to the critical activation volume for mechanical activation. Once α-pinene molecules are activated, association reactions occur between the newly attached oxygen and one of the carbon atoms in another molecule, forming ether bonds. These findings have general implications for mechanochemistry because they reveal that shear-driven reactions may occur through reaction pathways very different from their thermally induced counterparts and specifically the critical role of molecular distortion in such reactions.

Site Transfer Functions of Three-Component Ground Motion in Western Turkey

NASA Astrophysics Data System (ADS)

Ozgur Kurtulmus, Tevfik; Akyol, Nihal; Camyildiz, Murat; Gungor, Talip

2015-04-01

Because of high seismicity accommodating crustal deformation and deep graben structures, on which have, urbanized and industrialized large cities in western Turkey, the importance of site-specific seismic hazard assessments becomes more crucial. Characterizing source, site and path effects is important for both assessing the seismic hazard in a specific region and generation of the building codes/or renewing previous ones. In this study, we evaluated three-component recordings for micro- and moderate-size earthquakes with local magnitudes ranging between 2.0 and 5.6. This dataset is used for site transfer function estimations, utilizing two different spectral ratio approaches 'Standard Spectral Ratio-(SSR)' and 'Horizontal to Vertical Spectral Ratio-(HVSR)' and a 'Generalized Inversion Technique-(GIT)' to highlight site-specific seismic hazard potential of deep basin structures of the region. Obtained transfer functions revealed that the sites located near the basin edges are characterized by broader HVSR curves. Broad HVSR peaks could be attributed to the complexity of wave propagation related to significant 2D/3D velocity variations at the sediment-bedrock interface near the basin edges. Comparison of HVSR and SSR estimates for the sites located on the grabens showed that SSR estimates give larger values at lower frequencies which could be attributed to lateral variations in regional velocity and attenuation values caused by basin geometry and edge effects. However, large amplitude values of vertical component GIT site transfer functions were observed at varying frequency ranges for some of the stations. These results imply that vertical component of ground motion is not amplification free. Contamination of HVSR site transfer function estimates at different frequency bands could be related to complexities in the wave field caused by deep or shallow heterogeneities in the region such as differences in the basin geometries, fracturing and fluid saturation along different propagation paths. The results also show that, even if the site is located on a horst, the presence of weathered zones near the surface could cause moderate frequency dependent site effects.

First-principles theoretical investigation of monoatomic and dimer Mn adsorption on noble metal (111) surfaces

NASA Astrophysics Data System (ADS)

Muñoz, Francisco; Romero, Aldo H.; Mejía-López, Jose; Morán-López, J. L.

2012-03-01

A theoretical investigation of the adsorption of Mn single atoms and dimers on the (111) surface of Cu, Ag, and Au, within the framework of the density functional theory, is presented. First, the bulk and the clean (111) surface electronic structures are calculated, with results that agree well with previous reports. To understand the adatom-substrate interaction, also the electronic characteristics of the free Mn dimer are determined. Then, the electronic structure of the Mn adatom, chemisorbed on four different surface geometries, is analyzed for the three noble metals. It is found that the most stable geometry, in all three cases, Cu, Ag, and Au, occurs when the Mn atom is chemisorbed on threefold coordinated sites. For the dimer, the lowest-energy configuration corresponds to the molecule lying parallel to the surface. In the three noble metals, the geometry corresponds to both atoms chemisorbed in threefold coordinated sites, but with different local symmetry. It is also found that the magnetic configuration with the lowest energy corresponds to the antiferromagnetic arrangement of Mn atoms, with individual magnetic moments close to 5μB. The ferromagnetic and antiferromagnetic solutions, in the case of a Ag substrate, are close in energy. It is also found that in this case the Mn2 molecule is chemisorbed with very similar energy on various geometries. To study the dynamical motion of the dimer components, we calculated the potential energy barriers for the Mn motion in the various surfaces. In contrast to Cu and Au, this leads to the conclusion that on Ag the Mn dimer moves relatively freely.

A modeling of the structure and favorable H-docking sites and defects for the high-pressure silica polymorph stishovite

NASA Astrophysics Data System (ADS)

Gibbs, G. V.; Cox, D. F.; Ross, N. L.

Employing first-principles methods, the docking sites for H were determined and H, Al, and vacancy defects were modeled with an infinite periodic array of super unit cells each consisting of 27 contiguous symmetry nonequivalent unit cells of the crystal structure of stishovite. A geometry optimization of the super-cell structure reproduces the observed bulk structure within the experimental error when P1 translational symmetry was assumed and an array of infinite extent was generated. A mapping of the valence electrons for the structure displays mushroom-shaped isosurfaces on the O atom, one on each side of the plane of the OSi3 triangle in the nonbonded region. An H atom, placed in a cell near the center of the super cell, was found to dock upon geometry optimization at a distance of 1.69 Å from the O atom with the OH vector oriented nearly perpendicular to the plane of the triangle such that the OH vector makes a angle of 91° with respect to [001]. However, an optimization of a super cell with an Al atom replacing Si and an H atom placed nearby in a centrally located cell resulted in an OH distance of 1.02 Å with the OH vector oriented perpendicular to [001] as observed in infrared studies. The geometry-optimized position of the H atom was found to be in close agreement with that (0.44, 0.12, 0.0) determined in an earlier study of the theoretical electron density distribution. The docking of the H atom at this site was found to be 330 kJ mol-1 more stable than a docking of the atom just off the shared OO edge of the octahedra as determined for rutile. A geometry optimization of a super cell with a missing Si generated a vacant octahedra that is 20% larger than that of the SiO6 octahedra. The valence electron density distribution displayed by the two-coordinate O atoms that coordinate the vacant octahedral site is very similar to those displayed by the bent SiOSi angles in coesite. The internal distortions induced by the defect were found to diminish rather rapidly with distance, with the structure annealing to that observed in the bulk crystal to within about three coordination spheres.

Impact of copper ligand mutations on a cupredoxin with a green copper center.

PubMed

Roger, Magali; Sciara, Giuliano; Biaso, Frédéric; Lojou, Elisabeth; Wang, Xie; Bauzan, Marielle; Giudici-Orticoni, Marie-Thérèse; Vila, Alejandro J; Ilbert, Marianne

2017-05-01

Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP. We show that even though AcoP possesses a classical copper ligand set, it has a highly perturbed copper center. In depth studies of mutant's properties suggest a high degree of constraint existing in the copper center of the wild type protein and even the addition of exogenous ligands does not lead to the reconstitution of the initial copper center. Not only the chemical nature of the axial ligand but also constraints brought by its covalent binding to the protein backbone might be critical to maintain a green copper site with high redox potential. This work illustrates the importance of experimentally dissecting the molecular diversity of cupredoxins to determine the molecular determinants responsible for their copper center geometry and redox potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction of CO with an Au monatomic chain at different strains: Electronic structure and ballistic transport

NASA Astrophysics Data System (ADS)

Sclauzero, Gabriele; Dal Corso, Andrea; Smogunov, Alexander

2012-04-01

We study the energetics, the electronic structure, and the ballistic transport of an infinite Au monatomic chain with an adsorbed CO molecule. We find that the bridge adsorption site is energetically favored with respect to the atop site, both at the equilibrium Au-Au spacing of the chain and at larger spacings. Instead, a substitutional configuration requires a very elongated Au-Au bond, well above the rupture distance of the pristine Au chain. The electronic structure properties can be described by the Blyholder model, which involves the formation of bonding/antibonding pairs of 5σ and 2π states through the hybridization between molecular levels of CO and metallic states of the chain. In the atop geometry, we find an almost vanishing conductance due to the 5σ antibonding states giving rise to a Fano-like destructive interference close to the Fermi energy. In the bridge geometry, instead, the same states are shifted to higher energies and the conductance reduction with respect to pristine Au chain is much smaller. We also examine the effects of strain on the ballistic transport, finding opposite behaviors for the atop and bridge conductances. Only the bridge geometry shows a strain dependence compatible with the experimental conductance traces.

Pu-239 organ specific dosimetric model applied to non-human biota

NASA Astrophysics Data System (ADS)

Kaspar, Matthew Jason

There are few locations throughout the world, like the Maralinga nuclear test site located in south western Australia, where sufficient plutonium contaminate concentration levels exist that they can be utilized for studies of the long-term radionuclide accumulation in non-human biota. The information obtained will be useful for the potential human users of the site while also keeping with international efforts to better understand doses to non-human biota. In particular, this study focuses primarily on a rabbit sample set collected from the population located within the site. Our approach is intended to employ the same dose and dose rate methods selected by the International Commission on Radiological Protection and adapted by the scientific community for similar research questions. These models rely on a series of simplifying assumptions on biota and their geometry; in particular; organisms are treated as spherical and ellipsoidal representations displaying the animal mass and volume. These simplifications assume homogeneity of all animal tissues. In collaborative efforts between Colorado State University and the Australian Nuclear Science and Technology Organisation (ANSTO), we are expanding current knowledge on radionuclide accumulation in specific organs causing organ-specific dose rates, such as Pu-239 accumulating in bone, liver, and lungs. Organ-specific dose models have been developed for humans; however, little has been developed for the dose assessment to biota, in particular rabbits. This study will determine if it is scientifically valid to use standard software, in particular ERICA Tool, as a means to determine organ-specific dosimetry due to Pu-239 accumulation in organs. ERICA Tool is normally applied to whole organisms as a means to determine radiological risk to whole ecosystems. We will focus on the aquatic model within ERICA Tool, as animal organs, like aquatic organisms, can be assumed to lie within an infinite uniform medium. This model would scientifically be valid for radionuclides emitting short-range radiation, as with Pu-239, where the energy is deposited locally. Two MCNPX models have been created and evaluated against ERICA Tool's aquatic model. One MCNPX model replicates ERICA Tool's intrinsic assumptions while the other uses a more realistic animal model adopted by ICRP Publication 108 and ERICA Tool for the organs "infinite" surrounding universe. In addition, the role of model geometry will be analyzed by focusing on four geometry sets for the same organ, including a spherical geometry. ERICA Tool will be compared to MCNPX results within and between each organ geometry set. In addition, the organ absorbed dose rate will be calculated for six rabbits located on the Maralinga nuclear test site as a preliminary test for further investigation. Data in all cases will be compared using percent differences and Student's t-test with respect to ERICA Tool's results and the overall average organ mean absorbed dose rate.

Origami, geometry and art

NASA Astrophysics Data System (ADS)

Wares, Arsalan; Elstak, Iwan

2017-02-01

The purpose of this paper is to describe the mathematics that emanates from the construction of an origami box. We first construct a simple origami box from a rectangular sheet and then discuss some of the mathematical questions that arise in the context of geometry and algebra. The activity can be used as a context for illustrating how algebra and geometry, like other branches of mathematics, are interrelated.

Using Transmural Regularization and Dynamic Modeling for Non-Invasive Cardiac Potential Imaging of Endocardial Pacing with Imprecise Thoracic Geometry

PubMed Central

Erem, Burak; Coll-Font, Jaume; Orellana, Ramon Martinez; Štóvíček, Petr; Brooks, Dana H.

2014-01-01

Cardiac electrical imaging from body surface potential measurements is increasingly being seen as a technology with the potential for use in the clinic, for example for pre-procedure planning or during-treatment guidance for ventricular arrhythmia ablation procedures. However several important impediments to widespread adoption of this technology remain to be effectively overcome. Here we address two of these impediments: the difficulty of reconstructing electric potentials on the inner (endocardial) as well as outer (epicardial) surfaces of the ventricles, and the need for full anatomical imaging of the subject’s thorax to build an accurate subject-specific geometry. We introduce two new features in our reconstruction algorithm: a non-linear low-order dynamic parameterization derived from the measured body surface signals, and a technique to jointly regularize both surfaces. With these methodological innovations in combination, it is possible to reconstruct endocardial activation from clinically acquired measurements with an imprecise thorax geometry. In particular we test the method using body surface potentials acquired from three subjects during clinical procedures where the subjects’ hearts were paced on their endocardia using a catheter device. Our geometric models were constructed using a set of CT scans limited in axial extent to the immediate region near the heart. The catheter system provides a reference location to which we compare our results. We compare our estimates of pacing site localization, in terms of both accuracy and stability, to those reported in a recent clinical publication [1], where a full set of CT scans were available and only epicardial potentials were reconstructed. PMID:24595345

Comparison of hip geometry, strength, and estimated fracture risk in women with anorexia nervosa and overweight/obese women.

PubMed

Bachmann, Katherine Neubecker; Fazeli, Pouneh K; Lawson, Elizabeth A; Russell, Brian M; Riccio, Ariana D; Meenaghan, Erinne; Gerweck, Anu V; Eddy, Kamryn; Holmes, Tara; Goldstein, Mark; Weigel, Thomas; Ebrahimi, Seda; Mickley, Diane; Gleysteen, Suzanne; Bredella, Miriam A; Klibanski, Anne; Miller, Karen K

2014-12-01

Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. This was a cross-sectional study. The study was conducted at a Clinical Research Center. PATIENTS included 368 women (aged 19-45 y): 246 AN, 53 overweight/obese, and 69 lean controls. HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φ(attenuated)) were measured. Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φ(attenuated) was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φ(attenuated) (P < .05). Mean φ(attenuated) (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD.

Comparison of Hip Geometry, Strength, and Estimated Fracture Risk in Women With Anorexia Nervosa and Overweight/Obese Women

PubMed Central

Bachmann, Katherine Neubecker; Fazeli, Pouneh K.; Lawson, Elizabeth A.; Russell, Brian M.; Riccio, Ariana D.; Meenaghan, Erinne; Gerweck, Anu V.; Eddy, Kamryn; Holmes, Tara; Goldstein, Mark; Weigel, Thomas; Ebrahimi, Seda; Mickley, Diane; Gleysteen, Suzanne; Bredella, Miriam A.; Klibanski, Anne

2014-01-01

Context: Data suggest that anorexia nervosa (AN) and obesity are complicated by elevated fracture risk, but skeletal site-specific data are lacking. Traditional bone mineral density (BMD) measurements are unsatisfactory at both weight extremes. Hip structural analysis (HSA) uses dual-energy X-ray absorptiometry data to estimate hip geometry and femoral strength. Factor of risk (φ) is the ratio of force applied to the hip from a fall with respect to femoral strength; higher values indicate higher hip fracture risk. Objective: The objective of the study was to investigate hip fracture risk in AN and overweight/obese women. Design: This was a cross-sectional study. Setting: The study was conducted at a Clinical Research Center. Patients: Patients included 368 women (aged 19–45 y): 246 AN, 53 overweight/obese, and 69 lean controls. Main Outcome Measures: HSA-derived femoral geometry, peak factor of risk for hip fracture, and factor of risk for hip fracture attenuated by trochanteric soft tissue (φattenuated) were measured. Results: Most HSA-derived parameters were impaired in AN and superior in obese/overweight women vs controls at the narrow neck, intertrochanteric, and femoral shaft (P ≤ .03). The φattenuated was highest in AN and lowest in overweight/obese women (P < .0001). Lean mass was associated with superior, and duration of amenorrhea with inferior, HSA-derived parameters and φattenuated (P < .05). Mean φattenuated (P = .036), but not femoral neck BMD or HSA-estimated geometry, was impaired in women who had experienced fragility fractures. Conclusions: Femoral geometry by HSA, hip BMD, and factor of risk for hip fracture attenuated by soft tissue are impaired in AN and superior in obesity, suggesting higher and lower hip fracture risk, respectively. Only attenuated factor of risk was associated with fragility fracture prevalence, suggesting that variability in soft tissue padding may help explain site-specific fracture risk not captured by BMD. PMID:25062461

Combined Structural and Trajectory Control of Variable-Geometry Planetary Entry Systems

NASA Technical Reports Server (NTRS)

Quadrelli, Marco B.; Pellegrino, Sergio; Kwok, Kawai

2011-01-01

Some of the key challenges of planetary entry are to dissipate the large kinetic energy of the entry vehicle and to land with precision. Past missions to Mars were based on unguided entry, where entry vehicles carried payloads of less than 0.6 T and landed within 100 km of the designated target. The Mars Science Laboratory (MSL) is expected to carry a mass of almost 1 T to within 20 km of the target site. Guided lifting entry is needed to meet these higher deceleration and targeting demands. If the aerodynamic characteristics of the decelerator are variable during flight, more trajectory options are possible, and can be tailored to specific mission requirements. In addition to the entry trajectory modulation, having variable aerodynamic properties will also favor maneuvering of the vehicle prior to descent. For proper supersonic parachute deployment, the vehicle needs to turn to a lower angle of attack. One approach to entry trajectory improvement and angle of attack control is to embed a variable geometry decelerator in the design of the vehicle. Variation in geometry enables the vehicle to adjust its aerodynamic performance continuously without additional fuel cost because only electric power is needed for actuating the mechanisms that control the shape change. Novel structural and control concepts have been developed that enable the decelerator to undergo variation in geometry. Changing the aerodynamic characteristics of a flight vehicle by active means can potentially provide a mechanically simple, affordable, and enabling solution for entry, descent, and landing across a wide range of mission types, sample capture and return, and reentry to Earth, Titan, Venus, or Mars. Unguided ballistic entry is not sufficient to meet this more stringent deceleration, heating, and targeting demands. Two structural concepts for implementing the cone angle variation, a segmented shell, and a corrugated shell, have been presented.

Modeling of a possible conformational change associated with the catalytic mechanism in the hammerhead ribozyme

NASA Technical Reports Server (NTRS)

Setlik, R. F.; Shibata, M.; Sarma, R. H.; Sarma, M. H.; Kazim, A. L.; Ornstein, R. L.; Tomasi, T. B.; Rein, R.

1995-01-01

Here we describe a possible model of the cleavage mechanism in the hammerhead ribozyme. In this model, the 2' hydroxyl of C17 is moved into an appropriate orientation for an in-line attack on the G1.1 phosphate through a change in its sugar pucker from C3' endo to C2' endo. This conformational change in the active site is caused by a change in the uridine turn placing the N2 and N3 atoms of G5 of the conserved core in hydrogen bonding geometry with the N3 and N2 atoms on the conserved G16.2 residue. The observed conformational change in the uridine turn suggests an explanation for the conservation of G5. In the crystal structure of H.M. Pley et al., Nature 372, 68-74 (1994), G5 is situated 5.3A away from G16.2. However, the uridine turn is sufficiently flexible to allow this conformational change with relatively modest changes in the backbone torsion angles (average change of 14.2 degrees). Two magnesium ions were modeled into the active site with positions analogous to those described in the functionally similar Klenow fragment 3'-5' exonuclease (L.S. Beese and T.A. Steitz, EMBO J. 10, 25-33 (1991)), the Group I intron (T.A. Steitz and J.A. Steitz, P.N.A.S. U.S.A. 90, 6498-6502 (1993); R.F. Setlik et al., J. Biomol. Str. Dyn. 10, 945-972 (1993)) and other phosphotransferases. Comparison of this model with one in which the uridine turn conformation was not changed showed that although the changes in the C17 sugar pucker could be modeled, insufficient space existed for the magnesium ions in the active site.

Preliminary Analysis of an Oscillating Surge Wave Energy Converter with Controlled Geometry: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tom, Nathan; Lawson, Michael; Yu, Yi-Hsiang

The aim of this paper is to present a novel wave energy converter device concept that is being developed at the National Renewable Energy Laboratory. The proposed concept combines an oscillating surge wave energy converter with active control surfaces. These active control surfaces allow for the device geometry to be altered, which leads to changes in the hydrodynamic properties. The device geometry will be controlled on a sea state time scale and combined with wave-to-wave power-take-off control to maximize power capture, increase capacity factor, and reduce design loads. The paper begins with a traditional linear frequency domain analysis of themore » device performance. Performance sensitivity to foil pitch angle, the number of activated foils, and foil cross section geometry is presented to illustrate the current design decisions; however, it is understood from previous studies that modeling of current oscillating wave energy converter designs requires the consideration of nonlinear hydrodynamics and viscous drag forces. In response, a nonlinear model is presented that highlights the shortcomings of the linear frequency domain analysis and increases the precision in predicted performance.« less

Cation binding to a Bacillus (1,3-1,4)-beta-glucanase. Geometry, affinity and effect on protein stability.

PubMed

Keitel, T; Meldgaard, M; Heinemann, U

1994-05-15

The hybrid Bacillus (1,3-1,4)-beta-glucanase H(A16-M), consisting of 16 N-terminal amino acids derived from the mature form of the B. amyloliquefaciens enzyme and of 198 C-proximal amino acids from the B. macerans enzyme, binds a calcium ion at a site at its molecular surface remote from the active center [T. Keitel, O. Simon, R. Borriss & U. Heinemann (1993) Proc. Natl Acad. Sci. USA 90, 5287-5291]. X-ray diffraction analysis at 0.22-nm resolution of crystals grown in the absence of calcium and in the presence of EDTA shows this site to be occupied by a sodium ion. Whereas the calcium ion has six oxygen atoms in its coordination sphere, two of which are from water molecules, sodium is fivefold coordinated with a fifth ligand belonging to a symmetry-related protein molecule in the crystal lattice. The affinity of H(A16-M) for calcium over sodium has been determined calorimetrically. Calcium binding stabilizes the native three-dimensional structure of the protein as shown by guanidinium chloride unfolding and thermal inactivation experiments. The enhanced enzymic activity of Bacillus beta-glucanases at elevated temperatures in the presence of calcium ions is attributed to a general stabilizing effect by the cation.

A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.

PubMed

Singh, Satendra; Singh, Atul Kumar; Wadhwa, Gulshan; Singh, Dev Bukhsh; Dwivedi, Seema; Gautam, Budhayash; Ramteke, Pramod W

2016-06-01

Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.

Foreshock and aftershocks in simple earthquake models.

PubMed

Kazemian, J; Tiampo, K F; Klein, W; Dominguez, R

2015-02-27

Many models of earthquake faults have been introduced that connect Gutenberg-Richter (GR) scaling to triggering processes. However, natural earthquake fault systems are composed of a variety of different geometries and materials and the associated heterogeneity in physical properties can cause a variety of spatial and temporal behaviors. This raises the question of how the triggering process and the structure interact to produce the observed phenomena. Here we present a simple earthquake fault model based on the Olami-Feder-Christensen and Rundle-Jackson-Brown cellular automata models with long-range interactions that incorporates a fixed percentage of stronger sites, or asperity cells, into the lattice. These asperity cells are significantly stronger than the surrounding lattice sites but eventually rupture when the applied stress reaches their higher threshold stress. The introduction of these spatial heterogeneities results in temporal clustering in the model that mimics that seen in natural fault systems along with GR scaling. In addition, we observe sequences of activity that start with a gradually accelerating number of larger events (foreshocks) prior to a main shock that is followed by a tail of decreasing activity (aftershocks). This work provides further evidence that the spatial and temporal patterns observed in natural seismicity are strongly influenced by the underlying physical properties and are not solely the result of a simple cascade mechanism.

Facile O-atom insertion into CC and CH bonds by a trinuclear copper complex designed to harness a singlet oxene

PubMed Central

Chen, Peter P.-Y.; Yang, Richard B.-G.; Lee, Jason C.-M.; Chan, Sunney I.

2007-01-01

Two trinuclear copper [CuICuICuI(L)]1+ complexes have been prepared with the multidentate ligands (L) 3,3′-(1,4-diazepane-1,4-diyl)bis(1-((2-(dimethylamino)ethyl)(methyl)amino)propan-2-ol) (7-Me) and (3,3′-(1,4-diazepane-1,4-diyl)bis(1-((2-(diethylamino) ethyl)(ethyl) amino)propan-2-ol) (7-Et) as models for the active site of the particulate methane monooxygenase (pMMO). The ligands were designed to form the proper spatial and electronic geometry to harness a “singlet oxene,” according to the mechanism previously suggested by our laboratory. Consistent with the design strategy, both [CuICuICuI(L)]1+ reacted with dioxygen to form a putative bis(μ3-oxo)CuIICuIICuIII species, capable of facile O-atom insertion across the central CC bond of benzil and 2,3-butanedione at ambient temperature and pressure. These complexes also catalyze facile O-atom transfer to the CH bond of CH3CN to form glycolonitrile. These results, together with our recent biochemical studies on pMMO, provide support for our hypothesis that the hydroxylation site of pMMO contains a trinuclear copper cluster that mediates CH bond activation by a singlet oxene mechanism. PMID:17804786

Structural changes at the metal ion binding site during the phosphoglucomutase reaction.

PubMed

Ray, W J; Post, C B; Liu, Y; Rhyu, G I

1993-01-12

An electron density map of the reactive, Cd2+ form of crystalline phosphoglucomutase from X-ray diffraction studies shows that the enzymic phosphate donates a nonbridging oxygen to the ligand sphere of the bound metal ion, which appears to be tetracoordinate. 31P and 113Cd NMR spectroscopy are used to assess changes in the properties of bound Cd2+ produced by substrate/product and by substrate/product analog inhibitors. The approximately 50 ppm downfield shift of the 113Cd resonance on formation of the complex of dephosphoenzyme and glucose 1,6-bisphosphate is associated with the initial sugar-phosphate binding step and likely involves a change in the geometry of the coordinating ligands. This interpretation is supported by spectral studies involving various complexes of the active Co2+ and Ni(2+)-enzyme. In addition, there is a loss of the 31P-113Cd J coupling that characterizes the monophosphate complexes of the Cd2+ enzyme either during or immediately after the PO3- transfer step that produces the bisphosphate complex, indicating a further change at the metal binding site. The implications of these observations with respect to the PO3- transfer process in the phosphoglucomutase reaction are considered. The apparent plasticity of the ligand sphere of the active site metal ion in this system may allow a single metal ion to act as a chaperone for a nonbridging oxygen during PO3- transfer or to allow a change in metal ion coordination during catalysis. A general NMR line shape/chemical-exchange analysis for evaluating binding in protein-ligand systems when exchange is intermediate to fast on the NMR time scale is described. Its application to the present system involves multiple exchange sites that depend on a single binding rate, thereby adding further constraints to the analysis.

A Global Survey and Interactive Map Suite of Deep Underground Facilities; Examples of Geotechnical and Engineering Capabilities, Achievements, Challenges: (Mines, Shafts, Tunnels, Boreholes, Sites and Underground Facilities for Nuclear Waste and Physics R&D)

NASA Astrophysics Data System (ADS)

Tynan, M. C.; Russell, G. P.; Perry, F.; Kelley, R.; Champenois, S. T.

2017-12-01

This global survey presents a synthesis of some notable geotechnical and engineering information reflected in four interactive layer maps for selected: 1) deep mines and shafts; 2) existing, considered or planned radioactive waste management deep underground studies, sites, or disposal facilities; 3) deep large diameter boreholes, and 4) physics underground laboratories and facilities from around the world. These data are intended to facilitate user access to basic information and references regarding deep underground "facilities", history, activities, and plans. In general, the interactive maps and database [http://gis.inl.gov/globalsites/] provide each facility's approximate site location, geology, and engineered features (e.g.: access, geometry, depth, diameter, year of operations, groundwater, lithology, host unit name and age, basin; operator, management organization, geographic data, nearby cultural features, other). Although the survey is not all encompassing, it is a comprehensive review of many of the significant existing and historical underground facilities discussed in the literature addressing radioactive waste management and deep mined geologic disposal safety systems. The global survey is intended to support and to inform: 1) interested parties and decision makers; 2) radioactive waste disposal and siting option evaluations, and 3) safety case development as a communication tool applicable to any mined geologic disposal facility as a demonstration of historical and current engineering and geotechnical capabilities available for use in deep underground facility siting, planning, construction, operations and monitoring.

Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael E; Ratterman, Joseph D; Smith, Brian E

2014-02-11

Endpoint-based parallel data processing in a parallel active messaging interface ('PAMI') of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective opeartion through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

2014-08-12

Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

Neotectonics of interior Alaska and the late Quaternary slip rate along the Denali fault system

USGS Publications Warehouse

Haeussler, Peter J.; Matmon, Ari; Schwartz, David P.; Seitz, Gordon G.

2017-01-01

The neotectonics of southern Alaska (USA) are characterized by a several hundred kilometers–wide zone of dextral transpressional that spans the Alaska Range. The Denali fault system is the largest active strike-slip fault system in interior Alaska, and it produced a Mw 7.9 earthquake in 2002. To evaluate the late Quaternary slip rate on the Denali fault system, we collected samples for cosmogenic surface exposure dating from surfaces offset by the fault system. This study includes data from 107 samples at 19 sites, including 7 sites we previously reported, as well as an estimated slip rate at another site. We utilize the interpreted surface ages to provide estimated slip rates. These new slip rate data confirm that the highest late Quaternary slip rate is ∼13 mm/yr on the central Denali fault near its intersection with the eastern Denali and the Totschunda faults, with decreasing slip rate both to the east and west. The slip rate decreases westward along the central and western parts of the Denali fault system to 5 mm/yr over a length of ∼575 km. An additional site on the eastern Denali fault near Kluane Lake, Yukon, implies a slip rate of ∼2 mm/yr, based on geological considerations. The Totschunda fault has a maximum slip rate of ∼9 mm/yr. The Denali fault system is transpressional and there are active thrust faults on both the north and south sides of it. We explore four geometric models for southern Alaska tectonics to explain the slip rates along the Denali fault system and the active fault geometries: rotation, indentation, extrusion, and a combination of the three. We conclude that all three end-member models have strengths and shortcomings, and a combination of rotation, indentation, and extrusion best explains the slip rate observations.

Moving Iron through ferritin protein nanocages depends on residues throughout each four α-helix bundle subunit.

PubMed

Haldar, Suranjana; Bevers, Loes E; Tosha, Takehiko; Theil, Elizabeth C

2011-07-22

Eukaryotic H ferritins move iron through protein cages to form biologically required, iron mineral concentrates. The biominerals are synthesized during protein-based Fe²⁺/O₂ oxidoreduction and formation of [Fe³⁺O](n) multimers within the protein cage, en route to the cavity, at sites distributed over ~50 Å. Recent NMR and Co²⁺-protein x-ray diffraction (XRD) studies identified the entire iron path and new metal-protein interactions: (i) lines of metal ions in 8 Fe²⁺ ion entry channels with three-way metal distribution points at channel exits and (ii) interior Fe³⁺O nucleation channels. To obtain functional information on the newly identified metal-protein interactions, we analyzed effects of amino acid substitution on formation of the earliest catalytic intermediate (diferric peroxo-A(650 nm)) and on mineral growth (Fe³⁺O-A(350 nm)), in A26S, V42G, D127A, E130A, and T149C. The results show that all of the residues influenced catalysis significantly (p < 0.01), with effects on four functions: (i) Fe²⁺ access/selectivity to the active sites (Glu¹³⁰), (ii) distribution of Fe²⁺ to each of the three active sites near each ion channel (Asp¹²⁷), (iii) product (diferric oxo) release into the Fe³⁺O nucleation channels (Ala²⁶), and (iv) [Fe³⁺O](n) transit through subunits (Val⁴², Thr¹⁴⁹). Synthesis of ferritin biominerals depends on residues along the entire length of H subunits from Fe²⁺ substrate entry at 3-fold cage axes at one subunit end through active sites and nucleation channels, at the other subunit end, inside the cage at 4-fold cage axes. Ferritin subunit-subunit geometry contributes to mineral order and explains the physiological impact of ferritin H and L subunits.

Evaluation of large-truck fixed-object crashes at bridge structures in Kansas.

DOT National Transportation Integrated Search

2012-12-01

The aim of this study was to investigate any possible relationships between roadway geometry, pavement conditions, and : large-truck, fixed object crashes at bridge sites. Data on single-vehicle and multiple-vehicle large-truck crashes were : extract...

Summary and Comparison of Multiphase Streambed Scour Analysis at Selected Bridge Sites in Alaska

USGS Publications Warehouse

Conaway, Jeffrey S.

2004-01-01

The U.S. Geological Survey and the Alaska Department of Transportation and Public Facilities undertook a cooperative multiphase study of streambed scour at selected bridges in Alaska beginning in 1994. Of the 325 bridges analyzed for susceptibility to scour in the preliminary phase, 54 bridges were selected for a more intensive analysis that included site investigations. Cross-section geometry and hydraulic properties for each site in this study were determined from field surveys and bridge plans. Water-surface profiles were calculated for the 100- and 500-year floods using the Hydrologic Engineering Center?s River Analysis System and scour depths were calculated using methods recommended by the Federal Highway Administration. Computed contraction-scour depths for the 100- and 500-year recurrence-interval discharges exceeded 5 feet at six bridges, and pier-scour depths exceeded 10 feet at 24 bridges. Complex pier-scour computations were made at 10 locations where the computed contraction-scour depths would expose pier footings. Pressure scour was evaluated at three bridges where the modeled flood water-surface elevations intersected the bridge structure. Site investigation at the 54 scour-critical bridges was used to evaluate the effectiveness of the preliminary scour analysis. Values for channel-flow angle of attack and approach-channel width were estimated from bridge survey plans for the preliminary study and were measured during a site investigation for this study. These two variables account for changes in scour depths between the preliminary analysis and subsequent reanalysis for most sites. Site investigation is needed for best estimates of scour at bridges with survey plans that indicate a channel-flow angle of attack and for locations where survey plans did not include sufficient channel geometry upstream of the bridge.

Tracking plant physiological properties from multi-angular tower-based remote sensing.

PubMed

Hilker, Thomas; Gitelson, Anatoly; Coops, Nicholas C; Hall, Forrest G; Black, T Andrew

2011-04-01

Imaging spectroscopy is a powerful technique for monitoring the biochemical constituents of vegetation and is critical for understanding the fluxes of carbon and water between the land surface and the atmosphere. However, spectral observations are subject to the sun-observer geometry and canopy structure which impose confounding effects on spectral estimates of leaf pigments. For instance, the sun-observer geometry influences the spectral brightness measured by the sensor. Likewise, when considering pigment distribution at the stand level scale, the pigment content observed from single view angles may not necessarily be representative of stand-level conditions as some constituents vary as a function of the degree of leaf illumination and are therefore not isotropic. As an alternative to mono-angle observations, multi-angular remote sensing can describe the anisotropy of surface reflectance and yield accurate information on canopy structure. These observations can also be used to describe the bi-directional reflectance distribution which then allows the modeling of reflectance independently of the observation geometry. In this paper, we demonstrate a method for estimating pigment contents of chlorophyll and carotenoids continuously over a year from tower-based, multi-angular spectro-radiometer observations. Estimates of chlorophyll and carotenoid content were derived at two flux-tower sites in western Canada. Pigment contents derived from inversion of a CR model (PROSAIL) compared well to those estimated using a semi-analytical approach (r(2) = 0.90 and r(2) = 0.69, P < 0.05 for both sites, respectively). Analysis of the seasonal dynamics indicated that net ecosystem productivity was strongly related to total canopy chlorophyll content at the deciduous site (r(2) = 0.70, P < 0.001), but not at the coniferous site. Similarly, spectral estimates of photosynthetic light-use efficiency showed strong seasonal patterns in the deciduous stand, but not in conifers. We conclude that multi-angular, spectral observations can play a key role in explaining seasonal dynamics of fluxes of carbon and water and provide a valuable addition to flux-tower-based networks.

Telencephalic Neuronal Activation Associated with Spatial Memory in the Terrestrial Toad Rhinella arenarum: Participation of the Medial Pallium during Navigation by Geometry.

PubMed

Sotelo, María Inés; Daneri, M Florencia; Bingman, Verner Peter; Muzio, Rubén N

2016-01-01

Amphibians are central to discussions of vertebrate evolution because they represent the transition from aquatic to terrestrial life, a transition with profound consequences for the selective pressures shaping brain evolution. Spatial navigation is one class of behavior that has attracted the interest of comparative neurobiologists because of the relevance of the medial pallium/hippocampus, yet, surprisingly, in this regard amphibians have been sparsely investigated. In the current study, we trained toads to locate a water goal relying on the boundary geometry of a test environment (Geometry-Only) or boundary geometry coupled with a prominent, visual feature cue (Geometry-Feature). Once learning had been achieved, the animals were given one last training session and their telencephali were processed for c-Fos activation. Compared to control toads exposed to the test environment for the first time, geometry-only toads were found to have increased neuronal labeling in the medial pallium, the presumptive hippocampal homologue, while geometry-feature toads were found to have increased neuronal labeling in the medial, dorsal, and lateral pallia. The data indicate medial pallial participation in guiding navigation by environmental geometry and lateral, and to a lesser extent dorsal, pallial participation in guiding navigation by a prominent visual feature. As such, participation of the medial pallium/hippocampus in spatial cognition appears to be a conserved feature of terrestrial vertebrates even if their life history is still tied to water, a brain-behavior feature seemingly at least as ancient as the evolutionary transition to life on land. © 2016 S. Karger AG, Basel.

Relation of local scour to hydraulic properties at selected bridges in New York

USGS Publications Warehouse

Butch, Gerard K.; ,

1993-01-01

Hydraulic properties, bridge geometry, and basin characteristics at 31 bridges in New York are being investigated to identify factors that affect local scour. Streambed elevations measured by the U.S. Geological Survey and New York State Department of Transportation are used to estimate local-scour depth. Data that show zero or minor scour were included in the analysis to decrease bias and to estimate hydraulic properties related to local scour. The maximum measured local scour at the 31 bridges for a single peak flow was 5.4 feet, but the deepening of scour holes at two sites to 6.1 feet and 7.8 feet by multiple peak flows could indicate that the number or duration of high flows is a factor. Local scour at a pier generally increased as the recurrence interval (magnitude) of the discharge increased, but the correlation between local-scour depth and recurrence interval was inconsistent among study sites. For example, flows with a 2-year recurrence interval produced 2 feet of local scour at two sites, whereas a flow with a recurrence interval produced 2 feet of local scour at two sites, whereas a flow with a recurrence interval of 50 years produced only 0.5 feet of local scour at another site. Local-scour depth increased with water depth, stream velocity, and Reynolds number but did not correlate well with bed-material size, Froude number, pier geometry, friction slope, or several other hydraulic and basin characteristics.

Embedding the Ni-SOD mimetic Ni-NCC within a polypeptide sequence alters the specificity of the reaction pathway.

PubMed

Krause, Mary E; Glass, Amanda M; Jackson, Timothy A; Laurence, Jennifer S

2013-01-07

The unique metal abstracting peptide asparagine-cysteine-cysteine (NCC) binds nickel in a square planar 2N:2S geometry and acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD). The Ni-NCC tripeptide complex undergoes rapid, site-specific chiral inversion to dld-NCC in the presence of oxygen. Superoxide scavenging activity increases proportionally with the degree of chiral inversion. Characterization of the NCC sequence within longer peptides with absorption, circular dichroism (CD), and magnetic CD (MCD) spectroscopies and mass spectrometry (MS) shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent because of bis-amide, rather than amine/amide, coordination. In addition, both Ni-tripeptide and Ni-pentapeptide complexes have charges of -2. This study demonstrates that the chiral inversion chemistry does not occur when NCC is embedded in a longer polypeptide sequence. Nonetheless, the superoxide scavenging reactivity of the embedded Ni-NCC module is similar to that of the chirally inverted tripeptide complex, which is consistent with a minor change in the reduction potential for the Ni-pentapeptide complex. Together, this suggests that the charge of the complex could affect the SOD activity as much as a change in the primary coordination sphere. In Ni-NCC and other Ni-SOD mimics, changes in chirality, superoxide scavenging activity, and oxidation of the peptide itself all depend on the presence of dioxygen or its reduced derivatives (e.g., superoxide), and the extent to which each of these distinct reactions occurs is ruled by electronic and steric effects that emenate from the organization of ligands around the metal center.

Geomorphological and geophysical investigations for the characterization of the Roman Carsulae site (Tiber basin, Central Italy)

NASA Astrophysics Data System (ADS)

Bottari, C.; Aringoli, D.; Carluccio, R.; Castellano, C.; D'Ajello Caracciolo, F.; Gasperini, M.; Materazzi, M.; Nicolosi, I.; Pambianchi, G.; Pieruccini, P.; Sepe, V.; Urbini, S.; Varazi, F.

2017-08-01

This paper aims to bring to light the possible linkage between karstic phenomena and the human occupation of the Roman site of Carsulae (Tiber basin, Central Italy). Dolines are a typical morphological expression of karst rocks' dissolution and collapse and, usually, they represent a potential hazard for human activities and, in particular, in the care and maintenance of cultural heritage sites. In this study, we observed that the development of a subsidence doline caused severe damage to some archaeological structures at the Carsulae monumental site. According to the results obtained in our investigation, three sites at least with karst dissolution phenomena in the shallow calcareous tufa layer have been identified. One of them subsided probably in Roman times and produced a sharp deformation of the decumanus. In order to understand the evolution of this territory an integrated geomorphological and geophysical survey was carried out. The combination between the information derived from different geophysical techniques, such as: Electrical Resistivity Tomography (ERT), Frequency-Domain Electromagnetism (FDEM), and Ground Penetrating Radar (GPR) clearly pointed out that the calcareous tufa layer is characterized by an irregular geometry and this resulted in the investigated area being affected by karst dissolution in several parts. Four boreholes opportunely located, provided direct information about the depth and the alteration of the calcareous tufa basement and precious calibration data for the geophysical methods. This study contributes to improving our knowledge on the evolution of the Carsulae archaeological site providing a new insight into the adaptation of ancient human societies in this problematic territory.

Siting, design and operational controls for snow disposal sites.

PubMed

Wheaton, S R; Rice, W J

2003-01-01

The Municipality of Anchorage (MOA), at 61 degrees north latitude, ploughs and hauls snow from urban streets throughout the winter, incorporating grit and chloride applied to street surfaces for traffic safety. Hauled snow is stored at snow disposal facilities, where it melts at ambient spring temperatures. MOA studies performed from 1998 through 2001 show that disposal site melt processes can be manipulated, through site design and operation practices, to control chloride and turbidity in meltwater. An experimental passive "V-swale" pad configuration tested by MOA investigators reduced site meltwater turbidity by an order of magnitude (to about 50 NTU from the 500 NTU typical of more conventional planar pad geometry). The MOA has developed new siting, design and operational criteria for snow disposal facilities to conform to the tested V-swale pad configuration.

Cilia driven flow networks in the brain

NASA Astrophysics Data System (ADS)

Wang, Yong; Faubel, Regina; Westendorf, Chrsitian; Eichele, Gregor; Bodenschatz, Eberhard

Neurons exchange soluble substances via the cerebrospinal fluid (CSF) that fills the ventricular system. The walls of the ventricular cavities are covered with motile cilia that constantly beat and thereby induce a directional flow. We recently discovered that cilia in the third ventricle generate a complex flow pattern leading to partitioning of the ventricular volume and site-directed transport paths along the walls. Transient and daily recurrent alterations in the cilia beating direction lead to changes in the flow pattern. This has consequences for delivery of CSF components along the near wall flow. The contribution of this cilia-induced flow to overall CSF flow remains to be investigated. The state-of-art lattice Boltzmann method is adapted for studying the CFS flow. The 3D geometry of the third ventricle at high resolution was reconstructed. Simulation of CSF flow without cilia in this geometry confirmed that the previous idea about unidirectional flow does not explain how different components of CSF can be delivered to their various target sites. We study the contribution of the cilia-induced flow pattern to overall CSF flow and identify target areas for site-specific delivery of CSF-constituents with respect to the temporal changes.

Structure and catalytic activities of ferrous centers confined on the interface between carbon nanotubes and humic acid

NASA Astrophysics Data System (ADS)

Wang, Bing; Zhou, Xiaoyan; Wang, Dongqi; Yin, Jun-Jie; Chen, Hanqing; Gao, Xingfa; Zhang, Jing; Ibrahim, Kurash; Chai, Zhifang; Feng, Weiyue; Zhao, Yuliang

2015-01-01

Preparation of heterogeneous catalysts with active ferrous centers is of great significance for industrial and environmental catalytic processes. Nanostructured carbon materials (NCM), which possess free-flowing π electrons, can coordinate with transition metals, provide a confinement environment for catalysis, and act as potential supports or ligands to construct analogous complexes. However, designing such catalysts using NCM is still seldom studied to date. Herein, we synthesized a sandwich structured ternary complex via the coordination of Fe-loaded humic acid (HA) with C&z.dbd;C bonds in the aromatic rings of carbon nanotubes (CNTs), in which the O/N-Fe-C interface configuration provides the confinement environment for the ferrous sites. The experimental and theoretical results revealed octahedrally/tetrahedrally coordinated geometry at Fe centers, and the strong hybridization between CNT C π* and Fe 3d orbitals induces discretization of the atomic charges on aromatic rings of CNTs, which facilitates O2 adsorption and electron transfer from carbon to O2, which enhances O2 activation. The O2 activation by the novel HA/Fe-CNT complex can be applied in the oxidative degradation of phenol red (PR) and bisphenol A (BPA) in aqueous media.Preparation of heterogeneous catalysts with active ferrous centers is of great significance for industrial and environmental catalytic processes. Nanostructured carbon materials (NCM), which possess free-flowing π electrons, can coordinate with transition metals, provide a confinement environment for catalysis, and act as potential supports or ligands to construct analogous complexes. However, designing such catalysts using NCM is still seldom studied to date. Herein, we synthesized a sandwich structured ternary complex via the coordination of Fe-loaded humic acid (HA) with C&z.dbd;C bonds in the aromatic rings of carbon nanotubes (CNTs), in which the O/N-Fe-C interface configuration provides the confinement environment for the ferrous sites. The experimental and theoretical results revealed octahedrally/tetrahedrally coordinated geometry at Fe centers, and the strong hybridization between CNT C π* and Fe 3d orbitals induces discretization of the atomic charges on aromatic rings of CNTs, which facilitates O2 adsorption and electron transfer from carbon to O2, which enhances O2 activation. The O2 activation by the novel HA/Fe-CNT complex can be applied in the oxidative degradation of phenol red (PR) and bisphenol A (BPA) in aqueous media. Electronic supplementary information (ESI) available: Optimization of the mass ratios of HA to CNTs and the reaction pH conditions for Fe loading; scanning electron microscope (SEM), UV-Vis-near-infrared, Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR) for CNT-HA; EPR experiment and UPLC-ESI-MS analysis; and DFT calculation. See DOI: 10.1039/c4nr06665k

Atomic Force Microscopy Mechanical Mapping of Micropatterned Cells Shows Adhesion Geometry-Dependent Mechanical Response on Local and Global Scales

PubMed Central

Rigato, Annafrancesca; Rico, Felix; Eghiaian, Frédéric; Piel, Mathieu; Scheuring, Simon

2015-01-01

In multicellular organisms cell shape and organization are dictated by cell-cell or cell-extracellular matrix adhesion interactions. Adhesion complexes crosstalk with the cytoskeleton enabling cells to sense their mechanical environment. Unfortunately, most of cell biology studies, and cell mechanics studies in particular, are conducted on cultured cells adhering to a hard, homogeneous and unconstrained substrate with non-specific adhesion sites – thus far from physiological and reproducible conditions. Here, we grew cells on three different fibronectin patterns with identical overall dimensions but different geometries (▽, T and Y), and investigated their topography and mechanics by atomic force microscopy (AFM). The obtained mechanical maps were reproducible for cells grown on patterns of the same geometry, revealing pattern-specific subcellular differences. We found that local Young’s moduli variations are related to the cell adhesion geometry. Additionally, we detected local changes of cell mechanical properties induced by cytoskeletal drugs. We thus provide a method to quantitatively and systematically investigate cell mechanics and their variations, and present further evidence for a tight relation between cell adhesion and mechanics. PMID:26013956

Atomic Force Microscopy Mechanical Mapping of Micropatterned Cells Shows Adhesion Geometry-Dependent Mechanical Response on Local and Global Scales.

PubMed

Rigato, Annafrancesca; Rico, Felix; Eghiaian, Frédéric; Piel, Mathieu; Scheuring, Simon

2015-06-23

In multicellular organisms, cell shape and organization are dictated by cell-cell or cell-extracellular matrix adhesion interactions. Adhesion complexes crosstalk with the cytoskeleton enabling cells to sense their mechanical environment. Unfortunately, most of cell biology studies, and cell mechanics studies in particular, are conducted on cultured cells adhering to a hard, homogeneous, and unconstrained substrate with nonspecific adhesion sites, thus far from physiological and reproducible conditions. Here, we grew cells on three different fibronectin patterns with identical overall dimensions but different geometries (▽, T, and Y), and investigated their topography and mechanics by atomic force microscopy (AFM). The obtained mechanical maps were reproducible for cells grown on patterns of the same geometry, revealing pattern-specific subcellular differences. We found that local Young's moduli variations are related to the cell adhesion geometry. Additionally, we detected local changes of cell mechanical properties induced by cytoskeletal drugs. We thus provide a method to quantitatively and systematically investigate cell mechanics and their variations, and present further evidence for a tight relation between cell adhesion and mechanics.

Minimizing Actuator-Induced Residual Error in Active Space Telescope Primary Mirrors

DTIC Science & Technology

2010-09-01

actuator geometry, and rib-to-facesheet intersection geometry are exploited to achieve improved performance in silicon carbide ( SiC ) mirrors . A...are exploited to achieve improved performance in silicon carbide ( SiC ) mirrors . A parametric finite element model is used to explore the trade space...MOST) finite element model. The move to lightweight actively-controlled silicon carbide ( SiC ) mirrors is traced back to previous generations of space

Geomagnetic activity: Dependence on solar wind parameters

NASA Technical Reports Server (NTRS)

Svalgaard, L.

1977-01-01

Current ideas about the interaction between the solar wind and the earth's magnetosphere are reviewed. The solar wind dynamic pressure as well as the influx of interplanetary magnetic field lines are both important for the generation of geomagnetic activity. The influence of the geometry of the situation as well as the variability of the interplanetary magnetic field are both found to be important factors. Semi-annual and universal time variations are discussed as well as the 22-year cycle in geomagnetic activity. All three are found to be explainable by the varying geometry of the interaction. Long term changes in geomagnetic activity are examined.

On the active site of mononuclear B1 metallo β-lactamases: a computational study

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; Magistrato, Alessandra; Dal Peraro, Matteo; Vila, Alejandro J.; Carloni, Paolo; Pierattelli, Roberta

2012-04-01

Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called `3H' and `DCH' sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum-classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the ɛɛδ and δɛδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.

Enhancing rescue-archaeology using geomorphological approaches: Archaeological sites in Paredes (Asturias, NW Spain)

NASA Astrophysics Data System (ADS)

Jiménez-Sánchez, M.; González-Álvarez, I.; Requejo-Pagés, O.; Domínguez-Cuesta, M. J.

2011-09-01

Palaeolithic remnants, a Necropolis (Roman villa), and another minor archaeological site were discovered in Paredes (Spain). These sites were the focus of multidisciplinary research during the construction of a large shopping centre in Asturias (NW Spain). The aims of this study are (1) to contribute to archaeological prospection in the sites and (2) to develop evolutionary models of the sites based on geomorphological inferences. Detailed archaeological prospection (103 trenches), geomorphologic mapping, stratigraphic studies (36 logs) and ground penetration radar (GPR) surveys on five profiles indicate that the location of the settlement source of the Necropolis is outside the construction perimeter, farther to the southeast. The Pre-Holocene evolution of the fluvial landscape is marked by the development of two terraces (T1 and T2) that host the Early Palaeolithic remains in the area (ca 128-71 ka). The Holocene evolution of the landscape was marked by the emplacement of the Nora River flood plain, covered by alluvial fans after ca. 9 ka BP (cal BC 8252-7787). Subsequently, Neolithic pebble pits dated ca. 5.3 ka BP (cal BC 4261-3963 and 4372-4051) were constructed on T2, at the area reoccupied as a Necropolis during the Late Roman period, 1590 ± 45 years BP (cal AD 382-576). Coeval human activity during the Late Roman period at 1670 ± 60 years BP (cal AD 320-430) is also recorded by channel infill sediments in a minor site at the margin of an alluvial fan located to the southeast. This work shows that a rescue-archaeological study can be significantly enhanced by the implementation of multidisciplinary scientific studies, in which the holistic view of geomorphologic settings provide key insights into the geometry and evolution of archaeological sites.

Relating soil pore geometry to soil water content dynamics decomposed at multiple frequencies

NASA Astrophysics Data System (ADS)

Qin, Mingming; Gimenez, Daniel; Cooper, Miguel

2016-04-01

Soil structure is a critical factor determining the response of soil water content to meteorological inputs such as precipitation. Wavelet analysis can be used to filter a signal into several wavelet components, each characterizing a given frequency. The purpose of this research was to investigate relationships between the geometry of soil pore systems and the various wavelet components derived from soil water content dynamics. The two study sites investigated were located in the state of São Paulo, Brazil. Each site was comprised of five soil profiles, the first site was situated along a 300-meter transect with about 10% slope in a tropical semi-deciduous forest, while the second one spanned 230-meter over a Brazilian savanna with a slope of about 6%. For each profile, between two to four Water Content Reflectometer CS615 (Campbell Scientific, Inc.) probes were installed according to horizonation at depths varying between 0.1 m and 2.3 m. Bulk soil, three soil cores, and one undisturbed soil block were sampled from selected horizons for determining particle size distributions, water retention curves, and pore geometry, respectively. Pore shape and size were determined from binary images obtained from resin-impregnated blocks and used to characterize pore geometry. Soil water contents were recorded at a 20-minute interval over a 4-month period. The Mexican hat wavelet was used to decompose soil water content measurements into wavelet components. The responses of wavelet components to wetting and drying cycles were characterized by the median height of the peaks in each wavelet component and were correlated with particular pore shapes and sizes. For instance, large elongated and irregular pores, largely responsible for the transmission of water, were significantly correlated with wavelet components at high frequencies (40 minutes to 48 hours) while rounded pores, typically associated to water retention, were only significantly correlated to lower frequency ranges (48 hours and two months). These results will be further discussed in the context of the location of the soil horizons within the toposequence.

Porosity, Mineralization, Tissue Type and Morphology Interactions at the Human Tibial Cortex

NASA Astrophysics Data System (ADS)

Hampson, Naomi A.

Prior research has shown a relationship between tibia robustness (ratio of cross-sectional area to bone length) and stress fracture risk, with less robust bones having a higher risk, which may indicate a compensatory increase in elastic modulus to increase bending strength. Previous studies of human tibiae have shown higher ash content in slender bones. In this study, the relationships between variations in volumetric porosity, ash content, tissue mineral density, secondary bone tissue, and cross sectional geometry, were investigated in order to better understand the tissue level adaptations that may occur in the establishment of cross-sectional properties. In this research, significant differences were found between porosity, ash content, and tissue type around the cortex between robust and slender bones, suggesting that there was a level of co-adaption occurring. Variation in porosity correlated with robustness, and explained large parts of the variation in tissue mineral density. The nonlinear relationship between porosity and ash content may support that slender bones compensate for poor geometry by increasing ash content through reduced remodeling, while robust individuals increase porosity to decrease mass, but only to a point. These results suggest that tissue level organization plays a compensatory role in the establishment of adult bone mass, and may contribute to differences in bone aging between different bone phenotypes. The results suggest that slender individuals have significantly less remodeled bone, however the proportion of remodeled bone was not uniform around the tibia. In the complex results of the study of 38% vs. 66% sites the distal site was subject to higher strains than the 66% site, indicating both local and global regulators may be affecting overall remodeling rates and need to be teased apart in future studies. This research has broad clinical implications on the diagnosis and treatment of fragility fractures. The relationships that were found between local variables and global geometry indicate that there was a fundamental difference between robust and slender bones, which affect the overall properties of the bone. This could allow for simple testing of bone geometry to predict an individual's fracture risk.

A molecular model for proflavine-DNA intercalation.

PubMed Central

Neidle, S; Pearl, L H; Herzyk, P; Berman, H M

1988-01-01

A molecular model has been derived for the intercalation of proflavine into the CpG site of the decamer duplex of d(GATACGATAC). The starting geometry of the intercalation site was taken from previous crystallographic studies on the d(CpG)-proflavine complex, and molecular mechanics used to obtain a stereochemically acceptable structure. This has widened grooves compared to standard A- or B- double helices, as well as distinct conformational, roll, twist and tilt features. PMID:3174439

Tetraammine(carbonato-κ(2) O,O')cobalt(III) perchlorate.

PubMed

Mohan, Singaravelu Chandra; Jenniefer, Samson Jegan; Muthiah, Packianathan Thomas; Jothivenkatachalam, Kandasamy

2013-01-01

In the title complex, [Co(CO3)(NH3)4]ClO4, both the cation and anion lie on a mirror plane. The Co(III) ion is coordinated by two NH3 ligands and a chelating carbonato ligand in the equatorial sites and by two NH3 groups in the axial sites, forming a distorted octa-hedral geometry. In the crystal, N-H⋯O hydrogen bonds connect the anions and cations, forming a three-dimensional network.

Bridging Scales: A Model-Based Assessment of the Technical Tidal-Stream Energy Resource off Massachusetts, USA

NASA Astrophysics Data System (ADS)

Cowles, G. W.; Hakim, A.; Churchill, J. H.

2016-02-01

Tidal in-stream energy conversion (TISEC) facilities provide a highly predictable and dependable source of energy. Given the economic and social incentives to migrate towards renewable energy sources there has been tremendous interest in the technology. Key challenges to the design process stem from the wide range of problem scales extending from device to array. In the present approach we apply a multi-model approach to bridge the scales of interest and select optimal device geometries to estimate the technical resource for several realistic sites in the coastal waters of Massachusetts, USA. The approach links two computational models. To establish flow conditions at site scales ( 10m), a barotropic setup of the unstructured grid ocean model FVCOM is employed. The model is validated using shipboard and fixed ADCP as well as pressure data. For device scale, the structured multiblock flow solver SUmb is selected. A large ensemble of simulations of 2D cross-flow tidal turbines is used to construct a surrogate design model. The surrogate model is then queried using velocity profiles extracted from the tidal model to determine the optimal geometry for the conditions at each site. After device selection, the annual technical yield of the array is evaluated with FVCOM using a linear momentum actuator disk approach to model the turbines. Results for several key Massachusetts sites including comparison with theoretical approaches will be presented.

Exploration of the Ca2+ interaction modes of the nifedipine calcium channel antagonist.

PubMed

Liu, Huichun; Zhang, Liang; Li, Ping; Cukier, Robert I; Bu, Yuxiang

2007-02-02

A comprehensive study is carried out using quantum chemical computation and molecular dynamics (MD) simulations to gain insight into the interaction between Ca(2+) ions and the most important class of calcium channel antagonists--nifedipine. First, the chelating structures and energetic characters of nifedipine-Ca(2+) in the gas phase are explored, and 25 isomers are found. The most favorable chelating mode is a tridentate one, that is, Ca(2+) binds to two carbonyl O atoms and one nitryl O atom, where Ca(2+) is above the plane of the three O atoms to form a pyramidal structure. Accurate geometric structures, relative stabilities, vertical and adiabatic binding energies, and charge distributions are discussed. The differences in the geometries and energies among these isomers are analyzed from the contributions of chelating sites, electrostatics and polarizations, steric repulsions, and charge distributions. The interconversions among isomers with similar geometries and energies are also investigated because of the importance of the geometric transformation in the biological system. Furthermore, certain numbers of water molecules are added to the nifedipine-Ca(2+) system to probe the effect of water. A detailed study is performed on the hydrated geometries on the basis of the most stable isomer 1. Stepwise hydration can weaken the nifedipine-Ca(2+) interaction, and the chelating sites of nifedipine are gradually replaced by the added water molecules. Hexacoordination is found to be the most favorable geometry no matter how many water molecules were added, which can be verified by the MD simulations. The transfer of water molecules from the inner shell to the outer shell is also supported by MD simulations of the hexahydrated complexes.

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study.

PubMed

Falisi, G; Severino, M; Rastelli, C; Bernardi, S; Caruso, S; Galli, M; Lamazza, L; Di Paolo, C

2017-03-01

The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized.

Near surface geophysics techniques and geomorphological approach to reconstruct the hazard cave map in historical and urban areas

NASA Astrophysics Data System (ADS)

Lazzari, M.; Loperte, A.; Perrone, A.

2010-03-01

This work, carried out with an integrated methodological approach, focuses on the use of near surface geophysics techniques, such as ground penetrating radar and electrical resistivity tomography (ERT), and geomorphological analysis, in order to reconstruct the cave distribution and geometry in a urban context and, in particular, in historical centres. The interaction during recent centuries between human activity (caves excavation, birth and growth of an urban area) and the characters of the natural environment were the reasons of a progressive increase in hazard and vulnerability levels of several sites. The reconstruction of a detailed cave map distribution is the first step to define the anthropic and geomorphological hazard in urban areas, fundamental basis for planning and assessing the risk.

Solution NMR Structures of Productive and Non-productive Complexes between the A and B Domains of the Cytoplasmic Subunit of the Mannose Transporter of the Escherichia coli Phosphotransferase System*

PubMed Central

Hu, Jun; Hu, Kaifeng; Williams, David C.; Komlosh, Michal E.; Cai, Mengli; Clore, G. Marius

2008-01-01

Solution structures of complexes between the isolated A (IIAMan) and B (IIBMan) domains of the cytoplasmic component of the mannose transporter of Escherichia coli have been solved by NMR. The complex of wild-type IIAMan and IIBMan is a mixture of two species comprising a productive, phosphoryl transfer competent complex and a non-productive complex with the two active site histidines, His-10 of IIAMan and His-175 of IIBMan, separated by ∼25Å. Mutation of the active site histidine, His-10, of IIAMan to a glutamate, to mimic phosphorylation, results in the formation of a single productive complex. The apparent equilibrium dissociation constants for the binding of both wild-type and H10E IIAMan to IIBMan are approximately the same (KD ∼ 0.5 mm). The productive complex can readily accommodate a transition state involving a pentacoordinate phosphoryl group with trigonal bipyramidal geometry bonded to the Nε2 atom of His-10 of IIAMan and the Nδ1 atom of His-175 of IIBMan with negligible (<0.2Å) local backbone conformational changes in the immediate vicinity of the active site. The non-productive complex is related to the productive one by a ∼90° rotation and ∼37Å translation of IIBMan relative to IIAMan, leaving the active site His-175 of IIBMan fully exposed to solvent in the non-productive complex. The interaction surface on IIAMan for the non-productive complex comprises a subset of residues used in the productive complex and in both cases involves both subunits of IIAMan. The selection of the productive complex by IIAMan(H10E) can be attributed to neutralization of the positively charged Arg-172 of IIBMan at the center of the interface. The non-productive IIAMan-IIBMan complex may possibly be relevant to subsequent phosphoryl transfer from His-175 of IIBMan to the incoming sugar located on the transmembrane IICMan-IIDMan complex. PMID:18270202

Preparation and characterization of a supported system of Ni2P/Ni12P5 nanoparticles and their use as the active phase in chemoselective hydrogenation of acetophenone

NASA Astrophysics Data System (ADS)

Costa, Dolly C.; Soldati, Analía L.; Pecchi, Gina; Bengoa, José Fernando; Marchetti, Sergio Gustavo; Vetere, Virginia

2018-05-01

Ni2P/Ni12P5 nanoparticles were obtained by thermal decomposition of nickel organometallic salt at low temperature. The use of different characterization techniques allowed us to determine that this process produced a mixture of two nickel phosphide phases: Ni2P and Ni12P5. These nickel phosphides nanoparticles, supported on mesoporous silica, showed activity and high selectivity for producing the hydrogenation of the acetophenone carbonyl group to obtain 1-phenylethanol. This is a first report that demonstrates the ability of supported Ni2P/Ni12P5 nanoparticles to produce the chemoselective hydrogenation of acetophenone. We attribute these special catalytic properties to the particular geometry of the Ni–P sites on the surface of the nanoparticles. This is an interesting result because the nickel phosphides have a wide composition range (from Ni3P to NiP3), with different crystallographic structures, therefore we think that different phases could be active and selective to hydrogenate many important molecules with more than one functional group.

Sediment and channel-geometry investigations for the Kansas River bank stabilization study, Kansas, Nebraska, and Colorado

USGS Publications Warehouse

Osterkamp, W.R.; Curtis, R.E.; Crowther, H.G.

1982-01-01

Analysis of hydrologic data from the Kansas River basin suggests that the channels of the lower Solomon, Saline, and Smoky Hill Rivers have narrowed and stabilized as a result of construction of upstream reservoirs. The Kansas River channel, however, remains relatively unstable and locally active. Streamflow regulation and sediment trapping by reservoirs are possible causes of changes occurring at various Kansas River sites. An inferred deficiency of the suspended-sediment load, however, is likely to cause continuing instability. Suspended sediment in the Kansas River apparently is too sparse to form and maintain stable alluvial banks. The deficiency probably results in an increase of bed material movement, general channel widening, and local braiding. Significant channel degradation is lacking at most sites, but may occur in response to long-term (decades-to-centuries) regulation. Recent degradation near Bonner Springs, Kans., may be the result of sand and gravel removal. Any imposed changes that shorten the channel or reduce the suspended-sediment discharge of the Kansas River are expected to cause additional channel instability. (USGS)

Spectroscopic (FTIR, FT-Raman), molecular electrostatic potential, NBO and HOMO-LUMO analysis of P-bromobenzene sulfonyl chloride based on DFT calculations

NASA Astrophysics Data System (ADS)

Jeyavijayan, S.

2015-02-01

The FTIR and FT-Raman spectra of P-bromobenzene sulfonyl chloride (P-BBSC) have been recorded in the regions 4000-400 cm-1 and 3500-50 cm-1, respectively. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, were calculated by density functional theory (DFT/B3LYP) method. A good agreement between experimental and calculated normal modes of vibrations has been observed. A detailed interpretation of the infrared and Raman spectra of P-BBSC is also reported based on total energy distribution (TED). Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The MEP map shows the negative potential sites are on oxygen atoms as well as the positive potential sites are around the hydrogen atoms. The UV-vis spectral analysis of P-BBSC has also been done which confirms the charge transfer of the molecule.

Mean-Field Scaling of the Superfluid to Mott Insulator Transition in a 2D Optical Superlattice.

PubMed

Thomas, Claire K; Barter, Thomas H; Leung, Tsz-Him; Okano, Masayuki; Jo, Gyu-Boong; Guzman, Jennie; Kimchi, Itamar; Vishwanath, Ashvin; Stamper-Kurn, Dan M

2017-09-08

The mean-field treatment of the Bose-Hubbard model predicts properties of lattice-trapped gases to be insensitive to the specific lattice geometry once system energies are scaled by the lattice coordination number z. We test this scaling directly by comparing coherence properties of ^{87}Rb gases that are driven across the superfluid to Mott insulator transition within optical lattices of either the kagome (z=4) or the triangular (z=6) geometries. The coherent fraction measured for atoms in the kagome lattice is lower than for those in a triangular lattice with the same interaction and tunneling energies. A comparison of measurements from both lattices agrees quantitatively with the scaling prediction. We also study the response of the gas to a change in lattice geometry, and observe the dynamics as a strongly interacting kagome-lattice gas is suddenly "hole doped" by introducing the additional sites of the triangular lattice.

Mispairs with Watson-Crick base-pair geometry observed in ternary complexes of an RB69 DNA polymerase variant.

PubMed

Xia, Shuangluo; Konigsberg, William H

2014-04-01

Recent structures of DNA polymerase complexes with dGMPCPP/dT and dCTP/dA mispairs at the insertion site have shown that they adopt Watson-Crick geometry in the presence of Mn(2+) indicating that the tautomeric or ionization state of the base has changed. To see whether the tautomeric or ionization state of base-pair could be affected by its microenvironment, we determined 10 structures of an RB69 DNA polymerase quadruple mutant with dG/dT or dT/dG mispairs at position n-1 to n-5 of the Primer/Template duplex. Different shapes of the mispairs, including Watson-Crick geometry, have been observed, strongly suggesting that the local environment of base-pairs plays an important role in their tautomeric or ionization states. © 2014 The Protein Society.

Electronic and geometric properties of ETS-10: QM/MM studies of cluster models.

PubMed

Zimmerman, Anne Marie; Doren, Douglas J; Lobo, Raul F

2006-05-11

Hybrid DFT/MM methods have been used to investigate the electronic and geometric properties of the microporous titanosilicate ETS-10. A comparison of finite length and periodic models demonstrates that band gap energies for ETS-10 can be well represented with relatively small cluster models. Optimization of finite clusters leads to different local geometries for bulk and end sites, where the local bulk TiO6 geometry is in good agreement with recent experimental results. Geometry optimizations reveal that any asymmetry within the axial O-Ti-O chain is negligible. The band gap in the optimized model corresponds to a O(2p) --> Tibulk(3d) transition. The results suggest that the three Ti atom, single chain, symmetric, finite cluster is an effective model for the geometric and electronic properties of bulk and end TiO6 groups in ETS-10.

Probing the geometry of copper and silver adatoms on magnetite: quantitative experiment versus theory† †Electronic supplementary information (ESI) available: Experimental and computational details, as well as further details on the results and analyses. See DOI: 10.1039/c7nr07319d

PubMed Central

Meier, Matthias; Jakub, Zdeněk; Balajka, Jan; Hulva, Jan; Bliem, Roland; Thakur, Pardeep K.; Lee, Tien-Lin; Franchini, Cesare; Schmid, Michael; Diebold, Ulrike; Allegretti, Francesco; Parkinson, Gareth S.

2018-01-01

Accurately modelling the structure of a catalyst is a fundamental prerequisite for correctly predicting reaction pathways, but a lack of clear experimental benchmarks makes it difficult to determine the optimal theoretical approach. Here, we utilize the normal incidence X-ray standing wave (NIXSW) technique to precisely determine the three dimensional geometry of Ag1 and Cu1 adatoms on Fe3O4(001). Both adatoms occupy bulk-continuation cation sites, but with a markedly different height above the surface (0.43 ± 0.03 Å (Cu1) and 0.96 ± 0.03 Å (Ag1)). HSE-based calculations accurately predict the experimental geometry, but the more common PBE + U and PBEsol + U approaches perform poorly. PMID:29334395

Integrated geophysical investigations in a fault zone located on southwestern part of İzmir city, Western Anatolia, Turkey

NASA Astrophysics Data System (ADS)

Drahor, Mahmut G.; Berge, Meriç A.

2017-01-01

Integrated geophysical investigations consisting of joint application of various geophysical techniques have become a major tool of active tectonic investigations. The choice of integrated techniques depends on geological features, tectonic and fault characteristics of the study area, required resolution and penetration depth of used techniques and also financial supports. Therefore, fault geometry and offsets, sediment thickness and properties, features of folded strata and tectonic characteristics of near-surface sections of the subsurface could be thoroughly determined using integrated geophysical approaches. Although Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT) and Seismic Refraction Tomography (SRT) methods are commonly used in active tectonic investigations, other geophysical techniques will also contribute in obtaining of different properties in the complex geological environments of tectonically active sites. In this study, six different geophysical methods used to define faulting locations and characterizations around the study area. These are GPR, ERT, SRT, Very Low Frequency electromagnetic (VLF), magnetics and self-potential (SP). Overall integrated geophysical approaches used in this study gave us commonly important results about the near surface geological properties and faulting characteristics in the investigation area. After integrated interpretations of geophysical surveys, we determined an optimal trench location for paleoseismological studies. The main geological properties associated with faulting process obtained after trenching studies. In addition, geophysical results pointed out some indications concerning the active faulting mechanism in the area investigated. Consequently, the trenching studies indicate that the integrated approach of geophysical techniques applied on the fault problem reveals very useful and interpretative results in description of various properties of faulting zone in the investigation site.

Revisiting and re-engineering the classical zinc finger peptide: consensus peptide-1 (CP-1).

PubMed

Besold, Angelique N; Widger, Leland R; Namuswe, Frances; Michalek, Jamie L; Michel, Sarah L J; Goldberg, David P

2016-04-01

Zinc plays key structural and catalytic roles in biology. Structural zinc sites are often referred to as zinc finger (ZF) sites, and the classical ZF contains a Cys2His2 motif that is involved in coordinating Zn(II). An optimized Cys2His2 ZF, named consensus peptide 1 (CP-1), was identified more than 20 years ago using a limited set of sequenced proteins. We have reexamined the CP-1 sequence, using our current, much larger database of sequenced proteins that have been identified from high-throughput sequencing methods, and found the sequence to be largely unchanged. The CCHH ligand set of CP-1 was then altered to a CAHH motif to impart hydrolytic activity. This ligand set mimics the His2Cys ligand set of peptide deformylase (PDF), a hydrolytically active M(II)-centered (M = Zn or Fe) protein. The resultant peptide [CP-1(CAHH)] was evaluated for its ability to coordinate Zn(II) and Co(II) ions, adopt secondary structure, and promote hydrolysis. CP-1(CAHH) was found to coordinate Co(II) and Zn(II) and a pentacoordinate geometry for Co(II)-CP-1(CAHH) was implicated from UV-vis data. This suggests a His2Cys(H2O)2 environment at the metal center. The Zn(II)-bound CP-1(CAHH) was shown to adopt partial secondary structure by 1-D (1)H NMR spectroscopy. Both Zn(II)-CP-1(CAHH) and Co(II)-CP-1(CAHH) show good hydrolytic activity toward the test substrate 4-nitrophenyl acetate, exhibiting faster rates than most active synthetic Zn(II) complexes.

Dependence of astigmatism, far-field pattern, and spectral envelope width on active layer thickness of gain guided lasers with narrow stripe geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mamine, T.

1984-06-15

The effects of active layer thickness on the astigmatism, the angle of far-field pattern width parallel to the junction, and the spectral envelope width of a gain guided laser with a narrow stripe geometry have been investigated analytically and experimentally. It is concluded that a large level of astigmatism, a narrow far-field pattern width, and a rapid convergence of the spectral envelope width are inherent to the gain guided lasers with thin active layers.

Virtual Reality Calibration for Telerobotic Servicing

NASA Technical Reports Server (NTRS)

Kim, W.

1994-01-01

A virtual reality calibration technique of matching a virtual environment of simulated graphics models in 3-D geometry and perspective with actual camera views of the remote site task environment has been developed to enable high-fidelity preview/predictive displays with calibrated graphics overlay on live video.

Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs.

PubMed

Bortolozzi, Roberta; Mattiuzzo, Elena; Dal Pra, Matteo; Sturlese, Mattia; Moro, Stefano; Hamel, Ernest; Carta, Davide; Viola, Giampietro; Ferlin, Maria Grazia

2018-01-01

Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI 50 values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of β-tubulin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Modeling Active Contraction and Relaxation of Left Ventricle Using Different Zero-load Diastole and Systole Geometries for Better Material Parameter Estimation and Stress/Strain Calculations

PubMed Central

Fan, Longling; Yao, Jing; Yang, Chun; Xu, Di; Tang, Dalin

2018-01-01

Modeling ventricle active contraction based on in vivo data is extremely challenging because of complex ventricle geometry, dynamic heart motion and active contraction where the reference geometry (zero-stress geometry) changes constantly. A new modeling approach using different diastole and systole zero-load geometries was introduced to handle the changing zero-load geometries for more accurate stress/strain calculations. Echo image data were acquired from 5 patients with infarction (Infarct Group) and 10 without (Non-Infarcted Group). Echo-based computational two-layer left ventricle models using one zero-load geometry (1G) and two zero-load geometries (2G) were constructed. Material parameter values in Mooney-Rivlin models were adjusted to match echo volume data. Effective Young’s moduli (YM) were calculated for easy comparison. For diastole phase, begin-filling (BF) mean YM value in the fiber direction (YMf) was 738% higher than its end-diastole (ED) value (645.39 kPa vs. 76.97 kPa, p=3.38E-06). For systole phase, end-systole (ES) YMf was 903% higher than its begin-ejection (BE) value (1025.10 kPa vs. 102.11 kPa, p=6.10E-05). Comparing systolic and diastolic material properties, ES YMf was 59% higher than its BF value (1025.10 kPa vs. 645.39 kPa. p=0.0002). BE mean stress value was 514% higher than its ED value (299.69 kPa vs. 48.81 kPa, p=3.39E-06), while BE mean strain value was 31.5% higher than its ED value (0.9417 vs. 0.7162, p=0.004). Similarly, ES mean stress value was 562% higher than its BF value (19.74 kPa vs. 2.98 kPa, p=6.22E-05), and ES mean strain value was 264% higher than its BF value (0.1985 vs. 0.0546, p=3.42E-06). 2G models improved over 1G model limitations and may provide better material parameter estimation and stress/strain calculations. PMID:29399004

Modeling Active Contraction and Relaxation of Left Ventricle Using Different Zero-load Diastole and Systole Geometries for Better Material Parameter Estimation and Stress/Strain Calculations.

PubMed

Fan, Longling; Yao, Jing; Yang, Chun; Xu, Di; Tang, Dalin

2016-01-01

Modeling ventricle active contraction based on in vivo data is extremely challenging because of complex ventricle geometry, dynamic heart motion and active contraction where the reference geometry (zero-stress geometry) changes constantly. A new modeling approach using different diastole and systole zero-load geometries was introduced to handle the changing zero-load geometries for more accurate stress/strain calculations. Echo image data were acquired from 5 patients with infarction (Infarct Group) and 10 without (Non-Infarcted Group). Echo-based computational two-layer left ventricle models using one zero-load geometry (1G) and two zero-load geometries (2G) were constructed. Material parameter values in Mooney-Rivlin models were adjusted to match echo volume data. Effective Young's moduli (YM) were calculated for easy comparison. For diastole phase, begin-filling (BF) mean YM value in the fiber direction (YM f ) was 738% higher than its end-diastole (ED) value (645.39 kPa vs. 76.97 kPa, p=3.38E-06). For systole phase, end-systole (ES) YM f was 903% higher than its begin-ejection (BE) value (1025.10 kPa vs. 102.11 kPa, p=6.10E-05). Comparing systolic and diastolic material properties, ES YM f was 59% higher than its BF value (1025.10 kPa vs. 645.39 kPa. p=0.0002). BE mean stress value was 514% higher than its ED value (299.69 kPa vs. 48.81 kPa, p=3.39E-06), while BE mean strain value was 31.5% higher than its ED value (0.9417 vs. 0.7162, p=0.004). Similarly, ES mean stress value was 562% higher than its BF value (19.74 kPa vs. 2.98 kPa, p=6.22E-05), and ES mean strain value was 264% higher than its BF value (0.1985 vs. 0.0546, p=3.42E-06). 2G models improved over 1G model limitations and may provide better material parameter estimation and stress/strain calculations.

Designing an Earthquake-Resistant Building

ERIC Educational Resources Information Center

English, Lyn D.; King, Donna T.

2016-01-01

How do cross-bracing, geometry, and base isolation help buildings withstand earthquakes? These important structural design features involve fundamental geometry that elementary school students can readily model and understand. The problem activity, Designing an Earthquake-Resistant Building, was undertaken by several classes of sixth- grade…

Synthesis, spectral characterization and catalytic activity of Co(II) complexes of drugs: crystal structure of Co(II)-trimethoprim complex.

PubMed

Madhupriya, Selvaraj; Elango, Kuppanagounder P

2014-01-24

New Co(II) complexes with drugs such as trimethoprim (TMP), cimetidine (CTD), niacinamide (NAM) and ofloxacin (OFL) as ligands were synthesized. The complexes were characterized by analytical analysis, various spectral techniques such as FT-IR, UV-Vis, magnetic measurements and molar conductivity. The magnetic susceptibility results coupled with the electronic spectra suggested a tetrahedral geometry for the complexes. The coordination mode of trimethoprim ligand and geometry of the complex were confirmed by single crystal X-ray studies. In this complex the metal ion possesses a tetrahedral geometry with two nitrogen atom from two TMP ligands and two chloride ions coordinated to it. The catalytic activity of the complexes in aryl-aryl coupling reaction was screened and the results indicated that among the four complexes [Co(OFL)Cl(H2O)] exhibited excellent catalytic activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Lower limb estimation from sparse landmarks using an articulated shape model.

PubMed

Zhang, Ju; Fernandez, Justin; Hislop-Jambrich, Jacqui; Besier, Thor F

2016-12-08

Rapid generation of lower limb musculoskeletal models is essential for clinically applicable patient-specific gait modeling. Estimation of muscle and joint contact forces requires accurate representation of bone geometry and pose, as well as their muscle attachment sites, which define muscle moment arms. Motion-capture is a routine part of gait assessment but contains relatively sparse geometric information. Standard methods for creating customized models from motion-capture data scale a reference model without considering natural shape variations. We present an articulated statistical shape model of the left lower limb with embedded anatomical landmarks and muscle attachment regions. This model is used in an automatic workflow, implemented in an easy-to-use software application, that robustly and accurately estimates realistic lower limb bone geometry, pose, and muscle attachment regions from seven commonly used motion-capture landmarks. Estimated bone models were validated on noise-free marker positions to have a lower (p=0.001) surface-to-surface root-mean-squared error of 4.28mm, compared to 5.22mm using standard isotropic scaling. Errors at a variety of anatomical landmarks were also lower (8.6mm versus 10.8mm, p=0.001). We improve upon standard lower limb model scaling methods with shape model-constrained realistic bone geometries, regional muscle attachment sites, and higher accuracy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of NBG-18, NBG-17, IG-110 and IG-11 oxidation kinetics in air

NASA Astrophysics Data System (ADS)

Lee, Jo Jo; Ghosh, Tushar K.; Loyalka, Sudarshan K.

2018-03-01

The oxidation rates of several nuclear-grade graphites, NBG-18, NBG-17, IG-110 and IG-11, were measured in air using thermogravimetry. Kinetic parameters and oxidation behavior for each grade were compared by coke type, filler grain size and microstructure. The thickness of the oxidized layer for each grade was determined by layer peeling and direct density measurements. The results for NBG-17 and IG-11 were compared with those available in the literature and our recently reported results for NBG-18 and IG-110 oxidation in air. The finer-grained graphites IG-110 and IG-11 were more oxidized than medium-grained NBG-18 and NBG-17 because of deeper oxidant penetration, higher porosity and higher probability of available active sites. Variation in experimental conditions also had a marked effect on the reported kinetic parameters by several studies. Kinetic parameters such as activation energy and transition temperature were sensitive to air flow rates as well as sample size and geometry.

The relationship between strain geometry and geometrically necessary dislocations

NASA Astrophysics Data System (ADS)

Hansen, Lars; Wallis, David

2016-04-01

The kinematics of past deformations are often a primary goal in structural analyses of strained rocks. Details of the strain geometry, in particular, can help distinguish hypotheses about large-scale tectonic phenomena. Microstructural indicators of strain geometry have been heavily utilized to investigate large-scale kinematics. However, many of the existing techniques require structures for which the initial morphology is known, and those structures must undergo the same deformation as imposed macroscopically. Many deformed rocks do not exhibit such convenient features, and therefore the strain geometry is often difficult (if not impossible) to ascertain. Alternatively, crystallographic textures contain information about the strain geometry, but the influence of strain geometry can be difficult to separate from other environmental factors that might affect slip system activity and therefore the textural evolution. Here we explore the ability for geometrically necessary dislocations to record information about the deformation geometry. It is well known that crystallographic slip due to the motion of dislocations yields macroscopic plastic strain, and the mathematics are established to relate dislocation glide on multiple slip systems to the strain tensor of a crystal. This theoretical description generally assumes that dislocations propagate across the entire crystal. However, at any point during the deformation, dislocations are present that have not fully transected the crystal, existing either as free dislocations or as dislocations organized into substructures like subgrain boundaries. These dislocations can remain in the lattice after deformation if the crystal is quenched sufficiently fast, and we hypothesize that this residual dislocation population can be linked to the plastic strain geometry in a quantitative manner. To test this hypothesis, we use high-resolution electron backscatter diffraction to measure lattice curvatures in experimentally deformed single crystals and aggregates of olivine for which the strain geometry is known. Tested geometries include constrictional strain, flattening strain, and plane strain. We use measured lattice curvatures to calculate the densities and spatial distributions of geometrically necessary dislocations. Dislocation densities are calculated for each of the major dislocation types in olivine. These densities are then used to estimate the plastic strain geometry under the assumption that the population of geometrically necessary dislocations accurately represents the relative activity of different dislocations during deformation. Our initial results demonstrate compelling relationships between the imposed strain geometry and the calculated plastic strain geometry. In addition, the calculated plastic strain geometry is linked to the distribution of crystallographic orientations, giving insight into the nature of plastic anisotropy in textured olivine aggregates. We present this technique as a new microstructural tool for assessing the kinematic history of deformed rocks.

Using the Sonoran and Libyan Desert test sites to monitor the temporal stability of reflective solar bands for Landsat 7 enhanced thematic mapper plus and Terra moderate resolution imaging spectroradiometer sensors

USGS Publications Warehouse

Angal, Amit; Xiong, Xiaoxiong; Choi, Tae-young; Chander, Gyanesh; Wu, Aisheng

2010-01-01

Remote sensing imagery is effective for monitoring environmental and climatic changes because of the extent of the global coverage and long time scale of the observations. Radiometric calibration of remote sensing sensors is essential for quantitative & qualitative science and applications. Pseudo-invariant ground targets have been extensively used to monitor the long-term radiometric calibration stability of remote sensing sensors. This paper focuses on the use of the Sonoran Desert site to monitor the radiometric stability of the Landsat 7 (L7) Enhanced Thematic Mapper Plus (ETM+) and Terra Moderate Resolution Imaging Spectroradiometer (MODIS) sensors. The results are compared with the widely used Libya 4 Desert site in an attempt to evaluate the suitability of the Sonoran Desert site for sensor inter-comparison and calibration stability monitoring. Since the overpass times of ETM+ and MODIS differ by about 30 minutes, the impacts due to different view geometries or test site Bi-directional Reflectance Distribution Function (BRDF) are also presented. In general, the long-term drifts in the visible bands are relatively large compared to the drift in the near-infrared bands of both sensors. The lifetime Top-of-Atmosphere (TOA) reflectance trends from both sensors over 10 years are extremely stable, changing by no more than 0.1% per year (except ETM+ Band 1 and MODIS Band 3) over the two sites used for the study. The use of a semi-empirical BRDF model can reduce the impacts due to view geometries, thus enabling a better estimate of sensor temporal drifts.

Comparative Study on Various Geometrical Core Design of 300 MWth Gas Cooled Fast Reactor with UN-PuN Fuel Longlife without Refuelling

NASA Astrophysics Data System (ADS)

Dewi Syarifah, Ratna; Su'ud, Zaki; Basar, Khairul; Irwanto, Dwi

2017-07-01

Nuclear power has progressive improvement in the operating performance of exiting reactors and ensuring economic competitiveness of nuclear electricity around the world. The GFR use gas coolant and fast neutron spectrum. This research use helium coolant which has low neutron moderation, chemical inert and single phase. Comparative study on various geometrical core design for modular GFR with UN-PuN fuel long life without refuelling has been done. The calculation use SRAC2006 code both PIJ calculation and CITATION calculation. The data libraries use JENDL 4.0. The variation of fuel fraction is 40% until 65%. In this research, we varied the geometry of core reactor to find the optimum geometry design. The variation of the geometry design is balance cylinder; it means that the diameter active core (D) same with height active core (H). Second, pancake cylinder (D>H) and third, tall cylinder (D

Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

PubMed

Meiselbach, Heike; Sticht, Heinrich

2011-08-01

The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

Template engineered biopotent macrocyclic complexes involving furan moiety: Molecular modeling and molecular docking

NASA Astrophysics Data System (ADS)

Rathi, Parveen; Singh, D. P.

2015-08-01

Bioactive cobalt(II), nickel(II), copper(II) and zinc(II) complexes of octaazamacrocycle, 19, 20-dioxa-2,3,5,6,11,12,14,15-octaazatricyclo[14.2.1.1]icosa-1,6,8,10,15,17-hexaene-4,13-dithione, derived from furan-2,5-dione and thiocarbonohydrazide in the mole ratio 2:2:1 have been engineered via template methodology. The synthesized metal complexes have also been structurally characterized in the light of various physicochemical techniques and evaluated for antimicrobial and antioxidant activities. All these studies point toward the formation of divalent macrocyclic complexes possessing distorted octahedral geometry and having significant antimicrobial and antioxidant properties as compared to the starting precursors. Virtual screening of a representative complex was done through docking to the binding site of COX-2 to evaluate the anti-inflammatory activity of the series. Non-electrolytic nature of the complexes has been predicted on the basis of low value of molar conductivity in DMSO. All the complexes were having notable activities against pathogenic microbes as compared to precursors-thiocarbonohydrazide and furan-2,5-dione however, the complex 5, [Ni (C10H8N8O2S2) (NO3)2], shows the best antimicrobial activity.

Some Remarks on Navajo Geometry and Piagetian Genetic Theory.

ERIC Educational Resources Information Center

Pinxten, Rik

1991-01-01

Examines aspects of Navajo cosmology relevant to understanding Navajo spatial representations. Compares Navajo children's spatial knowledge with Piaget's findings about the development of geometric concepts in Swiss children. Describes classroom activities whereby Navajo children explore the geometry inherent in their cultural and physical…

Dendritic spine geometry can localize GTPase signaling in neurons

PubMed Central

Ramirez, Samuel A.; Raghavachari, Sridhar; Lew, Daniel J.

2015-01-01

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia. PMID:26337387

Inertial confinement fusion method producing line source radiation fluence

DOEpatents

Rose, Ronald P.

1984-01-01

An inertial confinement fusion method in which target pellets are imploded in sequence by laser light beams or other energy beams at an implosion site which is variable between pellet implosions along a line. The effect of the variability in position of the implosion site along a line is to distribute the radiation fluence in surrounding reactor components as a line source of radiation would do, thereby permitting the utilization of cylindrical geometry in the design of the reactor and internal components.

Tetraammine(carbonato-κ2 O,O′)cobalt(III) perchlorate

PubMed Central

Mohan, Singaravelu Chandra; Jenniefer, Samson Jegan; Muthiah, Packianathan Thomas; Jothivenkatachalam, Kandasamy

2013-01-01

In the title complex, [Co(CO3)(NH3)4]ClO4, both the cation and anion lie on a mirror plane. The CoIII ion is coordinated by two NH3 ligands and a chelating carbonato ligand in the equatorial sites and by two NH3 groups in the axial sites, forming a distorted octa­hedral geometry. In the crystal, N—H⋯O hydrogen bonds connect the anions and cations, forming a three-dimensional network. PMID:24109252

Bivalent transition metal complexes of o-hydroxyacetophenone [N-(3-hydroxy-2-naphthoyl)] hydrazone: Spectroscopic, antibacterial, antifungal activity and thermogravimetric studies

NASA Astrophysics Data System (ADS)

Zaky, R. R.; Ibrahim, K. M.; Gabr, I. M.

2011-10-01

Schiff base complexes of Cu(II), Ni(II) and Zn(II) with the o-hydroxyacetophenone [N-(3-hydroxy-2-naphthoyl)] hydrazone (H 2o-HAHNH) containing N and O donor sites have been synthesized. Both ligand and its metal complexes were characterized by different physicochemical methods, elemental analysis, molar conductivity ( 1H NMR, 13C NMR, IR, UV-visible, ESR, MS spectra) and also thermal analysis (TG and DTG) techniques. The discussion of the outcome data of the prepared complexes indicates that the ligand behave as a bidentate and/or tridentate ligand. The electronic spectra of the complexes as well as their magnetic moments suggest octahedral geometries for all isolated complexes. The room temperature solid state ESR spectrum of the Cu(II) complex shows d x2- y2 as a ground state, suggesting tetragonally distorted octahedral geometry around Cu(II) centre. The molar conductance measurements proved that the complexes are non-electrolytes. The kinetic thermodynamic parameters such as: E#, Δ H#, Δ G#, Δ S# are calculated from the DTG curves, for the [Ni(H O-HAHNH) 2] and [Zn(H 2 O-HAHNH)(OAc) 2]·H 2O complexes using the Coats-Redfern equation. Also, the antimicrobial properties of all compounds were studied using a wide spectrum of bacterial and fungal strains. The [Cu(H o-HAHNH)(OAc)(H 2O) 2] complex was the most active against all strains, including Aspergillus sp., Stemphylium sp. and Trichoderma sp. Fungi; E. coli and Clostridium sp. Bacteria.

Using an Instrumented Drone to Sample Dust Devils

NASA Astrophysics Data System (ADS)

Jackson, Brian; Lorenz, Ralph; Davis, Karan; Lipple, Brock

2017-10-01

Dust devils are low-pressure, small (many to tens of meters) convective vortices powered by surface heating and rendered visible by lofted dust. Dust devils occur in arid climates on Earth, where they degrade air quality and pose a hazard to small aircraft. They also occur ubiquitously on Mars, where they may dominate the supply of atmospheric dust. Since dust contributes significantly to Mars’ atmospheric heat budget, dust devils probably play an important role in its climate. The dust-lifting capacity of a devil likely depends sensitively on its structure, particularly the wind and pressure profiles, but the exact dependencies are poorly constrained. Thus, the exact contribution to Mars’ atmosphere remains unresolved. Moreover, most previous studies of martian dust devils have relied on passive sampling of the profiles via meteorology packages on landed spacecraft, resulting in random encounter geometries which non-trivially skew the retrieved profiles. Analog studies of terrestrial devils have employed more active sampling (instrumented vehicles or manned aircraft) but have been limited to near-surface (few meters) or relatively high altitude (hundreds of meters) sampling. Unmanned aerial vehicles (UAVs) or drones, combined with miniature, digital instrumentation, promise a novel and uniquely powerful platform from which to sample dust devils via (relatively) controlled geometries at a wide variety of altitudes. In this presentation, we will describe a pilot study using an instrumented quadcopter on an active field site in southeastern Oregon, which (to our knowledge) has not previously been surveyed for dust devils. We will present preliminary results from the resulting encounters, including stereo image analysis and encounter footage collected onboard the drone.

Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2

NASA Astrophysics Data System (ADS)

Pal, Avishek; Dey, T. K.; Debnath, A. K.; Bhushan, Bharat; Sahu, A. K.; Bindal, R. C.; Kar, Soumitra

2017-09-01

Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO2 (nano-TiO2) by using two different organoligands, viz. Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, FT-nano-TiO2 and FC-nano-TiO2, respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for FT-nano-TiO2, whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for FC-nano-TiO2. The surface chemistry of the studied membranes, polysulfone (Psf): FT-nano-TiO2 UF and Psf: FC-nano-TiO2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites (-SO3 -H+ ), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz. 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance.

Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2

PubMed Central

Pal, Avishek; Dey, T. K.; Debnath, A. K.; Bhushan, Bharat; Sahu, A. K.; Bindal, R. C.

2017-01-01

Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO2 (nano-TiO2) by using two different organoligands, viz. Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, FT-nano-TiO2 and FC-nano-TiO2, respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for FT-nano-TiO2, whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for FC-nano-TiO2. The surface chemistry of the studied membranes, polysulfone (Psf): FT-nano-TiO2 UF and Psf: FC-nano-TiO2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites (−SO3−H+), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz. 3500–4000 and 3400–4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance. PMID:28989744

Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2.

PubMed

Pal, Avishek; Dey, T K; Debnath, A K; Bhushan, Bharat; Sahu, A K; Bindal, R C; Kar, Soumitra

2017-09-01

Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO 2 (nano-TiO 2 ) by using two different organoligands, viz . Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, F T -nano-TiO 2 and F C -nano-TiO 2 , respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for F T -nano-TiO 2 , whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for F C -nano-TiO 2 . The surface chemistry of the studied membranes, polysulfone (Psf): F T -nano-TiO 2 UF and Psf: F C -nano-TiO 2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites ([Formula: see text]), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz . 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance.

A systematic analysis of directional site effects at stations of the Italian Seismic Network to test the role of local topography

NASA Astrophysics Data System (ADS)

Pischiutta, Marta; Cianfarra, Paola; Salvini, Francesco; Cara, Fabrizio; Vannoli, Paola

2018-03-01

Directional site effects observed at seismological stations on pronounced relief are analyzed. We investigate the ground motion properties calculating horizontal-to-vertical spectral ratios and horizontal polarization of both ambient vibrations and earthquake records using broadband seismograms of the Italian Seismic Network. We find that a subset of 47 stations with pronounced relief, results in a significant (>2) directional amplification of the horizontal component, with a well defined, site-specific direction of motion. However, the horizontal spectral response of sites is not uniform, varying from an isolated (resonant) frequency peak to a broadband amplification, interesting frequency bands as large as 1-10 Hz in many cases. Using the 47 selected stations, we have tried to establish a relation between directional amplification and topography geometry in a 2D-vision, when applicable, through a morphological analysis of the Digital Elevation Model using Geographic Information Systems. The procedure computes the parameters that characterize the geometry of topographic irregularities (size and slope), in combination with a principal component analysis that automatically yields the orientation of the elongated ridges. In seeking a relation between directional amplification and the surface morphology, we have found that it is impossible to fit the variety of observations with a resonant topography model as well as to identify common features in the ground motion behavior for stations with similar topography typologies. We conclude that, rather than the shape of the topography, local structural complexities and details of the near-surface structure must play a predominant role in controlling ground motion properties at sites with pronounced relief.

Backreef and beach carbonate sediments of the Red Sea, Saudi Arabia: impacts of reef geometry and currents on sediment composition

NASA Astrophysics Data System (ADS)

Missimer, T. M.; Al-Mashharawi, S.; Dehwah, A. H. A.; Coulibaly, K.

2017-12-01

Three sites in the Red Sea were investigated to assess the variability of composition in Holocene sediments of the backreef environment within 0-2 m of water depth. This is important because composition of the sediment is commonly used to estimate water depth in ancient carbonate rocks. The site located at the King Abdullah Economic City (Saudi Arabia) contains a fringing reef with the reef tract located very close to the beach at the north end, flaring to the south to produce a narrower backreef area compared to the other two sites. This geometry produces a north to south current with a velocity of up to 15 cm s-1, particularly during high onshore winds. The sediments contain predominantly non-skeletal grains, including peloids, coated grains, ooids, and grapestones that form on the bottom. The percentage of coralgal grains in the sediment was significantly lower than at the other two sites studied. Om Al Misk Island and Shoaiba have a much lower-velocity current within the backreef zone and contain predominantly coralgal sediments from the beach to the landward edge of the reef tract. The two locations containing the predominantly coralgal microfacies were statistically similar, but the King Abdullah Economic City site was statistically different despite having a similar water depth profile. Slight differences in reef configuration, including reef orientation and distance from the shore, can produce considerable differences in sediment thickness and composition within the backreef environment, which should induce caution in the interpretation of water depth in ancient carbonate rocks using composition.

A systematic analysis of directional site effects at stations of the Italian seismic network to test the role of local topography

NASA Astrophysics Data System (ADS)

Pischiutta, Marta; Cianfarra, Paola; Salvini, Francesco; Cara, Fabrizio; Vannoli, Paola

2018-07-01

Directional site effects observed at seismological stations on pronounced relief are analysed. We investigate the ground motion properties calculating horizontal-to-vertical spectral ratios and horizontal polarization of both ambient vibrations and earthquake records using broad-band seismograms of the Italian seismic network. We find that a subset of 47 stations with pronounced relief results in a significant (>2) directional amplification of the horizontal component, with a well-defined, site-specific direction of motion. However, the horizontal spectral response of sites is not uniform, varying from an isolated (resonant) frequency peak to a broad-band amplification, interesting frequency bands as large as 1-10 Hz in many cases. Using 47 selected stations, we have tried to establish a relation between directional amplification and topography geometry in a 2-D vision, when applicable, through a morphological analysis of the digital elevation model using geographic information systems. The procedure computes the parameters that characterize the geometry of topographic irregularities (size and slope), in combination with a principal component analysis that automatically yields the orientation of the elongated ridges. In seeking a relation between directional amplification and the surface morphology, we have found that it is impossible to fit the variety of observations with a resonant topography model as well as to identify common features in the ground motion behaviour for stations with similar topography typologies. We conclude that, rather than the shape of the topography, local structural complexities and details of the near-surface structure must play a predominant role in controlling ground motion properties at sites with pronounced relief.

Soapy Science. Teaching Science.

ERIC Educational Resources Information Center

Leyden, Michael

1997-01-01

Describes a science and math activity that involves bubbles, shapes, colors, and solid geometry. Students build geometric shapes with soda straws and submerge the shapes in soapy water, allowing them to review basic geometry concepts, test hypotheses, and learn about other concepts such as diffraction, interference colors, and evaporation. (TJQ)

Compressible flow in fluidic oscillators

NASA Astrophysics Data System (ADS)

Graff, Emilio; Hirsch, Damian; Gharib, Mory

2013-11-01

We present qualitative observations on the internal flow characteristics of fluidic oscillator geometries commonly referred to as sweeping jets in active flow control applications. We also discuss the effect of the geometry on the output jet in conditions from startup to supersonic exit velocity. Supported by the Boeing Company.

Investigation of Surface Phenomena in Shocked Tin in Converging Geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rousculp, Christopher L.; Oro, David Michael; Griego, Jeffrey Randall

2016-04-14

There is a great interest in RMI as source of ejecta from metal shells. Previous experiments have explored wavelength amplitude (kA) variation but they have a small range of drive pressures and are in planer geometry. Simulations, both MD and hydro, have explored RMI in planer geometry. The ejecta source model from RMI is an area of active algorithm and code development in ASCI-IC Lagrangian Applications Project. PHELIX offers precise, reproducible variable driver for Hydro and material physics diagnoses with proton radiography.

First-principles theoretical assessment of catalysis by confinement: NO-O2 reactions within voids of molecular dimensions in siliceous crystalline frameworks.

PubMed

Maestri, Matteo; Iglesia, Enrique

2018-06-01

Density functional theory methods that include dispersive forces are used to show how voids of molecular dimensions enhance reaction rates by the mere confinement of transition states analogous to those involved in homogeneous routes and without requiring specific binding sites or structural defects within confining voids. These van der Waals interactions account for the observed large rate enhancements for NO oxidation in the presence of purely siliceous crystalline frameworks. The minimum free energy paths for NO oxidation within chabazite (CHA) and silicalite (SIL) frameworks involve intermediates similar in stoichiometry, geometry, and kinetic relevance to those involved in the homogeneous route. The termolecular transition state for the kinetically-relevant cis-NOO2NO isomerization to trans-NOO2NO is strongly stabilized by confinement within CHA (by 36.3 kJ mol-1 in enthalpy) and SIL (by 39.2 kJ mol-1); such enthalpic stabilization is compensated, in part, by concomitant entropy losses brought forth by confinement (CHA: 44.9; SIL: 45.3, J mol-1 K-1 at 298 K). These enthalpy and entropy changes upon confinement agree well with those measured and combine to significantly decrease activation free energies and are consistent with the rate enhancements that become larger as temperature decreases because of the more negative apparent activation energies in confined systems compared with homogeneous routes. Calculated free energies of confinement are in quantitative agreement with measured rate enhancements and with their temperature sensitivity. Such quantitative agreements reflect preeminent effects of geometry in determining the van der Waals contributions from contacts between the transition states (TS) and the confining walls and the weak effects of the level of theory on TS geometries. NO oxidation reactions are chosen here to illustrate these remarkable effects of confinement because detailed kinetic analysis of rate data are available, but also because of their critical role in the treatment of combustion effluents and in the synthesis of nitric acid and nitrates. Similar effects are evident from rate enhancements by confinement observed for Diels-Alder and alkyne oligomerization reactions. These reactions also occur in gaseous media at near ambient temperatures, for which enthalpic stabilization upon confinement of their homogeneous transition states becomes the preeminent component of activation free energies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stein, Joshua S.; Rautman, Christopher Arthur

The Bryan Mound salt dome, located near Freeport, Texas, is home to one of four underground crude oil-storage facilities managed by the U. S. Department of Energy Strategic Petroleum Reserve (SPR) Program. Sandia National Laboratories, as the geotechnical advisor to the SPR, conducts site-characterization investigations and other longer-term geotechnical and engineering studies in support of the program. This report describes the conversion of two-dimensional geologic interpretations of the Bryan Mound site into three-dimensional geologic models. The new models include the geometry of the salt dome, the surrounding sedimentary units, mapped faults, and the 20 oil-storage caverns at the site. Thismore » work provides an internally consistent geologic model of the Bryan Mound site that can be used in support of future work.« less

Multiscale characterization and mechanical modeling of an Al-Zn-Mg electron beam weld

NASA Astrophysics Data System (ADS)

Puydt, Quentin; Flouriot, Sylvain; Ringeval, Sylvain; Parry, Guillaume; De Geuser, Frédéric; Deschamps, Alexis

Welding of precipitation hardening alloys results in multi-scale microstructural heterogeneities, from the hardening nano-scale precipitates to the micron-scale solidification structures and to the component geometry. This heterogeneity results in a complex mechanical response, with gradients in strength, stress triaxiality and damage initiation sites.

Methods for estimating magnitude and frequency of floods in Montana based on data through 1983

USGS Publications Warehouse

Omang, R.J.; Parrett, Charles; Hull, J.A.

1986-01-01

Equations are presented for estimating flood magnitudes for ungaged sites in Montana based on data through 1983. The State was divided into eight regions based on hydrologic conditions, and separate multiple regression equations were developed for each region. These equations relate annual flood magnitudes and frequencies to basin characteristics and are applicable only to natural flow streams. In three of the regions, equations also were developed relating flood magnitudes and frequencies to basin characteristics and channel geometry measurements. The standard errors of estimate for an exceedance probability of 1% ranged from 39% to 87%. Techniques are described for estimating annual flood magnitude and flood frequency information at ungaged sites based on data from gaged sites on the same stream. Included are curves relating flood frequency information to drainage area for eight major streams in the State. Maximum known flood magnitudes in Montana are compared with estimated 1 %-chance flood magnitudes and with maximum known floods in the United States. Values of flood magnitudes for selected exceedance probabilities and values of significant basin characteristics and channel geometry measurements for all gaging stations used in the analysis are tabulated. Included are 375 stations in Montana and 28 nearby stations in Canada and adjoining States. (Author 's abstract)

Data collected to support monitoring of constructed emergent sandbar habitat on the Missouri River downstream from Gavins Point Dam, South Dakota and Nebraska, 2004-06

USGS Publications Warehouse

Thompson, Ryan F.; Johnson, Michaela R.; Andersen, Michael J.

2007-01-01

The U.S. Army Corps of Engineers has constructed emergent sandbar habitat on sections of the Missouri River bordering South Dakota and Nebraska downstream from Gavins Point Dam to create and enhance habitat for threatened and endangered bird species. Two areas near river miles 761.3 and 769.8 were selected for construction of emergent sandbar habitat. Pre- and postconstruction data were collected by the U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers, to evaluate the success of the habitat management techniques. Data collected include pre- and postconstruction channel-geometry data (bathymetric and topographic) for areas upstream from, downstream from, and within each construction site. Water-velocity data were collected for selected parts of the site near river mile 769.8. Instruments and methods used in data collection, as well as quality-assurance and quality-control measures, are described. Geospatial channel-geometry data are presented for transects of the river channel as cross sections and as geographical information system shapefiles. Geospatial land-surface elevation data are provided for part of each site in the form of a color-shaded relief map. Geospatial water-velocity data also are provided as color-shaded maps and geographical information system shapefiles.

Extending rule-based methods to model molecular geometry and 3D model resolution.

PubMed

Hoard, Brittany; Jacobson, Bruna; Manavi, Kasra; Tapia, Lydia

2016-08-01

Computational modeling is an important tool for the study of complex biochemical processes associated with cell signaling networks. However, it is challenging to simulate processes that involve hundreds of large molecules due to the high computational cost of such simulations. Rule-based modeling is a method that can be used to simulate these processes with reasonably low computational cost, but traditional rule-based modeling approaches do not include details of molecular geometry. The incorporation of geometry into biochemical models can more accurately capture details of these processes, and may lead to insights into how geometry affects the products that form. Furthermore, geometric rule-based modeling can be used to complement other computational methods that explicitly represent molecular geometry in order to quantify binding site accessibility and steric effects. We propose a novel implementation of rule-based modeling that encodes details of molecular geometry into the rules and binding rates. We demonstrate how rules are constructed according to the molecular curvature. We then perform a study of antigen-antibody aggregation using our proposed method. We simulate the binding of antibody complexes to binding regions of the shrimp allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo simulation, and we analyze the aggregate sizes. Then, using our novel approach, we optimize a rule-based model according to the geometry of the Pen a 1 molecule and the data from the Monte Carlo simulation. We use the distances between the binding regions of Pen a 1 to optimize the rules and binding rates. We perform this procedure for multiple conformations of Pen a 1 and analyze the impact of conformation and resolution on the optimal rule-based model. We find that the optimized rule-based models provide information about the average steric hindrance between binding regions and the probability that antibodies will bind to these regions. These optimized models quantify the variation in aggregate size that results from differences in molecular geometry and from model resolution.

Carbon- versus sulphur-based zinc binding groups for carbonic anhydrase inhibitors?

PubMed

Supuran, Claudiu T

2018-12-01

A set of compounds incorporating carbon-based zinc-binding groups (ZBGs), of the type PhX (X = COOH, CONH 2 , CONHNH 2 , CONHOH, CONHOMe), and the corresponding derivatives with sulphur(VI)-based ZBGs (X = SO 3 H, SO 2 NH 2 , SO 2 NHNH 2 , SO 2 NHOH, SO 2 NHOMe) were tested as inhibitors of all mammalian isoforms of carbonic anhydrase (CA, EC 4.2.1.1), CA I-XV. Three factors connected with the ZBG influenced the efficacy as CA inhibitor (CAI) of the investigated compounds: (i) the pKa of the ZBG; (ii) its geometry (tetrahedral, i.e. sulphur-based, versus trigonal, i.e. carbon-based ZBGs), and (iii) orientation of the organic scaffold induced by the nature of the ZBG. Benzenesulphonamide was the best inhibitor of all isoforms, but other ZBGs led to interesting inhibition profiles, although with an efficacy generally reduced when compared to the sulphonamide. The nature of the ZBG also influenced the CA inhibition mechanism. Most of these derivatives were zinc binders, but some of them (sulfonates, carboxylates) may interact with the enzyme by anchoring to the zinc-coordinated water molecule or by other inhibition mechanisms (occlusion of the active site entrance, out of the active site binding, etc.). Exploring structurally diverse ZBGs may lead to interesting new developments in the field of CAIs.

Geometrical Constructions in Dynamic and Interactive Mathematics Learning Environment

ERIC Educational Resources Information Center

Kondratieva, Margo

2013-01-01

This paper concerns teaching Euclidean geometry at the university level. It is based on the authors' personal experience. It describes a sequence of learning activities that combine geometrical constructions with explorations, observations, and explanations of facts related to the geometry of triangle. Within this approach, a discussion of the…

Analyzing Group Coordination when Solving Geometry Problems with Dynamic Geometry Software

ERIC Educational Resources Information Center

Oner, Diler

2013-01-01

In CSCL research, collaborative activity is conceptualized along various yet intertwined dimensions. When functioning within these multiple dimensions, participants make use of several resources, which can be social or content-related (and sometimes temporal) in nature. It is the effective coordination of these resources that appears to…

Dragging and Making Sense of Invariants in Dynamic Geometry

ERIC Educational Resources Information Center

Baccaglini-Frank, Anna E.

2012-01-01

Perceiving and interpreting invariants is a complex task for a nonexpert geometry student, as various studies have shown. Nevertheless, having students work through particular kinds of activities that involve perception and interpretation of invariants and engage in discussions with classmates, guided by the teacher, can help them learn…

Constructing Spatial Understanding

ERIC Educational Resources Information Center

Obara, Samuel

2010-01-01

Activities that enable students to move between two and three dimensions will help them understand solid geometry. This knowledge is critical for teachers, and they need to learn this skill so that they can give their students the opportunity to experience hands-on geometry and benefit from the challenge of creating nets, building models, and…

Influence of cooling face masks on nasal air conditioning and nasal geometry.

PubMed

Lindemann, J; Hoffmann, T; Koehl, A; Walz, E M; Sommer, F

2017-06-01

Nasal geometries and temperature of the nasal mucosa are the primary factors affecting nasal air conditioning. Data on intranasal air conditioning after provoking the trigeminal nerve with a cold stimulus simulating the effects of an arctic condition is still missing. The objective was to investigate the influence of skin cooling face masks on nasal air conditioning, mucosal temperature and nasal geometry. Standardized in vivo measurements of intranasal air temperature, humidity and mucosal temperature were performed in 55 healthy subjects at defined detection sites before and after wearing a cooling face mask. Measurements of skin temperature, rhinomanometry and acoustic rhinometry were accomplished. After wearing the face mask the facial skin temperature was significantly reduced. Intranasal air temperature did not change. Absolute humidity and mucosal temperature increased significantly. The acoustic rhinometric results showed a significant increase of the volumes and the cross-sectional areas. There was no change in nasal airflow. Nasal mucosal temperature, humidity of inhaled air, and volume of the anterior nose increased after application of a cold face mask. The response is mediated by the trigeminal nerve. Increased mucosal temperatures as well as changes in nasal geometries seem to guarantee sufficient steady intranasal nasal air conditioning.

Channel geometry change of a first-order stream after a small debris flow in Ashio Mountains of central Japan

NASA Astrophysics Data System (ADS)

Hattanji, T.; Wasklewicz, T.

2006-12-01

We examined geometry change of a steep first-order channel with a laserscanner before and after a small debris flow. The study site is located in chert area, Ashio Mountains, Japan. On August 12, 2005, a 20-year storm event with maximum 1-hour rainfall of 75.4 mm/h triggered a small landslide at a steep channel head. The sliding material moved as a debris flow along the first-order channel (C3) to the mouth. We successfully measured high-resolution channel topography with the Leica Geosystems High-Definition Surveying Laser Scanner before (April 30) and after the debris-flow event (October 9-11). Width, depth and other related parameters were measured for 30 selected cross sections. Bankfull stage of this first-order channel after the debris-flow event is much higher than two-year flood stage. The magnitude of channel geometry change varies non-linearly in downstream direction. The non-linear variability is attributed to differences in stream bed and bank characteristics. Bedrock-channel reach is less impacted by the debris flow. The largest magnitude changes in the channel geometry parameters occur along colluvially confined channel reaches.

Characteristics of Fault Zones in Volcanic Rocks Near Yucca Flat, Nevada Test Site, Nevada

USGS Publications Warehouse

Sweetkind, Donald S.; Drake II, Ronald M.

2007-01-01

During 2005 and 2006, the USGS conducted geological studies of fault zones at surface outcrops at the Nevada Test Site. The objectives of these studies were to characterize fault geometry, identify the presence of fault splays, and understand the width and internal architecture of fault zones. Geologic investigations were conducted at surface exposures in upland areas adjacent to Yucca Flat, a basin in the northeastern part of the Nevada Test Site; these data serve as control points for the interpretation of the subsurface data collected at Yucca Flat by other USGS scientists. Fault zones in volcanic rocks near Yucca Flat differ in character and width as a result of differences in the degree of welding and alteration of the protolith, and amount of fault offset. Fault-related damage zones tend to scale with fault offset; damage zones associated with large-offset faults (>100 m) are many tens of meters wide, whereas damage zones associated with smaller-offset faults are generally a only a meter or two wide. Zeolitically-altered tuff develops moderate-sized damage zones whereas vitric nonwelded, bedded and airfall tuff have very minor damage zones, often consisting of the fault zone itself as a deformation band, with minor fault effect to the surrounding rock mass. These differences in fault geometry and fault zone architecture in surface analog sites can serve as a guide toward interpretation of high-resolution subsurface geophysical results from Yucca Flat.

Sediment sorting along tidal sand waves: A comparison between field observations and theoretical predictions

NASA Astrophysics Data System (ADS)

Van Oyen, Tomas; Blondeaux, Paolo; Van den Eynde, Dries

2013-07-01

A site-by-site comparison between field observations and theoretical predictions of sediment sorting patterns along tidal sand waves is performed for ten locations in the North Sea. At each site, the observed grain size distribution along the bottom topography and the geometry of the bed forms is described in detail and the procedure used to obtain the model parameters is summarized. The model appears to accurately describe the wavelength of the observed sand waves for the majority of the locations; still providing a reliable estimate for the other sites. In addition, it is found that for seven out of the ten locations, the qualitative sorting process provided by the model agrees with the observed grain size distribution. A discussion of the site-by-site comparison is provided which, taking into account uncertainties in the field data, indicates that the model grasps the major part of the key processes controlling the phenomenon.

LEED STUDY OF Ag(111)-(√ 7×√ 7)R19.1^o-4Ar

NASA Astrophysics Data System (ADS)

Caragiu, Mellita; Diehl, Renee D.; Leatherman, Gerry S.

2000-03-01

Recent LEED studies of the adsorption geometries of Xe and Kr on metal surfaces have indicated that, contrary to expectations, the low-coordination adsorption sites are generally preferred, even on relatively corrugated surfaces such as Cu(1\\overline 1 0). This study extends the range of this phenomenon to include Ar. On Ag(111), Ar can form a commensurate structure, Ag(111)-(√ 7×√ 7)R19.1^o-4Ar, if the step sites are first blocked by preadsorbing another species such as CO. A dynamical LEED analysis of this structure at 33K indicates that the structure includes one atom per unit cell on a top site and the remaining three on bridge sites. This structure is clearly preferred over ones in which hollow sites are occupied, providing evidence that the preference of noble gases atoms for low-coordination sites on metals extends to Ar.

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Evidence for Watson-Crick and not Hoogsteen or wobble base pairing in the selection of nucleotides for insertion opposite pyrimidines and a thymine dimer by yeast DNA pol eta.

PubMed

Hwang, Hanshin; Taylor, John-Stephen

2005-03-29

We have recently reported that pyrene nucleotide is preferentially inserted opposite an abasic site, the 3'-T of a thymine dimer, and most undamaged bases by yeast DNA polymerase eta (pol eta). Because pyrene is a nonpolar molecule with no H-bonding ability, the unusually high efficiencies of dPMP insertion are ascribed to its superior base stacking ability, and underscore the importance of base stacking in the selection of nucleotides by pol eta. To investigate the role of H-bonding and base pair geometry in the selection of nucleotides by pol eta, we determined the insertion efficiencies of the base-modified nucleotides 2,6-diaminopurine, 2-aminopurine, 6-chloropurine, and inosine which would make a different number of H-bonds with the template base depending on base pair geometry. Watson-Crick base pairing appears to play an important role in the selection of nucleotide analogues for insertion opposite C and T as evidenced by the decrease in the relative insertion efficiencies with a decrease in the number of Watson-Crick H-bonds and an increase in the number of donor-donor and acceptor-acceptor interactions. The selectivity of nucleotide insertion is greater opposite the 5'-T than the 3'-T of the thymine dimer, in accord with previous work suggesting that the 5'-T is held more rigidly than the 3'-T. Furthermore, insertion of A opposite both Ts of the dimer appears to be mediated by Watson-Crick base pairing and not by Hoogsteen base pairing based on the almost identical insertion efficiencies of A and 7-deaza-A, the latter of which lacks H-bonding capability at N7. The relative efficiencies for insertion of nucleotides that can form Watson-Crick base pairs parallel those for the Klenow fragment, whereas the Klenow fragment more strongly discriminates against mismatches, in accord with its greater shape selectivity. These results underscore the importance of H-bonding and Watson-Crick base pair geometry in the selection of nucleotides by both pol eta and the Klenow fragment, and the lesser role of shape selection in insertion by pol eta due to its more open and less constrained active site.

Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer

DOE PAGES

Michalczyk, Ryszard; Unkefer, Clifford J.; Bacik, John -Paul; ...

2015-05-05

Proton transfer is a fundamental mechanism at the core of many enzyme-catalyzed reactions. It is also exquisitely sensitive to a number of factors, including pH, electrostatics, proper active-site geometry, and chemistry. Carbonic anhydrase has evolved a fast and efficient way to conduct protons through a combination of hydrophilic amino acid side chains that coordinate a highly ordered H-bonded water network. This study uses a powerful approach, combining NMR solution studies with neutron protein crystallography, to determine the effect of pH and divalent cations on key residues involved in proton transfer in human carbonic anhydrase. Lastly, the results have broad implicationsmore » for our understanding of proton transfer and how subtle changes in ionization and H-bonding interactions can modulate enzyme catalysis.« less

The November 2017 Mw 5.5 Pohang earthquake: A possible case of induced seismicity in South Korea

NASA Astrophysics Data System (ADS)

Grigoli, F.; Cesca, S.; Rinaldi, A. P.; Manconi, A.; López-Comino, J. A.; Clinton, J. F.; Westaway, R.; Cauzzi, C.; Dahm, T.; Wiemer, S.

2018-06-01

The moment magnitude (Mw) 5.5 earthquake that struck South Korea in November 2017 was one of the largest and most damaging events in that country over the past century. Its proximity to an enhanced geothermal system site, where high-pressure hydraulic injection had been performed during the previous 2 years, raises the possibility that this earthquake was anthropogenic. We have combined seismological and geodetic analyses to characterize the mainshock and its largest aftershocks, constrain the geometry of this seismic sequence, and shed light on its causal factors. According to our analysis, it seems plausible that the occurrence of this earthquake was influenced by the aforementioned industrial activities. Finally, we found that the earthquake transferred static stress to larger nearby faults, potentially increasing the seismic hazard in the area.

Measuring nanoparticle diffusion in an ABELtrap

NASA Astrophysics Data System (ADS)

Dienerowitz, M.; Dienerowitz, F.; Börsch, M.

2018-03-01

Monitoring the Brownian motion of individual nanoscopic objects is key to investigate their transport properties and interactions with their close environment. Most techniques rely on transient diffusion through a detection volume or immobilisation, which restrict observation times or motility. We measure the diffusion coefficient and surface charge of individual nanoparticles and DNA molecules in an anti-Brownian electrokinetic trap (ABELtrap). This instrument is an active feedback trap confining the Brownian motion of a nanoparticle to the detection site by applying an electric field based on the particle’s current position. We simulate the Brownian motion of nanospheres in our sample geometry, including wall effects, due to partial confinement in the third dimension. The theoretically predicted values are in excellent agreement with our diffusion measurements in the ABELtrap. We also demonstrate the ABELtrap’s ability to measure varying sizes of DNA origami structures during denaturation.

Intraflow width variations in Martian and terrestrial lava flows

NASA Astrophysics Data System (ADS)

Peitersen, Matthew N.; Crown, David A.

1997-03-01

Flow morphology is used to interpret emplacement processes for lava flows on Earth and Mars. Accurate measurements of flow geometry are essential, particularly for planetary flows where neither compositional sampling nor direct observations of active flows may be possible. Width behavior may indicate a flow's response to topography, its emplacement regime, and its physical properties. Variations in width with downflow distance from the vent may therefore provide critical clues to flow emplacement processes. Flow width is also one of the few characteristics that can be readily measured from planetary mission data with accuracy. Recent analyses of individual flows at two terrestrial and four Martian sites show that widths within an individual flow vary by up to an order of magnitude. Width is generally thought to be correlated to topography; however, recent studies show that this relationship is neither straightforward nor easily quantifiable.

Sentinel-2: State of the Image Quality Calibration at the End of the Commissioning

NASA Astrophysics Data System (ADS)

Tremas, Thierry; Lonjou, Vincent; Lacherade, Sophie; Gaudel-Vacaresse, Angelique; Languille, Florie

2016-08-01

This article summarizes the activity of CNES during the In Orbit Calibration Phase of Sentinel 2A as well as the transfer of production of GIPP (Ground Image Processing Parameters) from CNES to ESRIN. The state of the main calibration parameters and performances, few months before PDGS is declared fully operational, are listed and explained.In radiometry a special attention is paid to the absolute calibration using the on-board diffuser, and the vicarious calibration methods using instrumented or statistically well characterized sites and inter- comparisons with other sensors. Regarding geometry, the presentation focuses on the performances of absolute location with and without reference points. The requirements of multi-band and multi-temporal registration are exposed. Finally, the construction and the rule of the GRI (Ground Reference Images) in the future are explained.

Improved neutron activation prediction code system development

NASA Technical Reports Server (NTRS)

Saqui, R. M.

1971-01-01

Two integrated neutron activation prediction code systems have been developed by modifying and integrating existing computer programs to perform the necessary computations to determine neutron induced activation gamma ray doses and dose rates in complex geometries. Each of the two systems is comprised of three computational modules. The first program module computes the spatial and energy distribution of the neutron flux from an input source and prepares input data for the second program which performs the reaction rate, decay chain and activation gamma source calculations. A third module then accepts input prepared by the second program to compute the cumulative gamma doses and/or dose rates at specified detector locations in complex, three-dimensional geometries.

Validating a new methodology for optical probe design and image registration in fNIRS studies

PubMed Central

Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin; Boas, David A.; Magnotta, Vincent A.

2015-01-01

Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing. PMID:25705757

Left Ventricular Diastolic and Systolic Material Property Estimation from Image Data

PubMed Central

Krishnamurthy, Adarsh; Villongco, Christopher; Beck, Amanda; Omens, Jeffrey; McCulloch, Andrew

2015-01-01

Cardiovascular simulations using patient-specific geometries can help researchers understand the mechanical behavior of the heart under different loading or disease conditions. However, to replicate the regional mechanics of the heart accurately, both the nonlinear passive and active material properties must be estimated reliably. In this paper, automated methods were used to determine passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Two different approaches were used to model systole. In the first, a physiologically-based active contraction model [1] coupled to a hemodynamic three-element Windkessel model of the circulation was used to simulate ventricular ejection. In the second, developed active tension was directly adjusted to match ventricular volumes at end-systole while prescribing the known end-systolic pressure. These methods were tested in four normal dogs using the data provided for the LV mechanics challenge [2]. The resulting end-diastolic and end-systolic geometry from the simulation were compared with measured image data. PMID:25729778

Modeling the Geometry of Plate Boundary and Seismic Structure in the Southern Ryukyu Trench Subduction Zone, Japan, Using Amphibious Seismic Observations

NASA Astrophysics Data System (ADS)

Yamamoto, Y.; Takahashi, T.; Ishihara, Y.; Kaiho, Y.; Arai, R.; Obana, K.; Nakanishi, A.; Miura, S.; Kodaira, S.; Kaneda, Y.

2018-02-01

Here we present the new model, the geometry of the subducted Philippine Sea Plate interface beneath the southern Ryukyu Trench subduction zone, estimated from seismic tomography and focal mechanism estimation by using passive and active data from a temporary amphibious seismic network and permanent land stations. Using relocated low-angle thrust-type earthquakes, repeating earthquakes, and structural information, we constrained the geometry of plate boundary from the trench axis to a 60 km depth with uncertainties of less than 5 km. The estimated plate geometry model exhibited large variation, including a pronounced convex structure that may be evidence of a subducted seamount in the eastern portion of study area, whereas the western part appeared smooth. We also found that the active earthquake region near the plate boundary, defined by the distance from our plate geometry model, was clearly separated from the area dominated by short-term slow-slip events (SSEs). The oceanic crust just beneath the SSE-dominant region, the western part of the study area, showed high Vp/Vs ratios (>1.8), whereas the eastern side showed moderate or low Vp/Vs (<1.75). We interpreted this as an indication that high fluid pressures near the surface of the slab are contributing to the SSE activities. Within the toe of the mantle wedge, P and S wave velocities (<7.5 and <4.2 km/s, respectively) lower than those observed through normal mantle peridotite might suggest that some portions of the mantle may be at least 40% serpentinized.

Report of the Working Design Group

NASA Technical Reports Server (NTRS)

1992-01-01

The engineering study group in the LOUISA workshop was responsible for producing a preliminary general design for an optical synthetic aperture telescope on the Moon. This design is intended to be a test case for focusing continuing design studies. The scope of the design included consideration of the array geometry, individual telescopes, metrology, site attributes, and construction. However, no attempt was made to go into further depth in the design than to cover the essential characteristics of the instrument. The starting point for the array design was the lunar optical array discussed by Burke (1985). His array geometry followed the design and correlation procedure of the 27-element Very Large Array (VLA) radio telescopes near Socorro, New Mexico.

Lidar arc scan uncertainty reduction through scanning geometry optimization

NASA Astrophysics Data System (ADS)

Wang, Hui; Barthelmie, Rebecca J.; Pryor, Sara C.; Brown, Gareth.

2016-04-01

Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annual energy production prediction. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30 % of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. Large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation.

Lidar arc scan uncertainty reduction through scanning geometry optimization

NASA Astrophysics Data System (ADS)

Wang, H.; Barthelmie, R. J.; Pryor, S. C.; Brown, G.

2015-10-01

Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annual energy production. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30 % of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. Large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation when arc scans are used for wind resource assessment.

Containment-enhanced Ho:YAG photofragmentation of soft tissues

NASA Astrophysics Data System (ADS)

Christens-Barry, William A.; Guarnieri, Michael; Carson, Benjamin S.

1998-01-01

Laser surgery of soft tissue can exploit the power of brief, intense pulses of light to cause localized disruption of tissue with minimal effect upon surrounding tissue. In particular, studies of Ho:YAG laser surgery have shown that the effects of cavitation upon tissues and bone depend upon the physical composition of structures in the vicinity of the surgical site. For photofragmentation of occluding structures within catheters and other implant devices, it is possible to exploit the particular geometry of the catheter to amplify the effects of photofragmentation beyond those seen in bulk tissue. A Ho:YAG laser was used to photofragment occlusive material (tissue and tissue analogs) contained in glass capillary tubing and catheter tubing of the kind used in ventricular shunt implants for the management of hydrocephalus. Occluded catheters obtained from patient explants were also employed. Selection of operational parameters used in photoablation and photofragmentation of soft tissue must consider the physical composition and geometry of the treatment site. In the present case, containment of the soft tissue within relatively inelastic catheters dramatically alters the extent of photofragmentation relative to bulk (unconstrained) material. Our results indicate that the disruptive effect of cavitation bubbles is increased in catheters, due to the rapid displacement of material by cavitation bubbles comparable in size to the inner diameter of the catheter. The cylindrical geometry of the catheter lumen may additionally influence the propagation of acoustic shock waves that result from the collapse of the condensing cavitation bubbles.

Directed Evolution of a Thermostable Quorum-quenching Lactonase from the Amidohydrolase Superfamily*

PubMed Central

Chow, Jeng Yeong; Xue, Bo; Lee, Kang Hao; Tung, Alvin; Wu, Long; Robinson, Robert C.; Yew, Wen Shan

2010-01-01

A thermostable quorum-quenching lactonase from Geobacillus kaustophilus HTA426 (GI: 56420041) was used as an initial template for in vitro directed evolution experiments. This enzyme belongs to the phosphotriesterase-like lactonase (PLL) group of enzymes within the amidohydrolase superfamily that hydrolyze N-acylhomoserine lactones (AHLs) that are involved in virulence pathways of quorum-sensing pathogenic bacteria. Here we have determined the N-butyryl-l-homoserine lactone-liganded structure of the catalytically inactive D266N mutant of this enzyme to a resolution of 1.6 Å. Using a tunable, bioluminescence-based quorum-quenching molecular circuit, the catalytic efficiency was enhanced, and the AHL substrate range increased through two point mutations on the loops at the C-terminal ends of the third and seventh β-strands. This E101N/R230I mutant had an increased value of kcat/Km of 72-fold toward 3-oxo-N-dodecanoyl-l-homoserine lactone. The evolved mutant also exhibited lactonase activity toward N-butyryl-l-homoserine lactone, an AHL that was previously not hydrolyzed by the wild-type enzyme. Both the purified wild-type and mutant enzymes contain a mixture of zinc and iron and are colored purple and brown, respectively, at high concentrations. The origin of this coloration is suggested to be because of a charge transfer complex involving the β-cation and Tyr-99 within the enzyme active site. Modulation of the charge transfer complex alters the lactonase activity of the mutant enzymes and is reflected in enzyme coloration changes. We attribute the observed enhancement in catalytic reactivity of the evolved enzyme to favorable modulations of the active site architecture toward productive geometries required for chemical catalysis. PMID:20980257

Directed evolution of a thermostable quorum-quenching lactonase from the amidohydrolase superfamily.

PubMed

Chow, Jeng Yeong; Xue, Bo; Lee, Kang Hao; Tung, Alvin; Wu, Long; Robinson, Robert C; Yew, Wen Shan

2010-12-24

A thermostable quorum-quenching lactonase from Geobacillus kaustophilus HTA426 (GI: 56420041) was used as an initial template for in vitro directed evolution experiments. This enzyme belongs to the phosphotriesterase-like lactonase (PLL) group of enzymes within the amidohydrolase superfamily that hydrolyze N-acylhomoserine lactones (AHLs) that are involved in virulence pathways of quorum-sensing pathogenic bacteria. Here we have determined the N-butyryl-L-homoserine lactone-liganded structure of the catalytically inactive D266N mutant of this enzyme to a resolution of 1.6 Å. Using a tunable, bioluminescence-based quorum-quenching molecular circuit, the catalytic efficiency was enhanced, and the AHL substrate range increased through two point mutations on the loops at the C-terminal ends of the third and seventh β-strands. This E101N/R230I mutant had an increased value of k(cat)/K(m) of 72-fold toward 3-oxo-N-dodecanoyl-L-homoserine lactone. The evolved mutant also exhibited lactonase activity toward N-butyryl-L-homoserine lactone, an AHL that was previously not hydrolyzed by the wild-type enzyme. Both the purified wild-type and mutant enzymes contain a mixture of zinc and iron and are colored purple and brown, respectively, at high concentrations. The origin of this coloration is suggested to be because of a charge transfer complex involving the β-cation and Tyr-99 within the enzyme active site. Modulation of the charge transfer complex alters the lactonase activity of the mutant enzymes and is reflected in enzyme coloration changes. We attribute the observed enhancement in catalytic reactivity of the evolved enzyme to favorable modulations of the active site architecture toward productive geometries required for chemical catalysis.

Evaluation of Earthquake Detection Performance in Terms of Quality and Speed in SEISCOMP3 Using New Modules Qceval, Npeval and Sceval

NASA Astrophysics Data System (ADS)

Roessler, D.; Weber, B.; Ellguth, E.; Spazier, J.

2017-12-01

The geometry of seismic monitoring networks, site conditions and data availability as well as monitoring targets and strategies typically impose trade-offs between data quality, earthquake detection sensitivity, false detections and alert times. Network detection capabilities typically change with alteration of the seismic noise level by human activity or by varying weather and sea conditions. To give helpful information to operators and maintenance coordinators, gempa developed a range of tools to evaluate earthquake detection and network performance including qceval, npeval and sceval. qceval is a module which analyzes waveform quality parameters in real-time and deactivates and reactivates data streams based on waveform quality thresholds for automatic processing. For example, thresholds can be defined for latency, delay, timing quality, spikes and gaps count and rms. As changes in the automatic processing have a direct influence on detection quality and speed, another tool called "npeval" was designed to calculate in real-time the expected time needed to detect and locate earthquakes by evaluating the effective network geometry. The effective network geometry is derived from the configuration of stations participating in the detection. The detection times are shown as an additional layer on the map and updated in real-time as soon as the effective network geometry changes. Yet another new tool, "sceval", is an automatic module which classifies located seismic events (Origins) in real-time. sceval evaluates the spatial distribution of the stations contributing to an Origin. It confirms or rejects the status of Origins, adds comments or leaves the Origin unclassified. The comments are passed to an additional sceval plug-in where the end user can customize event types. This unique identification of real and fake events in earthquake catalogues allows to lower network detection thresholds. In real-time monitoring situations operators can limit the processing to events with unclassified Origins, reducing their workload. Classified Origins can be treated specifically by other procedures. These modules have been calibrated and fully tested by several complex seismic monitoring networks in the region of Indonesia and Northern Chile.

Bridging Algebra & Geometry with "n"-Gram Proofs

ERIC Educational Resources Information Center

Craven, Joshua D.

2010-01-01

For many students, geometry is the first course in which mathematical proof takes center stage. To help ease students into writing proofs, the author tries to create lessons and activities throughout the year that challenge students to prove their own conjectures by using tools learned in previous mathematics courses. Teachers cannot get all…

Assessing the Effectiveness of Learning Solid Geometry by Using an Augmented Reality-Assisted Learning System

ERIC Educational Resources Information Center

Lin, Hao-Chiang Koong; Chen, Mei-Chi; Chang, Chih-Kai

2015-01-01

This study integrates augmented reality (AR) technology into teaching activities to design a learning system that assists junior high-school students in learning solid geometry. The following issues are addressed: (1) the relationship between achievements in mathematics and performance in spatial perception; (2) whether system-assisted learning…

Origami, Geometry and Art

ERIC Educational Resources Information Center

Wares, Arsalan; Elstak, Iwan

2017-01-01

The purpose of this paper is to describe the mathematics that emanates from the construction of an origami box. We first construct a simple origami box from a rectangular sheet and then discuss some of the mathematical questions that arise in the context of geometry and algebra. The activity can be used as a context for illustrating how algebra…

Australian Curriculum Linked Lessons

ERIC Educational Resources Information Center

Hurrell, Derek; O'Neil, Jennifer

2011-01-01

In providing a continued focus on tasks and activities that help to illustrate key ideas embedded in the new Australian Curriculum, this issue the authors focus, on Geometry in the Measurement and Geometry strand with strong links for an integrated focus on the Statistics and Probability strand. The small unit of work on the sorting and…

Rugby and Mathematics: A Surprising Link among Geometry, the Conics, and Calculus.

ERIC Educational Resources Information Center

Jones, Troy; Jackson, Steven

2001-01-01

Describes a rugby problem designed to help students understand the maximum-minimum situation. Presents a series of explorations that locate an optimal place for kicking the ball to maximize the angle at the goalposts. Uses interactive geometry software to construct a model of the situation. Includes a sample student activity. (KHR)

Brain Activity Associated with Logical Inferences in Geometry: Focusing on Students with Different Levels of Ability

ERIC Educational Resources Information Center

Waisman, Ilana; Leikin, Mark; Leikin, Roza

2016-01-01

Mathematical processing associated with solving short geometry problems requiring logical inference was examined among students who differ in their levels of general giftedness (G) and excellence in mathematics (EM) using ERP research methodology. Sixty-seven male adolescents formed four major research groups designed according to various…

Shielded resistive electromagnets of arbitrary surface geometry using the boundary element method and a minimum energy constraint.

PubMed

Harris, Chad T; Haw, Dustin W; Handler, William B; Chronik, Blaine A

2013-09-01

Eddy currents are generated in MR by the use of rapidly switched electromagnets, resulting in time varying and spatially varying magnetic fields that must be either minimized or corrected. This problem is further complicated when non-cylindrical insert magnets are used for specialized applications. Interruption of the coupling between an insert coil and the MR system is typically accomplished using active magnetic shielding. A new method of actively shielding insert gradient and shim coils of any surface geometry by use of the boundary element method for coil design with a minimum energy constraint is presented. This method was applied to shield x- and z-gradient coils for two separate cases: a traditional cylindrical primary gradient with cylindrical shield and, to demonstrate its versatility in surface geometry, the same cylindrical primary gradients with a rectangular box-shaped shield. For the cylindrical case this method produced shields that agreed with analytic solutions. For the second case, the rectangular box-shaped shields demonstrated very good shielding characteristics despite having a different geometry than the primary coils. Copyright © 2013 Elsevier Inc. All rights reserved.

Cylindrical cellular geometry ensures fidelity of division site placement in fission yeast.

PubMed

Mishra, Mithilesh; Huang, Yinyi; Srivastava, Pragya; Srinivasan, Ramanujam; Sevugan, Mayalagu; Shlomovitz, Roie; Gov, Nir; Rao, Madan; Balasubramanian, Mohan

2012-08-15

Successful cytokinesis requires proper assembly of the contractile actomyosin ring, its stable positioning on the cell surface and proper constriction. Over the years, many of the key molecular components and regulators of the assembly and positioning of the actomyosin ring have been elucidated. Here we show that cell geometry and mechanics play a crucial role in the stable positioning and uniform constriction of the contractile ring. Contractile rings that assemble in locally spherical regions of cells are unstable and slip towards the poles. By contrast, actomyosin rings that assemble on locally cylindrical portions of the cell under the same conditions do not slip, but uniformly constrict the cell surface. The stability of the rings and the dynamics of ring slippage can be described by a simple mechanical model. Using fluorescence imaging, we verify some of the quantitative predictions of the model. Our study reveals an intimate interplay between geometry and actomyosin dynamics, which are likely to apply in a variety of cellular contexts.

Method and system for simulating heat and mass transfer in cooling towers

DOEpatents

Bharathan, Desikan; Hassani, A. Vahab

1997-01-01

The present invention is a system and method for simulating the performance of a cooling tower. More precisely, the simulator of the present invention predicts values related to the heat and mass transfer from a liquid (e.g., water) to a gas (e.g., air) when provided with input data related to a cooling tower design. In particular, the simulator accepts input data regarding: (a) cooling tower site environmental characteristics; (b) cooling tower operational characteristics; and (c) geometric characteristics of the packing used to increase the surface area within the cooling tower upon which the heat and mass transfer interactions occur. In providing such performance predictions, the simulator performs computations related to the physics of heat and mass transfer within the packing. Thus, instead of relying solely on trial and error wherein various packing geometries are tested during construction of the cooling tower, the packing geometries for a proposed cooling tower can be simulated for use in selecting a desired packing geometry for the cooling tower.

Observation and modelling of urban dew

NASA Astrophysics Data System (ADS)

Richards, Katrina

Despite its relevance to many aspects of urban climate and to several practical questions, urban dew has largely been ignored. Here, simple observations an out-of-doors scale model, and numerical simulation are used to investigate patterns of dewfall and surface moisture (dew + guttation) in urban environments. Observations and modelling were undertaken in Vancouver, B.C., primarily during the summers of 1993 and 1996. Surveys at several scales (0.02-25 km) show that the main controls on dew are weather, location and site configuration (geometry and surface materials). Weather effects are discussed using an empirical factor, FW . Maximum dew accumulation (up to ~ 0.2 mm per night) is seen on nights with moist air and high FW , i.e., cloudless conditions with light winds. Favoured sites are those with high Ysky and surfaces which cool rapidly after sunset, e.g., grass and well insulated roofs. A 1/8-scale model is designed, constructed, and run at an out-of-doors site to study dew patterns in an urban residential landscape which consists of house lots, a street and an open grassed park. The Internal Thermal Mass (ITM) approach is used to scale the thermal inertia of buildings. The model is validated using data from full-scale sites in Vancouver. Patterns in the model agree with those seen at the full-scale, i.e., dew distribution is governed by weather, site geometry and substrate conditions. Correlation is shown between Ysky and surface moisture accumulation. The feasibility of using a numerical model to simulate urban dew is investigated using a modified version of a rural dew model. Results for simple isolated surfaces-a deciduous tree leaf and an asphalt shingle roof-show promise, especially for built surfaces.

Internal waves and modern and ancient hiatuses in pelagic caps of Pacific guyots and seamounts

NASA Astrophysics Data System (ADS)

Mitchell, Neil; Simmons, Harper; Lear, Carrie

2013-04-01

Locations of recent non-deposition and ancient hiatuses in the pelagic caps of guyots and seamounts are compared with paleotemperature and physiographic information to speculate on the character of internal tidal waves in the upper Pacific Ocean through the Cenozoic. Internal tidal waves are generated where the ocean barotropic tide passes over the Hawaiian and other major ridges in the Pacific basin. Drill core and geophysical evidence for sediment accumulation, non-deposition or erosion are used to classify broadly sites as either accumulating or eroding/non-depositing in the recent geological past. When these classified sites are compared against results of a numerical model of the internal tide field (Simmons, Ocean Mod. 2008), the sites accumulating particles over the past few million years are all found to lie away from beams of the modeled internal tide, while those that have not been accumulating are in areas of high internal wave energy. Given the correspondence to modern internal wave conditions, we examine whether internal tides can explain ancient hiatuses at the drill sites. For example, Late Cenozoic pelagic caps on guyots among the Marshall Islands contain two hiatuses of broadly similar age, but the dates of the first pelagic sediments deposited following each hiatus do not correlate between guyots, suggesting that they originate not from universal factors (e.g., water chemistry) but local, probably physical factors, such as internal tides. We investigate how changing boundary conditions such as ocean temperature and basin physiography may have affected the geometry and vigour of internal tides through the Cenozoic. Changes in the geometry of ridges underlying the Solomon, Bonin and Marianas Island chains caused by plate tectonics and subsidence may be responsible for sediment hiatuses at these far-field guyot sites.

Internal waves and modern and ancient hiatuses in pelagic caps of Pacific guyots and seamounts

NASA Astrophysics Data System (ADS)

Mitchell, N. C.; Simmons, H. L.; Lear, C. H.

2012-12-01

Locations of recent non-deposition and ancient hiatuses in the pelagic caps of guyots and seamounts are compared with paleotemperature and physiographic information to speculate on the character of internal tidal waves in the upper Pacific Ocean through the Cenozoic. Internal tidal waves are generated where the ocean barotopic tide passes over the Hawaiian and other major ridges in the Pacific basin. Drill core and geophysical evidence for sediment accumulation, non-deposition or erosion are used to classify broadly sites as either accumulating or eroding/non-depositing in the recent geological past. When these classified sites are compared against results of a numerical model of the internal tide field (Simmons, Ocean Mod. 2008), the sites accumulating particles over the past few million years are all found to lie away from beams of the modeled internal tide, while those that have not been accumulating are in areas of high internal wave energy. Given the correspondence to modern internal wave conditions, we examine whether internal tides can explain ancient hiatuses at the drill sites. For example, Late Cenozoic pelagic caps on guyots among the Marshall Islands contain two hiatuses of broadly similar age, but the dates of the first pelagic sediments deposited following each hiatus do not correlate between guyots, suggesting that they originate not from universal factors (e.g., water chemistry) but local, probably physical factors, such as internal tides. We investigate how changing boundary conditions such as ocean temperature and basin physiography may have affected the geometry and vigour of internal tides through the Cenozoic. Changes in the geometry of ridges underlying the Solomon, Bonin and Marianas Island chains caused by plate tectonics and subsidence may be responsible for sediment hiatuses at these far-field guyot sites.

Theoretical investigation of structures and energetics of sodium adatom and its dimer on graphene: DFT study

NASA Astrophysics Data System (ADS)

Kaur, Gagandeep; Gupta, Shuchi; Rani, Pooja; Dharamvir, Keya

2015-11-01

Extensive ab initio calculations have been performed to study the energetics of a sodium (Na) atom and its dimer adsorbed on graphene using the SIESTA package Soler et al. (2002) [1] which works within a DFT(density functional theory)-GGA (generalized gradient approximation) pseudopotential framework. The adsorption energy, geometry, charge transfer, ionization potential and density of states (DOS), partial density states (PDOS) of adatom/dimer-graphene system have been calculated. After considering various sites for adsorption of Na on graphene, the center of a hexagonal ring of carbon atoms is found to be the preferred site of adsorption while the Na2 dimer prefers to rest parallel to the graphene sheet. We find insignificant energy differences among adsorption configurations involving different possible sites in parallel orientation, which implies high mobility of the dimer on the graphene sheet. We also notice only a slight distortion of the graphene sheet perpendicular to its plane upon adatom adsorption. However, some lateral displacements seen are more perceptible. Summary The adsorption energy, geometry, charge transfer, ionization potential and density of states (DOS) and PDOS of adatom/dimer-graphene system have been calculated using SIESTA package Soler et al. (2002) [1] which works within a DFT(density functional theory)-GGA (generalized gradient approximation) pseudopotential framework. Preferred site for adsorption of a sodium atom on graphene is the hollow site. For the Na dimer adsorption, we found that horizontal orientation is favored over the vertical one. From DOS plots, it is clear that graphene's states are nearly unaffected by the adsorption of Na adatom and Interaction between sodium and graphene is predominantly ionic

Hexahedral Finite Element Mesh Capturing Realistic Geometries of Bayou Choctaw Strategic Petroleum Reserve

NASA Astrophysics Data System (ADS)

Park, B. Y.; Roberts, B. L.; Sobolik, S. R.

2016-12-01

The U.S. Strategic Petroleum Reserve (SPR) stores crude oil in 60 caverns located at four sites located along the Gulf Coast. As a matter of normal operation of caverns in a salt dome, the continuous mechanical creep of salt, along with the change in internal cavern and casing pressure due to cavern closure and fluid exchanges, impose several mechanical conditions on the skin, well, and casing of a cavern that could potentially create damage. Sandia, on behalf of DOE, is evaluating the structural integrity of the salt surrounding existing caverns in the Bayou Choctaw (BC) salt dome in Louisiana. In reality, the geometry, spacing, and depths of the caverns are irregular. It is not easy to realize the naturally and artificially formed cavern and salt dome for numerical analysis. It is harder to convert the geometries into the meshed mass consisting of only hexahedral finite elements. A three-dimensional (3D) finite element mesh capturing realistic geometries of the Bayou Choctaw site has been constructed using the seismic and sonar survey data obtained from the field (see Figures below). The mesh consists of hexahedral elements because the salt constitutive model is coded using hexahedral elements. Techniques to reduce the number of elements as much as possible to save on computer run time while maintaining computational accuracy are also developed. These methodologies could also be applied to construct computational meshes for the Big Hill, Bryan Mound, and West Hackberry SPR sites. The methodology could be applied to the complicated shape masses for not only various civil and geological structures but also biological applications such as artificial limbs. The newly developed mesh is expected to provide more accurate solutions of geotechnical concerns that arise due to the close proximity of the caverns to each other or to the edge of salt. Also, there are nine abandoned caverns, one of which is believed to be in a quasi-stable condition. Stability issues for these abandoned caverns must be evaluated and, if necessary, addressed to prevent potential cavern collapse. The integrity of wellbores at the interbed between the caprock and salt is another concern because oil leaks could occur due to the horizontal and downward movements of the salt top relative to the caprock.

Real-time Estimation of Fault Rupture Extent for Recent Large Earthquakes

NASA Astrophysics Data System (ADS)

Yamada, M.; Mori, J. J.

2009-12-01

Current earthquake early warning systems assume point source models for the rupture. However, for large earthquakes, the fault rupture length can be of the order of tens to hundreds of kilometers, and the prediction of ground motion at a site requires the approximated knowledge of the rupture geometry. Early warning information based on a point source model may underestimate the ground motion at a site, if a station is close to the fault but distant from the epicenter. We developed an empirical function to classify seismic records into near-source (NS) or far-source (FS) records based on the past strong motion records (Yamada et al., 2007). Here, we defined the near-source region as an area with a fault rupture distance less than 10km. If we have ground motion records at a station, the probability that the station is located in the near-source region is; P = 1/(1+exp(-f)) f = 6.046log10(Za) + 7.885log10(Hv) - 27.091 where Za and Hv denote the peak values of the vertical acceleration and horizontal velocity, respectively. Each observation provides the probability that the station is located in near-source region, so the resolution of the proposed method depends on the station density. The information of the fault rupture location is a group of points where the stations are located. However, for practical purposes, the 2-dimensional configuration of the fault is required to compute the ground motion at a site. In this study, we extend the methodology of NS/FS classification to characterize 2-dimensional fault geometries and apply them to strong motion data observed in recent large earthquakes. We apply a cosine-shaped smoothing function to the probability distribution of near-source stations, and convert the point fault location to 2-dimensional fault information. The estimated rupture geometry for the 2007 Niigata-ken Chuetsu-oki earthquake 10 seconds after the origin time is shown in Figure 1. Furthermore, we illustrate our method with strong motion data of the 2007 Noto-hanto earthquake, 2008 Iwate-Miyagi earthquake, and 2008 Wenchuan earthquake. The on-going rupture extent can be estimated for all datasets as the rupture propagates. For earthquakes with magnitude about 7.0, the determination of the fault parameters converges to the final geometry within 10 seconds.

Real-time control of geometry and stiffness in adaptive structures

NASA Technical Reports Server (NTRS)

Ramesh, A. V.; Utku, S.; Wada, B. K.

1991-01-01

The basic theory is presented for the geometry, stiffness, and damping control of adaptive structures, with emphasis on adaptive truss structures. Necessary and sufficient conditions are given for stress-free geometry control in statically determinate and indeterminate adaptive discrete structures. Two criteria for selecting the controls are proposed, and their use in real-time control is illustrated by numerical simulation results. It is shown that the stiffness and damping control of adaptive truss structures for vibration suppression is possible by elongation and elongation rate dependent feedback forces from the active elements.

Endpoint-based parallel data processing with non-blocking collective instructions in a parallel active messaging interface of a parallel computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Archer, Charles J; Blocksome, Michael A; Cernohous, Bob R

Endpoint-based parallel data processing with non-blocking collective instructions in a PAMI of a parallel computer is disclosed. The PAMI is composed of data communications endpoints, each including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task. The compute nodes are coupled for data communications through the PAMI. The parallel application establishes a data communications geometry specifying a set of endpoints that are used in collective operations of the PAMI by associating with the geometry a list of collective algorithms valid for use with themore » endpoints of the geometry; registering in each endpoint in the geometry a dispatch callback function for a collective operation; and executing without blocking, through a single one of the endpoints in the geometry, an instruction for the collective operation.« less

Method and apparatus for enhancing vortex pinning by conformal crystal arrays

DOEpatents

Janko, Boldizsar; Reichhardt, Cynthia; Reichhardt, Charles; Ray, Dipanjan

2015-07-14

Disclosed is a method and apparatus for strongly enhancing vortex pinning by conformal crystal arrays. The conformal crystal array is constructed by a conformal transformation of a hexagonal lattice, producing a non-uniform structure with a gradient where the local six-fold coordination of the pinning sites is preserved, and with an arching effect. The conformal pinning arrays produce significantly enhanced vortex pinning over a much wider range of field than that found for other vortex pinning geometries with an equivalent number of vortex pinning sites, such as random, square, and triangular.

Active Flexural-Slip Faulting: Controls Exerted by Stratigraphy, Geometry, and Fold Kinematics

NASA Astrophysics Data System (ADS)

Li, Tao; Chen, Jie; Thompson Jobe, Jessica A.; Burbank, Douglas W.

2017-10-01

Flexural slip plays an important role in accommodating fold growth, and its topographic expression, flexural-slip fault (FSF) scarps, may be one of the most commonly occurring secondary structures in areas dominated by active thrusts and folds. Where FSF scarps are present and what factors control their occurrence, however, are typically poorly known. Through an investigation of clearly expressed FSF scarps, well-preserved fluvial terraces, and well-exposed bedrock at eight sites in the Pamir-Tian Shan convergent zone and Kuche fold belt, NW China, we summarize the most favorable conditions for active flexural-slip faulting. Our study yields six key results. First, flexural slip operates commonly in well-layered beds, although uncommonly can occur in massive, poorly layered beds as well. Second, in well-layered beds, the slip surface is commonly located either (a) close to the contact of competent and incompetent beds or (b) within thin incompetent beds. Third, FSF scarps are always found overlying steep beds with dips of 30-100°. Fourth, slip surfaces are typically spaced between 10 and 440 m but can reach up to 600 m. Fifth, FSF scarps at most sites can be observed far away from the hinge-migrated fold scarps, suggesting that compared to hinge migration, limb rotation is generally required to accumulate flexural slip and produce associated topographic scarps. Finally, a higher regional convergent rate seems to facilitate the creation of FSF scarps more often than lower rates, whereas well-preserved, old terraces capped by thin deposits are more likely to record FSF scarps than unevenly preserved, young terraces with thick sedimentary caps.

Building a viable decollement geometry for the Central Nepal Himalaya through integrating surface geology, thermochronology and data from the 2015 Gorkha Earthquake

NASA Astrophysics Data System (ADS)

Ghoshal, S.; McQuarrie, N.; Robinson, D. M.; Olree, E.; Valentino, C.; Olsen, J.

2017-12-01

Recent field mapping in the Central Himalaya revealed a marked change in the location and orientation of exposed Greater Himalayan rocks around the epicenter of the April 2015 Gorkha earthquake, arguing for a lateral structure in the Main Himalayan Thrust (MHT). The earthquake provided new insight into the geometry of the MHT, but left the position and depth of the mid-crustal ramp in dispute. Combining new field data with existing thermochronometric data from the region emphasizes that both the mapped geology and young cooling ages step abruptly southward from east to west, immediately adjacent to the earthquake epicenter. The distribution of cooling ages is strongly influenced by the location of ramps in the decollement surface, as the vertical component of uplift concentrates exhumation over the ramp, producing the youngest ages there. We propose that the existence and location of frontal and lateral ramps can be evaluated using the regional distribution of thermochronometric ages. Sequentially deformed cross-sections present a model of how structurally induced uplift varies in time and space, as well as a predicted geometry of the active, modern fault. We created new balanced cross-sections, constrained by surface geology and the proposed decollement geometries. For an accurate representation of the subsurface, the geometries must reproduce cooling ages measured at the surface. Each cross section was sequentially deformed, allowing for flexure and erosion. The resulting displacement field was used to predict cooling ages for muscovite 40Ar/39Ar, zircon (U-Th)/He, and apatite fission-track, using the thermokinematic model Pecube. The different closure temperatures for these systems allow them to represent different times and locations of exhumation driven by evolving fault geometries. The modeled cooling ages are the cumulative effect of the entire deformational sequence. However, the ages are particularly sensitive to the modern active decollement fault geometry, allowing us to evaluate the different proposed cross-section geometries, and identify the best match to the regional distribution of cooling ages. We argue that this final geometry is the most accurate representation of the subsurface, being constrained by surface geology, thermochronological ages, and data from the earthquake.

Modifications of highway air pollution models for complex geometries, volume II : wind tunnel test program.

DOT National Transportation Integrated Search

2002-09-01

This is volume I1 of a two-volume report of a study to increase the scope and clarity of air pollution models for : depressed highway and street canyon sites. It presents the atmospheric wind tunnel program conducted to increase the : data base and i...

Coefficient of friction: tribological studies in man - an overview.

PubMed

Sivamani, Raja K; Goodman, Jack; Gitis, Norm V; Maibach, Howard I

2003-08-01

Compared to other studies of skin, relatively few studies have focused on the friction of skin. This work reviews existing skin friction, emphasizing test apparatuses and parameters that have added to information regarding the friction coefficient. This review also outlines what factors are important to consider in future friction studies. Past studies have utilized numerous designs for a test apparatus, including probe geometry and material, as well as various probe motions (rotational vs. linear). Most tests were performed in vivo; a few were performed in vitro and on porcine skin. Differences in probe material, geometry and smoothness affect friction coefficient measurements. An increase in skin hydration, either through water or through moisturizer application, increases its friction coefficient; a decrease in skin hydration, either through clinical dermatitis or through alcohol addition, decreases the coefficient. Differences are present between anatomical sites. Conflicting results are found regarding age and no differences are apparent as a result of gender or race. Skin friction appears to be dependent on several factors - such as age, anatomical site and skin hydration. The choice of the probe and the test apparatus also influence the measurement.

Physical, chemical, and biological data for two sites on the upper Kenai River, Alaska, 1998

USGS Publications Warehouse

Dorava, Joseph M.; Ness, Lee

1999-01-01

Water-quality data were collected and stream characteristics were documented from two sites along the upper Kenai River in the Kenai National Wildlife Refuge, Alaska. These data were collected to describe the current status of the sites and to provide baseline information from which changes in the future could be evaluated. Physical characteristics included channel geometry surveys, and measurements of channel widths and water discharge at each site. Chemical data included stream water temperature, dissolved-oxygen concentration, pH, specific conductance, E. coli and fecal coliform counts, and nutrient concentration. Data on concentrations of trace elements and various organic compounds in bed sediments and the tissue of slimy sculpin were also collected. Biological characteristics were evaluated using measurements of the bacteria, benthic macroinvertebrate, and fish communities.

Tests and applications of nonlinear force-free field extrapolations in spherical geometry

NASA Astrophysics Data System (ADS)

Guo, Y.; Ding, M. D.

2013-07-01

We test a nonlinear force-free field (NLFFF) optimization code in spherical geometry with an analytical solution from Low and Lou. The potential field source surface (PFSS) model is served as the initial and boundary conditions where observed data are not available. The analytical solution can be well recovered if the boundary and initial conditions are properly handled. Next, we discuss the preprocessing procedure for the noisy bottom boundary data, and find that preprocessing is necessary for NLFFF extrapolations when we use the observed photospheric magnetic field as bottom boundaries. Finally, we apply the NLFFF model to a solar area where four active regions interacting with each other. An M8.7 flare occurred in one active region. NLFFF modeling in spherical geometry simultaneously constructs the small and large scale magnetic field configurations better than the PFSS model does.

Comparison of organ dose and dose equivalent using ray tracing of male and female Voxel phantoms to space flight phantom torso data

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee; Qualls, Garry; Slaba, Tony; Cucinotta, Francis A.

Phantom torso experiments have been flown on the space shuttle and International Space Station (ISS) providing validation data for radiation transport models of organ dose and dose equivalents. We describe results for space radiation organ doses using a new human geometry model based on detailed Voxel phantoms models denoted for males and females as MAX (Male Adult voXel) and Fax (Female Adult voXel), respectively. These models represent the human body with much higher fidelity than the CAMERA model currently used at NASA. The MAX and FAX models were implemented for the evaluation of directional body shielding mass for over 1500 target points of major organs. Radiation exposure to solar particle events (SPE), trapped protons, and galactic cosmic rays (GCR) were assessed at each specific site in the human body by coupling space radiation transport models with the detailed body shielding mass of MAX/FAX phantom. The development of multiple-point body-shielding distributions at each organ site made it possible to estimate the mean and variance of space dose equivalents at the specific organ. For the estimate of doses to the blood forming organs (BFOs), active marrow distributions in adult were accounted at bone marrow sites over the human body. We compared the current model results to space shuttle and ISS phantom torso experiments and to calculations using the CAMERA model.

Comparison of Organ Dose and Dose Equivalent Using Ray Tracing of Male and Female Voxel Phantoms to Space Flight Phantom Torso Data

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Qualls, Garry D.; Cucinotta, Francis A.

2008-01-01

Phantom torso experiments have been flown on the space shuttle and International Space Station (ISS) providing validation data for radiation transport models of organ dose and dose equivalents. We describe results for space radiation organ doses using a new human geometry model based on detailed Voxel phantoms models denoted for males and females as MAX (Male Adult voXel) and Fax (Female Adult voXel), respectively. These models represent the human body with much higher fidelity than the CAMERA model currently used at NASA. The MAX and FAX models were implemented for the evaluation of directional body shielding mass for over 1500 target points of major organs. Radiation exposure to solar particle events (SPE), trapped protons, and galactic cosmic rays (GCR) were assessed at each specific site in the human body by coupling space radiation transport models with the detailed body shielding mass of MAX/FAX phantom. The development of multiple-point body-shielding distributions at each organ site made it possible to estimate the mean and variance of space dose equivalents at the specific organ. For the estimate of doses to the blood forming organs (BFOs), active marrow distributions in adult were accounted at bone marrow sites over the human body. We compared the current model results to space shuttle and ISS phantom torso experiments and to calculations using the CAMERA model.

Characterization of the 3-D fracture setting of an unstable rock mass: From surface and seismic investigations to numerical modeling

NASA Astrophysics Data System (ADS)

Colombero, C.; Baillet, L.; Comina, C.; Jongmans, D.; Vinciguerra, S.

2017-08-01

The characterization of the fracturing state of a potentially unstable rock cliff is a crucial requirement for stability assessments and mitigation purposes. Classical measurements of fracture location and orientation can however be limited by inaccessible rock exposures. The steep topography and high-rise morphology of these cliffs, together with the widespread presence of fractures, can additionally condition the success of geophysical prospecting on these sites. In order to mitigate these limitations, an innovative approach combining noncontact geomechanical measurements, active and passive seismic surveys, and 3-D numerical modeling is proposed in this work to characterize the 3-D fracture setting of an unstable rock mass, located in NW Italian Alps (Madonna del Sasso, VB). The 3-D fracture geometry was achieved through a combination of field observations and noncontact geomechanical measurements on oriented pictures of the cliff, resulting from a previous laser-scanning and photogrammetric survey. The estimation of fracture persistence within the rock mass was obtained from surface active seismic surveys. Ambient seismic noise and earthquakes recordings were used to assess the fracture control on the site response. Processing of both data sets highlighted the resonance properties of the unstable rock volume decoupling from the stable massif. A finite element 3-D model of the site, including all the retrieved fracture information, enabled both validation and interpretation of the field measurements. The integration of these different methodologies, applied for the first time to a complex 3-D prone-to-fall mass, provided consistent information on the internal fracturing conditions, supplying key parameters for future monitoring purposes and mitigation strategies.

Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors.

PubMed

Dowling, Daniel P; Gantt, Stephanie L; Gattis, Samuel G; Fierke, Carol A; Christianson, David W

2008-12-23

Metal-dependent histone deacetylases (HDACs) require Zn(2+) or Fe(2+) to regulate the acetylation of lysine residues in histones and other proteins in eukaryotic cells. Isozyme HDAC8 is perhaps the archetypical member of the class I HDAC family and serves as a paradigm for studying structure-function relationships. Here, we report the structures of HDAC8 complexes with trichostatin A and 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA) in a new crystal form. The structure of the APHA complex reveals that the hydroxamate CO group accepts a hydrogen bond from Y306 but does not coordinate to Zn(2+) with favorable geometry, perhaps due to the constraints of its extended pi system. Additionally, since APHA binds to only two of the three protein molecules in the asymmetric unit of this complex, the structure of the third monomer represents the first structure of HDAC8 in the unliganded state. Comparison of unliganded and liganded structures illustrates ligand-induced conformational changes in the L2 loop that likely accompany substrate binding and catalysis. Furthermore, these structures, along with those of the D101N, D101E, D101A, and D101L variants, support the proposal that D101 is critical for the function of the L2 loop. However, amino acid substitutions for D101 can also trigger conformational changes of Y111 and W141 that perturb the substrate binding site. Finally, the structure of H143A HDAC8 complexed with an intact acetylated tetrapeptide substrate molecule confirms the importance of D101 for substrate binding and reveals how Y306 and the active site zinc ion together bind and activate the scissile amide linkage of acetyllysine.

Time scale of diffusion in molecular and cellular biology

NASA Astrophysics Data System (ADS)

Holcman, D.; Schuss, Z.

2014-05-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

Effect of the mileage of a passenger car on changes in its body geometry

NASA Astrophysics Data System (ADS)

Gonera, Jarosław; Napiórkowski, Jerzy

2018-04-01

This study analyses the effect of the mileage of a passenger car on changes in its body geometry in regards to its safety. Ninety-six passenger cars used in similar environmental conditions were examined. The required position of twelve base points was compared to their actual position. Those were the points responsible for the active and passive safety of a car on the left and right side of the floor panel. The geometry of the floor panel was measured with a GYSMETER device manufactured by GYS and Allvis Light software. Increasing mileage was found to result in increasing changes in the floor panel geometry, which take place mainly on the right side of a car and at points affecting passive safety.

Representational geometry: integrating cognition, computation, and the brain

PubMed Central

Kriegeskorte, Nikolaus; Kievit, Rogier A.

2013-01-01

The cognitive concept of representation plays a key role in theories of brain information processing. However, linking neuronal activity to representational content and cognitive theory remains challenging. Recent studies have characterized the representational geometry of neural population codes by means of representational distance matrices, enabling researchers to compare representations across stages of processing and to test cognitive and computational theories. Representational geometry provides a useful intermediate level of description, capturing both the information represented in a neuronal population code and the format in which it is represented. We review recent insights gained with this approach in perception, memory, cognition, and action. Analyses of representational geometry can compare representations between models and the brain, and promise to explain brain computation as transformation of representational similarity structure. PMID:23876494

The Most Remote Point Method for the Site Selection of the Future VGOS Network

NASA Astrophysics Data System (ADS)

Hase, Hayo; Pedreros, Felipe

2014-12-01

The VLBI Global Observing System (VGOS) will be part of the Global Geodetic Observing System (GGOS) and will consist of globally well distributed geodetic observatories. The most remote point (MRP) method is used to identify gaps in the network geometry. In each iteration step the identified most remote points are assumed to become new observatory sites improving the homogeneity of the global network. New locations for VGOS observatories have been found in La Plata, Tahiti, O'Higgins, Galapagos, Colombo, and Syowa. This contribution is an excerpt of a work published in Journal of Geodesy (DOI: 10.1007/s00190-014-0731-y) covering the site selection for the GGOS.%

Spectral bidirectional and hemispherical reflectance characteristics of selected sites in the Streletskaya steppe

NASA Technical Reports Server (NTRS)

Eck, Thomas F.; Deering, Donald W.

1992-01-01

Measurements of plant canopy bidirectional reflectance made by the PARABOLA (portable apparatus for rapid acquisition of bidirectional observations of the land and atmosphere) instrument in three spectral bands are analyzed for steppe grassland sites of differing productivity levels. The variation of spectral reflectance and the normalized difference vegetation index in the solar principal plane is presented. Comparisons are made with PARABOLA measurements from selected first ISLSCP field experiment (FIFE) grassland sites in the Konza prairie, Kansas. The Streletskaya steppe sites showed no strong hot spot reflectance, while this effect was present in some FIFE sites but absent in others. The hot spot effect seems to be dependent on canopy geometry and background reflectance characteristics of these sites. Spectral hemispherical reflectance was computed from the angular integration of the bidirectional measurements for the steppe sites. Total shortwave albedo was estimated from these hemispherical reflectance measurements and compared to albedo measured by pyranometers. The albedo estimates from PARABOLA were found to be approximately 12-17 percent higher than the pyranometer measurements.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez-Orozco, Carlos; Florez, Elizabeth; Moreno, Andres

A systematic study of ethylene adsorption over δ-MoC(001), TiC(001), and ZrC(001) surfaces was conducted by means of calculations based on periodic density functional theory. The structure and electronic properties of each carbide pristine surface had a strong influence in the bonding of ethylene. It was found that the metal and carbon sites of the carbide could participate in the adsorption process. As a consequence of this, very different bonding mechanisms were seen on δ-MoC(001) and TiC(001). The bonding of the molecule on the TMC(001) systems showed only minor similarities to the type of bonding found on a typical metal likemore » Pt(111). In general, the ethylene binding energy follow the trend in stability: ZrC(001) < TiC(001) < δ-MoC(001) < Pt(111). The van der Waals correction to the energy produces large binding energy values, modifies the stability orders and drives the ethylene closer to the surface but the adsorbate geometry parameters remain unchanged. Ethylene was activated on clearly defined binding geometries, changing its hybridization from sp 2 to sp 3 with an elongation (0.16–0.31 Å) of the C=C bond. As a result, on the basis of this theoretical study, δ-MoC(001) is proposed as a potential catalyst for the hydrogenation of olefins, whereas TiC(001) could be useful for their hydrogenolysis.« less

Alternating magnetic field optimization for IONP hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Kastner, Elliot J.; Reeves, Russell; Bennett, William; Misra, Aditi; Petryk, Jim D.; Petryk, Alicia A.; Hoopes, P. Jack

2015-03-01

Iron oxide nanoparticles (IONP) have therapeutic potential to deliver a thermal dose to tumors when activated in an alternating magnetic field (AMF). Through various targeting methods such as antibody labeling or injection site choice, delivery of IONPs to tumors yields enhanced treatment accuracy and efficacy. Despite this advantage, delivery an AMF, which is sufficient to result in clinically relevant IONP heating, can result in nonspecific tissue heating via the generation of eddy currents and tissue permeated by local electric fields (joule heating). The production of eddy current heating is a function of tissue size, geometry and composition as well as coil design and operation. The purpose of this research is to increase the level of energy deposited into the IONPs versus the non-target tissue (power ratio/PR)1 in order to improve target heating and reduce nonspecific tissue damage. We propose to improve the PR using two primary concepts: (1) reduce power deposition into non-target tissue by manipulating the fields and eddy current flow and (2) enhance heat removal from non-target tissue. We have shown that controlling tissue placement within the AMF field, accounting for tissue geometry, utilizing external cooling devices, and modifying the field properties can decrease non-target heating by more than 50%, at clinically relevant AMF levels, thereby allowing for an increase in thermal dose to the tumor and increasing the therapeutic ratio.

Different integrated geophysical approaches to investigate archaeological sites in urban and suburban area.

NASA Astrophysics Data System (ADS)

Piro, Salvatore; Papale, Enrico; Zamuner, Daniela

2016-04-01

Geophysical methods are frequently used in archaeological prospection in order to provide detailed information about the presence of structures in the subsurface as well as their position and their geometrical reconstruction, by measuring variations of some physical properties. Often, due to the limited size and depth of an archaeological structure, it may be rather difficult to single out its position and extent because of the generally low signal-to-noise ratio. This problem can be overcome by improving data acquisition, processing techniques and by integrating different geophysical methods. In this work, two sites of archaeological interest, were investigated employing several methods (Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT), Fluxgate Differential Magnetic) to obtain precise and detailed maps of subsurface bodies. The first site, situated in a suburban area between Itri and Fondi, in the Aurunci Natural Regional Park (Central Italy), is characterized by the presence of remains of past human activity dating from the third century B.C. The second site, is instead situated in an urban area in the city of Rome (Basilica di Santa Balbina), where historical evidence is also present. The methods employed, allowed to determine the position and the geometry of some structures in the subsurface related to this past human activity. To have a better understanding of the subsurface, we then performed a qualitative and quantitative integration of this data, which consists in fusing the data from all the methods used, to have a complete visualization of the investigated area. Qualitative integration consists in graphically overlaying the maps obtained by the single methods; this method yields only images, not new data that may be subsequently analyzed. Quantitative integration is instead performed by mathematical and statistical solutions, which allows to have a more accurate reconstruction of the subsurface and generates new data with high information content.

Interests of long-term hydrogeological observatories for characterizing and modelling heterogeneous groundwater systems at multiple temporal and spatial scales: the example of Ploemeur, a crystalline rock aquifer (Brittany).

NASA Astrophysics Data System (ADS)

Bour, Olivier; Longuervergne, Laurent; Le Borgne, Tanguy; Lavenant, Nicolas; de Dreuzy, Jean-Raynald; Schuite, Jonathan; Labasque, Thierry; Aquilina, Luc; Davy, Philippe

2017-04-01

Characterizing groundwater flows and surface interactions in heterogeneous groundwater systems such as crystalline fractured rock is often extremely complex. In particular, hydraulic properties are highly variable while groundwater chemical properties may vary both in space and time, especially due to the impact of groundwater abstraction. Here, we show the interest of hydrological observatories and long-term monitoring for characterizing hydrological processes occurring in a crystalline rock aquifer. We present results from the site of Ploemeur (French Brittany) that belongs to the network of hydrogeological sites H+ and the research infrastructure OZCAR, and where interdisciplinary and integrated research at multiple temporal and spatial scales has been developed for almost twenty years. This outstandingly heterogeneous crystalline rock aquifer is also used for groundwater supply since 1991. In particular, we show how cross-borehole flowmeter tests, pumping tests and a frequency domain analysis of groundwater levels allow quantifying the hydraulic properties of the aquifer at different scales. In addition, groundwater temperature evolution was used as an excellent tracer for characterizing groundwater flow. At the site scale, measurements of ground surface deformation through long-base tiltmeters provide robust estimates of aquifer storage and allow identifying the active structures, including those acting during recharge process. Finally, a numerical model of the watershed scale that combines hydraulic data and groundwater ages confirms the geometry of this complex aquifer and the consistency of the different datasets. In parallel, this hydrological observatory is also used for developing hydrogeophysical methods and to characterize groundwater transport and biogeochemical reactivity in the sub-surface. The Ploemeur hydrogeological observatory is a good example of the interest of focusing research activities on a site during long-term as it provides a thorough understanding of both hydrological and biogeochemical processes that can be extended to many heterogeneous aquifers.

Cytotoxicity of Cyclometalated Platinum Complexes Based on Tridentate NCN and CNN-coordinating ligands: Remarkable Coordination Dependence

PubMed Central

Vezzu, Dileep A. k.; Lu, Qun; Chen, Yan-Hua; Huo, Shouquan

2014-01-01

A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the NʌCʌN-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the CʌNʌN-coordinated platinum complex based on 6-phenyl-2,2′-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by NʌCʌN- and CʌNʌN-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the NʌCʌN-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis was studied by western blot analysis and the activation of PARP via caspase 7 was observed. PMID:24531534

The role of extended Fe4S4 cluster ligands in mediating sulfite reductase hemoprotein activity.

PubMed

Cepeda, Marisa R; McGarry, Lauren; Pennington, Joseph M; Krzystek, J; Elizabeth Stroupe, M

2018-05-28

The siroheme-containing subunit from the multimeric hemoflavoprotein NADPH-dependent sulfite reductase (SiR/SiRHP) catalyzes the six electron-reduction of SO 3 2- to S 2- . Siroheme is an iron-containing isobacteriochlorin that is found in sulfite and homologous siroheme-containing nitrite reductases. Siroheme does not work alone but is covalently coupled to a Fe 4 S 4 cluster through one of the cluster's ligands. One long-standing hypothesis predicted from this observation is that the environment of one iron-containing cofactor influences the properties of the other. We tested this hypothesis by identifying three amino acids (F437, M444, and T477) that interact with the Fe 4 S 4 cluster and probing the effect of altering them to alanine on the function and structure of the resulting enzymes by use of activity assays, X-ray crystallographic analysis, and EPR spectroscopy. We showed that F437 and M444 gate access for electron transfer to the siroheme-cluster assembly and the direct hydrogen bond between T477 and one of the cluster sulfides is important for determining the geometry of the siroheme active site. Copyright © 2018. Published by Elsevier B.V.

QSAR models based on quantum topological molecular similarity.

PubMed

Popelier, P L A; Smith, P J

2006-07-01

A new method called quantum topological molecular similarity (QTMS) was fairly recently proposed [J. Chem. Inf. Comp. Sc., 41, 2001, 764] to construct a variety of medicinal, ecological and physical organic QSAR/QSPRs. QTMS method uses quantum chemical topology (QCT) to define electronic descriptors drawn from modern ab initio wave functions of geometry-optimised molecules. It was shown that the current abundance of computing power can be utilised to inject realistic descriptors into QSAR/QSPRs. In this article we study seven datasets of medicinal interest : the dissociation constants (pK(a)) for a set of substituted imidazolines , the pK(a) of imidazoles , the ability of a set of indole derivatives to displace [(3)H] flunitrazepam from binding to bovine cortical membranes , the influenza inhibition constants for a set of benzimidazoles , the interaction constants for a set of amides and the enzyme liver alcohol dehydrogenase , the natriuretic activity of sulphonamide carbonic anhydrase inhibitors and the toxicity of a series of benzyl alcohols. A partial least square analysis in conjunction with a genetic algorithm delivered excellent models. They are also able to highlight the active site, of the ligand or the molecule whose structure determines the activity. The advantages and limitations of QTMS are discussed.

Built Heritage Documentation and Management: AN Integrated Conservation Approach in Bagan

NASA Astrophysics Data System (ADS)

Mezzino, D.; Chan, L.; Santana Quintero, M.; Esponda, M.; Lee, S.; Min, A.; Pwint, M.

2017-08-01

Good practices in heritage conservation are based on accurate information about conditions, materials, and transformation of built heritage sites. Therefore, heritage site documentation and its analysis are essential parts for their conservation. In addition, the devastating effects of recent catastrophic events in different geographical areas have highly affected cultural heritage places. Such areas include and are not limited to South Europe, South East Asia, and Central America. Within this framework, appropriate acquisition of information can effectively provide tools for the decision-making process and management. Heritage documentation is growing in innovation, providing dynamic opportunities for effectively responding to the alarming rate of destruction by natural events, conflicts, and negligence. In line with these considerations, a multidisciplinary team - including students and faculty members from Carleton University and Yangon Technological University, as well as staff from the Department of Archaeology, National Museum and Library (DoA) and professionals from the CyArk foundation - developed a coordinated strategy to document four temples in the site of Bagan (Myanmar). On-field work included capacity-building activities to train local emerging professionals in the heritage field (graduate and undergraduate students from the Yangon Technological University) and to increase the technical knowledge of the local DoA staff in the digital documentation field. Due to the short time of the on-field activity and the need to record several monuments, a variety of documentation techniques, including image and non-image based ones, were used. Afterwards, the information acquired during the fieldwork was processed to develop a solid base for the conservation and monitoring of the four documented temples. The relevance of developing this kind of documentation in Bagan is related to the vulnerability of the site, often affected by natural seismic events and flooding, as well as the lack of maintenance. Bagan provided an excellent case study to test the effectiveness of the proposed approach, to prevent and manage the damages of catastrophic events, and to support retrofitting actions. In order to test the flexibility of adopted methodology and workflow, temples with different features - in terms of architectural design, shape, and geometry - were selected. The goals of these documentation activities range from testing digital documentation workflows for the metric and visual recording of the site (reviewing strengths and limitations of particular recording techniques), to the definition of effective conditions assessment strategies.

Structure and builtup of the Middle Bengal Fan at 8°N from multichannel seismic surveys and the IODP Expedition 354 drilling transect

NASA Astrophysics Data System (ADS)

Spiess, V.; Bergmann, F.; Schwenk, T.; Lantzsch, H.; Bahk, J. J.; Weber, M. E.; France-Lanord, C.; Klaus, A.

2016-12-01

IODP Expedition 354 to the Bengal Fan drilled a 320 km long e-W transect at 8°N with 7 drill sites, fully covering the uppermost 150-200 meters of fan deposits at distances of 50 km, originating from Himalayan mountain ranges and the Ganges-Brahmaputra river system. A major goal of this transect approach was to ensure a continuous record of turbiditic material delivered over the last appx. 1 million year, considering frequent longitudinal depocenter shifts of the active channel. By extensively utilizing the new half-APC coring technique, high quality and high recovery cores could be retrieved representing a wide range of grain sizes from hemipelagic deposits through clay rich turbidites to coarse silt and sandy units. Up to medium sand grain sizes were retrieved within the basal units of levees, which correspond to high-reflectivity units in high-resolution multichannel seismic profiles. Finely laminated sections with mm to cm-thick turbidites represents levee formations. At Site U1453 for example, core logging and downhole logging data confirm the representative sampling based on a very good match of several physical property data sets. An expanded section was cored at Site U1454, where the presumably currently active channel has built a levee, which likely represents major sediment supply within the last 30 kyr. A spatial grid of seismic and echosounder data in the vicinity of the active channel reveals a high spatial variability in sedimentation rates and distinct depocenter shifts in response to changes in channel geometry. Site U1452 has provided a full record a levee growth including interlevee sedimentation, sandy basal units characterized by a lobe formation, and a pronounced fining upward trend following the phase of channel erosion and levee builtup. From all sites, detailed comparisons of physical and sedimentological shipboard results with seismic data will be presented. Expedition 354 has provided a unique sample and data set to better understand fan deposition and channel-levee growth including silt and sand grain sizes. It will also provide valuable constraints on the volume, nature and composition of suspension flows contributing to fan growth in the Middle Bengal Fan.

High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI

NASA Astrophysics Data System (ADS)

Yazdan-Shahmorad, Azadeh; Kipke, Daryl R.; Lehmkuhle, Mark J.

2013-12-01

Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time-frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V-VI) following CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures of unit activity observed as changes in high gamma power in ECoGs suggest that future cortical stimulation studies could rely on less invasive feedback schemes that incorporate surface stimulation with ECoG reporting of stimulation efficacy.

Scales of columnar jointing in igneous rocks: field measurements and controlling factors

NASA Astrophysics Data System (ADS)

Hetényi, György; Taisne, Benoît; Garel, Fanny; Médard, Étienne; Bosshard, Sonja; Mattsson, Hannes B.

2012-03-01

Columnar jointing is a common feature of solidified lavas, sills and dikes, but the factors controlling the characteristic stoutness of columns remain debated, and quantitative field observations are few in number. In this paper, we provide quantitative measurements on sizing of columnar joint sets and our assessment of the principal factors controlling it. We focus on (1) chemistry, as it is the major determinant of the physical (mechanical and thermal) properties of the lava, and (2) geology, as it influences the style of emplacement and lava geometry, setting boundary conditions for the cooling process and the rate of heat loss. In our analysis, we cover lavas with a broad range of chemical compositions (from basanite to phonolite, for six of which we provide new geochemical analyses) and of geological settings. Our field measurements cover 50 columnar jointing sites in three countries. We provide reliable, manually digitized data on the size of individual columns and focus the mathematical analysis on their geometry (23,889 data on side length, of which 17,312 are from full column sections and 3,033 data on cross-sectional area and order of polygonality). The geometrical observations show that the variation in characteristic size of columns between different sites exceeds one order of magnitude (side length ranging from 8 to 338 cm) and that the column-bounding polygons' average order is less than 6. The network of fractures is found to be longer than required by a minimum-energy hexagonal configuration, indicating a non-equilibrium, geologically quick process. In terms of the development and characteristic sizing of columnar joint sets, our observations suggest that columns are the result of an interplay between the geological setting of emplacement and magma chemistry. When the geological setting constrains the geometry of the emplaced body, it exerts a stronger control on characteristic column stoutness. At unconstrained geometries (e.g. unconfined lava flows), chemistry plays the major role, resulting in stouter columns in felsic lavas and slenderer columns in mafic lavas.

Quaternary geomorphology and modern coastal development in response to an inherent geologic framework: An example from Charleston, South Carolina

USGS Publications Warehouse

Harris, M.S.; Gayes, P.T.; Kindinger, J.L.; Flocks, J.G.; Krantz, D.E.; Donovan, P.

2005-01-01

Coastal landscapes evolve over wide-ranging spatial and temporal scales in response to physical and biological pro-cesses that interact with a wide range of variables. To develop better predictive models for these dynamic areas, we must understand the influence of these variables on coastal morphologies and ultimately how they influence coastal processes. This study defines the influence of geologic framework variability on a classic mixed-energy coastline, and establishes four categorical scales of spatial and temporal influence on the coastal system. The near-surface, geologic framework was delineated using high-resolution seismic profiles, shallow vibracores, detailed geomorphic maps, historical shorelines, aerial photographs, and existing studies, and compared to the long- and short-term development of two coastal compartments near Charleston, South Carolina. Although it is clear that the imprint of a mixed-energy tidal and wave signal (basin-scale) dictates formation of drumstick barriers and that immediate responses to wave climate are dramatic, island size, position, and longer-term dynamics are influenced by a series of inherent, complex near-surface stratigraphic geometries. Major near-surface Tertiary geometries influence inlet placement and drainage development (island-scale) through multiple interglacial cycles and overall channel morphology (local-scale). During the modern marine transgression, the halo of ebb-tidal deltas greatly influence inlet region dynamics, while truncated beach ridges and exposed, differentially erodable Cenozoic deposits in the active system influence historical shoreline dynamics and active shoreface morphologies (blockscale). This study concludes that the mixed-energy imprint of wave and tide theories dominates general coastal morphology, but that underlying stratigraphic influences on the coast provide site-specific, long-standing imprints on coastal evolution.

Rational Design, Synthesis and Evaluation of First Generation Inhibitors of the Giardia lamblia Fructose-1,6-biphosphate Aldolase

PubMed Central

Li, Zhimin; Liu, Zhengang; Cho, Dae Won; Zou, Jiwen; Gong, Maozhen; Breece, Robert M.; Galkin, Andrey; Li, Ling; Zhao, Hong; Maestas, Gabriel D.; Tierney, David L.; Herzberg, Osnat; Dunaway-Mariano, Debra; Mariano, Patrick S.

2011-01-01

Inhibitors of the Giardia lamblia fructose 1,6-bisphosphate aldolase (GlFBPA), which transforms fructose 1,6-bisphosphate (FBP) to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, were designed based on 3-hydroxy-2-pyridone and 1,2-dihydroxypyridine scaffolds that position two negatively charged tetrahedral groups for interaction with substrate phosphate binding residues, a hydrogen bond donor to the catalytic Asp83, and a Zn2+ binding group. The inhibition activities for the GlFBPA catalyzed reaction of FBP of the prepared alkyl phosphonate/phosphate substituted 3-hydroxy-2-pyridinones and a dihydroxypyridine were determined. The 3-hydroxy-2-pyridone inhibitor 8 was found to bind to GlFBPA with an affinity (Ki = 14 μM) that is comparable to that of FBP (Km = 2 μM) or its inert analog TBP (Ki = 1 μM). The X-ray structure of the GlFBPA-inhibitor 8 complex (2.3 Å) shows that 8 binds to the active site in the manner predicted by in silico docking with the exception of coordination with Zn2+. The observed distances and orientation of the pyridone ring O=C-C-OH relative to Zn2+ are not consistent with a strong interaction. To determine if Zn2+coordination occurs in the GlFBPA-inhibitor 8 complex in solution, EXAFS spectra were measured. A four coordinate geometry comprised of the three enzyme histidine ligands and an oxygen atom from the pyridone ring O=C-C-OH was indicated. Analysis of the Zn2+ coordination geometries in recently reported structures of class II FBPAs suggests that strong Zn2+ coordination is reserved for the enediolate-like transition state, accounting for minimal contribution of Zn2+ coordination to binding of 8 to GlFBPA. PMID:21333622

A Density Functional Study of Atomic Hydrogen and Oxygen Chemisorptions on the (0001) Surface of Double Hexagonal Close Packed Americium

NASA Astrophysics Data System (ADS)

Dholabhai, Pratik; Atta-Fynn, Raymond; Ray, Asok

2008-03-01

Ab initio total energy calculations within the framework of density functional theory have been performed for atomic hydrogen and oxygen chemisorptions on the (0001) surface of double hexagonal packed americium using a full-potential all-electron linearized augmented plane wave plus local orbitals (FLAPW+lo) method. The three-fold hollow hcp site was found to be the most stable site for H adsorption, while the two-fold bridge adsorption site was found to be the most stable site for O adsorption. Chemisorption energies and adsorption geometries for different adsorption sites will be discussed. The change in work functions, magnetic moments, partial charges inside muffin-tins, difference charge density distributions and density of states for the bare Am slab and the Am slab after adsorption of the adatom will be discussed. The implications of chemisorption on Am 5f electron localization-delocalization will also be discussed.

Geometries and Electronic Structures of Cyanide Adducts of the Non-Heme Iron Active Site of Superoxide Reductases: Vibrational and ENDOR Studies†

PubMed Central

Clay, Michael D.; Yang, Tran-Chin; Jenney, Francis E.; Kung, Irene Y.; Cosper, Christopher A.; Krishnan, Rangan; Kurtz, Donald M.; Adams, Michael W.W.; Hoffman, Brian M.; Johnson, Michael K.

2008-01-01

We have added cyanide to oxidized 1Fe and 2Fe superoxide reductase (SOR) as a surrogate for the putative ferric-(hydro)peroxo intermediate in the reaction of the enzymes with superoxide, and have used vibrational and ENDOR spectroscopies to study the properties of the active-site paramagnetic iron center. Addition of cyanide changes the active-site iron center in oxidized SOR from rhombic high-spin ferric (S = 5/2) to axial-like low-spin ferric (S = 1/2). Low-temperature resonance Raman and ENDOR data show that the bound cyanide adopts three distinct conformations in Fe(III)-CN SOR. On the basis of 13CN, C15N, and 13C15N isotope shifts of the Fe–CN stretching/Fe–C–N bending modes, resonance Raman studies of 1Fe-SOR indicate one near-linear conformation (Fe–C–N angle ∼175°) and two distinct bent conformations (Fe–C–N angles < 140°). FTIR studies of 1Fe-SOR at ambient temperatures reveals three bound C–N stretching frequencies in the oxidized (ferric) state and one in the reduced (ferrous) state indicating that the conformational heterogeneity in cyanide binding is a characteristic of the ferric state and is not caused by freezing-in of conformational substates at low temperature. 13C-ENDOR spectra for the 13CN-bound ferric active sites in both 1Fe- and 2Fe-SORs also show three well-resolved Fe–C–N conformations. Analysis of the 13C hyperfine tensors for the three substates of the 2Fe-SOR within a simple heuristic model for the Fe-C bonding gives values for the Fe–C–N angles in the three substates of ca. 123° (C3), 133° (C2), taking a reference value from vibrational studies of 175° (C1 species). Resonance Raman and ENDOR studies of SOR variants, in which the conserved glutamate and lysine residues in a flexible loop above the substrate binding pocket have been individually replaced by alanine, indicate that the side chains of these two residues are not involved in direct interaction with bound cyanide. The implications of these results for understanding the mechanism of SOR are discussed. PMID:16401073

On the Use of CAD-Native Predicates and Geometry in Surface Meshing

NASA Technical Reports Server (NTRS)

Aftosmis, M. J.

1999-01-01

Several paradigms for accessing CAD geometry during surface meshing for CFD are discussed. File translation, inconsistent geometry engines and non-native point construction are all identified as sources of non-robustness. The paper argues in favor of accessing CAD parts and assemblies in their native format, without translation, and for the use of CAD-native predicates and constructors in surface mesh generation. The discussion also emphasizes the importance of examining the computational requirements for exact evaluation of triangulation predicates during surface meshing. The native approach is demonstrated through an algorithm for the generation of closed manifold surface triangulations from CAD geometry. CAD parts and assemblies are used in their native format, and a part's native geometry engine is accessed through a modeler-independent application programming interface (API). In seeking a robust and fully automated procedure, the algorithm is based on a new physical space manifold triangulation technique specially developed to avoid robustness issues associated with poorly conditioned mappings. In addition, this approach avoids the usual ambiguities associated with floating-point predicate evaluation on constructed coordinate geometry in a mapped space. The technique is incremental, so that each new site improves the triangulation by some well defined quality measure. The algorithm terminates after achieving a prespecified measure of mesh quality and produces a triangulation such that no angle is less than a given angle bound, a or greater than pi - 2alpha. This result also sets bounds on the maximum vertex degree, triangle aspect-ratio and maximum stretching rate for the triangulation. In addition to the output triangulations for a variety of CAD parts, the discussion presents related theoretical results which assert the existence of such an angle bound, and demonstrate that maximum bounds of between 25 deg and 30 deg may be achieved in practice.

Informal Geometry for Young Children; Cambridge Conference on School Mathematics; Feasibility Study No. 34b.

ERIC Educational Resources Information Center

Walter, Marion

These materials were written with the aim of reflecting the thinking of The Cambridge Conference on School Mathematics (CCSM) regarding the goals and objectives for school mathematics. These materials are intended to provide children with a variety of informal activities in intuitive geometry in the elementary school. Opportunities are provided…

Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

PubMed

Biasetti, Jacopo; Hussain, Fazle; Gasser, T Christian

2011-10-07

Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the λ(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.

Quantitative analysis of the patella following the harvest of a quadriceps tendon autograft with a bone block.

PubMed

Ferrer, Gerald A; Miller, R Matthew; Murawski, Christopher D; Tashman, Scott; Irrgang, James J; Musahl, Volker; Fu, Freddie H; Debski, Richard E

2016-09-01

The objective of this study was to determine parameters associated with patellar fracture after quadriceps tendon autograft harvest. Thirteen non-fractured and five fractured patella surface models were created based on patient data obtained from a prospective randomized clinical trial in order to assess geometric parameters and bending stress. Measurements that describe the bone block harvest site geometry were used to calculate three normalized parameters. The relative depth parameter describes the thickness of the bone block harvest site with respect to the thickness of the patella at the harvest site. The asymmetry parameter defines the medial-lateral location of the bone bock harvest site. The normalized bending stress parameter assesses the bending stress experienced by the remaining bone beneath the bone block harvest site. The relative depth of the bone block harvest site in the non-fractured patellae was 27 ± 12 % and for the fractured patellae was 42 ± 14 % (p < 0.05). With a value <1 indicating a more lateral location of the harvest site, asymmetry for the non-fractured group was 1.0 ± 0.5 and 0.7 ± 0.4 for the fractured group (n.s.). The maximum bending stress experienced by the non-fractured patellae was (1.8 × 10(-3) ± 1.3 × 10(-3)) mm(-3) × M and for the fractured patellae was over three times greater (6.3 × 10(-3) ± 3.7 × 10(-3)) mm(-3) × M (p < 0.05). Based on the non-uniform geometry of the patella, an emphasis should be made on harvesting a standard percentage of patella thickness rather than a fixed depth. In order to minimize the incidence of a patellar fracture, bone blocks should not be taken laterally and should not exceed 30 % of the total patella thickness at the harvest site.

Ideal versus real: simulated annealing of experimentally derived and geometric platinum nanoparticles

NASA Astrophysics Data System (ADS)

Ellaby, Tom; Aarons, Jolyon; Varambhia, Aakash; Jones, Lewys; Nellist, Peter; Ozkaya, Dogan; Sarwar, Misbah; Thompsett, David; Skylaris, Chris-Kriton

2018-04-01

Platinum nanoparticles find significant use as catalysts in industrial applications such as fuel cells. Research into their design has focussed heavily on nanoparticle size and shape as they greatly influence activity. Using high throughput, high precision electron microscopy, the structures of commercially available Pt catalysts have been determined, and we have used classical and quantum atomistic simulations to examine and compare them with geometric cuboctahedral and truncated octahedral structures. A simulated annealing procedure was used both to explore the potential energy surface at different temperatures, and also to assess the effect on catalytic activity that annealing would have on nanoparticles with different geometries and sizes. The differences in response to annealing between the real and geometric nanoparticles are discussed in terms of thermal stability, coordination number and the proportion of optimal binding sites on the surface of the nanoparticles. We find that annealing both experimental and geometric nanoparticles results in structures that appear similar in shape and predicted activity, using oxygen adsorption as a measure. Annealing is predicted to increase the catalytic activity in all cases except the truncated octahedra, where it has the opposite effect. As our simulations have been performed with a classical force field, we also assess its suitability to describe the potential energy of such nanoparticles by comparing with large scale density functional theory calculations.

Rational geometrical engineering of palladium sulfide multi-arm nanostructures as a superior bi-functional electrocatalyst.

PubMed

Nandan, R; Nanda, K K

2017-08-31

Geometrical tunability offers sharp edges and an open-armed structure accompanied with a high electrochemical active surface area to ensure the efficient and effective utilization of materials by exposing the electrochemical active sites for facile accessibility of reactant species. Herein, we report a one-step, single-pot, surfactant-free, electroless, and economic route to synthesize palladium sulfide nanostructures with different geometries at mild temperatures and their catalytic properties towards the oxygen reduction reaction (ORR) and methanol electro-oxidation (MOR). For ORR, the positive on-set, half wave potentials, smaller Tafel slope, high electrochemical active surface area, large roughness factor, and better cyclic stability of the proposed nanostructures as compared to those of the commercial state-of-the-art Pt-C/PdS catalysts suggest their superiority in an alkaline medium. In addition, high mass activity (J f ∼ 715 mA mg -1 ), in comparison with that of the commercial state-of-the-art Pt-C/PdS catalysts (J f ∼ 138/41 mA mg -1 , respectively), and high J f /J b (1.52) along with the superior operational stability of the multi-arm palladium sulfide nanostructures towards MOR advocates the bi-functional behavior of the catalyst and its potential as a promising Pt-free anode/cathode electrocatalyst in fuel cells.

Active faulting at Delphi, Greece: Seismotectonic remarks and a hypothesis for the geologic environment of a myth

NASA Astrophysics Data System (ADS)

Piccardi, Luigi

2000-07-01

Historical data are fundamental to the understanding of the seismic history of an area. At the same time, knowledge of the active tectonic processes allows us to understand how earthquakes have been perceived by past cultures. Delphi is one of the principal archaeological sites of Greece, the main oracle of Apollo. It was by far the most venerated oracle of the Greek ancient world. According to tradition, the mantic proprieties of the oracle were obtained from an open chasm in the earth. Delphi is directly above one of the main antithetic active faults of the Gulf of Corinth Rift, which bounds Mount Parnassus to the south. The geometry of the fault and slip-parallel lineations on the main fault plane indicate normal movement, with minor right-lateral slip component. Combining tectonic data, archaeological evidence, historical sources, and a reexamination of myths, it appears that the Helice earthquake of 373 B.C. ruptured not only the master fault of the Gulf of Corinth Rift at Helice, but also the antithetic fault at Delphi, similarly to the Corinth earthquake of 1981. Moreover, the presence of an active fault directly below the temples of the oldest sanctuary suggests that the mythological oracular chasm might well have been an ancient tectonic surface rupture.

Crystal Structure of a Human IκB Kinase β Asymmetric Dimer

PubMed Central

Liu, Shenping; Misquitta, Yohann R.; Olland, Andrea; Johnson, Mark A.; Kelleher, Kerry S.; Kriz, Ron; Lin, Laura L.; Stahl, Mark; Mosyak, Lidia

2013-01-01

Phosphorylation of inhibitor of nuclear transcription factor κB (IκB) by IκB kinase (IKK) triggers the degradation of IκB and migration of cytoplasmic κB to the nucleus where it promotes the transcription of its target genes. Activation of IKK is achieved by phosphorylation of its main subunit, IKKβ, at the activation loop sites. Here, we report the 2.8 Å resolution crystal structure of human IKKβ (hIKKβ), which is partially phosphorylated and bound to the staurosporine analog K252a. The hIKKβ protomer adopts a trimodular structure that closely resembles that from Xenopus laevis (xIKKβ): an N-terminal kinase domain (KD), a central ubiquitin-like domain (ULD), and a C-terminal scaffold/dimerization domain (SDD). Although hIKKβ and xIKKβ utilize a similar dimerization mode, their overall geometries are distinct. In contrast to the structure resembling closed shears reported previously for xIKKβ, hIKKβ exists as an open asymmetric dimer in which the two KDs are further apart, with one in an active and the other in an inactive conformation. Dimer interactions are limited to the C-terminal six-helix bundle that acts as a hinge between the two subunits. The observed domain movements in the structures of IKKβ may represent trans-phosphorylation steps that accompany IKKβ activation. PMID:23792959

In situ electrochemical high-energy X-ray diffraction using a capillary working electrode cell geometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, Matthias J.; Bedford, Nicholas M.; Jiang, Naisheng

The ability to generate new electrochemically active materials for energy generation and storage with improved properties will likely be derived from an understanding of atomic-scale structure/function relationships during electrochemical events. Here, the design and implementation of a new capillary electrochemical cell designed specifically forin situhigh-energy X-ray diffraction measurements is described. By increasing the amount of electrochemically active material in the X-ray path while implementing low-Zcell materials with anisotropic scattering profiles, an order of magnitude enhancement in diffracted X-ray signal over traditional cell geometries for multiple electrochemically active materials is demonstrated. This signal improvement is crucial for high-energy X-ray diffraction measurementsmore » and subsequent Fourier transformation into atomic pair distribution functions for atomic-scale structural analysis. As an example, clear structural changes in LiCoO 2under reductive and oxidative conditions using the capillary cell are demonstrated, which agree with prior studies. Accurate modeling of the LiCoO 2diffraction data using reverse Monte Carlo simulations further verifies accurate background subtraction and strong signal from the electrochemically active material, enabled by the capillary working electrode geometry.« less

Pleural Puncture that Excludes the Ablation Zone Decreases the Risk of Pneumothorax after Percutaneous Microwave Ablation in Porcine Lung

PubMed Central

Lee, Kyungmouk Steve; Takaki, Haruyuki; Yarmohammadi, Hooman; Srimathveeravalli, Govindarajan; Luchins, Kerith; Monette, Sébastien; Nair, Sreejit; Kishore, Sirish; Erinjeri, Joseph P.

2017-01-01

Purpose To test the hypothesis that the geometry of probe placement with respect to the pleural puncture site affects the risk of pneumothorax after microwave (MW) ablation in the lung. Materials and Methods Computed tomography–guided MW ablation of the lung was performed in 8 swine under general anesthesia and mechanical ventilation. The orientation of the 17-gauge probe was either perpendicular (90°) or parallel (< 30°) with respect to the pleural puncture site, and the ablation power was 30 W or 65 W for 5 minutes. After MW ablation, swine were euthanized, and histopathologic changes were assessed. Frequency and factors affecting pneumothorax were evaluated by multivariate analysis. Results Among 62 lung MW ablations, 13 (21%) pneumothoraces occurred. No statistically significant difference was noted in the rate of pneumothorax between the perpendicular and the parallel orientations of the probe (31% vs 14%; odds ratio [OR], 2.8; P = .11). The pneumothorax rate was equal for 65-W and 30-W ablation powers (21% and 21%; OR, 1.0; P = .94). Under multivariate analysis, 2 factors were independent positive predictors of pneumothorax: ablation zone inclusive of pleural insertion point (OR, 7.7; P = .02) and time since intubation (hours) (OR, 2.7; P = .02). Conclusions Geometries where the pleural puncture site excluded the ablation zone decreased pneumothorax in swine undergoing MW ablation in the lung. Treatment planning to ensure that the pleural puncture site excludes the subsequent ablation zone may reduce the rate of pneumothorax in patients undergoing MW ablation in the lung. PMID:25753501

Fission gas in thoria

NASA Astrophysics Data System (ADS)

Kuganathan, Navaratnarajah; Ghosh, Partha S.; Galvin, Conor O. T.; Arya, Ashok K.; Dutta, Bijon K.; Dey, Gautam K.; Grimes, Robin W.

2017-03-01

The fission gases Xe and Kr, formed during normal reactor operation, are known to degrade fuel performance, particularly at high burn-up. Using first-principles density functional theory together with a dispersion correction (DFT + D), in ThO2 we calculate the energetics of neutral and charged point defects, the di-vacancy (DV), different neutral tri-vacancies (NTV), the charged tetravacancy (CTV) defect cluster geometries and their interaction with Xe and Kr. The most favourable incorporation point defect site for Xe or Kr in defective ThO2 is the fully charged thorium vacancy. The lowest energy NTV in larger supercells of ThO2 is NTV3, however, a single Xe atom is most stable when accommodated within a NTV1. The di-vacancy (DV) is a significantly less favoured incorporation site than the NTV1 but the CTV offers about the same incorporation energy. Incorporation of a second gas atom in a NTV is a high energy process and more unfavourable than accommodation within an existing Th vacancy. The bi-NTV (BNTV) cluster geometry studied will accommodate one or two gas atoms with low incorporation energies but the addition of a third gas atom incurs a high energy penalty. The tri-NTV cluster (TNTV) forms a larger space which accommodates three gas atoms but again there is a penalty to accommodate a fourth gas atom. By considering the energy to form the defect sites, solution energies were generated showing that in ThO2-x the most favourable solution equilibrium site is the NTV1 while in ThO2 it is the DV.

Testing high resolution numerical models for analysis of contaminant storage and release from low permeability zones

NASA Astrophysics Data System (ADS)

Chapman, Steven W.; Parker, Beth L.; Sale, Tom C.; Doner, Lee Ann

2012-08-01

It is now widely recognized that contaminant release from low permeability zones can sustain plumes long after primary sources are depleted, particularly for chlorinated solvents where regulatory limits are orders of magnitude below source concentrations. This has led to efforts to appropriately characterize sites and apply models for prediction incorporating these effects. A primary challenge is that diffusion processes are controlled by small-scale concentration gradients and capturing mass distribution in low permeability zones requires much higher resolution than commonly practiced. This paper explores validity of using numerical models (HydroGeoSphere, FEFLOW, MODFLOW/MT3DMS) in high resolution mode to simulate scenarios involving diffusion into and out of low permeability zones: 1) a laboratory tank study involving a continuous sand body with suspended clay layers which was 'loaded' with bromide and fluorescein (for visualization) tracers followed by clean water flushing, and 2) the two-layer analytical solution of Sale et al. (2008) involving a relatively simple scenario with an aquifer and underlying low permeability layer. All three models are shown to provide close agreement when adequate spatial and temporal discretization are applied to represent problem geometry, resolve flow fields and capture advective transport in the sands and diffusive transfer with low permeability layers and minimize numerical dispersion. The challenge for application at field sites then becomes appropriate site characterization to inform the models, capturing the style of the low permeability zone geometry and incorporating reasonable hydrogeologic parameters and estimates of source history, for scenario testing and more accurate prediction of plume response, leading to better site decision making.

Synthesis, spectroscopic, anticancer, antibacterial and antifungal studies of Ni(II) and Cu(II) complexes with hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene

NASA Astrophysics Data System (ADS)

Chandra, Sulekh; Vandana; Kumar, Suresh

2015-01-01

Schiff's base ligand(L) hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene] and its metal complexes have been synthesized and characterized by elemental analysis, molar conductance, various spectroscopic techniques such as electronic, IR, 1H NMR, mass, EPR. Molar conductance of complexes in DMF solution corresponds to non-electrolyte. Complexes have general composition [M(L)2X2], where M = Ni(II) and Cu(II), X = Cl-, NO3-, CH3COO- and ½SO42-. On the basis of above spectral studies, an octahedral geometry has been assigned for Ni(II) complexes and tetragonal geometry for Cu(II) complexes except [Cu(L)2SO4] which possesses five coordinated trigonal bipyramidal geometry. These metal complexes were also tested for their anticancer, antibacterial and antifungal activities to assess their inhibition potential. Anticancer activity of ligand and its metal complexes were evaluated using SRB fluorometric assay and Adriamycin (ADR) was applied as positive control. Schiff's base ligand and its metal complexes were screened for their antibacterial and antifungal activity against Escherichia coli, Bacillus cereus and Aspergillus niger, Aspergillus flavus, respectively. Kirby-Bauer single disk susceptibility test was used for antibacterial activity and well diffusion method for antifungal activity of the compounds on the used fungi.

Theoretical background of retrieving Green's function by cross-correlation: one-dimensional case

NASA Astrophysics Data System (ADS)

Nakahara, Hisashi

2006-06-01

Recently, an assertion has been verified experimentally and theoretically that Green's function between two receivers can be reproduced by cross-correlating the records at the receivers. In this paper, we have theoretically proved the assertion for 1-D media with the free surface by using the Thomson-Haskell matrix method. Strictly speaking, one side of the cross-correlation between records at two receivers is the convolution between Green's function and the autocorrelation function of the source wavelet. This study extends the geometry considered by Claerbout to two receivers vertically apart, and is a special case of the proof by Wapenaar et al. which dealt with 3-D arbitrary inhomogeneous media. However, a simple geometry in 1-D problems enables us to make the proof without any approximations and to better understand the physical background with more ease. That is the main advantage of this study. Though a 1-D geometry seems far from reality, it may be sufficient if an appropriate combination of receivers and earthquakes is selected. In fact, such a geometry is often seen in seismological observations by a vertical array of seismographs in the shallow subsurface. Therefore, we refer to a possibility that the proof in this paper is applied to the estimation of site amplification factors by using records of a vertical seismographic array.

Improved Microseismicity Detection During Newberry EGS Stimulations

DOE Data Explorer

Templeton, Dennise

2013-10-01

Effective enhanced geothermal systems (EGS) require optimal fracture networks for efficient heat transfer between hot rock and fluid. Microseismic mapping is a key tool used to infer the subsurface fracture geometry. Traditional earthquake detection and location techniques are often employed to identify microearthquakes in geothermal regions. However, most commonly used algorithms may miss events if the seismic signal of an earthquake is small relative to the background noise level or if a microearthquake occurs within the coda of a larger event. Consequently, we have developed a set of algorithms that provide improved microearthquake detection. Our objective is to investigate the microseismicity at the DOE Newberry EGS site to better image the active regions of the underground fracture network during and immediately after the EGS stimulation. Detection of more microearthquakes during EGS stimulations will allow for better seismic delineation of the active regions of the underground fracture system. This improved knowledge of the reservoir network will improve our understanding of subsurface conditions, and allow improvement of the stimulation strategy that will optimize heat extraction and maximize economic return.

Improved Microseismicity Detection During Newberry EGS Stimulations

DOE Data Explorer

Templeton, Dennise

2013-11-01

Effective enhanced geothermal systems (EGS) require optimal fracture networks for efficient heat transfer between hot rock and fluid. Microseismic mapping is a key tool used to infer the subsurface fracture geometry. Traditional earthquake detection and location techniques are often employed to identify microearthquakes in geothermal regions. However, most commonly used algorithms may miss events if the seismic signal of an earthquake is small relative to the background noise level or if a microearthquake occurs within the coda of a larger event. Consequently, we have developed a set of algorithms that provide improved microearthquake detection. Our objective is to investigate the microseismicity at the DOE Newberry EGS site to better image the active regions of the underground fracture network during and immediately after the EGS stimulation. Detection of more microearthquakes during EGS stimulations will allow for better seismic delineation of the active regions of the underground fracture system. This improved knowledge of the reservoir network will improve our understanding of subsurface conditions, and allow improvement of the stimulation strategy that will optimize heat extraction and maximize economic return.

Three-dimensional analysis of flow-chemical interaction within a single square channel of a lean NO x trap catalyst.

PubMed

Fornarelli, Francesco; Dadduzio, Ruggiero; Torresi, Marco; Camporeale, Sergio Mario; Fortunato, Bernardo

2018-02-01

A fully 3D unsteady Computational Fluid Dynamics (CFD) approach coupled with heterogeneous reaction chemistry is presented in order to study the behavior of a single square channel as part of a Lean [Formula: see text] Traps. The reliability of the numerical tool has been validated against literature data considering only active BaO site. Even though the input/output performance of such catalyst has been well known, here the spatial distribution within a single channel is investigated in details. The square channel geometry influences the flow field and the catalyst performance being the flow velocity distribution on the cross section non homogeneous. The mutual interaction between the flow and the active catalyst walls influences the spatial distribution of the volumetric species. Low velocity regions near the square corners and transversal secondary flows are shown in several cross-sections along the streamwise direction at different instants. The results shed light on the three-dimensional characteristic of both the flow field and species distribution within a single square channel of the catalyst with respect to 0-1D approaches.

Comparison of NBG-18, NBG-17, IG-110 and IG-11 oxidation kinetics in air

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jo Jo; Ghosh, Tushar K.; Loyalka, Sudarshan K.

In this paper, the oxidation rates of several nuclear-grade graphites, NBG-18, NBG-17, IG-110 and IG-11, were measured in air using thermogravimetry. Kinetic parameters and oxidation behavior for each grade were compared by coke type, filler grain size and microstructure. The thickness of the oxidized layer for each grade was determined by layer peeling and direct density measurements. The results for NBG-17 and IG-11 were compared with those available in the literature and our recently reported results for NBG-18 and IG-110 oxidation in air. The finer-grained graphites IG-110 and IG-11 were more oxidized than medium-grained NBG-18 and NBG-17 because of deepermore » oxidant penetration, higher porosity and higher probability of available active sites. Variation in experimental conditions also had a marked effect on the reported kinetic parameters by several studies. Finally, kinetic parameters such as activation energy and transition temperature were sensitive to air flow rates as well as sample size and geometry.« less

Comparison of NBG-18, NBG-17, IG-110 and IG-11 oxidation kinetics in air

DOE PAGES

Lee, Jo Jo; Ghosh, Tushar K.; Loyalka, Sudarshan K.

2017-12-14

In this paper, the oxidation rates of several nuclear-grade graphites, NBG-18, NBG-17, IG-110 and IG-11, were measured in air using thermogravimetry. Kinetic parameters and oxidation behavior for each grade were compared by coke type, filler grain size and microstructure. The thickness of the oxidized layer for each grade was determined by layer peeling and direct density measurements. The results for NBG-17 and IG-11 were compared with those available in the literature and our recently reported results for NBG-18 and IG-110 oxidation in air. The finer-grained graphites IG-110 and IG-11 were more oxidized than medium-grained NBG-18 and NBG-17 because of deepermore » oxidant penetration, higher porosity and higher probability of available active sites. Variation in experimental conditions also had a marked effect on the reported kinetic parameters by several studies. Finally, kinetic parameters such as activation energy and transition temperature were sensitive to air flow rates as well as sample size and geometry.« less

Radio- and photoluminescence properties of Ce/Tb co-doped glasses with huntite-like composition

NASA Astrophysics Data System (ADS)

Lorenzi, Roberto; Golubev, Nikita V.; Ziaytdinova, Mariyam Z.; Jarý, Vítězslav; Babin, Vladimir; Malashkevich, Georgii E.; Paleari, Alberto; Sigaev, Vladimir N.; Fasoli, Mauro; Nikl, Martin

2018-04-01

Optical properties of yttria-aluminoborate (YAB) glasses with general composition 10(CexTbyY(1-x-y))-30Al2O3-60B2O3 are investigated and compared with data available on YAB crystals with huntite-like structure. Ce doped samples show optical features ascribable to preferential location of rare earth ions in sites with specific geometry similar to that observed in crystalline structures. Samples prepared with Tb ions as emission activator and Ce ions as sensitizer have been studied within the framework of non-radiative energy transfer. The resulting Förster radius is of 4.6 ± 0.5 Å comparable with that observed in Ce/Tb co-doped YAl3(BO3)4 crystals. The investigated materials possess radio- and photoluminescence emission efficiencies and performances comparable to that of crystalline counterparts with the advantage of having easiness of preparation and workability typical of glassy systems.

Columnar shifts as symmetry-breaking degrees of freedom in molecular perovskites

NASA Astrophysics Data System (ADS)

Boström, Hanna L. B.; Hill, Joshua A.; Goodwin, Andrew L.

We introduce columnar shifts---collective rigid-body translations---as a structural degree of freedom relevant to the phase behaviour of molecular perovskites ABX$_{\\textrm3}$ (X = molecular anion). Like the well-known octahedral tilts of conventional perovskites, shifts also preserve the octahedral coordination geometry of the B-site cation in molecular perovskites, and so are predisposed to influencing the low-energy dynamics and displacive phase transitions of these topical systems. We present a qualitative overview of the interplay between shift activation and crystal symmetry breaking, and introduce a generalised terminology to allow characterisation of simple shift distortions, drawing analogy to the "Glazer notation" for octahedral tilts. We apply our approach to the interpretation of a representative selection of azide and formate perovskite structures, and discuss the implications for functional exploitation of shift degrees of freedom in negative thermal expansion materials and hybrid ferroelectrics.

Design and construction of pulsed neutron diagnostic system for plasma focus device (SBUPF1).

PubMed

Moghadam, Sahar Rajabi; Davani, Fereydoon Abbasi

2010-07-01

In this paper, two designs of pulsed neutron counter structure are introduced. To increase the activation counter efficiency, BC-400 plastic scintillator plates along with silver foils are utilized. Rectangular cubic and cylindrical geometries for activation counter cell are modeled using MCNP4C code. Eventually, an optimum length of 14 cm is calculated for the detector cell and optimum numbers of 20 silver foils for rectangular cubic geometry and ten foils for cylindrical geometry have been acquired. Due to the high cost of cutting, polishing of plastics, and etc., the rectangular cubic design is found to be more economical than the other design. In order to examine the functionality and ensure the detector output and corresponding designing, neutron yield of a 2.48 kJ plasma focus device (SBUPF1) in 8 mbar pressure with removal source method for calibration was measured (3.71+/-0.32)x10(7) neutrons per shot.

A Global Survey of Deep Underground Facilities; Examples of Geotechnical and Engineering Capabilities, Achievements, Challenges (Mines, Shafts, Tunnels, Boreholes, Sites and Underground Facilities for Nuclear Waste and Physics R&D): A Guide to Interactive Global Map Layers, Table Database, References and Notes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tynan, Mark C.; Russell, Glenn P.; Perry, Frank V.

These associated tables, references, notes, and report present a synthesis of some notable geotechnical and engineering information used to create four interactive layer maps for selected: 1) deep mines and shafts; 2) existing, considered or planned radioactive waste management deep underground studies or disposal facilities 3) deep large diameter boreholes, and 4) physics underground laboratories and facilities from around the world. These data are intended to facilitate user access to basic information and references regarding “deep underground” facilities, history, activities, and plans. In general, the interactive maps and database provide each facility’s approximate site location, geology, and engineered features (e.g.:more » access, geometry, depth, diameter, year of operations, groundwater, lithology, host unit name and age, basin; operator, management organization, geographic data, nearby cultural features, other). Although the survey is not comprehensive, it is representative of many of the significant existing and historical underground facilities discussed in the literature addressing radioactive waste management and deep mined geologic disposal safety systems. The global survey is intended to support and to inform: 1) interested parties and decision makers; 2) radioactive waste disposal and siting option evaluations, and 3) safety case development applicable to any mined geologic disposal facility as a demonstration of historical and current engineering and geotechnical capabilities available for use in deep underground facility siting, planning, construction, operations and monitoring.« less

National Seismic Network of Georgia

NASA Astrophysics Data System (ADS)

Tumanova, N.; Kakhoberashvili, S.; Omarashvili, V.; Tserodze, M.; Akubardia, D.

2016-12-01

Georgia, as a part of the Southern Caucasus, is tectonically active and structurally complex region. It is one of the most active segments of the Alpine-Himalayan collision belt. The deformation and the associated seismicity are due to the continent-continent collision between the Arabian and Eurasian plates. Seismic Monitoring of country and the quality of seismic data is the major tool for the rapid response policy, population safety, basic scientific research and in the end for the sustainable development of the country. National Seismic Network of Georgia has been developing since the end of 19th century. Digital era of the network started from 2003. Recently continuous data streams from 25 stations acquired and analyzed in the real time. Data is combined to calculate rapid location and magnitude for the earthquake. Information for the bigger events (Ml>=3.5) is simultaneously transferred to the website of the monitoring center and to the related governmental agencies. To improve rapid earthquake location and magnitude estimation the seismic network was enhanced by installing additional 7 new stations. Each new station is equipped with coupled Broadband and Strong Motion seismometers and permanent GPS system as well. To select the sites for the 7 new base stations, we used standard network optimization techniques. To choose the optimal sites for new stations we've taken into account geometry of the existed seismic network, topographic conditions of the site. For each site we studied local geology (Vs30 was mandatory for each site), local noise level and seismic vault construction parameters. Due to the country elevation, stations were installed in the high mountains, no accessible in winter due to the heavy snow conditions. To secure online data transmission we used satellite data transmission as well as cell data network coverage from the different local companies. As a result we've already have the improved earthquake location and event magnitudes. We've analyzed data from each station to calculate signal-to-nose ratio. Comparing these calculations with the ones for the existed stations showed that signal-to-nose ratio for new stations has much better value. National Seismic Network of Georgia is planning to install more stations to improve seismic network coverage.

Results of the first detection units of KM3NeT

NASA Astrophysics Data System (ADS)

Biagi, Simone; KM3NeT Collaboration

2017-12-01

The KM3NeT collaboration is building a km3-scale neutrino telescope in the Mediterranean Sea. The current phase of construction comprises the deep-sea and onshore infrastructures at two installation sites and the installation of the first detection units for the "ARCA" (Astroparticle Research with Cosmics in the Abyss) and "ORCA" (Oscillation Research with Cosmics in the Abyss) detector. At the KM3NeT-It site, 80 km offshore Capo Passero, Italy, the first 32 detection units for the ARCA detector are being installed and at the KM3Net-Fr site, 40 km offshore Toulon, France, 7 detection units for the ORCA detector will be deployed. The second phase of KM3NeT foresees the completion of ARCA for neutrino astronomy at energies above TeV and ORCA for neutrino mass hierarchy studies at energies in the GeV range. The basic element of the KM3NeT detector is the detection unit. In the ARCA geometry, the detection unit is a 700 m long vertical structure hosting 18 optical modules. Each optical module comprises 31 3 in photomultiplier tubes, instruments to monitor environmental parameters, and the electronic boards for the digitisation of the PMT signals and the management of data acquisition. In their final configuration, both ARCA and ORCA will be composed of about 200 detection units. The first detection unit was installed at the KM3NeT-It site in December 2015. It is active and taking data since its connection to the subsea network. The time of arrival and the duration of photon hits on each of the photomultipliers is measured with a time resolution of 1 ns and transferred onshore where the measurements are processed, triggered and stored on disk. A time calibration procedure, based on data recorded with flashing LED beacons during dedicated periods, allows for time synchronisation of the signals from the optical modules at the nanosecond level. In May 2016, an additional detection unit was installed at the KM3NeT-It site. The first results with two active detection units are presented. An update of the detector status and construction is given.

Spectroscopic determination of surface geometry: Ti(0001)-H(1×1)

NASA Astrophysics Data System (ADS)

Feibelman, Peter J.; Hamann, D. R.

1980-02-01

The electronic structure of a Ti(0001) film covered by a monolayer of H is shown to depend strongly on the location of the H atom in the surface unit cell. Best agreement with experiment is found with the H's in three-fold sites, 0.8 a.u. outside the outer Ti layer. In this geometry the H atoms "heal" the surface-the clean Ti(0001) surface state near the Fermi level is removed and the outer layer d-like local density of states (LDOS) is quite similar to that of the interior. Additionally, the calculated work function is 4.0 eV and an H-derived peak in the calculated LDOS appears 5 eV below EF, in agreement with photoemission measurements.

Dynamics and control of state-dependent networks for probing genomic organization

PubMed Central

Rajapakse, Indika; Groudine, Mark; Mesbahi, Mehran

2011-01-01

A state-dependent dynamic network is a collection of elements that interact through a network, whose geometry evolves as the state of the elements changes over time. The genome is an intriguing example of a state-dependent network, where chromosomal geometry directly relates to genomic activity, which in turn strongly correlates with geometry. Here we examine various aspects of a genomic state-dependent dynamic network. In particular, we elaborate on one of the important ramifications of viewing genomic networks as being state-dependent, namely, their controllability during processes of genomic reorganization such as in cell differentiation. PMID:21911407

Density functional theory study of homologous organometallic molecules of the [RhXL2]2 (X=Cl, Br, or I; L=CO, PH3, or PF3) type

NASA Astrophysics Data System (ADS)

Seuret, P.; Weber, J.; Wesolowski, T. A.

Density functional theory generalized gradient approximation calculations, which were tested in our previous detailed study of [RhCl(PF3)2]2 (Seuret et al., 2003, Phys. Chem. chem. Phys., 5, 268-274), were applied for a series of homologous organometallic compounds of the [RhXL2]2 (X = Cl, Br, or I; L = CO, PH3, or PF3) type. Various properties of the studied compounds were obtained. Optimized geometries of [RhCl(PH3)2]2 and [RhCl(CO)2]2 are in very good agreement with available experimental data. Geometries of other compounds as well as other properties (thermochemistry of selected fragmentation channels, barriers to structural changes, frontier orbitals) which are not available experimentally were predicted. All the considered compounds are not planar. Enforcing planarity of the central [RhX]2 moiety requires only a small energetic cost ranging from 2.2 to 3.9 kcal mol-1. The analysis of frontier orbitals indicates that the metals provide the most favourable site for the electrophilic attack in all considered compounds. The analysis of the shape of the lowest unoccupied molecular orbitals indicates that the halogens and ligands provide the most favourable site for the nucleophilic attack for [RhCl(CO)2]2 or [RhCl(PF3)2]. For [RhBr(PF3)2]2, [RhI(PF3)2]2 and [RhCl(PH3)2]2, the nucleophilic attack on the halogen is less probable. Except for [RhCl(CO)2]2, the least energetically expensive decomposition channel involves initial separation of ligands. For [RhCl(CO)2]2, its decomposition into the RhCl(CO)2 fragments was found to be the least energetically expensive fragmentation reaction which is probably one of the reasons for the known catalytic activity of this compound.

Optimized Finite Difference Method for the Full-Potential XANES Simulations: Application to Molecular Adsorption Geometries in MOFs and Metal-Ligand Intersystem Crossing Transients.

PubMed

Guda, Sergey A; Guda, Alexander A; Soldatov, Mikhail A; Lomachenko, Kirill A; Bugaev, Aram L; Lamberti, Carlo; Gawelda, Wojciech; Bressler, Christian; Smolentsev, Grigory; Soldatov, Alexander V; Joly, Yves

2015-09-08

Accurate modeling of the X-ray absorption near-edge spectra (XANES) is required to unravel the local structure of metal sites in complex systems and their structural changes upon chemical or light stimuli. Two relevant examples are reported here concerning the following: (i) the effect of molecular adsorption on 3d metals hosted inside metal-organic frameworks and (ii) light induced dynamics of spin crossover in metal-organic complexes. In both cases, the amount of structural models for simulation can reach a hundred, depending on the number of structural parameters. Thus, the choice of an accurate but computationally demanding finite difference method for the ab initio X-ray absorption simulations severely restricts the range of molecular systems that can be analyzed by personal computers. Employing the FDMNES code [Phys. Rev. B, 2001, 63, 125120] we show that this problem can be handled if a proper diagonalization scheme is applied. Due to the use of dedicated solvers for sparse matrices, the calculation time was reduced by more than 1 order of magnitude compared to the standard Gaussian method, while the amount of required RAM was halved. Ni K-edge XANES simulations performed by the accelerated version of the code allowed analyzing the coordination geometry of CO and NO on the Ni active sites in CPO-27-Ni MOF. The Ni-CO configuration was found to be linear, while Ni-NO was bent by almost 90°. Modeling of the Fe K-edge XANES of photoexcited aqueous [Fe(bpy)3](2+) with a 100 ps delay we identified the Fe-N distance elongation and bipyridine rotation upon transition from the initial low-spin to the final high-spin state. Subsequently, the X-ray absorption spectrum for the intermediate triplet state with expected 100 fs lifetime was theoretically predicted.

Kinetic and CD/MCD spectroscopic studies of the atypical, three-His-ligated, non-heme Fe2+ center in diketone dioxygenase: the role of hydrophilic outer shell residues in catalysis.

PubMed

Straganz, Grit D; Diebold, Adrienne R; Egger, Sigrid; Nidetzky, Bernd; Solomon, Edward I

2010-02-09

Diketone cleaving enzyme (Dke1) is a dioxygenase with an atypical, three-histidine-ligated, mononuclear non-heme Fe(2+) center. To assess the role in enzyme catalysis of the hydrophilic residues in the active site pocket, residues Glu98, Arg80, Tyr70, and Thr107 were subjected to mutational analysis. Steady state and pre-steady state kinetics indicated a role for Glu98 in promoting both substrate binding and O(2) reduction. Additionally, the Glu98 substitution eliminated the pH dependence of substrate binding (k(cat)(app)/K(M)(app)-pH profile) present in wild-type Dke1 (pK(a) = 6.3 +/- 0.4 and 8.4 +/- 0.4). MCD spectroscopy revealed that the Glu98 --> Gln mutation leads to the conversion of the six-coordinate (6C) resting Fe(2+) center present in the wild-type enzyme at pH 7.0 to a mixture of five-coordinate (5C) and 6C sites. The 6C geometry was restored with a pH shift to 9.5 which also resulted in ligand field (LF) energy splittings identical to that found for wild-type (WT) Dke1 at pH 9.5. In WT Dke1, these LF transitions are shifted up in energy by approximately 300 cm(-1) at pH 9.5 relative to pH 7.0. These data, combined with CD pH titrations which reveal a pK(a) of approximately 8.2 for resting WT Dke1 and the Glu98 --> Gln variant, indicate the deprotonation of a metal-ligated water. Together, the kinetic and spectroscopic data reveal a stabilizing effect of Glu98 on the 6C geometry of the metal center, priming it for substrate ligation. Arg80 and Tyr70 are shown to promote O(2) reduction, while Thr107 stabilizes the Fe(II) cofactor.

5D Modelling: An Efficient Approach for Creating Spatiotemporal Predictive 3D Maps of Large-Scale Cultural Resources

NASA Astrophysics Data System (ADS)

Doulamis, A.; Doulamis, N.; Ioannidis, C.; Chrysouli, C.; Grammalidis, N.; Dimitropoulos, K.; Potsiou, C.; Stathopoulou, E.-K.; Ioannides, M.

2015-08-01

Outdoor large-scale cultural sites are mostly sensitive to environmental, natural and human made factors, implying an imminent need for a spatio-temporal assessment to identify regions of potential cultural interest (material degradation, structuring, conservation). On the other hand, in Cultural Heritage research quite different actors are involved (archaeologists, curators, conservators, simple users) each of diverse needs. All these statements advocate that a 5D modelling (3D geometry plus time plus levels of details) is ideally required for preservation and assessment of outdoor large scale cultural sites, which is currently implemented as a simple aggregation of 3D digital models at different time and levels of details. The main bottleneck of such an approach is its complexity, making 5D modelling impossible to be validated in real life conditions. In this paper, a cost effective and affordable framework for 5D modelling is proposed based on a spatial-temporal dependent aggregation of 3D digital models, by incorporating a predictive assessment procedure to indicate which regions (surfaces) of an object should be reconstructed at higher levels of details at next time instances and which at lower ones. In this way, dynamic change history maps are created, indicating spatial probabilities of regions needed further 3D modelling at forthcoming instances. Using these maps, predictive assessment can be made, that is, to localize surfaces within the objects where a high accuracy reconstruction process needs to be activated at the forthcoming time instances. The proposed 5D Digital Cultural Heritage Model (5D-DCHM) is implemented using open interoperable standards based on the CityGML framework, which also allows the description of additional semantic metadata information. Visualization aspects are also supported to allow easy manipulation, interaction and representation of the 5D-DCHM geometry and the respective semantic information. The open source 3DCityDB incorporating a PostgreSQL geo-database is used to manage and manipulate 3D data and their semantics.

Computational chemistry of modified [MFe3S4] and [M2Fe2S4] clusters: assessment of trends in electronic structure and properties.

PubMed

Jensen, Kasper P; Ooi, Bee-Lean; Christensen, Hans E M

2008-12-18

The aim of this work is to understand the molecular evolution of iron-sulfur clusters in terms of electronic structure and function. Metal-substituted models of biological [Fe(4)S(4)] clusters in oxidation states [M(x)Fe(4-x)S(4)](3+/2+/1+) have been studied by density functional theory (M = Cr, Mn, Fe, Co, Ni, Cu, Zn, and Pd, with x = 1 or 2). Most of these clusters have not been characterized before. For those that have been characterized experimentally, very good agreement is obtained, implying that also the predicted structures and properties of new clusters are accurate. Mean absolute errors are 0.024 A for bond lengths ([Fe(4)S(4)], [NiFe(3)S(4)], [CoFe(3)S(4)]) and 0.09 V for shifts in reduction potentials relative to the [Fe(4)S(4)] cluster. All structures form cuboidal geometries similar to the all-iron clusters, except the Pd-substituted clusters, which instead form highly distorted trigonal and tetragonal local sites in compromised, pseudocuboidal geometries. In contrast to other electron-transfer sites, cytochromes, blue copper proteins, and smaller iron-sulfur clusters, we find that the [Fe(4)S(4)] clusters are very insensitive to metal substitution, displaying quite small changes in reorganization energies and reduction potentials upon substitution. Thus, the [Fe(4)S(4)] clusters have an evolutionary advantage in being robust to pollution from other metals, still retaining function. We analyze in detail the electronic structure of individual clusters and rationalize spin couplings and redox activity. Often, several configurations are very close in energy, implying possible use as spin-crossover systems, and spin states are predicted accurately in all but one case ([CuFe(3)S(4)]). The results are anticipated to be helpful in defining new molecular systems with catalytic and magnetic properties.

Nondestructive determination of activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chabalier, B.

1996-08-01

Characterization and appraisal tests include the measurement of activity in raw waste and waste packages. After conditioning, variations in density, matrix composition, and geometry make evaluation of the radionuclide activity in a package destined for storage nearly impossible without measurements and with a low uncertainty. Various nondestructive measuring techniques that use ionizing radiation are employed to characterize waste packages and raw waste. Gamma spectrometry is the most widely used technique because of its simple operation and low cost. This technique is used to quantify the beta-gamma and alpha activity of gamma-emitting radionuclides as well as to check the radioactive homogeneitymore » of the waste packages. Numerous systems for directly measuring waste packages have been developed. Two types of methods may be distinguished, depending on whether results that come from the measurements are weighted by an experimentally determined corrective term or by calculation. Through the MARCO and CARACO measuring systems, a method is described that allows one to quantify the activity of the beta-gamma and alpha radionuclides contained in either a waste package or raw waste whose geometries and material compositions are more or less accurately known. This method is based on (a) measurement by gamma spectrometry of the beta-gamma and alpha activity of the gamma-emitting radionuclides contained in the waste package and (b) the application of calculated corrections; thus, the limitations imposed by reference package geometry and matrix are avoided.« less

Survey of large circular and octagonal tanks operated at Norwegian commercial smolt and post-smolt sites

USDA-ARS?s Scientific Manuscript database

A survey was conducted to determine the geometry, operating parameters, and other key features of large circular or octagonal culture tanks used to produce Atlantic salmon smolt and post-smolt at six major Norwegian Atlantic salmon production companies. A total of 55 large tanks were reported at sev...

Failure Analysis Handbook

DTIC Science & Technology

1989-08-18

conditions, strain rate , geometry, manufacturing variables, microstructure, surface conditions, and alloy contamination. Exzvples of service failures are...depends on the ductility of the material, strain rate and stress concentration. The macrosocpic appearances of two ductile overstress fractures are shown...distribution of nucleation sites, stress orientation, temperature, ductility and strain rate . The size of the dimples is oontrolled by the size, number ard

Representational geometry: integrating cognition, computation, and the brain.

PubMed

Kriegeskorte, Nikolaus; Kievit, Rogier A

2013-08-01

The cognitive concept of representation plays a key role in theories of brain information processing. However, linking neuronal activity to representational content and cognitive theory remains challenging. Recent studies have characterized the representational geometry of neural population codes by means of representational distance matrices, enabling researchers to compare representations across stages of processing and to test cognitive and computational theories. Representational geometry provides a useful intermediate level of description, capturing both the information represented in a neuronal population code and the format in which it is represented. We review recent insights gained with this approach in perception, memory, cognition, and action. Analyses of representational geometry can compare representations between models and the brain, and promise to explain brain computation as transformation of representational similarity structure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Axi-symmetric patterns of active polar filaments on spherical and composite surfaces

NASA Astrophysics Data System (ADS)

Srivastava, Pragya; Rao, Madan

2014-03-01

Experiments performed on Fission Yeast cells of cylindrical and spherical shapes, rod-shaped bacteria and reconstituted cylindrical liposomes suggest the influence of cell geometry on patterning of cortical actin. A theoretical model based on active hydrodynamic description of cortical actin that includes curvature-orientation coupling predicts spontaneous formation of acto-myosin rings, cables and nodes on cylindrical and spherical geometries [P. Srivastava et al, PRL 110, 168104(2013)]. Stability and dynamics of these patterns is also affected by the cellular shape and has been observed in experiments performed on Fission Yeast cells of spherical shape. Motivated by this, we study the stability and dynamics of axi-symmetric patterns of active polar filaments on the surfaces of spherical, saddle shaped and conical geometry and classify the stable steady state patterns on these surfaces. Based on the analysis of the fluorescence images of Myosin-II during ring slippage we propose a simple mechanical model for ring-sliding based on force balance and make quantitative comparison with the experiments performed on Fission Yeast cells. NSF Grant DMR-1004789 and Syracuse Soft Matter Program.

Lidar arc scan uncertainty reduction through scanning geometry optimization

DOE PAGES

Wang, Hui; Barthelmie, Rebecca J.; Pryor, Sara C.; ...

2016-04-13

Doppler lidars are frequently operated in a mode referred to as arc scans, wherein the lidar beam scans across a sector with a fixed elevation angle and the resulting measurements are used to derive an estimate of the n minute horizontal mean wind velocity (speed and direction). Previous studies have shown that the uncertainty in the measured wind speed originates from turbulent wind fluctuations and depends on the scan geometry (the arc span and the arc orientation). This paper is designed to provide guidance on optimal scan geometries for two key applications in the wind energy industry: wind turbine power performance analysis and annualmore » energy production prediction. We present a quantitative analysis of the retrieved wind speed uncertainty derived using a theoretical model with the assumption of isotropic and frozen turbulence, and observations from three sites that are onshore with flat terrain, onshore with complex terrain and offshore, respectively. The results from both the theoretical model and observations show that the uncertainty is scaled with the turbulence intensity such that the relative standard error on the 10 min mean wind speed is about 30% of the turbulence intensity. The uncertainty in both retrieved wind speeds and derived wind energy production estimates can be reduced by aligning lidar beams with the dominant wind direction, increasing the arc span and lowering the number of beams per arc scan. As a result, large arc spans should be used at sites with high turbulence intensity and/or large wind direction variation.« less