Crystallographic Studies of Prion Protein (PrP) Segments Suggest How Structural Changes Encoded by Polymorphism at Residue 129 Modulate Susceptibility to Human Prion Disease

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

Apostol, Marcin I.; Sawaya, Michael R.; Cascio, Duilio

2010-09-23

A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene, leading to a change from methionine to valine at residue 129 of prion protein (PrP), has been shown to be a determinant in the susceptibility to prion disease. However, the molecular basis of this effect remains unexplained. In the current study, we determined crystal structures of prion segments having either Met or Val at residue 129. These 6-residue segments of PrP centered on residue 129 are 'steric zippers,' pairs of interacting {beta}-sheets. Both structures of these 'homozygous steric zippers' reveal direct intermolecular interactions between Met or Valmore » in one sheet and the identical residue in the mating sheet. These two structures, plus a structure-based model of the heterozygous Met-Val steric zipper, suggest an explanation for the previously observed effects of this locus on prion disease susceptibility and progression.« less

Influence of aggregated morphology on carbon dioxide uptake of polythiophene conjugated organic networks

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

Qiao, Shanlin; University of Chinese Academy of Sciences, Beijing 100049; Du, Zhengkun

2014-04-01

Two novel thiophene-based conjugated networks CMPs-TTT and CMPs-DTBT were designed and prepared with different steric configuration building blocks by FeCl{sub 3} oxidative coupling polymerization. UV–vis spectra, FE-SEM and TEM images showed CMPs-TTT and CMPs-DTBT having the different aggregated morphologies. After porous analysis and gas adsorption test, the result showed CO{sub 2} uptake capacity of CMPs-DTBT with amorphous aggregation model is 2.88 times and 2.66 times greater than that of CMPs-TTT with large lamellar structure model at 273 K and 298 K (1.0 bar), respectively. As a result, this communication proved that change the topological structure of the polymer can influencemore » the CO{sub 2} adsorption capacity significantly. - Graphical abstract: Two thiophene-based conjugated networks were prepared with different steric configuration building blocks, and they show various CO{sub 2} uptake capacity and sorption isosteric enthalpies, although they have identical chemical constitution. - Highlights: • Topological-directed design and synthesis two conjugated porous polymers. • Two thiophene-based CMPs show different aggregated morphologies. • They exhibit similar porosity structure and different CO{sub 2} uptake capacity.« less

Modulated nematic structures induced by chirality and steric polarization

NASA Astrophysics Data System (ADS)

Longa, Lech; PajÄ k, Grzegorz

2016-04-01

What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (NLP) and transverse (NTP) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (NTB) and the splay-bend nematic phase (NSB), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral NTP and NSB into new NTB phases. Surprisingly, the nonchiral NLP phase can stay stable even in the presence of intrinsic chirality.

Controlling site selectivity in Pd-catalyzed oxidative cross-coupling reactions.

PubMed

Lyons, Thomas W; Hull, Kami L; Sanford, Melanie S

2011-03-30

This paper presents a detailed investigation of the factors controlling site selectivity in the Pd-mediated oxidative coupling of 1,3-disubstituted and 1,2,3-trisubstituted arenes (aryl-H) with cyclometalating substrates (L~C-H). The influence of both the concentration and the steric/electronic properties of the quinone promoter are studied in detail. In addition, the effect of steric/electronic modulation of the carboxylate ligand is discussed. Finally, we demonstrate that substitution of the carboxylate for a carbonate X-type ligand leads to a complete reversal in site selectivity for many arene substrates. The origins of these trends in site selectivity are discussed in the context of the mechanism of Pd-catalyzed oxidative cross-coupling.

RNA therapeutics: Beyond RNA interference and antisense oligonucleotides

PubMed Central

Kole, Ryszard; Krainer, Adrian R.; Altman, Sidney

2016-01-01

Here we discuss three RNA therapeutic technologies exploiting various oligonucleotides that bind RNA by base-pairing in a sequence-specific manner yet have different mechanisms of action and effects. RNA interference and antisense oligonucleotides downregulate gene expression by enzyme-dependent degradation of targeted mRNA. Steric blocking oligonucleotides block access of cellular machinery to pre-mRNA and mRNA without degrading the RNA. Through this mechanism, blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production or also downregulate gene expression. Moreover, they can be extensively chemically modified, resulting in more drug-like properties. The ability of RNA blocking oligonucleotides to restore gene function makes them suited for treatment of genetic disorders. Positive results from clinical trials for the treatment of Duchenne muscular dystrophy show that this technology is close to realizing its clinical potential. PMID:22262036

Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

PubMed Central

Francica, Joseph R.; Varela-Rohena, Angel; Medvec, Andrew; Plesa, Gabriela; Riley, James L.; Bates, Paul

2010-01-01

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection. PMID:20844579

Function-blocking antithrombospondin-1 monoclonal antibodies

PubMed Central

ANNIS, D. S.; MURPHY-ULLRICH, J. E.; MOSHER, D. F.

2006-01-01

Summary Background Thrombospondin-1 (TSP-1) has been implicated in many different processes based in part on inhibitory activities of anti-TSP-1 monoclonal antibodies (mAbs). Objective To map epitopes of 13 anti-TSP-1 mAbs to individual modules or groups of modules spanning TSP-1 and the closely related TSP-2 homolog. Results The mapping has led to assignment or reassignment of the epitopes of four mAbs, refinement of the epitopes of six mAbs, and confirmation of the epitopes of the remaining three mAbs. ESTs10, P12, and MA-II map to the N-terminal domain; 5G11, TSP127.6, and ESTs12 to the third properdin module; C6.7, HB8432, and P10 to epidermal growth factor (EGF)-like modules 1 and/or 2; and A6.1, mAb133, MA-I, and D4.6 to the calcium-binding wire module. A6.1, which recognizes a region of the wire that is identical in mouse and human TSP-1, reacts with TSP-1 from both species, and also reacts weakly with human TSP-2. Two other mouse antihuman TSP-1 mAbs, A4.1 and D4.6, also react with mouse TSP-1. Conclusions Consideration of previous literature and mapping of epitopes of inhibitory mAbs suggest that biological activities are present throughout TSP-1, including the EGF-like modules that have not been implicated in the past. Because the epitopes for 10 of the antibodies likely are within 18 nm of one another in calcium-replete TSP-1, some of the inhibitory effects may result from steric hindrance. Such seems to be the case for mAb133, which binds the calcium-binding wire but is still able to interfere with the activation of latent TGF-β by the properdin modules. PMID:16420580

Adsorption of Small Cationic Nanoparticles onto Large Anionic Particles from Aqueous Solution: A Model System for Understanding Pigment Dispersion and the Problem of Effective Particle Density.

PubMed

North, S M; Jones, E R; Smith, G N; Mykhaylyk, O O; Annable, T; Armes, S P

2017-02-07

The present study focuses on the use of copolymer nanoparticles as a dispersant for a model pigment (silica). Reversible addition-fragmentation chain transfer (RAFT) alcoholic dispersion polymerization was used to synthesize sterically stabilized diblock copolymer nanoparticles. The steric stabilizer block was poly(2-(dimethylamino)ethyl methacrylate) (PDMA) and the core-forming block was poly(benzyl methacrylate) (PBzMA). The mean degrees of polymerization for the PDMA and PBzMA blocks were 71 and 100, respectively. Transmission electron microscopy (TEM) studies confirmed a near-monodisperse spherical morphology, while dynamic light scattering (DLS) studies indicated an intensity-average diameter of 30 nm. Small-angle X-ray scattering (SAXS) reported a volume-average diameter of 29 ± 0.5 nm and a mean aggregation number of 154. Aqueous electrophoresis measurements confirmed that these PDMA 71 -PBzMA 100 nanoparticles acquired cationic character when transferred from ethanol to water as a result of protonation of the weakly basic PDMA chains. Electrostatic adsorption of these nanoparticles from aqueous solution onto 470 nm silica particles led to either flocculation at submonolayer coverage or steric stabilization at or above monolayer coverage, as judged by DLS. This technique indicated that saturation coverage was achieved on addition of approximately 465 copolymer nanoparticles per silica particle, which corresponds to a fractional surface coverage of around 0.42. These adsorption data were corroborated using thermogravimetry, UV spectroscopy and X-ray photoelectron spectroscopy. TEM studies indicated that the cationic nanoparticles remained intact on the silica surface after electrostatic adsorption, while aqueous electrophoresis confirmed that surface charge reversal occurred below pH 7. The relatively thick layer of adsorbed nanoparticles led to a significant reduction in the effective particle density of the silica particles from 1.99 g cm -3 to approximately 1.74 g cm -3 , as judged by disk centrifuge photosedimentometry (DCP). Combining the DCP and SAXS data suggests that essentially no deformation of the PBzMA cores occurs during nanoparticle adsorption onto the silica particles.

Allosteric Coupling of CARMIL and V-1 Binding to Capping Protein Revealed by Hydrogen-Deuterium Exchange.

PubMed

Johnson, Britney; McConnell, Patrick; Kozlov, Alex G; Mekel, Marlene; Lohman, Timothy M; Gross, Michael L; Amarasinghe, Gaya K; Cooper, John A

2018-05-29

Actin assembly is important for cell motility. The ability of actin subunits to join or leave filaments via the barbed end is critical to actin dynamics. Capping protein (CP) binds to barbed ends to prevent subunit gain and loss and is regulated by proteins that include V-1 and CARMIL. V-1 inhibits CP by sterically blocking one binding site for actin. CARMILs bind at a distal site and decrease the affinity of CP for actin, suggested to be caused by conformational changes. We used hydrogen-deuterium exchange with mass spectrometry (HDX-MS) to probe changes in structural dynamics induced by V-1 and CARMIL binding to CP. V-1 and CARMIL induce changes in both proteins' binding sites on the surface of CP, along with a set of internal residues. Both also affect the conformation of CP's ββ subunit "tentacle," a second distal actin-binding site. Concerted regulation of actin assembly by CP occurs through allosteric couplings between CP modulator and actin binding sites. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Structural Basis of Tonic Inhibition by Dimers of Dimers in Hyperpolarization-Activated Cyclic-Nucleotide-Modulated (HCN) Ion Channels.

PubMed

VanSchouwen, Bryan; Melacini, Giuseppe

2016-10-03

The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates HCN activity through cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN. In the absence of cAMP, the IR cAMP-binding domain (CBD) mainly samples its inactive conformation, resulting in steric clashes that destabilize the IR tetramer. Although these clashes with the inactive CBD are released through tetramer dissociation into monomers, functional mutagenesis suggests that the apo IR is not fully monomeric. To investigate the inhibitory non-monomeric IR species, we performed molecular dynamics simulations starting from "hybrid" structures that are tetrameric, but contain inactive apo-state CBD conformations. The ensemble of simulated trajectories reveals that full dissociation of the tetramer into monomers is not necessary to release the steric hindrance with the inactive CBD. Specifically, we found that partial dissociation of the tetramer into dimers is sufficient to accommodate four inactive CBDs, while reduction of the quaternary symmetry of the non-dissociated tetramer from four- to two-fold permits accommodation of two inactive CBDs. Our findings not only rationalize available electrophysiological, fluorometry and sedimentation equilibrium data, but they also provide unprecedented structural insight into previously elusive non-monomeric auto-inhibitory HCN species.

Role of Thermochemical Decomposition in Energetic Material Initiation Sensitivity and Explosive Performance

DTIC Science & Technology

2007-02-05

Electronic excitation has been suggested as one contributing mechanistic step in a multiprocess detonation model [18], and such electronic...and, (b) Dick, J. J., Orientation Dependence of the Shock Initiation Sensitivity of PETN: A Steric Hindrance Model , Workshop on Desensitization of...Explosives and Propellants, Rijswijk, The Netherlands, 11-13 Nov 1991. [15] Piermarini, G. J., Block, S., Miller , P. J., Effects of Pressure on

Geometry of proteins: hydrogen bonding, sterics, and marginally compact tubes.

PubMed

Banavar, Jayanth R; Cieplak, Marek; Flammini, Alessandro; Hoang, Trinh X; Kamien, Randall D; Lezon, Timothy; Marenduzzo, Davide; Maritan, Amos; Seno, Flavio; Snir, Yehuda; Trovato, Antonio

2006-03-01

The functionality of proteins is governed by their structure in the native state. Protein structures are made up of emergent building blocks of helices and almost planar sheets. A simple coarse-grained geometrical model of a flexible tube barely subject to compaction provides a unified framework for understanding the common character of globular proteins. We argue that a recent critique of the tube idea is not well founded.

Geometry of proteins: Hydrogen bonding, sterics, and marginally compact tubes

NASA Astrophysics Data System (ADS)

Banavar, Jayanth R.; Cieplak, Marek; Flammini, Alessandro; Hoang, Trinh X.; Kamien, Randall D.; Lezon, Timothy; Marenduzzo, Davide; Maritan, Amos; Seno, Flavio; Snir, Yehuda; Trovato, Antonio

2006-03-01

The functionality of proteins is governed by their structure in the native state. Protein structures are made up of emergent building blocks of helices and almost planar sheets. A simple coarse-grained geometrical model of a flexible tube barely subject to compaction provides a unified framework for understanding the common character of globular proteins. We argue that a recent critique of the tube idea is not well founded.

Evidence for single metal two electron oxidative addition and reductive elimination at uranium.

PubMed

Gardner, Benedict M; Kefalidis, Christos E; Lu, Erli; Patel, Dipti; McInnes, Eric J L; Tuna, Floriana; Wooles, Ashley J; Maron, Laurent; Liddle, Stephen T

2017-12-01

Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a single-metal two-electron oxidative addition. Thermolysis of this complex promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that nitrenes are not generated and thus a reductive elimination has occurred. Though not optimally balanced in this case, this work presents evidence that classical d-block redox chemistry can be performed reversibly by f-block metals, and that uranium can thus mimic elementary transition metal reactivity, which may lead to the discovery of new f-block catalysis.

Conformation of single block copolymer chain in two-dimensional microphase-separated structure studied by scanning near-field optical microscopy.

PubMed

Sekine, Ryojun; Aoki, Hiroyuki; Ito, Shinzaburo

2009-05-21

The localization and orientation of the symmetric diblock copolymer chain in a quasi-two-dimensional microphase-separated structure were studied by scanning near-field optical microscopy (SNOM). In the monolayer of poly(isobutyl methacrylate)-block-poly(octadecyl methacrylate) (PiBMA-b-PODMA), the individual PiBMA subchains were directly observed by SNOM, and the center of mass (CM) and orientational angle relative to the phase interface were examined at the single chain level. It was found that the position of the CM and the orientation of the PiBMA subchain in the lamellar structure were dependent on the curvature of the PiBMA/PODMA interface. As the interface was bent toward the objective chain, the block chain preferred the CM position closer to the domain center, and the conformation was strongly oriented perpendicularly to the domain interface. With increase of the curvature, the steric hindrance among the block chain increases, resulting in the stretched conformation.

Environmental testing of block 2 solar cell modules

NASA Technical Reports Server (NTRS)

Griffith, J. S.

1979-01-01

The testing procedures and results of samples of the LSA Project Block 2 procurement of silicon solar cell modules are described. Block 2 was the second large scale procurement of silicon solar cell modules made by the JPL Low-cost Solar Array Project with deliveries in 1977 and early 1978. The results showed that the Block 2 modules were greatly improved over Block 1 modules. In several cases it was shown that design improvements were needed to reduce environmental test degradation. These improvements were incorporated during this production run.

Rational Modulation of the Induced-Fit Conformational Change for Slow-Onset Inhibition in Mycobacterium tuberculosis InhA.

PubMed

Lai, Cheng-Tsung; Li, Huei-Jiun; Yu, Weixuan; Shah, Sonam; Bommineni, Gopal R; Perrone, Victoria; Garcia-Diaz, Miguel; Tonge, Peter J; Simmerling, Carlos

2015-08-04

Slow-onset enzyme inhibitors are the subject of considerable interest as an approach to increasing the potency of pharmaceutical compounds by extending the residence time of the inhibitor on the target (the lifetime of the drug-receptor complex). However, rational modulation of residence time presents significant challenges because it requires additional mechanistic insight, such as the nature of the transition state for postbinding isomerization. Our previous work, based on X-ray crystallography, enzyme kinetics, and molecular dynamics simulation, suggested that the slow step in inhibition of the Mycobacterium tuberculosis enoyl-ACP reductase InhA involves a change in the conformation of the substrate binding loop from an open state in the initial enzyme-inhibitor complex to a closed state in the final enzyme-inhibitor complex. Here, we use multidimensional free energy landscapes for loop isomerization to obtain a computational model for the transition state. The results suggest that slow-onset inhibitors crowd key side chains on helices that slide past each other during isomerization, resulting in a steric clash. The landscapes become significantly flatter when residues involved in the steric clash are replaced with alanine. Importantly, this lower barrier can be increased by rational inhibitor redesign to restore the steric clash. Crystallographic studies and enzyme kinetics confirm the predicted effects on loop structure and flexibility, as well as inhibitor residence time. These loss and regain of function studies validate our mechanistic hypothesis for interactions controlling substrate binding loop isomerization, providing a platform for the future design of inhibitors with longer residence times and better in vivo potency. Similar opportunities for slow-onset inhibition via the same mechanism are identified in other pathogens.

Reverse actin sliding triggers strong myosin binding that moves tropomyosin

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

Bekyarova, T.I.; Reedy, M.C.; Baumann, B.A.J.

2008-09-03

Actin/myosin interactions in vertebrate striated muscles are believed to be regulated by the 'steric blocking' mechanism whereby the binding of calcium to the troponin complex allows tropomyosin (TM) to change position on actin, acting as a molecular switch that blocks or allows myosin heads to interact with actin. Movement of TM during activation is initiated by interaction of Ca{sup 2+} with troponin, then completed by further displacement by strong binding cross-bridges. We report x-ray evidence that TM in insect flight muscle (IFM) moves in a manner consistent with the steric blocking mechanism. We find that both isometric contraction, at highmore » [Ca{sup 2+}], and stretch activation, at lower [Ca{sup 2+}], develop similarly high x-ray intensities on the IFM fourth actin layer line because of TM movement, coinciding with x-ray signals of strong-binding cross-bridge attachment to helically favored 'actin target zones.' Vanadate (Vi), a phosphate analog that inhibits active cross-bridge cycling, abolishes all active force in IFM, allowing high [Ca{sup 2+}] to elicit initial TM movement without cross-bridge attachment or other changes from relaxed structure. However, when stretched in high [Ca{sup 2+}], Vi-'paralyzed' fibers produce force substantially above passive response at pCa {approx} 9, concurrent with full conversion from resting to active x-ray pattern, including x-ray signals of cross-bridge strong-binding and TM movement. This argues that myosin heads can be recruited as strong-binding 'brakes' by backward-sliding, calcium-activated thin filaments, and are as effective in moving TM as actively force-producing cross-bridges. Such recruitment of myosin as brakes may be the major mechanism resisting extension during lengthening contractions.« less

Synthesis of Photocrosslinkable and Amine Containing Multifunctional Nanoparticles via Polymerization-Induced Self-Assembly.

PubMed

Huang, Jianbing; Li, Decai; Liang, Hui; Lu, Jiang

2017-08-01

Photo-crosslinkable and amine-containing block copolymer nanoparticles are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly of a multifunctional core-forming monomer, 2-((3-(4-(diethylamino)phenyl)acryloyl)oxy)ethyl methacrylate (DEMA), using poly(2-hydroxypropyl methacrylate) macromolecular chain transfer agent as a steric stabilizer in methanol at 65 °C. By tuning the chain length of PDEMA, a range of nanoparticle morphologies (sphere, worm, and vesicle) can be obtained. Since cinnamate groups can easily undergo a [2 + 2] cycloaddition of the carbon-carbon double bonds upon UV irradiation, the as-prepared block copolymer nanoparticles are readily stabilized by photo-crosslinking to produce anisotropic nanoparticles. The crosslinked block copolymer nanoparticles can be used as templates for in situ formation polymer/gold hybrid nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis - a patent evaluation.

PubMed

Schoenberger, Matthias; Althaus, Mike

2013-10-01

Novel molecular platforms for epithelial sodium channel (ENaC) modulators are claimed in the following six patents: WO2012035158(A1); WO2009074575(A2); WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These ENaC inhibitors may be used in blocking transepithelial sodium and consequently water absorption across airway epithelia. This may result in airway rehydration and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung disease. All inhibitors resemble the classical ENaC blocker amiloride but follow different strategies to increase structural diversity in a sterically tolerant region. These substitutions can be modified to i) enhance potency of ENaC inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in order to be used as potential drugs for CF therapy. Most of the claims and patent data are supported by the currently available literature. The patents deliver a solid chemical basis for a variety of chemical modifications of the ENaC inhibitor amiloride. These modifications may result in the development of a novel, applicable ENaC inhibitors which may have lasting effects on diseased airways and may achieve airway rehydration and enhanced mucociliary clearance in CF lung disease.

Successful Stabilization of Graphene Oxide in Electrolyte Solutions: Enhancement of Bio-functionalization and Cellular Uptake

PubMed Central

Hong, Bong Jin; Compton, Owen C.; An, Zhi; Eryzazici, Ibrahim; Nguyen, SonBinh T.

2013-01-01

Aqueous dispersions of graphene oxide are inherently unstable in the presence of electrolytes, which screen the electrostatic surface charge on these nanosheets and induce irreversible aggregation. Two complementary strategies, utilizing either electrostatic or steric stabilization, have been developed to enhance the stability of graphene oxide in electrolyte solutions, allowing it to stay dispersed in cell culture media and serum. The electrostatic stabilization approach entails further oxidation of graphene oxide to low C/O ratio (~1.03) and increases ionic tolerance of these nanosheets. The steric stabilization technique employs an amphiphilic block copolymer that serves as a non-covalently bound surfactant to minimize the aggregate-induced nanosheets-nanosheet interactions. Both strategies can stabilize graphene oxide nanosheets with large dimensions (>300 nm) in biological media, allowing for an enhancement of >250% in the bioconjugation efficiency of streptavidin in comparison to untreated nanosheets. Notably, both strategies allow the stabilized nanosheets to be readily uptake by cells, demonstrating their excellent performance as potential drug delivery vehicles. PMID:22017285

Steric and electrostatic surface forces on sulfonated PEG graft surfaces with selective albumin adsorption.

PubMed

Bremmell, Kristen E; Britcher, Leanne; Griesser, Hans J

2013-06-01

Addition of ionized terminal groups to PEG graft layers may cause additional interfacial forces to modulate the net interfacial interactions between PEG graft layers and proteins. In this study we investigated the effect of terminal sulfonate groups, characterizing PEG-aldehyde (PEG-CHO) and sulfonated PEG (PEG-SO3) graft layers by XPS and colloid probe AFM interaction force measurements as a function of ionic strength, in order to determine surface forces relevant to protein resistance and models of bio-interfacial interaction of such graft coatings. On the PEG-CHO surface the measured interaction force does not alter with ionic strength, typical of a repulsive steric barrier coating. An analogous repulsive interaction force of steric origin was also observed on the PEG-SO3 graft coating; however, the net interaction force changed with ionic strength. Interaction forces were modelled by steric and electrical double layer interaction theories, with fitting to a scaling theory model enabling determination of the spacing and stretching of the grafted chains. Albumin, fibrinogen, and lysozyme did not adsorb on the PEG-CHO coating, whereas the PEG graft with terminal sulfonate groups showed substantial adsorption of albumin but not fibrinogen or lysozyme from 0.15 M salt solutions. Under lower ionic strength conditions albumin adsorption was again minimized as a result of the increased electrical double-layer interaction observed with the PEG-SO3 modified surface. This unique and unexpected adsorption behaviour of albumin provides an alternative explanation to the "negative cilia" model used by others to rationalize observed thromboresistance on PEG-sulfonate coatings. Copyright © 2013 Elsevier B.V. All rights reserved.

Multilevel Concatenated Block Modulation Codes for the Frequency Non-selective Rayleigh Fading Channel

NASA Technical Reports Server (NTRS)

Lin, Shu; Rhee, Dojun

1996-01-01

This paper is concerned with construction of multilevel concatenated block modulation codes using a multi-level concatenation scheme for the frequency non-selective Rayleigh fading channel. In the construction of multilevel concatenated modulation code, block modulation codes are used as the inner codes. Various types of codes (block or convolutional, binary or nonbinary) are being considered as the outer codes. In particular, we focus on the special case for which Reed-Solomon (RS) codes are used as the outer codes. For this special case, a systematic algebraic technique for constructing q-level concatenated block modulation codes is proposed. Codes have been constructed for certain specific values of q and compared with the single-level concatenated block modulation codes using the same inner codes. A multilevel closest coset decoding scheme for these codes is proposed.

Recognition and Blocking of Innate Immunity Cells by Candida albicans Chitin ▿ †

PubMed Central

Mora-Montes, Héctor M.; Netea, Mihai G.; Ferwerda, Gerben; Lenardon, Megan D.; Brown, Gordon D.; Mistry, Anita R.; Kullberg, Bart Jan; O'Callaghan, Chris A.; Sheth, Chirag C.; Odds, Frank C.; Brown, Alistair J. P.; Munro, Carol A.; Gow, Neil A. R.

2011-01-01

Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls. PMID:21357722

Multi-level bandwidth efficient block modulation codes

NASA Technical Reports Server (NTRS)

Lin, Shu

1989-01-01

The multilevel technique is investigated for combining block coding and modulation. There are four parts. In the first part, a formulation is presented for signal sets on which modulation codes are to be constructed. Distance measures on a signal set are defined and their properties are developed. In the second part, a general formulation is presented for multilevel modulation codes in terms of component codes with appropriate Euclidean distances. The distance properties, Euclidean weight distribution and linear structure of multilevel modulation codes are investigated. In the third part, several specific methods for constructing multilevel block modulation codes with interdependency among component codes are proposed. Given a multilevel block modulation code C with no interdependency among the binary component codes, the proposed methods give a multilevel block modulation code C which has the same rate as C, a minimum squared Euclidean distance not less than that of code C, a trellis diagram with the same number of states as that of C and a smaller number of nearest neighbor codewords than that of C. In the last part, error performance of block modulation codes is analyzed for an AWGN channel based on soft-decision maximum likelihood decoding. Error probabilities of some specific codes are evaluated based on their Euclidean weight distributions and simulation results.

Patients' and procedural characteristics of AV-block during slow pathway modulation for AVNRT-single center 10year experience.

PubMed

Wasmer, Kristina; Dechering, Dirk G; Köbe, Julia; Leitz, Patrick; Frommeyer, Gerrit; Lange, Phillip S; Kochhäuser, Simon; Reinke, Florian; Pott, Christian; Mönnig, Gerold; Breithardt, Günter; Eckardt, Lars

2017-10-01

Permanent AV-block is a recognized and feared complication of slow pathway modulation for AVNRT. We aimed to assess incidence of transient and permanent AV-block as well as consequences of transient AV-block in a large contemporary AVNRT ablation cohort. We searched our single center prospective ablation database for occurrence of transient and permanent AV-block during slow pathway modulation between January 2004 and October 2015. We analyzed patients' and procedural characteristics as well as outcome of patients in whom transient or permanent AV-block occurred. Of 9170 patients who underwent a catheter ablation at our institution between January 2004 and October 2015, 2101 patients (64% women, mean age 50±18years) underwent slow pathway modulation. In three patients, permanent AV-block occurred during RF application. Additional two patients had transient AV-block that recovered (after a few minutes and 25min), but recurred within two days of the procedure. All five patients underwent dual chamber pacemaker implantation (0.2%). Transient AV-block related to RF delivery occurred in 44 patients (2%). Transient mechanical AV-block occurred in additional 17 patients (0.8%). In 12 patients, ablation was continued despite transient AV-block. One of these patients developed permanent AV-block. Permanent AV-block following slow pathway modulation is a rare event, occurring in 0.2% of patients in a large contemporary single center cohort. Transient AV-block is more frequent (2%). Copyright © 2017 Elsevier B.V. All rights reserved.

Method for improving product yields in an anionic metalloporphyrin-based artificial photosynthesis system

DOEpatents

Shelnutt, John A.

1986-01-01

A method for improving product yields in an anionic metalloporphyrin-based artificial photosynthesis system for hydrogen generation which comprises forming an aqueous solution comprising an electron donor, methylviologen, and certain metalloporphyrins and metallochlorins, and irradiating said aqueous solution with light in the presence of a catalyst. In the photosynthesis process, solar energy is collected and stored in the form of a gas hydrogen. Ligands attached above and below the metalloporphyrin and metallochlorin plane are capable of sterically blocking photochemically inactive electrostatically bound .pi.--.pi. complexes which can develop.

Method for improving product yields in an anionic metalloporphyrin-based artificial photosynthesis system

DOEpatents

Shelnutt, J.A.

1984-11-29

A method is disclosed improving product yields in an anionic metalloporphyrin-based artificial photosynthesis system for hydrogen generation. The method comprises forming an aqueous solution comprising an electron donor, methylviologen, and certain metalloporphyrins and metallochlorins, and irradiating said aqueous solution with light in the presence of a catalyst. In the photosynthesis process, solar energy is collected and stored in the form of a hydrogen. Ligands attached above and below the metalloporphyrin and metallochlorin plane are capable of sterically blocking photochemically inactive electrostatically bound ..pi..-..pi.. complexes which can develop.

Design, fabrication and test of block 4 design solar cell modules. Part 2: Residential module

NASA Technical Reports Server (NTRS)

Jester, T. L.

1982-01-01

Design, fabrication and test of the Block IV residential load module are reported. Design changes from the proposed module design through three iterations to the discontinuance of testing are outlined.

Structural Basis of Rap Phosphatase Inhibition by Phr Peptides

PubMed Central

Gallego del Sol, Francisca; Marina, Alberto

2013-01-01

Two-component systems, composed of a sensor histidine kinase and an effector response regulator (RR), are the main signal transduction devices in bacteria. In Bacillus, the Rap protein family modulates complex signaling processes mediated by two-component systems, such as competence, sporulation, or biofilm formation, by inhibiting the RR components involved in these pathways. Despite the high degree of sequence homology, Rap proteins exert their activity by two completely different mechanisms of action: inducing RR dephosphorylation or blocking RR binding to its target promoter. However the regulatory mechanism involving Rap proteins is even more complex since Rap activity is antagonized by specific signaling peptides (Phr) through a mechanism that remains unknown at the molecular level. Using X-ray analyses, we determined the structure of RapF, the anti-activator of competence RR ComA, alone and in complex with its regulatory peptide PhrF. The structural and functional data presented herein reveal that peptide PhrF blocks the RapF-ComA interaction through an allosteric mechanism. PhrF accommodates in the C-terminal tetratricopeptide repeat domain of RapF by inducing its constriction, a conformational change propagated by a pronounced rotation to the N-terminal ComA-binding domain. This movement partially disrupts the ComA binding site by triggering the ComA disassociation, whose interaction with RapF is also sterically impaired in the PhrF-induced conformation of RapF. Sequence analyses of the Rap proteins, guided by the RapF-PhrF structure, unveil the molecular basis of Phr recognition and discrimination, allowing us to relax the Phr specificity of RapF by a single residue change. PMID:23526880

Interlocking Toy Building Blocks as Hands-On Learning Modules for Blind and Visually Impaired Chemistry Students

ERIC Educational Resources Information Center

Melaku, Samuel; Schreck, James O.; Griffin, Kameron; Dabke, Rajeev B.

2016-01-01

Interlocking toy building blocks (e.g., Lego) as chemistry learning modules for blind and visually impaired (BVI) students in high school and undergraduate introductory or general chemistry courses are presented. Building blocks were assembled on a baseplate to depict the relative changes in the periodic properties of elements. Modules depicting…

Conformational Preferences of α-Substituted Proline Analogues

PubMed Central

Flores-Ortega, Alejandra; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Casanovas, Jordi

2009-01-01

DFT calculations at the B3LYP/6-31+G(d,p) level have been used to investigate how the replacement of the α hydrogen by a more sterically demanding group affects the conformational preferences of proline. Specifically, the N-acetyl-N’-methylamide derivatives of L-proline, L-α-methylproline and L-α-phenylproline have been calculated, with both the cis/trans isomerism of the peptide bonds and the puckering of the pyrrolidine ring being considered. The effects of solvation have been evaluated using a Self Consistent Reaction Field model. As expected, tetrasubstitution at the α carbon destabilizes the conformers with one or more peptide bonds arranged in cis. The lowest energy minimum has been found to be identical for the three compounds investigated, but important differences are observed regarding other energetically accessible backbone conformations. The results obtained provide evidence that the distinct steric requirements of the substituent at Cα may play a significant role in modulating the conformational preferences of proline. PMID:18351745

Block 5 documentation and solar modules

NASA Technical Reports Server (NTRS)

1985-01-01

Design and fabrication of Spire Corporation's Block 5 photovoltaic flat plate module is reviewed. These modules exhibited power of about 70 watts under standard test conditions. Results of performance and environmental testing are provided.

The PriA Replication Restart Protein Blocks Replicase Access Prior to Helicase Assembly and Directs Template Specificity through Its ATPase Activity*

PubMed Central

Manhart, Carol M.; McHenry, Charles S.

2013-01-01

The PriA protein serves as an initiator for the restart of DNA replication on stalled replication forks and as a checkpoint protein that prevents the replicase from advancing in a strand displacement reaction on forks that do not contain a functional replicative helicase. We have developed a primosomal protein-dependent fluorescence resonance energy transfer (FRET) assay using a minimal fork substrate composed of synthetic oligonucleotides. We demonstrate that a self-loading reaction, which proceeds at high helicase concentrations, occurs by threading of a preassembled helicase over free 5′-ends, an event that can be blocked by attaching a steric block to the 5′-end or coating DNA with single-stranded DNA binding protein. The specificity of PriA for replication forks is regulated by its intrinsic ATPase. ATPase-defective PriA K230R shows a strong preference for substrates that contain no gap between the leading strand and the duplex portion of the fork, as demonstrated previously. Wild-type PriA prefers substrates with larger gaps, showing maximal activity on substrates on which PriA K230R is inactive. We demonstrate that PriA blocks replicase function on forks by blocking its binding. PMID:23264623

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants

PubMed Central

Tikhonov, Denis B.

2017-01-01

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. PMID:28258204

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

PubMed

Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

Electrochemical aptasensor based on the dual-amplification of G-quadruplex horseradish peroxidase-mimicking DNAzyme and blocking reagent-horseradish peroxidase.

PubMed

Yuan, Yali; Gou, Xuxu; Yuan, Ruo; Chai, Yaqin; Zhuo, Ying; Mao, Li; Gan, Xianxue

2011-06-15

A simple electrochemical aptasensor for sensitive detection of thrombin was fabricated with G-quadruplex horseradish peroxidase-mimicking DNAzyme (hemin/G-quadruplex system) and blocking reagent-horseradish peroxidase as dual signal-amplification scheme. Gold nanoparticles (nano-Au) were firstly electrodeposited onto single wall nanotube (SWNT)-graphene modified electrode surface for the immobilization of electrochemical probe of nickel hexacyanoferrates nanoparticles (NiHCFNPs). Subsequently, another nano-Au layer was electrodeposited for further immobilization of thrombin aptamer (TBA), which later formed hemin/G-quadruplex system with hemin. Horseradish peroxidases (HRP) then served as blocking reagent to block possible remaining active sites and avoided the non-specific adsorption. In the presence of thrombin, the TBA binded to thrombin and the hemin released from the hemin/G-quadruplex electrocatalytic structure, increasing steric hindrance of the aptasensor and decomposing hemin/G-quadruplex electrocatalytic structure, which finally decreased the electrocatalytic efficiency of aptasensor toward H(2)O(2) in the presence of NiHCFNPs with a decreased electrochemical signal. On the basis of the synergistic amplifying action, a detection limit as low as 2 pM for thrombin was obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Fault-tolerant computer study. [logic designs for building block circuits

NASA Technical Reports Server (NTRS)

Rennels, D. A.; Avizienis, A. A.; Ercegovac, M. D.

1981-01-01

A set of building block circuits is described which can be used with commercially available microprocessors and memories to implement fault tolerant distributed computer systems. Each building block circuit is intended for VLSI implementation as a single chip. Several building blocks and associated processor and memory chips form a self checking computer module with self contained input output and interfaces to redundant communications buses. Fault tolerance is achieved by connecting self checking computer modules into a redundant network in which backup buses and computer modules are provided to circumvent failures. The requirements and design methodology which led to the definition of the building block circuits are discussed.

Multi-purpose greenhouse of changeable geometry (MGCG)

NASA Astrophysics Data System (ADS)

Kordium, V.; Kornejchuk, A.

In the frames of scientific program of National Cosmic Agency of Ukraine the multipurpose greenhouse is being developed. It is destined for the performance of biological and biotechnological experiments as well as for planting of fast growing vegetable cultures for crew ration enrichment and positive psychological influence under the conditions of long-term flight in the international space station or in other cosmic flying objects. Main principle of greenhouse arrangement is the existence of unified modules. Their sets and combinations permit to form executively different space greenhouse configurations. The minimal structural greenhouse unit suitable either for construction of total configuration or for autonomous functioning, is a carrying composite platform (CCP). The experimental vegetative module (EVM) and the module, supporting microclimate needed inside EVM, are launched to CCP. The amount of these modules and their configuration depend on quantity and complexity of tasks to be solved as well as on duration of their performance. These modules form the experimental block. Four modules of much larger sizes, which form experimentally technological block, are used for further studies of objectives approved in the experimental block. The technologies developed for growing plants are used in the third, technological block, which is a one large vegetative module. All three greenhouse blocks can be changed in their sizes in three dimensions, and function either in a complete greenhouse structure, or autonomously. The control is performed from a board computer, or, if necessary, it is governed with automation devices placed on a front panel of blocks. All three blocks are pulled out along the directing base into the station passage, and this makes free access to the base modules, convenient work with them, and à good survey.

Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

PubMed

Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

2018-05-04

Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

Program structure-based blocking

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

Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.

2017-09-26

Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

User handbook for block IV silicon solar cell modules

NASA Technical Reports Server (NTRS)

Smokler, M. I.

1982-01-01

The essential electrical and mechanical characteristics of block 4 photovoltaic solar cell modules are described. Such module characteristics as power output, nominal operating voltage, current-voltage characteristics, nominal operating cell temperature, and dimensions are tabulated. The limits of the environmental and other stress tests to which the modules are subjected are briefly described.

Novel azepino-perylenebisimides: synthesis, structure, and properties.

PubMed

Mishra, Ruchika; Panini, Piyush; Sankar, Jeyaraman

2014-08-01

The first example of an azepine ring formation by counterintuitive nucleophilic participation of DBU was observed at the sterically crowded bay area of electron-deficient perylenebisimide (PBI). This is also a rare example of the formation of a seven-membered ring via two consecutive C-N bond formations in a single step. Azepino-PBIs reveal panchromatic absorption covering the whole visible region. Further novelty of these PBIs lies within the fact that their photophysical characteristics can easily be modulated by suitable substituents.

Mechanism of Acetylcholinesterase Inhibition by Fasciculin: A 5-ns Molecular Dynamics Simulation

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

Tai, Kaihsu; Shen, T Y.; Henchman, Richard H.

Our previous molecular dynamics simulation (10 ns) of mouse acetylcholinesterase (EC 3.1.1.7) revealed complex fluctuation of the enzyme active site gorge. Now we report a 5-ns simulation of acetylcholinesterase complexed with fasciculin 2. Fasciculin 2 binds to the gorge entrance of acetylcholinesterase with excellent complementarity and many polar and hydrophobic interactions. In this simulation of the protein-protein complex, where fasciculin 2 appears to sterically block access of ligands to the gorge, again we observe a two-peaked probability distribution of the gorge width. When fasciculin is present, the gorge width distribution is altered such that the gorge is more likely tomore » be narrow. Moreover, there are large increases in the opening of alternative passages, namely, the side door (near Thr 75) and the back door (near Tyr 449). Finally, the catalytic triad arrangement in the acetylcholinesterase active site is disrupted with fasciculin bound. These data support that, in addition to the steric obstruction seen in the crystal structure, fasciculin may inhibit acetylcholinesterase by combined allosteric and dynamical means. Additional data from these simulations can be found at http://mccammon.ucsd.edu/.« less

Stability of biogenic metal(loid) nanomaterials related to the colloidal stabilization theory of chemical nanostructures.

PubMed

Piacenza, Elena; Presentato, Alessandro; Turner, Raymond J

2018-02-25

In the last 15 years, the exploitation of biological systems (i.e. plants, bacteria, mycelial fungi, yeasts, and algae) to produce metal(loid) (Me)-based nanomaterials has been evaluated as eco-friendly and a cost-effective alternative to the chemical synthesis processes. Although the biological mechanisms of biogenic Me-nanomaterial (Bio-Me-nanomaterials) production are not yet completely elucidated, a key advantage of such bio-nanostructures over those chemically synthesized is related to their natural thermodynamic stability, with several studies ascribed to the presence of an organic layer surrounding these Bio-Me-nanostructures. Different macromolecules (e.g. proteins, peptides, lipids, DNA, and polysaccharides) or secondary metabolites (e.g. flavonoids, terpenoids, glycosides, organic acids, and alkaloids) naturally produced by organisms have been indicated as main contributors to the stabilization of Bio-Me-nanostructures. Nevertheless, the chemical-physical mechanisms behind the ability of these molecules in providing stability to Bio-Me-nanomaterials are unknown. In this context, transposing the stabilization theory of chemically synthesized Me-nanomaterials (Ch-Me-nanomaterials) to biogenic materials can be used towards a better comprehension of macromolecules and secondary metabolites role as stabilizing agents of Bio-Me-nanomaterials. According to this theory, nanomaterials are generally featured by high thermodynamic instability in suspension, due to their high surface area and surface energy. This feature leads to the necessity to stabilize chemical nanostructures, even during or directly after their synthesis, through the development of (i) electrostatic, (ii) steric, or (iii) electrosteric interactions occurring between molecules and nanomaterials in suspension. Based on these three mechanisms, this review is focused on parallels between the stabilization of biogenic or chemical nanomaterials, suggesting which chemical-physical mechanisms may be involved in the natural stability of Bio-Me-nanomaterials. As a result, macromolecules such as DNA, polyphosphates and proteins may electrostatically interact with Bio-Me-nanomaterials in suspension through their charged moieties, showing the same properties of counterions in Ch-Me-nanostructure suspensions. Since several biomolecules (e.g. neutral lipids, nonionic biosurfactants, polysaccharides, and secondary metabolites) produced by metal(loid)-grown organisms can develop similar steric hindrance as compared to nonionic amphiphilic surfactants and block co-polymers generally used to sterically stabilize Ch-Me-nanomaterials. These biomolecules, most likely, are involved in the development of steric stabilization, because of their bulky structures. Finally, charged lipids and polysaccharides, ionic biosurfactants or proteins with amphiphilic properties can exert a dual effect (i.e. electrostatic and steric repulsion interactions) in the contest of Bio-Me-nanomaterials, leading to the high degree of stability observed.

Mechanism for CARMIL Protein Inhibition of Heterodimeric Actin-capping Protein*

PubMed Central

Kim, Taekyung; Ravilious, Geoffrey E.; Sept, David; Cooper, John A.

2012-01-01

Capping protein (CP) controls the polymerization of actin filaments by capping their barbed ends. In lamellipodia, CP dissociates from the actin cytoskeleton rapidly, suggesting the possible existence of an uncapping factor, for which the protein CARMIL (capping protein, Arp2/3 and myosin-I linker) is a candidate. CARMIL binds to CP via two motifs. One, the CP interaction (CPI) motif, is found in a number of unrelated proteins; the other motif is unique to CARMILs, the CARMIL-specific interaction motif. A 115-aa CARMIL fragment of CARMIL with both motifs, termed the CP-binding region (CBR), binds to CP with high affinity, inhibits capping, and causes uncapping. We wanted to understand the structural basis for this function. We used a collection of mutants affecting the actin-binding surface of CP to test the possibility of a steric-blocking model, which remained open because a region of CBR was not resolved in the CBR/CP co-crystal structure. The CP actin-binding mutants bound CBR normally. In addition, a CBR mutant with all residues of the unresolved region changed showed nearly normal binding to CP. Having ruled out a steric blocking model, we tested an allosteric model with molecular dynamics. We found that CBR binding induces changes in the conformation of the actin-binding surface of CP. In addition, ∼30-aa truncations on the actin-binding surface of CP decreased the affinity of CBR for CP. Thus, CARMIL promotes uncapping by binding to a freely accessible site on CP bound to a filament barbed end and inducing a change in the conformation of the actin-binding surface of CP. PMID:22411988

Stereotypes of Aging. Module A-2. Block A. Basic Knowledge of the Aging Process.

ERIC Educational Resources Information Center

Harvey, Dexter; Cap, Orest

This instructional module on stereotypes of aging is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Three sections present informative…

Modular support blocks for fluid lines

NASA Technical Reports Server (NTRS)

Dimino, J. M.; Deskin, R. D.

1974-01-01

Modular line block comprises matched modular elements machined to accept fluid lines of different diameters. Modules can support different fluid-line configurations. Top and bottom surfaces are machined to accept dovetail strip used for holding modules together. End modules have holes drilled through to accept fastening screws.

Physiological Aspects of Aging. Module A-5. Block A. Basic Knowledge of the Aging Process.

ERIC Educational Resources Information Center

Harvey, Dexter; Cap, Orest

This instructional module on physiological aspects of aging is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Nine sections present…

Confusion and the Older Adult. Module A-8. Block A. Basic Knowledge of the Aging Process.

ERIC Educational Resources Information Center

Harvey, Dexter; Cap, Orest

This instructional module on confusion and the older adult is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Three sections present…

Inexpensive position sensitive detector block for dedicated PET cameras using 40-mm diameter PMT in quadrant sharing configuration

NASA Astrophysics Data System (ADS)

Uribe, J.; Aykac, M.; Baghaei, H.; Li, Hongdi; Wang, Yu; Liu, Yaqiang; Wong, V.; Xing, Tao; Ramirez, R.; Wong, Wai-Hoi

2003-06-01

Recent approvals by CMS (HCFA) for reimbursement of positron emission tomography (PET) scans fuels the rapid grow of the PET market, thus creating the need for more affordable dedicated PET scanners. The objective of the work presented here was the development of a BGO position-sensitive block with similar detector area (40 mm /spl times/ 40 mm) and same number of crystals (8 /spl times/ 8) as the block of a commercial BGO PET, using the less expensive photomultiplier quadrant sharing (PQS) technique. This block is coupled to four single-anode 40-mm diameter photomultipliers (PMT) instead of the 19-mm PMT used in a popular commercial BGO PET, and each PMT is shared by four adjacent detector blocks. Potentially, this design needs only 25% of the number of PMT used in the commercial BGO PET. In order not to waste the unused half-row of PMT at the edges of a detector panel/module when the module is made up solely of square blocks, an extended rectangular block has to be developed for the edge-blocks in the module, which maximized the use of the PMT and minimized the gap between modules. Only the extended block needs to be developed to derive the design for all the blocks in the module because the symmetric square block uses the same light-distributing partitions as those along the short side of the extended rectangular block. White-paint masks applied with accurate templates and airbrush were fine-tuned for every pair of adjacent crystals. The experimental block developed in this study provided good crystal-decoding. The composite energy spectrum of all 64 crystals showed a prominent photopeak. The worst crystal sitting in the air space between 4 round PMTs still has 60% of the signal pulse height as the best crystal. The average energy resolution was 21.8% for 511 keV gamma (range 17% - 28.7%) that compared well with the 22% - 44% measured with GE and CTI blocks. The image resolution provided by the PQS blocks is expected to be comparable to that of commercial BGO PETs as similar size crystals were decoded.

Module performance and failure analysis area: Flat-plate solar array project

NASA Technical Reports Server (NTRS)

Tornstrom, E.

1984-01-01

A redesign of the initial (Group I) Mobile Solar Block V module was done and documented. Manufacturing experience and accelerated test data from Group I formed the basis for the redesign. Ten Block V Group II modules were submitted for evaluation and the results are presented.

Electrophilic Triterpenoid Enones: A Comparative Thiol-Trapping and Bioactivity Study.

PubMed

Del Prete, Danilo; Taglialatela-Scafati, Orazio; Minassi, Alberto; Sirignano, Carmina; Cruz, Cristina; Bellido, Maria L; Muñoz, Eduardo; Appendino, Giovanni

2017-08-25

Bardoxolone methyl (1) is the quintessential member of triterpenoid cyanoacrylates, an emerging class of bioactive compounds capable of transient covalent binding to thiols. The mechanistic basis for this unusual "pulsed reactivity" profile and the mode of its biological translation are unknown. To provide clues on these issues, a series of Δ 1 -dehydrooleanolates bearing an electron-withdrawing group at C-2 (7a-m) were prepared from oleanolic acid (3a) and comparatively investigated in terms of reactivity with thiols and bioactivity against a series of electrophile-sensitive transcription factors (Nrf2, NF-κB, STAT3). The emerging picture suggests that the triterpenoid scaffold sharply decreases the reactivity of the enone system by steric encumbrance and that only strongly electrophilic and sterically undemanding substituents such as a cyanide or a carboxylate group can re-establish Michael reactivity, albeit in a transient way for the cyanide group. In general, a substantial dissection between the thiol-trapping ability and the modulation of biological end-points sensitive to thiol alkylation was observed, highlighting the role of shape complementarity for the activity of triterpenoid thia-Michael acceptors.

Steric engineering of metal-halide perovskites with tunable optical band gaps

NASA Astrophysics Data System (ADS)

Filip, Marina R.; Eperon, Giles E.; Snaith, Henry J.; Giustino, Feliciano

2014-12-01

Owing to their high energy-conversion efficiency and inexpensive fabrication routes, solar cells based on metal-organic halide perovskites have rapidly gained prominence as a disruptive technology. An attractive feature of perovskite absorbers is the possibility of tailoring their properties by changing the elemental composition through the chemical precursors. In this context, rational in silico design represents a powerful tool for mapping the vast materials landscape and accelerating discovery. Here we show that the optical band gap of metal-halide perovskites, a key design parameter for solar cells, strongly correlates with a simple structural feature, the largest metal-halide-metal bond angle. Using this descriptor we suggest continuous tunability of the optical gap from the mid-infrared to the visible. Precise band gap engineering is achieved by controlling the bond angles through the steric size of the molecular cation. On the basis of these design principles we predict novel low-gap perovskites for optimum photovoltaic efficiency, and we demonstrate the concept of band gap modulation by synthesising and characterising novel mixed-cation perovskites.

The blocking probability of Geiger-mode avalanche photo-diodes

NASA Technical Reports Server (NTRS)

Moision, Bruce; Srinivasan, Meera; Hamkins, Jon

2005-01-01

When a photo is detected by a Geiger-mode avalanche photo-diode (GMAPD), the detector is rendered inactive, or blocked, for a certain period of time. In this paper we derive the blocking probability for a GMAPD whose input is either an unmodulated, Benoulli modulated or pulse-position-modulated Poisson process.

Mass-induced sea level variations in the Red Sea from steric-corrected altimetry, GRACE, in-situ bottom pressure records, and hydrographic observations

NASA Astrophysics Data System (ADS)

Feng, Wei; Lemoine, Jean-Michel; Zhong, Min; Xu, Houze

2014-05-01

An annual amplitude of ~18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from steric-corrected altimetry and the Gravity Recovery and Climate Experiment (GRACE) satellites from 2003 to 2011, which dominates the mean sea level in the region. Seawater mass variations here generally reach maximum in late January/early February. The steric component of SLV calculated from oceanographic temperature and salinity data is relatively small and peaks about seven months later than mass variations. The phase difference between the steric SLV and the mass-induced SLV indicates that when the Red Sea gains the mass from inflow water in winter, the steric SLV fall, and vice versa in summer. In-situ bottom pressure records in the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. Furthermore, we compare the horizontal water mass flux in the Red Sea from steric-corrected altimetry and GRACE with that estimated from hydrographic observations.

Steric and mass-induced Mediterranean sea level trends from 14 years of altimetry data

NASA Astrophysics Data System (ADS)

Criado-Aldeanueva, Francisco; Del Río Vera, Jorge; García-Lafuente, Jesús

2008-02-01

Long-term series of almost 14 years of altimetry data (1992-2005) have been analysed along with Sea Surface Temperature (SST) and temperature and salinity profiles to investigate sea level trends over the Mediterranean Sea. Although sea level variations are mainly driven by the steric contribution, the mass-induced component plays some role in modulating its oscillation. A spatially averaged positive trend of 2.1 ± 0.6 mm/year has been observed, but a change in sign in 2001 seems to appear. Steric effects (mainly on thermal origin) account for ˜ 55% of sea level trend. Although Mediterranean Sea is a semi-enclosed basin, this value is comparable to that reported for the global ocean. Sea level rise is particularly important in the Levantine basin south of Crete with values up to 10 ± 1 mm/year. Other areas of sea level rise are localised throughout the Levantine basin and in the Adriatic and Alboran Seas, with more moderate values. Sea level drop areas are localised in the Algerian basin, between the Balearic Islands and the African coasts and, particularly, in the Ionian basin. In this area, negative trends as high as - 10 ± 0.8 mm/year are detected mainly due to the mass-induced contribution, which suggests decadal changes of surface circulation. The inferred sea level trends have been correlated with North Atlantic Oscillation (NAO) indices and a low but significant correlation has been detected between sea level in the Levantine and Balearic basins and NAO index.

Modulation format identification aided hitless flexible coherent transceiver.

PubMed

Xiang, Meng; Zhuge, Qunbi; Qiu, Meng; Zhou, Xingyu; Zhang, Fangyuan; Tang, Ming; Liu, Deming; Fu, Songnian; Plant, David V

2016-07-11

We propose a hitless flexible coherent transceiver enabled by a novel modulation format identification (MFI) scheme for dynamic agile optical networks. The modulation format transparent digital signal processing (DSP) is realized by a block-wise decision-directed least-mean-square (DD-LMS) equalizer for channel tracking, and a pilot symbol aided superscalar phase locked loop (PLL) for carrier phase estimation (CPE). For the MFI, the modulation format information is encoded onto the pilot symbols initially used for CPE. Therefore, the proposed MFI method does not require extra overhead. Moreover, it can identify arbitrary modulation formats including multi-dimensional formats, and it enables tracking of the format change for short data blocks. The performance of the proposed hitless flexible coherent transceiver is successfully evaluated with five modulation formats including QPSK, 16QAM, 64QAM, Hybrid QPSK/8QAM and set-partitioning (SP)-512-QAM. We show that the proposed MFI method induces a negligible performance penalty. Moreover, we experimentally demonstrate that such a hitless transceiver can adapt to fast block-by-block modulation format switching. Finally, the performance improvement of the proposed MFI method is experimentally verified with respect to other commonly used MFI methods.

Defining space around conducting polymers: reversible protonic doping of a canopied polypyrrole.

PubMed

Lee, Dongwhan; Swager, Timothy M

2003-06-11

A canopy-shaped pyrrole derivative 2 was prepared, in which a sterically demanding pendant group is juxtaposed to the pyrrole fragment to minimize interstrand pi-pi stacking interactions in the resulting polymer. Anodic polymerization of 2 afforded highly conductive poly(2), the electronic structure of which was probed by various spectroelectrochemical techniques. A limited charge delocalization within poly(2) translates into a well-defined conductivity profile, properties important for resistivity-based sensing. Notably, the bulk conductivity was precisely modulated by a rapid and reversible deprotonation and reprotonation of the polymer backbone.

A comparison of progestin and androgen receptor binding using the CoMFA technique

NASA Astrophysics Data System (ADS)

Loughney, Deborah A.; Schwender, Charles F.

1992-12-01

A series of 48 steroids has been studied with the SYBYL QSAR module using Relative Binding Affinities (RBAs) to progesterone and androgen receptors obtained from the literature. Models for the progesterone and androgen data were developed. Both models show regions where sterics and electrostatics correlate to binding affinity but are different for androgen and progesterone which suggests differences possibly important for receptor selectivity. The progesterone model is more predictive than the androgen (predictive r2 of 0.725 vs. 0.545 for progesterone and androgen, respectively).

Poisson-Nernst-Planck equations with steric effects - non-convexity and multiple stationary solutions

NASA Astrophysics Data System (ADS)

Gavish, Nir

2018-04-01

We study the existence and stability of stationary solutions of Poisson-Nernst-Planck equations with steric effects (PNP-steric equations) with two counter-charged species. We show that within a range of parameters, steric effects give rise to multiple solutions of the corresponding stationary equation that are smooth. The PNP-steric equation, however, is found to be ill-posed at the parameter regime where multiple solutions arise. Following these findings, we introduce a novel PNP-Cahn-Hilliard model, show that it is well-posed and that it admits multiple stationary solutions that are smooth and stable. The various branches of stationary solutions and their stability are mapped utilizing bifurcation analysis and numerical continuation methods.

Elderly Service Workers' Training Project. Block B: Cultural Gerontology. Module B.4: Native Culture.

ERIC Educational Resources Information Center

Harvey, Dexter; Cap, Orest

This learning module, which is part of a three-block series intended to help human service workers develop the skills necessary to solve the problems encountered in their daily contact with elderly clients of different cultural backgrounds, deals with the cultural heritage of Native Canadians. The module begins with a brief introduction and…

Construction and Self-Assembly of Single-Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water.

PubMed

Zhu, Zhengguang; Xu, Na; Yu, Qiuping; Guo, Lei; Cao, Hui; Lu, Xinhua; Cai, Yuanli

2015-08-01

Simultaneous coordination-association and electrostatic-repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self-assembly of artificial aqueous polymer single-chain nanoparticles (SCNPs). Herein, the construction and self-assembly of dative-bonded aqueous SCNPs are reported via simultaneous coordination-association and electrostatic-repulsion interactions within single chains of histamine-based hydrophilic block copolymer. The electrostatic-repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)-coordination leads to the intramolecular association and single-chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative-bonded block and steric shielding of nonionic water-soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media-sensitive phase-transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme-inspired smart aqueous catalysts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sequence-specific unusual (1-->2)-type helical turns in alpha/beta-hybrid peptides.

PubMed

Prabhakaran, Panchami; Kale, Sangram S; Puranik, Vedavati G; Rajamohanan, P R; Chetina, Olga; Howard, Judith A K; Hofmann, Hans-Jörg; Sanjayan, Gangadhar J

2008-12-31

This article describes novel conformationally ordered alpha/beta-hybrid peptides consisting of repeating l-proline-anthranilic acid building blocks. These oligomers adopt a compact, right-handed helical architecture determined by the intrinsic conformational preferences of the individual amino acid residues. The striking feature of these oligomers is their ability to display an unusual periodic pseudo beta-turn network of nine-membered hydrogen-bonded rings formed in the forward direction of the sequence by 1-->2 amino acid interactions both in solid-state and in solution. Conformational investigations of several of these oligomers by single-crystal X-ray diffraction, solution-state NMR, and ab initio MO theory suggest that the characteristic steric and dihedral angle restraints exerted by proline are essential for stabilizing the unusual pseudo beta-turn network found in these oligomers. Replacing proline by the conformationally flexible analogue alanine (Ala) or by the conformationally more constrained alpha-amino isobutyric acid (Aib) had an adverse effect on the stabilization of this structural architecture. These findings increase the potential to design novel secondary structure elements profiting from the steric and dihedral angle constraints of the amino acid constituents and help to augment the conformational space available for synthetic oligomer design with diverse backbone structures.

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus‐like particle

PubMed Central

Tekewe, Alemu; Connors, Natalie K.; Middelberg, Anton P. J.

2016-01-01

Abstract Virus‐like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co‐expression of unmodified VP1 and modular VP1‐RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. PMID:27222486

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus-like particle.

PubMed

Tekewe, Alemu; Connors, Natalie K; Middelberg, Anton P J; Lua, Linda H L

2016-08-01

Virus-like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co-expression of unmodified VP1 and modular VP1-RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. © 2016 The Protein Society.

X-ray structures and mechanism of the human serotonin transporter.

PubMed

Coleman, Jonathan A; Green, Evan M; Gouaux, Eric

2016-04-21

The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.

Two-dimensional honeycomb network through sequence-controlled self-assembly of oligopeptides.

PubMed

Abb, Sabine; Harnau, Ludger; Gutzler, Rico; Rauschenbach, Stephan; Kern, Klaus

2016-01-12

The sequence of a peptide programs its self-assembly and hence the expression of specific properties through non-covalent interactions. A large variety of peptide nanostructures has been designed employing different aspects of these non-covalent interactions, such as dispersive interactions, hydrogen bonding or ionic interactions. Here we demonstrate the sequence-controlled fabrication of molecular nanostructures using peptides as bio-organic building blocks for two-dimensional (2D) self-assembly. Scanning tunnelling microscopy reveals changes from compact or linear assemblies (angiotensin I) to long-range ordered, chiral honeycomb networks (angiotensin II) as a result of removal of steric hindrance by sequence modification. Guided by our observations, molecular dynamic simulations yield atomistic models for the elucidation of interpeptide-binding motifs. This new approach to 2D self-assembly on surfaces grants insight at the atomic level that will enable the use of oligo- and polypeptides as large, multi-functional bio-organic building blocks, and opens a new route towards rationally designed, bio-inspired surfaces.

Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions.

PubMed

Musa, H; Gough, J D; Lees, W J; Veenstra, R D

2001-12-01

The rat connexin40 gap junction channel is permeable to monovalent cations including tetramethylammonium and tetraethylammonium ions. Larger tetraalkyammonium (TAA(+)) ions beginning with tetrabutylammonium (TBA(+)) reduced KCl junctional currents disproportionately. Ionic blockade by tetrapentylammonium (TPeA(+)) and tetrahexylammonium (THxA(+)) ions were concentration- and voltage-dependent and occurred only when TAA(+) ions were on the same side as net K(+) efflux across the junction, indicative of block of the ionic permeation pathway. The voltage-dependent dissociation constants (K(m)(V(j))) were lower for THxA(+) than TPeA(+), consistent with steric effects within the pore. The K(m)-V(j) relationships for TPeA(+) and THxA(+) were fit with different reaction rate models for a symmetrical (homotypic) connexin gap junction channel and were described by either a one- or two-site model that assumed each ion traversed the entire V(j) field. Bilateral addition of TPeA(+) ions confirmed a common site of interaction within the pore that possessed identical K(m)(V(j)) values for cis-trans concentrations of TPeA(+) ions as indicated by the modeled I-V relations and rapid channel block that precluded unitary current measurements. The TAA(+) block of K(+) currents and bilateral TPeA(+) interactions did not alter V(j)-gating of Cx40 gap junctions. N-octyl-tributylammonium and -triethylammonium also blocked rCx40 channels with higher affinity and faster kinetics than TBA(+) or TPeA(+), indicative of a hydrophobic site within the pore near the site of block.

From information theory to quantitative description of steric effects.

PubMed

Alipour, Mojtaba; Safari, Zahra

2016-07-21

Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

Performance enhancement of perovskite solar cells with Mg-doped TiO{sub 2} compact film as the hole-blocking layer

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

Wang, Jing; Qin, Minchao; Tao, Hong

2015-03-23

In this letter, we report perovskite solar cells with thin dense Mg-doped TiO{sub 2} as hole-blocking layers (HBLs), which outperform cells using TiO{sub 2} HBLs in several ways: higher open-circuit voltage (V{sub oc}) (1.08 V), power conversion efficiency (12.28%), short-circuit current, and fill factor. These properties improvements are attributed to the better properties of Mg-modulated TiO{sub 2} as compared to TiO{sub 2} such as better optical transmission properties, upshifted conduction band minimum (CBM) and downshifted valence band maximum (VBM), better hole-blocking effect, and higher electron life time. The higher-lying CBM due to the modulation with wider band gap MgO and themore » formation of magnesium oxide and magnesium hydroxides together resulted in an increment of V{sub oc}. In addition, the Mg-modulated TiO{sub 2} with lower VBM played a better role in the hole-blocking. The HBL with modulated band position provided better electron transport and hole blocking effects within the device.« less

Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues.

PubMed

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-05-01

Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es ), electronic (σp ) and lipophilic (πp ) parameters of the para substituents. For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es ) are key determinants of this selectivity. © 2014 The British Pharmacological Society.

Altering DNA-Programmable Colloidal Crystallization Paths by Modulating Particle Repulsion

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

Wang, Mary X.; Brodin, Jeffrey D.; Millan, Jaime A.

Colloidal crystal engineering with DNA can be used to realize precise control over nanoparticle (NP) arrangement. Here, we investigate a case of DNA-based assembly where the properties of DNA as a polyelectrolyte brush are employed to alter a hybridization-driven NP crystallization pathway. Using the co-assembly of DNA-conjugated proteins and spherical gold 2 nanoparticles (AuNPs) as a model system, we explore how steric repulsion between non-complementary, neighboring DNA-NPs due to overlapping DNA shells can influence their ligand-directed behavior. Specifically, our experimental data coupled with coarse-grained molecular dynamics (MD) simulations reveal that by changing factors related to NP repulsion, two structurally distinctmore » outcomes can be achieved. When steric repulsion between DNA-AuNPs is significantly greater than that between DNA-proteins, a lower packing density crystal lattice is favored over the structure that is predicted by design rules based on DNA-hybridization considerations alone. This is enabled by the large difference in DNA density on AuNPs versus proteins and can be tuned by modulating the flexibility, and thus conformational entropy, of the DNA on the constituent particles. At intermediate ligand flexibility, the crystallization pathways are energetically similar and the structural outcome can be adjusted using the density of DNA duplexes on DNA-AuNPs and by screening the Coulomb potential between them. Such lattices are shown to undergo dynamic reorganization upon changing salt concentration. These data help elucidate the structural considerations necessary for understanding repulsive forces in DNA-assembly and lay the groundwork for using them to increase architectural diversity in engineering colloidal crystals.« less

Quantitative structure–activity relationship analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-01-01

Background and Purpose Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure–activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es), electronic (σp) and lipophilic (πp) parameters of the para substituents. Experimental Approach For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key Results MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and Implications Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es) are key determinants of this selectivity. PMID:25438806

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

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

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. This approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

DOE PAGES

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.; ...

2016-09-08

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. Lastly, this approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

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

Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.

The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. Lastly, this approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

Divergent Mechanistic Routes for the Formation of gem-Dimethyl Groups in the Biosynthesis of Complex Polyketides

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

Poust, S; Phelan, RM; Deng, K

The gem-dimethyl groups in polyketide-derived natural products add steric bulk and, accordingly, lend increased stability to medicinal compounds, however, our ability to rationally incorporate this functional group in modified natural products is limited. In order to characterize the mechanism of gem-dimethyl group formation, with a goal toward engineering of novel compounds containing this moiety, the gem-dimethyl group producing polyketide synthase (PKS) modules of yersiniabactin and epothilone were characterized using mass spectrometry. The work demonstrated, contrary to the canonical understanding of reaction order in PKSs, that methylation can precede condensation in gem-dimethyl group producing PKS modules. Experiments showed that both PKSsmore » are able to use dimethylmalonyl acyl carrier protein (ACP) as an extender unit. Interestingly, for epothilone module8, use of dimethylmalonyl-ACP appeared to be the sole route to form a gem-dimethylated product, while the yersiniabactin PKS could methylate before or after ketosynthase condensation.« less

World Wide Web-based system for the calculation of substituent parameters and substituent similarity searches.

PubMed

Ertl, P

1998-02-01

Easy to use, interactive, and platform-independent WWW-based tools are ideal for development of chemical applications. By using the newly emerging Web technologies such as Java applets and sophisticated scripting, it is possible to deliver powerful molecular processing capabilities directly to the desk of synthetic organic chemists. In Novartis Crop Protection in Basel, a Web-based molecular modelling system has been in use since 1995. In this article two new modules of this system are presented: a program for interactive calculation of important hydrophobic, electronic, and steric properties of organic substituents, and a module for substituent similarity searches enabling the identification of bioisosteric functional groups. Various possible applications of calculated substituent parameters are also discussed, including automatic design of molecules with the desired properties and creation of targeted virtual combinatorial libraries.

Peripheral Protein Unfolding Drives Membrane Bending.

PubMed

Siaw, Hew Ming Helen; Raghunath, Gokul; Dyer, R Brian

2018-06-20

Dynamic modulation of lipid membrane curvature can be achieved by a number of peripheral protein binding mechanisms such as hy-drophobic insertion of amphipathic helices and membrane scaffolding. Recently, an alternative mechanism was proposed in which crowding of peripherally bound proteins induces membrane curvature through steric pressure generated by lateral collisions. This effect was enhanced using intrinsically disordered proteins that possess high hydrodynamic radii, prompting us to explore whether membrane bending can be triggered by the folding-unfolding transition of surface-bound proteins. We utilized histidine-tagged human serum albumin bound to Ni-NTA-DGS containing liposomes as our model system to test this hypothesis. We found that reduction of the disulfide bonds in the protein resulted in unfolding of HSA, which subsequently led to membrane tubule formation. The frequency of tubule formation was found to be significantly higher when the proteins were unfolded while being localized to a phase-separated domain as opposed to randomly distributed in fluid phase liposomes, indicating that the steric pressure generated from protein unfolding is directly responsible for membrane deformation. Our results are critical for the design of peripheral membrane protein-immobilization strategies and open new avenues for exploring mechanisms of membrane bending driven by conformational changes of peripheral membrane proteins.

Nucleophilic substitution at silicon (SN2@Si) via a central reaction barrier.

PubMed

Bento, A Patrícia; Bickelhaupt, F Matthias

2007-03-16

It is textbook knowledge that nucleophilic substitution at carbon (SN2@C) proceeds via a central reaction barrier which disappears in the corresponding nucleophilic substitution reaction at silicon (SN2@Si). Here, we address the question why the central barrier disappears from SN2@C to SN2@Si despite the fact that these processes are isostructural and isoelectronic. To this end, we have explored and analyzed the potential energy surfaces (PES) of various Cl-+CR3Cl (R=H, CH3) and Cl-+SiR3Cl model reactions (R=H, CH3, C2H5, and OCH3). Our results show that the nature of the SN2 reaction barrier is in essence steric, but that it can be modulated by electronic factors. Thus, simply by increasing the steric demand of the substituents R around the silicon atom, the SN2@Si mechanism changes from its regular single-well PES (with a stable intermediate transition complex, TC), via a triple-well PES (with a pre- and a post-TS before and after the central TC), to a double-well PES (with a TS; R=OCH3), which is normally encountered for SN2@C reactions.

Tuned, driven, and active soft matter

NASA Astrophysics Data System (ADS)

Menzel, Andreas M.

2015-02-01

One characteristic feature of soft matter systems is their strong response to external stimuli. As a consequence they are comparatively easily driven out of their ground state and out of equilibrium, which leads to many of their fascinating properties. Here, we review illustrative examples. This review is structured by an increasing distance from the equilibrium ground state. On each level, examples of increasing degree of complexity are considered. In detail, we first consider systems that are quasi-statically tuned or switched to a new state by applying external fields. These are common liquid crystals, liquid crystalline elastomers, or ferrogels and magnetic elastomers. Next, we concentrate on systems steadily driven from outside e.g. by an imposed flow field. In our case, we review the reaction of nematic liquid crystals, of bulk-filling periodically modulated structures such as block copolymers, and of localized vesicular objects to an imposed shear flow. Finally, we focus on systems that are "active" and "self-driven". Here our range spans from idealized self-propelled point particles, via sterically interacting particles like granular hoppers, via microswimmers such as self-phoretically driven artificial Janus particles or biological microorganisms, via deformable self-propelled particles like droplets, up to the collective behavior of insects, fish, and birds. As we emphasize, similarities emerge in the features and behavior of systems that at first glance may not necessarily appear related. We thus hope that our overview will further stimulate the search for basic unifying principles underlying the physics of these soft materials out of their equilibrium ground state.

Single-Stranded Nucleic Acids Bind to the Tetramer Interface of SAMHD1 and Prevent Formation of the Catalytic Homotetramer.

PubMed

Seamon, Kyle J; Bumpus, Namandjé N; Stivers, James T

2016-11-08

Sterile alpha motif and HD domain protein 1 (SAMHD1) is a unique enzyme that plays important roles in nucleic acid metabolism, viral restriction, and the pathogenesis of autoimmune diseases and cancer. Although much attention has been focused on its dNTP triphosphohydrolase activity in viral restriction and disease, SAMHD1 also binds to single-stranded RNA and DNA. Here we utilize a UV cross-linking method using 5-bromodeoxyuridine-substituted oligonucleotides coupled with high-resolution mass spectrometry to identify the binding site for single-stranded nucleic acids (ssNAs) on SAMHD1. Mapping cross-linked amino acids on the surface of existing crystal structures demonstrated that the ssNA binding site lies largely along the dimer-dimer interface, sterically blocking the formation of the homotetramer required for dNTPase activity. Surprisingly, the disordered C-terminus of SAMHD1 (residues 583-626) was also implicated in ssNA binding. An interaction between this region and ssNA was confirmed in binding studies using the purified SAMHD1 583-626 peptide. Despite a recent report that SAMHD1 possesses polyribonucleotide phosphorylase activity, we did not detect any such activity in the presence of inorganic phosphate, indicating that nucleic acid binding is unrelated to this proposed activity. These data suggest an antagonistic regulatory mechanism in which the mutually exclusive oligomeric state requirements for ssNA binding and dNTP hydrolase activity modulate these two functions of SAMHD1 within the cell.

Mass-induced sea level variations in the Red Sea from GRACE, steric-corrected altimetry, in situ bottom pressure records, and hydrographic observations

NASA Astrophysics Data System (ADS)

Feng, W.; Lemoine, J.-M.; Zhong, M.; Hsu, H. T.

2014-08-01

An annual amplitude of ∼18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from the Gravity Recovery and Climate Experiment (GRACE) satellites and steric-corrected altimetry from 2003 to 2011. The annual mass variations in the region dominate the mean SLV, and generally reach maximum in late January/early February. The annual steric component of the mean SLV is relatively small (<3 cm) and out of phase of the mass-induced SLV. In situ bottom pressure records at the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. In addition, the horizontal water mass flux of the Red Sea estimated from GRACE and steric-corrected altimetry is validated by hydrographic observations.

Steric sea level change in the Bay of Bengal: investigating the most variable component of sea level change

NASA Astrophysics Data System (ADS)

Uebbing, Bernd; Kusche, Jürgen; Rietbroek, Roelof; Shum, Ck

2015-04-01

Regional sea level change is influenced by contributions from mass sources, like melting of glaciers and the ice-sheets in Greenland and Antarctica, as well as steric contributions from changes in temperature and salinity of the oceans. Radar altimetry indicates a sea level trend in the Bay of Bengal of about 6 mm- yr over the time period of 2002-2014, which is significantly larger than the global mean trend. Here, we explain 80% of this rise by steric contributions and 20% by mass-related contributions. The increased rise of sea level in the Bay of Bengal threatens the coastal vulnerability of the surrounding countries like Bangladesh, where this effect is exacerbated in combination with land subsidence of the very low lying coastal areas. The BanD-AID (Bangladesh Delta: Assessment of the Causes of Sea-level Rise Hazards and Integrated Development of Predictive Modeling Towards Mitigation and Adaptation) project tries to assess the current and future sea level rise and its impacts on the people living in the threatened coastal areas. As a part of this, it is necessary to analyze the different mass and steric contributors to the total sea level rise to aid in the prediction of future risks. We use data from radar altimetry and the GRACE mission to separate the total sea level rise into contributions from mass sources and steric changes. In our approach, temporal GRACE gravity data and Jason-1 and -2 along track altimetry data are fitted to time invariant spatial patterns (fingerprints) to avoid problems with GRACE resolution, filtering, geocenter and related issues. Our results show that in the Bay of Bengal the steric component is influenced by annual and interannual phenomena and, at the same time, it is significantly larger compared to the individual mass contributions, which show a linear and relatively stable behavior over time. We validate the steric component of our inversion by comparing it to independent steric estimates from 4-D gridded temperature and salinity products from different ARGO processing facilities. We also compare to the classical approach of subtracting the mass component, estimated by GRACE, from the total sea level change, measured by altimetry. Furthermore, we assess the sensitivity of our inversion to the normalized steric fingerprints, which are either based on ARGO fields or derived from ocean modeling. While most steric changes are taking place in the upper 700 m of the ocean, our inversion also allows us to (indirectly) assess the influence from the deep ocean, which is not negligible for the total steric trend.

Variable Coded Modulation software simulation

NASA Astrophysics Data System (ADS)

Sielicki, Thomas A.; Hamkins, Jon; Thorsen, Denise

This paper reports on the design and performance of a new Variable Coded Modulation (VCM) system. This VCM system comprises eight of NASA's recommended codes from the Consultative Committee for Space Data Systems (CCSDS) standards, including four turbo and four AR4JA/C2 low-density parity-check codes, together with six modulations types (BPSK, QPSK, 8-PSK, 16-APSK, 32-APSK, 64-APSK). The signaling protocol for the transmission mode is based on a CCSDS recommendation. The coded modulation may be dynamically chosen, block to block, to optimize throughput.

Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding

PubMed Central

Bar-On, Dana; Nachliel, Esther; Gutman, Menachem; Ashery, Uri

2011-01-01

The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins. Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members, syntaxin-1a. The established hypothesis is that the reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins, which interferes with their compatibility. The current study challenges this paradigm and offers a novel mechanistic explanation by revealing a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations. In the present study, using molecular dynamics simulations, we explored the dynamics of the wild-type munc18a versus phosphomimetic mutant munc18a. We focused on the structural changes that occur in the cavity between domains 3a and 1, which serves as the main syntaxin-binding site. The results of the simulations suggest that the free wild-type munc18a exhibits a dynamic equilibrium between several conformations differing in the size of its cavity (the main syntaxin-binding site). The flexibility of the cavity's size might facilitate the binding or unbinding of syntaxin. In silico insertion of phosphomimetic mutations into the munc18a structure induces the formation of a conformation where the syntaxin-binding area is rigid and blocked as a result of interactions between residues located on both sides of the cavity. Therefore, we suggest that the reduced affinity of the phosphomimetic mutant/phosphorylated munc18a is a result of the closed-cavity conformation, which makes syntaxin binding energetically and sterically unfavorable. The current study demonstrates the potential of phosphoryalation, an essential biological process, to serve as a driving force for dramatic conformational changes of proteins modulating their affinity to target proteins. PMID:21390273

Stabilization of the Nitric Oxide (NO) Prodrugs and Anti-Cancer Leads, PABA/NO and Double JS-K through Incorporation into PEG-Protected Nanoparticles

PubMed Central

Kumar, Varun; Hong, Sam Y.; Maciag, Anna E.; Saavedra, Joseph E.; Adamson, Douglas H.; Prud'homme, Robert K.; Keefer, Larry K.; Chakrapani, Harinath

2009-01-01

Here we report the stabilization of the nitric oxide (NO) prodrugs and anti-cancer lead compounds, PABA/NO (O2-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and “Double JS-K” (1,5-bis{[1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato]-2,4-dinitrobenzene), through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit. PMID:20000791

Stabilization of the nitric oxide (NO) prodrugs and anticancer leads, PABA/NO and Double JS-K, through incorporation into PEG-protected nanoparticles.

PubMed

Kumar, Varun; Hong, Sam Y; Maciag, Anna E; Saavedra, Joseph E; Adamson, Douglas H; Prud'homme, Robert K; Keefer, Larry K; Chakrapani, Harinath

2010-02-01

We report the stabilization of the nitric oxide (NO) prodrugs and anticancer lead compounds, PABA/NO (O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and "Double JS-K" 1,5-bis-{1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato}-2,4-dinitrobenzene, through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO are protected from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit.

Sterically controlled mechanochemistry under hydrostatic pressure

NASA Astrophysics Data System (ADS)

Yan, Hao; Yang, Fan; Pan, Ding; Lin, Yu; Hohman, J. Nathan; Solis-Ibarra, Diego; Li, Fei Hua; Dahl, Jeremy E. P.; Carlson, Robert M. K.; Tkachenko, Boryslav A.; Fokin, Andrey A.; Schreiner, Peter R.; Galli, Giulia; Mao, Wendy L.; Shen, Zhi-Xun; Melosh, Nicholas A.

2018-02-01

Mechanical stimuli can modify the energy landscape of chemical reactions and enable reaction pathways, offering a synthetic strategy that complements conventional chemistry. These mechanochemical mechanisms have been studied extensively in one-dimensional polymers under tensile stress using ring-opening and reorganization, polymer unzipping and disulfide reduction as model reactions. In these systems, the pulling force stretches chemical bonds, initiating the reaction. Additionally, it has been shown that forces orthogonal to the chemical bonds can alter the rate of bond dissociation. However, these bond activation mechanisms have not been possible under isotropic, compressive stress (that is, hydrostatic pressure). Here we show that mechanochemistry through isotropic compression is possible by molecularly engineering structures that can translate macroscopic isotropic stress into molecular-level anisotropic strain. We engineer molecules with mechanically heterogeneous components—a compressible (‘soft’) mechanophore and incompressible (‘hard’) ligands. In these ‘molecular anvils’, isotropic stress leads to relative motions of the rigid ligands, anisotropically deforming the compressible mechanophore and activating bonds. Conversely, rigid ligands in steric contact impede relative motion, blocking reactivity. We combine experiments and computations to demonstrate hydrostatic-pressure-driven redox reactions in metal-organic chalcogenides that incorporate molecular elements that have heterogeneous compressibility, in which bending of bond angles or shearing of adjacent chains activates the metal-chalcogen bonds, leading to the formation of the elemental metal. These results reveal an unexplored reaction mechanism and suggest possible strategies for high-specificity mechanosynthesis.

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

PubMed Central

Lim, Chaemin; Youn, Yu Seok; Lee, Kyung Soo; Hoang, Ngoc Ha; Sim, Taehoon; Lee, Eun Seong; Oh, Kyung Taek

2016-01-01

A polyelectrolyte ionomer complex (PIC) composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol)–poly(lactic acid)–poly(ethylene imine) triblock copolymer (PEG–PLA–PEI) and a poly(aspartic acid) (P[Asp]) homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp) blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp) blocks (C/A ratio). The doxorubicin (dox)-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8) increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy. PMID:26955270

Langevin and Fokker-Planck analyses of inhibited molecular passing processes controlling transport and reactivity in nanoporous materials

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

Wang, Chi-Jen; Ackerman, David M.; Slowing, Igor I.

2014-07-14

Inhibited passing of reactant and product molecules within the linear pores of nanoporous catalytic materials strongly reduces reactivity. The dependence of the passing propensity P on pore radius R is analyzed utilizing Langevin dynamics to account for solvent effects. We find that P~(R-R c) σ, where passing is sterically blocked for R≤R c, with σ below the transition state theory value. Deeper insight comes from analysis of the corresponding high-dimensional Fokker-Planck equation, which facilitates an effective small-P approximation, and dimensional reduction enabling utilization of conformal mapping ideas. We analyze passing for spherical molecules and also assess the effect of rotationalmore » degrees of freedom for elongated molecules.« less

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

Kohler, Lars; Hadt, Ryan G.; Hayes, Dugan

In this paper we describe the synthesis of a new phenanthroline ligand, 2,9-di(2,4,6-tri-isopropyl-phenyl)-1,10-phenanthroline (bL2) and its use as the blocking ligand in the preparation of two new heteroleptic Cu(I)diimine complexes. Analysis of the CuHETPHEN single crystal structures shows a distinct distortion from an ideal tetrahedral geometry around the Cu(I) center, forced by the secondary phenanthroline ligand rotating to accommodate the isopropyl groups of bL2. The increased steric bulk of bL2 as compared to the more commonly used 2,9-dimesityl-1,10-phenanthroline blocking ligand prohibits intramolecular ligand–ligand interaction, which is unique among CuHETPHEN complexes. The ground state optical and redox properties of CuHETPHEN complexesmore » are responsive to the substitution on the blocking ligand even though the differences in structure are far removed from the Cu(I) center. Transient optical spectroscopy was used to understand the excited state kinetics in both coordinating and non-coordinating solvents following visible excitation. Substitution of the blocking phenanthroline ligand has a significant impact on the 3MLCT decay and can be used to increase the excited state lifetime by 50%. Electronic structure calculations established relationships between ground and excited state properties, and general entatic state concepts are discussed for copper photosensitizers. This work contributes to the growing library of CuHETPHEN complexes and broadens the fundamental understanding of their ground and excited state properties.« less

Multifunctional hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release for enhanced tumor suppression.

PubMed

Liu, Xuhan; Li, Yinghuan; Tan, Xi; Rao, Rong; Ren, Yuanyuan; Liu, Lingyan; Yang, Xiangliang; Liu, Wei

2018-03-01

Therapeutic efficacy of conventional single PEGylated polymeric micelles is significantly reduced by limited endocytosis and intracellular drug release. To improve drug delivery efficiency, poly (ethylene glycol)-block-poly (l-lactic acid)/(Arg-Gly-Asp-Phe)-poly (aminoethyl ethylene phosphate)-block-poly (l-lactic acid) (PEG-PLLA/RGDF-PAEEP-PLLA) hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release are developed. The optimized hybrid micelles with 6 wt % of RGDF have favorable in vitro and in vivo activities. The hybrid micelles could temporarily shield the targeting efficacy of RGDF at pH 7.4 due to the steric effect exerted by concealment of RGDF peptides in the PEG corona, which strongly decreases the clearance by mononuclear phagocyte system and consequently improves the tumor accumulation. Inside the solid tumor with a lower acidic pH, the hybrid micelles restore the active tumor targeting property with exposed RGDF on the surface of the micelles because of the increased protonation and stretching degree of PAEEP blocks. RGDF-mediated endocytosis improves the tumor cell uptake. The hybrid micelles would also enhance intracellular drug release because of the hydrolysis of the acid/phosphatase-sensitivity of PAEEP blocks in endo/lysosome. Systemic administration of the hybrid micelles significantly inhibits tumor growth by 96% due to the integration of enhanced circulation time, tumor accumulation, cell uptake and intracellular drug release. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on steric transition in asymmetrical flow field-flow fractionation and application to characterization of high-energy material.

PubMed

Dou, Haiyang; Lee, Yong-Ju; Jung, Euo Chang; Lee, Byung-Chul; Lee, Seungho

2013-08-23

In field-flow fractionation (FFF), there is the 'steric transition' phenomenon where the sample elution mode changes from the normal to steric/hyperlayer mode. Accurate analysis by FFF requires understanding of the steric transition phenomenon, particularly when the sample has a broad size distribution, for which the effect by combination of different modes may become complicated to interpret. In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4) was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually decreases as the particle size increases (normal mode) and reaches a minimum (Ri) at diameter around 0.5μm, after which R increases with increasing diameter (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends to increase as the channel thickness (w) increases. The retention behavior of cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department explosive' (RDX)) particles in AF4 was investigated by varying experimental parameters including w and flow rates. AF4 showed a good reproducibility in size determination of RDX particles with the relative standard deviation of 4.1%. The reliability of separation obtained by AF4 was evaluated by transmission electron microscopy (TEM). Copyright © 2013 Elsevier B.V. All rights reserved.

Robot Task Commander with Extensible Programming Environment

NASA Technical Reports Server (NTRS)

Hart, Stephen W (Inventor); Wightman, Brian J (Inventor); Dinh, Duy Paul (Inventor); Yamokoski, John D. (Inventor); Gooding, Dustin R (Inventor)

2014-01-01

A system for developing distributed robot application-level software includes a robot having an associated control module which controls motion of the robot in response to a commanded task, and a robot task commander (RTC) in networked communication with the control module over a network transport layer (NTL). The RTC includes a script engine(s) and a GUI, with a processor and a centralized library of library blocks constructed from an interpretive computer programming code and having input and output connections. The GUI provides access to a Visual Programming Language (VPL) environment and a text editor. In executing a method, the VPL is opened, a task for the robot is built from the code library blocks, and data is assigned to input and output connections identifying input and output data for each block. A task sequence(s) is sent to the control module(s) over the NTL to command execution of the task.

Inorganic membranes for carbon capture and power generation

NASA Astrophysics Data System (ADS)

Snider, Matthew T.

Inorganic membranes are under consideration for cost-effective reductions of carbon emissions from coal-fired power plants, both in the capture of pollutants post-firing and in the direct electrochemical conversion of coal-derived fuels for improved plant efficiency. The suitability of inorganic membrane materials for these purposes stems as much from thermal and chemical stability in coal plant operating conditions as from high performance in gas separations and power generation. Hydrophilic, micro-porous zeolite membrane structures are attractive for separating CO2 from N2 in gaseous waste streams due to the attraction of CO2 to the membrane surface and micropore walls that gives the advantage to CO2 transport. Recent studies have indicated that retention of the templating agent used in zeolite synthesis can further block N2 from the micropore interior and significantly improve CO2/N2 selectivity. However, the role of the templating agent in micro-porous transport has not been well investigated. In this work, gas sorption studies were conducted by high-pressure thermo-gravimetric analysis on Zeolite Y membrane materials to quantify the effect of the templating agent on CO2, N2, and H2O adsorption/desorption, as well as to examine the effect of humidification on overall membrane performance. In equilibrium conditions, the N2 sorption enthalpy was nearly unchanged by the presence of the templating agent, but the N2 pore occupation was reduced ˜1000x. Thus, the steric nature of the blocking of N2 from the micropores by the templating agent was confirmed. CO2 and H2O sorption enthalpies were similarly unaffected by the templating agent, and the micropore occupations were only reduced as much as the void volume taken up by the templating agent. Thus, the steric blocking effect did not occur for molecules more strongly attracted to the micropore walls. Additionally, in time-transient measurements the CO 2 and H2O mobilities were significantly enhanced by the presence of the templating agent. This meant that small restrictions in the micropores were beneficial to the transport of molecules with some attraction to the micropore walls. Further evidence of this effect were discovered in transport studies on Zeolite Y membranes, in which small amounts of residual water were observed to enhance the CO2 permeance in a similar way as the templating agent in the powder. However, the effect was only observed for dry CO 2 streams and previously humidified membranes. H2O affinity for the zeolite framework was so high and mobility in the micropores was so low that even 0.8 mol% H2O included in the gas stream was enough to reduce CO2 transport by 100x. This poses a serious concern for carbon capture by zeolite Y membrane in coal-fired power plants: the waste stream must be dehumidified first. In the long-term, raising the efficiencies of fossil-fuel power plants is preferable to post-combustion capture for cost- and resource-effective carbon emissions reduction. Supplementing combustion of the fuel with electrochemical conversion by solid oxide fuel cell (SOFC) shows promise in this effort. Thin-film (<1microm thick) SOFCs have recently exhibited power densities at low temperature (LT) that rival those of thick-film, high-temperature designs, with improved stability and quick ramp times. Low operating temperatures also provide the potential for fast, high-volume production, but so far high-performing LT-SOFCs have all been made by micro-fabrication methods. In this work, thin-film LT-SOFC modules were fabricated by colloidal processing and their performance was demonstrated. Nano-particulate colloid syntheses, dip-coating, and rapid thermal processing methods yielded fine-particle membrane microstructures, with high porosity and conductivity in the platinum/gadolinium-doped ceria (GDC) composite electrodes and density in the yttria-stabilized zirconia (YSZ) electrolytes. Power densities of >1000 W/m2 at 450°C and ˜5000 W/m2 at 600°C were achieved, and the modules ran >100hrs at peak power after 8 thermal cycles. Thus it was demonstrated that high performing LT-SOFCs can be produced with large-scale methods.

Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

NASA Technical Reports Server (NTRS)

Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

1990-01-01

The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric vs. stereoelectronic effects.

PubMed

Crandell, Douglas W; Mazumder, Shivnath; Evans, P Andrew; Baik, Mu-Hyun

2015-12-01

Density functional theory calculations demonstrate that the reversal of regiochemical outcome of the addition for substituted methyl propiolates in the rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh 3 and ( S )-xyl-binap as ligands is both electronically and sterically controlled. For example, the ester functionality polarizes the alkyne π* orbital to favor overlap of the methyl-substituted terminus of the alkyne with the p π -orbital of the alkenyl fragment of the rhodacycle during alkyne insertion with PPh 3 as the ligand. In contrast, the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne orientation, thereby forcing insertion to occur at the sterically preferred ester terminus, overriding the electronically preferred orientation for alkyne insertion.

Large space erectable structures - building block structures study

NASA Technical Reports Server (NTRS)

Armstrong, W. H.; Skoumal, D. E.; Straayer, J. W.

1977-01-01

A modular planar truss structure and a long slender boom concept identified as building block approaches to construction of large spacecraft configurations are described. The concepts are compatible in weight and volume goals with the Space Transportation System, use standard structural units, and represent high on-orbit productivity in terms of structural area or beam length. Results of structural trade studies involving static and dynamic analyses of a single module and rigid body deployment analyses to assess kinetics and kinematics of automatic deployment of the building block modules are presented.

A double-headed cathepsin B inhibitor devoid of warhead

PubMed Central

Schenker, Patricia; Alfarano, Pietro; Kolb, Peter; Caflisch, Amedeo; Baici, Antonio

2008-01-01

Most synthetic inhibitors of peptidases have been targeted to the active site for inhibiting catalysis through reversible competition with the substrate or by covalent modification of catalytic groups. Cathepsin B is unique among the cysteine peptidase for the presence of a flexible segment, known as the occluding loop, which can block the primed subsites of the substrate binding cleft. With the occluding loop in the open conformation cathepsin B acts as an endopeptidase, and it acts as an exopeptidase when the loop is closed. We have targeted the occluding loop of human cathepsin B at its surface, outside the catalytic center, using a high-throughput docking procedure. The aim was to identify inhibitors that would interact with the occluding loop thereby modulating enzyme activity without the help of chemical warheads against catalytic residues. From a large library of compounds, the in silico approach identified [2-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethylamino]-2-oxoethyl] 2-(furan-2-carbonylamino) acetate, which fulfills the working hypothesis. This molecule possesses two distinct binding moieties and behaves as a reversible, double-headed competitive inhibitor of cathepsin B by excluding synthetic and protein substrates from the active center. The kinetic mechanism of inhibition suggests that the occluding loop is stabilized in its closed conformation, mainly by hydrogen bonds with the inhibitor, thus decreasing endoproteolytic activity of the enzyme. Furthermore, the dioxothiazolidine head of the compound sterically hinders binding of the C-terminal residue of substrates resulting in inhibition of the exopeptidase activity of cathepsin B in a physiopathologically relevant pH range. PMID:18796695

Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix

PubMed Central

De, Soumya; Okon, Mark; Graves, Barbara J.; McIntosh, Lawrence P.

2017-01-01

The ETS transcriptional repressor ETV6 (or TEL) is autoinhibited by an α-helix that sterically blocks its DNA-binding ETS domain. The inhibitory helix is marginally stable and unfolds when ETV6 binds to either specific or non-specific DNA. Using NMR spectroscopy, we show that folding of the inhibitory helix requires a buried charge–dipole interaction with helix H1 of the ETS domain. This interaction also contributes directly to autoinhibition by precluding a highly conserved dipole-enhanced hydrogen bond between the phosphodiester backbone of bound DNA and the N terminus of helix H1. To probe further the thermodynamic basis of autoinhibition, ETV6 variants were generated with amino acid substitutions introduced along the solvent exposed surface of the inhibitory helix. These changes were designed to increase the intrinsic helical propensity of the inhibitory helix without perturbing its packing interactions with the ETS domain. NMR-monitored amide hydrogen exchange measurements confirmed that the stability of the folded inhibitory helix increases progressively with added helix-promoting substitutions. This also results in progressively reinforced autoinhibition and decreased DNA-binding affinity. Surprisingly, locking the inhibitory helix onto the ETS domain by a disulfide bridge severely impairs, but does not abolish DNA binding. Weak interactions still occur via an interface displaced from the canonical ETS domain DNA-binding surface. Collectively, these studies establish a direct thermodynamic linkage between inhibitory helix stability and ETV6 autoinhibition, and demonstrate that helix unfolding does not strictly precede DNA binding. Modulating inhibitory helix stability provides a potential route for the in vivo regulation of ETV6 activity. PMID:26920109

13C and 1H nuclear magnetic resonance of methyl-substituted acetophenones and methyl benzoates: steric hindrance and inhibited conjugation.

PubMed

Budesínský, Milos; Kulhánek, Jirí; Böhm, Stanislav; Cigler, Petr; Exner, Otto

2004-10-01

The 1H and 13C NMR spectra of 14 methyl-substituted acetophenones and 14 methyl-substituted methyl benzoates were assigned and interpreted with respect to the conformation of the C(ar)-C(O) bond. The substituent effects are proportional in the two series and can be divided into polar and steric: each has different effects on the 13C SCS of the individual atoms. In the case of C atoms C(O), C(1) and CH3(CO), the steric effects were quantitatively separated by comparing SCS in the ortho and para positions. The steric effects are proportional for the individual C atoms and also to steric effects estimated from other physical quantities. However, they do not depend simply on the angle of torsion phi of the functional group as anticipated hitherto. A better description distinguishes two classes of compounds: sterically not hindered or slightly hindered planar molecules and strongly sterically hindered, markedly non-planar. In order to confirm this reasoning without empirical correlations, the J(C,C) coupling constants were measured for three acetophenone derivatives labeled with 13C in the acetyl methyl group. The constants confirm unambiguously the conformation of 2-methylacetophenone; their zero values are in accord with the conformation of 2,6-dimethylacetophenone. The zero values in the unsubstituted acetophenone are at variance with previous erroneous report but all J(C,C) values are in accord with calculations at the B3LYP/6-311++G(2d,2p)//B3LYP/6-311+G(d,p) level. Copyright 2004 John Wiley & Sons, Ltd.

Elderly Service Workers' Training Project. Block B: Cultural Gerontology. Module B.3.1: Communication and Adjustment.

ERIC Educational Resources Information Center

Harvey, Dexter; Cap, Orest

This learning module, which is part of a three-block series intended to help human service workers develop the skills necessary to solve the problems encountered in their daily contact with elderly clients of different cultural backgrounds, deals with communication and adjustment from the standpoint of the way in which French-speaking Canadians…

Environmental testing of block 3 solar cell modules. Part 1: Qualification testing of standard production modules

NASA Technical Reports Server (NTRS)

Griffith, J. S.

1979-01-01

Qualification tests of solar cell modules are described. These modules continue to show improvement over earlier type modules tested. Cell cracking and delamination are less prevalent, and interconnect problems and electrical degradation from environmental testing are now rare.

Multi-stage decoding for multi-level block modulation codes

NASA Technical Reports Server (NTRS)

Lin, Shu; Kasami, Tadao

1991-01-01

Various types of multistage decoding for multilevel block modulation codes, in which the decoding of a component code at each stage can be either soft decision or hard decision, maximum likelihood or bounded distance are discussed. Error performance for codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. It was found that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. It was found that the difference in performance between the suboptimum multi-stage soft decision maximum likelihood decoding of a modulation code and the single stage optimum decoding of the overall code is very small, only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

FunBlocks. A modular framework for AmI system development.

PubMed

Baquero, Rafael; Rodríguez, José; Mendoza, Sonia; Decouchant, Dominique; Papis, Alfredo Piero Mateos

2012-01-01

The last decade has seen explosive growth in the technologies required to implement Ambient Intelligence (AmI) systems. Technologies such as facial and speech recognition, home networks, household cleaning robots, to name a few, have become commonplace. However, due to the multidisciplinary nature of AmI systems and the distinct requirements of different user groups, integrating these developments into full-scale systems is not an easy task. In this paper we propose FunBlocks, a minimalist modular framework for the development of AmI systems based on the function module abstraction used in the IEC 61499 standard for distributed control systems. FunBlocks provides a framework for the development of AmI systems through the integration of modules loosely joined by means of an event-driven middleware and a module and sensor/actuator catalog. The modular design of the FunBlocks framework allows the development of AmI systems which can be customized to a wide variety of usage scenarios.

FunBlocks. A Modular Framework for AmI System Development

PubMed Central

Baquero, Rafael; Rodríguez, José; Mendoza, Sonia; Decouchant, Dominique; Papis, Alfredo Piero Mateos

2012-01-01

The last decade has seen explosive growth in the technologies required to implement Ambient Intelligence (AmI) systems. Technologies such as facial and speech recognition, home networks, household cleaning robots, to name a few, have become commonplace. However, due to the multidisciplinary nature of AmI systems and the distinct requirements of different user groups, integrating these developments into full-scale systems is not an easy task. In this paper we propose FunBlocks, a minimalist modular framework for the development of AmI systems based on the function module abstraction used in the IEC 61499 standard for distributed control systems. FunBlocks provides a framework for the development of AmI systems through the integration of modules loosely joined by means of an event-driven middleware and a module and sensor/actuator catalog. The modular design of the FunBlocks framework allows the development of AmI systems which can be customized to a wide variety of usage scenarios. PMID:23112599

Temporal prediction modulates the evaluative processing of "good" action feedback: An electrophysiological study.

PubMed

Kimura, Kenta; Kimura, Motohiro; Iwaki, Sunao

2016-10-01

The present study aimed to investigate whether or not the evaluative processing of action feedback can be modulated by temporal prediction. For this purpose, we examined the effects of the predictability of the timing of action feedback on an ERP effect that indexed the evaluative processing of action feedback, that is, an ERP effect that has been interpreted as a feedback-related negativity (FRN) elicited by "bad" action feedback or a reward positivity (RewP) elicited by "good" action feedback. In two types of experimental blocks, the participants performed a gambling task in which they chose one of two cards and received an action feedback that indicated monetary gain or loss. In fixed blocks, the time interval between the participant's choice and the onset of the action feedback was fixed at 0, 500, or 1,000 ms in separate blocks; thus, the timing of action feedback was predictable. In mixed blocks, the time interval was randomly chosen from the same three intervals with equal probability; thus, the timing was less predictable. The results showed that the FRN/RewP was smaller in mixed than fixed blocks for the 0-ms interval trial, whereas there was no difference between the two block types for the 500-ms and 1,000-ms interval trials. Interestingly, the smaller FRN/RewP was due to the modulation of gain ERPs rather than loss ERPs. These results suggest that temporal prediction can modulate the evaluative processing of action feedback, and particularly good feedback, such as that which indicates monetary gain. © 2016 Society for Psychophysiological Research.

Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function.

PubMed

Chauhan, Jay; Chen, Shen-En; Fenstermacher, Katherine J; Naser-Tavakolian, Aurash; Reingewertz, Tali; Salmo, Rosene; Lee, Christian; Williams, Emori; Raje, Mithun; Sundberg, Eric; DeStefano, Jeffrey J; Freire, Ernesto; Fletcher, Steven

2015-11-01

Small-molecule mimetics of the β-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap-flap protein-protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis-Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition is through binding the active site or sterically blocking access to the active site and preventing flap closure, as designed. More generally, a new bioactive scaffold for HIV-1PR inhibition has been discovered, with the most potent compound inhibiting the protease with a modest K(i) of 11 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Theoretical analysis of the rotational barrier of ethane.

PubMed

Mo, Yirong; Gao, Jiali

2007-02-01

The understanding of the ethane rotation barrier is fundamental for structural theory and the conformational analysis of organic molecules and requires a consistent theoretical model to differentiate the steric and hyperconjugation effects. Due to recently renewed controversies over the barrier's origin, we developed a computational approach to probe the rotation barriers of ethane and its congeners in terms of steric repulsion, hyperconjugative interaction, and electronic and geometric relaxations. Our study reinstated that the conventional steric repulsion overwhelmingly dominates the barriers.

Emotional modulation of pain and spinal nociception in fibromyalgia

PubMed Central

Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

2013-01-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

ASD: a comprehensive database of allosteric proteins and modulators

PubMed Central

Huang, Zhimin; Zhu, Liang; Cao, Yan; Wu, Geng; Liu, Xinyi; Chen, Yingyi; Wang, Qi; Shi, Ting; Zhao, Yaxue; Wang, Yuefei; Li, Weihua; Li, Yixue; Chen, Haifeng; Chen, Guoqiang; Zhang, Jian

2011-01-01

Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloSteric Database (ASD), the first online database that provides a central resource for the display, search and analysis of structure, function and related annotation for allosteric molecules. Currently, ASD contains 336 allosteric proteins from 101 species and 8095 modulators in three categories (activators, inhibitors and regulators). Proteins are annotated with a detailed description of allostery, biological process and related diseases, and modulators with binding affinity, physicochemical properties and therapeutic area. Integrating the information of allosteric proteins in ASD should allow for the identification of specific allosteric sites of a given subtype among proteins of the same family that can potentially serve as ideal targets for experimental validation. In addition, modulators curated in ASD can be used to investigate potent allosteric targets for the query compound, and also help chemists to implement structure modifications for novel allosteric drug design. Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/. PMID:21051350

Cytosolic Nucleotides Block and Regulate the Arabidopsis Vacuolar Anion Channel AtALMT9*

PubMed Central

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-01-01

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al3+ to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. PMID:25028514

Cytosolic nucleotides block and regulate the Arabidopsis vacuolar anion channel AtALMT9.

PubMed

Zhang, Jingbo; Martinoia, Enrico; De Angeli, Alexis

2014-09-12

The aluminum-activated malate transporters (ALMTs) form a membrane protein family exhibiting different physiological roles in plants, varying from conferring tolerance to environmental Al(3+) to the regulation of stomatal movement. The regulation of the anion channels of the ALMT family is largely unknown. Identifying intracellular modulators of the activity of anion channels is fundamental to understanding their physiological functions. In this study we investigated the role of cytosolic nucleotides in regulating the activity of the vacuolar anion channel AtALMT9. We found that cytosolic nucleotides modulate the transport activity of AtALMT9. This modulation was based on a direct block of the pore of the channel at negative membrane potentials (open channel block) by the nucleotide and not by a phosphorylation mechanism. The block by nucleotides of AtALMT9-mediated currents was voltage dependent. The blocking efficiency of intracellular nucleotides increased with the number of phosphate groups and ATP was the most effective cellular blocker. Interestingly, the ATP block induced a marked modification of the current-voltage characteristic of AtALMT9. In addition, increased concentrations of vacuolar anions were able to shift the ATP block threshold to a more negative membrane potential. The block of AtALMT9-mediated anion currents by ATP at negative membrane potentials acts as a gate of the channel and vacuolar anion tune this gating mechanism. Our results suggest that anion transport across the vacuolar membrane in plant cells is controlled by cytosolic nucleotides and the energetic status of the cell. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Heavy Duty Mechanics Apprenticeship Training, Module One. Volume II.

ERIC Educational Resources Information Center

Batchelor, Leslie A.; Abercrombie, Richard, Ed.

This training manual, the second of two volumes, comprises the final three blocks in a nine-block in-service training course for apprentices working in heavy duty mechanics. Addressed in the individual blocks included in this volume are engines, basic electricity, and winches. Each block contains a section on parts theory that gives the purpose,…

Research of Modulation of Bilateral Frequency Difference Based on Load Mode

NASA Astrophysics Data System (ADS)

Lin, Shenghong; Mao, Chizu; Zhu, Jianquan; Lu, Junyu

2017-05-01

Owning to high reliability, simple operation and easy acquirement of signals, modulation of bilateral frequency difference (MBFD) in HVDC is worthy for application in practical engineering. With the example of an AC/DC hybrid network and the software PSD-BPA, this paper analyses the effect of MBFD to DC block. The modulators parameters are setting by means of simulation. Two types of loads modes are considered to research the impact of them on simulation. The results indicate that in cooperation with operation modes adjusting at AC system, MBFD will effectively release the impact from DC block and shortage of reactive power caused by rapid variation of DC power owning to modulation. To achieve the best effect, only modulators of some HVDC systems instead of all of them are opened.

Making Your Own Hollow Blocks. What We Make. Science and Technology Education in Philippine Society.

ERIC Educational Resources Information Center

Philippines Univ., Quezon City. Inst. for Science and Mathematics Education Development.

The procedures needed to make hollow blocks from palay hull, sawdust, soil, or sand are outlined in this module. Also outlined are the procedures needed to construct the wooden molds used to make the blocks. The hollow blocks can be used in building a one story house where the roof does not rest on the hollow block wall, an additional room to the…

Addition of an extra immunoglobulin domain to two anti-rodent TNF monoclonal antibodies substantially increased their potency.

PubMed

Scallon, Bernard; Cai, Ann; Radewonuk, Jennifer; Naso, Michael

2004-05-01

The functional valency of a monoclonal antibody (mAb) has important influences on such things as antigen avidity, Fc-mediated immune effector functions, and clearance of immune complexes. cV1q, a neutralizing rat/mouse chimeric anti-mouse tumor necrosis factor (TNF) monoclonal antibody (mAb), and Rt108, a neutralizing mouse anti-rat TNF (anti-raTNF) mAb, appear to be functionally monovalent for TNF-binding despite containing two antigen binding sites. The functional monovalency of these two independent anti-rodent TNF mAbs is presumably a result of steric hindrance from one TNF molecule binding to one Fab arm that prevents binding of a second TNF molecule to the other Fab arm. To test whether this steric hindrance could be overcome by introducing extra space and flexibility between the Fab arms, these mAbs were engineered to contain an extra CH1 immunoglobulin domain between the CH1 and hinge domains of their heavy chains. In vitro binding data showed that, compared to the original mAbs, the modified mAbs (S-mAbs) had greater capability of binding two TNF molecules simultaneously. In vitro activity assays showed that, compared to the original mAbs, the S-mAbs had significantly greater TNF-neutralization potency, with the S-mAb version of cV1q (S-cV1q) being 200-fold more effective at blocking mouse TNF (muTNF) and the S-mAb version of Rt108 (S-Rt108) being 20-fold more effective at blocking raTNF. Similar results were observed in vivo, where S-cV1q was between 100- and 500-fold more protective than cV1q in mice challenged with endotoxin. These data reveal that introduction of another constant region immunoglobulin domain into two unrelated mAbs dramatically enhanced their neutralization potency. Other mAbs may also show more potent activity using this engineering approach, particularly mAbs that recognize homopolymeric antigens.

Fisher information and steric effect: study of the internal rotation barrier of ethane.

PubMed

Esquivel, Rodolfo O; Liu, Shubin; Angulo, Juan Carlos; Dehesa, Jesús S; Antolín, Juan; Molina-Espíritu, Moyocoyani

2011-05-05

On the basis of a density-based quantification of the steric effect [Liu, S. B. J. Chem. Phys.2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane is systematically investigated in this work from an information-theoretical point of view by using the Fisher information measure in conjugated spaces. Two kinds of computational approaches are considered in this work: adiabatic (with optimal structure) and vertical (with fixed geometry). The analyses are performed systematically by following, in each case, the conformeric path by changing the dihedral angle from 0 to 180° . This is calculated at the HF, MP2, B3LYP, and CCSD(T) levels of theory and with several basis sets. Selected descriptors of the densities are utilized to support the observations. Our results show that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer, but in the vertical cases the staggered conformer retains a larger steric repulsion. Our results verify the plausibility for defining and computing the steric effect in the post-Hartree-Fock level of theory according to the scheme proposed by Liu.

Multi-stage decoding for multi-level block modulation codes

NASA Technical Reports Server (NTRS)

Lin, Shu

1991-01-01

In this paper, we investigate various types of multi-stage decoding for multi-level block modulation codes, in which the decoding of a component code at each stage can be either soft-decision or hard-decision, maximum likelihood or bounded-distance. Error performance of codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. Based on our study and computation results, we find that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. In particular, we find that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum decoding of the overall code is very small: only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

Morphological Transformation between Nanocoils and Nanoribbons via Defragmentation Structural Rearrangement or Fragmentation-recombination Mechanism

NASA Astrophysics Data System (ADS)

Zhang, Yibin; Zheng, Yingxuan; Xiong, Wei; Peng, Cheng; Zhang, Yifan; Duan, Ran; Che, Yanke; Zhao, Jincai

2016-06-01

Kinetic control over the assembly pathways towards novel metastable functional materials or far-from-equilibrium systems has been much less studied compared to the thermodynamic equilibrium self-assembly. Herein, we report the distinct morphological transformation between nanocoils and nanoribbons in the self-assembly of unsymmetric perylene diimide (PDI) molecules. We demonstrate that the morphological transformation of the kinetically trapped assemblies into the thermodynamically stable forms proceeds via two distinct mechanisms, i.e., a direct structural rearrangement (molecule 1 or 2) and a fragmentation-recombination mechanism (molecule 4), respectively. The subtle interplay of the steric hindrance of the bulky substituents and the flexibility of the linker structure between the bulky moiety and the perylene core was demonstrated to enable the effective modulation of the energetic landscape of the assemblies and thus modulation of the assembly pathways. Herein, our work presents a new approach to control the self-assembly pathways and thereby can be used to achieve novel far-from-equilibrium systems.

A Blocking Group Scan Using a Spherical Organometallic Complex Identifies an Unprecedented Binding Mode with Potent Activity In Vitro and In Vivo for the Opioid Peptide Dermorphin.

PubMed

Strack, Martin; Bedini, Andrea; Yip, King T; Lombardi, Sara; Siegmund, Daniel; Stoll, Raphael; Spampinato, Santi M; Metzler-Nolte, Nils

2016-10-04

Herein, the selective enforcement of one particular receptor-ligand interaction between specific domains of the μ-selective opioid peptide dermorphin and the μ opioid receptor is presented. For this, a blocking group scan is described which exploits the steric demand of a bis(quinolinylmethyl)amine rhenium(I) tricarbonyl complex conjugated to a number of different, strategically chosen positions of dermorphin. The prepared peptide conjugates lead to the discovery of two different binding modes: An expected N-terminal binding mode corresponds to the established view of opioid peptide binding, whereas an unexpected C-terminal binding mode is newly discovered. Surprisingly, both binding modes provide high affinity and agonistic activity at the μ opioid receptor in vitro. Furthermore, the unprecedented C-terminal binding mode shows potent dose-dependent antinociception in vivo. Finally, in silico docking studies support receptor activation by both dermorphin binding modes and suggest a biological relevance for dermorphin itself. Relevant ligand-protein interactions are similar for both binding modes, which is in line with previous protein mutation studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Georgetown University Photovoltaic Higher Education National Exemplar Facility (PHENEF)

NASA Technical Reports Server (NTRS)

Marshall, N.

1984-01-01

Several photographs of this facility using photovoltaic (PV) cells are shown. An outline is given of the systems requirements, system design and wiring topology, a simplified block design, module electrical characteristics, PV module and PV module matching.

The dependence of the modulation transfer function on the blocking layer thickness in amorphous selenium x-ray detectors

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

Hunter, David M.; Belev, Gueorgi; DeCrescenzo, Giovanni

2007-08-15

Blocking layers are used to reduce leakage current in amorphous selenium detectors. The effect of the thickness of the blocking layer on the presampling modulation transfer function (MTF) and on dark current was experimentally determined in prototype single-line CCD-based amorphous selenium (a-Se) x-ray detectors. The sampling pitch of the detectors evaluated was 25 {mu}m and the blocking layer thicknesses varied from 1 to 51 {mu}m. The blocking layers resided on the signal collection electrodes which, in this configuration, were used to collect electrons. The combined thickness of the blocking layer and a-Se bulk in each detector was {approx}200 {mu}m. Asmore » expected, the dark current increased monotonically as the thickness of the blocking layer was decreased. It was found that if the blocking layer thickness was small compared to the sampling pitch, it caused a negligible reduction in MTF. However, the MTF was observed to decrease dramatically at spatial frequencies near the Nyquist frequency as the blocking layer thickness approached or exceeded the electrode sampling pitch. This observed reduction in MTF is shown to be consistent with predictions of an electrostatic model wherein the image charge from the a-Se is trapped at a characteristic depth within the blocking layer, generally near the interface between the blocking layer and the a-Se bulk.« less

Diabetes Drug Discovery: hIAPP1-37 Polymorphic Amyloid Structures as Novel Therapeutic Targets.

PubMed

Fernández-Gómez, Isaac; Sablón-Carrazana, Marquiza; Bencomo-Martínez, Alberto; Domínguez, Guadalupe; Lara-Martínez, Reyna; Altamirano-Bustamante, Nelly F; Jiménez-García, Luis Felipe; Pasten-Hidalgo, Karina; Castillo-Rodríguez, Rosa Angélica; Altamirano, Perla; Marrero, Suchitil Rivera; Revilla-Monsalve, Cristina; Valdés-Sosa, Peter; Salamanca-Gómez, Fabio; Garrido-Magaña, Eulalia; Rodríguez-Tanty, Chryslaine; Altamirano-Bustamante, Myriam M

2018-03-19

Human islet amyloid peptide (hIAPP 1-37 ) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP 1-37 ) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP 1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP 1-37 . When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP 1-37 . Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP 1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A - F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.

Analyses of requirements for computer control and data processing experiment subsystems: Image data processing system (IDAPS) software description (7094 version), volume 2

NASA Technical Reports Server (NTRS)

1973-01-01

A description of each of the software modules of the Image Data Processing System (IDAPS) is presented. The changes in the software modules are the result of additions to the application software of the system and an upgrade of the IBM 7094 Mod(1) computer to a 1301 disk storage configuration. Necessary information about IDAPS sofware is supplied to the computer programmer who desires to make changes in the software system or who desires to use portions of the software outside of the IDAPS system. Each software module is documented with: module name, purpose, usage, common block(s) description, method (algorithm of subroutine) flow diagram (if needed), subroutines called, and storage requirements.

Emotional modulation of pain and spinal nociception in fibromyalgia.

PubMed

Rhudy, Jamie L; DelVentura, Jennifer L; Terry, Ellen L; Bartley, Emily J; Olech, Ewa; Palit, Shreela; Kerr, Kara L

2013-07-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological-emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Guidance system operations plan for manned LM earth orbital and lunar missions using program luminary 1E. Section 2: Data links

NASA Technical Reports Server (NTRS)

Hamilton, M. H.

1972-01-01

Data links for the guidance system of manned lunar module orbital and lunar missions are presented. Subjects discussed are: (1) digital uplink to lunar module, (2) lunar module liftoff time increment, (3) lunar module contiguous block update, (4) lunar module scatter update, (5) lunar module digital downlink, and (6) absolute addresses for update program.

Imidazoquinoxaline Src-family kinase p56Lck inhibitors: SAR, QSAR, and the discovery of (S)-N-(2-chloro-6-methylphenyl)-2-(3-methyl-1-piperazinyl)imidazo- [1,5-a]pyrido[3,2-e]pyrazin-6-amine (BMS-279700) as a potent and orally active inhibitor with excellent in vivo antiinflammatory activity.

PubMed

Chen, Ping; Doweyko, Arthur M; Norris, Derek; Gu, Henry H; Spergel, Steven H; Das, Jagabundhu; Moquin, Robert V; Lin, James; Wityak, John; Iwanowicz, Edwin J; McIntyre, Kim W; Shuster, David J; Behnia, Kamelia; Chong, Saeho; de Fex, Henry; Pang, Suhong; Pitt, Sydney; Shen, Ding Ren; Thrall, Sara; Stanley, Paul; Kocy, Octavian R; Witmer, Mark R; Kanner, Steven B; Schieven, Gary L; Barrish, Joel C

2004-08-26

A series of novel anilino 5-azaimidazoquinoxaline analogues possessing potent in vitro activity against p56Lck and T cell proliferation have been discovered. Subsequent SAR studies led to the identification of compound 4 (BMS-279700) as an orally active lead candidate that blocks the production of proinflammatory cytokines (IL-2 and TNFalpha) in vivo. In addition, an expanded set of imidazoquinoxalines provided several descriptive QSAR models highlighting the influence of significant steric and electronic features. The H-bonding (Met319) contribution to observed binding affinities within a tightly congeneric series was found to be significant.

Kinetics of photoinduced electron transfer reactions of ruthenium(II) complexes and phenols, tyrosine, N-acetyl-tyrosine and tryptophan in aqueous solutions measured with modulated fluorescence spectroscopy.

PubMed

Nguyen, Truong X; Landgraf, Stephan; Grampp, Günter

2017-01-01

Photooxidation kinetics of phenol, 1-naphthol, 2-naphthol, tyrosine (TyrOH) and N-acetyl-tyrosine (AcTyrOH), tryptophan (TrpH) by ruthenium(II) polypyridyl complexes: [Ru(bpy) 3 ]Cl 2 (1), [Ru(phen) 3 ]Cl 2 (2), [Ru(bpy)(phen)(bpg)]Cl 2 (3), and [Ru(dpq) 2 (bxbg)]Cl 2 (4) where bpy is 2,2'-bipyridine, phen - 1,10-phenanthroline, bpg - bipyridine-glycoluril, dpq - dipyrido[3,2-d:2',3'-f]quinoxaline, and bxbg - bis(o-xylene)bipyridine-glycoluril are investigated. Rate constants have been measured by steady-state luminescence and phase-modulation fluorometry in aqueous solutions at different pH's. The rates for the oxidation of the phenols and phenolic aromatic amino acids spreads over a wide range from 4.2×10 6 to 6.8×10 9 M -1 s -1 , depending on pH and the nature of solutes. At pH>pK a of the quenchers, the presence of reactive species (PhO - ) in the alkaline solutions is accounted for the rapid ET rates. In the pH range between 4 and 10 (pH

Sulfur-Specific Microbial Desulfurization of Sterically Hindered Analogs of Dibenzothiophene

PubMed Central

Lee, M. K.; Senius, J. D.; Grossman, M. J.

1995-01-01

Dibenzothiophenes (DBTs) bearing alkyl substitutions adjacent to the sulfur atom, such as 4,6-diethyldibenzothiophene (4,6-DEDBT), are referred to as sterically hindered with regard to access to the sulfur moiety. By using enrichment cultures with 4,6-DEDBT as the sole sulfur source, bacterial isolates which selectively remove sulfur from sterically hindered DBTs were obtained. The isolates were tentatively identified as Arthrobacter species. 4,6-DEDBT sulfone was shown to be an intermediate in the 4,6-DEDBT desulfurization pathway, and 2-hydroxy-3,3(prm1)-diethylbiphenyl (HDEBP) was identified as the sulfur-free end product. PMID:16535189

Time-varying metamaterials based on graphene-wrapped microwires: Modeling and potential applications

NASA Astrophysics Data System (ADS)

Salary, Mohammad Mahdi; Jafar-Zanjani, Samad; Mosallaei, Hossein

2018-03-01

The successful realization of metamaterials and metasurfaces requires the judicious choice of constituent elements. In this paper, we demonstrate the implementation of time-varying metamaterials in the terahertz frequency regime by utilizing graphene-wrapped microwires as building blocks and modulation of graphene conductivity through exterior electrical gating. These elements enable enhancement of light-graphene interaction by utilizing optical resonances associated with Mie scattering, yielding a large tunability and modulation depth. We develop a semianalytical framework based on transition-matrix formulation for modeling and analysis of periodic and aperiodic arrays of such time-varying building blocks. The proposed method is validated against full-wave numerical results obtained using the finite-difference time-domain method. It provides an ideal tool for mathematical synthesis and analysis of space-time gradient metamaterials, eliminating the need for computationally expensive numerical models. Moreover, it allows for a wider exploration of exotic space-time scattering phenomena in time-modulated metamaterials. We apply the method to explore the role of modulation parameters in the generation of frequency harmonics and their emerging wavefronts. Several potential applications of such platforms are demonstrated, including frequency conversion, holographic generation of frequency harmonics, and spatiotemporal manipulation of light. The presented results provide key physical insights to design time-modulated functional metadevices using various building blocks and open up new directions in the emerging paradigm of time-modulated metamaterials.

Adsorption of Poly(ethylene oxide)-Poly(lactide) Copolymers. Effects of Composition and Degradation.

PubMed

Muller, Dries; Carlsson, Fredrik; Malmsten, Martin

2001-04-01

The effect of chemical degradation of two diblock copolymers of poly(ethylene oxide) (E) and poly(lactide) (L), E(39)L(5) and E(39)L(20), on their adsorption at silica and methylated silica was investigated with in situ ellipsometry. Steric stablization of polystyrene dispersions was investigated in relation to degradation. Hydrolysis of the poly(lactide) block of the copolymers was followed at different temperatures and pH by using HPLC to measure the occurrence of lactic acid in solution. The block copolymers were quite stable in pH-unadjusted solution at low temperature, whereas degradation was facilitated by increasing temperature or lowering of the pH. Lower degradation rates of E(39)L(20) where observed at low temperature in comparison with those of E(39)L(5), whereas the degradation rates of the copolymers were quantitatively similar at high temperature. The adsorption of the copolymers at methylated silica substrates decreased with increasing degree of degradation due to the reduction in the ability of hydrophobic block to anchor the copolymer layer at the surface. At silica the adsorption initially increased with increasing degradation, particularly for E(39)L(20) due to deposition of aggregates onto the surface. After extensive degradation the adsorption of the copolymers at both silica and methylated silica resembled that of the corresponding poly(ethylene oxide) homopolymer. Overall, it was found that the eventual reduction in adsorption occurred at a lower degree of degradation for E(39)L(5) than for E(39)L(20). Mean-field calculations showed a reduced anchoring for the block copolymers with decreasing poly(lactide) block length at hydrophobic surfaces. In accordance with this finding, it was observed that polystyrene dispersions were stabilized by E(39)L(20) or E(39)L(5) in a way that depended on both the lactide block length and the degree of degradation. Upon degradation of the hydrophobic block, stabilization of the polystyrene dispersions was maintained initially, but eventually degradation resulted in destabilization. The average residual copolymer concentration required for stabilization of the polystyrene dispersions was much higher than the corresponding concentration of intact copolymer required for stabilization. Copyright 2001 Academic Press.

Software Defined Radio with Parallelized Software Architecture

NASA Technical Reports Server (NTRS)

Heckler, Greg

2013-01-01

This software implements software-defined radio procession over multicore, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to approx.50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.

Software Defined Radio with Parallelized Software Architecture

NASA Technical Reports Server (NTRS)

Heckler, Greg

2013-01-01

This software implements software-defined radio procession over multi-core, multi-CPU systems in a way that maximizes the use of CPU resources in the system. The software treats each processing step in either a communications or navigation modulator or demodulator system as an independent, threaded block. Each threaded block is defined with a programmable number of input or output buffers; these buffers are implemented using POSIX pipes. In addition, each threaded block is assigned a unique thread upon block installation. A modulator or demodulator system is built by assembly of the threaded blocks into a flow graph, which assembles the processing blocks to accomplish the desired signal processing. This software architecture allows the software to scale effortlessly between single CPU/single-core computers or multi-CPU/multi-core computers without recompilation. NASA spaceflight and ground communications systems currently rely exclusively on ASICs or FPGAs. This software allows low- and medium-bandwidth (100 bps to .50 Mbps) software defined radios to be designed and implemented solely in C/C++ software, while lowering development costs and facilitating reuse and extensibility.

Antisense Oligonucleotides for the Treatment of Spinal Muscular Atrophy

PubMed Central

Porensky, Paul N.

2013-01-01

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ∼1 in 10,000 live births. The most striking component is the loss of α-motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment paradigm other than supportive care, though the past 15 years has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease-modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials, including the application of antisense oligonucleotide (ASO) therapy for the correction of aberrant RNA splicing characteristic of SMA. Survival motor neuron (SMN) is a ubiquitously expressed 38-kD protein. Humans have two genes that produce SMN, SMN1 and SMN2, the former of which is deleted or nonfunctional in the majority of patients with SMA. These two genes are nearly identical with one exception, a C to T transition (C6T) within exon 7 of SMN2. C6T disrupts a modulator of splicing, leading to the exclusion of exon 7 from ∼90% of the mRNA transcript. The resultant truncated Δ7SMN protein does not oligomerize efficiently and is rapidly degraded. SMA can therefore be considered a disease of too little SMN protein. A number of cis-acting splice modifiers have been identified in the region of exon 7, the steric block of which enhances the retention of the exon and a resultant full-length mRNA sequence. ASOs targeted to these splice motifs have shown impressive phenotype rescue in multiple SMA mouse models. PMID:23544870

STS-88 Onboard Photograph - Unity and Zarya Modules

NASA Technical Reports Server (NTRS)

1998-01-01

This photograph, taken during the STS-88 mission, shows the cornected Unity Module or Node 1 and Zarya or the Functional Cargo Block (FGB) after having been released from the Orbiter Endeavour's cargo bay. The Unity (also called Node 1), the first U.S. Module for the International Space Station (ISS), is a six-sided connector to which all future U.S. Station modules will attach. It was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity Module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

Metal-Free Approaches to Sterically-Hindered Bonds

NASA Astrophysics Data System (ADS)

Dunham, Veronica Vin-yi

Developing methods to perform cross coupling reactions by means of catalysis is highly desirable in chemistry. Many industries in today's society, such as the petroleum, agriculture, pharmaceutical, electronics, and polymer industry, use catalysis to some extent whether it is to make molecules that offer crop protection or toward the synthesis of the active ingredient of a medication. It is noteworthy that over 90% of chemicals are made through catalytic processes and that the catalyst market reached $17 billion in 2014, which demonstrates the demand for such methods. While transition metal catalysts have advantages such as low catalyst loading, broad reactivity, and that they have been well studied, some disadvantages are that they can be relatively expensive and sometimes air sensitive which can make them challenging to use. Organocatalysis, specifically noncovalent catalysis operating through hydrogen bond donating interactions, offers an environmentally-friendly alternative to transition metal catalysis. Our lab utilizes organocatalysis as a strategy to synthesize challenging, sterically-hindered bonds. Nitrimines have been identified as powerful coupling partners for the sustainable construction of new sterically congested carbon-carbon and carbon-heteroatom bonds. Using urea catalysis, a metal-free method to synthesize previously inaccessible enamines has been developed. Conventional routes to synthesize enamines as important building blocks toward target molecules generally require Lewis/Bronsted acids or expensive transition metals; however, these methods are often unsuccessful when stericallyhindered substrates are used. To address this synthetic challenge, it was hypothesized that hydrogen bonding interactions between a urea organocatalyst and nitrimine would generate a reactive species suited for the effective carbon-nitrogen coupling with amines to give the desired enamine products. This reaction provides high yields (up to 99%) of enamines using a variety of nitrimines and amines including piperidine, pyrrolidine, dibenzylamine, substituted indolines, and substituted N-methylanilines. Further investigations into the applicability of nitrimines for the synthesis of sterically-hindered bonds led to the discovery of formal carbon-carbon cross coupling reactions involving nitrimines and carbon nucleophiles such as indole, pyrrole, and hydroxycoumarin. Under optimized conditions, moderate to high yields of the desired dior tri-substituted alkene product were obtained with electron-rich and electron-poor nitrimines. Furthermore, by strategic modification of the reaction conditions, control over the E/Z selectivity of the tri-substituted alkene products gave up to 19:1 ratio of Z:E isomers. This nitrimine-based formal carbon-carbon cross coupling methodology was then applied to the synthesis of a small target molecule, phenprocoumon, which was obtained in an overall 67% yield. The undeniable utility of urea catalysis operating through hydrogen bond donor (HBD) interactions has prompted the examination into enhanced HBD catalysts. Through the incorporation of a strategically placed Lewis acid on a urea scaffold, a new family of highly tunable HBD catalysts benefitting from enhanced activity was established. After determining the pKa of various urea catalysts using Bordwell's method of overlapping indicators and comparing catalysts in two reaction systems, it was observed that the choice of Lewis acid and its associated ligands had an effect on urea reactivity, acidity, and polarization. In addition to Lewis acid assisted urea catalysts, silanediols have been discovered to participate as enhanced HBD catalysts. Taking advantage of the ability of our silanediol catalysts to participate in asymmetric anion-binding catalysis, a strategy toward an enantioselective synthesis of the sterically-encumbered molecule gonytolide A, an innate immune promoter, is underway.

An antibody to the lutheran glycoprotein (Lu) recognizing the LU4 blood type variant inhibits cell adhesion to laminin α5.

PubMed

Kikkawa, Yamato; Miwa, Takahiro; Tohara, Yukiko; Hamakubo, Takayuki; Nomizu, Motoyoshi

2011-01-01

The Lutheran blood group glycoprotein (Lu), an Ig superfamily (IgSF) transmembrane receptor, is also known as basal cell adhesion molecule (B-CAM). Lu/B-CAM is a specific receptor for laminin α5, a major component of basement membranes in various tissues. Previous reports have shown that Lu/B-CAM binding to laminin α5 contributes to sickle cell vaso-occlusion. However, as there are no useful tools such as function-blocking antibodies or drugs, it is unclear how epithelial and sickled red blood cells adhere to laminin α5 via Lu/B-CAM. In this study, we discovered a function-blocking antibody that inhibits Lu binding to laminin α5 using a unique binding assay on tissue sections. To characterize the function-blocking antibody, we identified the site on Lu/B-CAM recognized by this antibody. The extracellular domain of Lu/B-CAM contains five IgSF domains, D1-D2-D3-D4-D5. The antibody epitope was localized to D2, but not to the D3 domain containing the major part of the laminin α5 binding site. Furthermore, mutagenesis studies showed that Arg(175), the LU4 blood group antigenic site, was crucial for forming the epitope and the antibody bound sufficiently close to sterically hinder the interaction with α5. Cell adhesion assay using the antibody also showed that Lu/B-CAM serves as a secondary receptor for the adhesion of carcinoma cells to laminin α5. This function-blocking antibody against Lu/B-CAM should be useful for not only investigating cell adhesion to laminin α5 but also for developing drugs to inhibit sickle cell vaso-occlusion.

RAFT Dispersion Alternating Copolymerization of Styrene with N-Phenylmaleimide: Morphology Control and Application as an Aqueous Foam Stabilizer

PubMed Central

2016-01-01

We report a new nonaqueous polymerization-induced self-assembly (PISA) formulation based on the reversible addition–fragmentation chain transfer (RAFT) dispersion alternating copolymerization of styrene with N-phenylmaleimide using a nonionic poly(N,N-dimethylacrylamide) stabilizer in a 50/50 w/w ethanol/methyl ethyl ketone (MEK) mixture. The MEK cosolvent is significantly less toxic than the 1,4-dioxane cosolvent reported previously [YangP.; Macromolecules2013, 46, 8545−8556]. The core-forming alternating copolymer block has a relatively high glass transition temperature (Tg), which leads to vesicular morphologies being observed during PISA, as well as the more typical sphere and worm phases. Each of these copolymer morphologies has been characterized by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) studies. TEM studies reveal micrometer-sized elliptical particles with internal structure, with SAXS analysis suggesting an oligolamellar vesicle morphology. This structure differs from that previously reported for a closely related PISA formulation utilizing a poly(methacrylic acid) stabilizer block for which unilamellar platelet-like particles are observed by TEM and SAXS. This suggests that interlamellar interactions are governed by the nature of the steric stabilizer layer. Moreover, using the MEK cosolvent also enables access to a unilamellar vesicular morphology, despite the high Tg of the alternating copolymer core-forming block. This was achieved by simply conducting the PISA synthesis at a higher temperature for a longer reaction time (80 °C for 24 h). Presumably, MEK solvates the core-forming block more than the previously utilized 1,4-dioxane cosolvent, which leads to greater chain mobility. Finally, preliminary experiments indicate that the worms are much more efficient stabilizers for aqueous foams than either the spheres or the oligolamellar elliptical vesicles. PMID:27708458

Influence of nonelectrostatic ion-ion interactions on double-layer capacitance

NASA Astrophysics Data System (ADS)

Zhao, Hui

2012-11-01

Recently a Poisson-Helmholtz-Boltzmann (PHB) model [Bohinc , Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.85.031130 85, 031130 (2012)] was developed by accounting for solvent-mediated nonelectrostatic ion-ion interactions. Nonelectrostatic interactions are described by a Yukawa-like pair potential. In the present work, we modify the PHB model by adding steric effects (finite ion size) into the free energy to derive governing equations. The modified PHB model is capable of capturing both ion specificity and ion crowding. This modified model is then employed to study the capacitance of the double layer. More specifically, we focus on the influence of nonelectrostatic ion-ion interactions on charging a double layer near a flat surface in the presence of steric effects. We numerically compute the differential capacitance as a function of the voltage under various conditions. At small voltages and low salt concentrations (dilute solution), we find out that the predictions from the modified PHB model are the same as those from the classical Poisson-Boltzmann theory, indicating that nonelectrostatic ion-ion interactions and steric effects are negligible. At moderate voltages, nonelectrostatic ion-ion interactions play an important role in determining the differential capacitance. Generally speaking, nonelectrostatic interactions decrease the capacitance because of additional nonelectrostatic repulsion among excess counterions inside the double layer. However, increasing the voltage gradually favors steric effects, which induce a condensed layer with crowding of counterions near the electrode. Accordingly, the predictions from the modified PHB model collapse onto those computed by the modified Poisson-Boltzmann theory considering steric effects alone. Finally, theoretical predictions are compared and favorably agree with experimental data, in particular, in concentrated solutions, leading one to conclude that the modified PHB model adequately predicts the diffuse-charge dynamics of the double layer with ion specificity and steric effects.

Steric, Quantum, and Electrostatic Effects on SN2 Reaction Barriers in Gas Phase

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

Liu, Shubin; Hu, Hao; Pedersen, Lee G.

2010-05-13

Biomolecular nucleophilic substitution reactions, S{sub N}2, are fundamental and commonplace in chemistry. It is the well-documented experimental finding in the literature that vicinal substitution with bulkier groups near the reaction center significantly slows the reaction due to steric hindrance, but theoretical understanding in the quantitative manner about factors dictating the S{sub N}2 reaction barrier height is still controversial. In this work, employing the new quantification approach that we recently proposed for the steric effect from the density functional theory framework, we investigate the relative contribution of three independent effects—steric, electrostatic, and quantum—to the S{sub N}2 barrier heights in gas phasemore » for substituted methyl halide systems, R{sub 1}R{sub 2}R{sub 3}CX, reacting with the fluorine anion, where R{sub 1}, R{sub 2}, and R{sub 3} denote substituting groups and X = F or Cl. We found that in accordance with the experimental finding, for these systems, the steric effect dominates the transition state barrier, contributing positively to barrier heights, but this contribution is largely compensated by the negative, stabilizing contribution from the quantum effect due to the exchange-correlation interactions. Moreover, we find that it is the component from the electrostatic effect that is linearly correlated with the S{sub N}2 barrier height for the systems investigated in the present study. In addition, we compared our approach with the conventional method of energy decomposition in density functional theory as well as examined the steric effect from the wave function theory for these systems via natural bond orbital analysis.« less

On the mechanisms of interference between mobile phones and pacemakers: parasitic demodulation of GSM signal by the sensing amplifier.

PubMed

Barbaro, V; Bartolini, P; Calcagnini, G; Censi, F; Beard, B; Ruggera, P; Witters, D

2003-06-07

The aim of this study was to investigate the mechanisms by which the radiated radiofrequency (RF) GSM (global system for mobile communication) signal may affect pacemaker (PM) function. We measured the signal at the output of the sensing amplifier of PMs with various configurations of low-pass filters. We used three versions of the same PM model: one with a block capacitor which short circuits high-frequency signals; one with a ceramic feedthrough capacitor, a hermetically sealed mechanism connecting the internal electronics to the external connection block, and one with both. The PMs had been modified to have an electrical shielded connection to the output of the sensing amplifier. For each PM, the output of the sensing amplifier was monitored under exposure to modulated and non-modulated RF signals, and to GSM signals (900 and 1800 MHz). Non-modulated RF signals did not alter the response of the PM sensing amplifier. Modulated RF signals showed that the block capacitor did not succeed in short circuiting the RF signal, which is somehow demodulated by the PM internal non-linear circuit elements. Such a demodulation phenomenon poses a critical problem because digital cellular phones use extremely low-frequency modulation (as low as 2 Hz). which can be mistaken for normal heartbeat.

Analog Building Blocks for Communications Modems.

DTIC Science & Technology

1977-01-01

x*—*- A0-A039 82b ELECTRONIC COMMUNICATIONS INC ST PETERSBURG FLA F/6 9/5 ANALOG BUILDING BLOCKS FOR COMMUNICATIONS MODEMS .(U) JAN 77 B BLACK...F33615-7<t-C-1120 UNCLASSIFIED AFAL-TR-76-29 NL ANALOG BUILDING BLOCKS FOR COMMUNICATIONS MODEMS ELECTRONIC COMMUNICATIONS INC. A SUBSIDIARY OF...Idantltr Or Mac* numb*,; Avionics Building-Block modules Frequency Synthesize* Costas Demodulator Amplifier Modem Frequency Multiplier ’ -^ « TRACT

OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

EPA Science Inventory

Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


Thomas M. Becker, Michael A. Gonzalez*

United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric vs. stereoelectronic effects† †Electronic supplementary information (ESI) available: Computational details, Cartesian coordinates and vibrational frequencies of all optimized structures. See DOI: 10.1039/c5sc02307f Click here for additional data file.

PubMed Central

Crandell, Douglas W.; Mazumder, Shivnath

2015-01-01

Density functional theory calculations demonstrate that the reversal of regiochemical outcome of the addition for substituted methyl propiolates in the rhodium-catalyzed [(2 + 2) + 2] carbocyclization with PPh3 and (S)-xyl-binap as ligands is both electronically and sterically controlled. For example, the ester functionality polarizes the alkyne π* orbital to favor overlap of the methyl-substituted terminus of the alkyne with the pπ-orbital of the alkenyl fragment of the rhodacycle during alkyne insertion with PPh3 as the ligand. In contrast, the sterically demanding xyl-binap ligand cannot accommodate the analogous alkyne orientation, thereby forcing insertion to occur at the sterically preferred ester terminus, overriding the electronically preferred orientation for alkyne insertion. PMID:28757978

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects.

PubMed

Wu, Kevin; Doyle, Abigail G

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp 3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment-cone angle and % buried volume-are not equivalent, despite their treatment in the literature.

Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

NASA Astrophysics Data System (ADS)

Wu, Kevin; Doyle, Abigail G.

2017-08-01

The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

More Metric Measurement Concepts. Fundamentals of Occupational Mathematics. Module 10.

ERIC Educational Resources Information Center

Engelbrecht, Nancy; And Others

This module is the 10th in a series of 12 learning modules designed to teach occupational mathematics. Blocks of informative material and rules are followed by examples and practice problems. The solutions to the practice problems are found at the end of the module. Specific topics covered include the metric concepts of mass, weight, and volume…

Powers and Roots. Fundamentals of Occupational Mathematics. Module 11.

ERIC Educational Resources Information Center

Engelbrecht, Nancy; And Others

This module is the 11th in a series of 12 learning modules designed to teach occupational mathematics. Blocks of informative material and rules are followed by examples and practice problems. The solutions to the practice problems are found at the end of the module. Specific topics covered include multiplication, powers, calculator use, and roots.…

Unlocking the sugar "steric gate" of DNA polymerases.

PubMed

Brown, Jessica A; Suo, Zucai

2011-02-22

To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2'-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the "steric gate", establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review.

Unlocking the Sugar ‘Steric Gate’ of DNA Polymerases†

PubMed Central

Brown, Jessica A.; Suo, Zucai

2011-01-01

To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2′-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the ‘steric gate’, establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review article. PMID:21226515

Using Systems Thinking to Evaluate Formative Feedback in UK Higher Education: The Case of Classroom Response Technology

ERIC Educational Resources Information Center

Pagano, Rosane; Paucar-Caceres, Alberto

2013-01-01

Providing high quality formative feedback to large and very diverse cohorts of students taking short intensive blocks of teaching (block release) has become crucial in management education provision. The paper proposes the exploitation of classroom response technology (CRT) to evaluate learning activities of students taking block release modules.…

Knowledge and Processes in Design

DTIC Science & Technology

1992-09-03

Orqanization Name(s) and Address(es). Self-explanatory. Block 16. Price Code. Enter approoriate price Block 8. Performing Organization Report code...NTIS on/y). Number. Enter the unique alphanumerc report number(s) assigned by the organization periorming the report. Blocks 17.-19...statement codings were then organized into larger control-flow structures centered around design components called modules. The general assumption was

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, Gregory C.; Brinker, C. Jeffrey; Doughty, Daniel H.; Bein, Thomas; Moller, Karin

1996-01-01

Coatings and sensors having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, Gregory C.; Brinker, C. Jeffrey; Doughty, Daniel H.; Bein, Thomas; Moller, Karin

1993-01-01

Coatings and sensors having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials in the central neuron of snail, Achatina fulica Ferussac.

PubMed

Lin, Chia-Hsien; Tsai, Ming-Cheng

2005-05-01

The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials were studied on the RP1 central neuron of giant African snails (Achatina fulica Ferussac). Extra-cellular application of d-amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin, propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d-amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP. U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP, whereas they did not block the d-amphetamine-elicited BoP in the same neuron. These results suggest that BoP elicited by d-amphetamine or procaine were associated with protein kinase A and phospholipase C activity in the neuron.

Multi-equilibrium property of metabolic networks: SSI module.

PubMed

Lei, Hong-Bo; Zhang, Ji-Feng; Chen, Luonan

2011-06-20

Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI) metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module.

Multi-equilibrium property of metabolic networks: SSI module

PubMed Central

2011-01-01

Background Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI) metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. Results In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. Conclusions In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module. PMID:21689474

Practice-induced and sequential modulations of the Simon effect.

PubMed

Soetens, Eric; Maetens, Kathleen; Zeischka, Peter

2010-05-01

People react more quickly and more accurately to stimuli presented in locations corresponding to the response, as compared with noncorresponding locations, even when stimulus location is irrelevant (Simon effect [SE]). The explanation that SEs are caused by the automatic priming of a corresponding response has been questioned, because of the many exceptions to the effect. We replicated practice-induced and sequential modulations of the SE in two experiments--first, by training participants with blocks of location-relevant stimuli, and second, by mixing location-relevant and location-irrelevant trials. The decrease of the SE with incompatible training was relatively permanent in the blocked experiment, whereas the effect was temporary in the mixed experiment. The difference was caused by a more permanent reversal of the SE after incongruent trials, showing that sequential modulations depend on long-term practice effects. We suggest that there is a formation of a contralateral long-term memory stimulus-response link in blocked conditions and that short-term and long-term memory links are primed by preceding events.

Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies.

PubMed

Outchkourov, Nikolay; Vermunt, Adriaan; Jansen, Josephine; Kaan, Anita; Roeffen, Will; Teelen, Karina; Lasonder, Edwin; Braks, Anneke; van de Vegte-Bolmer, Marga; Qiu, Li Yan; Sauerwein, Robert; Stunnenberg, Hendrik G

2007-06-08

Pfs48/45, a member of a Plasmodium-specific protein family, displays conformation-dependent epitopes and is an important target for malaria transmission-blocking (TB) immunity. To design a recombinant Pfs48/45-based TB vaccine, we analyzed the conformational TB epitopes of Pfs48/45. The Pfs48/45 protein was found to consist of a C-terminal six-cysteine module recognized by anti-epitope I antibodies, a middle four-cysteine module recognized by anti-epitopes IIb and III, and an N-terminal module recognized by anti-epitope V antibodies. Refolding assays identified that a fragment of 10 cysteines (10C), comprising the middle four-cysteine and the C-terminal six-cysteine modules, possesses superior refolding capacity. The refolded and partially purified 10C conformer elicited antibodies in mice that targeted at least two of the TB epitopes (I and III). The induced antibodies could block the fertilization of Plasmodium falciparum gametes in vivo in a concentration-dependent manner. Our results provide important insight into the structural organization of the Pfs48/45 protein and experimental support for a Pfs48/45-based subunit vaccine.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, G.C.; Brinker, C.J.; Doughty, D.H.; Bein, T.; Moller, K.

1996-12-31

Coatings and sensors are disclosed having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided. 7 figs.

Coatings with controlled porosity and chemical properties

DOEpatents

Frye, G.C.; Brinker, C.J.; Doughty, D.H.; Bein, T.; Moller, K.

1993-07-06

Coatings and sensors are described having both steric and chemical selectivity. Controlled porosity provides the steric selectivity, whereas chemically tailored film properties, using controlled composition or modification by coupling agents, chemical species replacement, or chemical species within pores, provide the chemical selectivity. Single or multiple layers may be provided.

Sterically shielded diboron-containing metallocene olefin polymerization catalysts

DOEpatents

Marks, Tobin J.; Ja, Li; Yang, Xinmin

1995-09-05

A non-coordinating anion, preferably containing a sterically shielded diboron hydride, if combined with a cyclopenta-dienyl-substituted metallocene cation component, such as a zirconocene metallocene, is a useful olefin polymerization catalyst component. The anion preferably has the formula ##STR1## where R is branched lower alkyl, such as t-butyl.

Iodine(III) Derivatives as Halogen Bonding Organocatalysts.

PubMed

Heinen, Flemming; Engelage, Elric; Dreger, Alexander; Weiss, Robert; Huber, Stefan M

2018-03-26

Hypervalent iodine(III) derivatives are known as versatile reagents in organic synthesis, but there is only one previous report on their use as Lewis acidic organocatalysts. Herein, we present first strong indications for the crucial role of halogen bonding in this kind of catalyses. To this end, the solvolysis of benzhydryl chloride and the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone served as benchmark reactions for halide abstraction and the activation of neutral compounds. Iodolium compounds (cyclic diaryl iodonium species) were used as activators or catalysts, and we were able to markedly reduce or completely switch off their activity by sterically blocking one or two of their electrophilic axes. Compared with previously established bidentate cationic halogen bond donors, the monodentate organoiodine derivatives used herein are at least similarly active (in the Diels-Alder reaction) or even decidedly more active (in benzhydryl chloride solvolysis). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics.

PubMed

Duchstein, Patrick; Milek, Theodor; Zahn, Dirk

2015-01-01

Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization) and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle. Molecular dynamics simulations reveal different solvent shells and distance-dependent mobility of ions and solvent molecules. From this, we provide a molecular rationale of effective particle size, net charge and polarizability of the nanoparticles in solution.

Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics

PubMed Central

Duchstein, Patrick; Milek, Theodor; Zahn, Dirk

2015-01-01

Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization) and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle. Molecular dynamics simulations reveal different solvent shells and distance-dependent mobility of ions and solvent molecules. From this, we provide a molecular rationale of effective particle size, net charge and polarizability of the nanoparticles in solution. PMID:25962096

Effect of the platinum content on the microstructure and micropore size distribution of Pt/alumina-pillared clays.

PubMed

Barrera-Vargas, M; Valencia-Rios, J; Vicente, M A; Korili, S A; Gil, A

2005-12-15

The aim of this work is to study the effect of the platinum content (0-1.8 wt % Pt) on the microstructure of an alumina-pillared clay. For this purpose, the nitrogen physisorption data at -196 degrees C, the micropore size distributions of the supported platinum catalysts, and the hydrogen chemisorption results at 30 degrees C have been analyzed and compared. The preparation of the catalysts has modified the textural properties of the Al-pillared clay support, giving rise to a loss of surface area and micropore volume. After reduction at 420 degrees C, the presence of dispersed metallic platinum with mean crystallite size in the 22-55 A range has been found by hydrogen adsorption. Comparison of all results reveals that the platinum species block the micropore entrances by steric hindrance to nitrogen access as the platinum content increases.

Elucidating bonding preferences in tetrakis(imido)uranate(VI) dianions

NASA Astrophysics Data System (ADS)

Anderson, Nickolas H.; Xie, Jing; Ray, Debmalya; Zeller, Matthias; Gagliardi, Laura; Bart, Suzanne C.

2017-09-01

Actinyl species, [AnO2]2+, are well-known derivatives of the f-block because of their natural occurrence and essential roles in the nuclear fuel cycle. Along with their nitrogen analogues, [An(NR)2]2+, actinyls are characterized by their two strong trans-An-element multiple bonds, a consequence of the inverse trans influence. We report that these robust bonds can be weakened significantly by increasing the number of multiple bonds to uranium, as demonstrated by a family of uranium(VI) dianions bearing four U-N multiple bonds, [M]2[U(NR)4] (M = Li, Na, K, Rb, Cs). Their geometry is dictated by cation coordination and sterics rather than by electronic factors. Multiple bond weakening by the addition of strong π donors has the potential for applications in the processing of high-valent actinyls, commonly found in environmental pollutants and spent nuclear fuels.

Enhancing adsorption of U(VI) onto EDTA modified L. cylindrica using epichlorohydrin and ethylenediamine as a bridge

PubMed Central

Su, Shouzheng; Liu, Qi; Liu, Jingyuan; Zhang, Hongsen; Li, Rumin; Jing, Xiaoyan; Wang, Jun

2017-01-01

Benefiting from strong coordination ability and unique vascular structure, EDTA modified L. cylindrica opens up an alternative way for uranium recovery from seawater. However, limitations, such as poor adsorption capacity and slow adsorption rate due to low graft ratio of EDTA via one-step esterification block its practical application. Here, a strategy for increasing the graft ratio is proposed in order to improve the adsorption performance. The strategy initially involves immobilization of epichlorohydrin (EPI) onto L. cylindrica and then ethylenediamine (EDA) is introduced via facile ring-opening reaction. EPI and EDA serve as a bridge between L. cylindrica and EDTA. The graft ratio is promoted (15.01 to 21.44%) contributing to the smaller steric hindrance of EPI and EDA than EDTA and improvement in adsorption performance. In addition, the adsorbent prepared by the new strategy exhibits excellent adsorption properties in simulated seawater. PMID:28272435

New dendritic gelator bearing carbazole in each branching unit: selected response to fluoride ion in gel phase.

PubMed

Xu, Defang; Liu, Xingliang; Lu, Ran; Xue, Pengchong; Zhang, Xiaofei; Zhou, Huipeng; Jia, Junhui

2011-03-07

A new dendritic gelator with carbazole as the building block (HBCD) was synthesized. It was found that H-bonding between the amide groups and π-π interaction between the aromatic rings played predominant roles in the gel formation. Meanwhile, significant aggregation-induced emission enhancement was observed in the gel state due to the formation of J-aggregates and the restricted molecular motion. Notably, the gel state of HBCD can be destroyed upon addition of F(-), accompanied by fluorescence enhancement on account of the formation of N-HF(-), which could further lead to the increased coplanarity of HBCD. The sensory capability of HBCD exhibited a high selectivity towards F(-) instead of the Cl(-), Br(-), I(-) and AcO(-) anions, which could be explained by the fact that the steric hindrance of the dendrimer would go against the interactions between the larger anions and HBCD.

Stable dimeric magnesium(I) compounds: from chemical landmarks to versatile reagents.

PubMed

Stasch, Andreas; Jones, Cameron

2011-06-07

The chemistry of the s-block metals is dominated by the +1 oxidation state for the Alkali metals (group 1) and the +2 oxidation state for the Alkaline Earth metals (group 2). In recent years, a series of stable dimeric magnesium(I) compounds has been prepared and their chemistry has started to develop. These complexes feature "deformable" Mg-Mg single bonds and are stabilised by sterically demanding and chelating anionic N-ligands that prevent their disproportionation. They have rapidly proven useful in organic and organometallic/inorganic reduction reactions as hydrocarbon soluble, stoichiometric, selective and safe reducing agents. The scope of this perspective focuses on stable molecular compounds of the general type LMgMgL and describes their synthesis, structures, theoretical and spectroscopic studies as well as their further chemistry. Also, comparisons are drawn with related complexes including magnesium(II) hydrides and dimeric zinc(I) compounds.

Perfect mixing of immiscible macromolecules at fluid interfaces

NASA Astrophysics Data System (ADS)

Sheiko, Sergei; Matyjaszewski, Krzysztof; Tsukruk, Vladimir; Carrillo, Jan-Michael; Rubinstein, Michael; Dobrynin, Andrey; Zhou, Jing

2014-03-01

Macromolecules typically phase separate unless their shapes and chemical compositions are tailored to explicitly drive mixing. But now our research has shown that physical constraints can drive spontaneous mixing of chemically different species. We have obtained long-range 2D arrays of perfectly mixed macromolecules having a variety of molecular architectures and chemistries, including linear chains, block-copolymer stars, and bottlebrush copolymers with hydrophobic, hydrophilic, and lipophobic chemical compositions. This is achieved by entropy-driven enhancement of steric repulsion between macromolecules anchored on a substrate. By monitoring the kinetics of mixing, we have proved that molecular intercalation is an equilibrium state. The array spacing is controlled by the length of the brush side chains. This entropic templating strategy opens new ways for generating patterns on sub-100 nm length scales with potential application in lithography, directed self-assembly, and biomedical assays. Financial support from the National Science Foundation DMR-0906985, DMR-1004576, DMR-1122483, and DMR-0907515.

Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae

PubMed Central

Schmidt, Christian; Berninghausen, Otto; Becker, Thomas

2017-01-01

Mechanistic understanding of eukaryotic ribosome formation requires a detailed structural knowledge of the numerous assembly intermediates, generated along a complex pathway. Here, we present the structure of a late pre-40S particle at 3.6 Å resolution, revealing in molecular detail how assembly factors regulate the timely folding of pre-18S rRNA. The structure shows that, rather than sterically blocking 40S translational active sites, the associated assembly factors Tsr1, Enp1, Rio2 and Pno1 collectively preclude their final maturation, thereby preventing untimely tRNA and mRNA binding and error prone translation. Moreover, the structure explains how Pno1 coordinates the 3’end cleavage of the 18S rRNA by Nob1 and how the late factor’s removal in the cytoplasm ensures the structural integrity of the maturing 40S subunit. PMID:29155690

Ultra-Tuning of the Rare-Earth fcu-MOF Aperture Size for Selective Molecular Exclusion of Branched Paraffins.

PubMed

Assen, Ayalew H; Belmabkhout, Youssef; Adil, Karim; Bhatt, Prashant M; Xue, Dong-Xu; Jiang, Hao; Eddaoudi, Mohamed

2015-11-23

Using isoreticular chemistry allows the design and construction of a new rare-earth metal (RE) fcu-MOF with a suitable aperture size for practical steric adsorptive separations. The judicious choice of a relatively short organic building block, namely fumarate, to bridge the 12-connected RE hexanuclear clusters has afforded the contraction of the well-defined RE-fcu-MOF triangular window aperture, the sole access to the two interconnected octahedral and tetrahedral cages. The newly constructed RE (Y(3+) and Tb(3+)) fcu-MOF analogues display unprecedented total exclusion of branched paraffins from normal paraffins. The resultant window aperture size of about 4.7 Å, regarded as a sorbate-size cut-off, enabled a complete sieving of branched paraffins from normal paraffins. The results are supported by collective single gas and mixed gas/vapor adsorption and calorimetric studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Frustration-guided motion planning reveals conformational transitions in proteins

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

Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid

Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here in this paper, we present a new, robotics-inspired motion planning procedure called dCCRRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eightmore » proteins determined in two conformations separated by, on average, 7.5Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. Additionally, we then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions.Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/.« less

Frustration-guided motion planning reveals conformational transitions in proteins.

PubMed

Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; van den Bedem, Henry

2017-10-01

Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25 Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/. © 2017 Wiley Periodicals, Inc.

Frustration-guided motion planning reveals conformational transitions in proteins

DOE PAGES

Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; ...

2017-07-12

Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here in this paper, we present a new, robotics-inspired motion planning procedure called dCCRRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eightmore » proteins determined in two conformations separated by, on average, 7.5Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. Additionally, we then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions.Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/.« less

Signal-Conditioning Block of a 1 × 200 CMOS Detector Array for a Terahertz Real-Time Imaging System

PubMed Central

Yang, Jong-Ryul; Lee, Woo-Jae; Han, Seong-Tae

2016-01-01

A signal conditioning block of a 1 × 200 Complementary Metal-Oxide-Semiconductor (CMOS) detector array is proposed to be employed with a real-time 0.2 THz imaging system for inspecting large areas. The plasmonic CMOS detector array whose pixel size including an integrated antenna is comparable to the wavelength of the THz wave for the imaging system, inevitably carries wide pixel-to-pixel variation. To make the variant outputs from the array uniform, the proposed signal conditioning block calibrates the responsivity of each pixel by controlling the gate bias of each detector and the voltage gain of the lock-in amplifiers in the block. The gate bias of each detector is modulated to 1 MHz to improve the signal-to-noise ratio of the imaging system via the electrical modulation by the conditioning block. In addition, direct current (DC) offsets of the detectors in the array are cancelled by initializing the output voltage level from the block. Real-time imaging using the proposed signal conditioning block is demonstrated by obtaining images at the rate of 19.2 frame-per-sec of an object moving on the conveyor belt with a scan width of 20 cm and a scan speed of 25 cm/s. PMID:26950128

Signal-Conditioning Block of a 1 × 200 CMOS Detector Array for a Terahertz Real-Time Imaging System.

PubMed

Yang, Jong-Ryul; Lee, Woo-Jae; Han, Seong-Tae

2016-03-02

A signal conditioning block of a 1 × 200 Complementary Metal-Oxide-Semiconductor (CMOS) detector array is proposed to be employed with a real-time 0.2 THz imaging system for inspecting large areas. The plasmonic CMOS detector array whose pixel size including an integrated antenna is comparable to the wavelength of the THz wave for the imaging system, inevitably carries wide pixel-to-pixel variation. To make the variant outputs from the array uniform, the proposed signal conditioning block calibrates the responsivity of each pixel by controlling the gate bias of each detector and the voltage gain of the lock-in amplifiers in the block. The gate bias of each detector is modulated to 1 MHz to improve the signal-to-noise ratio of the imaging system via the electrical modulation by the conditioning block. In addition, direct current (DC) offsets of the detectors in the array are cancelled by initializing the output voltage level from the block. Real-time imaging using the proposed signal conditioning block is demonstrated by obtaining images at the rate of 19.2 frame-per-sec of an object moving on the conveyor belt with a scan width of 20 cm and a scan speed of 25 cm/s.

Disaster management curricula: strategy to create doctors with disaster resilience in Aceh, Indonesia

NASA Astrophysics Data System (ADS)

Wahyuniati, N.; Maulana, R.; Ichsan, I.

2017-02-01

Faculty of Medicine of Syiah Kuala University has one special block called Disaster Management block (the last block on the curricula) on Competency-Based Curriculum of Medical Sciences with the Problem-Based Learning method. This block has four credits, allocated seven weeks learning period including one week for evaluation. The placement of disaster management block in the 7th semester (last semester) aims to allow students to implement more easily the complete basic and clinical medical knowledge and then have it integrated with the management capabilities during adisaster. This article evaluates two components: 1) Disaster management module, by comparing the content of modules used in three different academic years, the academic year 2013/2014, 2014/2015 and 2015/2016, 2) The final grade, by comparing the final grade of disaster management block in 4 years (comparing students class of 2008, 2009, 2010 and 2011). The results revealed that on every academic year there were additions and strengthening of the material to ensure that students achieve a complete learning experience, and there was a slight increase in student’s grades where the number of students who receive grades A has increased while the number of students who receive grades E decreased.

Space shuttle on-orbit flight control software requirements, preliminary version

NASA Technical Reports Server (NTRS)

1975-01-01

Software modules associated with various flight control functions for the space shuttle orbiter are described. Data flow, interface requirements, initialization requirements and module sequencing requirements are considered. Block diagrams and tables are included.

Allostery and the dynamic oligomerization of porphobilinogen synthase

PubMed Central

Jaffe, Eileen K.; Lawrence, Sarah H.

2011-01-01

The structural basis for allosteric regulation of porphobilinogen synthase (PBGS) is modulation of a quaternary structure equilibrium between octamer and hexamer (via dimers), which is represented schematically as 8mer ⇔ 2mer ⇔ 2mer* ⇔ 6mer*. The “*” represents a reorientation between two domains of each subunit that occurs in the dissociated state because it is sterically forbidden in the larger multimers. Allosteric effectors of PBGS are both intrinsic and extrinsic and are phylogenetically variable. In some species this equilibrium is modulated intrinsically by magnesium which binds at a site specific to the 8mer. In other species this equilibrium is modulated intrinsically by pH; the guanidinium group of an arginine being spatially equivalent to the allosteric magnesium ion. In humans, disease associated variants all shift the equilibrium toward the 6mer* relative to wild type. The 6mer* has a surface cavity that is not present in the 8mer and is proposed as a small molecule allosteric binding site. In silico and in vitro approaches have revealed species-specific allosteric PBGS inhibitors that stabilize the 6mer*. Some of these inhibitors are drugs in clinical use leading to the hypothesis that extrinsic allosteric inhibition of human PBGS could be a mechanism for drug side effects. PMID:22037356

The structural chemistry of metallocorroles: combined X-ray crystallography and quantum chemistry studies afford unique insights.

PubMed

Thomas, Kolle E; Alemayehu, Abraham B; Conradie, Jeanet; Beavers, Christine M; Ghosh, Abhik

2012-08-21

Although they share some superficial structural similarities with porphyrins, corroles, trianionic ligands with contracted cores, give rise to fundamentally different transition metal complexes in comparison with the dianionic porphyrins. Many metallocorroles are formally high-valent, although a good fraction of them are also noninnocent, with significant corrole radical character. These electronic-structural characteristics result in a variety of fascinating spectroscopic behavior, including highly characteristic, paramagnetically shifted NMR spectra and textbook cases of charge-transfer spectra. Although our early research on corroles focused on spectroscopy, we soon learned that the geometric structures of metallocorroles provide a fascinating window into their electronic-structural characteristics. Thus, we used X-ray structure determinations and quantum chemical studies, chiefly using DFT, to obtain a comprehensive understanding of metallocorrole geometric and electronic structures. This Account describes our studies of the structural chemistry of metallocorroles. At first blush, the planar or mildly domed structure of metallocorroles might appear somewhat uninteresting particularly when compared to metalloporphyrins. Metalloporphyrins, especially sterically hindered ones, are routinely ruffled or saddled, but the missing meso carbon apparently makes the corrole skeleton much more resistant to nonplanar distortions. Ruffling, where the pyrrole rings are alternately twisted about the M-N bonds, is energetically impossible for metallocorroles. Saddling is also uncommon; thus, a number of sterically hindered, fully substituted metallocorroles exhibit almost perfectly planar macrocycle cores. Against this backdrop, copper corroles stand out as an important exception. As a result of an energetically favorable Cu(d(x2-y2))-corrole(π) orbital interaction, copper corroles, even sterically unhindered ones, are inherently saddled. Sterically hindered substituents accentuate this effect, sometimes dramatically. Thus, a crystal structure of a copper β-octakis(trifluoromethyl)-meso-triarylcorrole complex exhibits nearly orthogonal, adjacent pyrrole rings. Intriguingly, the formally isoelectronic silver and gold corroles are much less saddled than their copper congeners because the high orbital energy of the valence d(x2-y2) orbital discourages overlap with the corrole π orbital. A crystal structure of a gold β-octakis(trifluoromethyl)-meso-triarylcorrole complex exhibits a perfectly planar corrole core, which translates to a difference of 85° in the saddling dihedral angles between analogous copper and gold complexes. Gratifyingly, electrochemical, spectroscopic, and quantum chemical studies provide a coherent, theoretical underpinning for these fascinating structural phenomena. With the development of facile one-pot syntheses of corrole macrocycles in the last 10-15 years, corroles are now almost as readily accessible as porphyrins. Like porphyrins, corroles are promising building blocks for supramolecular constructs such as liquid crystals and metal-organic frameworks. However, because of their symmetry properties, corrole-based supramolecular constructs will probably differ substantially from porphyrin-based ones. We are particularly interested in exploiting the inherently saddled, chiral architectures of copper corroles to create novel oriented materials such as chiral liquid crystals. We trust that the fundamental structural principles uncovered in this Account will prove useful as we explore these fascinating avenues.

Magnetic Field Alignment of PS-P4VP: a Non-Liquid Crystalline Coil-Coil Block Copolymer

NASA Astrophysics Data System (ADS)

Rokhlenko, Yekaterina; Zhang, Kai; Larson, Steven; Gopalan, Padma; O'Hern, Corey; Osuji, Chinedum

2015-03-01

Magnetic fields provide the ability to control alignment of self-assembled soft materials such as block copolymers. Most prior work in this area has relied on the presence of ordered assemblies of anisotropic liquid crystalline species to ensure sufficient magnetic anisotropy to drive alignment. Recent experiments with poly(styrene-b-4-vinylpyridine), a non-liquid crystalline BCP, however, show field-induced alignment of a lamellar microstructure during cooling across the order-disorder transition. Using in situ x-ray scattering, we examine the roles of field strength and cooling rate on the alignment response of this low MW coil-coil BCP. Alignment is first observed at field strengths as low as 1 Tesla and improves markedly with both increasing field strength and slower cooling. We present a geometric argument to illustrate the origin of a finite, non-trivial magnetic susceptibility anisotropy for highly stretched surface-tethered polymer chains and corroborate this using coarse-grained molecular dynamics simulations. We rationalize the magnetic field response of the system in terms of the mobility afforded by the absence of entanglements, the intrinsic anisotropy resulting from the stretched polymer chains and sterically constrained conjugated rings, and the large grain size in these low molecular weight materials.

Influence of RNA Strand Rigidity on Polyion Complex Formation with Block Catiomers.

PubMed

Hayashi, Kotaro; Chaya, Hiroyuki; Fukushima, Shigeto; Watanabe, Sumiyo; Takemoto, Hiroyasu; Osada, Kensuke; Nishiyama, Nobuhiro; Miyata, Kanjiro; Kataoka, Kazunori

2016-03-01

Polyion complexes (b-PICs) are prepared by mixing single- or double-stranded oligo RNA (aniomer) with poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) (block catiomer) to clarify the effect of aniomer chain rigidity on association behaviors at varying concentrations. Here, a 21-mer single-stranded RNA (ssRNA) (persistence length: 1.0 nm) and a 21-mer double-stranded RNA (small interfering RNA, siRNA) (persistence length: 62 nm) are compared. Both oligo RNAs form a minimal charge-neutralized ionomer pair with a single PEG-PLL chain, termed unit b-PIC (uPIC), at low concentrations (<≈ 0.01 mg mL(-1)). Above the critical association concentration (≈ 0.01 mg mL(-1)), ssRNA b-PICs form secondary associates, PIC micelles, with sizes up to 30-70 nm, while no such multimolecular assembly is observed for siRNA b-PICs. The entropy gain associated with the formation of a segregated PIC phase in the multimolecular PIC micelles may not be large enough for rigid siRNA strands to compensate with appreciably high steric repulsion derived from PEG chains. Chain rigidity appears to be a critical parameter in polyion complex association. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-activity relationships among derivatives of dicarboxylic acid esters of tropine.

PubMed

Gyermek, Laszlo

2002-10-01

Several categories of neuromuscular blocking bisquaternary tropine and tropane derivatives were synthesized and studied in the past five decades, mainly with the purpose of arriving at meaningful information about structure-activity relationships. Such a structure-activity relationship database is important in the development of new muscle relaxants with improved pharmacological characteristics. Although quaternary tropine diesters were explored since 1952, most of them were developed in the last decade. Over 250 such agents are being reviewed here. The skeleton of the majority of them consists of two tropines, connected through their 3-OH group with various dicarboxylic acid ester linkages and quaternized by several mostly di- and trisubstituted benzyl groups. The significance of changing the quaternizing group; the diester linker; and, to a smaller extent, the substituents and their steric orientation on the tropane ring and some alterations of the tropane ring itself have been explored in in vivo experiments on anesthetized rats. Di- or trisubstituted alkoxy and/or acyloxybenzyl quaternaries of certain tropinyl diesters, e.g., glutaryl, fumaryl, and cyclobutane-1,2-dicarboxylyl, showed an optimal profile with respect to desirable neuromuscular blocking actions and side effects, which was confirmed on other experimental animal species. The details of the structural changes toward obtaining new ultrashort-acting nondepolarizing muscle relaxants are discussed.

Tarelin uses Liulin-5 Electronic Block in the MRM-1

NASA Image and Video Library

2013-01-10

ISS034-E-021230 (10 Jan. 2013) --- Russian cosmonaut Evgeny Tarelkin, Expedition 34 flight engineer, uses the Liulin-5 Electronic Block behind a panel in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

A heat flux modulator from carbon nanotubes.

PubMed

Jiang, Shaohui; Zhang, Guang; Xia, Dan; Liu, Changhong; Fan, Shoushan

2015-08-28

For a heat flux modulator, the most difficult problem is that the main carriers named 'phonons' have little response to external fields. Of the existing studies on heat flux modulators, most were theoretical work and the materials systems for the theoretical calculations were artificial lattices. In this paper, we made a heat modulator with ultrathin buckypaper which was made of multi-layer carbon nanotube sheets overlapped together, and achieved an on/off ratio whose value was 1.41 using an pendent block in experiments without special optimizations. When the temperatures of the two sides were of appropriate values, we could even see a negative heat flux. Intuitively, the heat flux was tuned by the gap between the buckypaper and the pendent gate, and we observed that there was heat transferred to the pendent block. The structure of the modulator is similar to a CNT transistor with a contactless gate, hence this type of micromodulator will be easy to manufacture in the future.

Temperature rise, sea level rise and increased radiative forcing - an application of cointegration methods

NASA Astrophysics Data System (ADS)

Schmith, Torben; Thejll, Peter; Johansen, Søren

2016-04-01

We analyse the statistical relationship between changes in global temperature, global steric sea level and radiative forcing in order to reveal causal relationships. There are in this, however, potential pitfalls due to the trending nature of the time series. We therefore apply a statistical method called cointegration analysis, originating from the field of econometrics, which is able to correctly handle the analysis of series with trends and other long-range dependencies. Further, we find a relationship between steric sea level and temperature and find that temperature causally depends on the steric sea level, which can be understood as a consequence of the large heat capacity of the ocean. This result is obtained both when analyzing observed data and data from a CMIP5 historical model run. Finally, we find that in the data from the historical run, the steric sea level, in turn, is driven by the external forcing. Finally, we demonstrate that combining these two results can lead to a novel estimate of radiative forcing back in time based on observations.

Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human Hepatocellular Carcinoma Cells unless Conjugated to a Targeting N-Acetyl-Galactosamine Block.

PubMed

Tan, Zhe; Dhande, Yogesh K; Reineke, Theresa M

2017-12-20

A series of 3-guanidinopropyl methacrylamide (GPMA)-based polymeric gene delivery vehicles were developed via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers have been evaluated for their cellular internalization ability, transfection efficiency, and cytotoxicity. Two homopolymers: P(GPMA 20 ), P(GPMA 34 ), were synthesized to study the effect of guanidium polymer length on delivery efficiency and toxicity. In addition, an N-acetyl-d-galactosamine (GalNAc)-based hydrophilic block was incorporated to produce diblock polymers, which provides a neutral hydrophilic block that sterically protects plasmid-polymer complexes (polyplexes) from colloidal aggregation and aids polyplex targeting to hepatocytes via binding to asialoglycoprotein receptors (ASGPRs). Polyplexes formed with P(GPMA x ) (x = 20, 34) homopolymers were shown to be internalized via both energy-dependent and independent pathways, whereas polyplexes formed with block polymers were internalized through endocytosis. Notably, P(GPMA x ) polyplexes enter cells very efficiently but are also very toxic to human hepatocellular carcinoma (HepG2) cells and triggered cell apoptosis. In comparison, the presence of a carbohydrate block in the polymer structures reduced the cytotoxicity of the polyplex formulations and increased gene delivery efficiency with HepG2 cells. Transfection efficiency and toxicity studies were also carried out with HEK 293T (human embryonic kidney) cells for comparison. Results showed that polyplexes formed with the P(GPMA x ) homopolymers exhibit much higher transfection efficiency and lower toxicity with HEK 293T cells. The presence of the carbohydrate block did not further increase transfection efficiency in comparison to the homopolymers with HEK 293T cells, likely due to the lack of ASGPRs on the HEK 293T cell line. This study revealed that although guanidinium-based polymers have high membrane permeability, their application as plasmid delivery vehicles may be limited by their high cytotoxicity to certain cell types. Thus, the use of cell penetrating structures in polyplex formulations should be used with caution and carefully tailored toward individual cell/tissue types.

Fabrication of Hyperbranched Block-Statistical Copolymer-Based Prodrug with Dual Sensitivities for Controlled Release.

PubMed

Zheng, Luping; Wang, Yunfei; Zhang, Xianshuo; Ma, Liwei; Wang, Baoyan; Ji, Xiangling; Wei, Hua

2018-01-17

Dendrimer with hyperbranched structure and multivalent surface is regarded as one of the most promising candidates close to the ideal drug delivery systems, but the clinical translation and scale-up production of dendrimer has been hampered significantly by the synthetic difficulties. Therefore, there is considerable scope for the development of novel hyperbranched polymer that can not only address the drawbacks of dendrimer but maintain its advantages. The reversible addition-fragmentation chain transfer self-condensing vinyl polymerization (RAFT-SCVP) technique has enabled facile preparation of segmented hyperbranched polymer (SHP) by using chain transfer monomer (CTM)-based double-head agent during the past decade. Meanwhile, the design and development of block-statistical copolymers has been proven in our recent studies to be a simple yet effective way to address the extracellular stability vs intracellular high delivery efficacy dilemma. To integrate the advantages of both hyperbranched and block-statistical structures, we herein reported the fabrication of hyperbranched block-statistical copolymer-based prodrug with pH and reduction dual sensitivities using RAFT-SCVP and post-polymerization click coupling. The external homo oligo(ethylene glycol methyl ether methacrylate) (OEGMA) block provides sufficient extracellularly colloidal stability for the nanocarriers by steric hindrance, and the interior OEGMA units incorporated by the statistical copolymerization promote intracellular drug release by facilitating the permeation of GSH and H + for the cleavage of the reduction-responsive disulfide bond and pH-liable carbonate link as well as weakening the hydrophobic encapsulation of drug molecules. The delivery efficacy of the target hyperbranched block-statistical copolymer-based prodrug was evaluated in terms of in vitro drug release and cytotoxicity studies, which confirms both acidic pH and reduction-triggered drug release for inhibiting proliferation of HeLa cells. Interestingly, the simultaneous application of both acidic pH and GSH triggers promoted significantly the cleavage and release of CPT compared to the exertion of single trigger. This study thus developed a facile approach toward hyperbranched polymer-based prodrugs with high therapeutic efficacy for anticancer drug delivery.

Rugged microelectronic module package supports circuitry on heat sink

NASA Technical Reports Server (NTRS)

Johnson, A. L.

1966-01-01

Rugged module package for thin film hybrid microcircuits incorporated a rigid, thermally conductive support structure, which serves as a heat sink, and a lead wire block in which T-shaped electrical connectors are potted. It protects the circuitry from shock and vibration loads, dissipates internal heat, and simplifies electrical connections between adjacent modules.

Effect of sterically demanding substituents on the conformational stability of the collagen triple helix.

PubMed

Erdmann, Roman S; Wennemers, Helma

2012-10-17

The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.

Seasonal variability of the Red Sea, from satellite gravity, radar altimetry, and in situ observations

NASA Astrophysics Data System (ADS)

Wahr, John; Smeed, David A.; Leuliette, Eric; Swenson, Sean

2014-08-01

Seasonal variations of sea surface height (SSH) and mass within the Red Sea are caused mostly by exchange of heat with the atmosphere and by flow through the strait opening into the Gulf of Aden to the south. That flow involves a net mass transfer into the Red Sea during fall and out during spring, though in summer there is an influx of cool water at intermediate depths. Thus, summer water in the south is warmer near the surface due to higher air temperatures, but cooler at intermediate depths. Summer water in the north experiences warming by air-sea exchange only. The temperature affects water density, which impacts SSH but has no effect on mass. We study this seasonal cycle by combining GRACE mass estimates, altimeter SSH measurements, and steric contributions derived from the World Ocean Atlas temperature climatology. Among our conclusions are: mass contributions are much larger than steric contributions; the mass is largest in winter, consistent with winds pushing water into the Red Sea in fall and out during spring; the steric signal is largest in summer, consistent with surface warming; and the cool, intermediate-depth water flowing into the Red Sea in spring has little impact on the steric signal, because contributions from the lowered temperature are offset by effects of decreased salinity. The results suggest that the combined use of altimeter and GRACE measurements can provide a useful alternative to in situ data for monitoring the steric signal.

Trends and interannual variability of mass and steric sea level in the Tropical Asian Seas

NASA Astrophysics Data System (ADS)

Kleinherenbrink, Marcel; Riva, Riccardo; Frederikse, Thomas; Merrifield, Mark; Wada, Yoshihide

2017-08-01

The mass and steric components of sea level changes have been separated in the Tropical Asian Seas (TAS) using a statistically optimal combination of Jason satellite altimetry, GRACE satellite gravimetry, and ocean reanalyses. Using observational uncertainties, statistically optimally weighted time series for both components have been obtained in four regions within the TAS over the period January 2005 to December 2012. The mass and steric sea level variability is regressed with the first two principal components (PC1&2) of Pacific equatorial wind stress and the Dipole Mode Index (DMI). Sea level in the South China Sea is not affected by any of the indices. Steric variability in the TAS is largest in the deep Banda and Celebes seas and is affected by both PCs and the DMI. Mass variability is largest on the continental shelves, which is primarily controlled by PC1. We argue that a water flux from the Western Tropical Pacific Ocean is the cause for mass variability in the TAS. The steric trends are about 2 mm yr-1 larger than the mass trends in the TAS. A significant part of the mass trend can be explained by the aforementioned indices and the nodal cycle. Trends obtained from fingerprints of mass redistribution are statistically equal to mass trends after subtracting the nodal cycle and the indices. Ultimately, the effect of omitting the TAS in global sea level budgets is estimated to be 0.3 mm yr-1.

SiC Multi-Chip Power Modules as Power-System Building Blocks

NASA Technical Reports Server (NTRS)

Lostetter, Alexander; Franks, Steven

2007-01-01

The term "SiC MCPMs" (wherein "MCPM" signifies "multi-chip power module") denotes electronic power-supply modules containing multiple silicon carbide power devices and silicon-on-insulator (SOI) control integrated-circuit chips. SiC MCPMs are being developed as building blocks of advanced expandable, reconfigurable, fault-tolerant power-supply systems. Exploiting the ability of SiC semiconductor devices to operate at temperatures, breakdown voltages, and current densities significantly greater than those of conventional Si devices, the designs of SiC MCPMs and of systems comprising multiple SiC MCPMs are expected to afford a greater degree of miniaturization through stacking of modules with reduced requirements for heat sinking. Moreover, the higher-temperature capabilities of SiC MCPMs could enable operation in environments hotter than Si-based power systems can withstand. The stacked SiC MCPMs in a given system can be electrically connected in series, parallel, or a series/parallel combination to increase the overall power-handling capability of the system. In addition to power connections, the modules have communication connections. The SOI controllers in the modules communicate with each other as nodes of a decentralized control network, in which no single controller exerts overall command of the system. Control functions effected via the network include synchronization of switching of power devices and rapid reconfiguration of power connections to enable the power system to continue to supply power to a load in the event of failure of one of the modules. In addition to serving as building blocks of reliable power-supply systems, SiC MCPMs could be augmented with external control circuitry to make them perform additional power-handling functions as needed for specific applications: typical functions could include regulating voltages, storing energy, and driving motors. Because identical SiC MCPM building blocks could be utilized in a variety of ways, the cost and difficulty of designing new, highly reliable power systems would be reduced considerably. Several prototype DC-to-DC power-converter modules containing SiC power-switching devices were designed and built to demonstrate the feasibility of the SiC MCPM concept. In anticipation of a future need for operation at high temperature, the circuitry in the modules includes high-temperature inductors and capacitors. These modules were designed to be stacked to construct a system of four modules electrically connected in series and/or parallel. The packaging of the modules is designed to satisfy requirements for series and parallel interconnection among modules, high power density, high thermal efficiency, small size, and light weight. Each module includes four output power connectors two for serial and two for parallel output power connections among the modules. Each module also includes two signal connectors, electrically isolated from the power connectors, that afford four zones for signal interconnections among the SOI controllers. Finally, each module includes two input power connectors, through which it receives power from an in-line power bus. This design feature is included in anticipation of a custom-designed power bus incorporating sockets compatible with snap-on type connectors to enable rapid replacement of failed modules.

Communications Effects Server (CES) Model for Systems Engineering Research

DTIC Science & Technology

2012-01-31

Visualization Tool Interface «logical» HLA Tool Interface «logical» DIS Tool Interface «logical» STK Tool Interface «module» Execution Kernels «logical...interoperate with STK when running simulations. GUI Components  Architect – The Architect represents the main network design and visualization ...interest» CES «block» Third Party Visualization Tool «block» Third Party Analysis Tool «block» Third Party Text Editor «block» HLA Tools Analyst User Army

Foale in Base Block with camera

NASA Image and Video Library

1997-11-03

STS086-405-008 (25 Sept-6 Oct 1997) --- Astronaut C. Michael Foale, sporting attire representing the STS-86 crew after four months aboard Russia?s Mir Space Station in Russian wear, operates a video camera in Mir?s Base Block Module. Photo credit: NASA

Possible steric control of the relative strength of chelation enhanced fluorescence for zinc(II) compared to cadmium(II): metal ion complexing properties of tris(2-quinolylmethyl)amine, a crystallographic, UV-visible, and fluorometric study.

PubMed

Williams, Neil J; Gan, Wei; Reibenspies, Joseph H; Hancock, Robert D

2009-02-16

The idea is examined that steric crowding in ligands can lead to diminution of the chelation enhanced fluorescence (CHEF) effect in complexes of the small Zn(II) ion as compared to the larger Cd(II) ion. Steric crowding is less severe for the larger ion and for the smaller Zn(II) ion leads to Zn-N bond length distortion, which allows some quenching of fluorescence by the photoinduced electron transfer (PET) mechanism. Some metal ion complexing properties of the ligand tris(2-quinolylmethyl)amine (TQA) are presented in support of the idea that more sterically efficient ligands, which lead to less M-N bond length distortion with the small Zn(II) ion, will lead to a greater CHEF effect with Zn(II) than Cd(II). The structures of [Zn(TQA)H(2)O](ClO(4))(2).1.5 H(2)O (1), ([Pb(TQA)(NO(3))(2)].C(2)H(5)OH) (2), ([Ag(TQA)(ClO(4))]) (3), and (TQA).C(2)H(5)OH (4) are reported. In 1, the Zn(II) is 5-coordinate, with four N-donors from the ligand and a water molecule making up the coordination sphere. The Zn-N bonds are all of normal length, showing that the level of steric crowding in 1 is not sufficient to cause significant Zn-N bond length distortion. This leads to the observation that, as expected, the CHEF effect in the Zn(II)/TQA complex is much stronger than that in the Cd(II)/TQA complex, in contrast to similar but more sterically crowded ligands, where the CHEF effect is stronger in the Cd(II) complex. The CHEF effect for TQA with the metal ions examined varies as Zn(II) > Cd(II) > Ni(II) > Pb(II) > Hg(II) > Cu(II). The structure of 2 shows an 8-coordinate Pb(II), with evidence of a stereochemically active lone pair, and normal Pb-N bond lengths. In 3, the Ag(I) is 5-coordinate, with four N-donors from the TQA and an oxygen from the perchlorate. The Ag(I) shows no distortion toward linear 2-coordinate geometry, and the Ag-N bonds fall slightly into the upper range for Ag-N bonds in 5-coordinate complexes. The structure of 4 shows the TQA ligand to be involved in pi-stacking between quinolyl groups from adjacent TQA molecules. Formation constants determined by UV-visible spectroscopy are reported in 0.1 M NaClO(4) at 25 degrees C for TQA with Zn(II), Cd(II), and Pb(II). When compared with other similar ligands, one sees that, as the level of steric crowding increases, the stability decreases most with the small Zn(II) ion and least with the large Pb(II) ion. This is in accordance with the idea that TQA has a moderate level of steric crowding and that steric crowding increases for TQA analogs tris(2-pyridylmethyl)amine (TPyA) < TQA < tris(6-methyl-2-pyridyl)amine (TMPyA).

The impact of intramolecular π-coupling and steric flexibility on the ordering of organic films at solid/liquid-interfaces

NASA Astrophysics Data System (ADS)

Saracino, Martino; Breuer, Stephan; Barati, Gholamreza; Sak, Emilia; Hingerl, Kurt; Müller, Ute; Müller, Manfred; Höger, Sigurd; Wandelt, Klaus

2013-01-01

In the present work the effect of the intramolecular steric flexibility on the structural self-assembly of organic cations and their redox activity at a chloride precovered Cu(100) electrode is investigated. In particular the adsorption of 1,1‧-dibenzyl-4,4‧-(propane-1,3-diyl)dipyridinium (C3-DBDP) is studied by means of cyclic voltametry (CV), in situ scanning tunneling microscopy (EC-STM) and ex situ X-ray photoelectron spectroscopy (XPS) and the experimental results are compared to previously published findings on related bipyridinium (“viologen”) molecules. The CV measurements reveal a loss of the redox activity of the more flexible C3-DBDP2 + compared to dibenzylviologen (DBV2 +), as the first electron reduction step of C3-DBDP2 + does not appear within the potential window of the Cu(100), but is shifted below the hydrogen evolution regime. This reduced redox activity is the result of the lifting of the extended π-system of the bipyridinium core by introducing the propyl chain between the two pyridinium rings. In agreement with this result, XP spectra prove that the C3-DBDP2 + cations retain their initial dicationic charge within the entire potential window in solution but also upon adsorption on the Cl-c(2x2)/Cu(100) substrate, where they are found to form an inter-linked stripe phase. The building blocks of each stripe are attributed to one pyridinium-benzyl moiety, which represents half of one C3-DBDP2 + molecule. The resulting consecutive arrangement of half C3-DBDP2 + molecules along one stripe is stabilized by electrostatic attraction between the positively charged pyridinium rings and the negatively charged π-system of the benzyl rings.

KM+, a mannose-binding lectin from Artocarpus integrifolia: amino acid sequence, predicted tertiary structure, carbohydrate recognition, and analysis of the beta-prism fold.

PubMed Central

Rosa, J. C.; De Oliveira, P. S.; Garratt, R.; Beltramini, L.; Resing, K.; Roque-Barreira, M. C.; Greene, L. J.

1999-01-01

The complete amino acid sequence of the lectin KM+ from Artocarpus integrifolia (jackfruit), which contains 149 residues/mol, is reported and compared to those of other members of the Moraceae family, particularly that of jacalin, also from jackfruit, with which it shares 52% sequence identity. KM+ presents an acetyl-blocked N-terminus and is not posttranslationally modified by proteolytic cleavage as is the case for jacalin. Rather, it possesses a short, glycine-rich linker that unites the regions homologous to the alpha- and beta-chains of jacalin. The results of homology modeling implicate the linker sequence in sterically impeding rotation of the side chain of Asp141 within the binding site pocket. As a consequence, the aspartic acid is locked into a conformation adequate only for the recognition of equatorial hydroxyl groups on the C4 epimeric center (alpha-D-mannose, alpha-D-glucose, and their derivatives). In contrast, the internal cleavage of the jacalin chain permits free rotation of the homologous aspartic acid, rendering it capable of accepting hydrogen bonds from both possible hydroxyl configurations on C4. We suggest that, together with direct recognition of epimeric hydroxyls and the steric exclusion of disfavored ligands, conformational restriction of the lectin should be considered to be a new mechanism by which selectivity may be built into carbohydrate binding sites. Jacalin and KM+ adopt the beta-prism fold already observed in two unrelated protein families. Despite presenting little or no sequence similarity, an analysis of the beta-prism reveals a canonical feature repeatedly present in all such structures, which is based on six largely hydrophobic residues within a beta-hairpin containing two classic-type beta-bulges. We suggest the term beta-prism motif to describe this feature. PMID:10210179

Regioselective Acylation of Diols and Triols: The Cyanide Effect.

PubMed

Peng, Peng; Linseis, Michael; Winter, Rainer F; Schmidt, Richard R

2016-05-11

Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at -78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was substantiated with 3,4-O-unproteced galacto- and fucopyranosides and 2,3-O-unprotected mannopyranosides. Even for 3,4,6-O-unprotected galactopyranosides as triols, axial 4-O-acylation is appreciably faster than O-acylation of the primary 6-hydroxy group. The importance of hydrogen bonding for this unusual regioselectivity could be confirmed by NMR studies and DFT calculations, which indicate favorable hydrogen bonding of cyanide to the most acidic axial hydroxy group supported by hydrogen bonding of the equatorial hydroxy group to the axial oxygen. Thus, the "cyanide effect" is due to dual hydrogen bonding of the axial hydroxy group which enhances the nucleophilicity of the respective oxygen atom, permitting an even faster reaction for diols than for mono-ols. In contrast, fluoride as a counterion favors dual hydrogen bonding to both hydroxy groups leading to equatorial O-acylation.

Fluoresceination of FepA during colicin B killing: effects of temperature, toxin and TonB.

PubMed

Smallwood, Chuck R; Marco, Amparo Gala; Xiao, Qiaobin; Trinh, Vy; Newton, Salete M C; Klebba, Phillip E

2009-06-01

We studied the reactivity of 35 genetically engineered Cys sulphydryl groups at different locations in Escherichia coli FepA. Modification of surface loop residues by fluorescein maleimide (FM) was strongly temperature-dependent in vivo, whereas reactivity at other sites was much less affected. Control reactions with bovine serum albumin showed that the temperature dependence of loop residue reactivity was unusually high, indicating that conformational changes in multiple loops (L2, L3, L4, L5, L7, L8, L10) transform the receptor to a more accessible form at 37 degrees C. At 0 degrees C colicin B binding impaired or blocked labelling at 8 of 10 surface loop sites, presumably by steric hindrance. Overall, colicin B adsorption decreased the reactivity of more than half of the 35 sites, in both the N- and C- domains of FepA. However, colicin B penetration into the cell at 37 degrees C did not augment the chemical modification of any residues in FepA. The FM modification patterns were similarly unaffected by the tonB locus. FepA was expressed at lower levels in a tonB host strain, but when we accounted for this decrease its FM labelling was comparable whether TonB was present or absent. Thus we did not detect TonB-dependent structural changes in FepA, either alone or when it interacted with colicin B at 37 degrees C. The only changes in chemical modification were reductions from steric hindrance when the bacteriocin bound to the receptor protein. The absence of increases in the reactivity of N-domain residues argues against the idea that the colicin B polypeptide traverses the FepA channel.

Fluoresceination of FepA during Colicin B Killing: Effects of Temperature, Toxin and TonB

PubMed Central

Smallwood, Chuck R.; Marco, Amparo Gala; Xiao, Qiaobin; Trinh, Vy; Newton, Salete M. C.; Klebba, Phillip E.

2009-01-01

We studied the reactivity of 35 genetically engineered Cys sulfhydryl groups at different locations in Escherichia coli FepA. Modification of surface loop residues by fluorescein maleimide (FM) was strongly temperature-dependent in vivo, whereas reactivity at other sites was much less affected. Control reactions with bovine serum albumin showed that the temperature dependence of loop residue reactivity was unusually high, indicating that conformational changes in multiple loops (L2, L3, L4, L5, L7, L8, L10) transform the receptor to a more accessible form at 37 °C. At 0 °C colicin B binding impaired or blocked labeling at 8 of 10 surface loop sites, presumably by steric hindrance. Overall, colicin B adsorption decreased the reactivity of more than half of the 35 sites, in both the N - and C- domains of FepA. However, colicin B penetration into the cell at 37 °C did not augment the chemical modification of any residues in FepA. The FM modification patterns were similarly unaffected by the tonB locus. FepA was expressed at lower levels in a tonB host strain, but when we accounted for this decrease its FM-labeling was comparable whether TonB was present or absent. Thus we did not detect TonB-dependent structural changes in FepA, either alone or when it interacted with colicin B at 37 °C. The only changes in chemical modification were reductions from steric hindrance when the bacteriocin bound to the receptor protein. The absence of increases in the reactivity of N-domain residues argues against the idea (Devanathan and Postle, Mol. Microbiol. 65: 441–453, 2007) that the colicin B polypeptide traverses the FepA channel. PMID:19432807

Dual Signal Amplification Using Gold Nanoparticles-Enhanced Zinc Selenide Nanoflakes and P19 Protein for Ultrasensitive Photoelectrochemical Biosensing of MicroRNA in Cell.

PubMed

Tu, Wenwen; Cao, Huijuan; Zhang, Long; Bao, Jianchun; Liu, Xuhui; Dai, Zhihui

2016-11-01

Using Au nanoparticles (NPs)-decorated, water-soluble, ZnSe-COOH nanoflakes (NFs), an ultrasensitive photoelectrochemical (PEC) biosensing strategy based on the dual signal amplification was proposed. As a result of the localized surface plasmon resonance (SPR) of Au NPs, the ultraviolet-visible absorption spectrum of Au NPs overlapped with emission spectrum of ZnSe-COOH NFs, which generated efficient resonant energy transfer (RET) between ZnSe-COOH NFs and Au NPs. The RET improved photoelectric conversion efficiency of ZnSe-COOH NFs and significantly amplified PEC signal. Taking advantage of the specificity and high affinity of p19 protein for 21-23 bp double-stranded RNA, p19 protein was introduced. P19 protein could generate remarkable steric hindrance, which blocked interfacial electron transfer and impeded the access of the ascorbic acid to electrode surface for scavenging holes. This led to the dramatic decrease of photocurrent intensity and the amplification of PEC signal change versus concentration change of target. Using microRNA (miRNA)-122a as a model analyte, an ultrasensitive signal-off PEC biosensor for miRNA detection was developed under 405 nm irradiation at -0.30 V. Owing to RET and remarkable steric hindrance of p19 protein as dual signal amplification, the proposed strategy exhibited a wide linear range from 350 fM to 5 nM, with a low detection limit of 153 fM. It has been successfully applied to analyze the level of miRNA-122a in HeLa cell, which would have promising prospects for early diagnosis of tumor.

Binding Isotope Effects for para-Aminobenzoic Acid with Dihydropteroate Synthase from Staphylococcus aureus and Plasmodium falciparum.

PubMed

Stratton, Christopher F; Namanja-Magliano, Hilda A; Cameron, Scott A; Schramm, Vern L

2015-10-16

Dihydropteroate synthase is a key enzyme in folate biosynthesis and is the target of the sulfonamide class of antimicrobials. Equilibrium binding isotope effects and density functional theory calculations indicate that the substrate binding sites for para-aminobenzoic acid on the dihydropteroate synthase enzymes from Staphylococcus aureus and Plasmodium falciparum present distinct chemical environments. Specifically, we show that para-aminobenzoic acid occupies a more sterically constrained vibrational environment when bound to dihydropteroate synthase from P. falciparum relative to that of S. aureus. Deletion of a nonhomologous, parasite-specific insert from the plasmodial dihydropteroate synthase abrogated the binding of para-aminobenzoic acid. The loop specific to P. falciparum is important for effective substrate binding and therefore plays a role in modulating the chemical environment at the substrate binding site.

Use of unnatural amino acids to probe structure-activity relationships and mode-of-action of antimicrobial peptides.

PubMed

Tossi, Alessandro; Scocchi, Marco; Zahariev, Sotir; Gennaro, Renato

2012-01-01

Endogenous antimicrobial peptides (AMPs) can have multimodal mechanisms of bacterial inactivation, such as membrane lysis, interference with cell wall biosynthesis or membrane-based protein machineries, or translocation through the membrane to intracellular targets. The controlled variation of side-chain characteristics in their amino acid residues can provide much useful information on structure-activity relationships and mode-of-action, and also lead to improved activities. The small size and relatively low complexity of AMPs make them amenable to solid-phase peptide synthesis, facilitating the use of nonproteinogenic amino acids and vastly increasing the accessible molecular diversity of side chains. Here, we describe how such residues can be used to modulate such key parameters as cationicity, hydrophobicity, steric factors conformational stability, and H-bonding.

Least reliable bits coding (LRBC) for high data rate satellite communications

NASA Technical Reports Server (NTRS)

Vanderaar, Mark; Budinger, James; Wagner, Paul

1992-01-01

LRBC, a bandwidth efficient multilevel/multistage block-coded modulation technique, is analyzed. LRBC uses simple multilevel component codes that provide increased error protection on increasingly unreliable modulated bits in order to maintain an overall high code rate that increases spectral efficiency. Soft-decision multistage decoding is used to make decisions on unprotected bits through corrections made on more protected bits. Analytical expressions and tight performance bounds are used to show that LRBC can achieve increased spectral efficiency and maintain equivalent or better power efficiency compared to that of BPSK. The relative simplicity of Galois field algebra vs the Viterbi algorithm and the availability of high-speed commercial VLSI for block codes indicates that LRBC using block codes is a desirable method for high data rate implementations.

Solid oxide fuel cell matrix and modules

DOEpatents

Riley, B.

1988-04-22

Porous refractory ceramic blocks arranged in an abutting, stacked configuration and forming a three dimensional array provide a support structure and coupling means for a plurality of solid oxide fuel cells (SOFCs). The stack of ceramic blocks is self-supporting, with a plurality of such stacked arrays forming a matrix enclosed in an insulating refractory brick structure having an outer steel layer. The necessary connections for air, fuel, burnt gas, and anode and cathode connections are provided through the brick and steel outer shell. The ceramic blocks are so designed with respect to the strings of modules that by simple and logical design the strings could be replaced by hot reloading if one should fail. The hot reloading concept has not been included in any previous designs. 11 figs.

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

Atmaram, G.H.; Ventre, G.G.; Maytrott, C.W.

This study evaluates the long-term effects of outdoor exposure and high voltage operation on the performance and reliability of flat-plate crystalline silicon photovoltaic modules. The photovoltaic modules selected for this study were employed in the arrays of grid-connected residential photovoltaic prototype systems for over ten years at the Southeast Regional Experiment Station (SE RES) in Cape Canaveral, Florida. The modules included Mobil Ra-180 EFG ribbon silicon modules, Photowatt MU-7061 and ARCO 16-2000 single-crystal silicon modules with round cells. The Mobil and Photowatt modules were Block 5 generation, while the ARCO modules were Block 4 generation type. In all three typesmore » of photovoltaic modules (Mobil, Photowatt and ARCO), no significant power loss occurred over more than ten years of outdoor operation in the warm, humid and ocean-salt environments of coastal Florida. However, the wet insulation resistance values of a majority of the modules in all three types were lower than the values recommended in IEEE Standard 1262. This indicates potential future safety, reliability and lifetime related problems. The visual defects were more pronounced in the ARCO modules, which were manufactured in 1980 than in the Mobil and Photowatt modules, both of which were fabricated in 1983. The ARCO modules showed significant damage to the back surface tedlar in the form of tearing of the tedlar. All of the Mobil and most of the ARCO modules showed significant browning of the encapsulant, while only about half of the Photowatt modules showed significant encapsulant browning. The encapsulant discoloration generally did not appear to have any effect on the modules` power generation.« less

Comment on "Rabbit-Ears Hybrids, VSEPR Sterics, and Other Orbital Anachronisms": A Reply to a Criticism

ERIC Educational Resources Information Center

Hiberty, Philippe C.; Danovich, David; Shaik, Sason

2015-01-01

This commentary summarizes the authors' basic disagreements with the paper, "Rabbit-Ears, VSEPR Sterics, and Other Orbital Anachronisms," which criticizes the authors' usage of the hybrid orbitals for H[subscript 2]O in their book, "A Chemist's Guide to Valence Bond Theory" (Shaik and Hiberty, 2008). The current article shows…

LFER and CoMFA studies on optical resolution of alpha-alkyl alpha-aryloxy acetic acid methyl esters on DACH-DNB chiral stationary phase.

PubMed

Carotti, A; Altomare, C; Cellamare, S; Monforte, A; Bettoni, G; Loiodice, F; Tangari, N; Tortorella, V

1995-04-01

The HPLC resolution of a series of racemic alpha-substituted alpha-aryloxy acetic acid methyl esters I on a pi-acid N,N'-(3,5-dinitrobenzoyl)-trans-1,2-diaminocyclohexane as chiral selector was modelled by linear free energy-related (LFER) equations and comparative molecular field analysis (CoMFA). Our results indicate that the retention process mainly depends on solute lipophilicity and steric properties, whereas enantioselectivity is primarily influenced by electrostatic and steric interactions. CoMFA provided additional information with respect to the LFER study, allowed the mixing of different subsets of I and led to a quantitative 3D model of steric and electrostatic factors responsible for chiral recognition.

Climbing fibers mediate vestibular modulation of both "complex" and "simple spikes" in Purkinje cells.

PubMed

Barmack, N H; Yakhnitsa, V

2015-10-01

Climbing and mossy fibers comprise two distinct afferent paths to the cerebellum. Climbing fibers directly evoke a large multispiked action potential in Purkinje cells termed a "complex spike" (CS). By logical exclusion, the other class of Purkinje cell action potential, termed "simple spike" (SS), has often been attributed to activity conveyed by mossy fibers and relayed to Purkinje cells through granule cells. Here, we investigate the relative importance of climbing and mossy fiber pathways in modulating neuronal activity by recording extracellularly from Purkinje cells, as well as from mossy fiber terminals and interneurons in folia 8-10. Sinusoidal roll-tilt vestibular stimulation vigorously modulates the discharge of climbing and mossy fiber afferents, Purkinje cells, and interneurons in folia 9-10 in anesthetized mice. Roll-tilt onto the side ipsilateral to the recording site increases the discharge of both climbing fibers (CSs) and mossy fibers. However, the discharges of SSs decrease during ipsilateral roll-tilt. Unilateral microlesions of the beta nucleus (β-nucleus) of the inferior olive blocks vestibular modulation of both CSs and SSs in contralateral Purkinje cells. The blockage of SSs occurs even though primary and secondary vestibular mossy fibers remain intact. When mossy fiber afferents are damaged by a unilateral labyrinthectomy (UL), vestibular modulation of SSs in Purkinje cells ipsilateral to the UL remains intact. Two inhibitory interneurons, Golgi and stellate cells, could potentially contribute to climbing fiber-induced modulation of SSs. However, during sinusoidal roll-tilt, only stellate cells discharge appropriately out of phase with the discharge of SSs. Golgi cells discharge in phase with SSs. When the vestibularly modulated discharge is blocked by a microlesion of the inferior olive, the modulated discharge of CSs and SSs is also blocked. When the vestibular mossy fiber pathway is destroyed, vestibular modulation of ipsilateral CSs and SSs persists. We conclude that climbing fibers are primarily responsible for the vestibularly modulated discharge of both CSs and SSs. Modulation of the discharge of SSs is likely caused by climbing fiber-evoked stellate cell inhibition.

Block 4 solar cell module design and test specification for intermediate load center applications

NASA Technical Reports Server (NTRS)

1978-01-01

Requirements for performance of terrestrial solar cell modules intended for use in various test applications are established. During the 1979-80 time period, such applications are expected to be in the 20 to 500 kilowatt size range. A series of characterization and qualification tests necessary to certify the module design for production, and the necessary performance test for acceptance of modules are specified.

Tarelin uses Liulin-5 Electronic Block in the MRM-1

NASA Image and Video Library

2013-01-10

ISS034-E-021232 (10 Jan. 2013) --- Russian cosmonaut Evgeny Tarelkin, Expedition 34 flight engineer, looks at his watch while using the Liulin-5 Electronic Block behind a panel in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

Solid oxide fuel cell matrix and modules

DOEpatents

Riley, Brian

1990-01-01

Porous refractory ceramic blocks arranged in an abutting, stacked configuration and forming a three dimensional array provide a support structure and coupling means for a plurality of solid oxide fuel cells (SOFCs). Each of the blocks includes a square center channel which forms a vertical shaft when the blocks are arranged in a stacked array. Positioned within the channel is a SOFC unit cell such that a plurality of such SOFC units disposed within a vertical shaft form a string of SOFC units coupled in series. A first pair of facing inner walls of each of the blocks each include an interconnecting channel hole cut horizontally and vertically into the block walls to form gas exit channels. A second pair of facing lateral walls of each block further include a pair of inner half circular grooves which form sleeves to accommodate anode fuel and cathode air tubes. The stack of ceramic blocks is self-supporting, with a plurality of such stacked arrays forming a matrix enclosed in an insulating refractory brick structure having an outer steel layer. The necessary connections for air, fuel, burnt gas, and anode and cathode connections are provided through the brick and steel outer shell. The ceramic blocks are so designed with respect to the strings of modules that by simple and logical design the strings could be replaced by hot reloading if one should fail. The hot reloading concept has not been included in any previous designs.

The neurochemical basis of the contextual interference effect.

PubMed

Chalavi, Sima; Pauwels, Lisa; Heise, Kirstin-Friederike; Zivari Adab, Hamed; Maes, Celine; Puts, Nicolaas A J; Edden, Richard A E; Swinnen, Stephan P

2018-06-01

Efficient practice organization maximizes learning outcome. Although randomization of practice as compared to blocked practice damages training performance, it boosts retention performance, an effect called contextual interference. Motor learning modulates the GABAergic (gamma-aminobutyric acid) system within the sensorimotor cortex (SM); however, it is unclear whether different practice regimes differentially modulate this system and whether this is impacted by aging. Young and older participants were trained on 3 variations of a visuomotor task over 3 days, following either blocked or random practice schedule and retested 6 days later. Using magnetic resonance spectroscopy, SM and occipital cortex GABA+ levels were measured before and after training during the first and last training days. We found that (1) behavioral data confirmed the contextual interference effects, (2) within-day occipital cortex GABA+ levels decreased in random and increased in blocked group. This effect was more pronounced in older adults; and (3) baseline SM GABA+ levels predicted initial performance. These findings indicate a differential modulation of GABA levels across practice groups that is amplified by aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Soft-Input Soft-Output Modules for the Construction and Distributed Iterative Decoding of Code Networks

NASA Technical Reports Server (NTRS)

Benedetto, S.; Divsalar, D.; Montorsi, G.; Pollara, F.

1998-01-01

Soft-input soft-output building blocks (modules) are presented to construct and iteratively decode in a distributed fashion code networks, a new concept that includes, and generalizes, various forms of concatenated coding schemes.

Prediction of Osmotic Pressure of Ionic Liquids Inside a Nanoslit by MD Simulation and Continuum Approach

NASA Astrophysics Data System (ADS)

Moon, Gi Jong; Yang, Yu Dong; Oh, Jung Min; Kang, In Seok

2017-11-01

Osmotic pressure plays an important role in the processes of charging and discharging of lithium batteries. In this work, osmotic pressure of the ionic liquids confined inside a nanoslit is calculated by using both MD simulation and continuum approach. In the case of MD simulation, an ionic liquid is modeled as singly charged spheres with a short-ranged repulsive Lennard-Jones potential. The radii of the spheres are 0.5nm, reflecting the symmetry of ion sizes for simplicity. The simulation box size is 11nm×11nm×7.5nm with 1050 ion pairs. The concentration of ionic liquid is about 1.922mol/L, and the total charge on an individual wall varies from +/-60e(7.944 μm/cm2) to +/-600e(79.44 μm/cm2) . In the case of continuum approach, we classify the problems according to the correlation length and steric factor, and considered the four separate cases: 1) zero correlation length and zero steric factor, 2) zero correlation length and non-zero steric factor, 3) non-zero correlation length and zero steric factor, and 4) non-zero correlation and non-zero steric factor. Better understanding of the osmotic pressure of ionic liquids confined inside a nanoslit can be achieved by comparing the results of MD simulation and continuum approach. This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP: Ministry of Science, ICT & Future Planning) (No. 2017R1D1A1B05035211).

Rhodium Carbenoid Approach for Introduction of 4-Substituted (Z)-Pent-2-enoates into Sterically Encumbered Pyrroles and Indoles

PubMed Central

Lian, Yajing; Davies, Huw M. L.

2010-01-01

An unusual rhodium-carbenoid approach for introduction of 4-substituted (Z)-pent-2-enoates into sterically encumbered pyrroles and indoles is described. These studies show that (Z)-vinylcarbenoids have a greater tendency than (E)-vinylcarbenoids to react at the vinylogous position of the carbenoid rather than at the carbenoid center. PMID:20121078

Influence of steric hindrance on enantioseparation of Dns-amino acids and pesticides on terguride based chiral selectors in capillary electrophoresis.

PubMed

Honzátko, Ales; Cvak, Jan; Vaingátová, Silvie; Flieger, Miroslav

2005-05-01

Three urea derivatives of ergoline-based chiral selectors (CSs), differing in the size of the urea side chain, i.e. dimethyl- (CSI), diethyl- (CSII), and diisopropylurea (CSIII), were used to study the effect of steric hindrance on the enantioseparation of dansyl amino acids (Dns-AAs), pesticides, and mandelic acid under condition of capillary electrophoresis (CE) in linear polyacrylamide coated capillaries. A mixture of organic modifiers (MeOH/THF, 4:1 v/v) in a BGE consisting of 100 mM beta-alanine-acetate was used to increase the solubility of CSs up to 25 mM. The capillary was filled with CS (high UV absorption), and the inlet and outlet vials contained buffer solutions only. The best enantioseparation of Dns-AAs was achieved on CSI. Increased steric hindrance of the chiral binding site led to reduction of both enantioselectivity and resolution. The opposite pattern was observed for the separation of mandelic acid enantiomers, where the best enantioseparation and resolution was obtained with CSIII. Most of the pesticides studied reached maximum selectivity on the diethylurea ergoline derivative (CSII). Enantioseparation of fenoxaprop was found to be independent of steric hindrance.

Laser flash photolysis and CIDNP studies of steric effects on coupling rate constants of imidazolidine nitroxide with carbon-centered radicals, methyl isobutyrate-2-yl and tert-butyl propionate-2-yl.

PubMed

Zubenko, Dmitry; Tsentalovich, Yuri; Lebedeva, Nataly; Kirilyuk, Igor; Roshchupkina, Galina; Zhurko, Irina; Reznikov, Vladimir; Marque, Sylvain R A; Bagryanskaya, Elena

2006-08-04

Time-resolved chemically induced dynamic nuclear polarization (TR-CIDNP) and laser flash photolysis (LFP) techniques have been used to measure rate constants for coupling between acrylate-type radicals and a series of newly synthesized stable imidazolidine N-oxyl radicals. The carbon-centered radicals under investigation were generated by photolysis of their corresponding ketone precursors RC(O)R (R = C(CH3)2-C(O)OCH3 and CH(CH3)-C(O)-OtBu) in the presence of stable nitroxides. The coupling rate constants kc for modeling studies of nitroxide-mediated polymerization (NMP) experiments were determined, and the influence of steric and electronic factors on kc values was addressed by using a Hammett linear free energy relationship. The systematic changes in kc due to the varied steric (Es,n) and electronic (sigmaL,n) characters of the substituents are well-described by the biparameter equation log(kc/M- 1s(-1)) = 3.52sigmaL,n + 0.47Es,n + 10.62. Hence, kc decreases with the increasing steric demand and increases with the increasing electron-withdrawing character of the substituents on the nitroxide.

Impact: a low cost, reconfigurable, digital beamforming common module building block for next generation phased arrays

NASA Astrophysics Data System (ADS)

Paulsen, Lee; Hoffmann, Ted; Fulton, Caleb; Yeary, Mark; Saunders, Austin; Thompson, Dan; Chen, Bill; Guo, Alex; Murmann, Boris

2015-05-01

Phased array systems offer numerous advantages to the modern warfighter in multiple application spaces, including Radar, Electronic Warfare, Signals Intelligence, and Communications. However, a lack of commonality in the underlying technology base for DoD Phased Arrays has led to static systems with long development cycles, slow technology refreshes in response to emerging threats, and expensive, application-specific sub-components. The IMPACT module (Integrated Multi-use Phased Array Common Tile) is a multi-channel, reconfigurable, cost-effective beamformer that provides a common building block for multiple, disparate array applications.

Telemedicine optoelectronic biomedical data processing system

NASA Astrophysics Data System (ADS)

Prosolovska, Vita V.

2010-08-01

The telemedicine optoelectronic biomedical data processing system is created to share medical information for the control of health rights and timely and rapid response to crisis. The system includes the main blocks: bioprocessor, analog-digital converter biomedical images, optoelectronic module for image processing, optoelectronic module for parallel recording and storage of biomedical imaging and matrix screen display of biomedical images. Rated temporal characteristics of the blocks defined by a particular triggering optoelectronic couple in analog-digital converters and time imaging for matrix screen. The element base for hardware implementation of the developed matrix screen is integrated optoelectronic couples produced by selective epitaxy.

Apollo experience report guidance and control systems: Primary guidance, navigation, and control system development

NASA Technical Reports Server (NTRS)

Holley, M. D.; Swingle, W. L.; Bachman, S. L.; Leblanc, C. J.; Howard, H. T.; Biggs, H. M.

1976-01-01

The primary guidance, navigation, and control systems for both the lunar module and the command module are described. Development of the Apollo primary guidance systems is traced from adaptation of the Polaris Mark II system through evolution from Block I to Block II configurations; the discussion includes design concepts used, test and qualification programs performed, and major problems encountered. The major subsystems (inertial, computer, and optical) are covered. Separate sections on the inertial components (gyroscopes and accelerometers) are presented because these components represent a major contribution to the success of the primary guidance, navigation, and control system.

Load control system. [for space shuttle external tank ground tests

NASA Technical Reports Server (NTRS)

Grosse, J. C.

1977-01-01

The load control system developed for the shuttle external structural tests is described. The system consists of a load programming/display module, and a load control module along with the following hydraulic system components: servo valves, dump valves, hydraulic system components, and servo valve manifold blocks. One load programming/display subsystem can support multiple load control subsystem modules.

On decoding of multi-level MPSK modulation codes

NASA Technical Reports Server (NTRS)

Lin, Shu; Gupta, Alok Kumar

1990-01-01

The decoding problem of multi-level block modulation codes is investigated. The hardware design of soft-decision Viterbi decoder for some short length 8-PSK block modulation codes is presented. An effective way to reduce the hardware complexity of the decoder by reducing the branch metric and path metric, using a non-uniform floating-point to integer mapping scheme, is proposed and discussed. The simulation results of the design are presented. The multi-stage decoding (MSD) of multi-level modulation codes is also investigated. The cases of soft-decision and hard-decision MSD are considered and their performance are evaluated for several codes of different lengths and different minimum squared Euclidean distances. It is shown that the soft-decision MSD reduces the decoding complexity drastically and it is suboptimum. The hard-decision MSD further simplifies the decoding while still maintaining a reasonable coding gain over the uncoded system, if the component codes are chosen properly. Finally, some basic 3-level 8-PSK modulation codes using BCH codes as component codes are constructed and their coding gains are found for hard decision multistage decoding.

THE ENDOCANNABINOID SYSTEM MODULATES THE VALENCE OF THE EMOTION ASSOCIATED TO FOOD INGESTION

PubMed Central

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, O.

2010-01-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant, or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide and if such CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. PMID:21182571

Wessex Helicopter/Sonar Dynamics Study. ARL Program Description and Operation.

DTIC Science & Technology

1979-02-01

s): 5. Document Date: S illiams, Neil V. February, 1979 Guy, Christopher R. Williams, Maxwell J. 6. Type of Report and Period Covered: Gilbert, Neil...form with the aid of an analog computer type of block diagram, comprising a number of linked modules (called blocks), each one representing a particular...three types of statement, viz. configuration, parameter and function statements. The configuration statements describe the blocks used and specify the

Modeling back-relaxation in ionic polymer metal composites: The role of steric effects and composite layers

NASA Astrophysics Data System (ADS)

Porfiri, Maurizio; Sharghi, Hesam; Zhang, Peng

2018-01-01

Ionic polymer metal composites (IPMCs) are a new class of active materials that are gaining traction as soft actuators in medical and industrial applications. IPMCs can undergo large deformations under modest voltage inputs, in dry and wet environments. Past studies have demonstrated that physical and geometric properties of all the IPMC constituents (ionomer, electrodes, and counterions) may all influence the time scales of the transient response and severity of the back-relaxation. In this study, we present a detailed mathematical model to investigate how the finite size of the counterions and the presence of metal particles in the vicinity of the electrodes modulate IPMC actuation. We build on previous work by our group on thermodynamically consistent modeling of IPMC mechanics and electrochemistry, which attributes IPMC actuation to the interplay between Maxwell stress and osmotic forces. To gain insight into the role of physical and geometric parameters, the resulting nonlinear partial differential equations are solved semianalytically using the method of matched asymptotic expansions, for the initial transient and the steady-state. A numerical solution in COMSOL Multiphysics® is developed to verify semianalytical findings and further explore IPMC actuation. Our model can successfully predict the entire response of IPMCs, from the initial bending toward the anode to the steady-state toward the cathode. We find that the steric effect can abolish the back-relaxation of IPMCs by restraining the counterions' concentration near the electrodes. We also find that increasing the thickness of the ionomer-metal composite layers may enhance IPMC actuation through increased osmotic forces and Maxwell stress.

Influence of ion sterics on diffusiophoresis and electrophoresis in concentrated electrolytes

NASA Astrophysics Data System (ADS)

Stout, Robert F.; Khair, Aditya S.

2017-01-01

We quantify the diffusiophoresis and electrophoresis of a uniformly charged, spherical colloid in a binary electrolyte using modified Poisson-Nernst-Planck equations that account for steric repulsion between finite sized ions. Specifically, we utilize the Bikerman (Bik) lattice gas model and the Carnahan-Starling (CS) and Boublik-Mansoori-Carnahan-Starling-Leland (BMCSL) equations of state for monodisperse and polydisperse, respectively, hard spheres. We compute the phoretic mobility for weak applied fields using an asymptotic approach for thin diffuse layers, where ion steric effects are expected to be most prevalent. The thin diffuse layer limit requires λD/R →0 , where λD is the Debye screening length and R is the particle radius; this limit is readily attained for micron-sized colloids in concentrated electrolytic solutions. It is well known that the classic Poisson-Boltzmann (PB) model for pointlike, noninteracting ions leads to a prediction of a maximum in both the diffusiophoretic and electrophoretic mobilities with increasing particle zeta potential (at fixed λD/R ). In contrast, we find that ion sterics essentially eliminate this maximum (for reasonably attainable zeta potentials) and increase the mobility relative to PB. Next, we consider the more experimentally relevant case of a particle with a constant surface charge density and vary the electrolyte concentration, neglecting charge regulation on surface active sites. Rather surprisingly, there is little difference between the predictions of the four models (PB, Bik, CS, and BMCSL) for electrophoretic mobility in concentrated solutions, at reasonable surface charge densities (˜1 -10 μ C /cm2 ). This is because as the concentration increases, the zeta potential is reduced (to below the thermal voltage for concentrations above about 1 M) and therefore the diffuse layer structure is largely unaffected by ion sterics. For gradients of symmetric electrolytes (equal diffusivities, charge, and size) diffusiophoresis is also essentially unaffected by ion sterics, with a mobility that approaches zero with increasing concentration, just as in electrophoresis. For gradients of asymmetric electrolytes, the difference in diffusivities of the cation and anions leads to an induced electric field that acts on the charged particle. Importantly, we show that ion sterics leads to an excess contribution to the induced electric field, which increases rapidly with concentration. This increase overwhelms the accompanying decrease in zeta potential. The result is the diffusiophoretic mobility increases with concentration, rather than approaching zero. Therefore, diffusiophoresis could be an appealing alternative transport mechanism to electrophoresis in concentrated electrolyte solutions.

Fourfold Diels-Alder reaction of tetraethynylsilane.

PubMed

Geyer, Florian L; Rode, Alexander; Bunz, Uwe H F

2014-12-08

A series of ethynylated silanes, including tetraethynylsilane, was treated with tetraphenylcyclopentadienone at 300 °C under microwave irradiation to give the aromatized Diels-Alder adducts as sterically encumbered mini-dendrimers with up to 20 benzene rings. The sterically most congested adducts display red-shifted emission through intramolecular π-π interactions in the excited state. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Block 2 solar cell module environmental test program

NASA Technical Reports Server (NTRS)

Holloway, K. L.

1978-01-01

Environmental tests were performed of on 76 solar cell modules produced by four different manufacturers. The following tests were performed: (1) 28 day temperature and humidity; (2) rain and icing; (3) salt fog; (4) sand and dust; (5) vacuum/steam/pressure; (6) fungus; (7) temperature/altitude; and (8) thermal shock. Environmental testing of the solar cell modules produced cracked cells, cracked encapsulant and encapsulant delaminations on various modules. In addition, there was some minor cell and frame corrosion.

Diffusion of radon through concrete block walls: A significant source of indoor radon

USGS Publications Warehouse

Lively, R.S.; Goldberg, L.F.

1999-01-01

Basement modules located in southern Minnesota have been the site of continuous radon and environmental measurements during heating seasons since 1993. Concentrations of radon within the basement modules ranged from 70 Bq.m-3 to over 4000 Bq.m-3 between November to April during the three measurement periods. In the soil gas for the same times, concentrations of radon ranged between 25,000 and 70,000 Bq.m-3. Levels of radon within the basement modules changed by factors of five or more within 24 h, in concert with pressure gradients of 4 to 20 Pa that developed between the basement modules and their surroundings. Diffusion is identified as the principal method by which radon is transferred into and out of the basement modules, and appears to be relatively independent of insulating materials and vapour retarders. The variability of radon and correlations with differential pressure gradients may be related to air currents in the block walls and soil that interrupt radon diffusing inward. This yields a net decrease of radon in the basement modules by decay and outward diffusion. Levels of radon within the basement modules increase when the pressure differential is zero and air flow ceases, allowing diffusion gradients to be re-established. Radon levels in both the soil and the basement modules then increase until an equilibrium is achieved.

Engineering aqueous fiber assembly into silk-elastin-like protein polymers.

PubMed

Zeng, Like; Jiang, Linan; Teng, Weibing; Cappello, Joseph; Zohar, Yitshak; Wu, Xiaoyi

2014-07-01

Self-assembled peptide/protein nanofibers are valuable 1D building blocks for creating complex structures with designed properties and functions. It is reported that the self-assembly of silk-elastin-like protein polymers into nanofibers or globular aggregates in aqueous solutions can be modulated by tuning the temperature of the protein solutions, the size of the silk blocks, and the charge of the elastin blocks. A core-sheath model is proposed for nanofiber formation, with the silk blocks in the cores and the hydrated elastin blocks in the sheaths. The folding of the silk blocks into stable cores--affected by the size of the silk blocks and the charge of the elastin blocks--plays a critical role in the assembly of silk-elastin nanofibers. Furthermore, enhanced hydrophobic interactions between the elastin blocks at elevated temperatures greatly influence the nanoscale features of silk-elastin nanofibers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of smart home terminal controller based on ZigBee

NASA Astrophysics Data System (ADS)

Li, Biqing; Li, Zhao; Zhang, Hongyan

2018-04-01

With the development in scienc and technology, and the improvement of living conditions, people pay more and more attention to the comfort of household life. Therefore, smart home has become the development trend of the future furniture. This design is composed of three blocks: transmitting module, receiving module and data acquisition module. ZigBee and STC89C52 belong to launch module as well as belong to receive module. Launch module contains ZigBee, serial communication module and monolithic STC89C52. The receiving module contains light control parts, curtain control part, ZigBee and microcontroller STC89C52. Data acquisition module includes temperature and humidity detection.

Role of a Modulator in the Synthesis of Phase-Pure NU-1000.

PubMed

Webber, Thomas E; Liu, Wei-Guang; Desai, Sai Puneet; Lu, Connie C; Truhlar, Donald G; Penn, R Lee

2017-11-15

NU-1000 is a robust, mesoporous metal-organic framework (MOF) with hexazirconium nodes ([Zr 6 O 16 H 16 ] 8+ , referred to as oxo-Zr 6 nodes) that can be synthesized by combining a solution of ZrOCl 2 ·8H 2 O and a benzoic acid modulator in N,N-dimethylformamide with a solution of linker (1,3,6,8-tetrakis(p-benzoic acid)pyrene, referred to as H 4 TBAPy) and by aging at an elevated temperature. Typically, the resulting crystals are primarily composed of NU-1000 domains that crystallize with a more dense phase that shares structural similarity with NU-901, which is an MOF composed of the same linker molecules and nodes. Density differences between the two polymorphs arise from the differences in the node orientation: in NU-1000, the oxo-Zr 6 nodes rotate 120° from node to node, whereas in NU-901, all nodes are aligned in parallel. Considering this structural difference leads to the hypothesis that changing the modulator from benzoic acid to a larger and more rigid biphenyl-4-carboxylic acid might lead to a stronger steric interaction between the modulator coordinating on the oxo-Zr 6 node and misaligned nodes or linkers in the large pore and inhibit the growth of the more dense NU-901-like material, resulting in phase-pure NU-1000. Side-by-side reactions comparing the products of synthesis using benzoic acid or biphenyl-4-carboxylic acid as a modulator produce structurally heterogeneous crystals and phase-pure NU-1000 crystals. It can be concluded that the larger and more rigid biphenyl-4-carboxylate inhibits the incorporation of nodes with an alignment parallel to the neighboring nodes already residing in the crystal.

Working the kinks out of nucleosomal DNA

PubMed Central

Olson, Wilma K.; Zhurkin, Victor B.

2011-01-01

Condensation of DNA in the nucleosome takes advantage of its double-helical architecture. The DNA deforms at sites where the base pairs face the histone octamer. The largest so-called kink-and-slide deformations occur in the vicinity of arginines that penetrate the minor groove. Nucleosome structures formed from the 601 positioning sequence differ subtly from those incorporating an AT-rich human α-satellite DNA. Restraints imposed by the histone arginines on the displacement of base pairs can modulate the sequence-dependent deformability of DNA and potentially contribute to the unique features of the different nucleosomes. Steric barriers mimicking constraints found in the nucleosome induce the simulated large-scale rearrangement of canonical B-DNA to kink-and-slide states. The pathway to these states shows non-harmonic behavior consistent with bending profiles inferred from AFM measurements. PMID:21482100

Reward Expectation Modulates Feedback-Related Negativity and EEG Spectra

PubMed Central

Cohen, Michael X; Elger, Christian E.; Ranganath, Charan

2007-01-01

The ability to evaluate outcomes of previous decisions is critical to adaptive decision-making. The feedback-related negativity (FRN) is an event-related potential (ERP) modulation that distinguishes losses from wins, but little is known about the effects of outcome probability on these ERP responses. Further, little is known about the frequency characteristics of feedback processing, for example, event-related oscillations and phase synchronizations. Here, we report an EEG experiment designed to address these issues. Subjects engaged in a probabilistic reinforcement learning task in which we manipulated, across blocks, the probability of winning and losing to each of two possible decision options. Behaviorally, all subjects quickly adapted their decision-making to maximize rewards. ERP analyses revealed that the probability of reward modulated neural responses to wins, but not to losses. This was seen both across blocks as well as within blocks, as learning progressed. Frequency decomposition via complex wavelets revealed that EEG responses to losses, compared to wins, were associated with enhanced power and phase coherence in the theta frequency band. As in the ERP analyses, power and phase coherence values following wins but not losses were modulated by reward probability. Some findings between ERP and frequency analyses diverged, suggesting that these analytic approaches provide complementary insights into neural processing. These findings suggest that the neural mechanisms of feedback processing may differ between wins and losses. PMID:17257860

Macrophage Integrins Modulate Response to Ultra-High Molecular Weight Polyethylene Particles and Direct Particle-Induced Osteolysis

PubMed Central

Zaveri, Toral D.; Dolgova, Natalia V.; Lewis, Jamal S.; Hamaker, Kiri; Clare-Salzler, Michael J.; Keselowsky, Benjamin G.

2016-01-01

Aseptic loosening due to peri-prosthetic osteolysis is one of the primary causes for failure of artificial joint replacements. Implant-derived wear particles, often ultra-high molecular weight polyethylene (UHMWPE) microparticles, initiate an inflammatory cascade upon phagocytosis by macrophages, which leads to osteoclast recruitment and activation, ultimately resulting in osteolysis. Investigation into integrin receptors, involved in cellular interactions with biomaterial-adsorbed adhesive proteins, is of interest to understand and modulate inflammatory processes. In this work, we investigate the role of macrophage integrins Mac-1 and RGD-binding integrins in response to UHMWPE wear particles. Using integrin knockout mice as well as integrin blocking techniques, reduction in macrophage phagocytosis and inflammatory cytokine secretion is demonstrated when these receptors are either absent or blocked. Along this line, various opsonizing proteins are shown to differentially modulate microparticle uptake and macrophage secretion of inflammatory cytokines. Furthermore, using a calvarial osteolysis model it is demonstrated that both Mac-1 integrin and RGD-binding integrins modulate the particle induced osteolysis response to UHMWPE microparticles, with a 40% decrease in the area of osteolysis by the absence or blocking of these integrins, in vivo. Altogether, these findings indicate Mac-1 and RGD-binding integrins are involved in macrophage-directed inflammatory responses to UHMWPE and may serve as therapeutic targets to mitigate wear particle induced peri-prosthetic osteolysis for improved performance of implanted joints. PMID:27889664

Tuning main group redox chemistry through steric loading: subvalent Group 13 metal complexes of carbazolyl ligands.

PubMed

Mansaray, Hassanatu B; Kelly, Michael; Vidovic, Dragoslav; Aldridge, Simon

2011-05-02

The ability of substituted carbazol-9-yl systems to ligate in σ fashion through the amido N-donor, or to adopt alternative coordination modes through the π system of the central five-membered ring, can be tuned by systematic variation in the steric demands of substituents in the 1- and 8-positions. The differing affinities of the two modes of coordination for hard and soft metal centres can be shown to influence not only cation selectivity, but also the redox properties of the metal centre. Thus, the highly sterically sterically demanding 1,3,6,8-tetra-tert-butylcarbazolyl ligand can be used to generate the structurally characterised amido-indium(I) complex, [{(tBu(4)carb)In}(n)], (together with its isostructural thallium counterpart) in which the metal centre interacts with the central pyrrolyl ring in η(3) fashion [d(In-N)=2.679(3) Å; d(In-C)=2.819(3), 2.899(3) Å]. By contrast, the smaller 3,6-di-tert-butylcarbazolyl system is less able to restrict the metal centre from binding at the anionic nitrogen donor in the plane of the carbazolyl ligand (i.e. in σ fashion). Analogous chemistry with In(I) precursors therefore leads to disproportionation to the much harder In(II) [and In(0)], and the formation of the mixed-valence product, [In(2){In(2)(tBu(2)carb)(6)}], a homoleptic molecular [In(4)(NR(2))(6)] system. This chemistry reveals a flexibility of ligation for carbazolyl systems that contrasts markedly with that of the similarly sterically encumbered terphenyl ligand family. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sustainable steric stabilization of colloidal titania nanoparticles

NASA Astrophysics Data System (ADS)

Elbasuney, Sherif

2017-07-01

A route to produce a stable colloidal suspension is essential if mono-dispersed particles are to be successfully synthesized, isolated, and used in subsequent nanocomposite manufacture. Dispersing nanoparticles in fluids was found to be an important approach for avoiding poor dispersion characteristics. However, there is still a great tendency for colloidal nanoparticles to flocculate over time. Steric stabilization can prevent coagulation by introducing a thick adsorbed organic layer which constitutes a significant steric barrier that can prevent the particle surfaces from coming into direct contact. One of the main features of hydrothermal synthesis technique is that it offers novel approaches for sustainable nanoparticle surface modification. This manuscript reports on the sustainable steric stabilization of titanium dioxide nanoparticles. Nanoparticle surface modification was performed via two main approaches including post-synthesis and in situ surface modification. The tuneable hydrothermal conditions (i.e. temperature, pressure, flow rates, and surfactant addition) were optimized to enable controlled steric stabilization in a continuous fashion. Effective post synthesis surface modification with organic ligand (dodecenyl succinic anhydride (DDSA)) was achieved; the optimum surface coating temperature was reported to be 180-240 °C to ensure DDSA ring opening and binding to titania nanoparticles. Organic-modified titania demonstrated complete change in surface properties from hydrophilic to hydrophobic and exhibited phase transfer from the aqueous phase to the organic phase. Exclusive surface modification in the reactor was found to be an effective approach; it demonstrated surfactant loading level 2.2 times that of post synthesis surface modification. Titania was also stabilized in aqueous media using poly acrylic acid (PAA) as polar polymeric dispersant. PAA-titania nanoparticles demonstrated a durable amorphous polymeric layer of 2 nm thickness. This manuscript revealed the state of the art for the real development of stable colloidal mono-dispersed particles with controlled surface properties.

Deep Ocean Warming Assessed from Altimeters, GRACE, 3 In-situ Measurements, and a Non-Boussinesq OGCM

NASA Technical Reports Server (NTRS)

Song, Y. Tony; Colberg, Frank

2011-01-01

Observational surveys have shown significant oceanic bottom water warming, but they are too spatially and temporally sporadic to quantify the deep ocean contribution to the present-day sea level rise (SLR). In this study, altimetry sea surface height (SSH), Gravity Recovery and Climate Experiment (GRACE) ocean mass, and in situ upper ocean (0-700 m) steric height have been assessed for their seasonal variability and trend maps. It is shown that neither the global mean nor the regional trends of altimetry SLR can be explained by the upper ocean steric height plus the GRACE ocean mass. A non-Boussinesq ocean general circulation model (OGCM), allowing the sea level to rise as a direct response to the heat added into the ocean, is then used to diagnose the deep ocean steric height. Constrained by sea surface temperature data and the top of atmosphere (TOA) radiation measurements, the model reproduces the observed upper ocean heat content well. Combining the modeled deep ocean steric height with observational upper ocean data gives the full depth steric height. Adding a GRACE-estimated mass trend, the data-model combination explains not only the altimetry global mean SLR but also its regional trends fairly well. The deep ocean warming is mostly prevalent in the Atlantic and Indian oceans, and along the Antarctic Circumpolar Current, suggesting a strong relation to the oceanic circulation and dynamics. Its comparison with available bottom water measurements shows reasonably good agreement, indicating that deep ocean warming below 700 m might have contributed 1.1 mm/yr to the global mean SLR or one-third of the altimeter-observed rate of 3.11 +/- 0.6 mm/yr over 1993-2008.

Preparation and Investigation of Amphiphilic Block Copolymers/Fullerene Nanocomposites as Nanocarriers for Hydrophobic Drug.

PubMed

Tan, Qinggang; Chu, Yanyan; Bie, Min; Wang, Zihao; Xu, Xiaoyan

2017-02-16

Biopolymer/inorganic material nanocomposites have attracted increasing interest as nanocarriers for delivering drugs owing to the combined advantages of both biopolymer and inorganic materials. Here, amphiphilic block copolymer/fullerene nanocomposites were prepared as nanocarriers for hydrophobic drug by incorporation of C60 in the core of methoxy polyethylene glycol-poly(d,l-lactic acid) (MPEG-PDLLA) micelles. The structure and morphology of MPEG-PDLLA/C60 nanocomposites were characterized using transmission electron microscopy, dynamic light scattering, high-resolution transmission electron microscopy, and thermal gravimetric analysis. It was found that the moderate amount of spherical C60 incorporated in the MPEG-PDLLA micelles may cause an increase in the molecular chain space of PDLLA segments in the vicinity of C60 and, thus, produce a larger cargo space to increase drug entrapment and accelerate the drug release from nanocomposites. Furthermore, sufficient additions of C60 perhaps resulted in an aggregation of C60 within the micelles that decreased the drug entrapment and produced a steric hindrance for DOX released from the nanocomposites. The results obtained provide fundamental insights into the understanding of the role of C60 in adjusting the drug loading and release of amphiphilic copolymer micelles and further demonstrate the future potential of the MPEG-PDLLA/C60 nanocomposites used as nanocarriers for controlled drug-delivery applications.

Specification/Verification of Temporal Properties for Distributed Systems: Issues and Approaches. Volume 1

DTIC Science & Technology

1990-02-01

copies Pl ,...,P. of a multiple module fp resolve nondeterminism (local or global) in an identical manner. 5. The copies PI,...,P, axe physically...recovery block. A recovery block consists of a conventional block (like in ALGOL or PL /I) which is provided with a means of error detection, called an...improved failures model for communicating processes. In Proceeding. NSF- SERC Seminar on Concurrency, volume 197 of Lecture Notes in Computer Science

Behavioral modulation by mutilation pictures in women.

PubMed

Pereira, M G; Volchan, E; Oliveira, L; Machado-Pinheiro, W; Rodrigues, J A; Nepomuceno, F V P; Pessoa, L

2004-03-01

Previous studies have shown that women are more emotionally expressive than men. It is unclear, however, if women are also more susceptible to the emotional modulation of behavior imposed by an affective stimulus. To investigate this issue, we devised a task in which female subjects performed six sequential trials of visual target detection following the presentation of emotional (mutilation and erotic) or neutral pictures (domestic utensils and objects) and compared the data obtained in the present study with those described in a previous study with male subjects. The experiment consisted of three blocks of 24 pictures and each block had an approximate duration of 4 min. Our sample consisted of 36 subjects (age range: 18 to 26 years) and each subject performed all blocks. Trials following the presentation of mutilation pictures (283 ms) had significantly slower reaction times than those following neutral (270 ms) pictures. None of the trials in the "pleasant block" (271 ms) was significantly different from those in the "neutral block". The increase in reaction time observed in the unpleasant block may be related in part to the activation of motivational systems leading to an avoidance behavior. The interference effect observed in this study was similar to the pattern previously described for men. Thus, although women may be more emotionally expressive, they were not more reactive to aversive stimuli than men, as measured by emotional interference in a simple reaction time task.

Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells

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

Kim, Oekyung; Sun Yan; Lai, Frances W.

2010-07-05

Porcine reproductive and respiratory syndrome (PRRS) is an emerged disease of swine characterized by negligible response of type I IFNs and viral persistence. We show that the PRRSV non-structural protein 1 (Nsp1) is the viral component responsible for modulation of IFN response. Nsp1 blocked dsRNA-induced IRF3 and IFN promoter activities. Nsp1 did not block phosphorylation and nuclear translocation of IRF3 but inhibited IRF3 association with CREB-binding protein (CBP) in the nucleus. While IRF3 was stable, CBP was degraded, and CBP degradation was proteasome-dependent, suggesting that CBP degradation is not due to the protease activity of Nsp1 but an intermediary ismore » involved. Our data suggest that the Nsp1-mediated CBP degradation inhibits the recruitment of CBP for enhanceosome assembly, leading to the block of IFN response. CBP degradation is a novel strategy for viral evasion from the host response, and Nsp1 may form a new class of viral antagonists for IFN modulation.« less

Steric effects in the design of Co-Schiff base complexes for the catalytic oxidation of lignin models to para-benzoquinones

Treesearch

Berenger Biannic; Joseph J. Bozell; Thomas Elder

2014-01-01

New Co-Schiff base complexes that incorporate a sterically hindered ligand and an intramolecular bulky piperazine base in close proximity to the Co center are synthesized. Their utility as catalysts for the oxidation of para-substituted lignin model phenols with molecular oxygen is examined. Syringyl and guaiacyl alcohol, as models of S and G units in lignin, are...

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies.

PubMed

Bardhan, Jaydeep P; Jungwirth, Pavel; Makowski, Lee

2012-09-28

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular "linear response" model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution).

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies

PubMed Central

Bardhan, Jaydeep P.; Jungwirth, Pavel; Makowski, Lee

2012-01-01

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular “linear response” model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution). PMID:23020318

Hydrological and oceanic excitations to polar motion andlength-of-day variation

NASA Astrophysics Data System (ADS)

Chen, J. L.; Wilson, C. R.; Chao, B. F.; Shum, C. K.; Tapley, B. D.

2000-04-01

Water mass redistributions in the global hydrosphere, including continental water storage change and non-steric sea level change, introduce variations in the hydrological angular momentum (HAM) and the oceanic angular momentum (OAM). Under the conservation of angular momentum, HAM and OAM variations are significant excitation sources of the Earth rotational variations at a wide range of timescales. In this paper, we estimate HAM and OAM variations and their excitations to polar motion and length-of-day variation using soil moisture and snow estimates andnon-steric sea level change determined by TOPEX/Poseidon satellite radar altimeter observations and a simplified steric sea level change model. The results are compared with the variations of polar motion and LOD that are not accounted for by the atmosphere. This study indicates that seasonal continental water storage change provides significant contributions to both polar motion and LOD variation, especially to polar motion X, and the non-steric sea level change is responsible for a major part of the remaining excitations at both seasonal scale and high frequencies, particularly in polar motion Y and LOD. The good correlation between OAM contributions and the remaining excitations shows that large-scale non-tidal mass variation exists in the oceans and can be detected by TOPEX/Poseidon altimeter observations.

Experimental verification of the steric-entropic mode of retention in centrifugal field-flow fractionation using illite clay plates.

PubMed

Tadjiki, Soheyl; Beckett, Ronald

2018-02-23

The commonly used theory to describe the normal Brownian mode of field-flow fractionation (FFF) assumes the particles to be point masses and hence the shape is ignored. Beckett and Giddings extended this theory to include the effect of thin rods and discs being forced very close to the accumulation wall. By including the decrease in the entropy this causes, they derived new expressions for the retention of such nonspherical particles in FFF. The steric-entropic theory predicts that when the sample cloud thickness is less than the major dimension of the rods or discs then particles elute earlier than predicted by the Brownian mode theory. This leads to an underestimation of the buoyant mass and equivalent spherical diameter calculated from FFF data. In this paper we report for the first time experimental data for the retention of thin illite particles in centrifugal FFF that agrees well with these steric-entropic predictions. Not only do the size distributions calculated using the Brownian mode theory shift to lower size when the field is increased but the shift in the retention ratio of the peak maxima of the FFF fractograms could be predicted fairly accurately by the steric-entropic equations. Copyright © 2018 Elsevier B.V. All rights reserved.

Protein unfolding with a steric trap.

PubMed

Blois, Tracy M; Hong, Heedeok; Kim, Tae H; Bowie, James U

2009-10-07

The study of protein folding requires a method to drive unfolding, which is typically accomplished by altering solution conditions to favor the denatured state. This has the undesirable consequence that the molecular forces responsible for configuring the polypeptide chain are also changed. It would therefore be useful to develop methods that can drive unfolding without the need for destabilizing solvent conditions. Here we introduce a new method to accomplish this goal, which we call steric trapping. In the steric trap method, the target protein is labeled with two biotin tags placed close in space so that both biotin tags can only be bound by streptavidin when the protein unfolds. Thus, binding of the second streptavidin is energetically coupled to unfolding of the target protein. Testing the method on a model protein, dihydrofolate reductase (DHFR), we find that streptavidin binding can drive unfolding and that the apparent binding affinity reports on changes in DHFR stability. Finally, by employing the slow off-rate of wild-type streptavidin, we find that DHFR can be locked in the unfolded state. The steric trap method provides a simple method for studying aspects of protein folding and stability in native solvent conditions, could be used to specifically unfold selected domains, and could be applicable to membrane proteins.

Ligand design for multidimensional magnetic materials: a metallosupramolecular perspective.

PubMed

Pardo, Emilio; Ruiz-García, Rafael; Cano, Joan; Ottenwaelder, Xavier; Lescouëzec, Rodrigue; Journaux, Yves; Lloret, Francesc; Julve, Miguel

2008-06-07

The aim and scope of this review is to show the general validity of the 'complex-as-ligand' approach for the rational design of metallosupramolecular assemblies of increasing structural and magnetic complexity. This is illustrated herein on the basis of our recent studies on oxamato complexes with transition metal ions looking for the limits of the research avenue opened by Kahn's pioneering research twenty years ago. The use as building blocks of mono-, di- and trinuclear metal complexes with a novel family of aromatic polyoxamato ligands allowed us to move further in the coordination chemistry-based approach to high-nuclearity coordination compounds and high-dimensionality coordination polymers. In order to do so, we have taken advantage of the new developments of metallosupramolecular chemistry and in particular, of the molecular-programmed self-assembly methods that exploit the coordination preferences of metal ions and specifically tailored ligands. The judicious choice of the oxamato metal building block (substitution pattern and steric requirements of the bridging ligand, as well as the electronic configuration and magnetic anisotropy of the metal ion) allowed us to control the overall structure and magnetic properties of the final multidimensional nD products (n = 0-3). These species exhibit interesting magnetic properties which are brand-new targets in the field of molecular magnetism, such as single-molecule or single-chain magnets, and the well-known class of molecule-based magnets. This unique family of molecule-based magnetic materials expands on the reported examples of nD species with cyanide and related oxalato and dithiooxalato analogues. Moreover, the development of new oxamato metal building blocks with potential photo or redox activity at the aromatic ligand counterpart will provide us with addressable, multifunctional molecular materials for future applications in molecular electronics and nanotechnology.

Block 4 solar cell module design and test specification for residential applications

NASA Technical Reports Server (NTRS)

1978-01-01

Near-term design, qualification and acceptance requirements are provided for terrestrial solar cell modules suitable for incorporation in photovoltaic power sources (2 kW to 10 kW) applied to single family residential installations. Requirement levels and recommended design limits for selected performance criteria are specified for modules intended principally for rooftop installations. Modules satisfying the requirements of this specification fall into one of two categories, residential panel or residential shingle, both meeting general performance requirements plus additional category peculiar constraints.

Light intensity modulation in phototherapy

NASA Astrophysics Data System (ADS)

Lukyanovich, P. A.; Zon, B. A.; Kunin, A. A.; Pankova, S. N.

2015-04-01

A hypothesis that blocking ATP synthesis is one of the main causes of the stimulating effect is considered based on analysis of the primary photostimulation mechanisms. The light radiation intensity modulation is substantiated and the estimates of such modulation parameters are made. An explanation is offered to the stimulation efficiency decrease phenomenon at the increase of the radiation dose during the therapy. The results of clinical research of the medical treatment in preventive dentistry are presented depending on the spectrum and parameters of the light flux modulation.

Design and Synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

PubMed Central

Banala, Ashwini K.; Zhang, Peng; Plenge, Per; Cyriac, George; Kopajtic, Theresa; Katz, Jonathan L.; Loland, Claus Juul; Newman, Amy Hauck

2013-01-01

The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N-, 4, 5, and 4’-positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51.) In addition, 8 analogues were identified with similar potencies to S-1 for decreasing the dissociation of [3H]S-1 from the S1 site, via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki=19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [3H]S-1 via S2. PMID:24237160

Photo-Activated Localization Microscopy of Single Carbohydrate Binding Modules on Cellulose Nanofibers

NASA Astrophysics Data System (ADS)

Hor, Amy; Dagel, Daryl; Luu, Quocanh; Savaikar, Madhusudan; Ding, Shi-You; Smith, Steve

2015-03-01

Photo Activated Localization Microscopy (PALM) is used to conduct an in vivo study of the binding affinity of polysaccharide-specific Carbohydrate Binding Modules (CBMs) to insoluble cellulose substrates. Two families of CBMs, namely TrCBM1 and CtCBM3, were modified to incorporate photo-activatable mCherry fluorescent protein (PAmCherry), and exposed to highly crystalline Valonia cellulose nano-fibrils. The resulting PALM images show CBMs binding along the nano-fibril long axis in a punctuated linear array, localized with, on average, 10 nm precision. Statistical analysis of the binding events results in nearest neighbor distributions between CBMs. A comparison between TrCBM1 and CtCBM3 reveals a similarity in the nearest neighbor distribution peaks but differences in the overall binding density. The former is attributed to steric hindrance among the CBMs on the nano-fibril whereas the latter is attributed to differences in the CBMs' binding strength. These results are compared to similar distributions derived from TEM measurements of dried samples of CtCBM3-CdSs quantum dot bioconjugates and AFM images of CtCBM3-GFP bound to similar Valonia nano-fibrils. Funding provided by NSF MPS/DMR/BMAT Award # 1206908.

Learning temporal context shapes prestimulus alpha oscillations and improves visual discrimination performance.

PubMed

Toosi, Tahereh; K Tousi, Ehsan; Esteky, Hossein

2017-08-01

Time is an inseparable component of every physical event that we perceive, yet it is not clear how the brain processes time or how the neuronal representation of time affects our perception of events. Here we asked subjects to perform a visual discrimination task while we changed the temporal context in which the stimuli were presented. We collected electroencephalography (EEG) signals in two temporal contexts. In predictable blocks stimuli were presented after a constant delay relative to a visual cue, and in unpredictable blocks stimuli were presented after variable delays relative to the visual cue. Four subsecond delays of 83, 150, 400, and 800 ms were used in the predictable and unpredictable blocks. We observed that predictability modulated the power of prestimulus alpha oscillations in the parieto-occipital sites: alpha power increased in the 300-ms window before stimulus onset in the predictable blocks compared with the unpredictable blocks. This modulation only occurred in the longest delay period, 800 ms, in which predictability also improved the behavioral performance of the subjects. Moreover, learning the temporal context shaped the prestimulus alpha power: modulation of prestimulus alpha power grew during the predictable block and correlated with performance enhancement. These results suggest that the brain is able to learn the subsecond temporal context of stimuli and use this to enhance sensory processing. Furthermore, the neural correlate of this temporal prediction is reflected in the alpha oscillations. NEW & NOTEWORTHY It is not well understood how the uncertainty in the timing of an external event affects its processing, particularly at subsecond scales. Here we demonstrate how a predictable timing scheme improves visual processing. We found that learning the predictable scheme gradually shaped the prestimulus alpha power. These findings indicate that the human brain is able to extract implicit subsecond patterns in the temporal context of events. Copyright © 2017 the American Physiological Society.

Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation.

PubMed

Yoo, Jejoong; Kim, Hajin; Aksimentiev, Aleksei; Ha, Taekjip

2016-03-22

Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine, a biological polycation. We find that AT-rich DNA duplexes associate more strongly than GC-rich duplexes, regardless of the sequence homology. Methyl groups of thymine acts as a steric block, relocating spermine from major grooves to interhelical regions, thereby increasing DNA-DNA attraction. Indeed, methylation of cytosines makes attraction between GC-rich DNA as strong as that between AT-rich DNA. Recent genome-wide chromosome organization studies showed that remote contact frequencies are higher for AT-rich and methylated DNA, suggesting that direct DNA-DNA interactions that we report here may play a role in the chromosome organization and gene regulation.

Effects of Chitin and Contact Insecticide Complexes on Rove Beetles in Commercial Orchards

PubMed Central

Balog, A.; Ferencz, L.; Hartel, T.

2011-01-01

A five-year research project was performed to explore the potential effects of contact insecticide applications on the change of abundance and species richness of predatory rove beetles (Coleoptera: Staphylinidae) in conventionally managed orchards. Twelve blocks of nine orchards were used for this study in Central Europe. High sensitivity atomic force microscopic examination was carried out for chitin structure analyses as well as computer simulation for steric energy calculation between insecticides and chitin. The species richness of rove beetles in orchards was relatively high after insecticide application. Comparing the mean abundance before and after insecticide application, a higher value was observed before spraying with alphacypermethrin and lambda-cyhalothrin, and a lower value was observed in the cases of diflubenzuron, malathion, lufenuron, and phosalone. The species richness was higher only before chlorpyrifos-methyl application. There was a negative correlation between abundance and stability value of chitin-insecticides, persistence time, and soil absorption coefficients. Positive correlation was observed with lipo- and water solubility. PMID:21870981

Base opening in RNA and DNA duplexes: implication for RNA stability.

PubMed

Chen, Y Z; Mohan, V; Griffey, R H

2000-05-01

The energetics of a low-energy single base opening in several RNA duplex crystal structures has been calculated and compared to DNA duplexes. Base opening in RNA appears to have an overall preference towards the major groove, similar to results previously reported for B-DNA. Movement of each of the adenine, uracil, and cytosine bases into the minor groove is blocked by a high-energy barrier due to severe close contact with neighboring bases. Guanine bases are able to open towards both grooves because of the unique orientation of the base that avoids steric clash along the opening pathway. RNA bases are found to have a substantially smaller major groove opening extent than that of their B-DNA counterparts. A comparison with base opening behavior of A-DNA duplexes suggests that this difference results from helix constraint associated with A-form backbone conformation. The reduced opening extent correlates with the RNA duplex stability and is consistent with observed slower imino proton exchange rates in RNA duplexes.

Conformational dimorphism in o-nitrobenzoic acid: alternative ways to avoid the O...O clash.

PubMed

Ibragimov, Aziz; Ashurov, Jamshid; Ibragimov, Bakhtiyar; Wang, Ai; Mouhib, Halima; Englert, Ulli

2016-07-01

Polymorphism is a challenging phenomenon and the competitive packing alternatives which are characteristic for polymorphs may be encountered for essentially rigid molecules. A second crystal form of the well known compound o-nitrobenzoic acid, C7H5NO4, an important intermediate in the production of dyes, pharmaceuticals and agrochemicals, is described. Although obtained serendipitously, its intra- and intermolecular features match expectations from database searches and theoretical calculations. O-H...O hydrogen-bonded carboxylic acid dimers represent the building blocks in both polymorphs. For steric reasons and in agreement with a calculated potential energy surface, the carboxylic acid and nitro groups cannot simultaneously be coplanar with the benzene ring but have to tilt. In the well established crystal form, this out-of-plane torsion is more pronounced for the nitro substituent. In contrast, the new polymorph is characterized by a major tilt of the carboxylic acid group. The molecules in both alternative crystal forms achieve a similar compromise with respect to acceptable intramolecular O...O contacts.

Flexible single-layer ionic organic-inorganic frameworks towards precise nano-size separation

NASA Astrophysics Data System (ADS)

Yue, Liang; Wang, Shan; Zhou, Ding; Zhang, Hao; Li, Bao; Wu, Lixin

2016-02-01

Consecutive two-dimensional frameworks comprised of molecular or cluster building blocks in large area represent ideal candidates for membranes sieving molecules and nano-objects, but challenges still remain in methodology and practical preparation. Here we exploit a new strategy to build soft single-layer ionic organic-inorganic frameworks via electrostatic interaction without preferential binding direction in water. Upon consideration of steric effect and additional interaction, polyanionic clusters as connection nodes and cationic pseudorotaxanes acting as bridging monomers connect with each other to form a single-layer ionic self-assembled framework with 1.4 nm layer thickness. Such soft supramolecular polymer frameworks possess uniform and adjustable ortho-tetragonal nanoporous structure in pore size of 3.4-4.1 nm and exhibit greatly convenient solution processability. The stable membranes maintaining uniform porous structure demonstrate precisely size-selective separation of semiconductor quantum dots within 0.1 nm of accuracy and may hold promise for practical applications in selective transport, molecular separation and dialysis systems.

Functional assay for T4 lysozyme-engineered G protein-coupled receptors with an ion channel reporter.

PubMed

Niescierowicz, Katarzyna; Caro, Lydia; Cherezov, Vadim; Vivaudou, Michel; Moreau, Christophe J

2014-01-07

Structural studies of G protein-coupled receptors (GPCRs) extensively use the insertion of globular soluble protein domains to facilitate their crystallization. However, when inserted in the third intracellular loop (i3 loop), the soluble protein domain disrupts their coupling to G proteins and impedes the GPCRs functional characterization by standard G protein-based assays. Therefore, activity tests of crystallization-optimized GPCRs are essentially limited to their ligand binding properties using radioligand binding assays. Functional characterization of additional thermostabilizing mutations requires the insertion of similar mutations in the wild-type receptor to allow G protein-activation tests. We demonstrate that ion channel-coupled receptor technology is a complementary approach for a comprehensive functional characterization of crystallization-optimized GPCRs and potentially of any engineered GPCR. Ligand-induced conformational changes of the GPCRs are translated into electrical signal and detected by simple current recordings, even though binding of G proteins is sterically blocked by the added soluble protein domain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Kinetic and Structural Insights into the Mechanism of AMPylation by VopS Fic Domain*

PubMed Central

Luong, Phi; Kinch, Lisa N.; Brautigam, Chad A.; Grishin, Nick V.; Tomchick, Diana R.; Orth, Kim

2010-01-01

The bacterial pathogen Vibrio parahemeolyticus manipulates host signaling pathways during infections by injecting type III effectors into the cytoplasm of the target cell. One of these effectors, VopS, blocks actin assembly by AMPylation of a conserved threonine residue in the switch 1 region of Rho GTPases. The modified GTPases are no longer able to interact with downstream effectors due to steric hindrance by the covalently linked AMP moiety. Herein we analyze the structure of VopS and its evolutionarily conserved catalytic residues. Steady-state analysis of VopS mutants provides kinetic understanding on the functional role of each residue for AMPylation activity by the Fic domain. Further mechanistic analysis of VopS with its two substrates, ATP and Cdc42, demonstrates that VopS utilizes a sequential mechanism to AMPylate Rho GTPases. Discovery of a ternary reaction mechanism along with structural insight provides critical groundwork for future studies for the family of AMPylators that modify hydroxyl-containing residues with AMP. PMID:20410310

Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation

NASA Astrophysics Data System (ADS)

Yoo, Jejoong; Kim, Hajin; Aksimentiev, Aleksei; Ha, Taekjip

2016-03-01

Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine, a biological polycation. We find that AT-rich DNA duplexes associate more strongly than GC-rich duplexes, regardless of the sequence homology. Methyl groups of thymine acts as a steric block, relocating spermine from major grooves to interhelical regions, thereby increasing DNA-DNA attraction. Indeed, methylation of cytosines makes attraction between GC-rich DNA as strong as that between AT-rich DNA. Recent genome-wide chromosome organization studies showed that remote contact frequencies are higher for AT-rich and methylated DNA, suggesting that direct DNA-DNA interactions that we report here may play a role in the chromosome organization and gene regulation.

Multiple Learning Strategies Project. Medical Assistant. Visually Impaired. [Vol. 1.

ERIC Educational Resources Information Center

Varney, Beverly; And Others

This instructional package, one of two designed for visually impaired students, focuses on the vocational area of medical assistant. Contained in this document are twelve learning modules organized into five units: language; receptioning; asepsis; supplies and equipment maintenance; and diagnostic tests. Each module, printed in block type,…

Drupal Contributed Modules

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

Fries, Samuel B.; French, Shelane

2014-10-01

These Drupal Modules extend the functionality of Drupal by including specific styles for dates and tabs, publishing options for scheduled and immediate publication of content modes, field visibility in content forms, keyword block filters (taxonomy based), adding content nodes to a specified queue for display in views, and status display of workflow settings.

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

PubMed

Thimm, Andreas; Funke, Klaus

2015-02-15

Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms). The effect increased with each of the five iTBS blocks applied. cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks. We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS-like effects with application of several blocks. Cortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta-burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast-spiking interneurons. Here, we used the well-studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane-anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi-unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW-PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4-5 stimulation blocks. Enhanced cortical c-Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent-type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Modulation of Rhamm (CD168) for selective adipose tissue development

DOEpatents

Turley, Eva A; Bissell, Mina J

2014-05-06

Herein is described the methods and compositions for modulation of Rhamm, also known as CD 186, and its effects on wound repair, muscle differentiation, bone density and adipogeneisis through its ability to regulate mesenchymal stem cell differentiation. Compositions and methods are provided for blocking Rhamm function for selectively increasing subcutaneous, but not, visceral fat. Compositions and methods for modulating Rhamm in wound repair are also described.

A polyvalent hybrid protein elicits antibodies against the diverse allelic types of block 2 in Plasmodium falciparum merozoite surface protein 1.

PubMed

Tetteh, Kevin K A; Conway, David J

2011-10-13

Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.

PubMed

Santafe, M M; Garcia, N; Lanuza, M A; Tomàs, M; Besalduch, N; Tomàs, J

2009-04-01

We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.

The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

PubMed

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, Oscar

2012-07-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive-valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. © 2010 The Authors. Addiction Biology © 2010 Society for the Study of Addiction.

Laser dynamics: The system dynamics and network theory of optoelectronic integrated circuit design

NASA Astrophysics Data System (ADS)

Tarng, Tom Shinming-T. K.

Laser dynamics is the system dynamics, communication and network theory for the design of opto-electronic integrated circuit (OEIC). Combining the optical network theory and optical communication theory, the system analysis and design for the OEIC fundamental building blocks is considered. These building blocks include the direct current modulation, inject light modulation, wideband filter, super-gain optical amplifier, E/O and O/O optical bistability and current-controlled optical oscillator. Based on the rate equations, the phase diagram and phase portrait analysis is applied to the theoretical studies and numerical simulation. The OEIC system design methodologies are developed for the OEIC design. Stimulating-field-dependent rate equations are used to model the line-width narrowing/broadening mechanism for the CW mode and frequency chirp of semiconductor lasers. The momentary spectra are carrier-density-dependent. Furthermore, the phase portrait analysis and the nonlinear refractive index is used to simulate the single mode frequency chirp. The average spectra of chaos, period doubling, period pulsing, multi-loops and analog modulation are generated and analyzed. The bifurcation-chirp design chart with modulation depth and modulation frequency as parameters is provided for design purpose.

Ligand Effects in Aluminum Cluster based Energetic Materials

DTIC Science & Technology

2017-09-01

was recently reported and the effect of their increased steric bulk is discussed here. Experimental results and density functional theory (DFT...analysis show that these clusters are enthalpically more stable than the Cp* variant, due primarily to non -covalent interactions (NCIs) across ligand...C5Me4iPr), two clusters similar to Al4Cp*4, was recently reported and the effect of their increased steric bulk is discussed here. Experimental

13C nuclear magnetic resonance data of lanosterol derivatives—Profiling the steric topology of the steroid skeleton via substituent effects on its 13C NMR

NASA Astrophysics Data System (ADS)

Dias, Jerry Ray; Gao, Hongwu

2009-12-01

The 13C NMR spectra of over 24 tetracyclic triterpenoid derivatives have been structurally analyzed. The 13C NMR chemical shifts allow one to probe the steric topology of the rigid steroid skeleton and inductive effects of its substituents. Use of deuterium labeling in chemical shift assignment and B-ring aromatic terpenoids are also featured.

Ion-Conserving Modified Poisson-Boltzmann Theory Considering a Steric Effect in an Electrolyte

NASA Astrophysics Data System (ADS)

Sugioka, Hideyuki

2016-12-01

The modified Poisson-Nernst-Planck (MPNP) and modified Poisson-Boltzmann (MPB) equations are well known as fundamental equations that consider a steric effect, which prevents unphysical ion concentrations. However, it is unclear whether they are equivalent or not. To clarify this problem, we propose an improved free energy formulation that considers a steric limit with an ion-conserving condition and successfully derive the ion-conserving modified Poisson-Boltzmann (IC-MPB) equations that are equivalent to the MPNP equations. Furthermore, we numerically examine the equivalence by comparing between the IC-MPB solutions obtained by the Newton method and the steady MPNP solutions obtained by the finite-element finite-volume method. A surprising aspect of our finding is that the MPB solutions are much different from the MPNP (IC-MPB) solutions in a confined space. We consider that our findings will significantly contribute to understanding the surface science between solids and liquids.

The helical structure of DNA facilitates binding

NASA Astrophysics Data System (ADS)

Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

2016-09-01

The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

Brownian dynamics of sterically-stabilized colloidal suspensions

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

TeGrotenhuis, W.E.; Radke, C.J.; Denn, M.M.

1994-02-01

One application where microstructure plays a critical role is in the production of specialty ceramics, where colloidal suspensions act as precursors; here the microstructure influences the structural, thermal, optical and electrical properties of the ceramic products. Using Brownian dynamics, equilibrium and dynamic properties are calculated for colloidal suspensions that are stabilized through the Milner, Witten and Cates (1988) steric potential. Results are reported for osmotic pressures, radial distributions functions, static structure factors, and self-diffusion coefficients. The sterically-stabilized systems are also approximated by equivalent hard spheres, with good agreement for osmotic pressure and long-range structure. The suitability of the potential tomore » model the behavior of a real system is explored by comparing static structure factors calculated from Brownian dynamics simulations to those measured using SANS. Finally, the effects of Hamaker and hydrodynamic forces on calculated properties are investigated.« less

Electronic Principles I, 7-5. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This first of 10 blocks of student and teacher materials for a secondary/postsecondary level course in electronic principles comprises one of a number of military-developed curriculum packages selected for adaptation to vocational instruction and curriculum development in a civilian setting. This block on DC circuits contains nine modules covering…

The 25 kW power module evolution study. Part 3: Conceptual designs for power module evolutions. Volume 3: Cost estimates

NASA Technical Reports Server (NTRS)

1979-01-01

Cost data generated for the evolutionary power module concepts selected are reported. The initial acquisition costs (design, development, and protoflight unit test costs) were defined and modeled for the baseline 25 kW power module configurations. By building a parametric model of this initial building block, the cost of the 50 kW and the 100 kW power modules were derived by defining only their configuration and programmatic differences from the 25 kW baseline module. Variations in cost for the quantities needed to fulfill the mission scenarios were derived by applying appropriate learning curves.

Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons.

PubMed

Chakraborty, Saikat; Rebecchi, Mario; Kaczocha, Martin; Puopolo, Michelino

2016-03-15

The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ∼60% and ∼48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN-93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Soft-decision decoding techniques for linear block codes and their error performance analysis

NASA Technical Reports Server (NTRS)

Lin, Shu

1996-01-01

The first paper presents a new minimum-weight trellis-based soft-decision iterative decoding algorithm for binary linear block codes. The second paper derives an upper bound on the probability of block error for multilevel concatenated codes (MLCC). The bound evaluates difference in performance for different decompositions of some codes. The third paper investigates the bit error probability code for maximum likelihood decoding of binary linear codes. The fourth and final paper included in this report is concerns itself with the construction of multilevel concatenated block modulation codes using a multilevel concatenation scheme for the frequency non-selective Rayleigh fading channel.

Regulation of protein multipoint adsorption on ion-exchange adsorbent and its application to the purification of macromolecules.

PubMed

Huang, Yongdong; Bi, Jingxiu; Zhao, Lan; Ma, Guanghui; Su, Zhiguo

2010-12-01

Ion-exchange chromatography (IEC) using commercial ionic absorbents is a widely used technique for protein purification. Protein adsorption onto ion-exchange adsorbents often involves a multipoint adsorption. In IEC of multimeric proteins or "soft" proteins, the intense multipoint binding would make the further desorption difficult, even lead to the destruction of protein structure and the loss of its biological activity. In this paper, DEAE Sepharose FF adsorbents with controllable ligand densities from 0.020 to 0.183 mmol/ml were synthesized, and then the effect of ligand density on the static ion-exchange adsorption of bovine serum albumin (BSA) onto DEAE Sepharose FF was studied by batch adsorption technique. Steric mass-action (SMA) model was employed to analyze the static adsorption behavior. The results showed that the SMA model parameters, equilibrium constant (K(a)), characteristic number of binding sites (υ) and steric factor (σ), increased gradually with ligand density. Thus, it was feasible to regulate BSA multipoint adsorption by modulating the ligand density of ion-exchange adsorbent. Furthermore, IEC of hepatitis B surface antigen (HBsAg) using DEAE Sepharose FF adsorbents with different ligand densities was carried out, and the activity recovery of HBsAg was improved from 42% to 67% when the ligand density was decreased from 0.183 to 0.020 mmol/ml. Taking the activity recovery of HBsAg, the purification factor and the binding capacity into account, DEAE Sepharose FF with a ligand density of 0.041 mmol/ml was most effective for the purification of HBsAg. Such a strategy may also be beneficial for the purification of macromolecules and multimeric proteins. Copyright © 2010 Elsevier Inc. All rights reserved.

Mixed-linker UiO-66: structure-property relationships revealed by a combination of high-resolution powder X-ray diffraction and density functional theory calculations.

PubMed

Taddei, Marco; Tiana, Davide; Casati, Nicola; van Bokhoven, Jeroen A; Smit, Berend; Ranocchiari, Marco

2017-01-04

The use of mixed-linker metal-organic frameworks (MIXMOFs) is one of the most effective strategies to modulate the physical-chemical properties of MOFs without affecting the overall crystal structure. In many instances, MIXMOFs have been recognized as solid solutions, with random distribution of ligands, in agreement with the empirical rule known as Vegard's law. In this work, we have undertaken a study combining high-resolution powder X-ray diffraction (HR-PXRD) and density functional theory (DFT) calculations with the aim of understanding the reasons why UiO-66-based amino- and bromo-functionalized MIXMOFs (MIXUiO-66) undergo cell expansion obeying Vegard's law and how this behaviour is related to their physical-chemical properties. DFT calculations predict that the unit cell in amino-functionalized UiO-66 experiences only minor expansion as a result of steric effects, whereas major modification to the electronic features of the framework leads to weaker metal-linker interaction and consequently to the loss of stability at higher degrees of functionalization. For bromo-functionalized UiO-66, steric repulsion due to the size of bromine yields a large cell expansion, but the electronic features remain very similar to pristine UiO-66, preserving the stability of the framework upon functionalization. MIXUiO-66 obtained by either direct synthesis or by post-synthetic exchange shows Vegard-like behaviour, suggesting that both preparation methods yield solid solutions, but the thermal stability and the textural properties of the post-synthetic exchanged materials do not display a clear dependence on the chemical composition, as observed for the MOFs obtained by direct synthesis.

Designing of phenol-based β-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach.

PubMed

Ahamad, Shahzaib; Hassan, Md Imtaiyaz; Dwivedi, Neeraja

2018-05-01

Tuberculosis (Tb) is an airborne infectious disease caused by Mycobacterium tuberculosis. Beta-carbonic anhydrase 1 ( β-CA1 ) has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based β-CA1 inhibitors. The developed 3D-QSAR model ( r 2  = 0.94, q 2  = 0.86, and pred_r 2  = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized β-CA1 receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

Structure of the intact ATM/Tel1 kinase

NASA Astrophysics Data System (ADS)

Wang, Xuejuan; Chu, Huanyu; Lv, Mengjuan; Zhang, Zhihui; Qiu, Shuwan; Liu, Haiyan; Shen, Xuetong; Wang, Weiwu; Cai, Gang

2016-05-01

The ataxia-telangiectasia mutated (ATM) protein is an apical kinase that orchestrates the multifaceted DNA-damage response. Normally, ATM kinase is in an inactive, homodimer form and is transformed into monomers upon activation. Besides a conserved kinase domain at the C terminus, ATM contains three other structural modules, referred to as FAT, FATC and N-terminal helical solenoid. Here we report the first cryo-EM structure of ATM kinase, which is an intact homodimeric ATM/Tel1 from Schizosaccharomyces pombe. We show that two monomers directly contact head-to-head through the FAT and kinase domains. The tandem N-terminal helical solenoid tightly packs against the FAT and kinase domains. The structure suggests that ATM/Tel1 dimer interface and the consecutive HEAT repeats inhibit the binding of kinase substrates and regulators by steric hindrance. Our study provides a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents.

Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the μ-opioid receptor

NASA Astrophysics Data System (ADS)

Barlocco, Daniela; Cignarella, Giorgio; Greco, Giovanni; Novellino, Ettore

1993-10-01

Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the μ-opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the μ-receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a `correct' orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.

Steric Effect on the Nucleophilic Reactivity of Nickel(III) Peroxo Complexes.

PubMed

Kim, Jalee; Shin, Bongki; Kim, Hyunjeong; Lee, Junhyung; Kang, Joongoo; Yanagisawa, Sachiko; Ogura, Takashi; Masuda, Hideki; Ozawa, Tomohiro; Cho, Jaeheung

2015-07-06

A set of nickel(III) peroxo complexes bearing tetraazamacrocyclic ligands, [Ni(III)(TBDAP)(O2)](+) (TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane) and [Ni(III)(CHDAP)(O2)](+) (CHDAP = N,N'-dicyclohexyl-2,11-diaza[3.3](2,6)pyridinophane), were prepared by reacting [Ni(II)(TBDAP)(NO3)(H2O)](+) and [Ni(II)(CHDAP)(NO3)](+), respectively, with H2O2 in the presence of triethylamine. The mononuclear nickel(III) peroxo complexes were fully characterized by various physicochemical methods, such as UV-vis, electrospray ionization mass spectrometry, resonance Raman, electron paramagnetic resonance, and X-ray analysis. The spectroscopic and structural characterization clearly shows that the NiO2 cores are almost identical where the peroxo ligand is bound in a side-on fashion. However, the different steric properties of the supporting ligands were confirmed by X-ray crystallography, where the CHDAP ligand gives enough space around the Ni core compared to the TBDAP ligand. The nickel(III) peroxo complexes showed reactivity in the oxidation of aldehydes. In the aldehyde deformylation reaction, the nucleophilic reactivity of the nickel(III) peroxo complexes was highly dependent on the steric properties of the macrocyclic ligands, with a reactivity order of [Ni(III)(TBDAP)(O2)](+) < [Ni(III)(CHDAP)(O2)](+). This result provides fundamental insight into the mechanism of the structure (steric)-reactivity relationship of metal peroxo intermediates.

Effect of Pendant Side-Chain Sterics and Dipole Forces on Short Range Ordering in Random Polyelectrolytes

NASA Astrophysics Data System (ADS)

Nwosu, Chinomso; Pandey, Tara; Herring, Andrew; Coughlin, Edward; University of Massachusetts, Amherst Collaboration; Colorado School of Mines Collaboration

Backbone-to-backbone spacing in polymers is known to be dictated by the length of the pendant side-chains. Dipole forces in random polyelectrolytes lead to ionic clusters with a characteristic spacing that can be observed by SAXS. Repulsion due to side-chain sterics will compete with dipole forces driving cluster formation in random polyelectrolytes. A model study on short range order in anion exchange membranes (AEMs) of quaternized P4VP-ran-PI is presented. Quaternization of P4VP with alkyl bromides having different numbers of carbons, CnBr, introduces pendant side-chains as well as charges. X-ray scattering performed on PQ4VP-ran-PI(CnBr) show that when n <5 the dipole forces dominate leading to the formation of ionic clusters. However, when n >4, the chains remain separated due to sterics, forming a distinct backbone-to-backbone spacing morphology. For n=3, both dipole clustering and backbone spacing can coexist. Crosslinking of the isoprene units increased the coexistence window from n=3 to n=6. Impedance measurements show that a maximum conductivity of 110mS/cm was obtained for PQ4VP-ran-PI(C3Br). A discussion on short range order due to competition, or counter balancing, of steric repulsion and dipole forces will be presented. US Army MURI project (W911NF1010520).

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Building a Three-Dimensional Nano-Bio Interface for Aptasensing: An Analytical Methodology Based on Steric Hindrance Initiated Signal Amplification Effect.

PubMed

Du, Xiaojiao; Jiang, Ding; Hao, Nan; Qian, Jing; Dai, Liming; Zhou, Lei; Hu, Jianping; Wang, Kun

2016-10-04

The development of novel detection methodologies in electrochemiluminescence (ECL) aptasensor fields with simplicity and ultrasensitivity is essential for constructing biosensing architectures. Herein, a facile, specific, and sensitive methodology was developed unprecedentedly for quantitative detection of microcystin-LR (MC-LR) based on three-dimensional boron and nitrogen codoped graphene hydrogels (BN-GHs) assisted steric hindrance amplifying effect between the aptamer and target analytes. The recognition reaction was monitored by quartz crystal microbalance (QCM) to validate the possible steric hindrance effect. First, the BN-GHs were synthesized via self-assembled hydrothermal method and then applied as the Ru(bpy) 3 2+ immobilization platform for further loading the biomolecule aptamers due to their nanoporous structure and large specific surface area. Interestingly, we discovered for the first time that, without the aid of conventional double-stranded DNA configuration, such three-dimensional nanomaterials can directly amplify the steric hindrance effect between the aptamer and target analytes to a detectable level, and this facile methodology could be for an exquisite assay. With the MC-LR as a model, this novel ECL biosensor showed a high sensitivity and a wide linear range. This strategy supplies a simple and versatile platform for specific and sensitive determination of a wide range of aptamer-related targets, implying that three-dimensional nanomaterials would play a crucial role in engineering and developing novel detection methodologies for ECL aptasensing fields.

High efficiency low cost monolithic module for SARSAT distress beacons

NASA Technical Reports Server (NTRS)

Petersen, Wendell C.; Siu, Daniel P.

1992-01-01

The program objectives were to develop a highly efficient, low cost RF module for SARSAT beacons; achieve significantly lower battery current drain, amount of heat generated, and size of battery required; utilize MMIC technology to improve efficiency, reliability, packaging, and cost; and provide a technology database for GaAs based UHF RF circuit architectures. Presented in viewgraph form are functional block diagrams of the SARSAT distress beacon and beacon RF module as well as performance goals, schematic diagrams, predicted performances, and measured performances for the phase modulator and power amplifier.

A novel role for the integrin-binding III-10 module in fibronectin matrix assembly.

PubMed

Hocking, D C; Smith, R K; McKeown-Longo, P J

1996-04-01

Fibronectin matrix assembly is a cell-dependent process which is upregulated in tissues at various times during development and wound repair to support the functions of cell adhesion, migration, and differentiation. Previous studies have demonstrated that the alpha 5 beta 1 integrin and fibronectin's amino terminus and III-1 module are important in fibronectin polymerization. We have recently shown that fibronectin's III-1 module contains a conformationally sensitive binding site for fibronectin's amino terminus (Hocking, D.C., J. Sottile, and P.J. McKeown-Longo. 1994. J. Biol. Chem. 269: 19183-19191). The present study was undertaken to define the relationship between the alpha 5 beta 1 integrin and fibronectin polymerization. Solid phase binding assays using recombinant III-10 and III-1 modules of human plasma fibronectin indicated that the III-10 module contains a conformation-dependent binding site for the III-1 module of fibronectin. Unfolded III-10 could support the formation of a ternary complex containing both III-1 and the amino-terminal 70-kD fragment, suggesting that the III-1 module can support the simultaneous binding of III-10 and 70 kD. Both unfolded III-10 and unfolded III-1 could support fibronectin binding, but only III-10 could promote the formation of disulfide-bonded multimers of fibronectin in the absence of cells. III-10-dependent multimer formation was inhibited by both the anti-III-1 monoclonal antibody, 9D2, and amino-terminal fragments of fibronectin. A fragment of III-10, termed III-10/A, was able to block matrix assembly in fibroblast monolayers. Similar results were obtained using the III-10A/RGE fragment, in which the RGD site had been mutated to RGE, indicating that III-I0/A was blocking matrix assembly by a mechanism distinct from disruption of integrin binding. Texas red-conjugated recombinant III-1,2 localized to beta 1-containing sites of focal adhesions on cells plated on fibronectin or the III-9,10 modules of fibronectin. Monoclonal antibodies against the III-1 or the III-9,10 modules of fibronectin blocked binding of III-1,2 to cells without disrupting focal adhesions. These data suggest that a role of the alpha 5 beta 1 integrin in matrix assembly is to regulate a series of sequential self-interactions which result in the polymerization of fibronectin.

Revisiting the contemporary sea-level budget on global and regional scales

PubMed Central

Brunnabend, Sandra-Esther; Kusche, Jürgen; Schröter, Jens; Dahle, Christoph

2016-01-01

Dividing the sea-level budget into contributions from ice sheets and glaciers, the water cycle, steric expansion, and crustal movement is challenging, especially on regional scales. Here, Gravity Recovery And Climate Experiment (GRACE) gravity observations and sea-level anomalies from altimetry are used in a joint inversion, ensuring a consistent decomposition of the global and regional sea-level rise budget. Over the years 2002–2014, we find a global mean steric trend of 1.38 ± 0.16 mm/y, compared with a total trend of 2.74 ± 0.58 mm/y. This is significantly larger than steric trends derived from in situ temperature/salinity profiles and models which range from 0.66 ± 0.2 to 0.94 ± 0.1 mm/y. Mass contributions from ice sheets and glaciers (1.37 ± 0.09 mm/y, accelerating with 0.03 ± 0.02 mm/y2) are offset by a negative hydrological component (−0.29 ± 0.26 mm/y). The combined mass rate (1.08 ± 0.3 mm/y) is smaller than previous GRACE estimates (up to 2 mm/y), but it is consistent with the sum of individual contributions (ice sheets, glaciers, and hydrology) found in literature. The altimetric sea-level budget is closed by coestimating a remaining component of 0.22 ± 0.26 mm/y. Well above average sea-level rise is found regionally near the Philippines (14.7 ± 4.39 mm/y) and Indonesia (8.3 ± 4.7 mm/y) which is dominated by steric components (11.2 ± 3.58 mm/y and 6.4 ± 3.18 mm/y, respectively). In contrast, in the central and Eastern part of the Pacific, negative steric trends (down to −2.8 ± 1.53 mm/y) are detected. Significant regional components are found, up to 5.3 ± 2.6 mm/y in the northwest Atlantic, which are likely due to ocean bottom pressure variations. PMID:26811469

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

PubMed

Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

2016-04-19

Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.

Revisiting the contemporary sea-level budget on global and regional scales.

PubMed

Rietbroek, Roelof; Brunnabend, Sandra-Esther; Kusche, Jürgen; Schröter, Jens; Dahle, Christoph

2016-02-09

Dividing the sea-level budget into contributions from ice sheets and glaciers, the water cycle, steric expansion, and crustal movement is challenging, especially on regional scales. Here, Gravity Recovery And Climate Experiment (GRACE) gravity observations and sea-level anomalies from altimetry are used in a joint inversion, ensuring a consistent decomposition of the global and regional sea-level rise budget. Over the years 2002-2014, we find a global mean steric trend of 1.38 ± 0.16 mm/y, compared with a total trend of 2.74 ± 0.58 mm/y. This is significantly larger than steric trends derived from in situ temperature/salinity profiles and models which range from 0.66 ± 0.2 to 0.94 ± 0.1 mm/y. Mass contributions from ice sheets and glaciers (1.37 ± 0.09 mm/y, accelerating with 0.03 ± 0.02 mm/y(2)) are offset by a negative hydrological component (-0.29 ± 0.26 mm/y). The combined mass rate (1.08 ± 0.3 mm/y) is smaller than previous GRACE estimates (up to 2 mm/y), but it is consistent with the sum of individual contributions (ice sheets, glaciers, and hydrology) found in literature. The altimetric sea-level budget is closed by coestimating a remaining component of 0.22 ± 0.26 mm/y. Well above average sea-level rise is found regionally near the Philippines (14.7 ± 4.39 mm/y) and Indonesia (8.3 ± 4.7 mm/y) which is dominated by steric components (11.2 ± 3.58 mm/y and 6.4 ± 3.18 mm/y, respectively). In contrast, in the central and Eastern part of the Pacific, negative steric trends (down to -2.8 ± 1.53 mm/y) are detected. Significant regional components are found, up to 5.3 ± 2.6 mm/y in the northwest Atlantic, which are likely due to ocean bottom pressure variations.

Membrane permeable local anesthetics modulate NaV1.5 mechanosensitivity

PubMed Central

Beyder, Arthur; Strege, Peter R.; Bernard, Cheryl; Farrugia, Gianrico

2012-01-01

Voltage-gated sodium selective ion channel NaV1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. NaV1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon NaV1.5 to modulate activity by multiple mechanisms. This study examined whether NaV1.5 mechanosensitivity is modulated by local anesthetics. NaV1.5 channels wereexpressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V1/2a) and inactivation (V1/2i) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V1/2a but not V1/2i. Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V1/2a. Lidocaine inhibited mechanosensitivity in NaV1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A NaV1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of NaV1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions. PMID:22874086

On the application of under-decimated filter banks

NASA Technical Reports Server (NTRS)

Lin, Y.-P.; Vaidyanathan, P. P.

1994-01-01

Maximally decimated filter banks have been extensively studied in the past. A filter bank is said to be under-decimated if the number of channels is more than the decimation ratio in the subbands. A maximally decimated filter bank is well known for its application in subband coding. Another application of maximally decimated filter banks is in block filtering. Convolution through block filtering has the advantages that parallelism is increased and data are processed at a lower rate. However, the computational complexity is comparable to that of direct convolution. More recently, another type of filter bank convolver has been developed. In this scheme, the convolution is performed in the subbands. Quantization and bit allocation of subband signals are based on signal variance, as in subband coding. Consequently, for a fixed rate, the result of convolution is more accurate than is direct convolution. This type of filter bank convolver also enjoys the advantages of block filtering, parallelism, and a lower working rate. Nevertheless, like block filtering, there is no computational saving. In this article, under-decimated systems are introduced to solve the problem. The new system is decimated only by half the number of channels. Two types of filter banks can be used in the under-decimated system: the discrete Fourier transform (DFT) filter banks and the cosine modulated filter banks. They are well known for their low complexity. In both cases, the system is approximately alias free, and the overall response is equivalent to a tunable multilevel filter. Properties of the DFT filter banks and the cosine modulated filter banks can be exploited to simultaneously achieve parallelism, computational saving, and a lower working rate. Furthermore, for both systems, the implementation cost of the analysis or synthesis bank is comparable to that of one prototype filter plus some low-complexity modulation matrices. The individual analysis and synthesis filters have complex coefficients in the DFT filter banks but have real coefficients in the cosine modulated filter banks.

The System Design, Engineering Architecture, and Preliminary Results of a Lower-Cost High-Sensitivity High-Resolution Positron Emission Mammography Camera.

PubMed

Zhang, Yuxuan; Ramirez, Rocio A; Li, Hongdi; Liu, Shitao; An, Shaohui; Wang, Chao; Baghaei, Hossain; Wong, Wai-Hoi

2010-02-01

A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.

On the application of under-decimated filter banks

NASA Astrophysics Data System (ADS)

Lin, Y.-P.; Vaidyanathan, P. P.

1994-11-01

Maximally decimated filter banks have been extensively studied in the past. A filter bank is said to be under-decimated if the number of channels is more than the decimation ratio in the subbands. A maximally decimated filter bank is well known for its application in subband coding. Another application of maximally decimated filter banks is in block filtering. Convolution through block filtering has the advantages that parallelism is increased and data are processed at a lower rate. However, the computational complexity is comparable to that of direct convolution. More recently, another type of filter bank convolver has been developed. In this scheme, the convolution is performed in the subbands. Quantization and bit allocation of subband signals are based on signal variance, as in subband coding. Consequently, for a fixed rate, the result of convolution is more accurate than is direct convolution. This type of filter bank convolver also enjoys the advantages of block filtering, parallelism, and a lower working rate. Nevertheless, like block filtering, there is no computational saving. In this article, under-decimated systems are introduced to solve the problem. The new system is decimated only by half the number of channels. Two types of filter banks can be used in the under-decimated system: the discrete Fourier transform (DFT) filter banks and the cosine modulated filter banks. They are well known for their low complexity. In both cases, the system is approximately alias free, and the overall response is equivalent to a tunable multilevel filter. Properties of the DFT filter banks and the cosine modulated filter banks can be exploited to simultaneously achieve parallelism, computational saving, and a lower working rate.

Synthetic fermentation of bioactive non-ribosomal peptides without organisms, enzymes or reagents

NASA Astrophysics Data System (ADS)

Huang, Yi-Lin; Bode, Jeffrey W.

2014-10-01

Microbial fermentation can rapidly provide potent compounds that can be easily screened for biological activity, and the active components can be isolated. Its success in drug discovery has inspired extensive efforts to modulate and control the products. In this Article, we document a ‘synthetic fermentation’ of bioactive, unnatural peptides ‘grown’ from small building blocks in water using amide-forming ligations. No organisms, enzymes or reagents are needed. The sequences, structures and compositions of the products can be modulated by adjusting the building blocks and conditions. No specialized knowledge of organic chemistry or handling of toxic material is required to produce complex organic molecules. The ‘fermentations’ can be conducted in arrays and screened for biological activity without isolation or workup. As a proof-of-concept, about 6,000 unnatural peptides were produced from just 23 building blocks, from which a hepatitis C virus NS3/4A protease inhibitor with a half-maximum inhibitory concentration of 1.0 μM was identified and characterized.

Identification of a unique Ca2+-binding site in rat acid-sensing ion channel 3.

PubMed

Zuo, Zhicheng; Smith, Rachel N; Chen, Zhenglan; Agharkar, Amruta S; Snell, Heather D; Huang, Renqi; Liu, Jin; Gonzales, Eric B

2018-05-25

Acid-sensing ion channels (ASICs) evolved to sense changes in extracellular acidity with the divalent cation calcium (Ca 2+ ) as an allosteric modulator and channel blocker. The channel-blocking activity is most apparent in ASIC3, as removing Ca 2+ results in channel opening, with the site's location remaining unresolved. Here we show that a ring of rat ASIC3 (rASIC3) glutamates (Glu435), located above the channel gate, modulates proton sensitivity and contributes to the formation of the elusive Ca 2+ block site. Mutation of this residue to glycine, the equivalent residue in chicken ASIC1, diminished the rASIC3 Ca 2+ block effect. Atomistic molecular dynamic simulations corroborate the involvement of this acidic residue in forming a high-affinity Ca 2+ site atop the channel pore. Furthermore, the reported observations provide clarity for past controversies regarding ASIC channel gating. Our findings enhance understanding of ASIC gating mechanisms and provide structural and energetic insights into this unique calcium-binding site.

Orion Heat Shield Foam Blocks Prefitting

NASA Image and Video Library

2016-10-24

Tile blocks have been prefitted around the heat shield for the Orion crew module inside the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida. The heat shield is one of the most critical elements of Orion and protects it and the future astronauts inside from searing temperatures experienced during reentry through Earth's atmosphere when they return home. For Exploration Mission-1, the top layer of Orion's heat shield that is primarily responsible for helping the crew module endure reentry heat will be composed of approximately 180 blocks, which are made of an ablative material called Avcoat designed to wear away as it heats up. Orion is being prepared for its flight on the agency's Space Launch System for Exploration Mission-1 in late 2018. Orion is the exploration spacecraft designed to carry astronauts to destinations not yet explored by humans, including an asteroid and NASA's Journey to Mars. It will have emergency abort capability, sustain the crew during space travel and provide safe re-entry from deep space return velocities.

Appendices for the Space Applications program, 1974

NASA Technical Reports Server (NTRS)

1974-01-01

To achieve truly low cost system design with direct evolution for inorbit shuttle resupply, a modular building block approach has been adopted. The heart of the modular building block concept lies in the ability to use a common set of nonoptimized subsystems in such a way that a wide variety of missions can be flown with no detrimental impact on performance. By standardizing the mechanical configurations and electrical interfaces of the subsystem modules, and by designing each of them to be structurally and thermally independent entities, it is possible to cluster these building blocks or modules about an instrument system so as to adequately perform the mission without the need for subsystem redevelopments for each mission. This system concept offers the following capabilities: (1) the ability to launch and orbit the observatory by either the Delta, the Titan, or the space shuttle. (2) the ability to completely reconfigure the spacecraft subsystems for different launch vehicles, and (3) the ability to perform in-orbit resupply and/or emergency retrieval of the observatory.

Visual Confirmation of Voice Takeoff Clearance (VICON) Operational Evaluation. Volume 2. Operations and Maintenance Manual

DTIC Science & Technology

1981-02-01

cabinet and the field. The momentary contacts from the switches of the control panel trigger the respective circuits in module I. This circuit then... module (approximately 40 milliamperes at 70-100 detector, filter, threshold circuit and alarm relay. A block volts) Into microwave energy at X-band...advantageous to use different N.C. Terminals. NOTE: If open circuit tamper switch is modulation frequencies on links operating within close prox

Expediting analog design retargeting by design knowledge re-use and circuit synthesis: a practical example on a Delta-Sigma modulator

NASA Astrophysics Data System (ADS)

Webb, Matthew; Tang, Hua

2016-08-01

In the past decade or two, due to constant and rapid technology changes, analog design re-use or design retargeting to newer technologies has been brought to the table in order to expedite the design process and improve time-to-market. If properly conducted, analog design retargeting could significantly cut down design cycle compared to designs starting from the scratch. In this article, we present an empirical and general method for efficient analog design retargeting by design knowledge re-use and circuit synthesis (CS). The method first identifies circuit blocks that compose the source system and extracts the performance parameter specifications of each circuit block. Then, for each circuit block, it scales the values of design variables (DV) from the source design to derive an initial design in the target technology. Depending on the performance of this initial target design, a design space is defined for synthesis. Subsequently, each circuit block is automatically synthesised using state-of-art analog synthesis tools based on a combination of global and local optimisation techniques to achieve comparable performance specifications to those extracted from the source system. Finally, the overall system is composed of those synthesised circuit blocks in the target technology. We illustrate the method using a practical example of a complex Delta-Sigma modulator (DSM) circuit.

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

Zarkesh, Ryan A.; Foster, Michael E.; Ichimura, Andrew S.

The ability to tune the steric envelope through redox events post-synthetically or in tandem with other chemical processes is a powerful tool that could assist in enabling new catalytic methodologies and understanding potential pitfalls in ligand design. The α-diimine ligand, dmp-BIAN, exhibits the peculiar and previously unreported feature of varying steric profiles depending on oxidation state when paired with a main group element. A study of the factors that give rise to this behaviour as well as its impact on the incorporation of other ligands is performed.

Sterics level the rates of proton transfer to [Ni(XPh){PhP(CH₂CH₂PPh₂)₂}]⁺ (X = O, S or Se).

PubMed

Alwaaly, Ahmed; Henderson, Richard A

2014-09-04

Rates of proton transfers between lutH(+) (lut = 2,6-dimethylpyridine) and [Ni(XPh)(PhP{CH2CH2PPh2}2)](+) (X = O, S or Se) are slow and show little variation (k(O) : k(S) : k(Se) = 1 : 12 : 9). This unusual behaviour is a consequence of sterics affecting the optimal interaction between the reactants prior to proton transfer.

Lutetium functionalities supported by a sterically encumbered β-diketiminate ligand

DOE PAGES

Beattie, Ross J.; Sutton, Andrew D.; Scott, Brian L.; ...

2018-01-06

The sterically encumbered NacNac ligand, [HC(MeCNAr) 2] – (Ar = 2,6- i-Pr 2C 6H 3), was investigated as a platform for supporting Lu-halide complexes, sought for their potential capability of being further converted into hydrocarbyl derivatives via metathetical chemistries with alkali metal alkyls. As a result, these substituted analogs were targeted as potentially viable candidates for alkane elimination chemistries, with an eye towards the formation of an isolable Lu-alkylidene fragment.

Diffuse-charge dynamics of ionic liquids in electrochemical systems.

PubMed

Zhao, Hui

2011-11-01

We employ a continuum theory of solvent-free ionic liquids accounting for both short-range electrostatic correlations and steric effects (finite ion size) [Bazant et al., Phys. Rev. Lett. 106, 046102 (2011)] to study the response of a model microelectrochemical cell to a step voltage. The model problem consists of a 1-1 symmetric ionic liquid between two parallel blocking electrodes, neglecting any transverse transport phenomena. Matched asymptotic expansions in the limit of thin double layers are applied to analyze the resulting one-dimensional equations and study the overall charge-time relation in the weakly nonlinear regime. One important conclusion is that our simple scaling analysis suggests that the length scale √(λ*(D)l*(c)) accurately characterizes the double-layer structure of ionic liquids with strong electrostatic correlations where l*(c) is the electrostatic correlation length (in contrast, the Debye screening length λ*(D) is the primary double-layer length for electrolytes) and the response time of λ(D)(*3/2)L*/(D*l(c)(1/2)) (not λ*(D)L*/D* that is the primary charging time of electrolytes) is the correct charging time scale of ionic liquids with strong electrostatic correlations where D* is the diffusivity and L* is the separation length of the cell. With these two new scales, data of both electric potential versus distance from the electrode and the total diffuse charge versus time collapse onto each individual master curve in the presence of strong electrostatic correlations. In addition, the dependance of the total diffuse charge on steric effects, short-range correlations, and driving voltages is thoroughly examined. The results from the asymptotic analysis are compared favorably with those from full numerical simulations. Finally, the absorption of excess salt by the double layer creates a depletion region outside the double layer. Such salt depletion may bring a correction to the leading order terms and break down the weakly nonlinear analysis. A criterion which justifies the weakly nonlinear analysis is verified with numerical simulations.

Poisson-Nernst-Planck-Fermi theory for modeling biological ion channels

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

Liu, Jinn-Liang, E-mail: jinnliu@mail.nhcue.edu.tw; Eisenberg, Bob, E-mail: beisenbe@rush.edu

2014-12-14

A Poisson-Nernst-Planck-Fermi (PNPF) theory is developed for studying ionic transport through biological ion channels. Our goal is to deal with the finite size of particle using a Fermi like distribution without calculating the forces between the particles, because they are both expensive and tricky to compute. We include the steric effect of ions and water molecules with nonuniform sizes and interstitial voids, the correlation effect of crowded ions with different valences, and the screening effect of water molecules in an inhomogeneous aqueous electrolyte. Including the finite volume of water and the voids between particles is an important new part ofmore » the theory presented here. Fermi like distributions of all particle species are derived from the volume exclusion of classical particles. Volume exclusion and the resulting saturation phenomena are especially important to describe the binding and permeation mechanisms of ions in a narrow channel pore. The Gibbs free energy of the Fermi distribution reduces to that of a Boltzmann distribution when these effects are not considered. The classical Gibbs entropy is extended to a new entropy form — called Gibbs-Fermi entropy — that describes mixing configurations of all finite size particles and voids in a thermodynamic system where microstates do not have equal probabilities. The PNPF model describes the dynamic flow of ions, water molecules, as well as voids with electric fields and protein charges. The model also provides a quantitative mean-field description of the charge/space competition mechanism of particles within the highly charged and crowded channel pore. The PNPF results are in good accord with experimental currents recorded in a 10{sup 8}-fold range of Ca{sup 2+} concentrations. The results illustrate the anomalous mole fraction effect, a signature of L-type calcium channels. Moreover, numerical results concerning water density, dielectric permittivity, void volume, and steric energy provide useful details to study a variety of physical mechanisms ranging from binding, to permeation, blocking, flexibility, and charge/space competition of the channel.« less

Unconscious Cognition Isn't that Smart: Modulation of Masked Repetition Priming Effect in the Word Naming Task

ERIC Educational Resources Information Center

Kinoshita, Sachiko; Forster, Kenneth I.; Mozer, Michael C.

2008-01-01

Masked repetition primes produce greater facilitation in naming in a block containing a high, rather than low proportion of repetition trials. [Bodner, G. E., & Masson, M. E. J. (2004). "Beyond binary judgments: Prime-validity modulates masked repetition priming in the naming task". "Memory & Cognition", 32, 1-11] suggested this phenomenon…

Attentional Capture by Salient Color Singleton Distractors Is Modulated by Top-Down Dimensional Set

ERIC Educational Resources Information Center

Muller, Hermann J.; Geyer, Thomas; Zehetleitner, Michael; Krummenacher, Joseph

2009-01-01

Three experiments examined whether salient color singleton distractors automatically interfere with the detection singleton form targets in visual search (e.g., J. Theeuwes, 1992), or whether the degree of interference is top-down modulable. In Experiments 1 and 2, observers started with a pure block of trials, which contained either never a…

International Space Station (ISS)

NASA Image and Video Library

2000-12-01

This image of the International Space Station in orbit was taken from the Space Shuttle Endeavour prior to docking. Most of the Station's components are clearly visible in this photograph. They are the Node 1 or Unity Module docked with the Functional Cargo Block or Zarya (top) that is linked to the Zvezda Service Module. The Soyuz spacecraft is at the bottom.

International Space Station (ISS)

NASA Image and Video Library

2000-09-01

This image of the International Space Station (ISS) was taken during the STS-106 mission. The ISS component nearest the camera is the U.S. built Node 1 or Unity module, which cornected with the Russian built Functional Cargo Block (FGB) or Zarya. The FGB was linked with the Service Module or Zvezda. On the far end is the Russian Progress supply ship.

Claudin-2-mediated cation and water transport share a common pore

PubMed Central

Rosenthal, Rita; Günzel, Dorothee; Krug, Susanne M.; Schulzke, Jörg-Dieter; Fromm, Michael; Yu, Alan S.L.

2016-01-01

Aim Claudin-2 is a tight junction protein typically located in “leaky” epithelia exhibiting large paracellular permeabilities like small intestine and proximal kidney tubule. Former studies revealed that claudin-2 forms paracellular channels for small cations like sodium and potassium and also paracellular channels for water. This study analyzes whether the diffusive transport of sodium and water occurs through a common pore of the claudin-2 channel. Methods Wild-type claudin-2 and different claudin-2 mutants were expressed in MDCK I kidney tubule cells using an inducible system. Ion and water permeability and the effect of blocking reagents on both were investigated on different clones of the mutants. Results Neutralization of a negatively charged cation interaction site in the pore with the mutation, D65N, decreased both, sodium permeability and water permeability. Claudin-2 mutants (I66C and S68C) with substitution of the pore-lining amino acids with cysteine were used to test the effect of steric blocking of the claudin-2 pore by thiol-reactive reagents. Addition of thiol-reactive reagents to these mutants simultaneously decreased conductance and water permeability. Remarkably, all experimental perturbations caused parallel changes in ion conductance and water permeability, disproving different or independent passage pathways. Conclusion Our results indicate that claudin-2-mediated cation and water transport are frictionally coupled and share a common pore. This pore is lined and determined in permeability by amino acid residues of the first extracellular loop of claudin-2. PMID:27359349

Unitary Responses in Frog Olfactory Epithelium to Sterically Related Molecules at Low Concentrations

PubMed Central

Getchell, Thomas V.

1974-01-01

Responses of receptor cells in the frog's olfactory epithelium were recorded using platinum-black metal-filled microelectrodes. Spontaneous activity varied over a wide range from 0.07 to 1.8 spikes/s. Mean interspike intervals ranged from 13.7 to 0.5 s. Excitatory responses to six sterically related compounds at low concentrations were investigated. Stimuli were delivered in an aqueous medium. Thresholds for impulse initiation varied from greater than 1 mM down to the nanomolar concentration range. Thresholds of different olfactory receptors to the same stimulus could vary by several log units. Thresholds of the same receptor cell to different stimuli could be within the same order of magnitude, or could vary by as much as 5 log units. Based upon quantitative measures of stimulus-evoked excitatory responses it appeared that some receptors did not discriminate among sterically related molecules, whereas other receptors clearly discriminated between stimuli which evoke similar odor sensations. PMID:4211101

Improving halide-containing magnesium-ion electrolyte performance via sterically hindered alkoxide ligands

NASA Astrophysics Data System (ADS)

Nist-Lund, Carl A.; Herb, Jake T.; Arnold, Craig B.

2017-09-01

While homoleptic magnesium dialkoxides (MgR2, R = alkoxide) have shown promise as precursors for magnesium-ion electrolytes, the effect of ligand steric bulk on the performance of electrolytes based on these compounds is not fully understood. Increasing steric hindrance, studied via R groups with additional phenyl moieties, produces electrolytes with sequentially lower deposition overpotentials (less than -90 mV), higher purity Mg deposits (ca. 100% Mg), and lower overall cell impedances. The two largest alkoxide ligands show consistent cycling behavior and low stripping and plating overpotentials over 200 constant-current plating/stripping cycles. A deep-red visual change and the presence of large solubilized magnesium particulates above 450 nm in size is observed in an electrolyte containing magnesium bis(triphenylmethoxide) and aluminum chloride in contact with an abraded magnesium anode. Further morphological and impedance characterization show that this electrolyte system rapidly activates the magnesium metal anode surface to produce low overpotentials and, as such, is a candidate for further investigation.

Small Molecule Activation by Intermolecular Zr(IV)-Phosphine Frustrated Lewis Pairs.

PubMed

Metters, Owen J; Forrest, Sebastian J K; Sparkes, Hazel A; Manners, Ian; Wass, Duncan F

2016-02-17

We report intermolecular transition metal frustrated Lewis pairs (FLPs) based on zirconocene aryloxide and phosphine moieties that exhibit a broad range of small molecule activation chemistry that has previously been the preserve of only intramolecular pairs. Reactions with D2, CO2, THF, and PhCCH are reported. By contrast with previous intramolecular examples, these systems allow facile access to a variety of steric and electronic characteristics at the Lewis acidic and Lewis basic components, with the three-step syntheses of 10 new intermolecular transition metal FLPs being reported. Systematic variation to the phosphine Lewis base is used to unravel steric considerations, with the surprising conclusion that phosphines with relatively small Tolman steric parameters not only give highly reactive FLPs but are often seen to have the highest selectivity for the desired product. DOSY NMR spectroscopic studies on these systems reveal for the first time the nature of the Lewis acid/Lewis base interactions in transition metal FLPs of this type.

Using steric hindrance to design new inhibitors of class C beta-lactamases

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

Trehan, Indi; Morandi, F.; Blaszczak, L.C.

{beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of themore » penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.« less

Steric Effects of Solvent Molecules on SN2 Substitution Dynamics.

PubMed

Liu, Xu; Xie, Jing; Zhang, Jiaxu; Yang, Li; Hase, William L

2017-04-20

Influences of solvent molecules on S N 2 reaction dynamics of microsolvated F - (H 2 O) n with CH 3 I, for n = 0-3, are uncovered by direct chemical dynamics simulations. The direct substitution mechanism, which is important without microsolvation, is quenched dramatically upon increasing hydration. The water molecules tend to force reactive encounters to proceed through the prereaction collision complex leading to indirect reaction. In contrast to F - (H 2 O), reaction with higher hydrated ions shows a strong propensity for ion desolvation in the entrance channel, diminishing steric hindrance for nucleophilic attack. Thus, nucleophilic substitution avoids the potential energy barrier with all of the solvent molecules intact and instead occurs through the less solvated barrier, which is energetically unexpected because the former barrier has a lower energy. The work presented here reveals a trade-off between reaction energetics and steric effects, with the latter found to be crucial in understanding how hydration influences microsolvated S N 2 dynamics.

OptoRadio: a method of wireless communication using orthogonal M-ary PSK (OMPSK) modulation

NASA Astrophysics Data System (ADS)

Gaire, Sunil Kumar; Faruque, Saleh; Ahamed, Md. Maruf

2016-09-01

Laser based radio communication system, i.e. OptoRadio, using Orthogonal M-ary PSK Modulation scheme is presented in this paper. In this scheme, when a block of data needs to be transmitted, the corresponding block of biorthogonal code is transmitted by means of multi-phase shift keying. At the receiver, two photo diodes are cross coupled. The effect is that the net output power due to ambient light is close to zero. The laser signal is then transmitted only into one of the receivers. With all other signals being cancelled out, the laser signal is an overwhelmingly dominant signal. The detailed design, bit error correction capabilities, and bandwidth efficiency are presented to illustrate the concept.

Update on Development of SiC Multi-Chip Power Modules

NASA Technical Reports Server (NTRS)

Lostetter, Alexander; Cilio, Edgar; Mitchell, Gavin; Schupbach, Roberto

2008-01-01

Progress has been made in a continuing effort to develop multi-chip power modules (SiC MCPMs). This effort at an earlier stage was reported in 'SiC Multi-Chip Power Modules as Power-System Building Blocks' (LEW-18008-1), NASA Tech Briefs, Vol. 31, No. 2 (February 2007), page 28. The following recapitulation of information from the cited prior article is prerequisite to a meaningful summary of the progress made since then: 1) SiC MCPMs are, more specifically, electronic power-supply modules containing multiple silicon carbide power integrated-circuit chips and silicon-on-insulator (SOI) control integrated-circuit chips. SiC MCPMs are being developed as building blocks of advanced expandable, reconfigurable, fault-tolerant power-supply systems. Exploiting the ability of SiC semiconductor devices to operate at temperatures, breakdown voltages, and current densities significantly greater than those of conventional Si devices, the designs of SiC MCPMs and of systems comprising multiple SiC MCPMs are expected to afford a greater degree of miniaturization through stacking of modules with reduced requirements for heat sinking; 2) The stacked SiC MCPMs in a given system can be electrically connected in series, parallel, or a series/parallel combination to increase the overall power-handling capability of the system. In addition to power connections, the modules have communication connections. The SOI controllers in the modules communicate with each other as nodes of a decentralized control network, in which no single controller exerts overall command of the system. Control functions effected via the network include synchronization of switching of power devices and rapid reconfiguration of power connections to enable the power system to continue to supply power to a load in the event of failure of one of the modules; and, 3) In addition to serving as building blocks of reliable power-supply systems, SiC MCPMs could be augmented with external control circuitry to make them perform additional power-handling functions as needed for specific applications. Because identical SiC MCPM building blocks could be utilized in such a variety of ways, the cost and difficulty of designing new, highly reliable power systems would be reduced considerably. This concludes the information from the cited prior article. The main activity since the previously reported stage of development was the design, fabrication, and testing a 120- VDC-to-28-VDC modular power-converter system composed of eight SiC MCPMs in a 4 (parallel)-by-2 (series) matrix configuration, with normally-off controllable power switches. The SiC MCPM power modules include closed-loop control subsystems and are capable of operating at high power density or high temperature. The system was tested under various configurations, load conditions, load-transient conditions, and failure-recovery conditions. Planned future work includes refinement of the demonstrated modular system concept and development of a new converter hardware topology that would enable sharing of currents without the need for communication among modules. Toward these ends, it is also planned to develop a new converter control algorithm that would provide for improved sharing of current and power under all conditions, and to implement advanced packaging concepts that would enable operation at higher power density.

Precision alignment and mounting apparatus

NASA Technical Reports Server (NTRS)

Preston, Dennis R. (Inventor)

1993-01-01

An alignment and mounting apparatus for mounting two modules (10,12) includes a first portion having a cylindrical alignment pin (16) projecting normal to a module surface, a second portion having a three-stage alignment guide (18) including a shoehorn flange (34), a Y-slot (42) and a V-block (22) which sequentially guide the alignment pin (16) with successively finer precision and a third portion in the form of a spring-loaded captive fastener (20) for connecting the two modules after alignment is achieved.

A Bond-Fluctuation Model of Translational Dynamics of Chain-like Particles through Mucosal Scaffolds.

PubMed

Bajd, Franci; Serša, Igor

2018-06-05

Mucus scaffolds represent one of the most common barriers in targeted drug delivery and can remarkably reduce the outcome of pharmacological therapies. An efficient transport of drug particles through a mucus barrier is a precondition for an efficient drug delivery. Understanding the transport mechanism is particularly important for treatment of disorders such as cystic fibrosis. These are characterized by an onset of high-density mucus scaffolds imposing an increased steric filtering. In this study, we employed the bond-fluctuation model to analyze the effect of steric interactions on slowing the translational dynamics of compound chain-like particles traversing through scaffolds of different configurations (regular isotropic and anisotropic versus irregular random). The model, which accounts for both the geometry-imposed steric interaction as well as the intrachain steric interaction between the chain subunits, yields a transient subdiffusive motional pattern persists between the short-time and long-time Gaussian diffusion limits. The motion is analyzed in terms of a mean-squared displacement, diffusion coefficient, and radius of gyration. With higher levels of restriction or larger particles, the subdiffusive motional regime persists longer. The study also demonstrates that an important feature of the motion is also geometry-induced chain accommodation. The presented model is generic and could also be applied to studying the translational dynamics of other particles with more complex architecture such as dendrites or chain-decorated nanoparticles. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mass-induced [|#8#|]Sea Level Variations in the Red Sea from Satellite Altimetry and GRACE

NASA Astrophysics Data System (ADS)

Feng, W.; Lemoine, J.; Zhong, M.; Hsu, H.

2011-12-01

We have analyzed mass-induced sea level variations (SLVs) in the Red Sea from steric-corrected altimetry and GRACE between January 2003 and December 2010. The steric component of SLVs in the Red Sea calculated from climatological temperature and salinity data is relatively small and anti-phase with the mass-induced SLV. The total SLV in the Red Sea is mainly driven by the mass-induced SLV, which increases in winter when the Red Sea gains the water mass from the Gulf of Aden and vice versa in summer. Spatial and temporal patterns of mass-induced SLVs in the Red Sea from steric-corrected altimetry agree very well with GRACE observations. Both of two independent observations show high annual amplitude in the central Red Sea (>20cm). Total mass-induced SLVs in the Red Sea from two independent observations have similar annual amplitude and phase. One main purpose of our work is to see whether GRGS's ten-day GRACE results can observe intra-seasonal mass change in the Red Sea. The wavelet coherence analysis indicates that GRGS's results show the high correlation with the steric-corrected SLVs on intra-seasonal time scale. The agreement is excellent for all the time-span until 1/3 year period and is patchy between 1/3 and 1/16 year period. Furthermore, water flux estimates from current-meter arrays and moorings show mass gain in winter and mass loss in summer, which is also consistent with altimetry and GRACE.

Stereodynamics in NO(X) + Ar inelastic collisions

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

Brouard, M., E-mail: mark.brouard@chem.ox.ac.uk; Chadwick, H.; Gordon, S. D. S.

2016-06-14

The effect of orientation of the NO(X) bond axis prior to rotationally inelastic collisions with Ar has been investigated experimentally and theoretically. A modification to conventional velocity-map imaging ion optics is described, which allows the orientation of hexapole state-selected NO(X) using a static electric field, followed by velocity map imaging of the resonantly ionized scattered products. Bond orientation resolved differential cross sections are measured experimentally for a series of spin-orbit conserving transitions and compared with quantum mechanical calculations. The agreement between experimental results and those from quantum mechanical calculations is generally good. Parity pairs, which have previously been observed inmore » collisions of unpolarized NO with various rare gases, are not observed due to the coherent superposition of the two j = 1/2, Ω = 1/2 Λ-doublet levels in the orienting field. The normalized difference differential cross sections are found to depend predominantly on the final rotational state, and are not very sensitive to the final Λ-doublet level. The differential steric effect has also been investigated theoretically, by means of quantum mechanical and classical calculations. Classically, the differential steric effect can be understood by considering the steric requirement for different types of trajectories that contribute to different regions of the differential cross section. However, classical effects cannot account quantitatively for the differential steric asymmetry observed in NO(X) + Ar collisions, which reflects quantum interference from scattering at either end of the molecule. This quantum interference effect is dominated by the repulsive region of the potential.« less

Electronic regioselectivity of diarylalkynes in cobalt-mediated Pauson-Khand reaction: an experimental and computational study with para- and meta-substituted diarylalkynes and norbornene.

PubMed

Fager-Jokela, Erika; Muuronen, Mikko; Patzschke, Michael; Helaja, Juho

2012-10-19

Both steric and electronic factors of substituted alkynes are known to guide α/β-cyclopentenone regioselectivity in the cobalt-mediated Pauson-Khand reaction (PKR). In synthetic applications of the PKR, the steric factors can often override or render possible electronic effects. This study examined alkyne-dependent electronic regioselectivity of cyclopentenone formation in PKR with norbornene and sterically equivalent, but electronically unsymmetrical, meta- and para-substituted diarylethynyls to unveil the role of electronic effects alone. In agreement with the literature reports, EDG para-substituted aryls, to some extent, favored the cyclopentenone α-regioisomer, while the EWG-substituted aryls correspondingly preferred the β-regioisomer. The cooperation of EGW and EDG in diaryl-substituted alkynes did not lead to any increased regioselectivities that could be expected by a "push-pull" effect. Both EWG and EDG meta-substituted aryls preferred the β-regioisomer, which was demonstrated by 3,5-dimethoxy- and 3,5-bis(trifluoromethyl)-1-phenylethynyls that yielded 1/1.6 and 1/2.0 α/β-regioselectivities, respectively. Theoretically, inspection of Hammett values of α-alkyne carbons gave qualitatively satisfactory prediction for para-substituted aryls but correlated only weakly with meta-substituted effects. Computational investigations at the DFT level revealed a correlation between NBO charges and the regioselectivity. Overall, the results suggest that the polarity of an alkyne, also designated by the relative polarization of aryl α-carbons, dictates the regioselectivity in the absence of steric effects.

Aternating current photovoltaic building block

DOEpatents

Bower, Ward Issac; Thomas, Michael G.; Ruby, Douglas S.

2004-06-15

A modular apparatus for and method of alternating current photovoltaic power generation comprising via a photovoltaic module, generating power in the form of direct current; and converting direct current to alternating current and exporting power via one or more power conversion and transfer units attached to the module, each unit comprising a unitary housing extending a length or width of the module, which housing comprises: contact means for receiving direct current from the module; one or more direct current-to-alternating current inverters; an alternating current bus; and contact means for receiving alternating current from the one or more inverters.

Strong G-Protein-Mediated Inhibition of Sodium Channels.

PubMed

Mattheisen, Glynis B; Tsintsadze, Timur; Smith, Stephen M

2018-05-29

Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons. This form of VGSC current block persisted in CaSR-deficient neurons, indicating a CaSR-independent mechanism. Cinacalcet-mediated blockade of VGSCs was prevented by the guanosine diphosphate (GDP) analog GDPβs, indicating that G-proteins mediated this effect. Cinacalcet inhibited VGSCs by increasing channel inactivation, and block was reversed by prolonged hyperpolarization. Strong cinacalcet inhibition of VGSC currents was also present in acutely isolated mouse cortical neurons. These data identify a dynamic signaling pathway by which G-proteins regulate VGSC current to indirectly modulate central neuronal excitability. Published by Elsevier Inc.

PLZT block data composers operated in differential phase mode. [lanthanum-modified lead zirconate titanate ceramic device for digital holographic memory

NASA Technical Reports Server (NTRS)

Drake, M. D.; Klingler, D. E.

1973-01-01

The use of PLZT ceramics with the 7/65/35 composition in block data composer (BDC) input devices for holographic memory systems has previously been described for operation in the strain biased, scattering, and edge effect modes. A new and promising mode of BDC operation is the differential phase mode in which each element of a matrix array BDC acts as a phase modulator. The phase modulation results from a phase difference in the optical path length between the electrically poled and depoled states of the PLZT. It is shown that a PLZT BDC can be used as a matrix-type phase modulator to record and process digital data by the differential phase mode in a holographic recording/processing system with readout contrast ratios of between 10:1 and 15:1. The differential phase mode has the advantages that strain bias is not required and that the thickness and strain variations in the PLZT are cancelled out.

Simulations of absorption spectra of conjugated oligomers: role of planar conformation and aggregation in condensed phase

NASA Astrophysics Data System (ADS)

Yuan, Xiang-Ai; Wen, Jin; Zheng, Dong; Ma, Jing

2018-04-01

This Review highlights the structure/property relationship underlying the morphology modulation through various factors towards the exploration of light-absorbing materials for efficient utilisation of solar power. Theoretical study using a combination of molecular dynamics imulations and the time-dependent density functional theory demonstrated that the planarity plays an important role in tuning spectral properties of oligomer aggregates. The aggregation-induced blue-shift in absorption spectra of oligothiophenes and the red-shift for oligofluorenols were rationalised in a unified way from the reduced (and increased) content of planar conformations in molecular aggregates. The planarity versus non-planarity of oligomers can be modulated by introduction of alkyl side chain or steric bulky substituents. The substitution with various groups in the ortho-position of azobenzene leads to the distorted backbone, breaking symmetry, and hence the red-shift in spectra, expanding the application in biological systems with visible light absorption. The donor-acceptor substituent groups in conjugated oligomers can increase the degree of planarity, electron delocalisation and polarisation, and charge separation, giving rise to the red-shift in spectra and enhancement in polarisability and charge mobility for device applications. The solvent dependent and pH-sensitive properties and intramolecular hydrogen bonds also caused the shift of absorption spectra with the appearance of planar conformers.

Introduction to MacDraft. High-Technology Training Module.

ERIC Educational Resources Information Center

Traxler, Gene

This training module on MacDraft is part of a computer drafting skills unit on communications technology for grades 9-12. The objective is for each student to complete a drawing on the MacIntosh computer using the MacDraft software program. This drawing is to be dimensioned with a dual system and is to include a border and title block. This module…

Computer-Aided Modeling and Analysis of Power Processing Systems (CAMAPPS), phase 1

NASA Technical Reports Server (NTRS)

Kim, S.; Lee, J.; Cho, B. H.; Lee, F. C.

1986-01-01

The large-signal behaviors of a regulator depend largely on the type of power circuit topology and control. Thus, for maximum flexibility, it is best to develop models for each functional block a independent modules. A regulator can then be configured by collecting appropriate pre-defined modules for each functional block. In order to complete the component model generation for a comprehensive spacecraft power system, the following modules were developed: solar array switching unit and control; shunt regulators; and battery discharger. The capability of each module is demonstrated using a simplified Direct Energy Transfer (DET) system. Large-signal behaviors of solar array power systems were analyzed. Stability of the solar array system operating points with a nonlinear load is analyzed. The state-plane analysis illustrates trajectories of the system operating point under various conditions. Stability and transient responses of the system operating near the solar array's maximum power point are also analyzed. The solar array system mode of operation is described using the DET spacecraft power system. The DET system is simulated for various operating conditions. Transfer of the software program CAMAPPS (Computer Aided Modeling and Analysis of Power Processing Systems) to NASA/GSFC (Goddard Space Flight Center) was accomplished.

New insights into the phenotypic covariance structure of the anthropoid cranium

PubMed Central

Makedonska, Jana

2014-01-01

In complex organisms, suites of non-random, highly intercorrelated phenotypic traits, organized according to their developmental history and forming semi-autonomous units (i.e. modules), have the potential to impose constraints on morphological diversification or to improve evolvability. Because of its structural, developmental and functional complexity, the cranium is arguably one of the best models for studying the interplay between developmental history and the need for various parts of a structure to specialize in different functions. This study evaluated the significance of two specific types of developmental imprints in the adult anthropoid cranium, those imposed by ossification pattern (i.e. ossification with and without a pre-existing cartilaginous phase) and those imposed by tissue origin (i.e. tissues derived principally from neural-crest vs. those derived from paraxial mesoderm). Specifically, this study tests the hypothesis that the face and the basicranium form two distinct modules with higher within-unit trait integration magnitudes compared with the cranium as a whole. Data on 12 anthropoid primate species were collected in the form of 23-dimensional landmarks digitized on cranial surface models that sample the basicranium as well as regions of functional importance during feeding. The presence of a significant modularity imprint in the adult cranium was assessed using a between-region within-species comparison of multivariate correlations (RV coefficients) obtained with partial least-squares, using within-module within-species eigenvalue variance (EV), and using cluster analyses and non-metric multidimensional scaling. In addition to addressing the validity of the cranial modularity hypothesis in anthropoids, this study addressed methodological aspects of the interspecific comparison of morphological integration, namely the effect of sample size and the effect of landmark number on integration magnitudes. Two methodological findings that are of significance to research in morphological integration are that: (i) a smaller sample size increases integration magnitude, but preserves the pattern of variation of integration magnitudes from block to block within species; and that (ii) the number of landmarks per cranial block does not significantly impact block integration magnitude measured as EV. Results from the analyses testing for cranial modularity imprints in the adult anthropoid cranium show that some facial landmarks covary more strongly with basicranial landmarks than with other facial landmarks. Cluster methods, non-metric multidimensional scaling and, to an extent, RV results show that the rostral and the zygomatic landmarks covary more strongly with the basicranial landmarks than they do with the molar landmarks. However, the rostral–zygomatic–basicranial block, the molar block, the facial block, the basicranial block and the other analyzed cranial and facial blocks are not more integrated than the cranium. Thus, the morphological variation in the adult anthropoid cranium is not significantly constrained by at least two of the potential developmental sources of its covariance structure. PMID:25406861

The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model.

PubMed

Wang, Dan; Fu, Jijun; Shi, Yujie; Peng, Dong; Yuan, Lan; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Tian, Jie; Zhang, Qiang

2016-09-28

The transport of nanocarriers is supposed to be based on EPR effect which is affected by diverse factors, so the modulation of EPR effect seems very significant for nanocarriers including targeted drug delivery systems (TDDSs). Besides, it is extremely unclear how the EPR effect impacts the fate of different types of TDDSs. To make the most advantage of EPR effect for TDDSs, it is definitely necessary to clarify these key issues. Here, we construct and characterize various TDDSs, including sterically-stabilized liposomes (SSL), RGD functionalized SSL (RGD-SSL) and novel 7PEP functionalized SSL (7PEP-SSL), loaded with doxorubicin (DOX), DIR or DID. Here, we modulate the permeability of tumor vessels by thalidomide (THD) in a sarcoma-bearing EPR mouse model via monitoring endogenous deoxygenated hemoglobin in circulation, and then we confirm the effect of THD on tumor vessel permeability by vessel density, vessel maturity, VEGF expression and so on. Importantly, we investigate and find the impacts of EPR effect on the antitumor efficacy, in vivo distribution and intratumoral microdistribution of the three TDDSs. Interestingly, the EPR effects affect different TDDSs differently. The elevated EPR effect enhances the tumor accumulation of SSL and RGD-SSL but fails to increase their efficacy. The RGD-SSL exhibits the best efficacy with the least fluctuation, demonstrating the advantage of angiogenesis targeted systems. 7PEP-SSL seems the biggest beneficiary of EPR effect, suggesting the significance of EPR modulation for cells targeted systems. Generally, this study demonstrates the feasibility of modulating EPR effect bidirectionally by THD as well as the impacts of EPR effect on different type of testing TDDSs based on this animal model. It certainly provides novel insight into the design and potential use of TDDSs. Copyright © 2016 Elsevier B.V. All rights reserved.

A scintillator geometry suitable for very small PET gantries

NASA Astrophysics Data System (ADS)

Gonzalez, A. J.; Gonzalez-Montoro, A.; Aguilar, A.; Cañizares, G.; Martí, R.; Iranzo, S.; Lamprou, E.; Sanchez, S.; Sanchez, F.; Benlloch, J. M.

2017-12-01

In this work we are describing a novel approach to the scintillator crystal configuration as used in nuclear medicine imaging. Our design is related to the coupling in one PET module of the two separate crystal configurations used so far there: monolithic and crystal arrays. The particular design we have studied is based on a two-layer scintillator approach (hybrid) composed of a monolithic LYSO crystal (5-6 mm thickness) and a LYSO crystal array with 4-5 mm height (0.8 and 1 mm pixels). We show here the detector block performance, in terms of spatial, energy and DOI information, to be used as a module in the design of PET scanners. The design we propose allows one to achieve accurate three-dimensional spatial resolution (including DOI information) while assuring high detection efficiency at reasonable cost. Moreover, the proposed design improves the spatial response uniformity across the whole detector module, and especially at the edge region. The crystal arrays are mounted in the front and were well resolved. The monolithic crystal inserted between crystal array and the photosensor, provided measured FWHM resolution as good as 1.5-1.7 mm including the 1 mm source size. The monolithic block achieved a DOI resolution (FWHM) nearing 3 mm. We compared these results with an approach in which we use a single monolithic block with total volume equals to the hybrid approach. In general, comparable performances were obtained.

Least Reliable Bits Coding (LRBC) for high data rate satellite communications

NASA Technical Reports Server (NTRS)

Vanderaar, Mark; Wagner, Paul; Budinger, James

1992-01-01

An analysis and discussion of a bandwidth efficient multi-level/multi-stage block coded modulation technique called Least Reliable Bits Coding (LRBC) is presented. LRBC uses simple multi-level component codes that provide increased error protection on increasingly unreliable modulated bits in order to maintain an overall high code rate that increases spectral efficiency. Further, soft-decision multi-stage decoding is used to make decisions on unprotected bits through corrections made on more protected bits. Using analytical expressions and tight performance bounds it is shown that LRBC can achieve increased spectral efficiency and maintain equivalent or better power efficiency compared to that of Binary Phase Shift Keying (BPSK). Bit error rates (BER) vs. channel bit energy with Additive White Gaussian Noise (AWGN) are given for a set of LRB Reed-Solomon (RS) encoded 8PSK modulation formats with an ensemble rate of 8/9. All formats exhibit a spectral efficiency of 2.67 = (log2(8))(8/9) information bps/Hz. Bit by bit coded and uncoded error probabilities with soft-decision information are determined. These are traded with with code rate to determine parameters that achieve good performance. The relative simplicity of Galois field algebra vs. the Viterbi algorithm and the availability of high speed commercial Very Large Scale Integration (VLSI) for block codes indicates that LRBC using block codes is a desirable method for high data rate implementations.

Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels

PubMed Central

Johannessen, Molly; Fontanilla, Dominique; Mavlyutov, Timur; Ruoho, Arnold E.

2011-01-01

σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ1- and σ2-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na+ channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na+ channel Nav1.5. Patch-clamp recording in this cell line tested Na+ current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ1-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ2-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ1-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions. PMID:21084640

Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels.

PubMed

Johannessen, Molly; Fontanilla, Dominique; Mavlyutov, Timur; Ruoho, Arnold E; Jackson, Meyer B

2011-02-01

σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ(1)- and σ(2)-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na(+) channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na(+) channel Na(v)1.5. Patch-clamp recording in this cell line tested Na(+) current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ(1)-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ(2)-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ(1)-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions.

An overview of the endodontic curriculum in Fiji from 2009 to 2013.

PubMed

Devi, Arpana A; Abbott, Paul V

2015-12-01

This paper seeks to provide the reader with an overview of the endodontic curriculum in Fiji from 2009 to 2013. It also intends to inform readers of the changes in endodontic teaching, the learning methods utilised, curriculum development, the transition from block teaching to partial block teaching combined with longitudinal teaching, and the future plans for the endodontic module. © 2015 Australian Society of Endodontology.

Communication Module for the Micro-Based Small Purchase Contracting Program

DTIC Science & Technology

1992-03-01

SUISISTUCI 2 3 SANDWICH COOKIES 3 CREAM FILLING, CHOCOLATE FLAVOR, VANILLA FLAVOR, OR 3 COM INATION BASE CAKES , ADCOP. 2 2 VARIATION PROVISIONS SAE AS CLII...SUBJECT TERMS (continue on reverse if necessary and identify by block number) FIELD I GROUP SUBGROUP Procurement Automation Telecommunications System...Information Management System 19 ABSTRACT (continue on reverse if necessary and identify by block number) This thesis conducted research and development of

Electrical control of superparamagnetism

NASA Astrophysics Data System (ADS)

Yamada, Kihiro T.; Koyama, Tomohiro; Kakizakai, Haruka; Miwa, Kazumoto; Ando, Fuyuki; Ishibashi, Mio; Kim, Kab-Jin; Moriyama, Takahiro; Ono, Shimpei; Chiba, Daichi; Ono, Teruo

2017-01-01

The electric field control of superparamagnetism is realized using a Cu/Ni system, in which the deposited Ni shows superparamagnetic behavior above the blocking temperature. An electric double-layer capacitor (EDLC) with the Cu/Ni electrode and a nonmagnetic counter electrode is fabricated to examine the electric field effect on magnetism in the magnetic electrode. By changing the voltage applied to the EDLC, the blocking temperature of the system is clearly modulated.

Facile solvolysis of a surprisingly twisted tertiary amide

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

Bloomfield, Aaron J.; Chaudhuri, Subhajyoti; Mercado, Brandon Q.

2016-01-05

In this study, a bicyclo[2.2.2]octane derivative containing both a tertiary amide and a methyl ester was shown crystallographically to adopt a conformation in which the amide is in the cis configuration, which is sterically disfavored, but electronically favored. The steric strain induces a significant torsion (15.9°) of the amide, thereby greatly increasing the solvolytic lability of the amide to the extent that we see competitive amide solvolysis in the presence of the normally more labile methyl ester also present in the molecule.

Studies on the contributions of steric and polarity effects to the H2S-binding properties of Vitreoscilla hemoglobin

NASA Astrophysics Data System (ADS)

Wang, Dandan; Wang, Hui; Li, Haichao; Liu, Li; Li, Zhengqiang

2017-01-01

We have reported recently that Vitreoscilla hemoglobin (VHb) is a potential H2S receptor and storage molecule in bacterial metabolism. In this study, molecular cloning and site-directed mutagenesis were employed to investigate the structural basis for H2S binding. Association and dissociation rate constants (kon and koff) were determined using stopped-flow rapid-scanning spectrophotometry and compared with those for wild type VHb. Several unanticipated factors were found to govern H2S binding properties, due to the distinct structure of VHb. The results presented in this paper show that: i) bulkier residues at positions E7 and E11 decrease H2S binding accessibility, while the residue located at position B10 blocks bound H2S from escaping. ii) hydroxyl sidechains within the distal heme pocket reduce H2S reactivity to VHb; iii) Pro(E8) is involved in moving the E7-E10 loop region to trigger opening of the distal heme pocket to facilitate H2S binding.

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

PubMed Central

Perz-Edwards, Robert J.; Irving, Thomas C.; Baumann, Bruce A. J.; Gore, David; Hutchinson, Daniel C.; Kržič, Uroš; Porter, Rebecca L.; Ward, Andrew B.; Reedy, Michael K.

2011-01-01

Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called “troponin bridges,” by analyzing real-time X-ray diffraction “movies” from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin’s steric blocking of myosin–actin binding. This enables subsequent force production, with cross-bridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection. PMID:21148419

Long-Circulating, pH-Sensitive Liposomes.

PubMed

Momekova, Denitsa; Rangelov, Stanislav; Lambov, Nikolay

2017-01-01

A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticuloendothelial system, which conditions a very short circulation half-life. Typically prolonged circulation of liposomes is achieved by grafting their membranes with pegylated phospholipids (PEG-lipids), which have been shown, however, to deteriorate membrane integrity on one hand and to hamper the pH-responsiveness on the other. Hence, the need for novel alternative surface modifying agents to ensure effective half-life prolongation of pH-sensitive liposomes is a subject of intensive research. A series of copolymers having short blocks of lipid-mimetic units has been shown to sterically stabilize conventional liposomes based on different phospholipids. This has prompted us to broaden their utilization to pH-sensitive liposomes, too. The present contribution gives a thorough account on the chemical synthesis of these copolymers their incorporation in DOPE:CHEMs pH-sensitive liposomes and detailed explanation on the battery of techniques for the biopharmaceutical characterization of the prepared formulations in terms of pH-responsiveness, cellular internalization, in vivo pharmacokinetics and biodistribution.

Long-circulating, pH-sensitive liposomes.

PubMed

Momekova, Denitsa; Rangelov, Stanislav; Lambov, Nikolay

2010-01-01

A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticulo-endothelial system, which conditions a very short circulation half-life. Typically prolonged circulation of liposomes is achieved by grafting their membranes with pegylated phospholipids (PEG-lipids), which have been shown, however, to deteriorate membrane integrity on one hand and to hamper the pH-responsiveness on the other. Hence, the need for novel alternative surface modifying agents to ensure effective half-life prolongation of pH-sensitive liposomes is a subject of intensive research. A series of copolymers having short blocks of lipid-mimetic units has been shown to sterically stabilize conventional liposomes based on different phospholipids. This has prompted us to broaden their utilization to pH-sensitive liposomes, too. The present contribution gives thorough account on the chemical synthesis of these copolymers their incorporation in DOPE:CHEMs pH-sensitive liposomes and detailed explanation on the battery of techniques for the biopharmaceutical characterization of the prepared formulations in terms of pH-responsiveness, cellular internalization, in vivo pharmacokinetics and biodistribution.

Constructing of DNA vectors with controlled nanosize and single dispersion by block copolymer coating gold nanoparticles as template assembly

NASA Astrophysics Data System (ADS)

Li, Junbo; Wu, Wenlan; Gao, Jiayu; Liang, Ju; Zhou, Huiyun; Liang, Lijuan

2017-03-01

Synthesized vectors with nanoscale size and stable colloid dispersion are highly desirable for improving gene delivery efficiency. Here, a core-shell template particle was constructed with polyethylene glycol- b-poly1-(3-aminopropyl)-3-(2-methacryloyloxy propylimidazolium bromine) (PEG- b-PAMPImB) coating gold nanoparticles (PEG- b-PAMPImB-@-Au NPs) for loading DNA and delivering in vitro. Data from transmission electron microscopy (TEM) and dynamic light scattering (DLS) suggest that these nanoplexes, by forming an electrostatic complex with DNA at the inner PAMPImB shell, offer steric protection for the outer PEG corona leading to single dispersion and small size. Notably, higher colloid stability and lower cytotoxicity were achieved with these nanoplexes when compared with PAMPImB monolayer-coated gold nanoparticles (Au NPs). Confocal laser scanning microscopy and intracellular trafficking TEM further indicate that the nanoplexes can translocate across the cell membrane and partly enter the nucleus for high efficient expression. Thus, template assembly represents a promising approach to control the size and colloid stability of gene vectors and ensure safety and efficiency of DNA delivery.

Synthesis and characterization of low-molecular-weight π-conjugated polymers covered by persilylated β-cyclodextrin

PubMed Central

Resmerita, Ana-Maria; Stefanache, Andreea; Balan, Mihaela; Harabagiu, Valeria

2012-01-01

Summary The paper reports the preparation of a poly[2,7-(9,9-dioctylfluorene)-alt-5,5'-bithiophene/PS-βCD] (PDOF-BTc) polyrotaxane copolymer, through a Suzuki coupling reaction between the 5,5'-dibromo-2,2'-bithiophene (BT) inclusion complex with persilylated β-cyclodextrin (PS-βCD), and 9,9-dioctylfluorene-2,7-bis(trimethylene borate) (DOF) as the blocking group. The chemical structure and the thermal and morphological properties of the resulting polyrotaxane were investigated by using NMR and FT-IR spectroscopy, TGA, DSC and AFM analysis. The encapsulation of BT inside the PS-βCD cavity results in improvements in the solubility, as well as in different surface morphology and thermal properties of the PDOF-BTc rotaxane copolymer compared to its noncomplexed PDOF-BT homologue. In contrast, the number-average molecular weight (M n) of PDOF-BTc rotaxane copolymer indicated lower values suggesting that the condensation reaction is subjected to steric effects of the bulkier silylated groups, affecting the ability of the diborate groups from the DOF molecule to partially penetrate the PS-βCD cavity. PMID:23019485

Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone

PubMed Central

Li, Frances; Tian, Geng; Langager, Deanna; Sokolova, Vladyslava; Finley, Daniel; Park, Soyeon

2017-01-01

The proteasome is assembled via the nine-subunit lid, nine-subunit base, and 28-subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base and antagonize base–CP interaction. Here, we show that the Nas6 chaperone also obstructs base–lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base–lid, but not base–CP, association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base–CP, but not base–lid, association. Modeling of Nas6 into cryoelectron microscopy structures of the proteasome suggests that Nas6 controls both base–lid affinity and base–CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP-hydrolysis–blocked proteasome, but clashes instead with the CP in the ATP-hydrolysis–competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome. PMID:28137839

Crystal Structure and Conformational Change Mechanism of a Bacterial Nramp-Family Divalent Metal Transporter.

PubMed

Bozzi, Aaron T; Bane, Lukas B; Weihofen, Wilhelm A; Singharoy, Abhishek; Guillen, Eduardo R; Ploegh, Hidde L; Schulten, Klaus; Gaudet, Rachelle

2016-12-06

The widely conserved natural resistance-associated macrophage protein (Nramp) family of divalent metal transporters enables manganese import in bacteria and dietary iron uptake in mammals. We determined the crystal structure of the Deinococcus radiodurans Nramp homolog (DraNramp) in an inward-facing apo state, including the complete transmembrane (TM) segment 1a (absent from a previous Nramp structure). Mapping our cysteine accessibility scanning results onto this structure, we identified the metal-permeation pathway in the alternate outward-open conformation. We investigated the functional impact of two natural anemia-causing glycine-to-arginine mutations that impaired transition metal transport in both human Nramp2 and DraNramp. The TM4 G153R mutation perturbs the closing of the outward metal-permeation pathway and alters the selectivity of the conserved metal-binding site. In contrast, the TM1a G45R mutation prevents conformational change by sterically blocking the essential movement of that helix, thus locking the transporter in an inward-facing state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

DOE PAGES

Yuan, Zuanning; Bai, Lin; Sun, Jingchuan; ...

2016-02-08

The CMG helicase is composed of Cdc45, Mcm2–7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7–4.8 Å. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2–7, braced by Cdc45–GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached tomore » a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2–7 double hexamer. In addition, the Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA-unwinding model.« less

Polyhedral Boranes: A Versatile Building Block for Nanoporous Materials

NASA Astrophysics Data System (ADS)

Clingerman, Daniel Jon

The studies described in this dissertation examine several new concepts related to polyhedral boranes and their applications towards the synthesis of novel nanoporous materials. The unique thermal and chemical robustness, rigidity, quasi-spherical geometry, and high boron content of polyhedral boranes are explored to generate materials not possible with typical organic synthons. Aside from the fundamental synthetic work, this work was also aimed at solving larger global issues such as energy storage and new routes to therapeutics. Chapter 2 highlights the discovery of the first highly porous carborane-based metal-organic framework, where the spherical nature of the carborane increases volumetric surface area without reducing pore volume. Chapter 3 examines the first tritopic carborane-based ligand and the stabilizing effect the rigid, sterically bulky carboranyl groups have on highly porous topologies not stable with typical organic ligands. Chapters 4 and 5 describe the use of polyhedral borane-based ligands as a means to influence and generate unexpected topologies. Lastly, chapter 6 explores using a simple carborane-based ligand that harnesses the power of coordination-driven assembly to rapidly generate a high boron-containing supramolecular cuboctahedron.

Approaching the design of a failsafe turbine monitor with simple microcontroller blocks

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

Zapolin, R.E.

1995-12-31

The proper approach to early instrumentation design for tasks like failsafe turbine monitoring permits meeting requirements without resorting to traditional complex special-purpose electronics. Instead a small network of basic microcontroller building blocks can split the effort with each block optimized for its portion of the overall system. This paper discusses approaching design by partitioning intricate system specifications to permit each block to be optimized to the safety level appropriate for its portion of the overall task while retaining and production and reliability advantages of having common simple modules. It illustrates that approach with a modular microcontroller-based speed monitor which metmore » user needs for the latest in power plant monitoring equipment.« less

Measurements and Quasi-Quantum Modeling of the Steric Asymmetry and Parity Propensities in State-to-State Rotationally Inelastic Scattering of NO ( 2Π 1/2) with D 2

DOE PAGES

Taatjes, Craig A.; Gijsbertsen, Arjan; de Lange, Marc J. L.; ...

2007-06-02

In this paper, relative integrated cross sections are measured for spin-orbit-conserving, rotationally inelastic scattering of NO ( 2Π 1/2), hexapole-selected in the upper Λ-doublet level of the ground rotational state (j = 0.5), in collisions with D 2 at a nominal energy of 551 cm -1. The final state of the NO molecule is detected by laser-induced fluorescence (LIF). The state-selected NO molecule is oriented with either the N end or the O end toward the incoming D 2 molecule by application of a static electric field E in the scattering region. This field is directed parallel or antiparallel tomore » the relative velocity vector v. Comparison of signals taken for the different applied field directions gives the experimental steric asymmetry SA, defined by SA = (σ v↑↓E - σ v↑↑E)/(σ v↑↓E + σ v↑↑E), which is equal to within a factor of -1 to the molecular steric effect, S i→f ≡ (σ D2→NO - σ D2→ON)/(σ D2→NO + σ D2→ON). The dependence of the integral inelastic cross section on the incoming Λ-doublet component is also measured as a function of the final rotational (j final) and Λ-doublet (ε final) state. The measured steric asymmetries are similar to those previously observed for NO-He scattering. Spin-orbit manifold-conserving collisions exhibit a larger propensity for parity conservation than their NO-He counterparts. The results are interpreted in the context of the recently developed quasi-quantum treatment (QQT) of rotationally inelastic scattering. The QQT predictions can be inverted to obtain a fitted hard-shell potential that reproduces the experimental steric asymmetry; this fitted potential gives an empirical estimate of the anisotropy of the repulsive interaction between NO and D 2. Finally, QQT computation of the differential cross section using this simple model potential shows reasonable agreement with the measured differential cross sections.« less

Dense blocks of energetic ions driven by multi-petawatt lasers

PubMed Central

Weng, S. M.; Liu, M.; Sheng, Z. M.; Murakami, M.; Chen, M.; Yu, L. L.; Zhang, J.

2016-01-01

Laser-driven ion accelerators have the advantages of compact size, high density, and short bunch duration over conventional accelerators. Nevertheless, it is still challenging to simultaneously enhance the yield and quality of laser-driven ion beams for practical applications. Here we propose a scheme to address this challenge via the use of emerging multi-petawatt lasers and a density-modulated target. The density-modulated target permits its ions to be uniformly accelerated as a dense block by laser radiation pressure. In addition, the beam quality of the accelerated ions is remarkably improved by embedding the target in a thick enough substrate, which suppresses hot electron refluxing and thus alleviates plasma heating. Particle-in-cell simulations demonstrate that almost all ions in a solid-density plasma of a few microns can be uniformly accelerated to about 25% of the speed of light by a laser pulse at an intensity around 1022 W/cm2. The resulting dense block of energetic ions may drive fusion ignition and more generally create matter with unprecedented high energy density. PMID:26924793

ROMPS critical design review. Volume 1: Hardware

NASA Technical Reports Server (NTRS)

Dobbs, M. E.

1992-01-01

Topics concerning the Robot-Operated Material Processing in Space (ROMPS) Program are presented in viewgraph form and include the following: a systems overview; servocontrol and servomechanisms; testbed and simulation results; system V controller; robot module; furnace module; SCL experiment supervisor; SCL script sample processing control; SCL experiment supervisor fault handling; block diagrams; hitchhiker interfaces; battery systems; watchdog timers; mechanical/thermal systems; and fault conditions and recovery.

International Space Station (ISS)

NASA Image and Video Library

2000-09-01

This image of the International Space Station (ISS) was taken when Space Shuttle Atlantis (STS-106 mission) approached the ISS for docking. At the top is the Russian Progress supply ship that is linked with the Russian built Service Module or Zvezda. The Zvezda is cornected with the Russian built Functional Cargo Block (FGB) or Zarya. The U.S. built Node 1 or Unity module is seen at the bottom.

A Neurophysiological examination of quality of learning in a feedback-based learning task.

PubMed

Arbel, Yael; Wu, Hao

2016-12-01

The efficiency with which one processes external feedback contributes to the speed and quality of one's learning. Previous findings that the feedback related negativity (FRN) event related potential (ERP) is modulated by learning outcomes suggested that this ERP reflects the extent to which feedback is used by the learner to improve performance. To further test this suggestion, we measured whether the FRN and the fronto-central positivity (FCP) that follows it are modulated by learning slopes, and as a function of individual differences in learning outcomes. Participants were tasked with learning names (non-words) of 42 novel objects in a two-choice feedback-based visual learning task. The items were divided into three sets of 14 items, each presented in five learning blocks and a sixth test block. Individual learning slopes based on performance on the task, as well as FRN and FCP slopes based on positive and negative feedback related activation in each block were created for 53 participants. Our data pointed to an interaction between slopes of the FRN elicited by negative feedback and learning slopes, such that a sharper decrease in the amplitude of the FRN to negative feedback was associated with sharper learning slopes. We further examined the predictive power of the FRN and FCP elicited in the training blocks on the learning outcomes as measured by performance on the test blocks. We found that small FRN to negative feedback, large FRN to positive feedback, and large FCP to negative feedback in the first training block predicted better learning outcomes. These results add to the growing evidence that the processes giving rise to the FRN and FCP are sensitive to individual differences in the extent to which feedback is used for learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sea level budget in the Arctic during the satellite altimetry era

NASA Astrophysics Data System (ADS)

Carret, Alice; Cazenave, Anny; Meyssignac, Benoît; Prandi, Pierre; Ablain, Michael; Andersen, Ole; Blazquez, Alejandro

2016-04-01

Studying sea level variations in the Arctic region is challenging because of data scarcity. Here we present results of the sea level budget in the Arctic (up to 82°N) during the altimetry era. We first investigate closure of the sea level budget since 2002 using altimetry data from Envisat and Cryosat for estimating sea level, temperature and salinity data from the ORAP5 reanalysis and GRACE space gravimetry to estimate the steric and mass components. Two altimetry sea level data sets are considered (from DTU and CLS), based on Envisat waveforms retracking. Regional sea level trends seen in the altimetric map, in particular over the Beaufort Gyre and along the eastern coast of Greenland are of steric origin. However, in terms of regional average, the steric component contributes very little to the observed sea level trend, suggesting a dominant mass contribution in the Arctic region. This is confirmed by GRACE-based ocean mass time series that agree very well with the altimetry-based sea level time series. Direct estimate of the mass component is not possible prior to GRACE. Thus we estimated the mass contribution over the whole altimetry era from the difference between altimetry-based sea level and the ORAP5 steric component. Finally we compared altimetry-based coastal sea level with tide gauge records available along Norwegian, Greenland and Siberian coastlines and investigated whether the Arctic Oscillation that was the main driver of coastal sea level in the Arctic during the past decades still plays a dominant role or if other factors (e.g., of anthropogenic origin) become detectable.

Establishment of Constraints on Amyloid Formation Imposed by Steric Exclusion of Globular Domains.

PubMed

Azizyan, Rafayel A; Garro, Adriana; Radkova, Zinaida; Anikeenko, Alexey; Bakulina, Anastasia; Dumas, Christian; Kajava, Andrey V

2018-06-01

In many disease-related and functional amyloids, the amyloid-forming regions of proteins are flanked by globular domains. When located in close vicinity of the amyloid regions along the chain, the globular domains can prevent the formation of amyloids because of the steric repulsion. Experimental tests of this effect are few in number and non-systematic, and their interpretation is hampered by polymorphism of amyloid structures. In this situation, modeling approaches that use such a clear-cut criterion as the steric tension can give us highly trustworthy results. In this work, we evaluated this steric effect by using molecular modeling and dynamics. As an example, we tested hybrid proteins containing an amyloid-forming fragment of Aβ peptide (17-42) linked to one or two globular domains of GFP. Searching for the shortest possible linker, we constructed models with pseudo-helical arrangements of the densely packed GFPs around the Aβ amyloid core. The molecular modeling showed that linkers of 7 and more residues allow fibrillogenesis of the Aβ-peptide flanked by GFP on one side and 18 and more residues when Aβ-peptide is flanked by GFPs on both sides. Furthermore, we were able to establish a more general relationship between the size of the globular domains and the length of the linkers by using analytical expressions and rigid body simulations. Our results will find use in planning and interpretation of experiments, improvement of the prediction of amyloidogenic regions in proteins, and design of new functional amyloids carrying globular domains. Copyright © 2018 Elsevier Ltd. All rights reserved.

3D-QSAR CoMFA of a series of DABO derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors.

PubMed

de Brito, Monique Araújo; Rodrigues, Carlos Rangel; Cirino, José Jair Vianna; de Alencastro, Ricardo Bicca; Castro, Helena Carla; Albuquerque, Magaly Girão

2008-08-01

A series of 74 dihydroalkoxybenzyloxopyrimidines (DABOs), a class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs), was retrieved from the literature and studied by comparative molecular field analysis (CoMFA) in order to derive three-dimensional quantitative structure-activity relationship (3D-QSAR) models. The CoMFA study has been performed with a training set of 59 compounds, testing three alignments and four charge schemes (DFT, HF, AM1, and PM3) and using defaults probe atom (Csp (3), +1 charge), cutoffs (30 kcal.mol (-1) for both steric and electrostatic fields), and grid distance (2.0 A). The best model ( N = 59), derived from Alignment 1 and PM3 charges, shows q (2) = 0.691, SE cv = 0.475, optimum number of components = 6, r (2) = 0.930, SEE = 0.226, and F-value = 115.544. The steric and electrostatic contributions for the best model were 43.2% and 56.8%, respectively. The external predictive ability (r (2) pred = 0.918) of the resultant best model was evaluated using a test set of 15 compounds. In order to design more potent DABO analogues as anti-HIV/AIDS agents, attention should be taken in order to select a substituent for the 4-oxopyrimidine ring, since, as revealed by the best CoMFA model, there are a steric restriction at the C2-position, a electron-rich group restriction at the C6-position ( para-substituent of the 6-benzyl group), and a steric allowed region at the C5-position.

Deterministic folding: The role of entropic forces and steric specificities

NASA Astrophysics Data System (ADS)

da Silva, Roosevelt A.; da Silva, M. A. A.; Caliri, A.

2001-03-01

The inverse folding problem of proteinlike macromolecules is studied by using a lattice Monte Carlo (MC) model in which steric specificities (nearest-neighbors constraints) are included and the hydrophobic effect is treated explicitly by considering interactions between the chain and solvent molecules. Chemical attributes and steric peculiarities of the residues are encoded in a 10-letter alphabet and a correspondent "syntax" is provided in order to write suitable sequences for the specified target structures; twenty-four target configurations, chosen in order to cover all possible values of the average contact order χ (0.2381⩽χ⩽0.4947 for this system), were encoded and analyzed. The results, obtained by MC simulations, are strongly influenced by geometrical properties of the native configuration, namely χ and the relative number φ of crankshafts-type structures: For χ<0.35 the folding is deterministic, that is, the syntax is able to encode successful sequences: The system presents larger encodability, minimum sequence-target degeneracies and smaller characteristic folding time τf. For χ⩾0.35 the above results are not reproduced any more: The folding success is severely reduced, showing strong correlation with φ. Additionally, the existence of distinct characteristic folding times suggests that different mechanisms are acting at the same time in the folding process. The results (all obtained from the same single model, under the same "physiological conditions") resemble some general features of the folding problem, supporting the premise that the steric specificities, in association with the entropic forces (hydrophobic effect), are basic ingredients in the protein folding process.

Synthesis and physicochemical studies of amyloidogenic hexapeptides derived from human cystatin C.

PubMed

Iłowska, Emilia; Sawicka, Justyna; Szymańska, Aneta

2018-06-01

Human cystatin C (hCC) is a low molecular mass protein that belongs to the cystatin superfamily. It is an inhibitor of extracellular cysteine proteinases, present in all human body fluids. At physiological conditions, hCC is a monomer, but it has a tendency to dimerization. Naturally occurring hCC mutant, with leucine in position 68 substituted by glutamine (L68Q), is directly involved in the formation of amyloid deposits, independently of other proteins. This process is the primary cause of hereditary cerebral amyloid angiopathy, observed mainly in the Icelandic population. Oligomerization and fibrillization processes of hCC are not explained equally well, but it is proposed that domain swapping is involved in both of them. Research carried out on the fibrillization process led to new hypothesis about the existence of a steric zipper motif in amyloidogenic proteins. In the hCC sequence, there are 2 fragments which may play the role of a steric zipper: the loop L1 region and the C-terminal fragment. In this work, we focused on the first of these. Nine hexapeptides covering studied hCC fragment were synthesized, and their fibrillogenic potential was assessed using an array of biophysical methods. The obtained results showed that the studied hCC fragment has strong profibrillogenic propensities because it contains 2 fragments fulfilling the requirements for an effective steric zipper located next to each other, forming 1 super-steric zipper motif. This hCC fragment might therefore be responsible for the enhanced amyloidogenic properties of dimeric or partially unfolded hCC. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

Revealing climate modes in steric sea levels: lessons learned from satellite geodesy, objective analyses and ocean reanalyses

NASA Astrophysics Data System (ADS)

Pfeffer, J.; Tregoning, P.; Purcell, A. P.

2017-12-01

Due to increased greenhouse gases emissions, the oceans are accumulating heat. In response to the ocean circulation and atmospheric forcing, the heat is irregularly redistributed within the oceans, causing sea level to rise at variable rates in space and time. These rates of steric expansion are extremely difficult to assess because of the sparsity of in-situ hydrographic observations available within the course of the 20th century. We compare here three methods to reconstruct the steric sea levels over the past 13, 25 and 58 years based on satellite geodesy, objective analyses and ocean reanalyses. The interannual to decadal variability of each dataset is explored with a model merging six climate indices representative of the natural variability of the ocean and climate system. Consistent regional patterns are identified for the Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) in all datasets at all timescales. Despite the short time coverage (13 years), the combination of satellite geodetic data (altimetry and GRACE) also reveals significant steric responses to the North Pacific Gyre Oscillation (NPGO), Indian Dipole (IOD) and Indian ocean basinwide (IOBM) mode. The richer information content in the ocean reanalyses allows us to recover the regional fingerprints of the PDO, ENSO, NPGO, IOD and IOBM, but also of the Atlantic Multidecadal Oscillation (AMO) acting over longer time scales (40 to 60 years). Therefore, ocean reanalyses, coupled with climate mode analyses, constitute innovative and promising tools to investigate the mechanisms triggering the variability of sea level rise over the past decades.

Study of limitations and attributes of microprocessor testing techniques

NASA Technical Reports Server (NTRS)

Mccaskill, R.; Sohl, W. E.

1977-01-01

All microprocessor units have a similar architecture from which a basic test philosophy can be adopted and used to develop an approach to test each module separately in order to verify the functionality of each module within the device using the input/output pins of the device and its instruction set; test for destructive interaction between functional modules; and verify all timing, status information, and interrupt operations of the device. Block and test flow diagrams are given for the 8080, 8008, 2901, 6800, and 1802 microprocessors. Manufacturers are listed and problems encountered in testing the modules are discussed. Test equipment and methods are described.

Structured Low-Density Parity-Check Codes with Bandwidth Efficient Modulation

NASA Technical Reports Server (NTRS)

Cheng, Michael K.; Divsalar, Dariush; Duy, Stephanie

2009-01-01

In this work, we study the performance of structured Low-Density Parity-Check (LDPC) Codes together with bandwidth efficient modulations. We consider protograph-based LDPC codes that facilitate high-speed hardware implementations and have minimum distances that grow linearly with block sizes. We cover various higher- order modulations such as 8-PSK, 16-APSK, and 16-QAM. During demodulation, a demapper transforms the received in-phase and quadrature samples into reliability information that feeds the binary LDPC decoder. We will compare various low-complexity demappers and provide simulation results for assorted coded-modulation combinations on the additive white Gaussian noise and independent Rayleigh fading channels.

The Design and Implementation of NASA's Advanced Flight Computing Module

NASA Technical Reports Server (NTRS)

Alkakaj, Leon; Straedy, Richard; Jarvis, Bruce

1995-01-01

This paper describes a working flight computer Multichip Module developed jointly by JPL and TRW under their respective research programs in a collaborative fashion. The MCM is fabricated by nCHIP and is packaged within a 2 by 4 inch Al package from Coors. This flight computer module is one of three modules under development by NASA's Advanced Flight Computer (AFC) program. Further development of the Mass Memory and the programmable I/O MCM modules will follow. The three building block modules will then be stacked into a 3D MCM configuration. The mass and volume of the flight computer MCM achieved at 89 grams and 1.5 cubic inches respectively, represent a major enabling technology for future deep space as well as commercial remote sensing applications.

The AC photovoltaic module is here!

NASA Astrophysics Data System (ADS)

Strong, Steven J.; Wohlgemuth, John H.; Wills, Robert H.

1997-02-01

This paper describes the design, development, and performance results of a large-area photovoltaic module whose electrical output is ac power suitable for direct connection to the utility grid. The large-area ac PV module features a dedicated, integrally mounted, high-efficiency dc-to-ac power inverter with a nominal output of 250 watts (STC) at 120 Vac, 60 H, that is fully compatible with utility power. The module's output is connected directly to the building's conventional ac distribution system without need for any dc wiring, string combiners, dc ground-fault protection or additional power-conditioning equipment. With its advantages, the ac photovoltaic module promises to become a universal building block for use in all utility-interactive PV systems. This paper discusses AC Module design aspects and utility interface issues (including islanding).

Fault tree safety analysis of a large Li/SOCl(sub)2 spacecraft battery

NASA Technical Reports Server (NTRS)

Uy, O. Manuel; Maurer, R. H.

1987-01-01

The results of the safety fault tree analysis on the eight module, 576 F cell Li/SOCl2 battery on the spacecraft and in the integration and test environment prior to launch on the ground are presented. The analysis showed that with the right combination of blocking diodes, electrical fuses, thermal fuses, thermal switches, cell balance, cell vents, and battery module vents the probability of a single cell or a 72 cell module exploding can be reduced to .000001, essentially the probability due to explosion for unexplained reasons.

Semantic distance effects on object and action naming.

PubMed

Vigliocco, Gabriella; Vinson, David P; Damian, Markus F; Levelt, Willem

2002-10-01

Graded interference effects were tested in a naming task, in parallel for objects and actions. Participants named either object or action pictures presented in the context of other pictures (blocks) that were either semantically very similar, or somewhat semantically similar or semantically dissimilar. We found that naming latencies for both object and action words were modulated by the semantic similarity between the exemplars in each block, providing evidence in both domains of graded semantic effects.

Series Fault Limiting Resistors for Atlas Marx Modules

DTIC Science & Technology

1995-07-01

use Reticulated Vitreous Carbon (RVC)2 foam blocks for the series resistor element. The blocks will serve as a resistive transmission line on the...3,4. 2. Joseph Wang, (Department of Chemistry, New Mexico State University, Las Cruces NM 88003, USA), " Reticulated Vitreous Carbon -A New Versatile...0.08 Ohm-em fitting our requirements well. The process of producing RVC results in a reproducibly refined form of continuous-fiber, vitreous Carbon

Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.

PubMed

Caballero, Julio; Fernández, Michael; Coll, Deysma

2010-12-01

Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies. © 2010 John Wiley & Sons A/S.

Microscopic Description of Thermodynamics of Lipid Membrane at Liquid-Gel Phase Transition

NASA Astrophysics Data System (ADS)

Kheyfets, B.; Galimzyanov, T.; Mukhin, S.

2018-05-01

A microscopic model of the lipid membrane is constructed that provides analytically tractable description of the physical mechanism of the first order liquid-gel phase transition. We demonstrate that liquid-gel phase transition is cooperative effect of the three major interactions: inter-lipid van der Waals attraction, steric repulsion and hydrophobic tension. The model explicitly shows that temperature-dependent inter-lipid steric repulsion switches the system from liquid to gel phase when the temperature decreases. The switching manifests itself in the increase of lateral compressibility of the lipids as the temperature decreases, making phase with smaller area more preferable below the transition temperature. The model gives qualitatively correct picture of abrupt change at transition temperature of the area per lipid, membrane thickness and volume per hydrocarbon group in the lipid chains. The calculated dependence of phase transition temperature on lipid chain length is in quantitative agreement with experimental data. Steric repulsion between the lipid molecules is shown to be the only driver of the phase transition, as van der Waals attraction and hydrophobic tension are weakly temperature dependent.

Mixed valency and site-preference chemistry for cerium and its compounds: A predictive density-functional theory study

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

Alam, Aftab; Johnson, Duane D.

Cerium and its technologically relevant compounds are examples of anomalous mixed valency, originating from two competing oxidation states—itinerant Ce4+ and localized Ce3+. Under applied stress, anomalous transitions are observed but not well understood. Here we treat mixed valency as an “alloy” problem involving two valences with competing and numerous site-occupancy configurations. We use density-functional theory with Hubbard U (i.e., DFT+U) to evaluate the effective valence and predict properties, including controlling the valence by pseudoternary alloying. For Ce and its compounds, such as (Ce,La)2(Fe,Co)14B permanent magnets, we find a stable mixed-valent α state near the spectroscopic value of νs=3.53. Ce valencymore » in compounds depends on its steric volume and local chemistry. For La doping, Ce valency shifts towards γ-like Ce3+, as expected from steric volume; for Co doping, valency depends on local Ce-site chemistry and steric volume. Our approach captures the key origins of anomalous valency and site-preference chemistry in complex compounds.« less

Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

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

Tomasello, Gaia; Altoe, Piero; Stenta, Marco

2007-12-26

Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutralmore » GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.« less

Internal gravity wave contributions to global sea surface variability

NASA Astrophysics Data System (ADS)

Savage, A.; Arbic, B. K.; Richman, J. G.; Shriver, J. F.; Buijsman, M. C.; Zamudio, L.; Wallcraft, A. J.; Sharma, H.

2016-02-01

High-resolution (1/12th and 1/25th degree) 41-layer simulations of the HYbrid Coordinate Ocean Model (HYCOM), forced by both atmospheric fields and the astronomical tidal potential, are used to construct global maps of sea-surface height (SSH). The HYCOM output has been separated into steric, non-steric, and total sea-surface height and the maps display variance in subtidal, tidal, and supertidal bands. Two of the global maps are of particular interest in planning for the upcoming Surface Water and Ocean Topography (SWOT) wide-swath satellite altimeter mission; (1) a map of the nonstationary tidal signal (estimated after removing the stationary tidal signal via harmonic analysis), and (2) a map of the steric supertidal contributions, which are dominated by the internal gravity wave continuum. Both of these maps display signals of order 1 cm2, the target accuracy for the SWOT mission. Therefore, both non-stationary internal tides and non-tidal internal gravity waves are likely to be important sources of "noise" that must be accurately removed before examination of lower-frequency phenomena can take place.

Steric interactions lead to collective tilting motion in the ribosome during mRNA-tRNA translocation

NASA Astrophysics Data System (ADS)

Nguyen, Kien; Whitford, Paul C.

2016-02-01

Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ~18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ~10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements.

Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O–H Insertion

PubMed Central

Chamni, Supakarn; He, Qing-Li; Dang, Yongjun; Bhat, Shridhar; Liu, Jun O.; Romo, Daniel

2011-01-01

Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure-activity relationship (SAR) studies of alcohol-containing natural products with a small steric footprint, namely an α-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed O–H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated and useful reactivity and both chemo- and site (chemosite) selectivities were observed. Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small molecule protein receptors. PMID:21894934

[Fe(bpb)(CN)2]- as a versatile building block for the design of novel low-dimensional heterobimetallic systems: synthesis, crystal structures, and magnetic properties of cyano-bridged Fe(III)-Ni(II) complexes [(bpb)(2-) = 1,2-bis(pyridine-2-carboxamido)benzenate].

PubMed

Ni, Zhong-Hai; Kou, Hui-Zhong; Zhao, Yi-Hua; Zheng, Lei; Wang, Ru-Ji; Cui, Ai-Li; Sato, Osamu

2005-03-21

A dicyano-containing [Fe(bpb)(CN)2]- building block has been employed for the synthesis of cyano-bridged heterometallic Ni(II)-Fe(III) complexes. The presence of steric bpb(2-) ligand around the iron ion results in the formation of low-dimensional species: five are neutral NiFe2 trimers and three are one-dimensional (1D). The structure of the 1D complexes consists of alternating [NiL]2+ and [Fe(bpb)(CN)2]- generating a cyano-bridged cationic polymeric chain and the perchlorate as the counteranion. In all complexes, the coordination geometry of the nickel ions is approximately octahedral with the cyano nitrogen atoms at the trans positions. Magnetic studies of seven complexes show the presence of ferromagnetic interaction between the metal ions through the cyano bridges. Variable temperature magnetic susceptibility investigations of the trimeric complexes yield the following J(NiFe) values (based on the spin exchange Hamiltonian H = -2J(NiFe) S(Ni) (S(Fe(1)) + S(Fe(2))): J(NiFe) = 6.40(5), 7.8(1), 8.9(2), and 6.03(4) cm(-1), respectively. The study of the magneto-structural correlation reveals that the cyanide-bridging bond angle is related to the strength of magnetic exchange coupling: the larger the Ni-N[triple bond]C bond angle, the stronger the Ni- - -Fe magnetic interaction. One 1D complex exhibits long-range antiferromagnetic ordering with T(N) = 3.5 K. Below T(N) (1.82 K), a metamagnetic behavior was observed with the critical field of approximately 6 kOe. The present research shows that the [Fe(bpb)(CN)2]- building block is a good candidate for the construction of low-dimensional magnetic materials.

Rate-Compatible LDPC Codes with Linear Minimum Distance

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Jones, Christopher; Dolinar, Samuel

2009-01-01

A recently developed method of constructing protograph-based low-density parity-check (LDPC) codes provides for low iterative decoding thresholds and minimum distances proportional to block sizes, and can be used for various code rates. A code constructed by this method can have either fixed input block size or fixed output block size and, in either case, provides rate compatibility. The method comprises two submethods: one for fixed input block size and one for fixed output block size. The first mentioned submethod is useful for applications in which there are requirements for rate-compatible codes that have fixed input block sizes. These are codes in which only the numbers of parity bits are allowed to vary. The fixed-output-blocksize submethod is useful for applications in which framing constraints are imposed on the physical layers of affected communication systems. An example of such a system is one that conforms to one of many new wireless-communication standards that involve the use of orthogonal frequency-division modulation

Morphology and conductivity of PEO-based polymers having various end functional groups

NASA Astrophysics Data System (ADS)

Jung, Ha Young; Mandal, Prithwiraj; Park, Moon Jeong

Poly(ethylene oxide) (PEO)-based polymers have been considered most promising candidates of polymer electrolytes for lithium batteries owing to the high ionic conductivity of PEO/lithium salt complexes. This positive aspect prompted researchers to investigate PEO-containing block copolymers prepared by linking mechanically robust block to PEO covalently. Given that the microphase separation of block copolymers can affect both mechanical properties and ion transport properties, various strategies have been reported to tune the morphology of PEO-containing block copolymers. In the present study, we describe a simple means for modulating the morphologies of PEO-based block copolymers with an aim to improve ion transport properties. By varying terminal groups of PEO in block copolymers, the disordered morphology can be readily transformed into ordered lamellae or gyroid phases, depending on the type and number density of end group. In particular, the existence of terminal groups resulted in a large reduction in crystallinity of PEO chains and thereby increasing room temperature ionic conductivity.

Enzymatic Continuous Flow Synthesis of Thiol-Terminated Poly(δ-Valerolactone) and Block Copolymers.

PubMed

Zhu, Ning; Huang, Weijun; Hu, Xin; Liu, Yihuan; Fang, Zheng; Guo, Kai

2018-04-01

Thiol-terminated poly(δ-valerolactone) is directly synthesized via enzymatic 6-mercapto-1-hexanol initiated ring-opening polymerization in both batch and microreactor. By using Candida antartica Lipase B immobilized tubular reactor, narrowly dispersed poly(δ-valerolactone) with higher thiol fidelity is more efficiently prepared in contrast to the batch reactor. Moreover, the integrated enzyme packed tubular reactor system is established to perform the chain extension experiments. Thiol-terminated poly(δ-valerolactone)-block-poly(ε-caprolactone) and poly(ε-caprolactone)-block-poly(δ-valerolactone) are easily prepared by modulating the monomer introduction sequence. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increased Attentional Focus Modulates Eye Movements in a Mixed Antisaccade Task for Younger and Older Adults

PubMed Central

Wang, Jingxin; Tian, Jing; Wang, Rong; Benson, Valerie

2013-01-01

We examined performance in the antisaccade task for younger and older adults by comparing latencies and errors in what we defined as high attentional focus (mixed antisaccades and prosaccades in the same block) and low attentional focus (antisaccades and prosaccades in separate blocks) conditions. Shorter saccade latencies for correctly executed eye movements were observed for both groups in mixed, compared to blocked, antisaccade tasks, but antisaccade error rates were higher for older participants across both conditions. The results are discussed in relation to the inhibitory hypothesis, the goal neglect theory and attentional control theory. PMID:23620767

Optical properties and progressive sterical hindering in pyridinium phenoxides

NASA Astrophysics Data System (ADS)

Boeglin, A.; Barsella, A.; Fort, A.; Mançois, F.; Rodriguez, V.; Diemer, V.; Chaumeil, H.; Defoin, A.; Jacques, P.; Carré, C.

2007-07-01

Pyridinium phenoxides are model compounds associating large dipole moments with high optical nonlinearities. A progression of sterically hindered forms of such zwitterions has been synthesized in order to investigate their structure/property relationships. Their UV-vis absorption in acetonitrile has been analyzed as a function of concentration in order to assess the presence of aggregates and the level of protonation. The quadratic optical properties have been measured by the EFISH and hyper-Rayleigh techniques and are interpreted via semi-empirical calculations. The solvation model used leads to results that agree with our experimental findings indicating an increased response for intermediate twist angles.

Correction: β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade.

PubMed

Ito, Ryousuke; Nakada, Chika; Hoshino, Tsutomu

2017-01-18

Correction for 'β-Amyrin synthase from Euphorbia tirucalli L. functional analyses of the highly conserved aromatic residues Phe413, Tyr259 and Trp257 disclose the importance of the appropriate steric bulk, and cation-π and CH-π interactions for the efficient catalytic action of the polyolefin cyclization cascade' by Ryousuke Ito et al., Org. Biomol. Chem., 2017, 15, 177-188.

Discovering the balance of steric and electronic factors needed to provide a new structural motif for photocatalytic hydrogen production from water.

PubMed

White, Travis A; Whitaker, Brittany N; Brewer, Karen J

2011-10-05

Ru,Rh,Ru supramolecules are known to undergo multielectron photoreduction and reduce H(2)O to H(2). Ru,Rh bimetallics were recently shown to photoreduce but not catalyze H(2)O reduction. Careful tuning of sterics and electronics for [(TL)(2)Ru(dpp)RhCl(2)(TL')](3+) produce active bimetallic photocatalysts (TL = terminal ligand). The system with TL,TL' = Ph(2)phen photocatalytically reduces H(2)O to H(2) while TL,TL' = phen,bpy or bpy,(t)Bu(2)bpy do not.

Capacitor blocks for linear transformer driver stages.

PubMed

Kovalchuk, B M; Kharlov, A V; Kumpyak, E V; Smorudov, G V; Zherlitsyn, A A

2014-01-01

In the Linear Transformer Driver (LTD) technology, the low inductance energy storage components and switches are directly incorporated into the individual cavities (named stages) to generate a fast output voltage pulse, which is added along a vacuum coaxial line like in an inductive voltage adder. LTD stages with air insulation were recently developed, where air is used both as insulation in a primary side of the stages and as working gas in the LTD spark gap switches. A custom designed unit, referred to as a capacitor block, was developed for use as a main structural element of the transformer stages. The capacitor block incorporates two capacitors GA 35426 (40 nF, 100 kV) and multichannel multigap gas switch. Several modifications of the capacitor blocks were developed and tested on the life time and self breakdown probability. Blocks were tested both as separate units and in an assembly of capacitive module, consisting of five capacitor blocks. This paper presents detailed design of capacitor blocks, description of operation regimes, numerical simulation of electric field in the switches, and test results.

Influence of pHo on calcium channel block by amlodipine, a charged dihydropyridine compound. Implications for location of the dihydropyridine receptor

PubMed Central

1989-01-01

We have investigated the modulation of L-type calcium channel currents in isolated ventricular cells by the dihydropyridine derivative amlodipine, a weak base with a pKa of 8.6. Under conditions that favor neutral drug molecules, amlodipine block resembles other, previously described, neutral dihydropyridine derivatives: block is more pronounced at depolarized voltages, repetitive pulsing is not needed to promote block, and recovery is complete at hyperpolarized voltages. When the drug is ionized, depolarized voltages still enhance block, however, the time course is slow and speeded by repetitive pulses that open channels. Recovery from block by ionized drug molecules is very slow and incomplete, but can be rapidly modified by changes in external hydrogen ion concentration. We conclude from these observations that the degree of ionization of the drug molecule can affect access to the dihydropyridine receptor and that external protons can interact with the drug-receptor complex even if channels are blocked and closed. These observations place limitations on the location of this receptor in the ventricular cell membrane. PMID:2549176

Design and evaluation of a fault-tolerant multiprocessor using hardware recovery blocks

NASA Technical Reports Server (NTRS)

Lee, Y. H.; Shin, K. G.

1982-01-01

A fault-tolerant multiprocessor with a rollback recovery mechanism is discussed. The rollback mechanism is based on the hardware recovery block which is a hardware equivalent to the software recovery block. The hardware recovery block is constructed by consecutive state-save operations and several state-save units in every processor and memory module. When a fault is detected, the multiprocessor reconfigures itself to replace the faulty component and then the process originally assigned to the faulty component retreats to one of the previously saved states in order to resume fault-free execution. A mathematical model is proposed to calculate both the coverage of multi-step rollback recovery and the risk of restart. A performance evaluation in terms of task execution time is also presented.

Guidance system operations plan for manned cm earth orbital and lunar missions using program Colossus 3. Section 2: Data links

NASA Technical Reports Server (NTRS)

Hamilton, M. H.

1971-01-01

The data links for use with the guidance system operations plan for manned command module earth orbital and lunar missions using program Colossus 3 are presented. The subjects discussed are: (1) digital uplink to CMC, (2) command module contiguous block update, (3) CMC retrofire external data update, (4) CMC digital downlink, and (5) CMC entry update.

Modulation of Mu Suppression in Children with Autism Spectrum Disorders in Response to Familiar or Unfamiliar Stimuli: The Mirror Neuron Hypothesis

ERIC Educational Resources Information Center

Oberman, Lindsay M.; Ramachandran, Vilayanur S.; Pineda, Jaime A.

2008-01-01

In an early description of the mu rhythm, Gastaut and Bert [Gastaut, H. J., & Bert, J. (1954). EEG changes during cinematographic presentation. "Clinical Neurophysiology", 6, 433-444] noted that it was blocked when an individual identified himself with an active person on the screen, suggesting that it may be modulated by the degree to which the…

Analysis of Neural Systems Involved in Modulation of Memory Storage

DTIC Science & Technology

1990-01-01

modulating effects of oxotremorine and scopolomine (a cholinergic agonist and antagonist, respec- tively) are blocked by lesions of the ST (Introini-Collison...Introini-Collison, I.B., Arai, Y. and McGaugh, J.L. Stria terminalis lesions attenuate the effects of posttraining oxotremorine and atropine on reten- tion...McGaugh, J.L. and Izquierdo, I. Amnesia induced by short-term treatment with ethanol: Attenuation by pre-test oxotremorine . Pharmacol- ogy

Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.

PubMed

Hojo, Yasushi; Munetomo, Arisa; Mukai, Hideo; Ikeda, Muneki; Sato, Rei; Hatanaka, Yusuke; Murakami, Gen; Komatsuzaki, Yoshimasa; Kimoto, Tetsuya; Kawato, Suguru

2015-08-01

This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. Copyright © 2015 Elsevier Inc. All rights reserved.

Logarithmic M(2,p) minimal models, their logarithmic couplings, and duality

NASA Astrophysics Data System (ADS)

Mathieu, Pierre; Ridout, David

2008-10-01

A natural construction of the logarithmic extension of the M(2,p) (chiral) minimal models is presented, which generalises our previous model of percolation ( p=3). Its key aspect is the replacement of the minimal model irreducible modules by reducible ones obtained by requiring that only one of the two principal singular vectors of each module vanish. The resulting theory is then constructed systematically by repeatedly fusing these building block representations. This generates indecomposable representations of the type which signify the presence of logarithmic partner fields in the theory. The basic data characterising these indecomposable modules, the logarithmic couplings, are computed for many special cases and given a new structural interpretation. Quite remarkably, a number of them are presented in closed analytic form (for general p). These are the prime examples of "gauge-invariant" data—quantities independent of the ambiguities present in defining the logarithmic partner fields. Finally, mere global conformal invariance is shown to enforce strong constraints on the allowed spectrum: It is not possible to include modules other than those generated by the fusion of the model's building blocks. This generalises the statement that there cannot exist two effective central charges in a c=0 model. It also suggests the existence of a second "dual" logarithmic theory for each p. Such dual models are briefly discussed.

Peripheral infrastructure vectors and an extended set of plant parts for the Modular Cloning system

PubMed Central

Kretschmer, Carola; Gruetzner, Ramona; Löfke, Christian; Dagdas, Yasin; Bürstenbinder, Katharina; Marillonnet, Sylvestre

2018-01-01

Standardized DNA assembly strategies facilitate the generation of multigene constructs from collections of building blocks in plant synthetic biology. A common syntax for hierarchical DNA assembly following the Golden Gate principle employing Type IIs restriction endonucleases was recently developed, and underlies the Modular Cloning and GoldenBraid systems. In these systems, transcriptional units and/or multigene constructs are assembled from libraries of standardized building blocks, also referred to as phytobricks, in several hierarchical levels and by iterative Golden Gate reactions. Here, a toolkit containing further modules for the novel DNA assembly standards was developed. Intended for use with Modular Cloning, most modules are also compatible with GoldenBraid. Firstly, a collection of approximately 80 additional phytobricks is provided, comprising e.g. modules for inducible expression systems, promoters or epitope tags. Furthermore, DNA modules were developed for connecting Modular Cloning and Gateway cloning, either for toggling between systems or for standardized Gateway destination vector assembly. Finally, first instances of a “peripheral infrastructure” around Modular Cloning are presented: While available toolkits are designed for the assembly of plant transformation constructs, vectors were created to also use coding sequence-containing phytobricks directly in yeast two hybrid interaction or bacterial infection assays. The presented material will further enhance versatility of hierarchical DNA assembly strategies. PMID:29847550

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

PubMed Central

Huber, Roland G.; Bond, Peter J.

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. PMID:29016650

Ultimate Osmosis Engineered by the Pore Geometry and Functionalization of Carbon Nanostructures

PubMed Central

Song, Zhigong; Xu, Zhiping

2015-01-01

Osmosis is the key process in establishing versatile functions of cellular systems and enabling clean-water harvesting technologies. Membranes with single-atom thickness not only hold great promises in approaching the ultimate limit of these functions, but also offer an ideal test-bed to explore the underlying physical mechanisms. In this work, we explore diffusive and osmotic transport of water and ions through carbon nanotube and porous graphene based membranes by performing molecular dynamics simulations. Our comparative study shows that the cylindrical confinement in carbon nanotubes offers much higher salt rejection at similar permeability in osmosis compared to porous graphene. Moreover, chemical functionalization of the pores modulates the membrane performance by its steric and electrostatic nature, especially at small-size pores due to the fact that the optimal transport is achieved by ordered water transport near pore edges. These findings lay the ground for the ultimate design of forward osmosis membranes with optimized performance trade-off, given the capability of nano-engineering nanostructures by their geometry and chemistry. PMID:26037602

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

PubMed

Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

The impact of physiological crowding on the diffusivity of membrane bound proteins.

PubMed

Houser, Justin R; Busch, David J; Bell, David R; Li, Brian; Ren, Pengyu; Stachowiak, Jeanne C

2016-02-21

Diffusion of transmembrane and peripheral membrane-bound proteins within the crowded cellular membrane environment is essential to diverse biological processes including cellular signaling, endocytosis, and motility. Nonetheless we presently lack a detailed understanding of the influence of physiological levels of crowding on membrane protein diffusion. Utilizing quantitative in vitro measurements, here we demonstrate that the diffusivities of membrane bound proteins follow a single linearly decreasing trend with increasing membrane coverage by proteins. This trend holds for homogenous protein populations across a range of protein sizes and for heterogeneous mixtures of proteins of different sizes, such that protein diffusivity is controlled by the total coverage of the surrounding membrane. These results demonstrate that steric exclusion within the crowded membrane environment can fundamentally limit the diffusive rate of proteins, regardless of their size. In cells this "speed limit" could be modulated by changes in local membrane coverage, providing a mechanism for tuning the rate of molecular interaction and assembly.

Crystal Facets Make a Profound Difference in Polyoxometalate-Containing Metal-Organic Frameworks as Catalysts for Biodiesel Production.

PubMed

Liu, Yiwei; Liu, Shumei; He, Danfeng; Li, Ning; Ji, Yujuan; Zheng, Zhiping; Luo, Fang; Liu, Shuxia; Shi, Zhan; Hu, Changwen

2015-10-07

An inherent challenge in using metal-organic frameworks (MOFs) for catalysis is how to access the catalytic sites generally confined inside the porous structure, in particular for substrates larger than the pores. We present here a promising solution to bypass this roadblock by modulating the facets of a crystalline MOF NENU-3a to enhance the facet exposure of the catalytic sites and the adsorption of substrates. Specifically, by transforming it with encapsulated catalysis-responsible polyoxometalate from octahedron characterized entirely by {111} facets to cube with only {100} facets, much enhanced catalytic activities were observed, especially for sterically demanding substrates that are otherwise hard to diffuse into the pores. Crystallographic analysis and adsorption/desorption experiments collectively established the critical effects of morphological control on the enhanced catalysis. The cubic crystals were then applied for biodiesel production, reaching more than 90% conversion of fatty acids (C12-C22) in comparison to <22% using octahedral crystals.

One-step synthesis of layered yttrium hydroxides in immiscible liquid-liquid systems: Intercalation of sterically-bulky hydrophobic organic anions and doping of europium ions

NASA Astrophysics Data System (ADS)

Watanabe, Mebae; Fujihara, Shinobu

2014-02-01

Inorganic-organic layered rare-earth compounds were synthesized on the basis of a biphasic liquid-liquid system in one pot. Layered yttrium hydroxides (LYHs) were chosen as a host material for the intercalation of hydrophobic organic guest anions such as benzoate, sebacate, or laurate. In a typical synthesis, an organic phase dissolving carboxylic acid was placed in contact with an equal amount of an aqueous phase dissolving yttrium nitrate n-hydrate and urea. At elevated temperatures up to 80 °C, urea was hydrolyzed to release hydroxyl anions which were used to form yttrium hydroxide layers. LYHs were then precipitated with the intercalation of carboxylate anions delivered from the organic phase under the distribution law. The structure and the morphology of the LYHs could be modulated by the intercalated anions. Doped with Eu3+ ions, the LYHs exhibited red photoluminescence which was enhanced by the intercalated anions due to the antenna effect.

A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity

NASA Astrophysics Data System (ADS)

Lee, Yen-Chun; Patil, Sumersing; Golz, Christopher; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2017-02-01

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

Clues for discovering a new biological function of Vitreoscilla hemoglobin in organisms: potential sulfide receptor and storage.

PubMed

Wang, Dandan; Liu, Li; Wang, Hui; Xu, Haoran; Chen, Lei; Ma, Li; Li, Zhengqiang

2016-04-01

The interaction between H2 S and Vitreoscilla hemoglobin (VHb) has been studied by UV-Vis and Resonance Raman spectroscopes to confirm the binding between the ligand and the protein. Kinetic constants, kon = 1.2 × 10(5) m(-1) ·s(-1) and koff = 2.5 × 10(-4) ·s(-1) , have been determined and compared with those for mammalian hemoglobins. Density Functional Theory study supports the binding of H2 S by modeling the configurations of HOMO dispersions. We hypothesized that VHb is involved in H2 S reception and storage. Different from Lucina pectinata HbI, a typical H2 S-binding hemoglobin, VHb, exhibits unusual properties on H2 S reactivity such as steric constraints playing an important role in modulating H2 S entry. A distinct mechanism of VHb interaction with H2 S is supported by studies of variant forms of VHb. © 2016 Federation of European Biochemical Societies.

Structural insights into the intertwined dimer of fyn SH2.

PubMed

Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

2015-12-01

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

Effect of osmolytes on the thermal stability of proteins: replica exchange simulations of Trp-cage in urea and betaine solutions.

PubMed

Adamczak, Beata; Kogut, Mateusz; Czub, Jacek

2018-04-25

Although osmolytes are known to modulate the folding equilibrium, the molecular mechanism of their effect on thermal denaturation of proteins is still poorly understood. Here, we simulated the thermal denaturation of a small model protein (Trp-cage) in the presence of denaturing (urea) and stabilizing (betaine) osmolytes, using the all-atom replica exchange molecular dynamics simulations. We found that urea destabilizes Trp-cage by enthalpically-driven association with the protein, acting synergistically with temperature to induce unfolding. In contrast, betaine is sterically excluded from the protein surface thereby exerting entropic depletion forces that contribute to the stabilization of the native state. In fact, we find that while at low temperatures betaine slightly increases the folding free energy of Trp-cage by promoting another near-native conformation, it protects the protein against temperature-induced denaturation. This, in turn, can be attributed to enhanced exclusion of betaine at higher temperatures that arises from less attractive interactions with the protein surface.

Antigenic and functional characterization of p57 produced by Renibacterium salmoninarum

USGS Publications Warehouse

Weins, G.; Chien, M.S.; Winton, J.R.; Kaatari, S.L.

1999-01-01

Renibacterium salmoninarum, the causative agent of bacterial kidney disease, produces large quantities of a 57-58 kDa protein (p57) during growth in broth culture and during infection of salmonid fish. Biological activities of secreted p57 include agglutination of salrnonid leucocytes and rabbit erythrocytes. We define the location of epitopes on p57 recognized by agglutination-blocking monoclonal antibodies (MAbs) 4Cl1, 4H8 and 4D3, and demonstrate that the majority of secreted p57 is a nlonomer that retains salrnonid leucocyte agglutinat~ng activity. The 3 MAbs bound a recombinant, amino-terminal fragment of p57 (211 aa) but not a carboxy-terminal fragment (315 aa) demonstrating that the neutralizing epitopes are located within the amino-terminal portion of p57. When combinations of the MAbs were used in an antigen capture ELISA. the epitopes recognized by the 3 MAbs were shown to be sterically separate. However, when the same MAb was used as both the coating and detection MAb, binding of the biotinylated detection MAb was not observed. These data indicate that the epitopes recognized by the 3 agglutination-blocking antibodies are functionally available only once per molecule and that native p57 exists as a monomer Similar ELISA results were obtained when kidney tissues from 3 naturally infected chinook salmon were assayed. Finally, a p57 monomer was purified using anion exchange and size exclusion chromatography that retained in vitro agglutinating activity. A model in which p57 is released from R. salmoninarum as a biologically active monomer during infection of salmonid fish is proposed.

Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

PubMed

Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

2016-03-15

Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and mechanisms of antifouling materials for surface plasmon resonance sensors.

PubMed

Liu, Boshi; Liu, Xia; Shi, Se; Huang, Renliang; Su, Rongxin; Qi, Wei; He, Zhimin

2016-08-01

Surface plasmon resonance (SPR) biosensors have many possible applications, but are limited by sensor chip surface fouling, which blocks immobilization and specific binding by the recognizer elements. Therefore, there is a pressing need for the development of antifouling surfaces. In this paper, the mechanisms of antifouling materials were firstly discussed, including both theories (hydration and steric hindrance) and factors influencing antifouling effects (molecular structures and self-assembled monolayer (SAM) architectures, surface charges, molecular hydrophilicity, and grafting thickness and density). Then, the most recent advances in antifouling materials applied on SPR biosensors were systematically reviewed, together with the grafting strategies, antifouling capacity, as well as their merits and demerits. These materials included, but not limited to, zwitterionic compounds, polyethylene glycol-based, and polysaccharide-based materials. Finally, the prospective research directions in the development of SPR antifouling materials were discussed. Surface plasmon resonance (SPR) is a powerful tool in monitoring biomolecular interactions. The principle of SPR biosensors is the conversion of refractive index change caused by molecular binding into resonant spectral shifts. However, the fouling on the surface of SPR gold chips is ubiquitous and troublesome. It limits the application of SPR biosensors by blocking recognition element immobilization and specific binding. Hence, we write this paper to review the antifouling mechanisms and the recent advances of the design of antifouling materials that can improve the accuracy and sensitivity of SPR biosensors. To our knowledge, this is the first review focusing on the antifouling materials that were applied or had potential to be applied on SPR biosensors. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Accelerated Disassembly of IgE:Receptor Complexes by a Disruptive Macromolecular Inhibitor

PubMed Central

Kim, Beomkyu; Eggel, Alexander; Tarchevskaya, Svetlana S.; Vogel, Monique; Prinz, Heino; Jardetzky, Theodore S.

2012-01-01

IgE antibodies bind the high affinity IgE Fc receptor (FcεRI), found primarily on mast cells and basophils, and trigger inflammatory cascades of the allergic response1,2. Inhibitors of IgE:FcεRI binding have been identified and an anti-IgE therapeutic antibody (omalizumab) is used to treat severe allergic asthma3,4. However, preformed IgE:FcεRI complexes that prime cells prior to allergen exposure dissociate extremely slowly5 and cannot be disrupted by strictly competitive inhibitors. IgE-Fc conformational flexibility indicated that inhibition could be mediated by allosteric or other non-classical mechanisms6–8. Here we demonstrate that an engineered protein inhibitor, DARPin E2_799–11, acts through a non-classical inhibition mechanism, not only blocking IgE:FcεRI interactions, but actively stimulating the dissociation of preformed ligand-receptor complexes. The structure of the E2_79:IgE-Fc3-4 complex predicts the presence of two non-equivalent E2_79 sites in the asymmetric IgE:FcεRI complex, with Site 1 distant from the receptor and Site 2 exhibiting partial steric overlap. While the structure is suggestive of an allosteric inhibition mechanism, mutational studies and quantitative kinetic modeling indicate that E2_79 acts through a facilitated dissociation mechanism at Site 2 alone. These results demonstrate that high affinity IgE:FcεRI complexes can be actively dissociated to block the allergic response and suggest that protein:protein complexes may be more generally amenable to active disruption by macromolecular inhibitors. PMID:23103871

Mapping the Complement Factor H-Related Protein 1 (CFHR1):C3b/C3d Interactions

PubMed Central

Laskowski, Jennifer; Thurman, Joshua M.; Hageman, Gregory S.; Holers, V. Michael

2016-01-01

Complement factor H-related protein 1 (CFHR1) is a complement regulator which has been reported to regulate complement by blocking C5 convertase activity and interfering with C5b surface association. CFHR1 also competes with complement factor H (CFH) for binding to C3b, and may act as an antagonist of CFH-directed regulation on cell surfaces. We have employed site-directed mutagenesis in conjunction with ELISA-based and functional assays to isolate the binding interaction that CFHR1 undertakes with complement components C3b and C3d to a single shared interface. The C3b/C3d:CFHR1 interface is identical to that which occurs between the two C-terminal domains (SCR19-20) of CFH and C3b. Moreover, we have been able to corroborate that dimerization of CFHR1 is necessary for this molecule to bind effectively to C3b and C3d, or compete with CFH. Finally, we have established that CFHR1 competes with complement factor H-like protein 1 (CFHL-1) for binding to C3b. CFHL-1 is a CFH gene splice variant, which is almost identical to the N-terminal 7 domains of CFH (SCR1-7). CFHR1, therefore, not only competes with the C-terminus of CFH for binding to C3b, but also sterically blocks the interaction that the N-terminus of CFH undertakes with C3b, and which is required for CFH-regulation. PMID:27814381

Time-resolved single-photon detection module based on silicon photomultiplier: A novel building block for time-correlated measurement systems

NASA Astrophysics Data System (ADS)

Martinenghi, E.; Di Sieno, L.; Contini, D.; Sanzaro, M.; Pifferi, A.; Dalla Mora, A.

2016-07-01

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm2 together with the suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics systems).

The Solar Constant, Climate, and Some Tests of the Storage Hypothesis

NASA Technical Reports Server (NTRS)

Eddy, J. A.

1984-01-01

Activity related modulation of the solar constant can have practical consequences for climate only if storage is involved, as opposed to a detailed balance between sunspot blocking and facular reemission. Four empirical tests are considered that might distinguish between these opposing interpretations: monochromatic measurements of positive and negative flux; comparison of modelled and measured irradiance variations; the interpretation of secular trends in irradiance data; and the direct test of an anticipated signal in climate records of surface air temperature. The yet unanswered question of the role of faculae as possible reemitters of blocked radiation precludes a definitive answer, although other tests suggest their role to be minor, and that storage and an 11 year modulation is implicated. A crucial test is the behavior of the secular trend in irradiance in the declining years of the present activity cycle.

Microscopy imaging system and method employing stimulated raman spectroscopy as a contrast mechanism

DOEpatents

Xie, Xiaoliang Sunney [Lexington, MA; Freudiger, Christian [Boston, MA; Min, Wei [Cambridge, MA

2011-09-27

A microscopy imaging system includes a first light source for providing a first train of pulses at a first center optical frequency .omega..sub.1, a second light source for providing a second train of pulses at a second center optical frequency .omega..sub.2, a modulator system, an optical detector, and a processor. The modulator system is for modulating a beam property of the second train of pulses at a modulation frequency f of at least 100 kHz. The optical detector is for detecting an integrated intensity of substantially all optical frequency components of the first train of pulses from the common focal volume by blocking the second train of pulses being modulated. The processor is for detecting, a modulation at the modulation frequency f, of the integrated intensity of the optical frequency components of the first train of pulses to provide a pixel of an image for the microscopy imaging system.

Letter of intent for KM3NeT 2.0

NASA Astrophysics Data System (ADS)

Adrián-Martínez, S.; Ageron, M.; Aharonian, F.; Aiello, S.; Albert, A.; Ameli, F.; Anassontzis, E.; Andre, M.; Androulakis, G.; Anghinolfi, M.; Anton, G.; Ardid, M.; Avgitas, T.; Barbarino, G.; Barbarito, E.; Baret, B.; Barrios-Martí, J.; Belhorma, B.; Belias, A.; Berbee, E.; van den Berg, A.; Bertin, V.; Beurthey, S.; van Beveren, V.; Beverini, N.; Biagi, S.; Biagioni, A.; Billault, M.; Bondì, M.; Bormuth, R.; Bouhadef, B.; Bourlis, G.; Bourret, S.; Boutonnet, C.; Bouwhuis, M.; Bozza, C.; Bruijn, R.; Brunner, J.; Buis, E.; Busto, J.; Cacopardo, G.; Caillat, L.; Calamai, M.; Calvo, D.; Capone, A.; Caramete, L.; Cecchini, S.; Celli, S.; Champion, C.; Cherkaoui El Moursli, R.; Cherubini, S.; Chiarusi, T.; Circella, M.; Classen, L.; Cocimano, R.; Coelho, J. A. B.; Coleiro, A.; Colonges, S.; Coniglione, R.; Cordelli, M.; Cosquer, A.; Coyle, P.; Creusot, A.; Cuttone, G.; D'Amico, A.; De Bonis, G.; De Rosa, G.; De Sio, C.; Di Capua, F.; Di Palma, I.; Díaz García, A. F.; Distefano, C.; Donzaud, C.; Dornic, D.; Dorosti-Hasankiadeh, Q.; Drakopoulou, E.; Drouhin, D.; Drury, L.; Durocher, M.; Eberl, T.; Eichie, S.; van Eijk, D.; El Bojaddaini, I.; El Khayati, N.; Elsaesser, D.; Enzenhöfer, A.; Fassi, F.; Favali, P.; Fermani, P.; Ferrara, G.; Filippidis, C.; Frascadore, G.; Fusco, L. A.; Gal, T.; Galatà, S.; Garufi, F.; Gay, P.; Gebyehu, M.; Giordano, V.; Gizani, N.; Gracia, R.; Graf, K.; Grégoire, T.; Grella, G.; Habel, R.; Hallmann, S.; van Haren, H.; Harissopulos, S.; Heid, T.; Heijboer, A.; Heine, E.; Henry, S.; Hernández-Rey, J. J.; Hevinga, M.; Hofestädt, J.; Hugon, C. M. F.; Illuminati, G.; James, C. W.; Jansweijer, P.; Jongen, M.; de Jong, M.; Kadler, M.; Kalekin, O.; Kappes, A.; Katz, U. F.; Keller, P.; Kieft, G.; Kießling, D.; Koffeman, E. N.; Kooijman, P.; Kouchner, A.; Kulikovskiy, V.; Lahmann, R.; Lamare, P.; Leisos, A.; Leonora, E.; Clark, M. Lindsey; Liolios, A.; Llorens Alvarez, C. D.; Lo Presti, D.; Löhner, H.; Lonardo, A.; Lotze, M.; Loucatos, S.; Maccioni, E.; Mannheim, K.; Margiotta, A.; Marinelli, A.; Mariş, O.; Markou, C.; Martínez-Mora, J. A.; Martini, A.; Mele, R.; Melis, K. W.; Michael, T.; Migliozzi, P.; Migneco, E.; Mijakowski, P.; Miraglia, A.; Mollo, C. M.; Mongelli, M.; Morganti, M.; Moussa, A.; Musico, P.; Musumeci, M.; Navas, S.; Nicolau, C. A.; Olcina, I.; Olivetto, C.; Orlando, A.; Papaikonomou, A.; Papaleo, R.; Păvălaş, G. E.; Peek, H.; Pellegrino, C.; Perrina, C.; Pfutzner, M.; Piattelli, P.; Pikounis, K.; Poma, G. E.; Popa, V.; Pradier, T.; Pratolongo, F.; Pühlhofer, G.; Pulvirenti, S.; Quinn, L.; Racca, C.; Raffaelli, F.; Randazzo, N.; Rapidis, P.; Razis, P.; Real, D.; Resvanis, L.; Reubelt, J.; Riccobene, G.; Rossi, C.; Rovelli, A.; Saldaña, M.; Salvadori, I.; Samtleben, D. F. E.; Sánchez García, A.; Sánchez Losa, A.; Sanguineti, M.; Santangelo, A.; Santonocito, D.; Sapienza, P.; Schimmel, F.; Schmelling, J.; Sciacca, V.; Sedita, M.; Seitz, T.; Sgura, I.; Simeone, F.; Siotis, I.; Sipala, V.; Spisso, B.; Spurio, M.; Stavropoulos, G.; Steijger, J.; Stellacci, S. M.; Stransky, D.; Taiuti, M.; Tayalati, Y.; Tézier, D.; Theraube, S.; Thompson, L.; Timmer, P.; Tönnis, C.; Trasatti, L.; Trovato, A.; Tsirigotis, A.; Tzamarias, S.; Tzamariudaki, E.; Vallage, B.; Van Elewyck, V.; Vermeulen, J.; Vicini, P.; Viola, S.; Vivolo, D.; Volkert, M.; Voulgaris, G.; Wiggers, L.; Wilms, J.; de Wolf, E.; Zachariadou, K.; Zornoza, J. D.; Zúñiga, J.

2016-08-01

The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary field of view, including the galactic plane. One building block will be densely configured to precisely measure atmospheric neutrino oscillations.

The pH dependence of cocaine interaction with cardiac sodium channels.

PubMed

Crumb, W J; Clarkson, C W

1995-09-01

Previous in vitro and in vivo studies have provided evidence implicating cocaine block of cardiac sodium channels as a putative mechanism for cocaine-induced arrhythmias and sudden death. Cocaine also has been shown to cause seizures which can result in respiratory and/or metabolic acidosis. In this study we investigated how changes in both internal pH (pHi) and external pH (pHo) over the range of 6.6 to 9.2 modify the sodium channel blocking properties of cocaine in isolated guinea pig ventricular myocytes by using the whole-cell variant of the patch clamp technique. Use-dependent block produced by a train of 1-sec pulses to -20 mV was not affected by changes in pHi, but both the amplitude and time constant for approaching steady-state block were significantly affected by changes in pHo. Characterization of the time course of cocaine binding during a depolarizing pulse indicated that the kinetics of drug interaction with inactivated channels were independent of pHi, but were significantly affected by changes in pHo. The rate of recovery from channel block at a holding potential of -140 mV also was independent of pHi, but strongly dependent on pHo, with the unblocking time constant decreasing exponentially as pHo was increased. The results of this study indicate that cocaine's effect on cardiac sodium channels can be modulated significantly by changes in pHo, and provide further support for previously poorly tested assumptions of the modulated receptor hypothesis.

The influence of anatase-rutile mixed phase and ZnO blocking layer on dye-sensitized solar cells based on TiO2nanofiberphotoanodes

PubMed Central

2013-01-01

High performance is expected in dye-sensitized solar cells (DSSCs) that utilize one-dimensional (1-D) TiO2 nanostructures owing to the effective electron transport. However, due to the low dye adsorption, mainly because of their smooth surfaces, 1-D TiO2 DSSCs show relatively lower efficiencies than nanoparticle-based ones. Herein, we demonstrate a very simple approach using thick TiO2 electrospun nanofiber films as photoanodes to obtain high conversion efficiency. To improve the performance of the DSCCs, anatase-rutile mixed-phase TiO2 nanofibers are achieved by increasing sintering temperature above 500°C, and very thin ZnO films are deposited by atomic layer deposition (ALD) method as blocking layers. With approximately 40-μm-thick mixed-phase (approximately 15.6 wt.% rutile) TiO2 nanofiber as photoanode and 15-nm-thick compact ZnO film as a blocking layer in DSSC, the photoelectric conversion efficiency and short-circuit current are measured as 8.01% and 17.3 mA cm−2, respectively. Intensity-modulated photocurrent spectroscopy and intensity-modulated photovoltage spectroscopy measurements reveal that extremely large electron diffusion length is the key point to support the usage of thick TiO2 nanofibers as photoanodes with very thin ZnO blocking layers to obtain high photocurrents and high conversion efficiencies. PMID:23286741

Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions

PubMed Central

Fineberg, Jeffrey D.; Szanto, Tibor G.; Panyi, Gyorgy; Covarrubias, Manuel

2016-01-01

Voltage-gated K+ (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate. PMID:27502553

The all-optical modulator in dielectric-loaded waveguide with graphene-silicon heterojunction structure

NASA Astrophysics Data System (ADS)

Sun, Feiying; Xia, Liangping; Nie, Changbin; Shen, Jun; Zou, Yixuan; Cheng, Guiyu; Wu, Hao; Zhang, Yong; Wei, Dongshan; Yin, Shaoyun; Du, Chunlei

2018-04-01

All-optical modulators based on graphene show great promise for on-chip optical interconnects. However, the modulation performance of all-optical modulators is usually based on the interaction between graphene and the fiber, limiting their potential in high integration. Based on this point, an all-optical modulator in a dielectric-loaded waveguide (DLW) with a graphene-silicon heterojunction structure (GSH) is proposed. The DLW raises the waveguide mode, which provides a strong light-graphene interaction. Sufficient tuning of the graphene Fermi energy beyond the Pauli blocking effect is obtained with the presented GSH structure. Under the modulation light with a wavelength of 532 nm and a power of 60 mW, a modulation efficiency of 0.0275 dB µm-1 is achieved for light with a communication wavelength of 1.55 µm in the experiment. This modulator has the advantage of having a compact footprint, which may make it a candidate for achieving a highly integrated all-optical modulator.

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

Yagi, Yukihiro; Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567; Nakamura, Yuji

Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) ormore » siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by siponimod. • I{sub Kr} inhibition may play a key role in the fingolimod-induced QT prolongation.« less

Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

NASA Astrophysics Data System (ADS)

Storto, Andrea; Masina, Simona; Balmaseda, Magdalena; Guinehut, Stéphanie; Xue, Yan; Szekely, Tanguy; Fukumori, Ichiro; Forget, Gael; Chang, You-Soon; Good, Simon A.; Köhl, Armin; Vernieres, Guillaume; Ferry, Nicolas; Peterson, K. Andrew; Behringer, David; Ishii, Masayoshi; Masuda, Shuhei; Fujii, Yosuke; Toyoda, Takahiro; Yin, Yonghong; Valdivieso, Maria; Barnier, Bernard; Boyer, Tim; Lee, Tony; Gourrion, Jérome; Wang, Ou; Heimback, Patrick; Rosati, Anthony; Kovach, Robin; Hernandez, Fabrice; Martin, Matthew J.; Kamachi, Masafumi; Kuragano, Tsurane; Mogensen, Kristian; Alves, Oscar; Haines, Keith; Wang, Xiaochun

2017-08-01

Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003-2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993-2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread.

Structural plasticity mediates distinct GAP-dependent GTP hydrolysis mechanisms in Rab33 and Rab5.

PubMed

Majumdar, Soneya; Acharya, Abhishek; Prakash, Balaji

2017-12-01

The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic glutamine provided in cis by the GTPase and an arginine supplied in trans by a GTPase activating protein (GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis. As the cis-Gln encounters a steric clash, the Rab GTPases employ the so-called dual finger mechanism where the interacting GAP supplies a trans-Gln for catalysis. Using experimental and computational methods, we demonstrate how the cis-Gln of Rab33 overcomes the steric clash when it is stabilized by a residue in the vicinity. In effect, this demonstrates how both cis-Gln- and trans-Gln-mediated mechanisms could operate in the same GTPase in different contexts, i.e. depending on the GAP that regulates its action. Interestingly, in the case of Rab5, which possesses a higher intrinsic GTP hydrolysis rate, a similar stabilization of the cis-Gln appears to overcome the steric clash. Taken together with the mechanisms seen for Rab1, it is evident that the observed variations in Rab and their GAP partners allow structural plasticity, or in other words, the choice of different catalytic mechanisms. © 2017 Federation of European Biochemical Societies.

pH controlled gating of toxic protein pores by dendrimers

NASA Astrophysics Data System (ADS)

Mandal, Taraknath; Kanchi, Subbarao; Ayappa, K. G.; Maiti, Prabal K.

2016-06-01

Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections.Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02963a

Chromatin loops as allosteric modulators of enhancer-promoter interactions.

PubMed

Doyle, Boryana; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A

2014-10-01

The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. Recent Chromosome Conformation Capture (3C) studies show that enhancers and promoters are embedded in a complex network of looping interactions. Here we use a polymer model of chromatin fiber to investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence their contact frequency. Our equilibrium polymer simulations show that a chromatin loop, formed by elements flanking either an enhancer or a promoter, suppresses enhancer-promoter interactions, working as an insulator. A loop formed by elements located in the region between an enhancer and a promoter, on the contrary, facilitates their interactions. We find that different mechanisms underlie insulation and facilitation; insulation occurs due to steric exclusion by the loop, and is a global effect, while facilitation occurs due to an effective shortening of the enhancer-promoter genomic distance, and is a local effect. Consistently, we find that these effects manifest quite differently for in silico 3C and microscopy. Our results show that looping interactions that do not directly involve an enhancer-promoter pair can nevertheless significantly modulate their interactions. This phenomenon is analogous to allosteric regulation in proteins, where a conformational change triggered by binding of a regulatory molecule to one site affects the state of another site.

Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry.

PubMed

Meyer, Nicole Andrea; Root, Katharina; Zenobi, Renato; Vidal-de-Miguel, Guillermo

2016-02-16

The potential of a Transversal Modulation Ion Mobility Spectrometry (TMIMS) instrument for protein analysis applications has been evaluated. The Collision Cross Section (CCS) of cytochrome c measured with the TMIMS is in agreement with values reported in the literature. Additionally, it enables tandem IMS-IMS prefiltration in dry gas and in vapor doped gas. The chemical specificity of the different dopants enables interesting studies on the structure of proteins as CCS changed strongly depending on the specific dopant. Hexane produced an unexpectedly high CCS shift, which can be utilized to evaluate the exposure of hydrophobic parts of the protein. Alcohols produced higher shifts with a dual behavior: an increase in CCS due to vapor uptake at specific absorption sites, followed by a linear shift typical for unspecific and unstable vapor uptake. The molten globule +8 shows a very specific transition. Initially, its CCS follows the trend of the compact folded states, and then it rapidly increases to the levels of the unfolded states. This strong variation suggests that the +8 charge state undergoes a dopant-induced conformational change. Interestingly, more sterically demanding alcohols seem to unfold the protein more effectively also in the gas phase. This study shows the capabilities of the TMIMS device for protein analysis and how tandem IMS-IMS with dopants could provide better understanding of the conformational changes of proteins.

Molecular modeling on structure-function analysis of human progesterone receptor modulators.

PubMed

Pal, Ria; Islam, Md Ataul; Hossain, Tabassum; Saha, Achintya

2011-01-01

Considering the significance of progesterone receptor (PR) modulators, the present study is explored to envisage the biophoric signals for binding to selective PR subtype-A using ligand-based quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus QSAR models (Training set (Tr): n(Tr)=100, R(2) (pred)=0.702; test set (Ts): n(Ts)=30, R(2) (pred)=0.705, R(2) (m)=0.635; validation set (Vs): n(Vs)=40, R(2) (pred)=0.715, R(2) (m)=0.680) suggest that molecular topology, atomic polarizability and electronegativity, atomic mass and van der Waals volume of the ligands have influence on the presence of functional atoms (F, Cl, N and O) and consequently contribute significant relations on ligand binding affinity. Receptor independent space modeling study (Tr: n(Tr)=26, Q(2)=0.927; Ts: n(Ts)=60, R(2) (pred)=0.613, R(2) (m)=0.545; Vs: n(Vs)=84, R(2) (pred)=0.611, R(2) (m)=0.507) indicates the importance of aromatic ring, hydrogen bond donor, molecular hydrophobicity and steric influence for receptor binding. The structure-function characterization is adjudged with the receptor-based docking study, explaining the significance of the mapped molecular attributes for ligand-receptor interaction in the catalytic cleft of PR-A.

Toward a low-cost, low-power, low-complexity DAC-based multilevel (M-ary QAM) coherent transmitter using compact linear optical field modulator

NASA Astrophysics Data System (ADS)

Dingel, Benjamin

2017-01-01

In this invited paper, we summarize the current developments in linear optical field modulators (LOFMs) for coherent multilevel optical transmitters. Our focus is the presentation of a new, novel LOFM design that provides beneficial and necessary features such as lowest hardware component counts, lowered insertion loss, smaller RF power consumption, smaller footprint, simple structure, and lowered cost. We refer to this modulator as called Double-Pass LOFM (DP-LOFM) that becomes the building block for high-performance, linear Dual-Polarization, In-Phase- Quadrature-Phase (DP-IQ) modulator. We analyze its performance in term of slope linearity, and present one of its unique feature -- a built-in compensation functionality that no other linear modulators possessed till now.

Impact of environmental hazards on internal soiling within concentrator photovoltaic (CPV) modules

NASA Astrophysics Data System (ADS)

Ellis, Sara

2014-09-01

Environmental conditions have a significant impact on internal soiling of a CPV system, which affects overall system performance and efficiency. The International Electrotechnical Commission (IEC) 62108, Section 10, standard includes accelerated testing such as temperature cycling, damp heat, and humidity freeze to assess a CPV module's ability to withstand environmental hazards that can compromise the typical 25-year lifetime. This paper discusses the IEC 60529 ingress protection (IP) test protocols and how they can be used to evaluate the performance of CPV modules to block water and particulate contaminants. Studies with GORE® Protective Vents installed in a CPV module and subjected to environmental hazard testing have shown increased reliability of the module over the lifetime of the system by protecting the seals from pressure differentials and keeping out contaminants.

Diode amplifier of modulated optical beam power

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

D'yachkov, N V; Bogatov, A P; Gushchik, T I

2014-11-30

Analytical relations are obtained between characteristics of modulated light at the output and input of an optical diode power amplifier operating in the highly saturated gain regime. It is shown that a diode amplifier may act as an amplitude-to-phase modulation converter with a rather large bandwidth (∼10 GHz). The low sensitivity of the output power of the amplifier to the input beam power and its high energy efficiency allow it to be used as a building block of a high-power multielement laser system with coherent summation of a large number of optical beams. (lasers)

Molecular Action of a Potential Tumor Suppression in Mammary Carcinogenesis

DTIC Science & Technology

2006-05-01

translocation in MDA-MB231 cells, as shown in Fig. 5D , indicating that Tid1 inhibits FVII -induced IL-8 production and cell migration by blocking NF-nB...tissue factor - FVIIa pathway modulates the migratory potential of cancer cells through IL-8 production (7). As Tid1 blocks the IL-8 production of...Introduction: ErbB family of growth factor receptors (ErbB1-4) are critically involved in the derivation of certain mammary cancers [1-3]. Among them

DMD-based implementation of patterned optical filter arrays for compressive spectral imaging.

PubMed

Rueda, Hoover; Arguello, Henry; Arce, Gonzalo R

2015-01-01

Compressive spectral imaging (CSI) captures multispectral imagery using fewer measurements than those required by traditional Shannon-Nyquist theory-based sensing procedures. CSI systems acquire coded and dispersed random projections of the scene rather than direct measurements of the voxels. To date, the coding procedure in CSI has been realized through the use of block-unblock coded apertures (CAs), commonly implemented as chrome-on-quartz photomasks. These apertures block or permit us to pass the entire spectrum from the scene at given spatial locations, thus modulating the spatial characteristics of the scene. This paper extends the framework of CSI by replacing the traditional block-unblock photomasks by patterned optical filter arrays, referred to as colored coded apertures (CCAs). These, in turn, allow the source to be modulated not only spatially but spectrally as well, entailing more powerful coding strategies. The proposed CCAs are synthesized through linear combinations of low-pass, high-pass, and bandpass filters, paired with binary pattern ensembles realized by a digital micromirror device. The optical forward model of the proposed CSI architecture is presented along with a proof-of-concept implementation, which achieves noticeable improvements in the quality of the reconstruction.

The Staphylococcus aureus Global Regulator MgrA Modulates Clumping and Virulence by Controlling Surface Protein Expression

PubMed Central

Crosby, Heidi A.; Schlievert, Patrick M.; Merriman, Joseph A.; King, Jessica M.; Salgado-Pabón, Wilmara; Horswill, Alexander R.

2016-01-01

Staphylococcus aureus is a human commensal and opportunistic pathogen that causes devastating infections in a wide range of locations within the body. One of the defining characteristics of S. aureus is its ability to form clumps in the presence of soluble fibrinogen, which likely has a protective benefit and facilitates adhesion to host tissue. We have previously shown that the ArlRS two-component regulatory system controls clumping, in part by repressing production of the large surface protein Ebh. In this work we show that ArlRS does not directly regulate Ebh, but instead ArlRS activates expression of the global regulator MgrA. Strains lacking mgrA fail to clump in the presence of fibrinogen, and clumping can be restored to an arlRS mutant by overexpressing either arlRS or mgrA, indicating that ArlRS and MgrA constitute a regulatory pathway. We used RNA-seq to show that MgrA represses ebh, as well as seven cell wall-associated proteins (SraP, Spa, FnbB, SasG, SasC, FmtB, and SdrD). EMSA analysis showed that MgrA directly represses expression of ebh and sraP. Clumping can be restored to an mgrA mutant by deleting the genes for Ebh, SraP and SasG, suggesting that increased expression of these proteins blocks clumping by steric hindrance. We show that mgrA mutants are less virulent in a rabbit model of endocarditis, and virulence can be partially restored by deleting the genes for the surface proteins ebh, sraP, and sasG. While mgrA mutants are unable to clump, they are known to have enhanced biofilm capacity. We demonstrate that this increase in biofilm formation is partially due to up-regulation of SasG, a surface protein known to promote intercellular interactions. These results confirm that ArlRS and MgrA constitute a regulatory cascade, and that they control expression of a number of genes important for virulence, including those for eight large surface proteins. PMID:27144398

Direct access to highly crystalline mesoporous nano TiO2 using sterically bulky organic acid templates

NASA Astrophysics Data System (ADS)

Bakre, Pratibha V.; Tilve, S. G.

2018-05-01

Sterically bulky monocarboxylic acid templates pivalic acid and phenoxyacetic acid are reported for the first time as organic templates in the sol-gel synthesis of TiO2. Mesoporous nanoparticulates of pure anatase phase and of well defined size were synthesized. The characterization of the materials prepared was done by various methods such as XRD, SEM, TEM, FTIR, UV-DRS, BET, etc. The prepared TiO2 samples were evaluated for the day light photodegradation of methylene blue by comparing with Degussa P25 and templates free synthesized TiO2 and were found to be more efficient.

Restricted amide rotation with steric hindrance induced multiple conformations

NASA Astrophysics Data System (ADS)

Krishnan, V. V.; Vazquez, Salvador; Maitra, Kalyani; Maitra, Santanu

2017-12-01

The Csbnd N bond character is dependent directly upon the resonance-contributor structure population driven by the delocalized nitrogen lone-pair of electrons. In the case of N, N-dibenzyl-ortho-toluamide (o-DBET), the molecule adopts subpopulations of conformers with distinct NMR spectral features, particularly at low temperatures. This conformational adaptation is unique to o-DBET, while the corresponding meta- and para- forms do not show such behavior. Variable-temperature (VT) NMR, two-dimensional exchange spectroscopy (EXSY), and qualitative molecular modeling studies are used to demonstrate how multiple competing interactions such as restricted amide rotation and steric hindrance effects can lead to versatile molecular adaptations in the solution state.

Steric hindrance effects in the use of heterocyclic azodyestuffs as spectrophotometric reagents.

PubMed

Geary, W J; Bottomley, F

1967-05-01

The heterocyclic azo dyestuffs 4-(n-methyl-2 -pyridylazo)-resorcinol (where n = 3', 4', 5', 6') have been prepared, and their possible use as spectrophotometric reagents investigated. The dyestuffs are shown to function analogously to the parent ligand 4-(2'-pyridylazo) resorcinol (PAR) in giving red complexes with the ions Co(2+), Ni(2+), Cu(2+), Zn(2+) and UO(2)(2+). Steric effects resulting from the position of the methyl group in the heterocyclic ring are shown to occur in relation both to the spectra of the dyestuffs themselves and to the sensitivity of their reactions with the metal ions.

A Novel Mechanism of Sugar Selection Utilized by a Human X-family DNA Polymerase†

PubMed Central

Brown, Jessica A.; Fiala, Kevin A.; Fowler, Jason D.; Sherrer, Shanen M.; Newmister, Sean A.; Dyum, Wade W.; Suo, Zucai

2009-01-01

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2′-hydroxyl group and the bulky side chain of an active site residue. Here, we demonstrated that human DNA polymerase λ used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2′-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such a steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2′ position. PMID:19900463

Total synthesis of (+/-)-taiwaniaquinol B via a domino intramolecular friedel-crafts acylation/carbonyl alpha-tert-alkylation reaction.

PubMed

Fillion, Eric; Fishlock, Dan

2005-09-28

The first synthesis of taiwaniaquinol B, a 6-nor-5(6-->7)abeoabietane-type diterpenoid exhibiting the uncommon fused 6-5-6 tricyclic carbon skeleton, was accomplished in 15 steps. A Lewis acid-promoted tandem intramolecular Friedel-Crafts/carbonyl alpha-tert-alkylation reaction was exploited as the core strategy for the synthesis of the sterically congested 1-indanone-containing tricyclic structure. This multiple carbon-carbon bond forming reaction exploits the unique reactivity of Meldrum's acid. The facile precursor synthesis makes this a useful methodology for the expedient modification and assembly of sterically congested 1-indanone-containing ring systems.

Evaluation of an active learning module to teach hazard and risk in Hazard Analysis and Critical Control Points (HACCP) classes.

PubMed

Oyarzabal, Omar A; Rowe, Ellen

2017-04-01

The terms hazard and risk are significant building blocks for the organization of risk-based food safety plans. Unfortunately, these terms are not clear for some personnel working in food manufacturing facilities. In addition, there are few examples of active learning modules for teaching adult participants the principles of hazard analysis and critical control points (HACCP). In this study, we evaluated the effectiveness of an active learning module to teach hazard and risk to participants of HACCP classes provided by the University of Vermont Extension in 2015 and 2016. This interactive module is comprised of a questionnaire; group playing of a dice game that we have previously introduced in the teaching of HACCP; the discussion of the terms hazard and risk; and a self-assessment questionnaire to evaluate the teaching of hazard and risk. From 71 adult participants that completed this module, 40 participants (56%) provided the most appropriate definition of hazard, 19 participants (27%) provided the most appropriate definition of risk, 14 participants (20%) provided the most appropriate definitions of both hazard and risk, and 23 participants (32%) did not provide an appropriate definition for hazard or risk. Self-assessment data showed an improvement in the understanding of these terms (P < 0.05). Thirty participants (42%) stated that the most valuable thing they learned with this interactive module was the difference between hazard and risk, and 40 participants (65%) responded that they did not attend similar presentations in the past. The fact that less than one third of the participants answered properly to the definitions of hazard and risk at baseline is not surprising. However, these results highlight the need for the incorporation of modules to discuss these important food safety terms and include more active learning modules to teach food safety classes. This study suggests that active learning helps food personnel better understand important food safety terms that serve as building blocks for the understanding of more complex food safety topics.

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

Zeno, Wade F.; Johnson, Kaitlin E.; Sasaki, Darryl Y.

We use fluorescence microscopy to examine the dynamics of the crowding-induced mixing transition of liquid ordered (L o)–liquid disordered (L d) phase separated lipid bilayers when the following particles of increasing size bind to either the L o or L d phase: Ubiquitin, green fluorescent protein (GFP), and nanolipoprotein particles (NLPs) of two diameters. These proteinaceous particles contained histidine-tags, which were phase targeted by binding to iminodiacetic acid (IDA) head groups, via a Cu 2+ chelating mechanism, of lipids that specifically partition into either the Lo phase or Ld phase. The degree of steric pressure was controlled by varying themore » size of the bound particle (10–240 kDa) and the amount of binding sites present (i.e., DPIDA concentrations of 9 and 12 mol%) in the supported lipid multibilayer platform used here. We develop a mass transfer-based diffusional model to analyze the observed L o phase domain dissolution that, along with visual observations and activation energy calculations, provides insight into the sequence of events in crowding-induced mixing. Furthermore, our results suggest that the degree of steric pressure and target phase influence not only the efficacy of steric-pressure induced mixing, but the rate and controlling mechanism for which it occurs.« less

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

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

Qu, Jianfei; Mu, Zhao; Lai, Hanjian

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Effect of the Molecular Configuration of Perylene Diimide Acceptors on Charge Transfer and Device Performance

DOE PAGES

Qu, Jianfei; Mu, Zhao; Lai, Hanjian; ...

2018-01-25

Three perylene diimides (PDI)-based small molecules, T2-SePDI2, T3B-SePDI3, and T4B-SePDI4, with different molecular configurations are synthesized. Due to a large steric hindrance, the molecular configuration of T3B-SePDI3 is the most distorted, followed by T4BSePDI4, while T2-SePDI2 shows the smallest steric hindrance. Inverted bulk heterojunction solar cells based on T3B-SePDI3 and PBDB-T show the highest power conversion efficiency (PCE) of 5.82% with an open-circuit voltage of 0.98 V, a high short-circuit current density of 10.52 mA/cm2, and a fill factor of 56.31%. The PCEs of the T2-SePDI2- and T4B-SePDI4- based devices are 4.10% and 5.10%, respectively. Furthermore, the results demonstrate thatmore » the molecular configuration of the PDI-based small molecule acceptor is critical and that increasing the steric hindrance is helpful in suppressing aggregation and improving device performance.« less

Conservation of direct dynamics in sterically hindered SN2/E2 reactions.

PubMed

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin; Wester, Roland

2018-01-21

Nucleophilic substitution (S N 2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl - and CN - with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct S N 2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern S N 2 and E2 pathways even in sterically hindered exchange reaction systems.

Conservation of direct dynamics in sterically hindered SN2/E2 reactions

PubMed Central

Carrascosa, Eduardo; Meyer, Jennifer; Michaelsen, Tim; Stei, Martin

2017-01-01

Nucleophilic substitution (SN2) and base-induced elimination (E2), two indispensable reactions in organic synthesis, are commonly assumed to proceed under stereospecific conditions. Understanding the way in which the reactants pre-orient in these reactions, that is its stereodynamics, is essential in order to achieve a detailed atomistic picture and control over such processes. Using crossed beam velocity map imaging, we study the effect of steric hindrance in reactions of Cl– and CN– with increasingly methylated alkyl iodides by monitoring the product ion energy and scattering angle. For both attacking anions the rebound mechanism, indicative of a direct SN2 pathway, is found to contribute to the reaction at high relative collision energies despite being increasingly hindered. An additional forward scattering mechanism, ascribed to a direct E2 reaction, also contributes at these energies. Inspection of the product energy distributions confirms the direct and fast character of both mechanisms as opposed to an indirect reaction mechanism which leads to statistical energy redistribution in the reaction complex. This work demonstrates that nonstatistical dynamics and energetics govern SN2 and E2 pathways even in sterically hindered exchange reaction systems. PMID:29629138

Heat Capacity of Spider Silk-like Block Copolymers

PubMed Central

Huang, Wenwen; Krishnaji, Sreevidhya; Hu, Xiao; Kaplan, David; Cebe, Peggy

2012-01-01

We synthesized and characterized a new family of di-block copolymers based on the amino acid sequences of Nephila clavipes major ampulate dragline spider silk, having the form HABn and HBAn (n=1–3), comprising an alanine-rich hydrophobic block, A, a glycine-rich hydrophilic block, B, and a histidine tag, H. The reversing heat capacities, Cp(T), for temperatures below and above the glass transition, Tg, were measured by temperature modulated differential scanning calorimetry. For the solid state, we then calculated the heat capacities of our novel block copolymers based on the vibrational motions of the constituent poly(amino acid)s, whose heat capacities are known or can be estimated from the ATHAS Data Bank. For the liquid state, the heat capacity was estimated by using the rotational and translational motions in the polymer chain. Excellent agreement was found between the measured and calculated values of the heat capacity, showing that this method can serve as a standard by which to assess the Cp for other biologically inspired block copolymers. The fraction of beta sheet crystallinity of spider silk block copolymers was also determined by using the predicted Cp, and was verified by wide angle X-ray diffraction and Fourier transform infrared spectroscopy. The glass transition temperatures of spider silk block copolymer were fitted by Kwei’s equation and the results indicate that attractive interaction exists between the A-block and B-block. PMID:23869111

A compact high resolution flat panel PET detector based on the new 4-side buttable MPPC for biomedical applications.

PubMed

Wang, Qiang; Wen, Jie; Ravindranath, Bosky; O'Sullivan, Andrew W; Catherall, David; Li, Ke; Wei, Shouyi; Komarov, Sergey; Tai, Yuan-Chuan

2015-09-11

Compact high-resolution panel detectors using virtual pinhole (VP) PET geometry can be inserted into existing clinical or pre-clinical PET systems to improve regional spatial resolution and sensitivity. Here we describe a compact panel PET detector built using the new Though Silicon Via (TSV) multi-pixel photon counters (MPPC) detector. This insert provides high spatial resolution and good timing performance for multiple bio-medical applications. Because the TSV MPPC design eliminates wire bonding and has a package dimension which is very close to the MPPC's active area, it is 4-side buttable. The custom designed MPPC array (based on Hamamatsu S12641-PA-50(x)) used in the prototype is composed of 4 × 4 TSV-MPPC cells with a 4.46 mm pitch in both directions. The detector module has 16 × 16 lutetium yttrium oxyorthosilicate (LYSO) crystal array, with each crystal measuring 0.92 × 0.92 × 3 mm 3 with 1.0 mm pitch. The outer diameter of the detector block is 16.8 × 16.8 mm 2 . Thirty-two such blocks will be arranged in a 4 × 8 array with 1 mm gaps to form a panel detector with detection area around 7 cm × 14 cm in the full-size detector. The flood histogram acquired with Ge-68 source showed excellent crystal separation capability with all 256 crystals clearly resolved. The detector module's mean, standard deviation, minimum (best) and maximum (worst) energy resolution were 10.19%, +/-0.68%, 8.36% and 13.45% FWHM, respectively. The measured coincidence time resolution between the block detector and a fast reference detector (around 200 ps single photon timing resolution) was 0.95 ns. When tested with Siemens Cardinal electronics the performance of the detector blocks remain consistent. These results demonstrate that the TSV-MPPC is a promising photon sensor for use in a flat panel PET insert composed of many high resolution compact detector modules.

The routing, modulation level, and spectrum allocation algorithm in the virtual optical network mapping

NASA Astrophysics Data System (ADS)

Wang, Yunyun; Li, Hui; Liu, Yuze; Ji, Yuefeng; Li, Hongfa

2017-10-01

With the development of large video services and cloud computing, the network is increasingly in the form of services. In SDON, the SDN controller holds the underlying physical resource information, thus allocating the appropriate resources and bandwidth to the VON service. However, for some services that require extremely strict QoT (quality of transmission), the shortest distance path algorithm is often unable to meet the requirements because it does not take the link spectrum resources into account. And in accordance with the choice of the most unoccupied links, there may be more spectrum fragments. So here we propose a new RMLSA (the routing, modulation Level, and spectrum allocation) algorithm to reduce the blocking probability. The results show about 40% less blocking probability than the shortest-distance algorithm and the minimum usage of the spectrum priority algorithm. This algorithm is used to satisfy strict request of QoT for demands.

Differential optical shadow sensor for sub-nanometer displacement measurement and its application to drag-free satellites.

PubMed

Zoellner, Andreas; Tan, Si; Saraf, Shailendhar; Alfauwaz, Abdul; DeBra, Dan; Buchman, Sasha; Lipa, John A

2017-10-16

We present a method for 3D sub-nanometer displacement measurement using a set of differential optical shadow sensors. It is based on using pairs of collimated beams on opposite sides of an object that are partially blocked by it. Applied to a sphere, our 3-axis sensor module consists of 8 parallel beam-detector sets for redundancy. The sphere blocks half of each beam's power in the nominal centered position, and any displacement can be measured by the differential optical power changes amongst the pairs of detectors. We have experimentally demonstrated a displacement sensitivity of 0.87nm/Hz at 1 Hz and 0.39nm/Hz at 10 Hz. We describe the application of the module to the inertial sensor of a drag-free satellite, which can potentially be used for navigation, geodesy and fundamental science experiments as well as ground based applications.

Rapid Optical Shutter, Chopper, Modulator and Deflector

NASA Technical Reports Server (NTRS)

Danehy, Paul M. (Inventor)

2017-01-01

An optical device with a light source and a detector is provided. A digital micromirror device positioned between the detector and the light source may deflect light beams projected from the light source. An aperture in front of the detector may block an incoming light beam from the detector when the incoming light beam is incident on the detector outside of a passable incident range and including an aperture opening configured to pass the incoming light beam to the detector when the incoming light beam is incident on the detector within a passable incident range. The digital micromirror device may rotate between a first position causing the light beam to pass through the aperture opening and a second position causing the light beam to be blocked by the aperture. The optical device may be configured to operate as a shutter, chopper, modulator and/or deflector.

Fault-tolerant building-block computer study

NASA Technical Reports Server (NTRS)

Rennels, D. A.

1978-01-01

Ultra-reliable core computers are required for improving the reliability of complex military systems. Such computers can provide reliable fault diagnosis, failure circumvention, and, in some cases serve as an automated repairman for their host systems. A small set of building-block circuits which can be implemented as single very large integration devices, and which can be used with off-the-shelf microprocessors and memories to build self checking computer modules (SCCM) is described. Each SCCM is a microcomputer which is capable of detecting its own faults during normal operation and is described to communicate with other identical modules over one or more Mil Standard 1553A buses. Several SCCMs can be connected into a network with backup spares to provide fault-tolerant operation, i.e. automated recovery from faults. Alternative fault-tolerant SCCM configurations are discussed along with the cost and reliability associated with their implementation.

Dynamics of living matter: can we ``see'' collective motions in proteins?

NASA Astrophysics Data System (ADS)

Hekstra, Doeke

2015-03-01

Proteins are ideal model systems for quantitative study of the interplay of physical and evolutionary forces. Collective, anharmonic motions of amino acid residues within proteins are thought to be central to their function, and to explain, in large part, the complex dependence of protein function on its constituent parts. Currently, the experimental characterization of such motions poses a major stumbling block on the way to a physical understanding of protein function and evolution. We are addressing this problem in two ways. First, alternate conformations of protein residues can often be distinguished in the electron density estimated from room-temperature X-ray crystallography. The dense packing of residues in the folded protein requires that such conformational variations must propagate through networks of amino acids to preclude local steric clashes. Fraser and colleagues showed that such steric conflicts can be used to extract contact networks of residues collectively switching conformation. We ask if these networks are conserved over homologous sequences and connected to the functional reaction coordinate, both of which would demonstrate their fundamental importance. I will describe initial results for the family of PDZ domains: small ligand-binding proteins for which a network of energetically and conformationally coupled residues controlling ligand affinity has been demonstrated previously by a range of methods. Second, the analysis of collective motions in proteins, by nearly any means, is indirect: nothing is seen moving. To directly induce and ``see'' motions on a range of time scales, we developed a new approach based on (a) electric field pulses to induce motions within a protein crystal and (b) time-resolved crystallography to observe these motions. Since proteins generically have a heterogeneous, modifiable charge distribution, this method could provide a powerful, general way of probing the collective motions, and excited states, of proteins in kinetic and atomic detail. I will present initial experiments showing the method is feasible. Taken together, these experiments begin to provide a basis for the development of a physical theory of proteins consistent with their function and adaptation - the source of their survival throughout the evolutionary process.

Understanding the interplay of weak forces in [3,3]-sigmatropic rearrangement for stereospecific synthesis of diamines.

PubMed

So, Soon Mog; Mui, Leo; Kim, Hyunwoo; Chin, Jik

2012-08-21

Chiral diamines are important building blocks for constructing stereoselective catalysts, including transition metal based catalysts and organocatalysts that facilitate oxidation, reduction, hydrolysis, and C-C bond forming reactions. These molecules are also critical components in the synthesis of drugs, including antiviral agents such as Tamiflu and Relenza and anticancer agents such as oxaliplatin and nutlin-3. The diaza-Cope rearrangement reaction provides one of the most versatile methods for rapidly generating a wide variety of chiral diamines stereospecifically and under mild conditions. Weak forces such as hydrogen bonding, electronic, steric, oxyanionic, and conjugation effects can drive this equilibrium process to completion. In this Account, we examine the effect of these individual weak forces on the value of the equilibrium constant for the diaza-Cope rearrangement reaction using both computational and experimental methods. The availability of a wide variety of aldehydes and diamines allows for the facile synthesis of the diimines needed to study the weak forces. Furthermore, because the reaction generally takes place cleanly at ambient temperature, we can easily measure equilibrium constants for rearrangement of the diimines. We use the Hammett equation to further examine the electronic and oxyanionic effects. In addition, computations and experiments provide us with new insights into the origin and extent of stereospecificity for this rearrangement reaction. The diaza-Cope rearrangement, with its unusual interplay between weak forces and the equilibrium constant of the reaction, provides a rare opportunity to study the effects of the fundamental weak forces on a chemical reaction. Among these many weak forces that affect the diaza-Cope rearrangement, the anion effect is the strongest (10.9 kcal/mol) followed by the resonance-assisted hydrogen-bond effect (7.1 kcal/mol), the steric effect (5.7 kcal/mol), the conjugation effect (5.5 kcal/mol), and the electronic effect (3.2 kcal/mol). Based on both computation and experimental data, the effects of these weak forces are additive. Understanding the interplay of the weak forces in the [3,3]-sigmatropic reaction is interesting in its own right and also provides valuable insights for the synthesis of chiral diamine based drugs and catalysts in excellent yield and enantiopurity.

Entropic formulation for the protein folding process: Hydrophobic stability correlates with folding rates

NASA Astrophysics Data System (ADS)

Dal Molin, J. P.; Caliri, A.

2018-01-01

Here we focus on the conformational search for the native structure when it is ruled by the hydrophobic effect and steric specificities coming from amino acids. Our main tool of investigation is a 3D lattice model provided by a ten-letter alphabet, the stereochemical model. This minimalist model was conceived for Monte Carlo (MC) simulations when one keeps in mind the kinetic behavior of protein-like chains in solution. We have three central goals here. The first one is to characterize the folding time (τ) by two distinct sampling methods, so we present two sets of 103 MC simulations for a fast protein-like sequence. The resulting sets of characteristic folding times, τ and τq were obtained by the application of the standard Metropolis algorithm (MA), as well as by an enhanced algorithm (Mq A). The finding for τq shows two things: (i) the chain-solvent hydrophobic interactions {hk } plus a set of inter-residues steric constraints {ci,j } are able to emulate the conformational search for the native structure. For each one of the 103MC performed simulations, the target is always found within a finite time window; (ii) the ratio τq / τ ≅ 1 / 10 suggests that the effect of local thermal fluctuations, encompassed by the Tsallis weight, provides to the chain an innate efficiency to escape from energetic and steric traps. We performed additional MC simulations with variations of our design rule to attest this first result, both algorithms the MA and the Mq A were applied to a restricted set of targets, a physical insight is provided. Our second finding was obtained by a set of 600 independent MC simulations, only performed with the Mq A applied to an extended set of 200 representative targets, our native structures. The results show how structural patterns should modulate τq, which cover four orders of magnitude; this finding is our second goal. The third, and last result, was obtained with a special kind of simulation performed with the purpose to explore a possible connection between the hydrophobic component of protein stability and the native structural topology. We simulated those same 200 targets again with the Mq A, only. However, this time we evaluated the relative frequency {ϕq } in which each target visits its corresponding native structure along an appropriate simulation time. Due to the presence of the hydrophobic effect in our approach we obtained a strong correlation between the stability and the folding rate (R = 0 . 85). So, as faster a sequence found its target, as larger is the hydrophobic component of its stability. The strong correlation fulfills our last goal. This final finding suggests that the hydrophobic effect could not be a general stabilizing factor for proteins.

Multi-functional Electric Module for a Vehicle

NASA Technical Reports Server (NTRS)

Waligora, Thomas M. (Inventor); Fraser-Chanpong, Nathan (Inventor); Figuered, Joshua M. (Inventor); Reed, Ryan (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Herrera, Eduardo (Inventor); Markee, Mason M. (Inventor); Bluethmann, William J. (Inventor)

2015-01-01

A multi-functional electric module (eModule) is provided for a vehicle having a chassis, a master controller, and a drive wheel having a propulsion-braking module. The eModule includes a steering control assembly, mounting bracket, propulsion control assembly, brake controller, housing, and control arm. The steering control assembly includes a steering motor controlled by steering controllers in response to control signals from the master controller. A mounting feature of the bracket connects to the chassis. The propulsion control assembly and brake controller are in communication with the propulsion-braking module. The control arm connects to the lower portion and contains elements of a suspension system, with the control arm being connectable to the drive wheel via a wheel input/output block. The controllers are responsive to the master controller to control a respective steering, propulsion, and braking function. The steering motor may have a dual-wound stator with windings controlled via the respective steering controllers.

[Effect of spatial location on the generality of block-wise conflict adaptation between different types of scripts].

PubMed

Watanabe, Yurina; Yoshizaki, Kazuhito

2014-10-01

This study aimed to investigate the generality of conflict adaptation associated with block-wise conflict frequency between two types of stimulus scripts (Kanji and Hiragana). To this end, we examined whether the modulation of the compatibility effect with one type of script depending on block-wise conflict frequency (75% versus 25% generalized to the other type of script whose block-wise conflict frequency was kept constant (50%), using the Spatial Stroop task. In Experiment 1, 16 participants were required to identify the target orientation (up or down) presented in the upper or lower visual-field. The results showed that block-wise conflict adaptation with one type of stimulus script generalized to the other. The procedure in Experiment 2 was the same as that in Experiment 1, except that the presentation location differed between the two types of stimulus scripts. We did not find a generalization from one script to the other. These results suggest that presentation location is a critical factor contributing to the generality of block-wise conflict adaptation.

Identification and Reconfigurable Control of Impaired Multi-Rotor Drones

NASA Technical Reports Server (NTRS)

Stepanyan, Vahram; Krishnakumar, Kalmanje; Bencomo, Alfredo

2016-01-01

The paper presents an algorithm for control and safe landing of impaired multi-rotor drones when one or more motors fail simultaneously or in any sequence. It includes three main components: an identification block, a reconfigurable control block, and a decisions making block. The identification block monitors each motor load characteristics and the current drawn, based on which the failures are detected. The control block generates the required total thrust and three axis torques for the altitude, horizontal position and/or orientation control of the drone based on the time scale separation and nonlinear dynamic inversion. The horizontal displacement is controlled by modulating the roll and pitch angles. The decision making algorithm maps the total thrust and three torques into the individual motor thrusts based on the information provided by the identification block. The drone continues the mission execution as long as the number of functioning motors provide controllability of it. Otherwise, the controller is switched to the safe mode, which gives up the yaw control, commands a safe landing spot and descent rate while maintaining the horizontal attitude.

Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and molecular determinants.

PubMed

Kacik, Michael; Oliván-Viguera, Aida; Köhler, Ralf

2014-01-01

Cytochrome P450- and ω-hydrolase products (epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraeonic acid (20-HETE)), natural omega-3 fatty acids (ω3), and pentacyclic triterpenes have been proposed to contribute to a wide range of vaso-protective and anti-fibrotic/anti-cancer signaling pathways including the modulation of membrane ion channels. Here we studied the modulation of intermediate-conductance Ca(2+)/calmodulin-regulated K(+) channels (K(Ca)3.1) by EETs, 20-HETE, ω3, and pentacyclic triterpenes and the structural requirements of these fatty acids to exert channel blockade. We studied modulation of cloned human hK(Ca)3.1 and the mutant hK(Ca)3.1(V275A) in HEK-293 cells, of rK(Ca)3.1 in aortic endothelial cells, and of mK(Ca)3.1 in 3T3-fibroblasts by inside-out and whole-cell patch-clamp experiments, respectively. In inside-out patches, Ca(2+)-activated hK(Ca)3.1 were inhibited by the ω3, DHA and α-LA, and the ω6, AA, in the lower µmolar range and with similar potencies. 5,6-EET, 8,9-EET, 5,6-DiHETE, and saturated arachidic acid, had no appreciable effects. In contrast, 14,15-EET, its stable derivative, 14,15-EEZE, and 20-HETE produced channel inhibition. 11,12-EET displayed less inhibitory activity. The K(Ca)3.1(V275A) mutant channel was insensitive to any of the blocking EETs. Non-blocking 5,6-EET antagonized the inhibition caused by AA and augmented cloned hK(Ca)3.1 and rK(Ca)3.1 whole-cell currents. Pentacyclic triterpenes did not modulate K(Ca)3.1 currents. Inhibition of K(Ca)3.1 by EETs (14,15-EET), 20-HETE, and ω3 critically depended on the presence of electron double bonds and hydrophobicity within the 10 carbons preceding the carboxyl-head of the molecules. From the physiological perspective, metabolism of AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to cellular signal transduction processes influenced by these fatty acids.

Nitric oxide-mediated modulation of the murine locomotor network

PubMed Central

Foster, Joshua D.; Dunford, Catherine; Sillar, Keith T.

2013-01-01

Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1–12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior. PMID:24259545

Time-resolved single-photon detection module based on silicon photomultiplier: A novel building block for time-correlated measurement systems

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

Martinenghi, E., E-mail: edoardo.martinenghi@polimi.it; Di Sieno, L.; Contini, D.

2016-07-15

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm{sup 2} together with themore » suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics systems).« less

Role of opioidergic and GABAergic neurotransmission of the nucleus raphe magnus in the modulation of tonic immobility in guinea pigs.

PubMed

da Silva, Luis Felipe Souza; Menescal-de-Oliveira, Leda

2007-04-02

Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. Previous results from our laboratory have demonstrated that nucleus raphe magnus (NRM) is also a structure involved in the modulation of TI behavior, as chemical stimulation through carbachol decreases the duration of TI in guinea pigs. In view of the fact that GABAergic and opioidergic circuits participate in the regulation of neuronal activity in the NRM and since these neurotransmitters are also involved in the modulation of TI, the objective of the present study was to evaluate the role of these circuits of the NRM in the modulation of the behavioral TI response. Microinjection of morphine (4.4 nmol/0.2 microl) or bicuculline (0.4 nmol/0.2 microl) into the NRM increased the duration of TI episodes while muscimol (0.5 nmol/0.2 microl) decreased it. The effect of morphine injection into the NRM was blocked by previous microinjection of naloxone (2.7 nmol/0.2 microl). Muscimol at 0.25 nmol did not produce any change in TI duration; however, it blocked the increased response induced by morphine. Our results indicate a facilitatory role of opioidergic neurotransmission in the modulation of the TI response within the NRM, whereas GABAergic activity plays an inhibitory role. In addition, in the present study the modulation of TI in the NRM possibly occurred via an interaction between opioidergic and GABAergic systems, where the opioidergic effect might be due to inhibition of tonically active GABAergic interneurons.

Combining CFD simulations with blockoriented heatflow-network model for prediction of photovoltaic energy-production

NASA Astrophysics Data System (ADS)

Haber, I. E.; Farkas, I.

2011-01-01

The exterior factors which influencing the working circumstances of photovoltaic modules are the irradiation, the optical air layer (Air Mass - AM), the irradiation angle, the environmental temperature and the cooling effect of the wind. The efficiency of photovoltaic (PV) devices is inversely proportional to the cell temperature and therefore the mounting of the PV modules can have a big affect on the cooling, due to wind flow-around and naturally convection. The construction of the modules could be described by a heatflow-network model, and that can define the equation which determines the cells temperature. An equation like this can be solved as a block oriented model with hybrid-analogue simulator such as Matlab-Simulink. In view of the flow field and the heat transfer, witch was calculated numerically, the heat transfer coefficients can be determined. Five inflow rates were set up for both pitched and flat roof cases, to let the trend of the heat transfer coefficient know, while these functions can be used for the Matlab/Simulink model. To model the free convection flows, the Boussinesq-approximation were used, integrated into the Navier-Stokes equations and the energy equation. It has been found that under a constant solar heat gain, the air velocity around the modules and behind the pitched-roof mounted module is increasing, proportionately to the wind velocities, and as result the heat transfer coefficient increases linearly, and can be described by a function in both cases. To the block based model the meteorological parameters and the results of the CFD simulations as single functions were attached. The final aim was to make a model that could be used for planning photovoltaic systems, and define their accurate performance for better sizing of an array of modules.

Coherent Multidecadal Atmospheric and Oceanic Variability in the North Atlantic: Blocking Corresponds with Warm Subpolar Ocean

NASA Technical Reports Server (NTRS)

Hakkinen, Sirpa M.; Rhines, P. B.; Worthen, D. L.

2012-01-01

Winters with frequent atmospheric blocking, in a band of latitudes from Greenland to Western Europe, are found to persist over several decades and correspond to a warm North Atlantic Ocean. This is evident in atmospheric reanalysis data, both modern and for the full 20th century. Blocking is approximately in phase with Atlantic multidecadal ocean variability (AMV). Wintertime atmospheric blocking involves a highly distorted jetstream, isolating large regions of air from the westerly circulation. It influences the ocean through windstress-curl and associated air/sea heat flux. While blocking is a relatively high-frequency phenomenon, it is strongly modulated over decadal timescales. The blocked regime (weaker ocean gyres, weaker air-sea heat flux, paradoxically increased transport of warm subtropical waters poleward) contributes to the warm phase of AMV. Atmospheric blocking better describes the early 20thC warming and 1996-2010 warm period than does the NAO index. It has roots in the hemispheric circulation and jet stream dynamics. Subpolar Atlantic variability covaries with distant AMOC fields: both these connections may express the global influence of the subpolar North Atlantic ocean on the global climate system.

Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels*♦

PubMed Central

VanSchouwen, Bryan; Akimoto, Madoka; Sayadi, Maryam; Fogolari, Federico; Melacini, Giuseppe

2015-01-01

The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically modulates HCN through the cAMP-dependent formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the apo versus holo conformational changes of the cAMP-binding domain (CBD) have been previously mapped, only limited information is currently available on the HCN IR dynamics, which have been hypothesized to play a critical role in the cAMP-dependent gating of HCN. Here, using molecular dynamics simulations validated and complemented by experimental NMR and CD data, we comparatively analyze HCN IR dynamics in the four states of the thermodynamic cycle arising from the coupling between cAMP binding and tetramerization equilibria. This extensive set of molecular dynamics trajectories captures the active-to-inactive transition that had remained elusive for other CBDs, and it provides unprecedented insight on the role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically, the IR tetramerization domain becomes more flexible in the monomeric states, removing steric clashes that the apo-CDB structure would otherwise impose. Furthermore, the simulations reveal that the active/inactive structural transition for the apo-monomeric CBD occurs through a manifold of pathways that are more divergent than previously anticipated. Upon cAMP binding, these pathways become disallowed, pre-confining the CBD conformational ensemble to a tetramer-compatible state. This conformational confinement primes the IR for tetramerization and thus provides a model of how cAMP controls HCN channel gating. PMID:25944904

General Purpose Heat Source Simulator

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.

2008-01-01

The General Purpose Heat Source (GPHS) project seeks to combine the development of an electrically heated, single GPHS module simulator with the evaluation of potential nuclear surface power systems. The simulator is designed to match the form, fit, and function of actual GPHS modules which normally generate heat through the radioactive decay of Pu238. The use of electrically heated modules rather than modules containing Pu238 facilitates the testing of the subsystems and systems without sacrificing the quantity and quality of the test data gathered. Current GPHS activities are centered on developing robust heater designs with sizes and weights which closely match those of actual Pu238 fueled GPHS blocks. Designs are being pursued which will allow operation up to 1100 C.

MRM1 during Mating to FGB

NASA Image and Video Library

2010-05-18

ISS023-E-047527 (18 May 2010) --- In the grasp of the station?s robotic Canadarm2, the Russian-built Mini-Research Module 1 (MRM-1) is attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB) of the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia. Rassvet will be used for cargo storage and will provide an additional docking port to the station.

Modulation/demodulation techniques for satellite communications. Part 1: Background

NASA Technical Reports Server (NTRS)

Omura, J. K.; Simon, M. K.

1981-01-01

Basic characteristics of digital data transmission systems described include the physical communication links, the notion of bandwidth, FCC regulations, and performance measurements such as bit rates, bit error probabilities, throughputs, and delays. The error probability performance and spectral characteristics of various modulation/demodulation techniques commonly used or proposed for use in radio and satellite communication links are summarized. Forward error correction with block or convolutional codes is also discussed along with the important coding parameter, channel cutoff rate.

Nicotine Induces Resistance to Chemotherapy by Modulating Mitochondrial Signaling in Lung Cancer

PubMed Central

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D.; Upadhyay, Daya

2009-01-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 μM) followed by cisplatin (35 μM) plus etoposide (20 μM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4′diisothiocyanatostilbene-2,2′disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-ρ0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer. PMID:18676776

Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

PubMed

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

2009-02-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer.

Modulation of enrofloxacin binding in OmpF by Mg2+ as revealed by the analysis of fast flickering single-porin current

PubMed Central

Brauser, Annemarie; Schroeder, Indra; Gutsmann, Thomas; Cosentino, Cristian; Moroni, Anna; Winterhalter, Mathias

2012-01-01

One major determinant of the efficacy of antibiotics on Gram-negative bacteria is the passage through the outer membrane. During transport of the fluoroquinolone enrofloxacin through the trimeric outer membrane protein OmpF of Escherichia coli, the antibiotic interacts with two binding sites within the pore, thus partially blocking the ionic current. The modulation of one affinity site by Mg2+ reveals further details of binding sites and binding kinetics. At positive membrane potentials, the slow blocking events induced by enrofloxacin in Mg2+-free media are converted to flickery sojourns at the highest apparent current level (all three pores flickering). This indicates weaker binding in the presence of Mg2+. Analysis of the resulting amplitude histograms with β distributions revealed the rate constants of blocking (kOB) and unblocking (kBO) in the range of 1,000 to 120,000 s−1. As expected for a bimolecular reaction, kOB was proportional to blocker concentration and kBO independent of it. kOB was approximately three times lower for enrofloxacin coming from the cis side than from the trans side. The block was not complete, leading to a residual conductivity of the blocked state being ∼25% of that of the open state. Interpretation of the results has led to the following model: fast flickering as caused by interaction of Mg2+ and enrofloxacin is related to the binding site at the trans side, whereas the cis site mediates slow blocking events which are also found without Mg2+. The difference in the accessibility of the binding sites also explains the dependency of kOB on the side of enrofloxacin addition and yields a means of determining the most plausible orientation of OmpF in the bilayer. The voltage dependence suggests that the dipole of the antibiotic has to be adequately oriented to facilitate binding. PMID:22689827

Treatment of cartilage with beta-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repair.

PubMed

McGowan, Kevin B; Sah, Robert L

2005-05-01

Integrative repair of cartilage was previously found to depend on collagen synthesis and maturation. beta-aminopropionitrile (BAPN) treatment, which irreversibly blocks lysyl oxidase, inhibited the formation of collagen crosslinks, prevented development of adhesive strength, and caused a buildup of GuHCl-extractable collagen crosslink precursors. This buildup of crosslink precursor in the tissue may be useful for enhancing integrative repair. We tested in vitro the hypothesis that pre-treatment of cartilage with BAPN, followed by washout before implantation, could be a useful therapeutic strategy to accelerate subsequent collagen maturation. In individual cartilage disks, collagen processing was reversibly blocked by BAPN treatment (0.1 mM) as indicated by a BAPN-induced increase in the total and proportion of incorporated radiolabel that was extractable by 4M guanidine-HCl, followed by a decrease, within 3-4 days of BAPN washout, in the proportion of extractable radiolabel to control levels. With a similar pattern, integration between pairs of apposed cartilage blocks was reversibly blocked by BAPN treatment, and followed by an enhancement of integration after BAPN washout. The low and high levels of integration were associated with enrichment in [(3)H]proline in a form that was susceptible and resistant, respectively, to extraction. With increasing duration up to 7 days after BAPN pre-treatment, the levels of [(3)H]proline extraction decreased, and the development of adhesive strength increased. Thus, BAPN can be used to modulate integrative cartilage repair.

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

Not Available

The Phase I program and the design plan for the Phase II Experiment Integration wherein the AAI Corporation's 24/1 concentrating collector is used to produce hot water to cure concrete blocks is described. This concept has a tremendous potential since each block requires about 1500 Btu for curing at a temperature of 140/sup 0/F to 180/sup 0/F. To demonstrate this process, the solar hot water system will be installed at the new block fabricating plant being built by the York Building Products Co., Inc. at Harrisburg, Pa. A circular underground curing tank will be the storage tank for the solarmore » system. Since the plane is new, no retrofitting is required. The collectors will be mounted on the roof of the new block producing facility. A full-scale 256 ft/sup 2/ module of the 24/1 collector has been built and tested by AAI Corporation. A 9216 ft/sup 2/ array of collectors is required for this experiment. AAI Corporation is pursuing a development program planned to culminate in the marketing of the 24/1 collector at a selling price of $7 to $10 per square foot. The collector is built in 9 ft by 34 ft modules and is self-supporting with pads located at the four corners. It can be inclined at the most favorable angle for solar performance, and can be located on a roof, or as a separate unit on the ground. A final design and performance analysis and an economic analysis are presented. (WHK)« less

Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches.

PubMed

Islam, Mohammed A

2010-01-01

Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.

Gene delivery to the neurulating embryo during culture

EPA Science Inventory

Modulating expression of specific genes during embryogenesis will help elucidate their role in development. Transient overexpression of specific genes can be accomplished by adding additional copies, or else antisense transcripts can be used to block expression. Manipulation of g...

A system for aerodynamic design and analysis of supersonic aircraft. Part 3: Computer program description

NASA Technical Reports Server (NTRS)

Middleton, W. D.; Lundry, J. L.; Coleman, R. G.

1980-01-01

The computer program documentation for the design and analysis of supersonic configurations is presented. Schematics and block diagrams of the major program structure, together with subroutine descriptions for each module are included.

Using Container Structures in Architecture and Urban Design

NASA Astrophysics Data System (ADS)

Grębowski, Karol; Kałdunek, Daniel

2017-10-01

The paper presents the use of shipping containers in architecture and urban design. Even today, houses and apartments are still too expensive. Since 1923 architects have been improving the living conditions of citizens by building very simple, repeatable forms. With prefabrication technology it became possible to build quicker, causing house prices to decrease. Apartments in block of flats became affordable to more and more people. Modernism had great impact on the quality of living spaces, despite the detrimental effect of large panel technology on social life. It gave people their own bathrooms, and gifted them with simple solutions we now consider indispensable. The ambition to build cheaply but effectively is still here. The future of housing lies in prefabricated apartment modules. A well optimized creation process is the key, but taking into consideration the mistakes made by past generations should be the second most important factor. Studies show that large panel buildings were too monumental and solid for a housing structure, and offered no public spaces between them. Lack of urban design transformed a great idea into blocks that are considered to be ugly and unfriendly. Diversity is something that large panel structures were missing. While most block of flats were being constructed out of the same module (Model 770), differentiated architecture was difficult to achieve. Nowadays, increasing numbers of shipping containers are being used for housing purposes. These constructions show that it is possible to create astonishing housing with modules. Shipping containers were not designed to be a building material, but in contrast to large panel modules, there are many more possibilities of their transformation. In this paper the authors propose a set of rules that, if followed, would result in cheaper apartments, while keeping in consideration both tremendous architecture and friendly urban design. What is more, the proposed solution is designed to adapt to personalized requirements. In this paper the authors include information about design guidelines for structures made from shipping containers.

GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

PubMed

Lane, Scott D; Gowin, Joshua L

2009-10-01

Recent work in neuroeconomics has used game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner's dilemma model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.