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Sample records for reversibly bound analogues

  1. L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Rinaldo-Matthis,A.; Murkin, A.; Ramagopal, U.; Clinch, K.; Mee, S.; Evans, G.; Tyler, P.; Furneaux, R.; Almo, S.; Schramm, v.

    2008-01-01

    Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.

  2. Stationary bound states of massless scalar fields around black holes and black hole analogues

    NASA Astrophysics Data System (ADS)

    Benone, Carolina L.; Crispino, Luís C. B.; Herdeiro, Carlos A. R.; Radu, Eugen

    2015-06-01

    We discuss stationary bound states, a.k.a. clouds, for a massless test scalar field around Kerr black holes (BHs) and spinning acoustic BH analogues. In view of the absence of a mass term, the trapping is achieved via enclosing the BH — scalar field system in a cavity and imposing Dirichlet or Neumann boundary conditions. We discuss the variation of these bounds states with the discrete parameters that label them, as well as their spatial distribution, complementing results in our previous work [C. L. Benone, L. C. B. Crispino, C. Herdeiro and E. Radu, Phys. Rev. D91 (2015) 104038].

  3. Structure of Mandelate Racemase with Bound Intermediate Analogues Benzohydroxamate and Cupferron

    SciTech Connect

    Lietzan, Adam D.; Nagar, Mitesh; Pellmann, Elise A.; Bourque, Jennifer R.; Bearne, Stephen L.; Maurice, Martin St.

    2012-05-09

    Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg{sup 2+}-dependent interconversion of the enantiomers of mandelate, stabilizing the altered substrate in the transition state by 26 kcal/mol relative to the substrate in the ground state. To understand the origins of this binding discrimination, we determined the X-ray crystal structures of wild-type MR complexed with two analogues of the putative aci-carboxylate intermediate, benzohydroxamate and Cupferron, to 2.2-{angstrom} resolution. Benzohydroxamate is shown to be a reasonable mimic of the transition state and/or intermediate because its binding affinity for 21 MR variants correlates well with changes in the free energy of transition state stabilization afforded by these variants. Both benzohydroxamate and Cupferron chelate the active site divalent metal ion and are bound in a conformation with the phenyl ring coplanar with the hydroxamate and diazeniumdiolate moieties, respectively. Structural overlays of MR complexed with benzohydroxamate, Cupferron, and the ground state analogue (S)-atrolactate reveal that the para carbon of the substrate phenyl ring moves by 0.8-1.2 {angstrom} between the ground state and intermediate state, consistent with the proposal that the phenyl ring moves during MR catalysis while the polar groups remain relatively fixed. Although the overall protein structure of MR with bound intermediate analogues is very similar to that of MR with bound (S)-atrolactate, the intermediate-Mg{sup 2+} distance becomes shorter, suggesting a tighter complex with the catalytic Mg{sup 2+}. In addition, Tyr 54 moves closer to the phenyl ring of the bound intermediate analogues, contributing to an overall constriction of the active site cavity. However, site-directed mutagenesis experiments revealed that the role of Tyr 54 in MR catalysis is relatively minor, suggesting that alterations in enzyme structure that contribute to discrimination between the altered substrate in the

  4. Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1

    PubMed Central

    Hou, Caixia; Weidenbach, Stevi; Cano, Kristin E.; Wang, Zhonghua; Mitra, Prithiba; Ivanov, Dmitri N.; Rohr, Jürgen; Tsodikov, Oleg V.

    2016-01-01

    Transcription factors have been considered undruggable, but this paradigm has been recently challenged. DNA binding natural product mithramycin (MTM) is a potent antagonist of oncogenic transcription factor EWS–FLI1. Structural details of MTM recognition of DNA, including the FLI1 binding sequence GGA(A/T), are needed to understand how MTM interferes with EWS–FLI1. We report a crystal structure of an MTM analogue MTM SA–Trp bound to a DNA oligomer containing a site GGCC, and two structures of a novel analogue MTM SA–Phe in complex with DNA. MTM SA–Phe is bound to sites AGGG and GGGT on one DNA, and to AGGG and GGGA(T) (a FLI1 binding site) on the other, revealing how MTM recognizes different DNA sequences. Unexpectedly, at sub-micromolar concentrations MTMs stabilize FLI1–DNA complex on GGAA repeats, which are critical for the oncogenic function of EWS–FLI1. We also directly demonstrate by nuclear magnetic resonance formation of a ternary FLI1–DNA–MTM complex on a single GGAA FLI1/MTM binding site. These biochemical and structural data and a new FLI1–DNA structure suggest that MTM binds the minor groove and perturbs FLI1 bound nearby in the major groove. This ternary complex model may lead to development of novel MTM analogues that selectively target EWS–FLI1 or other oncogenic transcription factors, as anti-cancer therapeutics. PMID:27587584

  5. Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

    SciTech Connect

    Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu )

    1990-01-09

    Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

  6. Supersymmetric analogue of BCN type rational integrable models with polarized spin reversal operators

    NASA Astrophysics Data System (ADS)

    Banerjee, P.; Basu-Mallick, B.; Bondyopadhaya, N.; Datta, C.

    2016-03-01

    We derive the exact spectra as well as partition functions for a class of BCN type of spin Calogero models, whose Hamiltonians are constructed by using supersymmetric analogues of polarized spin reversal operators (SAPSRO). The strong coupling limit of these spin Calogero models yields BCN type of Polychronakos-Frahm (PF) spin chains with SAPSRO. By applying the freezing trick, we obtain an exact expression for the partition functions of such PF spin chains. We also derive a formula which expresses the partition function of any BCN type of PF spin chain with SAPSRO in terms of partition functions of several AK types of supersymmetric PF spin chains, where K ⩽ N - 1. Subsequently we show that an extended boson-fermion duality relation is obeyed by the partition functions of the BCN type of PF chains with SAPSRO. Some spectral properties of these spin chains, like level density distribution and nearest neighbor spacing distribution, are also studied.

  7. Semi-synthetic ocotillol analogues as selective ABCB1-mediated drug resistance reversal agents

    PubMed Central

    Zhang, Guan-Nan; Wang, Yi-Jun; Kathawala, Rishil J.; Si, Rui; Patel, Bhargav A.; Xu, Jinyi; Chen, Zhe-Sheng

    2015-01-01

    Overexpression of ATP-Binding Cassette transporters leads to multidrug resistance in cancer cells and results in the failure of chemotherapy. In this in-vitro study, we investigated whether or not (20S, 24R/S)-epoxy-12β, 25-dihydroxy-dommarane-3β-amine (ORA and OSA), a pair of semi-synthetic ocotillol analogue epimers, could inhibit the ABCB1 transporter. ORA (1 μM and 3 μM) significantly reversed the resistance to paclitaxel and vincristine in ABCB1-overexpressing SW620/Ad300 and HEK/ABCB1 cells, whereas OSA had no significant effects. In addition, ORA (3 μM) significantly increased the intracellular accumulation of [3H]-paclitaxel by suppressing the efflux function of ABCB1. Meanwhile, both ORA (3 μM) and OSA (3 μM) did not significantly alter the expression level or the subcellular location of ABCB1 protein. Moreover, the ABCB1 ATPase study suggested that ORA had a stronger stimulatory effect on the ATPase activity than OSA. ORA also exhibited a higher docking score as compared with OSA inside transmembrane domain of ABCB1. Overall, we concluded that ORA reverse ABCB1-mediated MDR by competitively inhibiting the ABCB1 drug efflux function. PMID:26296969

  8. Characterization of the Pseudocapacitive Nature of Surface Bound Prussian Blue Analogues

    NASA Astrophysics Data System (ADS)

    Clark, Daniel; Hampton, Jennifer

    With the increased use of intermittent renewable energy sources, more efficient methods of energy storage must be explored. Electrochemical capacitors provide a larger volumetric charge density than physical capacitors while maintaining fast charge and discharge rates. Prussian Blue analogues (nickel and cobalt hexacyanoferrate) are ideal pseudocapacitors for frequent charge and discharge cycles since the crystalline structure does not physically change during switching, causing less stress on the film. This project examines the charge transfer and diffusion coefficients for nickel and nickel-cobalt thin films modified with potassium hexacyanoferrate. The films were examined using a scanning electron microscope, an atomic force microscope and an electrochemical workstation to determine their composition, topography and psuedocapacitive nature. Preliminary data suggest that nickel-cobalt films have a larger quantity of charge and have a lower diffusion coefficient per charge than nickel films. This work is supported by the Hope College Nyenhuis Faculty Development Fund, the Hope College Department of Physics Guess Research Fund, and the National Science Foundation under Grants RUI-DMR-1104725, MRI-CHE-0959282, and MRI-CHE-1126462.

  9. Insights into the electronic structure of Cu(II) bound to an imidazole analogue of westiellamide.

    PubMed

    Comba, Peter; Dovalil, Nina; Hanson, Graeme R; Harmer, Jeffrey R; Noble, Christopher J; Riley, Mark J; Seibold, Bjoern

    2014-12-01

    Three synthetic analogues of westiallamide, H3L(wa), have previously been synthesized (H3L(1-3)) that have a common backbone (derived from l-valine) with H3L(wa) but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu(II) complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(II)(H2L(1))(MeOH)2](+) reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent. DFT calculations confirm this and show similar spin densities on the distal heteroatoms in the heterocyclic rings coordinated to the Cu(II) ion in the other cyclic pseudo hexapeptide [Cu(II)(H2L(2,3,wa))(MeOH)2](+) complexes. The magnetic inequivalencies in [Cu(II)(H2L(1))(MeOH)2](+) arise from different orientations of the heterocyclic rings coordinated to the Cu(II) ion, and the delocalization of the unpaired electron onto the distal heteroatoms within these N-methylimidazole rings depends upon their location with respect to the Cu(II) d(x(2)-y(2)) orbital. A systematic study of DFT functionals and basis sets was undertaken to examine the ability to reproduce the experimentally determined spin Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ∼38% Hartree-Fock exchange gave the best predictions of the g and A((63)Cu) matrices. DFT calculations of the (14)N hyperfine and quadrupole parameters for the distal nitrogens of the coordinated heterocyclic

  10. The role of thin, mechanical discontinuities on the propagation of reverse faults: insights from analogue models

    NASA Astrophysics Data System (ADS)

    Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

    2016-04-01

    Fault-related folding kinematic models are widely used to explain accommodation of crustal shortening. These models, however, include simplifications, such as the assumption of constant growth rate of faults. This value sometimes is not constant in isotropic materials, and even more variable if one considers naturally anisotropic geological systems. , This means that these simplifications could lead to incorrect interpretations of the reality. In this study, we use analogue models to evaluate how thin, mechanical discontinuities, such as beddings or thin weak layers, influence the propagation of reverse faults and related folds. The experiments are performed with two different settings to simulate initially-blind master faults dipping at 30° and 45°. The 30° dip represents one of the Andersonian conjugate fault, and 45° dip is very frequent in positive reactivation of normal faults. The experimental apparatus consists of a clay layer placed above two plates: one plate, the footwall, is fixed; the other one, the hanging wall, is mobile. Motor-controlled sliding of the hanging wall plate along an inclined plane reproduces the reverse fault movement. We run thirty-six experiments: eighteen with dip of 30° and eighteen with dip of 45°. For each dip-angle setting, we initially run isotropic experiments that serve as a reference. Then, we run the other experiments with one or two discontinuities (horizontal precuts performed into the clay layer). We monitored the experiments collecting side photographs every 1.0 mm of displacement of the master fault. These images have been analyzed through PIVlab software, a tool based on the Digital Image Correlation method. With the "displacement field analysis" (one of the PIVlab tools) we evaluated, the variation of the trishear zone shape and how the master-fault tip and newly-formed faults propagate into the clay medium. With the "strain distribution analysis", we observed the amount of the on-fault and off-fault deformation

  11. Bound on Bell inequalities by fraction of determinism and reverse triangle inequality

    NASA Astrophysics Data System (ADS)

    Joshi, P.; Horodecki, K.; Horodecki, M.; Horodecki, P.; Horodecki, R.; Li, Ben; Szarek, S. J.; Szarek, T.

    2015-09-01

    It is an established fact that entanglement is a resource. Sharing an entangled state leads to nonlocal correlations and to violations of Bell inequalities. Such nonlocal correlations illustrate the advantage of quantum resources over classical resources. In this paper, we quantitatively study Bell inequalities with 2 ×n inputs. As found in Gisin et al. [Int. J. Quantum. Inform. 05, 525 (2007), 10.1142/S021974990700289X], quantum mechanical correlations cannot reach the algebraic bound for such inequalities. Here we uncover the heart of this effect, which we call the fraction of determinism. We show that any quantum statistics with two parties and 2 ×n inputs exhibit a nonzero fraction of determinism, and we supply a quantitative bound for it. We then apply it to provide an explicit universal upper bound for Bell inequalities with 2 ×n inputs. As our main mathematical tool, we introduce and prove a reverse triangle inequality, stating in a quantitative way that if some states are far away from a given state, then their mixture is also. The inequality is crucial in deriving the lower bound for the fraction of determinism, but is also of interest on its own.

  12. 8-Modified-2′-Deoxyadenosine Analogues Induce Delayed Polymerization Arrest during HIV-1 Reverse Transcription

    PubMed Central

    Sleiman, Marwan; Smyth, Redmond; Ben Gaied, Nouha; Barhoum, Patrick; Laumond, Géraldine; Bec, Guillaume; Götte, Matthias; Mak, Johnson; Aubertin, Anne-Marie; Burger, Alain; Marquet, Roland

    2011-01-01

    The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2′-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2′-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication. PMID:22087320

  13. Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase

    NASA Astrophysics Data System (ADS)

    Kuroda, Daniel G.; Bauman, Joseph D.; Challa, J. Reddy; Patel, Disha; Troxler, Thomas; Das, Kalyan; Arnold, Eddy; Hochstrasser, Robin M.

    2013-03-01

    The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase (RT), which is an essential enzyme for the replication of HIV. These changes allow it to retain potency against mutations that otherwise would render the enzyme resistant. Here we report that water molecules play an essential role in this binding process. Femtosecond experiments and theory expose the molecular level dynamics of rilpivirine bound to HIV-1 RT. Two nitrile substituents, one on each arm of the drug, are used as vibrational probes of the structural dynamics within the binding pocket. Two-dimensional vibrational echo spectroscopy reveals that one nitrile group is unexpectedly hydrogen-bonded to a mobile water molecule, not identified in previous X-ray structures. Ultrafast nitrile-water dynamics are confirmed by simulations. A higher (1.51 Å) resolution X-ray structure also reveals a water-drug interaction network. Maintenance of a crucial anchoring hydrogen bond may help retain the potency of rilpivirine against pocket mutations despite the structural variations they cause.

  14. Photochemistry of free and bound Zn-chlorophyll analogues to synthetic peptides depend on the quinone and pH.

    PubMed

    Razeghifard, Reza

    2015-11-01

    A synthetic peptide was used as a scaffold to bind Zn-Chlorophyll (ZnChl) analogues through histidine ligation to study their photochemistry in the presence of different type of quinones. The Chl analogues were chlorin e6 (Ce6), chlorin e6 trimethyl ester, pyropheophorbide a, and pheophorbide a while the quinones were PPBQ, DMBQ, NPHQ, DBTQ, DCBQ and PBQ. The binding of each ZnChl analogue to the peptide was verified by native gel electrophoresis. First the photo-stability of the ZnChl analogues were tested under continuous light. The ZnCe6 and ZnCe6TM analogues showed the least stability judged by the loss of optical signal intensity at their Qy band. The photoactivity of each ZnChl analogue was measured in the presence of each of the six quinones using time-resolved EPR spectroscopy. DMBQ was found to be the most efficient electron acceptor when all four ZnChl analogues were compared. The light-induced electron transfer between the ZnChl analogues complexed with the peptide and DMBQ were also measured using time-resolved EPR spectroscopy. The ZnCe6-peptide complex exhibited the highest photoactivity. The electron transfer in the complex was faster and the photoactivity yield was higher than those values obtained for free ZnCe6 and DMBQ. The fast phase of kinetics can be attributed to intra-protein electron transfer in the complex since it was not observed in the presence of DMBQ-glutathione adduct. Unlike free ZnCe6, the ZnCe6-peptide complex was robust and demonstrated very similar photoactivity efficiency in pH values 10, 8.0 and 5.0. The electron transfer kinetics were pH dependent and appeared to be modulated by the peptide charge and possibly fold. The charge recombination rate was slowed by an order of magnitude when the pH value was changed from 10.0 to 5.0. The implications of constructing the photoactive peptide complexes in terms of artificial photosynthesis are discussed.

  15. A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct.

    PubMed

    Arjunan, Palaniappa; Sax, Martin; Brunskill, Andrew; Chandrasekhar, Krishnamoorthy; Nemeria, Natalia; Zhang, Sheng; Jordan, Frank; Furey, William

    2006-06-01

    The crystal structure of the E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) has been determined with phosphonolactylthiamin diphosphate (PLThDP) in its active site. PLThDP serves as a structural and electrostatic analogue of the natural intermediate alpha-lactylthiamin diphosphate (LThDP), in which the carboxylate from the natural substrate pyruvate is replaced by a phosphonate group. This represents the first example of an experimentally determined, three-dimensional structure of a thiamin diphosphate (ThDP)-dependent enzyme containing a covalently bound, pre-decarboxylation reaction intermediate analogue and should serve as a model for the corresponding intermediates in other ThDP-dependent decarboxylases. Regarding the PDHc-specific reaction, the presence of PLThDP induces large scale conformational changes in the enzyme. In conjunction with the E1-PLThDP and E1-ThDP structures, analysis of a H407A E1-PLThDP variant structure shows that an interaction between His-407 and PLThDP is essential for stabilization of two loop regions in the active site that are otherwise disordered in the absence of intermediate analogue. This ordering completes formation of the active site and creates a new ordered surface likely involved in interactions with the lipoyl domains of E2s within the PDHc complex. The tetrahedral intermediate analogue is tightly held in the active site through direct hydrogen bonds to residues His-407, Tyr-599, and His-640 and reveals a new, enzyme-induced, strain-related feature that appears to aid in the decarboxylation process. This feature is almost certainly present in all ThDP-dependent decarboxylases; thus its inclusion in our understanding of general thiamin catalysis is important. PMID:16531404

  16. Efficiency Statistics and Bounds for Systems with Broken Time-Reversal Symmetry.

    PubMed

    Jiang, Jian-Hua; Agarwalla, Bijay Kumar; Segal, Dvira

    2015-07-24

    Universal properties of the statistics of stochastic efficiency for mesoscopic time-reversal symmetry broken energy transducers are revealed in the Gaussian approximation. We also discuss how the second law of thermodynamics restricts the statistics of stochastic efficiency. The tight-coupling limit becomes unfavorable, characterized by an infinitely broad distribution of efficiency at all times, when time-reversal symmetry breaking leads to an asymmetric Onsager response matrix. The underlying physics is demonstrated through the quantum Hall effect and further elaborated in a triple-quantum-dot three-terminal thermoelectric engine.

  17. Efficiency Statistics and Bounds for Systems with Broken Time-Reversal Symmetry

    NASA Astrophysics Data System (ADS)

    Jiang, Jian-Hua; Agarwalla, Bijay Kumar; Segal, Dvira

    2015-07-01

    Universal properties of the statistics of stochastic efficiency for mesoscopic time-reversal symmetry broken energy transducers are revealed in the Gaussian approximation. We also discuss how the second law of thermodynamics restricts the statistics of stochastic efficiency. The tight-coupling limit becomes unfavorable, characterized by an infinitely broad distribution of efficiency at all times, when time-reversal symmetry breaking leads to an asymmetric Onsager response matrix. The underlying physics is demonstrated through the quantum Hall effect and further elaborated in a triple-quantum-dot three-terminal thermoelectric engine.

  18. Copper(I)/S(8) reversible reactions leading to an end-on bound dicopper(II) disulfide complex: nucleophilic reactivity and analogies to copper-dioxygen chemistry.

    PubMed

    Maiti, Debabrata; Woertink, Julia S; Vance, Michael A; Milligan, Ashley E; Sarjeant, Amy A Narducci; Solomon, Edward I; Karlin, Kenneth D

    2007-07-18

    Elemental sulfur (S8) reacts reversibly with the copper(I) complex [(TMPA')CuI](+) (1), where TMPA' is a TMPA (tris(2-pyridylmethyl)amine) analogue with a 6-CH2OCH3 substituent on one pyridyl ligand arm, affording a spectroscopically pure end-on bound disulfido-dicopper(II) complex [{(TMPA')Cu(II)}2(mu-1,2-S2(2-))](2+) (2) {nu(S-S) = 492 cm(-1); nu(Cu-S)sym = 309 cm(-1)}; by contrast, [(TMPA)Cu(I)(CH3CN)](+) (3)/S8 chemistry produces an equilibrium mixture of at least three complexes. The reaction of excess PPh3 with 2 leads to formal "release" of zerovalent sulfur and reduction of copper ion to give the corresponding complex [(TMPA')Cu(I)(PPh3)](+) (11) along with S=PPh3 as products. Dioxygen displaces the disulfur moiety from 2 to produce the end-on Cu2O2 complex, [{(TMPA')Cu(II)}2(mu-1,2-O2(2-)](2+) (9). Addition of the tetradentate ligand TMPA to 2 generates the apparently more thermodynamically stable [{(TMPA)Cu(II)}2(mu-1,2-S2(2-))](2+) (4) and expected mixture of other species. Bubbling 2 with CO leads to the formation of the carbonyl adduct [(TMPA')CuI(CO)](+) (8). Carbonylation/sulfur-release/CO-removal cycles can be repeated several times. Sulfur atom transfer from 2 also occurs in a near quantitative manner when it is treated with 2,6-dimethylphenyl isocyanide (ArNC), leading to the corresponding isothiocyanate (ArNCS) and [(TMPA')Cu(I)(CNAr)](+) (12). Complex 2 readily reacts with PhCH2Br: [{(TMPA')Cu(II)}2(mu-1,2-S(2)(2-)](2+) (2) + 2 PhCH2Br --> [{(TMPA')Cu(II)(Br)}2](2+) (6) + PhCH2SSCH2Ph. The unprecedented substrate reactivity studies reveal that end-on bound mu-1,2-disulfide-dicopper(II) complex 2 provides a nucleophilic S2(2-) moiety, in striking contrast to the electrophilic behavior of a recently described side-on bound mu-eta(2):eta(2)-disulfido-dicopper(II) complex, [{(N3)Cu(II)}(2)(mu-eta(2):eta(2)-S2(2-))](2+) (5) with tridentate N3 ligand. The investigation thus reveals striking analogies of copper/sulfur and copper/dioxygen chemistries

  19. Spontaneous reverse movement of mRNA-bound tRNA through the ribosome.

    PubMed

    Konevega, Andrey L; Fischer, Niels; Semenkov, Yuri P; Stark, Holger; Wintermeyer, Wolfgang; Rodnina, Marina V

    2007-04-01

    During the translocation step of protein synthesis, a complex of two transfer RNAs bound to messenger RNA (tRNA-mRNA) moves through the ribosome. The reaction is promoted by an elongation factor, called EF-G in bacteria, which, powered by GTP hydrolysis, induces an open, unlocked conformation of the ribosome that allows for spontaneous tRNA-mRNA movement. Here we show that, in the absence of EF-G, there is spontaneous backward movement, or retrotranslocation, of two tRNAs bound to mRNA. Retrotranslocation is driven by the gain in affinity when a cognate E-site tRNA moves into the P site, which compensates the affinity loss accompanying the movement of peptidyl-tRNA from the P to the A site. These results lend support to the diffusion model of tRNA movement during translocation. In the cell, tRNA movement is biased in the forward direction by EF-G, which acts as a Brownian ratchet and prevents backward movement.

  20. Structure of HIV-1 Reverse Transcriptase with the Inhibitor -thujaplicinol Bound at the RNase H Active Site

    SciTech Connect

    Himmel, D.; Maegley, K; Pauly, T; Bauman, J; Das, K; Dharia, C; Clark, Jr., A; Ryan, K; Hickey, M; et al.

    2009-01-01

    Novel inhibitors are needed to counteract the rapid emergence of drug-resistant HIV variants. HIV-1 reverse transcriptase (RT) has both DNA polymerase and RNase H (RNH) enzymatic activities, but approved drugs that inhibit RT target the polymerase. Inhibitors that act against new targets, such as RNH, should be effective against all of the current drug-resistant variants. Here, we present 2.80 {angstrom} and 2.04 {angstrom} resolution crystal structures of an RNH inhibitor, {beta}-thujaplicinol, bound at the RNH active site of both HIV-1 RT and an isolated RNH domain. {beta}-thujaplicinol chelates two divalent metal ions at the RNH active site. We provide biochemical evidence that {beta}-thujaplicinol is a slow-binding RNH inhibitor with noncompetitive kinetics and suggest that it forms a tropylium ion that interacts favorably with RT and the RNA:DNA substrate.

  1. Rapid, Reversible Heterolytic Cleavage of Bound H2

    SciTech Connect

    Hulley, Elliott B.; Welch, Kevin D.; Appel, Aaron M.; DuBois, Daniel L.; Bullock, R. Morris

    2013-07-26

    Heterolytic cleavage of the H-H bond of H2 into a proton and hydride is a fundamentally important step in reactions of hydrogenase enzymes, oxidation of hydrogen in fuel cells, and catalytic hydrogenation of organic compounds. Incorporation of a pendant amine as a proton acceptor has been shown to facilitate reactions of the [FeFe]-hydrogenase enzyme as well as synthetic catalysts for oxidation of H2. We report the facile, reversible heterolytic cleavage of H2 in a Mn complex bearing a pendant amine, leading to an Mn-H and N-H bond, with an estimated rate of >107 s-1 at 25 ºC. We thank the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences, for support of the initial parts of this work. Current work is supported by the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.

  2. Inhibiting and reversing amyloid-β peptide (1-40) fibril formation with gramicidin S and engineered analogues.

    PubMed

    Luo, Jinghui; Otero, José M; Yu, Chien-Hung; Wärmländer, Sebastian K T S; Gräslund, Astrid; Overhand, Mark; Abrahams, Jan Pieter

    2013-12-16

    In Alzheimer's disease, amyloid-β (Aβ) peptides aggregate into extracellular fibrillar deposits. Although these deposits may not be the prime cause of the neurodegeneration that characterizes this disease, inhibition or dissolution of amyloid fibril formation by Aβ peptides is likely to affect its development. ThT fluorescence measurements and AFM images showed that the natural antibiotic gramicidin S significantly inhibited Aβ amyloid formation in vitro and could dissolve amyloids that had formed in the absence of the antibiotic. In silico docking suggested that gramicidin S, a cyclic decapeptide that adopts a β-sheet conformation, binds to the Aβ peptide hairpin-stacked fibril through β-sheet interactions. This may explain why gramicidin S reduces fibril formation. Analogues of gramicidin S were also tested. An analogue with a potency that was four-times higher than that of the natural product was identified.

  3. Thiazole-based γ-building blocks as reverse-turn mimetic to design a gramicidin S analogue: conformational and biological evaluation.

    PubMed

    Legrand, Baptiste; Mathieu, Loïc; Lebrun, Aurélien; Andriamanarivo, Soahary; Lisowski, Vincent; Masurier, Nicolas; Zirah, Séverine; Kang, Young Kee; Martinez, Jean; Maillard, Ludovic T

    2014-05-26

    This paper describes the ability of a new class of heterocyclic γ-amino acids named ATCs (4-amino(methyl)-1,3-thiazole-5-carboxylic acids) to induce turns when included in a tetrapeptide template. Both hybrid Ac-Val-(R or S)-ATC-Ile-Ala-NH2 sequences were synthesized and their conformations were studied by circular dichroism, NMR spectroscopy, MD simulations, and DFT calculations. It was demonstrated that the ATCs induced highly stable C9 pseudocycles in both compounds promoting a twist turn and a reverse turn conformation depending on their absolute configurations. As a proof of concept, a bioactive analogue of gramicidin S was successfully designed using an ATC building block as a turn inducer. The NMR solution structure of the analogue adopted an antiparallel β-pleated sheet conformation similar to that of the natural compound. The hybrid α,γ-cyclopeptide exhibited significant reduced haemotoxicity compared to gramicidin S, while maintaining strong antibacterial activity.

  4. Mutation V111I in HIV-2 Reverse Transcriptase Increases the Fitness of the Nucleoside Analogue-Resistant K65R and Q151M Viruses

    PubMed Central

    Deuzing, Ilona P.; Charpentier, Charlotte; Wright, David W.; Matheron, Sophie; Paton, Jack; Frentz, Dineke; van de Vijver, David A.; Coveney, Peter V.; Descamps, Diane; Boucher, Charles A. B.

    2014-01-01

    ABSTRACT Infection with HIV-2 can ultimately lead to AIDS, although disease progression is much slower than with HIV-1. HIV-2 patients are mostly treated with a combination of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and protease inhibitors designed for HIV-1. Many studies have described the development of HIV-1 resistance to NRTIs and identified mutations in the polymerase domain of RT. Recent studies have shown that mutations in the connection and RNase H domains of HIV-1 RT may also contribute to resistance. However, only limited information exists regarding the resistance of HIV-2 to NRTIs. In this study, therefore, we analyzed the polymerase, connection, and RNase H domains of RT in HIV-2 patients failing NRTI-containing therapies. Besides the key resistance mutations K65R, Q151M, and M184V, we identified a novel mutation, V111I, in the polymerase domain. This mutation was significantly associated with mutations K65R and Q151M. Sequencing of the connection and RNase H domains of the HIV-2 patients did not reveal any of the mutations that were reported to contribute to NRTI resistance in HIV-1. We show that V111I does not strongly affect drug susceptibility but increases the replication capacity of the K65R and Q151M viruses. Biochemical assays demonstrate that V111I restores the polymerization defects of the K65R and Q151M viruses but negatively affects the fidelity of the HIV-2 RT enzyme. Molecular dynamics simulations were performed to analyze the structural changes mediated by V111I. This showed that V111I changed the flexibility of the 110-to-115 loop region, which may affect deoxynucleoside triphosphate (dNTP) binding and polymerase activity. IMPORTANCE Mutation V111I in the HIV-2 reverse transcriptase enzyme was identified in patients failing therapies containing nucleoside analogues. We show that the V111I change does not strongly affect the sensitivity of HIV-2 to nucleoside analogues but increases the fitness of viruses with drug

  5. Reversals.

    ERIC Educational Resources Information Center

    National Center on Educational Media and Materials for the Handicapped, Columbus, OH.

    Selected from the National Instructional Materials Information System (NIMIS)--a computer based on-line interactive retrieval system on special education materials--the bibliography covers nine materials for remediating reversals in handicapped students at the early childhood and elementary levels. Entries are presented in order of NIMIS accession…

  6. The HEPT Analogue WPR-6 Is Active against a Broad Spectrum of Nonnucleoside Reverse Transcriptase Drug-Resistant HIV-1 Strains of Different Serotypes.

    PubMed

    Xu, Weisi; Zhao, Jianxiong; Sun, Jianping; Yin, Qianqian; Wang, Yan; Jiao, Yang; Liu, Junyi; Jiang, Shibo; Shao, Yiming; Wang, Xiaowei; Ma, Liying

    2015-08-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important components of the highly active antiretroviral therapy (HAART) used to treat human immunodeficiency type 1 virus (HIV-1). However, because of the emergence of drug resistance and the adverse effects of current anti-HIV drugs, it is essential to develop novel NNRTIs with an excellent safety profile, improved activity against NNRTI-resistant viruses, and enhanced activity against clinical isolates of different subtypes. Here, we have identified 1-[(benzyloxy)methyl]-6-(3,5-dimethylbenzyl)-5-iodopyrimidine-2,4(1H,3H)-dione (WPR-6), a novel NNRTI with a 50% effective concentration (EC50) of 2 to 4 nM against laboratory-adapted HIV-1 strain SF33 and an EC50 of 7 to 14 nM against nucleoside reverse transcriptase inhibitor-resistant HIV-1 strain 7391 with a therapeutic index of >1 × 10(4). A panel of five representative clinical virus isolates of different subtypes circulating predominantly in China was highly sensitive to WPR-6, with EC50s ranging from 1 to 6 nM. In addition, WPR-6 showed excellent antiviral potency against the most prevalent NNRTI-resistant viruses containing the K103N and Y181C mutations. To determine whether WPR-6 selects for novel resistant mutants, in vitro resistance selection was conducted with laboratory-adapted HIV-1 strain SF33 on MT-4 cells. The results demonstrated that V106I and Y188L were the two dominant NNRTI-associated resistance mutations detected in the breakthrough viruses. Taken together, these in vitro data indicate that WPR-6 has greater efficacy than the reference HEPT analogue TNK651 and the marketed drug nevirapine against HIV-1. However, to develop it as a new NNRTI, further improvement of its pharmacological properties is warranted. PMID:26055365

  7. A substrate variant as a high-affinity, reversible inhibitor: insight from the X-ray structure of cilastatin bound to membrane dipeptidase.

    PubMed

    Smyth, Timothy P; Wall, J Gerard; Nitanai, Yasushi

    2003-03-20

    An analysis of the X-ray structure of cilastatin bound to membrane dipeptidase, together with docking studies, is presented here to reveal how a simple amide may act as a high-affinity, reversible, amidase inhibitor. Cilastatin binds as a normal substrate and is orientated in a perfect near-attack conformer for formation of a tetrahedral intermediate with the zinc-bound water/hydroxide. This intermediate is fated, however, only to revert to its starting components as scission of the amide bond is prevented by the precise fit of cilastatin within the active site. The cilastatin alkyl end groups that are tightly buttressed against amino acid residues on opposite sides of the active site, are aligned along the C-N reaction coordinate axis thereby preventing collapse of the intermediate via rupture of the C-N bond. Such a feature could have more general applicability in the explicit design of substrate variants as selective, tight-binding, and reversible inhibitors.

  8. Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats.

    PubMed

    Flora, Swaran J S; Kannan, Gurusamy M; Pant, Bhagwat P; Jaiswal, Devendra K

    2002-06-01

    Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in the electronics industry. Exposure to GaAs in the semiconductor industry is a potential occupational hazard because cleaning and slicing GaAs ingots to yield the desired wafer could generate GaAs particles. The ability of GaAs to induce oxidative stress has not yet been reported. The present study reports the role of oxidative stress in GaAs-induced haematological and liver disorders and its possible reversal overturn by administration of meso-2,3-dimercaptosuccinic acid (DMSA) and one of its analogue, monoisoamyl DMSA (MiADMSA), either individually or in combination with oxalic acid. While DMSA and MiADMSA are potential arsenic chelators, oxalic acid is reported to be an effective gallium chelator. Male rats were exposed to 10 mg/kg GaAs orally, 5 days a week for 8 weeks. GaAs exposure was then stopped and rats were given a 0.5 mmol/kg dose of succimers (DMSA or MiADMSA), oxalic acid or a combination of the two, intraperitoneally once daily for 5 consecutive days. We found a significant fall in blood delta-aminolevulinic acid dehydratase (ALAD) activity and blood glutathione (GSH) level, and an increased urinary excretion of delta-aminolevulinic acid (ALA) and an increased malondialdehyde (MDA) level in erythrocytes of rats exposed to GaAs. Hepatic GSH levels decreased, whereas there was an increase in GSSG and MDA levels. The results suggest a role of oxidative stress in GaAs-induced haematological and hepatic damage. Administration of DMSA and MiADMSA produced effective recovery in most of the above variables. However, a greater effectiveness of the chelation treatment (i.e. removal of both gallium and arsenic from body organs) could be achieved by combined administration of succimer (DMSA) with oxalic acid since, after MiADMSA administration, a marked loss of essential metals (copper and zinc) is of concern.

  9. Detection and Time Course of Formation of Major Thiamin Diphosphate-Bound Covalent Intermediates Derived from a Chromophoric Substrate Analogue on Benzoylformate Decarboxylase

    SciTech Connect

    Chakraborty, Sumit; Nemeria, Natalia S.; Balakrishnan, Anand; Brandt, Gabriel S.; Kneen, Malea M.; Yep, Alejandra; McLeish, Michael J.; Kenyon, George L.; Petsko, Gregory A.; Ringe, Dagmar; Jordan, Frank

    2009-04-02

    The mechanism of the enzyme benzoylformate decarboxylase (BFDC), which carries out a typical thiamin diphosphate (ThDP)-dependent nonoxidative decarboxylation reaction, was studied with the chromophoric alternate substrate (E)-2-oxo-4(pyridin-3-yl)-3-butenoic acid (3-PKB). Addition of 3-PKB resulted in the appearance of two transient intermediates formed consecutively, the first one to be formed a predecarboxylation ThDP-bound intermediate with {lambda}{sub max} at 477 nm, and the second one corresponding to the first postdecarboxylation intermediate the enamine with {lambda}{sub max} at 437 nm. The time course of formation/depletion of the PKB-ThDP covalent complex and of the enamine showed that decarboxylation was slower than formation of the PKB-ThDP covalent adduct. When the product of decarboxylation 3-(pyridin-3-yl)acrylaldehyde (PAA) was added to BFDC, again an absorbance with {lambda}{sub max} at 473 nm was formed, corresponding to the tetrahedral adduct of PAA with ThDP. Addition of well-formed crystals of BFDC to a solution of PAA resulted in a high resolution (1.34 {angstrom}) structure of the BFDC-bound adduct of ThDP with PAA confirming the tetrahedral nature at the C2{alpha} atom, rather than of the enamine, and supporting the assignment of the {lambda}{sub max} at 473 nm to the PAA-ThDP adduct. The structure of the PAA-ThDP covalent complex is the first example of a product-ThDP adduct on BFDC. Similar studies with 3-PKB indicated that decarboxylation had taken place. Evidence was also obtained for the slow formation of the enamine intermediate when BFDC was incubated with benzaldehyde, the product of the decarboxylation reaction thus confirming its presence on the reaction pathway.

  10. Relation between the catalytic efficiency of the synthetic analogues of catechol oxidase with their electrochemical property in the free state and substrate-bound state.

    PubMed

    Chakraborty, Prateeti; Adhikary, Jaydeep; Ghosh, Bipinbihari; Sanyal, Ria; Chattopadhyay, Shyamal Kumar; Bauzá, Antonio; Frontera, Antonio; Zangrando, Ennio; Das, Debasis

    2014-08-18

    A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has been synthesized with the aim to determine the relationship between the electrochemical behavior of the dicopper(II) species in the absence as well as in the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the catalytic activity, kcat, in DMSO medium. The complexes have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis in some cases. Fifteen "end-off" compartmental ligands have been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R-phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2-aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N-(3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case of the combination of 2,6-diformyl-4-methylphenol and N-(2-aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 + 1 condensation becomes the reality and the ligands are denoted as L2(1-3). On reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all 15 complexes has been investigated in DMSO medium using 3,5-DTBC as model substrate. Treatment on the basis of Michaelis-Menten model has been applied for kinetic study, and thereby turnover number, kcat, values have been evaluated. Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the complexes in the presence as well as in the absence of 3,5-DTBC have been thoroughly investigated in DMSO medium. From those studies it is evident that oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps: first, semibenzoquinone followed by benzoquinone with concomitant

  11. HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site

    SciTech Connect

    Himmel,D.; Sarafianos, S.; Dharmasena, S.; Hossain, M.; McCoy-Simandle, K.; Ilina, T.; Clark, A.; Knight, J.; Julias, J.; et al.

    2007-01-01

    The rapid emergence of drug-resistant variants of human immunodeficiency virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency syndrome (AIDS) treatments, and new lead compounds that target novel binding sites are needed. We have determined the 3.15 {angstrom} resolution crystal structure of HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl hydrazone (DHBNH), an HIV-1 RT RNase H (RNH) inhibitor (RNHI). DHBNH is effective against a variety of drug-resistant HIV-1 RT mutants. While DHBNH has little effect on most aspects of RT-catalyzed DNA synthesis, at relatively high concentrations it does inhibit the initiation of RNA-primed DNA synthesis. Although primarily an RNHI, DHBNH binds >50 {angstrom} away from the RNH active site, at a novel site near both the polymerase active site and the non-nucleoside RT inhibitor (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain in the conformations seen in unliganded HIV-1 RT. DHBNH interacts with conserved residues (Asp186, Trp229) and has substantial interactions with the backbones of several less well-conserved residues. On the basis of this structure, we designed substituted DHBNH derivatives that interact with the NNRTI-binding pocket. These compounds inhibit both the polymerase and RNH activities of RT.

  12. Fractional diffusion on bounded domains

    SciTech Connect

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  13. Forward and reverse (retro) iron(III) or gallium(III) desferrioxamine E and ring-expanded analogues prepared using metal-templated synthesis from endo-hydroxamic acid monomers.

    PubMed

    Lifa, Tulip; Tieu, William; Hocking, Rosalie K; Codd, Rachel

    2015-04-01

    A metal-templated synthesis (MTS) approach was used to preorganize the forward endo-hydroxamic acid monomer 4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoic acid (for-PBH) about iron(III) in a 1:3 metal/ligand ratio to furnish the iron(III) siderophore for-[Fe(DFOE)] (ferrioxamine E) following peptide coupling. Substitution of for-PBH with the reverse (retro) hydroxamic acid analogue 3-(6-amino-N-hydroxyhexanamido)propanoic acid (ret-PBH) furnished ret-[Fe(DFOE)] (ret-ferrioxamine E). As isomers, for-[Fe(DFOE)] and ret-[Fe(DFOE)] gave identical mass spectrometry signals ([M + H(+)](+), m/zcalc 654.3, m/zobs 654.3), yet for-[Fe(DFOE)] eluted in a more polar window (tR = 23.44 min) than ret-[Fe(DFOE)] (tR = 28.13 min) on a C18 reverse-phase high-performance liquid chromatography (RP-HPLC) column. for-[Ga(DFOE)] (tR = 22.99 min) and ret-[Ga(DFOE)] (tR = 28.11 min) were prepared using gallium(III) as the metal-ion template and showed the same trend for the retention time. Ring-expanded analogues of for-[Fe(DFOE)] and ret-[Fe(DFOE)] were prepared from endo-hydroxamic acid monomers with one additional methylene unit in the amine-containing region, 4-[(6-aminohexyl)(hydroxy)amino]-4-oxobutanoic acid (for-HBH) or 3-(7-amino-N-hydroxyheptanamido)propanoic acid (ret-HBH), to give the corresponding tris(homoferrioxamine E) macrocycles, for-[Fe(HHDFOE)] or ret-[Fe(HHDFOE)] ([M + H(+)](+), m/zcalc 696.3, m/zobs 696.4). The MTS reaction using a constitutional isomer of for-HBH that transposed the methylene unit to the carboxylic acid containing region, 5-[(5-aminopentyl)(hydroxy)amino]-5-oxopentanoic acid (for-PPH), gave the macrocycle for-[Fe(HPDFOE)] in a yield significantly less than that for for-[Fe(HHDFOE)], with the gallium(III) analogue for-[Ga(HPDFOE)] unable to be detected. The work demonstrates the utility and limits of MTS for the assembly of macrocyclic siderophores from endo-hydroxamic acid monomers. Indirect measures (RP-HPLC order of elution, c log P values

  14. Amino acid polymorphism in the reverse transcriptase region of hepatitis B virus and the relationship with nucleos(t)ide analogues treatment for preventing mother-to-infant transmission.

    PubMed

    Chen, Jie; Yan, Ling; Zhu, Feng-Cai; Liu, Jian-Xun; Li, Rong-Cheng; Wang, Fu-Zhen; Li, Jie; Zhuang, Hui

    2014-08-01

    A high maternal serum hepatitis B virus (HBV) DNA level is associated with vaccine failure. The administration of nucleos(t)ide analogues (NAs) in pregnancy for decreasing serum HBV is regarded as an effective and safe method to reduce HBV perinatal transmission. However, the effect of NAs treatment is closely related to amino acid polymorphisms in the HBV reverse transcriptase (RT) region. The full-length RT coding region of 334 HBV isolates from untreated Chinese women of childbearing age with persistent HBV infection were sequenced and amino acid polymorphic analysis was performed to evaluate its impact on NAs treatment for decreasing HBV perinatal transmission. Of the 334 isolates, 36 (10.8%) harbored NAs resistance (NAr) mutations which were mainly putative drug mutations related to lamivudine. The primary drug mutation rtA181T/V was detected in three HBeAg-negative women with an HBV DNA level of <4 log IU/ml. These NAr mutations were rarely detected in women with an HBV DNA level of ≥7 log IU/ml (P = 0.014) or in women younger than 35 years (P = 0.001). The NAr mutation rate among young women (<35 years) who had a high HBV DNA level (≥7 log IU/ml) was significantly lower than in women who had lower HBV DNA levels (<7 log IU/ml) or who were older (≥35 years; P = 0.017). These results suggest that younger women with a high HBV DNA level harbor fewer NAr mutations and that this population may respond to NAs treatment for the prevention of mother-to-infant transmission.

  15. Dihydrogen catalysis of the reversible formation and cleavage of C-H and N-H bonds of aminopyridinate ligands bound to (η(5) -C5 Me5 )Ir(III.).

    PubMed

    Zamorano, Ana; Rendón, Nuria; López-Serrano, Joaquín; Valpuesta, José E V; Álvarez, Eleuterio; Carmona, Ernesto

    2015-02-01

    This study focuses on a series of cationic complexes of iridium that contain aminopyridinate (Ap) ligands bound to an (η(5) -C5 Me5 )Ir(III) fragment. The new complexes have the chemical composition [Ir(Ap)(η(5) -C5 Me5 )](+) , exist in the form of two isomers (1(+) and 2(+) ) and were isolated as salts of the BArF (-) anion (BArF =B[3,5-(CF3 )2 C6 H3 ]4 ). Four Ap ligands that differ in the nature of their bulky aryl substituents at the amido nitrogen atom and pyridinic ring were employed. In the presence of H2 , the electrophilicity of the Ir(III) centre of these complexes allows for a reversible prototropic rearrangement that changes the nature and coordination mode of the aminopyridinate ligand between the well-known κ(2) -N,N'-bidentate binding in 1(+) and the unprecedented κ-N,η(3) -pseudo-allyl-coordination mode in isomers 2(+) through activation of a benzylic C-H bond and formal proton transfer to the amido nitrogen atom. Experimental and computational studies evidence that the overall rearrangement, which entails reversible formation and cleavage of H-H, C-H and N-H bonds, is catalysed by dihydrogen under homogeneous conditions. PMID:25504864

  16. Dihydrogen catalysis of the reversible formation and cleavage of C-H and N-H bonds of aminopyridinate ligands bound to (η(5) -C5 Me5 )Ir(III.).

    PubMed

    Zamorano, Ana; Rendón, Nuria; López-Serrano, Joaquín; Valpuesta, José E V; Álvarez, Eleuterio; Carmona, Ernesto

    2015-02-01

    This study focuses on a series of cationic complexes of iridium that contain aminopyridinate (Ap) ligands bound to an (η(5) -C5 Me5 )Ir(III) fragment. The new complexes have the chemical composition [Ir(Ap)(η(5) -C5 Me5 )](+) , exist in the form of two isomers (1(+) and 2(+) ) and were isolated as salts of the BArF (-) anion (BArF =B[3,5-(CF3 )2 C6 H3 ]4 ). Four Ap ligands that differ in the nature of their bulky aryl substituents at the amido nitrogen atom and pyridinic ring were employed. In the presence of H2 , the electrophilicity of the Ir(III) centre of these complexes allows for a reversible prototropic rearrangement that changes the nature and coordination mode of the aminopyridinate ligand between the well-known κ(2) -N,N'-bidentate binding in 1(+) and the unprecedented κ-N,η(3) -pseudo-allyl-coordination mode in isomers 2(+) through activation of a benzylic C-H bond and formal proton transfer to the amido nitrogen atom. Experimental and computational studies evidence that the overall rearrangement, which entails reversible formation and cleavage of H-H, C-H and N-H bonds, is catalysed by dihydrogen under homogeneous conditions.

  17. Phosphonate analogue substrates for enolase.

    PubMed

    Anderson, V E; Cleland, W W

    1990-11-20

    Phosphonate analogues in which the bridge between C-2 and phosphorus is a CH2 group are slow substrates for yeast enolase. The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated. Primary deuterium isotope effects of 4-8 on V/KMg, but ones of only 1.15-1.32 on V for dehydration, show that proton removal to give the carbanion intermediate largely limits V/KMg and that a slow step follows which largely limits V (presumably carbanion breakdown). Since there is a D2O solvent isotope effect on V for the reverse reaction of 5, but not an appreciable one on the forward reaction, it appears that the slow rates with phosphonate analogues result from the fact that the carbanion intermediate is more stable than that formed from the normal substrates, and its reaction in both directions limits V. Increased stability as a result of replacement of oxygen by carbon at C-2 of the carbanion is the expected chemical behavior. PMID:2271661

  18. Outward Bound.

    ERIC Educational Resources Information Center

    Outward Bound, Inc., Andover, MA.

    The Outward Bound concept was developed in Germany and Great Britain with the saving of human life as the ultimate goal. Courses are designed to help students discover their true physical and mental limits through development of skills including emergency medical aid, firefighting, search and rescue, mountaineering, and sailing. Five Outward Bound…

  19. Quantum reverse hypercontractivity

    SciTech Connect

    Cubitt, Toby; Kastoryano, Michael; Montanaro, Ashley; Temme, Kristan

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  20. Survey of Analogue Spacetimes

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    Analogue spacetimes (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole,(mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid—and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  1. Nonstationary analogue black holes

    NASA Astrophysics Data System (ADS)

    Eskin, Gregory

    2014-12-01

    We study the existence of analogue nonstationary spherically symmetric black holes. The prime example is the acoustic model see Unruh (1981 Phys. Rev. Lett. 46 1351). We consider also a more general class of metrics that could be useful in other physical models of analogue black and white holes. We give examples of the appearance of black holes and of disappearance of white holes. We also discuss the relation between the apparent and the event horizons for the case of analogue black holes. In the end we study the inverse problem of determination of black or white holes by boundary measurements for the spherically symmetric nonstationary metrics.

  2. Presence of cobalamin analogues in animal tissues

    PubMed Central

    Kondo, Haruki; Kolhouse, Fred; Allen, Robert H.

    1980-01-01

    Cobalamin (Cbl, vitamin B-12) has been extracted and isolated from a number of animal tissues by using (i) reverse-affinity chromatography on R protein-Sepharose followed by adsorption to and elution from charcoal-coated agarose and (ii) paper chromatography. Radioisotope dilution assays showed that only 75-97% of the Cbl chromatographed in the position of crystalline Cbl. The remaining 3-25% was present in a number of slower and faster moving fractions. This suggested that Cbl analogues are present in animal tissues because appropriate controls ruled out the possibility that this material was artifactually derived from Cbl during the extraction and purification procedures. With a large-scale isolation from rabbit kidney, the material in five such fractions contained cobalt and had absorption spectra that were similar to but different from the spectrum of Cbl, indicating that they were Cbl analogues. Compared to Cbl, these Cbl analogues had decreased but definite affinities for Cbl-binding proteins with the following order of strength of binding: R protein > transcobalamin II > intrinsic factor. Compared to Cbl, they also had decreased but definite growth-promoting activity for two microorganisms, Euglena gracilis and Lactobacillus leichmannii, which require Cbl for growth. These Cbl analogues differed from each other and from 18 synthetic Cbl analogues, including the most common Cbl analogues synthesized by microorganisms, in at least one of the above features. These studies indicate that animal tissues contain a number of Cbl analogues whose origins, structures, and biologic activities remain to be determined. PMID:6928681

  3. 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

    PubMed Central

    Balzarini, J; Pérez-Pérez, M J; San-Félix, A; Schols, D; Perno, C F; Vandamme, A M; Camarasa, M J; De Clercq, E

    1992-01-01

    A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-ribofuranose as the pentose were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.06-0.8 microM but were not cytotoxic at a 1000- to 10,000-fold higher concentration. These nucleoside derivatives were also effective against various other HIV-1 strains, including those resistant to 3'-azido-3'-deoxythymidine, but not against HIV-2, simian immunodeficiency virus, Moloney murine sarcoma virus, or other RNA or DNA viruses. They proved to be highly specific inhibitors of the RNA-dependent DNA polymerase function of the HIV-1 reverse transcriptase, showing no marked inhibition of the HIV-1 reverse transcriptase-associated DNA-dependent DNA polymerase activity, HIV-2 reverse transcriptase, DNA polymerase alpha, herpes simplex virus 1 DNA polymerase, or Thermus aquaticus DNA polymerase. Images PMID:1374900

  4. Hydroxamate-based iron chelators: combinatorial syntheses of desferrioxamine B analogues and evaluation of binding affinities.

    PubMed

    Poreddy, Amruta R; Schall, Otto F; Osiek, Todd A; Wheatley, James R; Beusen, Denise D; Marshall, Garland R; Slomczynska, Urszula

    2004-01-01

    This article describes the solid-phase combinatorial methods developed for the synthesis of polyhydroxamate-based siderophores. This strategy was applied to generate several libraries of structural DFO (1a) analogues that include DFO variants, non-amide analogues, C-terminal modified analogues, reverse-amide analogues, and hybrid analogues. To assess the relative iron-binding affinities of these compounds, a high-throughput spectrophotometric screening method based on competition with 8-hydroxyquinoline-5-sulfonic acid was developed. Some of the promising candidates containing various terminal functional groups were identified and prepared on large scale to enable future studies in animal models for iron-overload diseases.

  5. Biodegradable analogues of DDT*

    PubMed Central

    Metcalf, Robert L.; Kapoor, Inder P.; Hirwe, Asha S.

    1971-01-01

    Despite the immense utility of DDT for vector control its usefulness is prejudiced by its stability in the environment and by the low rate at which it can be degraded biologically. Metabolic studies in insects, in mice, and in a model ecosystem with several food chains have shown that DDT analogues with substituent groups readily attacked by multifunction oxidases undergo a substantial degree of biological degradation and do not appear to be stored readily in animal tissues or concentrated in food chains. Detailed metabolic pathways have been worked out and it is clear that comparative biochemistry can be used to develop DDT analogues that are adequately persistent yet biodegradable. A number of new DDT analogues have been evaluated for insecticidal activity against flies and mosquitos and for their potential usefulness as safe, persistent, and biodegradable insecticides. PMID:5315354

  6. Natural Analogue Synthesis Report

    SciTech Connect

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

  7. Analogue models of pull-apart basins

    NASA Astrophysics Data System (ADS)

    McClay, Ken; Dooley, Tim

    1995-08-01

    Sandbox analogue models of pull-apart basins that developed in sedimentary strata above releasing steps in underlying basement faults are characterized by rhombic basins that are flat-bottomed box grabens with a subhorizontal synkinematic basin infill. Steep to nearly vertical, sigmoidal oblique-slip and segmented oblique-extensional faults are the dominant bounding structures of the pull-apart basins. Cross-basin, short-cut faults link the offset principal displacement zones that are characterized by flower structure development. The structural architectures of the physical models compare directly in form and dimensions to natural examples of strike-slip pull-apart basins.

  8. Carbocyclic nucleoside analogues: classification, target enzymes, mechanisms of action and synthesis

    NASA Astrophysics Data System (ADS)

    Matyugina, E. S.; Khandazhinskaya, A. P.; Kochetkov, Sergei N.

    2012-08-01

    Key biological targets (S-adenosyl-L-homocysteine hydrolase, telomerase, human immunodeficiency virus reverse transcriptase, herpes virus DNA polymerase and hepatitis B virus DNA polymerase) and the mechanisms of action of carbocyclic nucleoside analogues are considered. Structural types of analogues are discussed. Methods of synthesis for the most promising compounds and the spectrum of their biological activities are described. The bibliography includes 126 references.

  9. Coulomb Bound States of Strongly Interacting Photons

    NASA Astrophysics Data System (ADS)

    Maghrebi, M. F.; Gullans, M. J.; Bienias, P.; Choi, S.; Martin, I.; Firstenberg, O.; Lukin, M. D.; Büchler, H. P.; Gorshkov, A. V.

    2015-09-01

    We show that two photons coupled to Rydberg states via electromagnetically induced transparency can interact via an effective Coulomb potential. This interaction gives rise to a continuum of two-body bound states. Within the continuum, metastable bound states are distinguished in analogy with quasibound states tunneling through a potential barrier. We find multiple branches of metastable bound states whose energy spectrum is governed by the Coulomb potential, thus obtaining a photonic analogue of the hydrogen atom. Under certain conditions, the wave function resembles that of a diatomic molecule in which the two polaritons are separated by a finite "bond length." These states propagate with a negative group velocity in the medium, allowing for a simple preparation and detection scheme, before they slowly decay to pairs of bound Rydberg atoms.

  10. Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

    SciTech Connect

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Cravatt, Benjamin F.; Stevens, Raymond C.; Boger, Dale L.

    2011-11-02

    Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitor within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.

  11. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  12. Quantum analogue computing.

    PubMed

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  13. Using and interpreting analogue designs.

    PubMed

    Cook, Bryan G; Rumrill, Phillip D

    2005-01-01

    Researchers in rehabilitation counseling and disability studies sometimes use analogue research, which involves materials that approximate or describe reality (e.g., written vignettes, videotaped exemplars) rather than investigating phenomena in real-world settings. Analogue research often utilizes experimental designs, and it thereby frequently possesses a high degree of internal validity. Analogue research allows investigators to exercise tight control over the implementation of the independent or treatment variable and over potentially confounding variables, which enables them to isolate the effects of those treatment variables on selected outcome measures. However, the simulated nature of analogue research presents an important threat to external validity. As such, the generalizability of analogue research to real-life settings and situations may be problematic. These and other issues germane to analogue research in vocational rehabilitation are discussed in this article, illustrated with examples from the contemporary literature.

  14. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  15. Glutathione analogue sorbents selectively bind glutathione S-transferase isoenzymes.

    PubMed

    Castro, V M; Kelley, M K; Engqvist-Goldstein, A; Kauvar, L M

    1993-06-01

    Novel affinity sorbents for glutathione S-transferases (GSTs) were created by binding glutathione (GSH) analogues to Sepharose 6B. The GSH molecule was modified at the glycine moiety and at the group attached to the sulphur of cysteine. When tested by affinity chromatography in a flow-through microplate format, several of these sorbents selectively bound GST isoenzymes. gamma E-C(Hx)-phi G (glutathione with a hexyl moiety bound to cysteine and phenylglycine substituted for glycine) specifically bound rat GST 7-7, the Pi-class isoenzyme, from liver, kidney and small intestine. gamma E-C(Bz)-beta A (benzyl bound to cysteine and beta-alanine substituted for glycine) was highly selective for rat subunits 3 and 4, which are Mu-class isoenzymes. By allowing purification of the isoenzymes under mild conditions that preserve activity, the novel sorbents should be useful in characterizing the biological roles of GSTs in both normal animal and cancer tissues.

  16. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined. PMID:27575269

  17. Analogue modelling of syntectonic leucosomes in migmatitic schists

    NASA Astrophysics Data System (ADS)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  18. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  19. Incorporation of tryptophan analogues into the lantibiotic nisin.

    PubMed

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  20. A matrix lower bound

    SciTech Connect

    Grcar, Joseph F.

    2002-02-04

    A matrix lower bound is defined that generalizes ideas apparently due to S. Banach and J. von Neumann. The matrix lower bound has a natural interpretation in functional analysis, and it satisfies many of the properties that von Neumann stated for it in a restricted case. Applications for the matrix lower bound are demonstrated in several areas. In linear algebra, the matrix lower bound of a full rank matrix equals the distance to the set of rank-deficient matrices. In numerical analysis, the ratio of the matrix norm to the matrix lower bound is a condition number for all consistent systems of linear equations. In optimization theory, the matrix lower bound suggests an identity for a class of min-max problems. In real analysis, a recursive construction that depends on the matrix lower bound shows that the level sets of continuously differential functions lie asymptotically near those of their tangents.

  1. Separation and detection of cell wall-bound ferulic acid dehydrodimers and dehydrotrimers in cereals and other plant materials by reversed phase high-performance liquid chromatography with ultraviolet detection.

    PubMed

    Dobberstein, Diane; Bunzel, Mirko

    2010-08-25

    Ferulate dehydrodimers and the more recently discovered dehydrotrimers play an important role in the cell wall architecture of plant-based foods and forages. High-performance liquid chromatography methods to determine ferulate dimers often lack specificity; methods for trimers did not exist yet. A method for the determination of 11 cell wall-bound ferulate dehydrodimers and -trimers was developed, including the crucial separation of the di/trimers from the often dominating phenolic monomers. Validation parameters for the basic calibration of the dimers and trimers met our acceptance criteria. However, the matrix calibration revealed that lignin-rich matrices lead to problems with precision and accuracy that likely can be addressed by using a more specific detection, that is, mass spectrometric detection, next to improved sample preparation procedures. The method was used to analyze low-lignin fibers from corn, wheat, and rye grains, wild rice, asparagus, and sugar beet. With the exception of wild rice, the 5-5/8-O-4-, 8-O-4/8-O-4-, and 8-8(aryltetralin)/8-O-4-dehydrotrimers were detected in all analyzed samples, however, often in amounts below the limit of quantitation. PMID:23654229

  2. Physical Uncertainty Bounds (PUB)

    SciTech Connect

    Vaughan, Diane Elizabeth; Preston, Dean L.

    2015-03-19

    This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

  3. Potentials and bound states

    SciTech Connect

    Buell, W.F. ); Shadwick, B.A. )

    1995-03-01

    We discuss several quantum mechanical potential problems, focusing on those which highlight commonly held misconceptions about the existence of bound states. We present a proof, based on the variational principle, that certain one dimensional potentials always support at least one bound state, regardless of the potential's strength. We examine arguments concerning the existence of bound states based on the uncertainty principle and demonstrate, by explicit calculations, that such arguments must be viewed with skepticism.

  4. Mammalian folylpoly-. gamma. -glutamate synthetase. 3. Specificity for folate analogues

    SciTech Connect

    George, S.; Cichowicz, D.J.; Shane, B.

    1987-01-27

    A variety of folate analogues were synthesized to explore the specificity of the folate binding site of hog liver folypolyglutamate synthetase and the requirements for catalysis. Modifications of the internal and terminal glutamate moieties of folate cause large drops in on rates and/or affinity for the protein. The only exceptions are glutamine, homocysteate, and ornithine analogues, indicating a less stringent specificity around the delta-carbon of glutamate. It is proposed that initial folate binding to the enzyme involves low-affinity interactions at a pterin and a glutamate site and that the first glutamate bound is the internal residue adjacent to the benzoyl group. Processive movement of the polyglutamate chain through the glutamate site and a possible conformational change in the protein when the terminal residue is bound would result in tight binding and would position the ..gamma..-carboxyl of the terminal glutamate in the correct position for catalysis. The 4-amino substitution of folate increases the on rate for monoglutamate derivatives but severely impairs catalysis with diglutamate derivatives. Pteroylornithine derivatives are the first potent and specific inhibitors of folylpolyglutamate synthetase to be identified and may act as analogues of reaction intermediates. Other folate derivatives with tetrahedral chemistry replacing the peptide bond, such as pteroyl-..gamma..-glutamyl-(psi,CH/sub 2/-NH)-glutamate, retain affinity for the protein but are considerably less effective inhibitors than the ornithine derivatives. Enzyme activity was assayed using (/sup 14/C)glutamate.

  5. Probing the Active Center of Benzaldehyde Lyase with Substitutions and the Pseudosubstrate Analogue Benzoylphosphonic Acid Methyl Ester

    SciTech Connect

    Brandt, Gabriel S.; Nemeria, Natalia; Chakraborty, Sumit; McLeish, Michael J.; Yep, Alejandra; Kenyon, George L.; Petsko, Gregory A.; Jordan, Frank; Ringe, Dagmar

    2008-07-28

    Benzaldehyde lyase (BAL) catalyzes the reversible cleavage of (R)-benzoin to benzaldehyde utilizing thiamin diphosphate and Mg{sup 2+} as cofactors. The enzyme is important for the chemoenzymatic synthesis of a wide range of compounds via its carboligation reaction mechanism. In addition to its principal functions, BAL can slowly decarboxylate aromatic amino acids such as benzoylformic acid. It is also intriguing mechanistically due to the paucity of acid-base residues at the active center that can participate in proton transfer steps thought to be necessary for these types of reactions. Here methyl benzoylphosphonate, an excellent electrostatic analogue of benzoylformic acid, is used to probe the mechanism of benzaldehyde lyase. The structure of benzaldehyde lyase in its covalent complex with methyl benzoylphosphonate was determined to 2.49 {angstrom} (Protein Data Bank entry 3D7K) and represents the first structure of this enzyme with a compound bound in the active site. No large structural reorganization was detected compared to the complex of the enzyme with thiamin diphosphate. The configuration of the predecarboxylation thiamin-bound intermediate was clarified by the structure. Both spectroscopic and X-ray structural studies are consistent with inhibition resulting from the binding of MBP to the thiamin diphosphate in the active centers. We also delineated the role of His29 (the sole potential acid-base catalyst in the active site other than the highly conserved Glu50) and Trp163 in cofactor activation and catalysis by benzaldehyde lyase.

  6. Probing the active center of benzaldehyde lyase with substitutions and the pseudosubstrate analogue benzoylphosphonic acid methyl ester.

    PubMed

    Brandt, Gabriel S; Nemeria, Natalia; Chakraborty, Sumit; McLeish, Michael J; Yep, Alejandra; Kenyon, George L; Petsko, Gregory A; Jordan, Frank; Ringe, Dagmar

    2008-07-22

    Benzaldehyde lyase (BAL) catalyzes the reversible cleavage of ( R)-benzoin to benzaldehyde utilizing thiamin diphosphate and Mg (2+) as cofactors. The enzyme is important for the chemoenzymatic synthesis of a wide range of compounds via its carboligation reaction mechanism. In addition to its principal functions, BAL can slowly decarboxylate aromatic amino acids such as benzoylformic acid. It is also intriguing mechanistically due to the paucity of acid-base residues at the active center that can participate in proton transfer steps thought to be necessary for these types of reactions. Here methyl benzoylphosphonate, an excellent electrostatic analogue of benzoylformic acid, is used to probe the mechanism of benzaldehyde lyase. The structure of benzaldehyde lyase in its covalent complex with methyl benzoylphosphonate was determined to 2.49 A (Protein Data Bank entry 3D7K ) and represents the first structure of this enzyme with a compound bound in the active site. No large structural reorganization was detected compared to the complex of the enzyme with thiamin diphosphate. The configuration of the predecarboxylation thiamin-bound intermediate was clarified by the structure. Both spectroscopic and X-ray structural studies are consistent with inhibition resulting from the binding of MBP to the thiamin diphosphate in the active centers. We also delineated the role of His29 (the sole potential acid-base catalyst in the active site other than the highly conserved Glu50) and Trp163 in cofactor activation and catalysis by benzaldehyde lyase.

  7. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    PubMed Central

    Walmagh, Maarten; Zhao, Renfei; Desmet, Tom

    2015-01-01

    Trehalose (α-d-glucopyranosyl α-d-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside) or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside), offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis. PMID:26084050

  8. Similarity in drugs: reflections on analogue design.

    PubMed

    Wermuth, Camille G

    2006-04-01

    A survey of novel small-molecule therapeutics reveals that the majority of them result from analogue design and that their market value represents two-thirds of all small-molecule sales. In natural science, the term analogue, derived from the Latin and Greek analogia, has always been used to describe structural and functional similarity. Extended to drugs, this definition implies that the analogue of an existing drug molecule shares structural and pharmacological similarities with the original compound. Formally, this definition allows the establishment of three categories of drug analogues: analogues possessing chemical and pharmacological similarities (direct analogues); analogues possessing structural similarities only (structural analogues); and chemically different compounds displaying similar pharmacological properties (functional analogues). PMID:16580977

  9. Bounding species distribution models

    USGS Publications Warehouse

    Stohlgren, T.J.; Jarnevich, C.S.; Esaias, W.E.; Morisette, J.T.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used. ?? 2011 Current Zoology.

  10. Bounding Species Distribution Models

    NASA Technical Reports Server (NTRS)

    Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

  11. Reversible dementias

    PubMed Central

    Tripathi, Manjari; Vibha, Deepti

    2009-01-01

    In recent years, more attention has been given to the early diagnostic evaluation of patients with dementia which is essential to identify patients with cognitive symptoms who may have treatable conditions. Guidelines suggest that all patients presenting with dementia or cognitive symptoms should be evaluated with a range of laboratory tests, and with structural brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI). While many of the disorders reported as ‘reversible dementias’ are conditions that may well be associated with cognitive or behavioral symptoms, these symptoms are not always sufficiently severe to fulfill the clinical criteria for dementia. Thus, while the etiology of a condition may be treatable it should not be assumed that the associated dementia is fully reversible. Potentially reversible dementias should be identified and treatment considered, even if the symptoms are not sufficiently severe to meet the clinical criteria for dementia, and even if partial or full reversal of the cognitive symptoms cannot be guaranteed. In the literature, the most frequently observed potentially reversible conditions identified in patients with cognitive impairment or dementia are depression, adverse effects of drugs, drug or alcohol abuse, space-occupying lesions, normal pressure hydrocephalus, and metabolic conditions land endocrinal conditions like hypothyroidism and nutritional conditions like vitamin B-12 deficiency. Depression is by far the most common of the potentially reversible conditions. The review, hence addresses the common causes of reversible dementia and the studies published so far. PMID:21416018

  12. Bound infragravity waves

    NASA Astrophysics Data System (ADS)

    Okihiro, Michele; Guza, R. T.; Seymour, R. J.

    1992-07-01

    Model predictions of bound (i.e., nonlinearly forced by and coupled to wave groups) infragravity wave energy are compared with about 2 years of observations in 8- to 13-m depths at Imperial Beach, California, and Barbers Point, Hawaii. Frequency-directional spectra of free waves at sea and swell frequencies, estimated with a small array of four pressure sensors, are used to predict the bound wave spectra below 0.04 Hz. The predicted total bound wave energy is always less than the observed infragravity energy, and the underprediction increases with increasing water depth and especially with decreasing swell energy. At most half, and usually much less, of the observed infragravity energy is bound. Bound wave spectra are also predicted with data from a single wave gage in 183-m depth at Point Conception, California, and the assumption of unidirectional sea and swell. Even with energetic swell, less than 10% of the total observed infragravity energy in 183-m depth is bound. Free waves, either leaky or edge waves, are more energetic than bound waves at both the shallow and deep sites. The low level of infragravity energy observed in 183-m depth compared with 8- to 13-m depths, with similarly moderate sea and swell energy, suggests that leaky (and very high-mode edge) waves contribute less than 10% of the infragravity energy in 8-13 m. Most of the free infragravity energy in shallow water is refractively trapped and does not reach deep water.

  13. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  14. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  15. The effects of a series of capsaicin analogues on nociception and body temperature in the rat.

    PubMed

    Hayes, A G; Oxford, A; Reynolds, M; Shingler, A H; Skingle, M; Smith, C; Tyers, M B

    1984-03-26

    A series of capsaicin analogues have been synthesized in an attempt to try to separate the antinociceptive properties of capsaicin from its hypothermic effects. In capsaicin analogues with an unbranched alkyl side-chain of varying length, maximum antinociceptive and hypothermic activity was achieved with a chain length of 8-9 C atoms. Decreasing the chain length decreased both parameters equally. Substitution in the aromatic ring abolished activity. Several compounds related to homovanilloyl dodecylamide, an analogue of capsaicin in which the acylamide linkage is reversed, produced some antinociceptive activity without concomitant hypothermia, but the maximum antinociceptive effect achieved was very small. In the present series of capsaicin analogues good antinociception without hypothermia was not found.

  16. Validation of EMP bounds

    SciTech Connect

    Warne, L.K.; Merewether, K.O.; Chen, K.C.; Jorgenson, R.E.; Morris, M.E.; Solberg, J.E.; Lewis, J.G.; Derr, W.

    1996-07-01

    Test data on canonical weapon-like fixtures are used to validate previously developed analytical bounding results. The test fixtures were constructed to simulate (but be slightly worse than) weapon ports of entry but have known geometries (and electrical points of contact). The exterior of the test fixtures exhibited exterior resonant enhancement of the incident fields at the ports of entry with magnitudes equal to those of weapon geometries. The interior consisted of loaded transmission lines adjusted to maximize received energy or voltage but incorporating practical weapon geometrical constraints. New analytical results are also presented for bounding the energies associated with multiple bolt joints and for bounding the exterior resonant enhancement of the exciting fields.

  17. A novel NADPH:(bound) NADP+ reductase and NADH:(bound) NADP+ transhydrogenase function in bovine liver catalase.

    PubMed

    Gaetani, Gian F; Ferraris, Anna M; Sanna, Paola; Kirkman, Henry N

    2005-02-01

    Many catalases have the shared property of containing bound NADPH and being susceptible to inactivation by their own substrate, H2O2. The presence of additional (unbound) NADPH effectively prevents bovine liver and human erythrocytic catalase from becoming compound II, the reversibly inactivated state of catalase, and NADP+ is known to be generated in the process. The function of the bound NADPH, which is tightly bound in bovine liver catalase, has been unknown. The present study with bovine liver catalase and [14C]NADPH and [14C]NADH revealed that unbound NADPH or NADH are substrates for an internal reductase and transhydrogenase reaction respectively; the unbound NADPH or NADH cause tightly bound NADP+ to become NADPH without becoming tightly bound themselves. This and other results provide insight into the function of tightly bound NADPH. PMID:15456401

  18. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  19. Policy issues in space analogues

    NASA Astrophysics Data System (ADS)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  20. NMR studies of multiple conformations in complexes of Lactobacillus casei dihydrofolate reductase with analogues of pyrimethamine

    SciTech Connect

    Birdsall, B.; Tendler, S.J.B.; Feeney, J.; Carr, M.D. ); Arnold, J.R.P.; Thomas, J.A.; Roberts, G.C.K. ); Griffin, R.J.; Stevens, M.F.G. )

    1990-10-01

    {sup 1}H and {sup 19}F NMR signals from bound ligands have been assigned in one- and two-dimensional NMR spectra of complexes of Lactobacillus casei dihydrofolate reductase with various pyrimethamine analogues. The signals were identified mainly by correlating signals from bound and free ligands by using 2D exchange experiments. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotation about the pyrimidine-phenyl bond. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotation about the pyrimidine-phenyl bond. Analogues containing asymmetrically substituted aromatic rings exist as mixtures of two rotational isomers (an enantiomeric pair) because of this hindered rotation and the NMR spectra revealed that both isomers (forms A and B) bind to the enzyme with comparable, though unequal, binding energies. In this case two complete sets of bound proton signals were observed. The relative orientations of the two forms have been determined from NOE through-space connections between protons on the ligand and protein. Ternary complexes with NADP{sup {plus}} were also examined.

  1. Conformational restriction of angiotensin II: cyclic analogues having high potency.

    PubMed

    Spear, K L; Brown, M S; Reinhard, E J; McMahon, E G; Olins, G M; Palomo, M A; Patton, D R

    1990-07-01

    Cyclic analogues of angiotensin II (AII) were synthesized by connecting the side chains of residues 3 and 5 via a disulfide bridge. Appropriate conformational constraints afforded an analogue, [Hcy3,5]AII, having high contractile activity (pD2 = 8.48 vs 8.81 for AII) and excellent binding affinity (IC50 = 2.1 nM vs 2.2 nM for AII). This type of cyclization was also used to prepare a highly potent AII antagonist, [Sar1,Hcy3,5,Ile8]AII (pA2 = 9.09 vs 9.17 for [Sar1, Ile8]AII; IC50 = 0.9 nM vs 1.9 nM for [Sar1,Ile8]AII). Model building suggests that this ring structure is consistent with a receptor-bound conformation having any of a variety of three-residue turns, including a gamma-turn. In contrast, the receptor-bound conformation of AII does not appear to accommodate a beta-turn or an alpha-helix which includes residues 3-5.

  2. Inhibition of monoamine oxidase by benzoxathiolone analogues.

    PubMed

    Mostert, Samantha; Petzer, Anél; Petzer, Jacobus P

    2016-02-15

    Inhibitors of the monoamine oxidase (MAO) enzymes are considered useful therapeutic agents, and are used in the clinic for the treatment of depressive illness and Parkinson's disease. In addition, MAO inhibitors are also under investigation for the treatment of certain cardiovascular pathologies and as possible aids to smoking cessation. In an attempt to discover novel classes of compounds that inhibit the MAOs, the current study examines the human MAO inhibitory properties of a small series of 2H-1,3-benzoxathiol-2-one analogues. The results show that the benzoxathiolones are potent MAO-B inhibitors with IC50 values ranging from 0.003 to 0.051 μM. Although the benzoxathiolones are selective for the MAO-B isoform, two compounds display good MAO-A inhibition with IC50 values of 0.189 and 0.424 μM. Dialysis studies show that a selected compound inhibits the MAOs reversibly. It may thus be concluded that the benzoxathiolone class is suitable for the design and development of MAO-B inhibitors, and that in some instances good MAO-A inhibition may also be achieved.

  3. Synthesis and biological activity of a profluorescent analogue of coenzyme B12.

    PubMed Central

    Rosendahl, M S; Omann, G M; Leonard, N J

    1982-01-01

    We describe here the synthesis and chemical properties of linear(lin)-benzoadenosylcobalamin, a coenzyme B12 analogue that has a laterally extended nucleoside in the upper axial position. It is an effective competitive inhibitor of ribonucleotide reductase from Lactobacillus leichmannii. lin-Benzoadenosylcobalamin is nonfluorescent in solution but, on homolytic (light) or heterolytic (acid, cyanide) cleavage of the carbon-cobalt bond, forms fluorescent products. In addition, fluorescence is detectable on binding of the coenzyme analogue to ribonucleotide reductase, and the observed fluorescence polarization of the lin-benzoadenosyl moiety indicates that it is bound loosely to the enzyme when the coenzyme is partially dissociated. PMID:7048307

  4. Bradykinin antagonists with dehydrophenylalanine analogues at position 5.

    PubMed

    Greiner, G; Dornberger, U; Paegelow, I; Schölkens, B A; Liebmann, C; Reissmann, S

    1998-04-01

    Continuing the studies on structural requirements of bradykinin antagonists, it has been found that analogues with dehydrophenylalanine (deltaPhe) or its ring-substituted analogues (deltaPhe(X)) at position 5 act as antagonists on guinea pig pulmonary artery, and on guinea pig ileum. Because both organs are considered to be bradykinin B2 receptor tissues, the analogues with deltaPhe or deltaPhe(X) at position 5, but without any replacement at position 7, seem to represent a new structural type of B2 receptor antagonist. All the analogues investigated act as partial antagonists; they inhibit the bradykinin-induced contraction at low concentrations and act as agonists at higher concentrations. Ring substitutions by methyl groups or iodine reduce both the agonistic and antagonistic activity. Only substitution by fluorine gives a high potency. Incorporation of deltaPhe into different representative antagonists with key modifications at position 7 does not enhance the antagonist activity of the basic structures, with one exception. Only the combination of deltaPhe at position 5 with DPhe at position 7 increases the antagonistic potency on guinea pig ileum by about one order of magnitude. Radioligand binding studies indicate the importance of position 5 for the discrimination of B2 receptor subtypes. The binding affinity to the low-affinity binding site (KL) was not significantly changed by replacement of Phe by deltaPhe. In contrast, ring-methylation of deltaPhe results in clearly reduced binding to KL. The affinity to the high-affinity binding site (KH) was almost unchanged by the replacement of Phe in position 5 by deltaPhe, whereas the analogue with 2-methyl-dehydrophenylalanine completely failed to detect the KH-site. The peptides were synthesized on the Wang-resin according to the Fmoc/Bu(t) strategy using Mtr protection for the side chain of Arg. The dehydrophenylalanine analogues were prepared by a strategy involving PyBop couplings of the dipeptide unit Fmoc

  5. Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*

    PubMed Central

    Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

    2013-01-01

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5′-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5′-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  6. Vasectomy reversal.

    PubMed

    Belker, A M

    1987-02-01

    A vasovasostomy may be performed on an outpatient basis with local anesthesia, but also may be performed on an outpatient basis with epidural or general anesthesia. Local anesthesia is preferred by most of my patients, the majority of whom choose this technique. With proper preoperative and intraoperative sedation, patients sleep lightly through most of the procedure. Because of the length of time often required for bilateral microsurgical vasoepididymostomy, epidural or general anesthesia and overnight hospitalization are usually necessary. Factors influencing the preoperative choice for vasovasostomy or vasoepididymostomy in patients undergoing vasectomy reversal are considered. The preoperative planned choice of vasovasostomy or vasoepididymostomy for patients having vasectomy reversal described herein does not have the support of all urologists who regularly perform these procedures. My present approach has evolved as the data reported in Tables 1 and 2 have become available, but it may change as new information is evaluated. However, it offers a logical method for planning choices of anesthesia and inpatient or outpatient status for patients undergoing vasectomy reversal procedures. PMID:3811050

  7. Vasectomy reversal.

    PubMed

    Belker, A M

    1987-02-01

    A vasovasostomy may be performed on an outpatient basis with local anesthesia, but also may be performed on an outpatient basis with epidural or general anesthesia. Local anesthesia is preferred by most of my patients, the majority of whom choose this technique. With proper preoperative and intraoperative sedation, patients sleep lightly through most of the procedure. Because of the length of time often required for bilateral microsurgical vasoepididymostomy, epidural or general anesthesia and overnight hospitalization are usually necessary. Factors influencing the preoperative choice for vasovasostomy or vasoepididymostomy in patients undergoing vasectomy reversal are considered. The preoperative planned choice of vasovasostomy or vasoepididymostomy for patients having vasectomy reversal described herein does not have the support of all urologists who regularly perform these procedures. My present approach has evolved as the data reported in Tables 1 and 2 have become available, but it may change as new information is evaluated. However, it offers a logical method for planning choices of anesthesia and inpatient or outpatient status for patients undergoing vasectomy reversal procedures.

  8. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    DOEpatents

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  9. Bound Exciton Complexes

    NASA Astrophysics Data System (ADS)

    Meyer, B. K.

    In the preceding chapter, we concentrated on the properties of free excitons. These free excitons may move through the sample and hit a trap, a nonradiative or a radiative recombination center. At low temperatures, the latter case gives rise to either deep center luminescence, mentioned in Sect. 7.1 and discussed in detail in Chap. 9, or to the luminescence of bound exciton complexes (BE or BEC). The chapter continues with the most prominent of these BECs, namely A-excitons bound to neutral donors. The next aspects are the more weakly BEs at ionized donors. The Sect. 7.4 treats the binding or localization energies of BEC from a theoretical point of view, while Sect. 7.5 is dedicated to excited states of BECs, which contain either holes from deeper valence bands or an envelope function with higher quantum numbers. The last section is devoted to donor-acceptor pair transitions. There is no section devoted specifically to excitons bound to neutral acceptors, because this topic is still partly controversially discussed. Instead, information on these A0X complexes is scattered over the whole chapter, however, with some special emphasis seen in Sects. 7.1, 7.4, and 7.5.

  10. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    PubMed Central

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  11. The Canadian Analogue Research Network (CARN): Opportunities for Terrestrial Analogue Studies in Canada and Abroad

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Osinski, G. R.; Berinstain, A.; Léveillé, R.

    2007-03-01

    We will present an overview of the Canadian Analogue Research Network (CARN), including a description of the various analogue sites in CARN, potential new sites, and a discussion regarding how CARN is applicable to the global exploration strategy.

  12. Reverse preferential spread in complex networks

    NASA Astrophysics Data System (ADS)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  13. The Valles natural analogue project

    SciTech Connect

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  14. Universal bounds on current fluctuations

    NASA Astrophysics Data System (ADS)

    Pietzonka, Patrick; Barato, Andre C.; Seifert, Udo

    2016-05-01

    For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

  15. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

  16. Blog life: Entropy Bound

    NASA Astrophysics Data System (ADS)

    Steinberg, Peter

    2008-06-01

    Who is the blog written by? Peter Steinberg is a nuclear physicist at the Brookhaven National Laboratory in New York, US. He is acting project manager of the PHOBOS experiment, which used Brookhaven's Relativistic Heavy Ion Collider (RHIC) to search for unusual events produced during collisions between gold nuclei. He is also involved with the PHENIX experiment, which seeks to discover a new state of matter known as the quark-gluon plasma. In addition to his own blog Entropy Bound, Steinberg is currently blogging on a website that was set up last year to publicize the involvement of US scientists with the Large Hadron Collider (LHC) at CERN.

  17. A bound on chaos

    NASA Astrophysics Data System (ADS)

    Maldacena, Juan; Shenker, Stephen H.; Stanford, Douglas

    2016-08-01

    We conjecture a sharp bound on the rate of growth of chaos in thermal quantum systems with a large number of degrees of freedom. Chaos can be diagnosed using an out-of-time-order correlation function closely related to the commutator of operators separated in time. We conjecture that the influence of chaos on this correlator can develop no faster than exponentially, with Lyapunov exponent λ L ≤ 2π k B T/ℏ. We give a precise mathematical argument, based on plausible physical assumptions, establishing this conjecture.

  18. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  19. Discrete analogue of generalized Hardy spaces and multiplication operators on homogenous trees

    NASA Astrophysics Data System (ADS)

    Muthukumar, Perumal; Ponnusamy, Saminathan

    2016-08-01

    In this article, we define discrete analogue of generalized Hardy spaces and its separable subspace on a homogenous rooted tree and study some of its properties such as completeness, inclusion relations with other spaces, separability, growth estimate for functions in these spaces and their consequences. Equivalent conditions for multiplication operators to be bounded and compact are also obtained. Furthermore, we discuss about point spectrum, approximate point spectrum and spectrum of multiplication operators and discuss when a multiplication operator is an isometry.

  20. Continuous analogues of matrix factorizations

    PubMed Central

    Townsend, Alex; Trefethen, Lloyd N.

    2015-01-01

    Analogues of singular value decomposition (SVD), QR, LU and Cholesky factorizations are presented for problems in which the usual discrete matrix is replaced by a ‘quasimatrix’, continuous in one dimension, or a ‘cmatrix’, continuous in both dimensions. Two challenges arise: the generalization of the notions of triangular structure and row and column pivoting to continuous variables (required in all cases except the SVD, and far from obvious), and the convergence of the infinite series that define the cmatrix factorizations. Our generalizations of triangularity and pivoting are based on a new notion of a ‘triangular quasimatrix’. Concerning convergence of the series, we prove theorems asserting convergence provided the functions involved are sufficiently smooth. PMID:25568618

  1. Fully analogue photonic reservoir computer.

    PubMed

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-03-03

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers.

  2. Fully analogue photonic reservoir computer

    PubMed Central

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  3. Reversible fluorescence photoswitching in DNA.

    PubMed

    Smith, Darren A; Holliger, Philipp; Flors, Cristina

    2012-08-30

    We describe the engineering of reversible fluorescence photoswitching in DNA with high-density substitution, and its applications in advanced fluorescence microscopy methods. High-density labeling of DNA with cyanine dyes can be achieved by polymerase chain reaction using a modified DNA polymerase that has been evolved to efficiently incorporate Cy3- and Cy5-labeled cytosine base analogues into double-stranded DNA. The resulting biopolymer, "CyDNA", displays hundreds of fluorophores per DNA strand and is strongly colored and highly fluorescent, although previous observations suggest that fluorescence quenching at such high density might be a concern, especially for Cy5. Herein, we first investigate the mechanisms of fluorescence quenching in CyDNA and we suggest that two different mechanisms, aggregate formation and resonance energy transfer, are responsible for fluorescence quenching at high labeling densities. Moreover, we have been able to re-engineer CyDNA into a reversible fluorescence photoswitchable biopolymer by using the properties of the Cy3-Cy5 pair. This novel biopolymer constitutes a new class of photoactive DNA-based nanomaterial and is of great interest for advanced microscopy applications. We show that reversible fluorescence photoswitching in CyDNA can be exploited in optical lock-in detection imaging. It also lays the foundations for improved and sequence-specific super-resolution fluorescence microscopy of DNA. PMID:22861666

  4. About past interglacials as analogues to the Holocene and Anthropocene

    NASA Astrophysics Data System (ADS)

    Berger, Andre; Yin, Qiuzhen

    2014-05-01

    To understand better our current interglacial and its future, we have investigated the response of the climate system to insolation and CO2 at the peaks of the interglacials over the past 800,000 years using both LOVECLIM and CCSM3. If we identify these peaks with NH summer at perihelion, MIS-1, MIS-11 and MIS-19 show a pretty similar latitudinal and seasonal distribution of the incoming solar radiation, which leads to similar climate response to insolation. However, differences exist. When compared to the average of the last 9 interglacials, a warming over the Southern Ocean in austral winter occurs during MIS-1 and MIS-19 due to the summer remnant effect of insolation. However, this does not happen in MIS-11 because the large global cooling during this season is dominating the remnant effect of the austral summer. This leads to MIS-11 being a cool insolation-induced interglacial and thus not as good an analogue of MIS-1 as MIS-19, at least as far as insolation is concerned. The CO2 equivalent concentration is practically the same for MIS-1 and MIS-19 but is larger for MIS-11. The lower CO2 during MIS-1 and MIS-19 cools the Earth, reinforcing the insolation-induced cooling during boreal summer and moderating the warming during boreal winter. The reverse happens for MIS-11 for which its higher CO2 allows it to be finally classified among the warm interglacials. The interglacials MIS-9 and MIS-5 are the warmest over the last 800 ka and, as such, are considered as analogues for our CO2-induced future warm interglacial. However, their astronomical forcings are largely different from MIS-1 and its future, leading to a completely different seasonal and regional climate response compared to the simulated future climate. The best analogue to MIS-1 depends therefore upon the criteria used to select such an analogue. The climate simulated with insolation when NH summer at perihelion will be compared to climate resulting from other insolation scenario. If we look for

  5. Formation of "bound

    NASA Astrophysics Data System (ADS)

    Nowak, K.; Kästner, M.; Miltner, A.

    2009-04-01

    During degradation of organic pollutants in soil, metabolites, microbial biomass, CO2and "bound" residues ("non-extractable" residues in soil organic matter) are formed. Enhanced transformation of these contaminants into "bound" residues has been proposed as an alternative remediation method for polluted soils. However, this kind of residues may pose a potential risk for the environment due to their chemical structure and possible remobilization under different conditions. Therefore particular attention is given actually to "bound" residues. Part of these non-extractable residues may be "biogenic," because microorganisms use the carbon from the pollutant to form their biomass components (fatty acids, amino acids, amino sugars), which subsequently may be incorporated into soil organic matter. Furthermore, the CO2 originating from mineralization of xenobiotics, can be re-assimilated by microorganisms and also incorporated into "biogenic residue". The hazard posed by "bound" residues may be overestimated because they are "biogenic" (contain microbial fatty acids and amino acids). The knowledge about the pathways of "biogenic residue" formation is necessary for a proper assessment of the fate of tested pollutants and their turnover in the soil environment. Moreover, these data are needed to establish the realistic degradation rates of the contaminants in soil. The main objectives of this study are: to quantify the extent of "biogenic residue" (fatty acids, amino acids, amino sugars) formation during the degradation of a model pollutant (2,4-dichlorophenoxyacetic acid = 2,4-D) and during CO2 assimilation by microorganisms and to evaluate which components are mainly incorporated into "bound" residues. To investigate the extent of "biogenic residue" formation in soil during the degradation of 2,4-D, experiments with either 14C-U-ring and 13C6-2,4-D or carboxyl-14C 2,4-D were performed. The incubation experiments were performed according to OECD test guideline 307, in the

  6. Expanding the borononucleotide family: synthesis of borono-analogues of dCMP, dGMP and dAMP.

    PubMed

    Martin, Anthony R; Mohanan, Kishor; Luvino, Delphine; Floquet, Nicolas; Baraguey, Carine; Smietana, Michael; Vasseur, Jean-Jacques

    2009-11-01

    We previously reported the synthesis of a borononucleotide analogue of thymidine monophosphate and its association towards the formation of a new borono-linked dinucleotide. Here we describe the completion of the set of four 2'-deoxyborononucleotide analogues of natural nucleotide monophosphates, namely the previously unknown dCbn, dGbn and dAbn. These analogues were all prepared from the respective 5'-aldehydic nucleosides through a homologation/reduction sequence. The borononucleotides were subsequently obtained by either borylation (dCbn and dGbn) or cross-metathesis (CM) in the presence of the Hoveyda-Grubbs catalyst (dAbn). The reversible formation of the corresponding dinucleotides between these new analogues and uridine was studied by (1)H NMR, and semi-empirical calculations were carried out to provide bond length and electrostatic information that assess the structural similarities existing between these bioisosteres and their natural counterparts.

  7. Andreev-Majorana bound states in superfluids

    SciTech Connect

    Silaev, M. A. Volovik, G. E.

    2014-12-15

    We consider Andreev-Majorana (AM) bound states with zero energy on surfaces, interfaces, and vortices in different phases of the p-wave superfluids. We discuss the chiral superfluid {sup 3}He-A and time reversal invariant phases: superfluid {sup 3}He-B, planar and polar phases. The AM zero modes are determined by topology in the bulk and disappear at the quantum phase transition from the topological to nontopological state of the superfluid. The topology demonstrates the interplay of dimensions. In particular, the zero-dimensional Weyl points in chiral superfluids (the Berry phase monopoles in momentum space) give rise to the one-dimensional Fermi arc of AM bound states on the surface and to the one-dimensional flat band of AM modes in the vortex core. The one-dimensional nodal line in the polar phase produces a two-dimensional flat band of AM modes on the surface. The interplay of dimensions also connects the AM states in superfluids with different dimensions. For example, the topological properties of the spectrum of bound states in three-dimensional {sup 3}He-B are connected to the properties of the spectrum in the two-dimensional planar phase (thin film)

  8. Plant Volatile Analogues Strengthen Attractiveness to Insect

    PubMed Central

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A.; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  9. Synthesis and biological evaluation of febrifugine analogues.

    PubMed

    Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

    2014-12-01

    A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity. PMID:25632466

  10. Bound entangled states with a private key and their classical counterpart.

    PubMed

    Ozols, Maris; Smith, Graeme; Smolin, John A

    2014-03-21

    Entanglement is a fundamental resource for quantum information processing. In its pure form, it allows quantum teleportation and sharing classical secrets. Realistic quantum states are noisy and their usefulness is only partially understood. Bound-entangled states are central to this question--they have no distillable entanglement, yet sometimes still have a private classical key. We present a construction of bound-entangled states with a private key based on classical probability distributions. From this emerge states possessing a new classical analogue of bound entanglement, distinct from the long-sought bound information. We also find states of smaller dimensions and higher key rates than previously known. Our construction has implications for classical cryptography: we show that existing protocols are insufficient for extracting private key from our distributions due to their "bound-entangled" nature. We propose a simple extension of existing protocols that can extract a key from them. PMID:24702340

  11. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  12. Space analogue studies in Antarctica.

    PubMed

    Lugg, D; Shepanek, M

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  13. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-06-10

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity.

  14. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  15. Space analogue studies in Antarctica

    NASA Astrophysics Data System (ADS)

    Lugg, D.; Shepanek, M.

    1999-09-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mltogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  16. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  17. Reversibility conditions for quantum channels and their applications

    SciTech Connect

    Shirokov, M E

    2013-08-31

    Conditions for a quantum channel (noncommutative Markov operator) to be reversible with respect to complete families of quantum states with bounded rank are obtained. A description of all quantum channels reversible with respect to a given (orthogonal or nonorthogonal) complete family of pure states is given. Some applications in quantum information theory are considered. Bibliography: 20 titles.

  18. Sulfur analogues of psychotomimetic agents. Monothio analogues of mescaline and isomescaline.

    PubMed

    Jacob, P; Shulgin, A T

    1981-11-01

    Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase in vitro, but no positive correlation is apparent between the extent of enzymatic degradation and human psychotomimetic potency.

  19. [GnRH analogues for the treatment of fibroids].

    PubMed

    Murillo, Ester Ortiz; Cano, Antonio

    2013-07-01

    Uterine fibroids are benign tumors that are very common in women and may present significant symptoms in 20%-50% of cases. When they require action, their traditional management has been surgery (hysterectomy or fibroidectomy); however medical alternatives have been proposed, given that surgery is associated with a certain morbidity and mortality and involves healthcare costs. Within the pharmacological management of uterine fibroids, GnRH analogues are the best known and most commonly used drugs, although their indications are limited by the side effects associated with long-term treatment. Their primary indication is based on preoperative treatment (to hysterectomy or fibroidectomy) and in selected cases of patients close to menopause or who want more conservative management. These analogues are able to significantly reduce the uterine volume, the size of the fibroid and their accompanying symptoms. Their main disadvantage, however, lies in the reversibility of their effect when treatment is discontinued, along with the side effects associated with hypoestrogenism, such as climacteric symptoms and loss of bone mass. "Add-back" therapies, which associate low-dose estrogens to aGnRH, allow for extended use thanks to decreased side effects without affecting the benefits.

  20. The structure activity relationship of discodermolide analogues.

    PubMed

    Shaw, Simon J

    2008-03-01

    The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.

  1. Phosphorous-containing analogues of aspartame.

    PubMed

    Nelson, V; Mastalerz, P

    1984-12-01

    Four analogues of aspartame (aspartylphenylalanine methyl ester) were prepared in which one of the carboxylate groups was replaced by a phosphonate group. None of the peptides so obtained was sweet, in contrast with the parent compound which is over 100 times sweeter than sucrose. These results contrast with several published reports of phosphonate analogues of amino acids and peptides which are potent inhibitors of enzymes containing acceptor sites for the parent compound.

  2. Fundamental Bounds in Measurements for Estimating Quantum States

    NASA Astrophysics Data System (ADS)

    Lim, Hyang-Tag; Ra, Young-Sik; Hong, Kang-Hee; Lee, Seung-Woo; Kim, Yoon-Ho

    2014-07-01

    Quantum measurement unavoidably disturbs the state of a quantum system if any information about the system is extracted. Recently, the concept of reversing quantum measurement has been introduced and has attracted much attention. Numerous efforts have thus been devoted to understanding the fundamental relation of the amount of information obtained by measurement to either state disturbance or reversibility. Here, we experimentally prove the trade-off relations in quantum measurement with respect to both state disturbance and reversibility. By demonstrating the quantitative bound of the trade-off relations, we realize an optimal measurement for estimating quantum systems with minimum disturbance and maximum reversibility. Our results offer fundamental insights on quantum measurement and practical guidelines for implementing various quantum information protocols.

  3. Error Bounds for Interpolative Approximations.

    ERIC Educational Resources Information Center

    Gal-Ezer, J.; Zwas, G.

    1990-01-01

    Elementary error estimation in the approximation of functions by polynomials as a computational assignment, error-bounding functions and error bounds, and the choice of interpolation points are discussed. Precalculus and computer instruction are used on some of the calculations. (KR)

  4. Northwest Outward Bound Instructor's Manual.

    ERIC Educational Resources Information Center

    Northwest Outward Bound School, Portland, OR.

    Instructor responsibilities, procedures for completing activities safely, and instructional methods and techniques are outlined to assist instructors in the Northwest Outward Bound School (Portland, Oregon) as they strive for teaching excellence. Information is organized into six chapters addressing: history and philosophy of Outward Bound; course…

  5. Planetary habitability: lessons learned from terrestrial analogues

    NASA Astrophysics Data System (ADS)

    Preston, Louisa J.; Dartnell, Lewis R.

    2014-01-01

    Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which

  6. The Canadian Analogue Research Network (CARN): Opportunities for Mars Analogue Studies in the Canadian Arctic

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Berinstain, A.; Lebeuf, M.; Léveillé, R.

    2006-10-01

    The Canadian Analogue Research Network has been established by the Canadian Space Agency. This network of analogue sites, many of which are in the Arctic, provides a unique opportunity to further our understanding of the polar regions of Earth and Mars.

  7. Mechanism of benzaldehyde lyase studied via thiamin diphosphate-bound intermediates and kinetic isotope effects.

    PubMed

    Chakraborty, Sumit; Nemeria, Natalia; Yep, Alejandra; McLeish, Michael J; Kenyon, George L; Jordan, Frank

    2008-03-25

    Direct spectroscopic observation of thiamin diphosphate-bound intermediates was achieved on the enzyme benzaldehyde lyase, which carries out reversible and highly enantiospecific conversion of ( R)-benzoin to benzaldehyde. The key enamine intermediate could be observed at lambda max 393 nm in the benzoin breakdown direction and in the decarboxylase reaction starting with benzoylformate. With benzaldehyde as substrate, no intermediates could be detected, only formation of benzoin at 314 nm. To probe the rate-limiting step in the direction of ( R)-benzoin synthesis, the (1)H/ (2)H kinetic isotope effect was determined for benzaldehyde labeled at the aldehyde position and found to be small (1.14 +/- 0.03), indicating that ionization of the C2alphaH from C2alpha-hydroxybenzylthiamin diphosphate is not rate limiting. Use of the alternate substrates benzoylformic and phenylpyruvic acids (motivated by the observation that while a carboligase, benzaldehyde lyase could also catalyze the slow decarboxylation of 2-oxo acids) enabled the observation of the substrate-thiamin covalent intermediate via the 1',4'-iminopyrimidine tautomer, characteristic of all intermediates with a tetrahedral C2 substituent on ThDP. The reaction of benzaldehyde lyase with the chromophoric substrate analogue ( E)-2-oxo-4(pyridin-3-yl)-3-butenoic acid and its decarboxylated product ( E)-3-(pyridine-3-yl)acrylaldehyde enabled the detection of covalent adducts with both. Neither adduct underwent further reaction. An important finding of the studies is that all thiamin-related intermediates are in a chiral environment on benzaldehyde lyase as reflected by their circular dichroism signatures.

  8. Nonlocal spectroscopy of Andreev bound states

    NASA Astrophysics Data System (ADS)

    Schindele, J.; Baumgartner, A.; Maurand, R.; Weiss, M.; Schönenberger, C.

    2014-01-01

    We experimentally investigate Andreev bound states (ABSs) in a carbon nanotube quantum dot (QD) connected to a superconducting Nb lead (S). A weakly coupled normal metal contact acts as a tunnel probe that measures the energy dispersion of the ABSs. Moreover, we study the response of the ABS to nonlocal transport processes, namely, Cooper pair splitting and elastic co-tunnelling, which are enabled by a second QD fabricated on the same nanotube on the opposite side of S. We find an appreciable nonlocal conductance with a rich structure, including a sign reversal at the ground-state transition from the ABS singlet to a degenerate magnetic doublet. We describe our device by a simple rate equation model that captures the key features of our observations and demonstrates that the sign of the nonlocal conductance is a measure for the charge distribution of the ABS, given by the respective Bogoliubov-de Gennes amplitudes u and v.

  9. Saturating the holographic entropy bound

    SciTech Connect

    Bousso, Raphael; Freivogel, Ben; Leichenauer, Stefan

    2010-10-15

    The covariant entropy bound states that the entropy, S, of matter on a light sheet cannot exceed a quarter of its initial area, A, in Planck units. The gravitational entropy of black holes saturates this inequality. The entropy of matter systems, however, falls short of saturating the bound in known examples. This puzzling gap has led to speculation that a much stronger bound, S < or approx. A{sup 3/4}, may hold true. In this note, we exhibit light sheets whose entropy exceeds A{sup 3/4} by arbitrarily large factors. In open Friedmann-Robertson-Walker universes, such light sheets contain the entropy visible in the sky; in the limit of early curvature domination, the covariant bound can be saturated but not violated. As a corollary, we find that the maximum observable matter and radiation entropy in universes with positive (negative) cosmological constant is of order {Lambda}{sup -1} ({Lambda}{sup -2}), and not |{Lambda}|{sup -3/4} as had hitherto been believed. Our results strengthen the evidence for the covariant entropy bound, while showing that the stronger bound S < or approx. A{sup 3/4} is not universally valid. We conjecture that the stronger bound does hold for static, weakly gravitating systems.

  10. An HIV reverse transcriptase-selective nucleoside chain terminator.

    PubMed

    Fraley, Andrew W; Chen, Dongli; Johnson, Kenneth; McLaughlin, Larry W

    2003-01-22

    The synthesis of a 2',3'-dideoxynucleoside cytidine analogue, but one that lacks the O2-carbonyl, is described from 2-aminopyridine in an overall yield of 60%. The synthesis of the 2-pyridone C-nucleoside relies upon the use of a Heck-type coupling between an appropriately protected sugar glycal and the 5-iodo derivative of 2-aminopyridone. Upon conversion of the dideoxynucleoside to the corresponding 5'-triphosphate, the analogue ddNTP is observed to be a reasonable substrate with HIV reverse transcriptase (for a template dG residue), but is not a substrate for calf thymus DNA polymerase alpha or for human DNA polymerase beta. With the human mitochondrial DNA polymerase the analogue functions as a poor substrate. The observed polymerase selectivities appear to arise from the absence of the O2-carbonyl, which either results in a destabilized Watson-Crick base pair or represents a critical contact for some polymerases.

  11. Complementarity reveals bound entanglement of two twisted photons

    NASA Astrophysics Data System (ADS)

    Hiesmayr, Beatrix C.; Löffler, Wolfgang

    2013-08-01

    We demonstrate the detection of bipartite bound entanglement as predicted by the Horodecki's in 1998. Bound entangled states, being heavily mixed entangled quantum states, can be produced by incoherent addition of pure entangled states. Until 1998 it was thought that such mixing could always be reversed by entanglement distillation; however, this turned out to be impossible for bound entangled states. The purest form of bound entanglement is that of only two particles, which requires higher-dimensional (d > 2) quantum systems. We realize this using photon qutrit (d = 3) pairs produced by spontaneous parametric downconversion, that are entangled in the orbital angular momentum degrees of freedom, which is scalable to high dimensions. Entanglement of the photons is confirmed via a ‘maximum complementarity protocol’. This conceptually simple protocol requires only maximized complementary of measurement bases; we show that it can also detect bound entanglement. We explore the bipartite qutrit space and find that, also experimentally, a significant portion of the entangled states are actually bound entangled.

  12. Bounds on the information rate of quantum-secret-sharing schemes

    SciTech Connect

    Sarvepalli, Pradeep

    2011-04-15

    An important metric of the performance of a quantum-secret-sharing scheme is its information rate. Beyond the fact that the information rate is upper-bounded by one, very little is known in terms of bounds on the information rate of quantum-secret-sharing schemes. Furthermore, not every scheme can be realized with rate one. In this paper we derive upper bounds for the information rates of quantum-secret-sharing schemes. We show that there exist quantum access structures on n players for which the information rate cannot be better than O((log{sub 2}n)/n). These results are the quantum analogues of the bounds for classical-secret-sharing schemes proved by Csirmaz.

  13. The function of catalase-bound NADPH.

    PubMed

    Kirkman, H N; Galiano, S; Gaetani, G F

    1987-01-15

    Catalase (H2O2:H2O2 oxidoreductase, EC 1.11.1.6) is of historical interest for having been the subject of some of the earliest investigations of enzymes. A feature of catalase that has been poorly understood for several decades, however, is the mechanism by which catalase remains active in the presence of its own substrate, hydrogen peroxide. We reported recently that catalase contains tightly bound NADPH. The present study with bovine and human catalase revealed that NADPH both prevents and reverses the accumulation of compound II, an inactive form of catalase that is generated slowly when catalase is exposed to hydrogen peroxide. Since the effect of NADPH occurs even at NADPH concentrations below 0.1 microM, the protective mechanism is likely to operate in vivo. This discovery of the role of catalase-bound NADPH brings a unity to the concept of two different mechanisms for disposing of hydrogen peroxide (catalase and the glutathione reductase/peroxidase pathway) by revealing that both mechanisms are dependent on NADPH. PMID:3805001

  14. Synthesis and anticancer evaluation of spermatinamine analogues.

    PubMed

    Moosa, Basem A; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M

    2016-03-15

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. PMID:26874403

  15. Dolastatin 11 conformations, analogues and pharmacophore.

    PubMed

    Ali, Md Ahad; Bates, Robert B; Crane, Zackary D; Dicus, Christopher W; Gramme, Michelle R; Hamel, Ernest; Marcischak, Jacob; Martinez, David S; McClure, Kelly J; Nakkiew, Pichaya; Pettit, George R; Stessman, Chad C; Sufi, Bilal A; Yarick, Gayle V

    2005-07-01

    Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin 11 is a candidate for conversion to prodrugs.

  16. Bounding the elliptic Mahler measure

    NASA Astrophysics Data System (ADS)

    Pinner, Christopher

    1998-11-01

    We give a simple inequality relating the elliptic Mahler measure of a polynomial to the traditional Mahler measure (via the length of the polynomial). These bounds are essentially sharp. We also give the corresponding result for polynomials in several variables.

  17. Synthesis and κ-Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues

    PubMed Central

    2015-01-01

    The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure–activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the κ-opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred, suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other κ-opioid agonists. PMID:25426797

  18. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    PubMed Central

    Corcoran, Aoife; Nadkarni, Sharmin; Yasuda, Kaori; Sakaki, Toshiyuki; Brown, Geoffrey; Kutner, Andrzej; Marcinkowska, Ewa

    2016-01-01

    Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist. PMID:26840307

  19. Efficiency of Rectification: Reversible vs. Irreversible Regimes

    NASA Astrophysics Data System (ADS)

    Sokolov, I. M.

    2002-11-01

    Both man-made locomotive devices and molecular motors use gears to transform a reciprocating motion into a directed one. One of the most common gears is a rectifier, a mechanically irreversible appliance. The maximal energetic efficiency of an isothermic gear is bounded by unity, as a consequence of the Second Law. However, approaching this ideal efficiency does not imply approaching reversibility. We discuss what properties of a rectifier mostly influence the transduction efficiency and show that an appliance which locks under backward force is just the one which can approach the ideal efficiency either in the reversible or in the irreversible regime.

  20. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  1. Matrix algorithms for solving (in)homogeneous bound state equations

    PubMed Central

    Blank, M.; Krassnigg, A.

    2011-01-01

    In the functional approach to quantum chromodynamics, the properties of hadronic bound states are accessible via covariant integral equations, e.g. the Bethe–Salpeter equation for mesons. In particular, one has to deal with linear, homogeneous integral equations which, in sophisticated model setups, use numerical representations of the solutions of other integral equations as part of their input. Analogously, inhomogeneous equations can be constructed to obtain off-shell information in addition to bound-state masses and other properties obtained from the covariant analogue to a wave function of the bound state. These can be solved very efficiently using well-known matrix algorithms for eigenvalues (in the homogeneous case) and the solution of linear systems (in the inhomogeneous case). We demonstrate this by solving the homogeneous and inhomogeneous Bethe–Salpeter equations and find, e.g. that for the calculation of the mass spectrum it is as efficient or even advantageous to use the inhomogeneous equation as compared to the homogeneous. This is valuable insight, in particular for the study of baryons in a three-quark setup and more involved systems. PMID:21760640

  2. Effect of ATP analogues on the actin-myosin interface.

    PubMed

    Van Dijk, J; Fernandez, C; Chaussepied, P

    1998-06-01

    The interaction between skeletal myosin subfragment 1 (S1) and filamentous actin was examined at various intermediate states of the actomyosin ATPase cycle by chemical cross-linking experiments. Reaction of the actin-S1 complex with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysuccinimide generated products with molecular masses of 165 and 175 kDa, in which S1 loops of residues 626-647 and 567-578 were cross-linked independently to the N-terminal segment of residues 1-12 of one actin monomer, and of 265 kDa, in which the two loops were bound to the N termini of two adjacent monomers. In strong-binding complexes, i.e., without nucleotide or with ADP, S1 was sequentially cross-linked to one and then to two actin monomers. In the weak-binding complexes, two types of cross-linking pattern were observed. First, during steady-state hydrolysis of ATP or ATPgammaS at 20 degreesC, the cross-linking reaction gave rise to a small amount of unknown 200 kDa product. Second, in the presence of AMPPNP, ADP.BeFx, ADP.AlF4-, or ADP.VO43- or with S1 internally cross-linked by N,N'-p-phenylenedimaleimide, only the 265 kDa product was obtained. The presence of 200 mM salt inhibited cross-linking reactions in both weak- and strong-binding states, while it dissociated only weak-binding complexes. These results indicate that, in the weak-binding state populated with the ADP.Pi analogues, skeletal S1 interacts predominantly and with an apparent equal affinity with the N termini of two adjacent actin monomers, while these ionic contacts are much less significant in stabilizing the rigor actin-S1 complexes. They also suggest that the electrostatic actin-S1 interface is not influenced by the type of ADP.Pi analogue bound to the active site.

  3. Reversible Thermoset Adhesives

    NASA Technical Reports Server (NTRS)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  4. Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo.

    PubMed

    Roelofs, Anke J; Coxon, Fraser P; Ebetino, Frank H; Lundy, Mark W; Henneman, Zachary J; Nancollas, George H; Sun, Shuting; Blazewska, Katarzyna M; Bala, Joy Lynn F; Kashemirov, Boris A; Khalid, Aysha B; McKenna, Charles E; Rogers, Michael J

    2010-03-01

    Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647-labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14(high) bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14(+) cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo.

  5. Fluorescent Risedronate Analogues Reveal Bisphosphonate Uptake by Bone Marrow Monocytes and Localization Around Osteocytes In Vivo

    PubMed Central

    Roelofs, Anke J; Coxon, Fraser P; Ebetino, Frank H; Lundy, Mark W; Henneman, Zachary J; Nancollas, George H; Sun, Shuting; Blazewska, Katarzyna M; Bala, Joy Lynn F; Kashemirov, Boris A; Khalid, Aysha B; McKenna, Charles E; Rogers, Michael J

    2010-01-01

    Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647–labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research PMID:20422624

  6. Mechanistic Insights from the Binding of Substrate and Carbocation Intermediate Analogues to Aristolochene Synthase

    PubMed Central

    Chen, Mengbin; Al-lami, Naeemah; Janvier, Marine; D'Antonio, Edward L.; Faraldos, Juan A.; Cane, David E.; Allemann, Rudolf K.; Christianson, David W.

    2013-01-01

    Aristolochene synthase, a metal-dependent sesquiterpene cyclase from Aspergillus terreus, catalyzes the ionization-dependent cyclization of farnesyl diphosphate (FPP) to form the bicyclic eremophilane (+)-aristolochene with perfect structural and stereochemical precision. Here, we report the X-ray crystal structure of aristolochene synthase complexed with three Mg2+ ions and the unreactive substrate analogue farnesyl-S-thiolodiphosphate (FSPP), showing that the substrate diphosphate group is anchored by metal coordination and hydrogen bond interactions identical to those previously observed in the complex with three Mg2+ ions and inorganic pyrophosphate (PPi). Moreover, the binding conformation of FSPP directly mimics that expected for productively bound FPP, with the exception of the precise alignment of the C-S bond with regard to the C10-C11 π system that would be required for C1-C10 bond formation in the first step of catalysis. We also report crystal structures of aristolochene synthase complexed with Mg2+3-PPi and ammonium or iminium analogues of bicyclic carbocation intermediates proposed for the natural cyclization cascade. Various binding orientations are observed for these bicyclic analogues, and these orientations appear to be driven by favorable electrostatic interactions between the positively charged ammonium group of the analogue and the negatively charged PPi anion. Surprisingly, the active site is sufficiently flexible to accommodate analogues with partially or completely incorrect stereochemistry. Although this permissiveness in binding is unanticipated, based on the stereochemical precision of catalysis that leads exclusively to the (+)-aristolochene stereoisomer, it suggests the ability of the active site to enable controlled reorientation of intermediates during the cyclization cascade. Taken together, these structures illuminate important aspects of the catalytic mechanism. PMID:23905850

  7. Pyridopyrimidine analogues as novel adenosine kinase inhibitors.

    PubMed

    Zheng, G Z; Lee, C; Pratt, J K; Perner, R J; Jiang, M Q; Gomtsyan, A; Matulenko, M A; Mao, Y; Koenig, J R; Kim, K H; Muchmore, S; Yu, H; Kohlhaas, K; Alexander, K M; McGaraughty, S; Chu, K L; Wismer, C T; Mikusa, J; Jarvis, M F; Marsh, K; Kowaluk, E A; Bhagwat, S S; Stewart, A O

    2001-08-20

    A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.

  8. Analogues of thiolactomycin as potential antimalarial agents.

    PubMed

    Jones, Simon M; Urch, Jonathan E; Kaiser, Marcel; Brun, Reto; Harwood, John L; Berry, Colin; Gilbert, Ian H

    2005-09-22

    Analogues of the natural antibiotic thiolactomycin (TLM), an inhibitor of the condensing reactions of type II fatty acid synthase, were synthesized and evaluated for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum. Alkylation of the C4 hydroxyl group led to the most significant increase in growth inhibition (over a 100-fold increase in activity compared to TLM). To investigate the mode of action, the P. falciparum KASIII enzyme was produced for inhibitor assay. A number of TLM derivatives were identified that showed improved inhibition of this enzyme compared to TLM. Structure-activity relationships for enzyme inhibition were identified for some series of TLM analogues, and these also showed weak correlation with inhibition of parasite growth, but this did not hold for other series. On the basis of the lack of a clear correlation between inhibition of pfKASIII activity and parasite growth, we conclude that pfKASIII is not the primary target of TLM analogues. Some of the analogues also inhibited the growth of the parasitic protozoa Trypanosoma cruzi, T. brucei, and Leishmania donovani.

  9. Dumb holes: analogues for black holes.

    PubMed

    Unruh, W G

    2008-08-28

    The use of sonic analogues to black and white holes, called dumb or deaf holes, to understand the particle production by black holes is reviewed. The results suggest that the black hole particle production is a low-frequency and low-wavenumber process.

  10. Stilbenophane analogues of deoxycombretastatin A-4.

    PubMed

    Mateo, Carmen; Pérez-Melero, Concepción; Peláez, Rafael; Medarde, Manuel

    2005-08-01

    A new family of polyoxygenated stilbenophanes has been synthesized as conformationally restricted analogues of antimitotic combretastatins. By means of the McMurry olefination process, compounds derived from diethyleneglycol and 1,6-hexanediol were obtained, whereas Grubbs' catalyst failed in producing the ring-closing metathesis to this kind of macrocyclic products.

  11. Analogue Representations of Spatial Objects and Tranformations.

    ERIC Educational Resources Information Center

    Cooper, Lynn A.

    Considerable discussion and debate have been devoted to the extent and nature of structural or functional correspondence between internal representations and their external visual counterparts. An analogue representation or process is one in which the relational structure of external events is preserved in the corresponding internal…

  12. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-03-01

    Project overview provides background on carbonic anhydrase transport mechanism for CO2 in the human body and proposed approach for ARPA-E project to create a synthetic enzyme analogue and utilize it in a membrane for CO2 capture from flue gas.

  13. Synthesis and antimicrobial activity of squalamine analogue.

    PubMed

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  14. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    PubMed

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.

  15. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    PubMed

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. PMID:27301366

  16. Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors.

    PubMed

    Varga, Gergely; Docsa, Tibor; Gergely, Pál; Juhász, László; Somsák, László

    2013-03-15

    Di-O-cinnamoylated, -p-coumaroylated, and -feruloylated d-, l- and meso-tartaric acids were synthesized as analogues of the natural product FR258900, a glycogen phosphorylase (GP) inhibitor with in vivo antihyperglycaemic activity. The new compounds inhibited rabbit muscle GP in the low micromolar range, and bound to the allosteric site of the enzyme. The best inhibitor was 2,3-di-O-feruloyl meso-tartaric acid and had Ki values of 2.0μM against AMP (competitive) and 3.36μM against glucose-1-phosphate (non-competitive).

  17. Experimental activation of bound entanglement.

    PubMed

    Kaneda, Fumihiro; Shimizu, Ryosuke; Ishizaka, Satoshi; Mitsumori, Yasuyoshi; Kosaka, Hideo; Edamatsu, Keiichi

    2012-07-27

    Entanglement is one of the essential resources in quantum information and communication technology (QICT). The entanglement thus far explored and applied to QICT has been pure and distillable entanglement. Yet, there is another type of entanglement, called "bound entanglement," which is not distillable by local operations and classical communication. We demonstrate the experimental "activation" of the bound entanglement held in the four-qubit Smolin state, unleashing its immanent entanglement in distillable form, with the help of auxiliary two-qubit entanglement and local operations and classical communication. We anticipate that it opens the way to a new class of QICT applications that utilize more general classes of entanglement than ever, including bound entanglement.

  18. Bounds for nonlocality distillation protocols

    SciTech Connect

    Forster, Manuel

    2011-06-15

    Nonlocality can be quantified by the violation of a Bell inequality. Since this violation may be amplified by local operations, an alternative measure has been proposed--distillable nonlocality. The alternative measure is difficult to calculate exactly due to the double exponential growth of the parameter space. In this paper, we give a way to bound the distillable nonlocality of a resource by the solutions to a related optimization problem. Our upper bounds are exponentially easier to compute than the exact value and are shown to be meaningful in general and tight in some cases.

  19. Upper Bound for Induced Gravitation

    NASA Astrophysics Data System (ADS)

    Khuri, N. N.

    1982-08-01

    Given the assumption that Gind-1 given by the Adler-Zee formula is positive, an explicit and rigorous upper bound is derived for it. For pure SU(N) gauge theory, (16πG)-1<=(2512π2)(N2-1)ΛN2 is obtained where ΛN is the mass scale. In general the bound (16πG)-1<=25(π2144)CψΛ2 is obtained, where Cψ is the coefficient of the most singular anomaly contribution in x space, a constant easily determined by low-order perturbation theory for any gauge group.

  20. On lower bounds for polarisability

    NASA Astrophysics Data System (ADS)

    Montgomery, H. E.; Pupyshev, V. I.

    2013-09-01

    The response of molecular systems to external fields was one of the first areas studied after development of the new quantum mechanics. Early work by Kirkwood and Buckingham developed polarisability lower bounds that are still used today. This work uses an inequality proposed by Linderberg to develop a treatment of polarisability lower bounds that unifies the work of Kirkwood and Buckingham with Hylleraas' variational perturbation theory. In particular, the prehistory of the works of Kirkwood and Buckingham is described. Numerical examples are presented to demonstrate the convergence of approximate wavefunctions in the confined atom problem. The applicability of dimensional scaling and its utility in the analysis of confined systems are also discussed.

  1. Quantum Operation Time Reversal

    SciTech Connect

    Crooks, Gavin E.

    2008-03-25

    The dynamics of an open quantum system can be described by a quantum operation: A linear, complete positive map of operators. Here, I exhibit a compact expression for the time reversal of a quantum operation, which is closely analogous to the time reversal of a classical Markov transition matrix. Since open quantum dynamics are stochastic, and not, in general, deterministic, the time reversal is not, in general, an inversion of the dynamics. Rather, the system relaxes toward equilibrium in both the forward and reverse time directions. The probability of a quantum trajectory and the conjugate, time reversed trajectory are related by the heat exchanged with the environment.

  2. Wronskian Method for Bound States

    ERIC Educational Resources Information Center

    Fernandez, Francisco M.

    2011-01-01

    We propose a simple and straightforward method based on Wronskians for the calculation of bound-state energies and wavefunctions of one-dimensional quantum-mechanical problems. We explicitly discuss the asymptotic behaviour of the wavefunction and show that the allowed energies make the divergent part vanish. As illustrative examples we consider…

  3. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

    Discusses concept of covalent bonding as related to homonuclear diatomic molecules. Article draws attention to the existence of bound rare gas and alkaline earth diatomic molecules. Summarizes their molecular parameters and offers spectroscopic data. Strength and variation with distance of interatomic attractive forces is given. (Author/SA)

  4. Pieter Paul Rubens, "Prometheus Bound."

    ERIC Educational Resources Information Center

    Shoemaker, Marla K.

    1986-01-01

    Provides a full-color reproduction of Pieter Paul Rubens' painting, "Prometheus Bound," and a lesson plan for using it with students in grades 10 through 12. The goal of the lesson is to introduce students to the techniques of design and execution used by Rubens. (JDH)

  5. Entropic uncertainty and measurement reversibility

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Wehner, Stephanie; Wilde, Mark M.

    2016-07-01

    The entropic uncertainty relation with quantum side information (EUR-QSI) from (Berta et al 2010 Nat. Phys. 6 659) is a unifying principle relating two distinctive features of quantum mechanics: quantum uncertainty due to measurement incompatibility, and entanglement. In these relations, quantum uncertainty takes the form of preparation uncertainty where one of two incompatible measurements is applied. In particular, the ‘uncertainty witness’ lower bound in the EUR-QSI is not a function of a post-measurement state. An insightful proof of the EUR-QSI from (Coles et al 2012 Phys. Rev. Lett. 108 210405) makes use of a fundamental mathematical consequence of the postulates of quantum mechanics known as the non-increase of quantum relative entropy under quantum channels. Here, we exploit this perspective to establish a tightening of the EUR-QSI which adds a new state-dependent term in the lower bound, related to how well one can reverse the action of a quantum measurement. As such, this new term is a direct function of the post-measurement state and can be thought of as quantifying how much disturbance a given measurement causes. Our result thus quantitatively unifies this feature of quantum mechanics with the others mentioned above. We have experimentally tested our theoretical predictions on the IBM quantum experience and find reasonable agreement between our predictions and experimental outcomes.

  6. Titania bound sodium titanate ion exchanger

    DOEpatents

    DeFilippi, Irene C. G.; Yates, Stephen Frederic; Shen, Jian-Kun; Gaita, Romulus; Sedath, Robert Henry; Seminara, Gary Joseph; Straszewski, Michael Peter; Anderson, David Joseph

    1999-03-23

    This invention is method for preparing a titania bound ion exchange composition comprising admixing crystalline sodium titanate and a hydrolyzable titanium compound and, thereafter drying the titania bound crystalline sodium titanate and subjecting the dried titania bound ion exchange composition to optional compaction and calcination steps to improve the physical strength of the titania bound composition.

  7. Synthesis and biological evaluation of hydrazidomycin analogues.

    PubMed

    Meyer, Florian; Ueberschaar, Nico; Dahse, Hans-Martin; Hertweck, Christian

    2013-11-15

    Hydrazidomycin A is an unusual secondary metabolite of Streptomyces atratus that features a rare enehydrazide core. To learn more about structure-activity relationships of the reported cytotoxic and antiproliferative agent several synthetic routes were explored to synthesize a variety of hydrazidomycin derivatives. Specifically, the size of the side chains, the nature of the double bond and the polar head group were altered. Overall, fourteen analogues were tested for their cytotoxic and antiproliferative effects. Re-examination of synthetic hydrazidomycin A suggests that the antiproliferative activity is attributed to a yet unknown compound that results from degradation or rearrangement. Several of the less complex analogues, however, show antiproliferative activities against individual cancer cell lines and turned out to be more potent than hydrazidomycin A.

  8. Synthesis of constrained analogues of tryptophan

    PubMed Central

    Negrato, Marco; Abbiati, Giorgio; Dell’Acqua, Monica

    2015-01-01

    Summary A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. PMID:26664620

  9. Platinum analogues in preclinical and clinical development.

    PubMed

    Hamilton, T C; O'Dwyer, P J; Ozols, R F

    1993-11-01

    The impact of cisplatin on chemotherapy for solid tumors has led to the synthesis of many molecules with platinum as their central building block. These so-called platinum analogues have been developed with the obvious goals of improving the antitumor activity of cisplatin and hopefully, at the same time, altering the dose-limiting side effects of the prototype drug. At least 10 such molecules are in clinical development, whereas several others are at various stages of preclinical testing. PMID:8305533

  10. The Brookhaven electron analogue, 1953--1957

    SciTech Connect

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  11. Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases.

    PubMed

    Turek, T C; Gaon, I; Distefano, M D; Strickland, C L

    2001-05-18

    Protein prenylation is a posttranslational lipid modification in which C(15) and C(20) isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Ras protein is farnesylated coupled with the observation that mutant forms of Ras are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Ras-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with (32)P-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta-subunit of this enzyme. These results clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.

  12. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss. PMID:27626017

  13. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss.

  14. Hydrogen adsorption in thin films of Prussian blue analogue

    SciTech Connect

    Yang, Dali; Ding, Vivian; Luo, Junhua; Currier, Robert P; Obrey, Steve; Zhao, Yusheng

    2008-01-01

    Quartz crystal microbalance with dissipation (QCM-D) measurement was used to investigate the kinetics of the molecular hydrogen adsorption into thin films of prussian blue analogues - Cu{sub 3}[Co(CN){sub 6}]{sub 2} at ambient conditions. Although the equilibrium adsorption seems to be independent of the thickness, the adsorption rate substantially decreases with the thickness of the films. In addition, the reversibility of H{sub 2} adsorption into the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films was investigated. The results indicate that the Cu{sub 3}[Co(CN){sub 6}]{sub 2} maily interacts with H{sub 2} molecules physically. The highest H{sub 2} uptake by the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films is obtained when the gas phase is stagnant inside the testing cell. However, the unusual high H{sub 2} uptake obtained from the QCM-D measurement makes us question how reliable this analytic methodology is.

  15. Vasectomy reversal in humans.

    PubMed

    Bernie, Aaron M; Osterberg, E Charles; Stahl, Peter J; Ramasamy, Ranjith; Goldstein, Marc

    2012-10-01

    Vasectomy is the most common urological procedure in the United States with 18% of men having a vasectomy before age 45. A significant proportion of vasectomized men ultimately request vasectomy reversal, usually due to divorce and/or remarriage. Vasectomy reversal is a commonly practiced but technically demanding microsurgical procedure that restores patency of the male excurrent ductal system in 80-99.5% of cases and enables unassisted pregnancy in 40-80% of couples. The discrepancy between the anastomotic patency rates and clinical pregnancy rates following vasectomy reversal suggests that some of the biological consequences of vasectomy may not be entirely reversible in all men. Herein we review what is known about the biological sequelae of vasectomy and vasectomy reversal in humans, and provide a succinct overview of the evaluation and surgical management of men desiring vasectomy reversal.

  16. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math Science... Upward Bound Math Science Annual Performance Report. OMB Control Number: 1840-NEW. Type of Review: New... under the regular Upward Bound (UB) and Upward Bound Math and Science (UBMS) Programs. The Department...

  17. Climatic Forecasting of Net Infiltration at Yucca Montain Using Analogue Meteororological Data

    SciTech Connect

    B. Faybishenko

    2006-09-11

    At Yucca Mountain, Nevada, future changes in climatic conditions will most likely alter net infiltration, or the drainage below the bottom of the evapotranspiration zone within the soil profile or flow across the interface between soil and the densely welded part of the Tiva Canyon Tuff. The objectives of this paper are to: (a) develop a semi-empirical model and forecast average net infiltration rates, using the limited meteorological data from analogue meteorological stations, for interglacial (present day), and future monsoon, glacial transition, and glacial climates over the Yucca Mountain region, and (b) corroborate the computed net-infiltration rates by comparing them with the empirically and numerically determined groundwater recharge and percolation rates through the unsaturated zone from published data. In this paper, the author presents an approach for calculations of net infiltration, aridity, and precipitation-effectiveness indices, using a modified Budyko's water-balance model, with reference-surface potential evapotranspiration determined from the radiation-based Penman (1948) formula. Results of calculations show that net infiltration rates are expected to generally increase from the present-day climate to monsoon climate, to glacial transition climate, and then to the glacial climate. The forecasting results indicate the overlap between the ranges of net infiltration for different climates. For example, the mean glacial net-infiltration rate corresponds to the upper-bound glacial transition net infiltration, and the lower-bound glacial net infiltration corresponds to the glacial transition mean net infiltration. Forecasting of net infiltration for different climate states is subject to numerous uncertainties-associated with selecting climate analogue sites, using relatively short analogue meteorological records, neglecting the effects of vegetation and surface runoff and runon on a local scale, as well as possible anthropogenic climate changes.

  18. The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands.

    PubMed

    Lim, Kwang Su; Lee, Hobin; Kim, Sung Eun; Ha, Tae-Hwan; Ann, Jihyae; Son, Karam; Choi, Sun; Sun, Wei; Pearce, Larry V; DeAndrea-Lazarus, Ian A; Blumberg, Peter M; Lee, Jeewoo

    2013-10-01

    A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I>Br>Cl>F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with Ki(ant)=2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism.

  19. Aniline mustard analogues of the DNA-intercalating agent amsacrine: DNA interaction and biological activity.

    PubMed

    Fan, J Y; Valu, K K; Woodgate, P D; Baguley, B C; Denny, W A

    1997-04-01

    Two series of analogues of the clinical antileukemic drug and DNA-intercalating ligand amsacrine have been prepared, containing aniline mustard sidechains of varying reactivity, linked either at the 4-position of the intercalating acridine chromophore (type A) or at the 1'-position of the 9-anilino group (type B). DNase I footprinting assays showed that compounds of type B had stronger reversible binding to DNA than did compounds of type A. Compounds of each type showed similar patterns of alkylation-induced cleavage of DNA, and alkylate at the N7 of guanines in runs of guanines (similar to the pattern for untargeted mustards) as well as some adenines. Both classes of compounds crosslinked DNA, although those bearing relatively inactive mustards did so only at high drug/base pair ratios. However, while the patterns of DNA alkylation were broadly similar, the compounds were considerably more cytotoxic than analogous untargeted mustards. Comparison of their cytotoxicities in wild-type and DNA repair-deficient lines indicated this toxicity was due to DNA crosslinks (except for the least reactive SO2-linked mustards). The 4-linked analogues showed slightly higher in vivo antileukemic activity than the corresponding 1'-linked analogues.

  20. Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells.

    PubMed

    Jalewa, Jaishree; Sharma, Mohit Kumar; Hölscher, Christian

    2016-10-01

    Currently, there is no viable treatment available for Parkinson's disease (PD) that stops or reverses disease progression. Interestingly, studies testing the glucagon-like-peptide-1 (GLP-1) mimetic Exendin-4 have shown neuroprotective/neurorestorative properties in pre-clinical tests and in a pilot clinical study of PD. Incretin analogues were originally developed to treat type 2 diabetes and several are currently on the market. In this study, we tested novel incretin analogues on the dopaminergic SH-SY5Y neuroblastoma cells against a toxic mitochondrial complex I inhibitor, Rotenone. Here, we investigate for the first time the effects of six different incretin receptor agonists - Liraglutide, D-Ser2-Oxyntomodulin, a GLP-1/GIP Dual receptor agonist, dAla(2)-GIP-GluPal, Val(8)GLP-1-GluPal and exendin-4. Post-treatment with doses of 1, 10 or 100 nM of incretin analogues for 12 h increased the survival of SH-SY5Y cells treated with 1 μM Rotenone for 12 h. Furthermore, we studied the post-treatment effect of 100 nM incretin analogues against 1 μM Rotenone stress on apoptosis, mitochondrial stress and autophagy markers. We found significant protective effects of the analogues against Rotenone stress on cell survival and on mitochondrial and autophagy-associated markers. The novel GLP-1/GIP Dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. Using the Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, we further show that the neuroprotective effects are partially PI3K-independent. Our data suggest that the neuroprotective properties exhibited by incretin analogues against Rotenone stress involve enhanced autophagy, increased Akt-mediated cell survival and amelioration of mitochondrial dysfunction. These mechanisms can explain the neuroprotective effects of incretin analogues reported in clinical trials. GLP-1, GIP and dual incretin receptor agonists showed protective effects in SH-SY5Y cells

  1. Design of potent linear alpha-melanotropin 4-10 analogues modified in positions 5 and 10.

    PubMed

    Al-Obeidi, F; Hruby, V J; Castrucci, A M; Hadley, M E

    1989-01-01

    alpha-Melanocyte stimulating hormone (alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that has diverse physiological functions in addition to its reversible darkening of amphibian skins by stimulating melanosome dispersion within melanophores. On the basis of theoretical and experimental results from our laboratory and others, we have designed a group of 1-13, 4-13, and especially 4-10 analogues related to the superpotent analogue [Nle4,D-Phe7]alpha-MSH in which the Glu5 has been replaced with Asp5, and the Gly10 has been replaced with Lys10 and other basic amino acid residues in the 4-10 analogues, and in which Gly10 and Lys11 were interchanged in the longer peptide analogues. In the 1-13 and 4-13 series the Lys10, Gly11 analogues generally retained superpotency for the D-Phe7-containing analogues. Most interestingly, synthesis of Ac-[Nle4,Xxx5,Yyy7,Zzz10]alpha-MSH4-10-NH2 analogues where Xxx = Asp or Glu, Yyy = Phe or D-Phe, and Zzz = basic amino acids (Lys, Orn, alpha,gamma-diaminobutyric acid (Dab), and alpha,beta-diaminopropionic acid (Dpr] provided melanotropins with potencies up to 10 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening and 8-50 times more potent than alpha-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. To our knowledge, Ac-[Nle4,Asp5,D-Phe7,Dab10]alpha-MSH4-10-NH2, the most potent analogue, is the most potent melanotropin obtained thus far for the Anolis assay system. These results provide new insights into the structural and conformational requirements for biological potency of alpha-MSH and the differential structural and conformational requirements of alpha-MSH and its analogues at two different types of pigment cell receptors. PMID:2535874

  2. Quantum secret sharing schemes and reversibility of quantum operations

    SciTech Connect

    Ogawa, Tomohiro; Sasaki, Akira; Iwamoto, Mitsugu; Yamamoto, Hirosuke

    2005-09-15

    Quantum secret sharing schemes encrypting a quantum state into a multipartite entangled state are treated. The lower bound on the dimension of each share given by Gottesman [Phys. Rev. A 61, 042311 (2000)] is revisited based on a relation between the reversibility of quantum operations and the Holevo information. We also propose a threshold ramp quantum secret sharing scheme and evaluate its coding efficiency.

  3. Dissipation Bound for Thermodynamic Control.

    PubMed

    Machta, Benjamin B

    2015-12-31

    Biological and engineered systems operate by coupling function to the transfer of heat and/or particles down a thermal or chemical gradient. In idealized deterministically driven systems, thermodynamic control can be exerted reversibly, with no entropy production, as long as the rate of the protocol is made slow compared to the equilibration time of the system. Here we consider fully realizable, entropically driven systems where the control parameters themselves obey rules that are reversible and that acquire directionality in time solely through dissipation. We show that when such a system moves in a directed way through thermodynamic space, it must produce entropy that is on average larger than its generalized displacement as measured by the Fisher information metric. This distance measure is subextensive but cannot be made small by slowing the rate of the protocol. PMID:26764981

  4. Dissipation Bound for Thermodynamic Control

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin B.

    2015-12-01

    Biological and engineered systems operate by coupling function to the transfer of heat and/or particles down a thermal or chemical gradient. In idealized deterministically driven systems, thermodynamic control can be exerted reversibly, with no entropy production, as long as the rate of the protocol is made slow compared to the equilibration time of the system. Here we consider fully realizable, entropically driven systems where the control parameters themselves obey rules that are reversible and that acquire directionality in time solely through dissipation. We show that when such a system moves in a directed way through thermodynamic space, it must produce entropy that is on average larger than its generalized displacement as measured by the Fisher information metric. This distance measure is subextensive but cannot be made small by slowing the rate of the protocol.

  5. Justice and Reverse Discrimination.

    ERIC Educational Resources Information Center

    Goldman, Alan H.

    Defining reverse discrimination as hiring or admissions decisions based on normally irrelevant criteria, this book develops principles of rights, compensation, and equal opportunity applicable to the reverse discrimination issue. The introduction defines the issue and discusses deductive and inductive methodology as applied to reverse…

  6. Reverse Discrimination: Recent Cases.

    ERIC Educational Resources Information Center

    Steinhilber, August W.

    This paper discusses reverse discrimination cases with particular emphasis on Bakke v. Regents of University of California and those cases which preceded it. A brief history is given of court cases used by opponents and proponents in the discussion of reverse discrimination. Legal theory and a discussion of court cases that preceded Bakke follow.…

  7. Digitoxin Analogues with Improved Anticytomegalovirus Activity

    PubMed Central

    2014-01-01

    Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity. Structure–activity relationship (SAR) studies identified the l-sugar containing cardiac glycosides as having improved anti-CMV activity and may lead to better understanding of how these compounds inhibit CMV replication. PMID:24900847

  8. Materials analogue of zero-stiffness structures

    NASA Astrophysics Data System (ADS)

    Kumar, Arun; Subramaniam, Anandh

    2011-04-01

    Anglepoise lamps and certain tensegrities are examples of zero-stiffness structures. These structures are in a state of neutral equilibrium with respect to changes in configuration of the system. Using Eshelby's example of an edge dislocation in a thin plate that can bend, we report the discovery of a non-trivial new class of material structures as an analogue to zero-stiffness structures. For extended positions of the edge dislocation in these structures, the dislocation experiences a zero image force. Salient features of these material structures along with the key differences from conventional zero-stiffness structures are pointed out.

  9. Spectroscopic study of solar twins and analogues

    NASA Astrophysics Data System (ADS)

    Datson, Juliet; Flynn, Chris; Portinari, Laura

    2015-02-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims: This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48 000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods: The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar analogues versus a reference solar reflection spectrum. Results: We derive spectroscopic parameters for 148 solar analogues (about 70 are new entries to the literature) and verify with a-posteriori differential tests that our values are well-centred on the solar values. We use our dataset to assess the two alternative calibrations of the GCS parameters; our methods favour the latest revision. We show that the choice of spectral line list or the choice of asteroid or time of observation does not affect the results. We also identify seven solar twins in our sample, three of which are published here for the first time. Conclusions: Our methods provide an independent means to differentially test the calibration of stellar catalogues around the values of a well-known benchmark star, which makes our work interesting for calibration tests of upcoming Galactic surveys. Based on observations made with ESO Telescopes at the La Silla Observatory under programme ID 077.D

  10. U.S. Nuclear Regulatory Commission natural analogue research program

    SciTech Connect

    Kovach, L.A.; Ott, W.R.

    1995-09-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process.

  11. CO2 Removal using a Synthetic Analogue of Carbonic Anhydrase

    SciTech Connect

    Cordatos, Harry

    2010-09-14

    Project attempts to develop a synthetic analogue for carbonic anhydrase and incorporate it in a membrane for separation of CO2 from coal power plant flue gas. Conference poster presents result of first 9 months of project progress including concept, basic system architecture and membrane properties target, results of molecular modeling for analogue - CO2 interaction, and next steps of testing analogue resistance to flue gas contaminants.

  12. Structural analyses of covalent enzyme-substrate analogue complexes reveal strengths and limitations of de novo enzyme design

    PubMed Central

    Wang, Ling; Althoff, Eric A.; Bolduc, Jill; Jiang, Lin; Moody, James; Lassila, Jonathan K.; Giger, Lars; Hilvert, Donald; Stoddard, Barry; Baker, David

    2012-01-01

    We report the cocrystal structures of a computationally designed and experimentally optimized retro-aldol enzyme with covalently bound substrate analogs. The structure with covalently bound substrate analog is similar but not identical to the design model, with an RMSD over the active site residues and equivalent substrate atoms of 1.4Å. As in the design model, the binding pocket orients the substrate through hydrophobic interactions with the naphthyl moiety such that the oxygen atoms analogous to the carbinolamine and β-hydroxyl oxygens are positioned near a network of bound waters. However, there are differences between the design model and the structure: the orientation of the naphthyl group and the conformation of the catalytic lysine are slightly different; the bound water network appears to be more extensive; and the bound substrate analog exhibits more conformational heterogeneity than in typical native enzyme-inhibitor complexes. Alanine scanning of the active site residues shows that both the catalytic lysine and the residues around the binding pocket for the substrate naphthyl group make critical contributions to catalysis. Mutating the set of water-coordinating residues also significantly reduces catalytic activity. The crystal structure of the enzyme with a smaller substrate analogue that lacks the naphthyl rings shows the catalytic lysine to be more flexible than in the naphthyl substrate complex; increased preorganization of the active site would likely improve catalysis. The covalently bound complex structures and mutagenesis data highlight strengths and weaknesses of the de novo enzyme design strategy. PMID:22075445

  13. A novel adenylylation process in liver plasma membrane-bound proteins

    SciTech Connect

    San Jose, E.; Benguria, A.; Villalobo, A. )

    1990-11-25

    Rat liver plasma membrane contains five distinct polypeptides of apparent molecular mass of 130, 120, 110, 100, and 86 kDa which are labeled upon incubation with (alpha-32P)ATP as well as with (gamma-32P)ATP. Covalently bound adenosine 5'-monophosphate to some of the polypeptides was identified using nonhydrolyzable analogues of ATP. Chase experiments of alpha-32P-nucleotide-labeled polypeptides with different nonradiolabeled phosphocompounds and sensitivity to different inhibitors demonstrate that the 86-kDa polypeptide is a phosphoesterase, forming a catalytic intermediate. On the other hand, the comparative slow rate of turnover of the polypeptides of higher molecular mass (130, 120, 110, and 100 kDa) suggests that the bound AMP could play a regulatory rather than a catalytic role. Using the nonhydrolyzable ATP analogue (alpha, beta-methylene)ATP and dilution experiments with Triton X-100-solubilized membranes, it has been possible to identify the 130-kDa adenylylated polypeptide as a possible target of an adenylylating system. These polypeptides, except the 86-kDa phosphoesterase, are affected in their electrophoretic mobility in the absence of beta-mercaptoethanol. An intercatenary disulfide bond(s) appear(s) to link the polypeptide(s) of 120 kDa and/or 110 kDa in a dimeric structure of apparent molecular mass of 240 kDa. All five polypeptides labeled with (alpha-32P)ATP are glycoproteins bound to the cell plasma membrane.

  14. Bound potassium in muscle II.

    PubMed

    Hummel, Z

    1980-01-01

    Experiments were performed to decide between the alternatives a) the ionized K+ is in a dissolved state in the muscle water, or b) a part of the muscle potassium is in a "bound' state. Sartorius muscles of Rana esculenta were put into glicerol for about one hour at 0-2 degrees C. Most of muscle water came out, but most of muscle potassium remained in the muscles. In contrast to this: from muscle in heat rigor more potassium was released due to glicerol treating than from the intact ones. 1. Supposition a) is experimentally refuted. 2. Supposition b) corresponds to the experimental results. PMID:6969511

  15. Voronoi Diagrams Without Bounding Boxes

    NASA Astrophysics Data System (ADS)

    Sang, E. T. K.

    2015-10-01

    We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010) and Nerbonne et al (2011).

  16. Entropy bounds and dark energy

    NASA Astrophysics Data System (ADS)

    Hsu, Stephen D. H.

    2004-07-01

    Entropy bounds render quantum corrections to the cosmological constant Λ finite. Under certain assumptions, the natural value of Λ is of order the observed dark energy density ~10-10 eV4, thereby resolving the cosmological constant problem. We note that the dark energy equation of state in these scenarios is w≡p/ρ=0 over cosmological distances, and is strongly disfavored by observational data. Alternatively, Λ in these scenarios might account for the diffuse dark matter component of the cosmological energy density. Permanent address: Institute of Theoretical Science and Department of Physics, University of Oregon, Eugene, OR 97403.

  17. Bound Polaron Pair Formation in Poly (phenylenevinylenes)

    NASA Astrophysics Data System (ADS)

    Rothberg, Lewis

    The following sections are included: * INTRODUCTION * PHOTOGENERATED YIELD OF SINGLET EXCITONS * AGGREGRATION EFFECTS ON EXCITED STATE PHOTO-GENERATION * ASSIGNMENT TO BOUND POLARON PAIRS AND DISCUSSION * PROBLEMS WITH THE BOUND POLARON PAIR PICTURE AND CONCLUSION * REFERENCES

  18. Structural dynamics of actin during active interaction with myosin: different effects of weakly and strongly bound myosin heads.

    PubMed

    Prochniewicz, Ewa; Walseth, Timothy F; Thomas, David D

    2004-08-24

    We have used optical spectroscopy (transient phosphorescence anisotropy, TPA, and fluorescence resonance energy transfer, FRET) to detect the effects of weakly bound myosin S1 on actin during the actomyosin ATPase cycle. The changes in actin were reported by (a) a phosphorescent probe (ErIA) attached to Cys 374 and (b) a FRET donor-acceptor pair, IAEDANS attached to Cys 374 and a nucleotide analogue (TNPADP) in the nucleotide-binding cleft. Strong interactions were detected in the absence of ATP, and weak interactions were detected in the presence of ATP or its slowly hydrolyzed analogue ATP-gamma-S, under conditions where a significant fraction of weakly bound acto-S1 complex was present and the rate of nucleotide hydrolysis was low enough to enable steady-state measurements. The results show that actin in the weakly bound complex with S1 assumes a new structural state in which (a) the actin filament has microsecond rotational dynamics intermediate between that of free actin and the strongly bound complex and (b) S1-induced changes are not propagated along the actin filament, in contrast to the highly cooperative changes due to the strongly bound complex. We propose that the transition on the acto-myosin interface from weak to strong binding is accompanied by transitions in the structural dynamics of actin parallel to transitions in the dynamics of interacting myosin heads.

  19. Reversible Thermal-Stiffening in Polymer Nanocomposites

    NASA Astrophysics Data System (ADS)

    Senses, Erkan; Akcora, Pinar

    2015-03-01

    Silica nanoparticles adsorbed with a high glass-transition temperature polymer, PMMA (Tg: 130 °C) are shown to uniformly disperse in a low-Tg polymer matrix, PEO (Tg: -60 °C). These nanocomposites exhibit an unusual reversible liquid-to-solid transition at temperatures above Tg's of both polymers. Mechanical adaptivity of PEO nanocomposites to temperatures underlies the existence of dynamically asymmetric bound layers on particles, and more importantly their impact on mechanical behavior, which sets these materials apart from conventional polymer composites that soften upon heating. Moreover, the growth rate of elastic moduli at temperatures above Tg of PMMA presents an Arrhenius-type relaxation with activation energy well-matching with the α- β merging region of PMMA. These results suggest that the mobility of the surface-bound polymer is essential for reinforcement contrary to commonly accepted glassy-layer hypothesis.

  20. Bounds on multipartite concurrence and tangle

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Li, Ming; Li, Hongfang; Fei, Shao-Ming; Li-Jost, Xianqing

    2016-10-01

    We present an analytical lower bound of multipartite concurrence based on the generalized Bloch representations of density matrices. It is shown that the lower bound can be used as an effective entanglement witness of genuine multipartite entanglement. Tight lower and upper bounds for multipartite tangles are also derived. Since the lower bounds depend on just part of the correlation tensors, the result is experimentally feasible.

  1. Bound adenosine 5'-triphosphate formation, bound adenosine 5'-diphosphate and inorganic phosphate retention, and inorganic phosphate oxygen exchange by chloroplast adenosinetriphosphatase in the presence of Ca2+ or Mg2+.

    PubMed

    Wu, D; Boyer, P D

    1986-06-01

    When the heat-activated chloroplast F1 ATPase hydrolyzes [3H, gamma-32P]ATP, followed by the removal of medium ATP, ADP, and Pi, the enzyme has labeled ATP, ADP, and Pi bound to it in about equal amounts. The total of the bound [3H]ADP and [3H]ATP approaches 1 mol/mol of enzyme. Over a 30-min period, most of the bound [32P]Pi falls off, and the bound [3H]ATP is converted to bound [3H]ADP. Enzyme with such remaining tightly bound ADP will form bound ATP from relatively high concentrations of medium Pi with either Mg2+ or Ca2+ present. The tightly bound ADP is thus at a site that retains a catalytic capacity for slow single-site ATP hydrolysis (or synthesis) and is likely the site that participates in cooperative rapid net ATP hydrolysis. During hydrolysis of 50 microM [3H]ATP in the presence of either Mg2+ or Ca2+, the enzyme has a steady-state level of about one bound [3H]ADP per mole of enzyme. Because bound [3H]ATP is also present, the [3H]ADP is regarded as being present on two cooperating catalytic sites. The formation and levels of bound ATP, ADP, and Pi show that reversal of bound ATP hydrolysis can occur with either Ca2+ or Mg2+ present. They do not reveal why no phosphate oxygen exchange accompanies cleavage of low ATP concentrations with Ca2+ in contrast to Mg2+ with the heat-activated enzyme. Phosphate oxygen exchange does occur with either Mg2+ or Ca2+ present when low ATP concentrations are hydrolyzed with the octyl glucoside activated ATPase. Ligand binding properties of Ca2+ at the catalytic site rather than lack of reversible cleavage of bound ATP may underlie lack of oxygen exchange under some conditions. PMID:2873834

  2. Stable bound orbits around black rings

    SciTech Connect

    Igata, Takahisa; Ishihara, Hideki; Takamori, Yohsuke

    2010-11-15

    We examine bound orbits of particles around singly rotating black rings. We show that there exist stable bound orbits in toroidal spiral shape near the 'axis' of the ring, and also stable circular orbits on the axis as special cases. The stable bound orbits can have arbitrary large size if the thickness of the ring is less than a critical value.

  3. Counting Young Tableaux of Bounded Height

    NASA Astrophysics Data System (ADS)

    Bergeron, Francois; Gascon, Francis

    2000-03-01

    We show that formulas of Gessel, for the generating functions for Young standard tableaux of height bounded by k (see [2]), satisfy linear differential equations, with polynomial coefficients, equivalent to P-recurrences conjectured by Favreau, Krob and the first author (see [1]) for the number of bounded height tableaux and pairs of bounded height tableaux.

  4. Coefficient of performance and its bounds with the figure of merit for a general refrigerator

    NASA Astrophysics Data System (ADS)

    Long, Rui; Liu, Wei

    2015-02-01

    A general refrigerator model with non-isothermal processes is studied. The coefficient of performance (COP) and its bounds at maximum χ figure of merit are obtained and analyzed. This model accounts for different heat capacities during the heat transfer processes. So, different kinds of refrigerator cycles can be considered. Under the constant heat capacity condition, the upper bound of the COP is the Curzon-Ahlborn (CA) coefficient of performance and is independent of the time durations of the heat exchanging processes. With the maximum χ criterion, in the refrigerator cycles, such as the reversed Brayton refrigerator cycle, the reversed Otto refrigerator cycle and the reversed Atkinson refrigerator cycle, where the heat capacity in the heat absorbing process is not less than that in the heat releasing process, their COPs are bounded by the CA coefficient of performance; otherwise, such as for the reversed Diesel refrigerator cycle, its COP can exceed the CA coefficient of performance. Furthermore, the general refined upper and lower bounds have been proposed.

  5. Self-Powered Analogue Smart Skin.

    PubMed

    Shi, Mayue; Zhang, Jinxin; Chen, Haotian; Han, Mengdi; Shankaregowda, Smitha A; Su, Zongming; Meng, Bo; Cheng, Xiaoliang; Zhang, Haixia

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity. PMID:27010713

  6. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  7. Magnetohydrodynamical Analogue of a Black Hole

    NASA Astrophysics Data System (ADS)

    Zamorano, Nelson; Asenjo, Felipe

    2014-03-01

    We study the conditions that a plasma fluid and its container should meet to generate a magneto-acoustic horizon. This effect becomes an alternative to the analogue black hole found in a transonic fluid flow setting. In this context we use the magnetohydrodynamic formalism (MHD) to analyze the evolution of an irrotational plasma fluid interacting with an external constant magnetic field. Under certain plausible approximations, the dynamic of the field perturbations is described by a scalar field potential that follows a second order differential equation. As we prove here, this equation corresponds to the wave equation associated to a scalar field in a curved space-time. This horizon emerges when the local speed of the medium grows larger than the sound velocity. The magnetic field generates an effective pressure which contributes to the magneto-acoustic speed. We compare these results with the known physics of analogue black holes. We will also refer to our ongoing experiment that, in its first stage, attempts to reproduce the wave horizons found in an open channel with an obstacle: PRL 106, 021302 (2011).

  8. Quantum correlations beyond Tsirelson's bound

    NASA Astrophysics Data System (ADS)

    Berry, Dominic; Ringbauer, Martin; Fedrizzi, Alessandro; White, Andrew

    2014-03-01

    Violations of Bell inequalities show that there are correlations that cannot explained by any classical theory. Further violation, beyond Tsirelson's bound, shows that there are correlations that are not explained by quantum mechanics. Such super-quantum correlations would enable violation of information causality, where communication of one bit provides more than one bit of information [Nature 461, 1101 (2009)]. An unavoidable feature of all realistic Bell inequality experiments is loss. If one postselects on successful measurements, unentangled states can violate Bell inequalities. On the other hand, loss can be used to enhance the violation of Bell inequalities for entangled states. This can improve the ability to distinguish between entangled and unentangled states, despite loss. Here we report an optical experiment providing maximal violation of the CHSH-Bell inequality with entangled states. Due to loss and postselection, Tsirelson's bound is also violated. This enables us to more easily distinguish between entangled and unentangled states. In addition, it provides violation of information causality for the postselected data.

  9. Mechanism of muscarinic receptor-induced K+ channel activation as revealed by hydrolysis-resistant GTP analogues

    PubMed Central

    1988-01-01

    The role of a guanine nucleotide-binding protein (Gk) in the coupling between muscarinic receptor activation and opening of an inwardly rectifying K+ channel [IK(M)] was examined in cardiac atrial myocytes, using hydrolysis-resistant GTP analogues. In the absence of muscarinic agonist, GTP analogues produced a membrane current characteristic of IK(M). The initial rate of appearance of this receptor-independent IK(M) was measured for the various analogues in order to explore the kinetic properties of IK(M) activation. We found that IK(M) activation is controlled solely by the intracellular analogue/GTP ratio and not by the absolute concentrations of the nucleotides. Analogues competed with GTP for binding to Gk with the following relative affinities: GTP gamma S greater than GTP greater than GppNHp greater than GppCH2p. At sufficiently high intracellular concentrations, however, all GTP analogues produced the same rate of IK(M) activation. This analogue- independent limiting rate is likely to correspond to the rate of GDP release from inactive, GDP-bound Gk. Muscarinic receptor stimulation by nanomolar concentrations of acetylcholine (ACh), which do not elicit IK(M) under control conditions, catalyzed IK(M) activation in the presence of GTP analogues. The rate of Gk activation by ACh (kACh) was found to be described by the simple relationship kACh = 8.4 X 10(8) min- 1 M-1.[ACh] + 0.44 min-1, the first term of which presumably reflects the agonist-catalyzed rate of GDP release from the Gk.GDP complex, while the second term corresponds to the basal rate of receptor- independent GDP release. Combined with the estimated K0.5 of the IK(M)- [ACh] dose-effect relationship, 160 nM, this result also allowed us to estimate the rate of Gk.GTP hydrolysis, kcat, to be near 135 min-1. These results provide, for the first time, a quantitative description of the salient features of G-protein function in vivo. PMID:2455765

  10. Indenter growth in analogue models of Alpine-type deformation

    NASA Astrophysics Data System (ADS)

    Bonini, Marco; Sokoutis, Dimitrios; Talbot, Christopher J.; Boccaletti, Mario; Milnes, Alan G.

    1999-02-01

    A series of analogue experiments were carried out to simulate continental convergence, as seen in a profile through the Central Alps. A rigid indenter, representing the Adriatic plate, was driven laterally into a sand pack representing the brittle upper crust of Europe, detached and thickening above its subducting ductile lower crust. The rigid indenter advanced at the same steady rate in each experiment, but the dip of its front face was steepened in 15° increments from 15° to 90°. Where the rigid indenter face dipped at 45° or less, a sand wedge rose and was bound by a series of forekinks that nucleated at the toe of the indenter. Where the face of the rigid indenter dipped 60° or more, the wedge was defined by a single forekink and one or more backkinks that nucleated from a point advancing in front of the indenter toe. We interpret these results as indicating that slices of the sand pack and rising wedge are transferred across kink bands to build an "effective" indenter with a frontal dip closer to that dictated by the changing shear strength of the sand pile, which thickens vertically as it shortens laterally. One of our models (with a rigid indenter dipping 75°) simulates most of the major structures shown in recent syntheses of surface geology and deep seismic data in the Central Alps, without the isostatic lithospheric depression. This model accounts for the late collisional stage (Oligocene to Present) complex strain and metamorphic histories in the core of the orogenic wedge, the rapid rise and extrusion of small pips of Alpine eclogites, and the current passivity of the Insubric Line. It also emphasizes that lateral extension along gently dipping "thrusts" (orogen-normal horizontal escape) is confined to the extruded portion of the rising wedge.

  11. Time-reversal violation in beta decay

    SciTech Connect

    Herczeg, P.

    2003-01-01

    At present there is no unambigous direct evidence for time-reversal (T) violation in the fundamental interactions. But T-violation is intimately connected with CP-violation by the CPT theorem. A stringent bound on possible violation of CPT invariance comes from the properties of K{sup 0} - {bar K}{sup 0} mixing [I]. In the following we shall assume that CPT violating interactions, if present, can be neglected, and use the terms 'T-violation' and 'CP-violation' interchangably.

  12. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology.

    PubMed

    Sáez-Briones, P; Hernández, A

    2013-09-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, "Ecstasy") is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an "open mind state", may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

  13. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

    PubMed Central

    Sáez-Briones, P.; Hernández, A.

    2013-01-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues. PMID:24403876

  14. O2 reduction reaction by biologically relevant anionic ligand bound iron porphyrin complexes.

    PubMed

    Samanta, Subhra; Das, Pradip Kumar; Chatterjee, Sudipta; Sengupta, Kushal; Mondal, Biswajit; Dey, Abhishek

    2013-11-18

    Iron porphyrin complex with a covalently attached thiolate ligand and another with a covalently attached phenolate ligand has been synthesized. The thiolate bound complex shows spectroscopic features characteristic of P450, including the hallmark absorption spectrum of the CO adduct. Electrocatalytic O2 reduction by this complex, which bears a terminal alkyne group, is investigated by both physiabsorbing on graphite surfaces (fast electron transfer rates) and covalent attachment to azide terminated self-assembled monolayer (physiologically relevant electron transfer rates) using the terminal alkyne group. Analysis of the steady state electrochemical kinetics reveals that this catalyst can selectively reduce O2 to H2O with a second-order k(cat.) ~10(7) M(-1 )s(-1) at pH 7. The analogous phenolate bound iron porphyrin complex reduces O2 with a second-order rate constant of 10(5) M(-1) s(-1) under the same conditions. The anionic ligand bound iron porphyrin complexes catalyze oxygen reduction reactions faster than any known synthetic heme porphyrin analogues. The kinetic parameters of O2 reduction of the synthetic thiolate bound complex, which is devoid of any second sphere effects present in protein active sites, provide fundamental insight into the role of the protein environment in tuning the reactivity of thiolate bound iron porphyrin containing metalloenzymes. PMID:24171513

  15. Reversing the arms race

    SciTech Connect

    von Hippel, F. ); Sagdeev, R.Z. )

    1992-01-01

    This paper contains proceedings of Reversing The Arms Race. Topics covered include: Verifying Reductions of Nuclear Warheads; Verifying Limits on Nuclear-Armed Cruise Missiles; and The Technical Basis for Warhead Detection.

  16. Bound states in the continuum

    NASA Astrophysics Data System (ADS)

    Hsu, Chia Wei; Zhen, Bo; Stone, A. Douglas; Joannopoulos, John D.; Soljačić, Marin

    2016-09-01

    Bound states in the continuum (BICs) are waves that remain localized even though they coexist with a continuous spectrum of radiating waves that can carry energy away. Their very existence defies conventional wisdom. Although BICs were first proposed in quantum mechanics, they are a general wave phenomenon and have since been identified in electromagnetic waves, acoustic waves in air, water waves and elastic waves in solids. These states have been studied in a wide range of material systems, such as piezoelectric materials, dielectric photonic crystals, optical waveguides and fibres, quantum dots, graphene and topological insulators. In this Review, we describe recent developments in this field with an emphasis on the physical mechanisms that lead to BICs across seemingly very different materials and types of waves. We also discuss experimental realizations, existing applications and directions for future work.

  17. Performance Bounds of Quaternion Estimators.

    PubMed

    Xia, Yili; Jahanchahi, Cyrus; Nitta, Tohru; Mandic, Danilo P

    2015-12-01

    The quaternion widely linear (WL) estimator has been recently introduced for optimal second-order modeling of the generality of quaternion data, both second-order circular (proper) and second-order noncircular (improper). Experimental evidence exists of its performance advantage over the conventional strictly linear (SL) as well as the semi-WL (SWL) estimators for improper data. However, rigorous theoretical and practical performance bounds are still missing in the literature, yet this is crucial for the development of quaternion valued learning systems for 3-D and 4-D data. To this end, based on the orthogonality principle, we introduce a rigorous closed-form solution to quantify the degree of performance benefits, in terms of the mean square error, obtained when using the WL models. The cases when the optimal WL estimation can simplify into the SWL or the SL estimation are also discussed. PMID:25643416

  18. Space Analogue Environments: Are the Populations Comparable?

    NASA Astrophysics Data System (ADS)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  19. Reversibility of antibiotic resistance

    PubMed Central

    2014-01-01

    Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

  20. Adaptive Pairing Reversible Watermarking.

    PubMed

    Dragoi, Ioan-Catalin; Coltuc, Dinu

    2016-05-01

    This letter revisits the pairwise reversible watermarking scheme of Ou et al., 2013. An adaptive pixel pairing that considers only pixels with similar prediction errors is introduced. This adaptive approach provides an increased number of pixel pairs where both pixels are embedded and decreases the number of shifted pixels. The adaptive pairwise reversible watermarking outperforms the state-of-the-art low embedding bit-rate schemes proposed so far.

  1. The effects of the morphine analogue levorphanol on leukocytes

    PubMed Central

    Wurster, Nancy; Elsbach, Peter; Simon, Eric J.; Pettis, Penelope; Lebow, Sharon

    1971-01-01

    Studies on bacteria have suggested that morphine-like drugs have effects on the cell membrane. To determine the effect of this class of drugs on a mammalian cell, we selected the rabbit peritoneal exudate granulocyte, which undergoes striking membrane changes during phagocytosis. We examined the effect in vitro of the morphine analogue, levorphanol on phagocytosis and metabolism by granulocytes incubated with and without polystyrene particles or live Escherichia coli. Levorphanol (1 or 2 mmoles/liter) decreased: (a) acylation of lysolecithin or lysophosphatidylethanolamine in the medium (which is stimulated about two-fold during phagocytosis) both at rest (40%) and during phagocytosis (60%); (b) uptake of latex particles and Escherichia coli, as judged by electron microscopy; (c) killing of live Escherichia coli (10-fold); (d) 14CO2 production from glucose-1-14C during phagocytosis by at least 80%; (e) K+ content of granulocytes (35%); (f) oxidation of linoleate-1-14C by 50%, and its incorporation into triglyceride by more than 80%. However, levorphanol stimulated 2 to 3-fold the incorporation of linoleate-1-14C or palmitate-1-14C into several phospholipids. Glucose uptake, lactate production, and adenosine triphosphate (ATP) content are not affected by the drug. Thus, levorphanol does not appear to exert its effects through generalized metabolic suppression. Removal of levorphanol by twice resuspending the granulocytes completely reverses all inhibition. In line with observations on bacteria, it appears that the complex effects of levorphanol on granulocytes may be due at least in part to an effect on the cell membrane. PMID:4928264

  2. On thermodynamic and microscopic reversibility

    SciTech Connect

    Crooks, Gavin E.

    2011-07-12

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa.

  3. Solution Processed PEDOT Analogues in Electrochemical Supercapacitors.

    PubMed

    Österholm, Anna M; Ponder, James F; Kerszulis, Justin A; Reynolds, John R

    2016-06-01

    We have designed fully soluble ProDOTx-EDOTy copolymers that are electrochemically equivalent to electropolymerized PEDOT without using any surfactants or dispersants. We show that these copolymers can be incorporated as active layers in solution processed thin film supercapacitors to demonstrate capacitance, stability, and voltage similar to the values of those that use electrodeposited PEDOT as the active material with the added advantage of the possibility for large scale, high-throughput processing. These Type I supercapacitors provide exceptional cell voltages (up to 1.6 V), highly symmetrical charge/discharge behavior, promising long-term stability exceeding 50 000 charge/discharge cycles, as well as energy (4-18 Wh/kg) and power densities (0.8-3.3 kW/kg) that are comparable to those of electrochemically synthesized analogues. PMID:27195798

  4. Jupiter analogues and planets of active stars

    NASA Astrophysics Data System (ADS)

    Kürster, M.; Zechmeister, M.; Endl, M.; Lo Curto, G.; Hartman, H.; Nilsson, H.; Henning, T.; Hatzes, A. P.; Cochran, W. D.

    2013-04-01

    Combined results are now available from a 15 year long search for Jupiter analogues around solar-type stars using the ESO CAT + CES, ESO 3.6 m + CES, and ESO 3.6 m + HARPS instruments. They comprise planet (co-)discoveries (ι Hor and HR 506) and confirmations (three planets in HR 3259) as well as non-confirmations of planets (HR 4523 and ɛ Eri) announced elsewhere. A long-term trend in ɛ Ind found by our survey is probably attributable to a Jovian planet with a period >30 yr, but we cannot fully exclude stellar activity effects as the cause. A 3.8 year periodic variation in HR 8323 can be attributed to stellar activity.

  5. Current european regulatory perspectives on insulin analogues.

    PubMed

    Enzmann, Harald G; Weise, Martina

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  6. Natural analogues of nuclear waste glass corrosion.

    SciTech Connect

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  7. Terrestrial Analogues for Lunar Impact Melt Flows

    NASA Technical Reports Server (NTRS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2016-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pahoehoe and ?a ?a lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pahoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pahoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  8. Quantitative analysis of fault slip evolution in analogue transpression models

    NASA Astrophysics Data System (ADS)

    Leever, Karen; Gabrielsen, Roy H.; Schmid, Dani; Braathen, Alvar

    2010-05-01

    A quantitative analysis of fault slip evolution in crustal scale brittle and brittle-ductile analogue models of doubly vergent transpressional wedges was performed by means of Particle Image Velocimetry (PIV). The kinematic analyses allow detailed comparison between model results and field kinematic data. This novel approach leads to better understanding of the evolution of transpressional orogens such as the Tertiary West Spitsbergen fold and thrust belt in particular and will advance the understanding of transpressional wedge mechanics in general. We ran a series of basal-driven models with convergence angles of 4, 7.5, 15 and 30 degrees. In these crustal scale models, brittle rheology was represented by quartz sand; in one model a viscous PDMS layer was included at shallow depth. Total sand pack thickness was 6cm, its extent 120x60cm. The PIV method was used to calculate a vector field from pairs of images that were recorded from the top of the experiments at a 2mm displacement increment. The slip azimuth on discrete faults was calculated and visualized by means of a directional derivative of this vector field. From this data set, several stages in the evolution of the models could be identified. The stages were defined by changes in the degree of displacement partitioning, i.e. slip along-strike and orthogonal to the plate boundary. A first stage of distributed strain (with no visible faults at the model surface) was followed by a shear lens stage with oblique displacement on pro- and retro-shear. The oblique displacement became locally partitioned during progressive displacement. During the final stage, strain was more fully partitioned between a newly formed central strike slip zone and reverse faults at the sides. Strain partitioning was best developed in the 15 degrees model, which shows near-reverse faults along both sides of the wedge in addition to strike slip displacement in the center. In further analysis we extracted average slip vectors for

  9. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    PubMed

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  10. The structure of locally bounded finite-dimensional representations of connected locally compact groups

    SciTech Connect

    Shtern, A. I.

    2014-04-30

    An analogue of a Lie theorem is obtained for (not necessarily continuous) finite-dimensional representations of soluble finite-dimensional locally compact groups with connected quotient group by the centre. As a corollary, the following automatic continuity proposition is obtained for locally bounded finite-dimensional representations of connected locally compact groups: if G is a connected locally compact group, N is a compact normal subgroup of G such that the quotient group G/N is a Lie group, N{sub 0} is the connected identity component in N, H is the family of elements of G commuting with every element of N{sub 0}, and π is a (not necessarily continuous) locally bounded finite-dimensional representation of G, then π is continuous on the commutator subgroup of H (in the intrinsic topology of the smallest analytic subgroup of G containing this commutator subgroup). Bibliography: 23 titles. (paper)

  11. Bound anionic states of adenine

    SciTech Connect

    Haranczyk, Maciej; Gutowski, Maciej S; Li, Xiang; Bowen, Kit H

    2007-03-20

    Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases, are thought to be adiabatically unbound. Contrary to this expectation, we have demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the new-found anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The discovery of these valence anionic states of adenine was facilitated by the development of: (i) a new experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (ii) a new combinatorial/ quantum chemical approach for identification of the most stable tautomers of organic molecules. The computational portion of this work was supported by the: (i) Polish State Committee for Scientific Research (KBN) Grants: DS/8000-4-0140-7 (M.G.) and N204 127 31/2963 (M.H.), (ii) European Social Funds (EFS) ZPORR/2.22/II/2.6/ARP/U/2/05 (M.H.), and (iii) US DOE Office of Biological and Environmental Research, Low Dose Radiation Research Program (M.G.). M.H. holds the Foundation for Polish Science (FNP) award for young scientists. The calculations were performed at the Academic

  12. Reversible digital images

    NASA Astrophysics Data System (ADS)

    Knox, Keith T.

    1999-04-01

    A method has been developed to hide one image inside another with little loss in image quality. If the second image is a logo or watermark, then this method may be used to protect the ownership rights of the first image and to guarantee the authenticity of the image. The two images to be combined may be either black & white or color continuous tone images. A reversible image is created by incorporating the first image in the upper 4 bits and the second image in the lower 4 bits. When viewed normally, the reversible image appears to be the first image. To view the hidden image, the bits of the combined image are reversed, exchanging all of the lower and higher order bits. When viewed in the reversed mode, the image appears to be the second or hidden image. To maintain a high level of image quality for both images, two simultaneous error diffusion calculations are run to ensure that both views of the reversible image have the same visual appearance as the originals. Any alteration of one of the images locally destroys the other image at the site of the alterations. This provides a method to detect alterations of the original image.

  13. Reversible collisionless magnetic reconnection

    SciTech Connect

    Ishizawa, A.; Watanabe, T.-H.

    2013-10-15

    Reversible magnetic reconnection is demonstrated for the first time by means of gyrokinetic numerical simulations of a collisionless magnetized plasma. Growth of a current-driven instability in a sheared magnetic field is accompanied by magnetic reconnection due to electron inertia effects. Following the instability growth, the collisionless reconnection is accelerated with development of a cross-shaped structure of current density, and then all field lines are reconnected. The fully reconnected state is followed by the secondary reconnection resulting in a weakly turbulent state. A time-reversed simulation starting from the turbulent state manifests that the collisionless reconnection process proceeds inversely leading to the initial state. During the reversed reconnection, the kinetic energy is reconverted into the original magnetic field energy. In order to understand the stability of reversed process, an external perturbation is added to the fully reconnected state, and it is found that the accelerated reconnection is reversible when the deviation of the E × B streamlines due to the perturbation is comparable with or smaller than a current layer width.

  14. Bounds on double-diffusive convection

    NASA Astrophysics Data System (ADS)

    Balmforth, Neil J.; Ghadge, Shilpa A.; Kettapun, Atichart; Mandre, Shreyas D.

    2006-12-01

    We consider double-diffusive convection between two parallel plates and compute bounds on the flux of the unstably stratified species using the background method. The bound on the heat flux for Rayleigh Bénard convection also serves as a bound on the double-diffusive problem (with the thermal Rayleigh number equal to that of the unstably stratified component). In order to incorporate a dependence of the bound on the stably stratified component, an additional constraint must be included, like that used by Joseph (Stability of Fluid Motion, 1976, Springer) to improve the energy stability analysis of this system. Our bound extends Joseph's result beyond his energy stability boundary. At large Rayleigh number, the bound is found to behave like R_T(1/2) for fixed ratio R_S/R_T, where R_T and R_S are the Rayleigh numbers of the unstably and stably stratified components, respectively.

  15. Si:P as a laboratory analogue for hydrogen on high magnetic field white dwarf stars.

    PubMed

    Murdin, B N; Li, Juerong; Pang, M L Y; Bowyer, E T; Litvinenko, K L; Clowes, S K; Engelkamp, H; Pidgeon, C R; Galbraith, I; Abrosimov, N V; Riemann, H; Pavlov, S G; Hübers, H-W; Murdin, P G

    2013-01-01

    Laboratory spectroscopy of atomic hydrogen in a magnetic flux density of 10(5) T (1 gigagauss), the maximum observed on high-field magnetic white dwarfs, is impossible because practically available fields are about a thousand times less. In this regime, the cyclotron and binding energies become equal. Here we demonstrate Lyman series spectra for phosphorus impurities in silicon up to the equivalent field, which is scaled to 32.8 T by the effective mass and dielectric constant. The spectra reproduce the high-field theory for free hydrogen, with quadratic Zeeman splitting and strong mixing of spherical harmonics. They show the way for experiments on He and H(2) analogues, and for investigation of He(2), a bound molecule predicted under extreme field conditions. PMID:23403570

  16. Si:P as a laboratory analogue for hydrogen on high magnetic field white dwarf stars.

    PubMed

    Murdin, B N; Li, Juerong; Pang, M L Y; Bowyer, E T; Litvinenko, K L; Clowes, S K; Engelkamp, H; Pidgeon, C R; Galbraith, I; Abrosimov, N V; Riemann, H; Pavlov, S G; Hübers, H-W; Murdin, P G

    2013-01-01

    Laboratory spectroscopy of atomic hydrogen in a magnetic flux density of 10(5) T (1 gigagauss), the maximum observed on high-field magnetic white dwarfs, is impossible because practically available fields are about a thousand times less. In this regime, the cyclotron and binding energies become equal. Here we demonstrate Lyman series spectra for phosphorus impurities in silicon up to the equivalent field, which is scaled to 32.8 T by the effective mass and dielectric constant. The spectra reproduce the high-field theory for free hydrogen, with quadratic Zeeman splitting and strong mixing of spherical harmonics. They show the way for experiments on He and H(2) analogues, and for investigation of He(2), a bound molecule predicted under extreme field conditions.

  17. SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity

    PubMed Central

    2013-01-01

    It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure–activity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar. PMID:23930152

  18. Some Improved Nonperturbative Bounds for Fermionic Expansions

    NASA Astrophysics Data System (ADS)

    Lohmann, Martin

    2016-06-01

    We reconsider the Gram-Hadamard bound as it is used in constructive quantum field theory and many body physics to prove convergence of Fermionic perturbative expansions. Our approach uses a recursion for the amplitudes of the expansion, discovered in a model problem by Djokic (2013). It explains the standard way to bound the expansion from a new point of view, and for some of the amplitudes provides new bounds, which avoid the use of Fourier transform, and are therefore superior to the standard bounds for models like the cold interacting Fermi gas.

  19. Genuine modern analogues of Precambrian stromatolites from caldera lakes of Niuafo'ou Island, Tonga.

    PubMed

    Kazmierczak, Józef; Kempe, Stephan

    2006-03-01

    Calcareous or dolomitic, often secondarily silicified, laminated microbial structures known as stromatolites are important keys to reconstruct the chemical and biotic evolution of the early ocean. Most authors assume that cyanobacteria-associated microbialitic structures described from Shark Bay, Western Australia, and Exuma Sound, Bahamas, represent modern marine analogues for Precambrian stromatolites. Although they resemble the Precambrian forms macroscopically, their microstructure and mineralogical composition differ from those characterizing their purported ancient counterparts. Most Precambrian stromatolites are composed of presumably in situ precipitated carbonates, while their assumed modern marine analogues are predominantly products of accretion of grains trapped and bound by microbial, predominantly cyanobacterial, benthic mats and biofilms and only occasionally by their physicochemical activity. It has therefore been suggested that the carbonate chemistry of early Precambrian seawater differed significantly from modern seawater, and that some present-day quasi-marine or non-marine environments supporting growth of calcareous microbialites reflect the hydrochemical conditions controlling the calcification potential of Precambrian microbes better than modern seawater. Here we report the discovery of a non-marine environment sustaining growth of calcareous cyanobacterial microbialites showing macroscopic and microscopic features resembling closely those described from many Precambrian stromatolites.

  20. Trapping of a transcription complex using a new nucleotide analogue: AMP aluminium fluoride.

    PubMed

    Joly, Nicolas; Rappas, Mathieu; Buck, Martin; Zhang, Xiaodong

    2008-02-01

    Mechanochemical proteins rely on ATP hydrolysis to establish the different functional states required for their biological output. Studying the transient functional intermediate states these proteins adopt as they progress through the ATP hydrolysis cycle is key to understanding the molecular basis of their mechanism. Many of these intermediates have been successfully 'trapped' and functionally characterised using ATP analogues. Here, we present a new nucleotide analogue, AMP-AlF(x), which traps PspF, a bacterial enhancer binding protein, in a stable complex with the sigma(54)-RNA polymerase holoenzyme. The crystal structure of AMP-AlF(x)*PspF(1-275) provides new information on protein-nucleotide interactions and suggests that the beta and gamma phosphates are more important than the alpha phosphate in terms of sensing nucleotide bound states. In addition, functional data obtained with AMP-AlF(x) establish distinct roles for the conserved catalytic AAA(+) (ATPases associated with various cellular activities) residues, suggesting that AMP-AlF(x) is a powerful new tool to study AAA(+) protein family members and, more generally, Walker motif ATPases. PMID:18082766

  1. Sequential Polarity-Reversing Circuit

    NASA Technical Reports Server (NTRS)

    Labaw, Clayton C.

    1994-01-01

    Proposed circuit reverses polarity of electric power supplied to bidirectional dc motor, reversible electro-mechanical actuator, or other device operating in direction depending on polarity. Circuit reverses polarity each time power turned on, without need for additional polarity-reversing or direction signals and circuitry to process them.

  2. Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.

    PubMed

    Roselli, Mariagrazia; Carocci, Alessia; Budriesi, Roberta; Micucci, Matteo; Toma, Maddalena; Di Cesare Mannelli, Lorenzo; Lovece, Angelo; Catalano, Alessia; Cavalluzzi, Maria Maddalena; Bruno, Claudio; De Palma, Annalisa; Contino, Marialessandra; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Chiarini, Alberto; Franchini, Carlo; Ghelardini, Carla; Habtemariam, Solomon; Lentini, Giovanni

    2016-10-01

    Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation. PMID:27267000

  3. Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.

    PubMed

    Roselli, Mariagrazia; Carocci, Alessia; Budriesi, Roberta; Micucci, Matteo; Toma, Maddalena; Di Cesare Mannelli, Lorenzo; Lovece, Angelo; Catalano, Alessia; Cavalluzzi, Maria Maddalena; Bruno, Claudio; De Palma, Annalisa; Contino, Marialessandra; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Chiarini, Alberto; Franchini, Carlo; Ghelardini, Carla; Habtemariam, Solomon; Lentini, Giovanni

    2016-10-01

    Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation.

  4. Topological modes bound to dislocations in mechanical metamaterials

    NASA Astrophysics Data System (ADS)

    Paulose, Jayson; Chen, Bryan Gin-Ge; Vitelli, Vincenzo

    2015-02-01

    Mechanical metamaterials are artificial structures with unusual properties, such as negative Poisson ratio, bistability or tunable vibrational properties, that originate in the geometry of their unit cell. Often at the heart of such unusual behaviour is a soft mode: a motion that does not significantly stretch or compress the links between constituent elements. When activated by motors or external fields, soft modes become the building blocks of robots and smart materials. Here, we demonstrate the existence of topological soft modes that can be positioned at desired locations in a metamaterial while being robust against a wide range of structural deformations or changes in material parameters. These protected modes, localized at dislocations in deformed kagome and square lattices, are the mechanical analogue of topological states bound to defects in electronic systems. We create physical realizations of the topological modes in prototypes of kagome lattices built out of rigid triangular plates. We show mathematically that they originate from the interplay between two Berry phases: the Burgers vector of the dislocation and the topological polarization of the lattice. Our work paves the way towards engineering topologically protected nanomechanical structures for molecular robotics or information storage and read-out.

  5. Reversible Chemochromic Hydrogen Detectors

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Florida Solar Energy Center (FSEC), affiliated with the University of Central Florida, has invented a reversible pigment that changes from light beige to blue when exposed to hydrogen and back to light beige when exposed to atmospheric oxygen. In laboratory and environmental studies, the FSEC pigment in its tape form failed to change color adequately when exposed to hydrogen after one day of exposure at Kennedy Space Center's Beach Corrosion Test Facility. The reversible hydrogen-detecting tape also lost its ability to change color after being placed in an environmental chamber at 45 C for one day. The first attempts at extruding the reversible pigment into various polymers were unsuccessful because of the pigment's poor thermal stability. The goal of this project was to formulate a pigment with improved thermal and environmental stability for extrusion into a variety of appropriate polymer matrices. The formulation of the reversible hydrogen-detecting pigment was modified by removing one reagent and chemically modifying the hydrogen sensitive ingredient. This was intended to improve the hydrophobicity of the pigment and alter the thermal degradation mechanism.

  6. Reversing Discrimination: A Perspective

    ERIC Educational Resources Information Center

    Pati, Gopal; Reilly, Charles W.

    1977-01-01

    Examines the debate over affirmative action and reverse discrimination, and discusses how and why the present dilemma has developed. Suggests that organizations can best address the problem through an honest, in-depth analysis of their organizational structure and management practices. (JG)

  7. Reverse Coherent Information

    NASA Astrophysics Data System (ADS)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-04-01

    We define a family of entanglement distribution protocols assisted by classical feedback communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This protocol family leads to the definition of a new entanglement distribution capacity that exceeds the unassisted entanglement distribution capacity for some interesting channels.

  8. Reverse Coherent Information

    NASA Astrophysics Data System (ADS)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-05-01

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  9. Time reversal communication system

    DOEpatents

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  10. Reversing Underachievement through Enrichment.

    ERIC Educational Resources Information Center

    Renzulli, Joseph S.; Baum, Susan M.; Hebert, Thomas; McCluskey, Ken W.

    1999-01-01

    Discusses problems of underachievement, especially among potentially high ability students, and the difficulties inherent in reversing this process. Presents new perspective and strategies that promote success. Describes Type III enrichment experiences as a means to unleash students' potential. Speculates as to what causes turnaround within an…

  11. Reverse coherent information.

    PubMed

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H

    2009-05-29

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  12. Justice and Reverse Discrimination

    ERIC Educational Resources Information Center

    Strike, Kenneth A.

    1976-01-01

    Although this article does not necessarily recommend policies of reverse discrimination, arguments indicating that such policies are not contradictory to accepted concepts of justice are presented. The necessity of dispersing any consequent injury to society as a whole rather than to individuals is stressed. (RW)

  13. Insulin, insulin analogues and diabetic retinopathy.

    PubMed

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  14. Actions of Thyroid Hormone Analogues on Chemokines.

    PubMed

    Davis, Paul J; Glinsky, Gennadi V; Lin, Hung-Yun; Mousa, Shaker A

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3'-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  15. Fluorescent polyene ceramide analogues as membrane probes.

    PubMed

    Nieves, Ingrid; Artetxe, Ibai; Abad, José Luis; Alonso, Alicia; Busto, Jon V; Fajarí, Lluís; Montes, L Ruth; Sot, Jesús; Delgado, Antonio; Goñi, Félix M

    2015-03-01

    Three ceramide analogues have been synthesized, with sphingosine-like chains containing five conjugated double bonds. Pentaene I has an N-palmitoyl acyl chain, while the other two pentaenes contain also a doxyl radical, respectively, at C5 (Penta5dox) and at C16 (Penta16dox) positions of the N-acyl chain. Pentaene I maximum excitation and emission wavelengths in a phospholipid bilayer are 353 and 478 nm, respectively. Pentaene I does not segregate from the other lipids in the way natural ceramide does, but rather mixes with them in a selective way according to the lipid phases involved. Fluorescence confocal microscopy studies show that when lipid domains in different physical states coexist, Pentaene I emission is higher in gel than in fluid domains, and in liquid-ordered than in liquid-disordered areas. Electron paramagnetic resonance of the pentaene doxyl probes confirms that these molecules are sensitive to the physical state of the bilayer. Calorimetric and fluorescence quenching experiments suggest that the lipids under study orient themselves in lipid bilayers with their polar moieties located at the lipid-water interface. The doxyl radical in the N-acyl chain quenches the fluorescence of the pentaene group when in close proximity. Because of this property, Penta16dox can detect gel-fluid transitions in phospholipids. The availability of probes for lipids in the gel phase is important in view of novel evidence for the existence of gel microdomains in cell membranes.

  16. Inhibition of firefly luciferase by alkane analogues.

    PubMed

    Takehara, Kô; Kamaya, Hiroshi; Ueda, Issaku

    2005-01-18

    We reported that anesthetics increased the partial molal volume of firefly luciferase (FFL), while long-chain fatty acids (LCFA) decreased it. The present study measured the actions of dodecanol (neutral), dodecanoic acid (negatively charged), and dodecylamine (positively charged) hydrophobic molecules on FFL. The interaction modes are measured by (1) ATP-induced bioluminescence of FFL and (2) fluorescence of 2-(p-toluidino)naphthalene-6-sulfonate (TNS). TNS fluoresces brightly in hydrophobic media. It competes with the substrate luciferin on the FFL binding. From the Scatchard plot of TNS titration, the maximum binding number of TNS was 0.83, and its binding constant was 8.27 x 10(5) M(-1). Job's plot also showed that the binding number is 0.89. From the TNS titration of FFL, the binding constant was estimated to be 8.8 x 10(5) M(-1). Dodecanoic acid quenched the TNS fluorescence entirely. Dodecanol quenched about 25% of the fluorescence, whereas dodecylamine increased it. By comparing the fluorescence of TNS and bioluminescence of FFL, the binding modes and the inhibition mechanisms of these dodecane analogues are classified in three different modes: competitive (dodecanoic acid), noncompetitive (dodecylamine), and mixed (dodecanol).

  17. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer.

    PubMed

    Bodei, Lisa; Kwekkeboom, Dik J; Kidd, Mark; Modlin, Irvin M; Krenning, Eric P

    2016-05-01

    Peptide receptor radionuclide therapy (PRRT) has been utilized for more than two decades and has been accepted as an effective therapeutic modality in the treatment of inoperable or metastatic gastroenteropancreatic neuroendocrine neoplasms (NENs) or neuroendocrine tumors (NETs). The two most commonly used radiopeptides for PRRT, (90)Y-octreotide and (177)Lu-octreotate, produce disease-control rates of 68%-94%, with progression-free survival rates that compare favorably with chemotherapy, somatostatin analogues, and newer targeted therapies. In addition, biochemical and symptomatic responses are commonly observed. In general, PRRT is well tolerated with only low to moderate toxicity in most individuals. In line with the need to place PRRT in the therapeutic sequence of gastroenteropancreatic NENs, a recently sponsored phase III randomized trial in small intestine NENs treated with (177)Lu-octreotate vs high-dose octreotide long-acting release demonstrated that (177)Lu-octreotate significantly improved progression-free survival. Other strategies that are presently being developed include combinations with targeted therapies or chemotherapy, intra-arterial PRRT, and salvage treatments. Sophisticated molecular tools need to be incorporated into the management strategy to more effectively define therapeutic efficacy and for an early identification of adverse events. The strategy of randomized controlled trials is a key issue to standardize the treatment and establish the position of PRRT in the therapeutic algorithm of NENs. PMID:27067503

  18. Actions of Thyroid Hormone Analogues on Chemokines

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  19. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  20. Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing.

    PubMed

    Mpakali, Anastasia; Saridakis, Emmanuel; Harlos, Karl; Zhao, Yuguang; Papakyriakou, Athanasios; Kokkala, Paraskevi; Georgiadis, Dimitris; Stratikos, Efstratios

    2015-09-15

    Aminopeptidases that generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. The mechanisms that allow these enzymes to efficiently process a vast number of different long peptide substrates are poorly understood. In this work, we report the structure of insulin-regulated aminopeptidase, an enzyme that prepares antigenic epitopes for cross-presentation in dendritic cells, in complex with an antigenic peptide precursor analog. Insulin-regulated aminopeptidase is found in a semiclosed conformation with an extended internal cavity with limited access to the solvent. The N-terminal moiety of the peptide is located at the active site, positioned optimally for catalysis, whereas the C-terminal moiety of the peptide is stabilized along the extended internal cavity lodged between domains II and IV. Hydrophobic interactions and shape complementarity enhance peptide affinity beyond the catalytic site and support a limited selectivity model for antigenic peptide selection that may underlie the generation of complex immunopeptidomes.

  1. THE HOPF BIFURCATION WITH BOUNDED NOISE

    PubMed Central

    Botts, Ryan T.; Homburg, Ale Jan; Young, Todd R.

    2012-01-01

    We study Hopf-Andronov bifurcations in a class of random differential equations (RDEs) with bounded noise. We observe that when an ordinary differential equation that undergoes a Hopf bifurcation is subjected to bounded noise then the bifurcation that occurs involves a discontinuous change in the Minimal Forward Invariant set. PMID:24748762

  2. THE HOPF BIFURCATION WITH BOUNDED NOISE.

    PubMed

    Botts, Ryan T; Homburg, Ale Jan; Young, Todd R

    2012-08-01

    We study Hopf-Andronov bifurcations in a class of random differential equations (RDEs) with bounded noise. We observe that when an ordinary differential equation that undergoes a Hopf bifurcation is subjected to bounded noise then the bifurcation that occurs involves a discontinuous change in the Minimal Forward Invariant set.

  3. THE HOPF BIFURCATION WITH BOUNDED NOISE.

    PubMed

    Botts, Ryan T; Homburg, Ale Jan; Young, Todd R

    2012-08-01

    We study Hopf-Andronov bifurcations in a class of random differential equations (RDEs) with bounded noise. We observe that when an ordinary differential equation that undergoes a Hopf bifurcation is subjected to bounded noise then the bifurcation that occurs involves a discontinuous change in the Minimal Forward Invariant set. PMID:24748762

  4. Outward Bound: An Innovative Patient Education Program.

    ERIC Educational Resources Information Center

    Stich, Thomas F.; Gaylor, Michael S.

    A 1975 Dartmouth Outward Bound Mental Health Project, begun with a pilot project for disturbed adolescents, has evolved into an ongoing treatment option in three separate clinical settings for psychiatric patients and recovering alcoholics. Outward Bound consists of a series of prescribed physical and social tasks where the presence of stress,…

  5. Constrained bounds on measures of entanglement

    SciTech Connect

    Datta, Animesh; Flammia, Steven T.; Shaji, Anil; Caves, Carlton M.

    2007-06-15

    Entanglement measures constructed from two positive, but not completely positive, maps on density operators are used as constraints in placing bounds on the entanglement of formation, the tangle, and the concurrence of 4N mixed states. The maps are the partial transpose map and the phi map introduced by Breuer [H.-P. Breuer, Phys. Rev. Lett. 97, 080501 (2006)]. The norm-based entanglement measures constructed from these two maps, called negativity and phi negativity, respectively, lead to two sets of bounds on the entanglement of formation, the tangle, and the concurrence. We compare these bounds and identify the sets of 4N density operators for which the bounds from one constraint are better than the bounds from the other. In the process, we present a derivation of the already known bound on the concurrence based on the negativity. We compute bounds on the three measures of entanglement using both the constraints simultaneously. We demonstrate how such doubly constrained bounds can be constructed. We discuss extensions of our results to bipartite states of higher dimensions and with more than two constraints.

  6. Genomic sorting with length-weighted reversals.

    PubMed

    Pinter, Ron Y; Skiena, Steven

    2002-01-01

    Current algorithmic studies of genome rearrangement ignore the length of reversals (or inversions); rather, they only count their number. We introduce a new cost model in which the lengths of the reversed sequences play a role, allowing more flexibility in accounting for mutation phenomena. Our focus is on sorting unsigned (unoriented) permutations by reversals; since this problem remains difficult (NP-hard) in our new model, the best we can hope for are approximation results. We propose an efficient, novel algorithm that takes (a monotonic function f of) length into account as an optimization criterion and study its properties. Our results include an upper bound of O(fn lg2n) for any additive cost measure f on the cost of sorting any n-element permutation, and a guaranteed approximation ratio of O(lg2n) times optimal for sorting a given permutation. Our work poses some interesting questions to both biologists and computer scientists and suggests some new bioinformatic insights that are currently being studied. PMID:14571379

  7. Paired Magmatic-Metallogenic Belts in Myanmar - an Andean Analogue?

    NASA Astrophysics Data System (ADS)

    Gardiner, Nicholas; Robb, Laurence; Searle, Michael; Morley, Christopher

    2015-04-01

    Myanmar (Burma) is richly endowed in precious and base metals, having one of the most diverse collections of natural resources in SE Asia. Its geological history is dominated by the staged closing of Tethys and the suturing of Gondwana-derived continental fragments onto the South China craton during the Mesozoic-Cenozoic. The country is located at a crucial geologic juncture where the main convergent Tethyan collision zone swings south around the Namche Barwa Eastern Himalayan syntaxis. However, despite recent work, the geological and geodynamic history of Myanmar remains enigmatic. Plate margin processes, magmatism, metasomatism and the genesis of mineral deposits are intricately linked, and there has long been recognized a relationship between the distribution of certain mineral deposit types, and the tectonic settings which favour their genesis. A better knowledge of the regional tectonic evolution of a potential exploration jurisdiction is therefore crucial to understanding its minerals prospectivity. This strong association between tectonics and mineralization can equally be applied in reverse. By mapping out the spatial, and temporal, distribution of presumed co-genetic mineral deposits, coupled with an understanding of their collective metallogenetic origin, a better appreciation of the tectonic evolution of a terrane may be elucidated. Identification and categorization of metallotects within a geodynamically-evolving terrane thus provides a complimentary tool to other methodologies (e.g. geochemical, geochronological, structural, geophysical, stratigraphical), for determining the tectonic history and inferred geodynamic setting of that terrane through time. Myanmar is one such study area where this approach can be undertaken. Here are found two near-parallel magmatic belts, which together contain a significant proportion of that country's mineral wealth of tin, tungsten, copper, gold and silver. Although only a few 100 km's apart, these belts exhibit a

  8. Peptide sweeteners. 3. Effect of modifying the peptide bond on the sweet taste of L-aspartyl-L-phenylalanine methyl ester and its analogues.

    PubMed

    MacDonald, S A; Willson, C G; Chorev, M; Vernacchia, F S; Goodman, M

    1980-04-01

    A series of analogues designed to assess the importance of the amide bond in the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester has been synthesized and tested. The peptide bond was methylated, replaced by an ester bond, or reversed. all of these modifications produced compounds that did not have a sweet taste. We conclude that the steric, electronic, and directional characteristics of the amide bond are essential for biological activity in the dipeptide sweeteners. PMID:7381839

  9. Peptide sweeteners. 3. Effect of modifying the peptide bond on the sweet taste of L-aspartyl-L-phenylalanine methyl ester and its analogues.

    PubMed

    MacDonald, S A; Willson, C G; Chorev, M; Vernacchia, F S; Goodman, M

    1980-04-01

    A series of analogues designed to assess the importance of the amide bond in the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester has been synthesized and tested. The peptide bond was methylated, replaced by an ester bond, or reversed. all of these modifications produced compounds that did not have a sweet taste. We conclude that the steric, electronic, and directional characteristics of the amide bond are essential for biological activity in the dipeptide sweeteners.

  10. N-arylazido-. beta. -alanyl-NAD sup + , a new NAD sup + photoaffinity analogue. Synthesis and labeling of mitochondrial NADH dehydrogenase

    SciTech Connect

    Deng, P.S.K.; Chen, S. ); Hatefi, Y. )

    1990-01-30

    N-Arylaziod-{beta}-alanyl-NAD{sup +}(N3{prime}-0-(3-(N-(4-azido-2-nitrophenyl)amino)propionyl)NAD{sup +}) has been prepared by alkaline phosphatase treatment of arylaziod-{beta}-alanyl-NADP{sup +} (N3{prime}-O-(3-(N-(4-azido-2-nitrophenyl)amino)propionyl)NADP{sup +}). This NAD{sup +} analogue was found to be a potent competitive inhibitor with respect to NADH for the purified bovine heart mitochondrial NADH dehydrogenase. The enzyme was irreversibly inhibited as well as covalently labeled by this analogue upon photoirradiation. A stoichiometry of 1.15 mol of N-arylazido-{beta}-alanyl-NAD{sup +} bound/mol of enzyme, at 100% inactivation, was determined from incorporation studies using tritium-labeled analogue. Among the three subunits, 0.85 mol of the analogue was bound to the M{sub r} = 51,000 subunit, and each of the two smaller subunits contained 0.15 mol of the analogue when the dehydrogenase was completely inhibited upon photolysis. Both the irreversible inactivation and the covalent incorporation could be prevented by the presence of NADH during photolysis. These results indicate that N-arylaziod-{beta}-alanyl-NAD{sup +} is an active-site-directed photoaffinity label for the mitochondrial NADH dehydrogenase, and are further evidence that the M{sub r} = 51,000 subunit contain the NADH binding site. Results are also presented to show that N-arylazido-{beta}-alanyl-NAD{sup +} binds the dehydrogenase in a more effective manner than A-arylazido-{beta}-alanyl-NAD{sup +}.

  11. SHARP ENTRYWISE PERTURBATION BOUNDS FOR MARKOV CHAINS

    PubMed Central

    THIEDE, ERIK; VAN KOTEN, BRIAN; WEARE, JONATHAN

    2015-01-01

    For many Markov chains of practical interest, the invariant distribution is extremely sensitive to perturbations of some entries of the transition matrix, but insensitive to others; we give an example of such a chain, motivated by a problem in computational statistical physics. We have derived perturbation bounds on the relative error of the invariant distribution that reveal these variations in sensitivity. Our bounds are sharp, we do not impose any structural assumptions on the transition matrix or on the perturbation, and computing the bounds has the same complexity as computing the invariant distribution or computing other bounds in the literature. Moreover, our bounds have a simple interpretation in terms of hitting times, which can be used to draw intuitive but rigorous conclusions about the sensitivity of a chain to various types of perturbations. PMID:26491218

  12. Covariant entropy bound and loop quantum cosmology

    SciTech Connect

    Ashtekar, Abhay; Wilson-Ewing, Edward

    2008-09-15

    We examine Bousso's covariant entropy bound conjecture in the context of radiation filled, spatially flat, Friedmann-Robertson-Walker models. The bound is violated near the big bang. However, the hope has been that quantum gravity effects would intervene and protect it. Loop quantum cosmology provides a near ideal setting for investigating this issue. For, on the one hand, quantum geometry effects resolve the singularity and, on the other hand, the wave function is sharply peaked at a quantum corrected but smooth geometry, which can supply the structure needed to test the bound. We find that the bound is respected. We suggest that the bound need not be an essential ingredient for a quantum gravity theory but may emerge from it under suitable circumstances.

  13. Rigorous bounds for optimal dynamical decoupling

    SciTech Connect

    Uhrig, Goetz S.; Lidar, Daniel A.

    2010-07-15

    We present rigorous performance bounds for the optimal dynamical decoupling pulse sequence protecting a quantum bit (qubit) against pure dephasing. Our bounds apply under the assumption of instantaneous pulses and of bounded perturbing environment and qubit-environment Hamiltonians such as those realized by baths of nuclear spins in quantum dots. We show that if the total sequence time is fixed the optimal sequence can be used to make the distance between the protected and unperturbed qubit states arbitrarily small in the number of applied pulses. If, on the other hand, the minimum pulse interval is fixed and the total sequence time is allowed to scale with the number of pulses, then longer sequences need not always be advantageous. The rigorous bound may serve as a testbed for approximate treatments of optimal decoupling in bounded models of decoherence.

  14. Mutually unbiased bases and bound entanglement

    NASA Astrophysics Data System (ADS)

    Hiesmayr, Beatrix C.; Löffler, Wolfgang

    2014-04-01

    In this contribution we relate two different key concepts: mutually unbiased bases (MUBs) and entanglement. We provide a general toolbox for analyzing and comparing entanglement of quantum states for different dimensions and numbers of particles. In particular we focus on bound entanglement, i.e. highly mixed states which cannot be distilled by local operations and classical communications. For a certain class of states—for which the state-space forms a ‘magic’ simplex—we analyze the set of bound entangled states detected by the MUB criterion for different dimensions d and number of particles n. We find that the geometry is similar for different d and n, consequently the MUB criterion opens possibilities to investigate the typicality of positivity under partial transposition (PPT)-bound and multipartite bound entanglement more deeply and provides a simple experimentally feasible tool to detect bound entanglement.

  15. Entropy Bounds for Hierarchical Molecular Networks

    PubMed Central

    Dehmer, Matthias; Borgert, Stephan; Emmert-Streib, Frank

    2008-01-01

    In this paper we derive entropy bounds for hierarchical networks. More precisely, starting from a recently introduced measure to determine the topological entropy of non-hierarchical networks, we provide bounds for estimating the entropy of hierarchical graphs. Apart from bounds to estimate the entropy of a single hierarchical graph, we see that the derived bounds can also be used for characterizing graph classes. Our contribution is an important extension to previous results about the entropy of non-hierarchical networks because for practical applications hierarchical networks are playing an important role in chemistry and biology. In addition to the derivation of the entropy bounds, we provide a numerical analysis for two special graph classes, rooted trees and generalized trees, and demonstrate hereby not only the computational feasibility of our method but also learn about its characteristics and interpretability with respect to data analysis. PMID:18769487

  16. Upper bounds on sequential decoding performance parameters

    NASA Technical Reports Server (NTRS)

    Jelinek, F.

    1974-01-01

    This paper presents the best obtainable random coding and expurgated upper bounds on the probabilities of undetectable error, of t-order failure (advance to depth t into an incorrect subset), and of likelihood rise in the incorrect subset, applicable to sequential decoding when the metric bias G is arbitrary. Upper bounds on the Pareto exponent are also presented. The G-values optimizing each of the parameters of interest are determined, and are shown to lie in intervals that in general have nonzero widths. The G-optimal expurgated bound on undetectable error is shown to agree with that for maximum likelihood decoding of convolutional codes, and that on failure agrees with the block code expurgated bound. Included are curves evaluating the bounds for interesting choices of G and SNR for a binary-input quantized-output Gaussian additive noise channel.

  17. From BPA to its analogues: Is it a safe journey?

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful?

  18. Cell-Cycle Analyses Using Thymidine Analogues in Fission Yeast

    PubMed Central

    Anda, Silje; Boye, Erik; Grallert, Beata

    2014-01-01

    Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2′-deoxyuridine (EdU) and 5-Chloro-2′-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2′-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry. PMID:24551125

  19. From BPA to its analogues: Is it a safe journey?

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

  20. Effects of Prostaglandin Analogues on Aqueous Humor Outflow Pathways

    PubMed Central

    Winkler, Nelson S.

    2014-01-01

    Abstract Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. All treatments, whether surgical or pharmaceutical, are aimed at lowering IOP. Prostaglandin analogues are a first line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Whereas prostaglandin analogues have been known to alter aqueous humor outflow through the unconventional (uveoscleral) pathway, more recent evidence suggests their action also occurs through the conventional (trabecular) pathway. Understanding how prostaglandin analogues successfully lower IOP is important, as this information may lead to the discovery of new molecular targets for future therapeutic intervention. This review explores the current understanding of prostaglandin analogue biology as it pertains to IOP reduction and improved aqueous humor outflow facility. PMID:24359106

  1. Analogues for Wild2: Carbonaceous Chondrites Shot into Aerogel

    NASA Astrophysics Data System (ADS)

    Hicks, L. J.; Bridges, J. C.; MacArthur, J. L.; Wickham-Eade, J. E.; Price, M. C.; Burchell, M. J.; Butterworth, A. L.; Baker, S. H.

    2016-08-01

    Comet Wild2 particles show similarities to carbonaceous chondrites. We compare Wild2 grains to analogue shots of CV3 and CR2 powders in aerogel tracks, using the same techniques, to make accurate comparisons.

  2. Mars Methane Analogue Mission (M3): Analytical Techniques and Operations

    NASA Astrophysics Data System (ADS)

    Cloutis, E.; Vrionis, H.; Qadi, A.; Bell, J. F.; Berard, G.; Boivin, A.; Ellery, A.; Jamroz, W.; Kruzelecky, R.; Mann, P.; Samson, C.; Stromberg, J.; Strong, K.; Tremblay, A.; Whyte, L.; Wing, B.

    2011-03-01

    The Mars Methane Analogue Mission (M3) project is designed to simulate a rover-based search for, and analysis of, methane sources on Mars at a serpentinite open pit mine in Quebec, using a variety of instruments.

  3. Sulphur Spring: Busy Intersection and Possible Martian Analogue

    NASA Technical Reports Server (NTRS)

    Nankivell, A.; Andre, N.; Thomas-Keprta, K.; Allen, C.; McKay, D.

    2000-01-01

    Life in extreme environments exhibiting conditions similar to early Earth and Mars, such as Sulphur Spring, may harbor microbiota serving as both relics from the past as well as present day Martian analogues.

  4. Bound-free Spectra for Diatomic Molecules

    NASA Technical Reports Server (NTRS)

    Schwenke, David W.

    2012-01-01

    It is now recognized that prediction of radiative heating of entering space craft requires explicit treatment of the radiation field from the infrared (IR) to the vacuum ultra violet (VUV). While at low temperatures and longer wavelengths, molecular radiation is well described by bound-bound transitions, in the short wavelength, high temperature regime, bound-free transitions can play an important role. In this work we describe first principles calculations we have carried out for bound-bound and bound-free transitions in N2, O2, C2, CO, CN, NO, and N2+. Compared to bound ]bound transitions, bound-free transitions have several particularities that make them different to deal with. These include more complicated line shapes and a dependence of emission intensity on both bound state diatomic and atomic concentrations. These will be discussed in detail below. The general procedure we used was the same for all species. The first step is to generate potential energy curves, transition moments, and coupling matrix elements by carrying out ab initio electronic structure calculations. These calculations are expensive, and thus approximations need to be made in order to make the calculations tractable. The only practical method we have to carry out these calculations is the internally contracted multi-reference configuration interaction (icMRCI) method as implemented in the program suite Molpro. This is a widely used method for these kinds of calculations, and is capable of generating very accurate results. With this method, we must first of choose which electrons to correlate, the one-electron basis to use, and then how to generate the molecular orbitals.

  5. Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors.

    PubMed

    Zhu, Tian-Hua; Cao, Shu-Wen; Yu, Yan-Ying

    2013-11-01

    A series of hydroxy- and methoxy-substituted paeonol thiosemicarbazone analogues were synthesized as potential tyrosinase inhibitors and their inhibitory effects on mushroom tyrosinase and inhibitory mechanism were evaluated. Paeonol thiosemicarbazone analogues have been found exhibiting more remarkable inhibition than their indexcompounds on mushroom tyrosinase. Among them, compound 2,4-dihydroxy acetophenone-4-phenyl-3-thiosemicarbazone (d1) had the most potent inhibition activity with the IC50 value of 0.006 ± 0.001 mM, displayed as a reversible competitive inhibitor. The inhibitory ability of o- or p-substituted acetophenone thiosemicarbazones was: di-substituted acetophenone thiosemicarbazones>mono-substituted acetophenone thiosemicarbazones>non-substituted acetophenone thiosemicarbazones. Copper ions chelation assay explained that compound d1 exhibited competitive inhibition by forming a chelate with the copper ions at the catalytic domain of tyrosinase as well as indicate a 1.5:1 binding ratio of compound d1 with copper ions. In the fluorescence spectrum study, compound d1 behaved stronger fluorescence quenching on tyrosinase towards d1-Cu(2+) complex, inhibiting tyrosinase mainly by means of chelating the two copper ions in the active site. The newly synthesized compounds may serve as structural templates for designing and developing novel tyrosinase inhibitors.

  6. Cholecystokinin receptors: disparity between phosphoinositide breakdown and amylase releasing activity of CCK analogues in pancreas

    SciTech Connect

    Lin, C.W.; Grant, D.; Bianchi, B.; Miller, T.; Witte, D.; Shue, Y.K.; Nadzan, A.

    1986-03-05

    Cholecystokinin (CCK) peptides are a family of hormones which also occur in brain. In pancreas CCK stimulates the release of amylase, a process that is dependent on the mobilization of intracellular Ca/sup 2 +/. Recent evidence suggests that inositol 1,4,5-trisphosphate, the breakdown product of phosphatidylinositol 4,5-bisphosphate, is responsible for the rise in intracellular Ca/sup 2 +/. Their laboratory has developed assays to study synthetic CCK analogues using radioligand binding, PI breakdown and amylase release. They have shown that there are good correlations among these three assay systems for the carboxy terminal fragments of CCK/sub 8/. Recently, they have discovered synthetic analogues of CCK/sub 4/ that are full agonists in amylase release but are ineffective in causing PI breakdown. In particular, A-61576, Boc-5-amino-2-indolemethylene-pent-2-ene-1-oyl-Leu-Asp-Phe-NH/sub 2/, is a full agonist in the amylase releasing assay, but is devoid of PI stimulating activity. A-61576 completely reverses the stimulation of PI response induced by CCK/sub 8/, indicative of an antagonist. Since a mechanism other than the PI breakdown is responsible for amylase release by A-61576, they suggest that separate receptors are responsible for PI breakdown and amylase release.

  7. Structural Basis for Recognition of Guanosine by a Synthetic Tricyclic Cytosine Analogue: Guanidinium G-Clamp

    SciTech Connect

    Wilds, C.J.; Maier, M.A.; Manoharan, M.; Egli, M.

    2010-03-08

    An oligonucleotide analogue containing a novel heterocyclic analogue, the guanidinium G-clamp, was designed to allow formation of five H-bonds to guanosine. The guanidinium group was introduced postsynthetically by treatment of the deprotected oligonucleotide containing a free amino group with a solution of 1H-pyrazole-1-carboxamidine and purified by a combination of size-exclusion chromatography and reversed-phase HPLC. A single incorporation of this modification into an oligodeoxynucleotide sequence was found to increase duplex stability by 13{sup o} and 16{sup o} per modification to RNA and DNA, respectively. Crystals of a self-complementary decamer sequence containing this modification were grown and diffracted to 1-{angstrom} resolution. The structure was solved by molecular replacement and revealed that the modification forms additional H-bonds to O(6) and N(7) of guanosine through the amino and imino N-atoms, respectively. The origins of enhanced duplex stability are also attributed to increased stacking interactions mediated by the phenoxazine moiety of the G-clamp and formation of H-bond networks between the positively charged guanidinium group, H{sub 2}O molecules, and negatively charged O-atoms from phosphates on the adjacent strand.

  8. Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors.

    PubMed

    Zhu, Tian-Hua; Cao, Shu-Wen; Yu, Yan-Ying

    2013-11-01

    A series of hydroxy- and methoxy-substituted paeonol thiosemicarbazone analogues were synthesized as potential tyrosinase inhibitors and their inhibitory effects on mushroom tyrosinase and inhibitory mechanism were evaluated. Paeonol thiosemicarbazone analogues have been found exhibiting more remarkable inhibition than their indexcompounds on mushroom tyrosinase. Among them, compound 2,4-dihydroxy acetophenone-4-phenyl-3-thiosemicarbazone (d1) had the most potent inhibition activity with the IC50 value of 0.006 ± 0.001 mM, displayed as a reversible competitive inhibitor. The inhibitory ability of o- or p-substituted acetophenone thiosemicarbazones was: di-substituted acetophenone thiosemicarbazones>mono-substituted acetophenone thiosemicarbazones>non-substituted acetophenone thiosemicarbazones. Copper ions chelation assay explained that compound d1 exhibited competitive inhibition by forming a chelate with the copper ions at the catalytic domain of tyrosinase as well as indicate a 1.5:1 binding ratio of compound d1 with copper ions. In the fluorescence spectrum study, compound d1 behaved stronger fluorescence quenching on tyrosinase towards d1-Cu(2+) complex, inhibiting tyrosinase mainly by means of chelating the two copper ions in the active site. The newly synthesized compounds may serve as structural templates for designing and developing novel tyrosinase inhibitors. PMID:24120880

  9. Molecular features contributing to the lower viscosity of phosphonium ionic liquids compared to their ammonium analogues.

    PubMed

    Scarbath-Evers, Laura Katharina; Hunt, Patricia A; Kirchner, Barbara; MacFarlane, Douglas R; Zahn, Stefan

    2015-08-21

    Molecular features contributing to the lower viscosity of phosphonium based ionic liquids (ILs) compared to ammonium based ILs are investigated by static quantum chemistry calculations and classical molecular dynamics simulations. The larger bond distance and the higher flexibility of bond angles and dihedral angles in the phosphonium compounds tend to reduce their viscosity compared to ammonium analogues, while the strongly localized charge at the central atom has the opposite effect. Fast translational ion dynamics is also found to be related to a short counter-ion association lifetime in the investigated compounds. Furthermore, a weak structuring between the center of charges also seems to increase mobility. Interestingly, the order of ion pair interaction energies in the gas phase is reversed compared to the order of counter-ion association lifetimes in the liquid, which highlights the important role of solvation in ILs. Overall, the higher flexibility of the bond and dihedral angles of the phosphonium compounds appears to be the most important factor in producing the lower viscosity of these ILs compared to their ammonium analogues.

  10. Photochemical synthesis of nucleoside analogues from cyclobutanones: bicyclic and isonucleosides.

    PubMed

    Jaffer, Mileina; Ebead, Abdelaziz; Lee-Ruff, Edward

    2010-05-26

    The preparation of two nucleoside analogues are reported. Both syntheses involve a key photochemical ring-expansion of cyclobutanones to an oxacarbene and its subsequent scavenging by 6-chloropurine. The synthesis of a bicyclic (locked) purine starts from a oxabicycloheptanone with a hydroxymethyl pendant. The preparation of an isonucleoside uses a cyclobutanone with an alpha-substituted 6-chloropurine. Irradiation of the latter produces an isonucleoside and acyclic nucleoside analogues.

  11. Analogue and digital linear modulation techniques for mobile satellite

    NASA Technical Reports Server (NTRS)

    Whitmarsh, W. J.; Bateman, A.; Mcgeehan, J. P.

    1990-01-01

    The choice of modulation format for a mobile satellite service is complex. The subjective performance is summarized of candidate schemes and voice coder technologies. It is shown that good performance can be achieved with both analogue and digital voice systems, although the analogue system gives superior performance in fading. The results highlight the need for flexibility in the choice of signaling format. Linear transceiver technology capable of using many forms of narrowband modulation is described.

  12. Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics.

    PubMed

    Ichikawa, Satoshi; Yamaguchi, Mayumi; Hsuan, Lee Shang; Kato, Yuta; Matsuda, Akira

    2015-04-10

    Carbacaprazamycins, which are chemically stable analogues of caprazamycins, were designed and synthesized. These analogues were active against drug-resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and their activities were comparable to those of the parent caprazamycins. The effect of treatment with carbacaprazamycin on morphological changes in S. aureus indicated that the mode of action was completely different from those of existing peptidoglycan inhibitors. PMID:27622529

  13. New PDMP analogues inhibit process outgrowth in an insect cell line.

    PubMed

    Slavish, Jacob P; Friel, Donna K; Oland, Lynne A; Polt, Robin

    2004-03-22

    d-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (d-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New d-threo-PDMP analogues were synthesized from d-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than d-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies. PMID:15006387

  14. Photophysical and nonlinear optical studies of tetraakynyl zincphthalocyanine and its "clicked" analogue

    NASA Astrophysics Data System (ADS)

    Bankole, Owolabi M.; Nyokong, Tebello

    2015-06-01

    We report here for the first time on the photophysical and nonlinear optical behavior of tetra-substituted alkynyl zinc phthalocyanine and its "clicked" analogue (4 and 5). The compounds exhibited high triplet quantum yields in dimethylsulphoxide (DMSO). Nonlinear optical (NLO) properties were also evaluated for the two compounds at 532 nm and 10 ns in DMSO. We observed two-photon absorption (2PA) and strong reverse saturable absorption (RSA) as the dominant mechanisms at nanosecond laser excitation. The presence of electron acceptor groups fused with triazole linkers in the peripheral positions of 4 provide excellent coexistent features, such as enhanced triplet quantum yields and lifetimes compared to 5. Large third-order susceptibility (2.09 × 10-11 and 3.53 × 10-9 esu) and hyperpolarizability (1.09 × 10-30 and 9.13 × 10-29 esu) were estimated for complexs 4 and 5, respectively.

  15. Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides

    PubMed Central

    Satishkumar, Sakilam; Vuram, Prasanna K.; Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Zhou, Hong; Kreitman, Robert J.; Montemayor, Michelle M. Martínez; Yang, Lijia; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender; Lakshman, Mahesh K.

    2016-01-01

    Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest on the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL), and chronic lymphocytic leukemia (CLL) cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribo analogue of cladribine possessed activity, but was least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, only cladribine and its ribose analogue were most active. PMID:26556315

  16. Bisphenol A and Its Analogues Activate Human Pregnane X Receptor

    PubMed Central

    Sui, Yipeng; Ai, Ni; Park, Se-Hyung; Rios-Pilier, Jennifer; Perkins, Jordan T.; Welsh, William J.

    2012-01-01

    Background: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. Objective: We investigated the mechanism by which BPA interacts with and activates PXR and examined selected BPA analogues to determine whether they bind to and activate PXR. Methods: Cell-based reporter assays, in silico ligand–PXR docking studies, and site-directed mutagenesis were combined to study the interaction between BPA and PXR. We also investigated the influence of BPA and its analogues on the regulation of PXR target genes in human LS180 cells. Results: We found that BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity. We identified key residues within hPXR’s ligand-binding pocket that constitute points of interaction with BPA. We also deduced the structural requirements of BPA analogues that activate hPXR. BPA and its analogues can also induce PXR target gene expression in human LS180 cells. Conclusions: The present study advances our understanding of the mechanism by which BPA interacts with and activates human PXR. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans. PMID:22214767

  17. Gridded electron reversal ionizer

    NASA Technical Reports Server (NTRS)

    Chutjian, Ara (Inventor)

    1993-01-01

    A gridded electron reversal ionizer forms a three dimensional cloud of zero or near-zero energy electrons in a cavity within a filament structure surrounding a central electrode having holes through which the sample gas, at reduced pressure, enters an elongated reversal volume. The resultant negative ion stream is applied to a mass analyzer. The reduced electron and ion space-charge limitations of this configuration enhances detection sensitivity for material to be detected by electron attachment, such as narcotic and explosive vapors. Positive ions may be generated by generating electrons having a higher energy, sufficient to ionize the target gas and pulsing the grid negative to stop the electron flow and pulsing the extraction aperture positive to draw out the positive ions.

  18. Reversed field pinch diagnostics

    SciTech Connect

    Weber, P.G.

    1986-01-01

    The Reversed Field Pinch (RFP) is a toroidal, axisymmetric magnetic confinement configuration characterized by a magnetic field configuration in which the toroidal magnetic field is of similar strength to the poloidal field, and is reversed at the edge compared to the center. The RFP routinely operates at high beta, and is a strong candidate for a compact fusion device. Relevant attributes of the configuration will be presented, together with an overview of present and planned experiments and their diagnostics. RFP diagnostics are in many ways similar to those of other magnetic confinement devices (such as tokamaks); these lectures will point out pertinent differences, and will present some diagnostics which provide special insights into unique attributes of the RFP.

  19. Reverse genetics of mononegavirales.

    PubMed

    Conzelmann, K K

    2004-01-01

    "Reverse genetics" or de novo synthesis of nonsegmented negative-sense RNA viruses (Mononegavirales) from cloned cDNA has become a reliable technique to study this group of medically important viruses. Since the first generation of a negative-sense RNA virus entirely from cDNA in 1994, reverse genetics systems have been established for members of most genera of the Rhabdo-, Paramyxo-, and Filoviridae families. These systems are based on intracellular transcription of viral full-length RNAs and simultaneous expression of viral proteins required to form the typical viral ribonucleoprotein complex (RNP). These systems are powerful tools to study all aspects of the virus life cycle as well as the roles of virus proteins in virus-host interplay and pathogenicity. In addition, recombinant viruses can be designed to have specific properties that make them attractive as biotechnological tools and live vaccines. PMID:15298166

  20. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    NASA Astrophysics Data System (ADS)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International

  1. Match-bounded String Rewriting Systems

    NASA Technical Reports Server (NTRS)

    Geser, Alfons; Hofbauer, Dieter; Waldmann, Johannes

    2003-01-01

    We introduce a new class of automated proof methods for the termination of rewriting systems on strings. The basis of all these methods is to show that rewriting preserves regular languages. To this end, letters are annotated with natural numbers, called match heights. If the minimal height of all positions in a redex is h+1 then every position in the reduct will get height h+1. In a match-bounded system, match heights are globally bounded. Using recent results on deleting systems, we prove that rewriting by a match-bounded system preserves regular languages. Hence it is decidable whether a given rewriting system has a given match bound. We also provide a sufficient criterion for the abence of a match-bound. The problem of existence of a match-bound is still open. Match-boundedness for all strings can be used as an automated criterion for termination, for match-bounded systems are terminating. This criterion can be strengthened by requiring match-boundedness only for a restricted set of strings, for instance the set of right hand sides of forward closures.

  2. Chemotactic peptide analogues. Synthesis and chemotactic activity of N-formyl-Met-Leu-Phe analogues containing (S)-phenylalaninol derivatives.

    PubMed

    Zecchini, G P; Paradisi, M P; Torrini, I; Spisani, S

    1995-09-01

    The synthesis and the biological activity towards human neutrophils of some N-formyl-Met-Leu-Phe-OMe analogues containing (S)-phenylalaninol (Pheol) or its derivatives in place of the native phenylalanine are reported. While the analogue containing Pheol (4) was found to be devoid of significant biological activity, its esters 3 and 5, although inactive as chemoattractants, are able to strongly stimulate superoxide production and are active with a lower efficacy in the lysozyme release. PMID:7487425

  3. Reversible watermarking for images

    NASA Astrophysics Data System (ADS)

    van Leest, Arno J.; van der Veen, Michiel; Bruekers, Fons

    2004-06-01

    Reversible watermarking is a technique for embedding data in a digital host signal in such a manner that the original host signal can be restored in a bit-exact manner in the restoration process. In this paper, we present a general framework for reversible watermarking in multi-media signals. A mapping function, which is in general neither injective nor surjective, is used to map the input signal to a perceptually equivalent output signal. The resulting unused sample values of the output signal are used to encode additional (watermark) information and restoration data. At the 2003 SPIE conference, examples of this technique applied to digital audio were presented. In this paper we concentrate on color and gray-scale images. A particular challenge in this context is not only the optimization of rate-distortion, but also the measure of perceptual quality (i.e. the distortion). In literature distortion is often expressed in terms of PSNR, making comparison among different techniques relatively straightforward. We show that our general framework for reversible watermarking applies to digital images and that results can be presented in terms of PSNR rate-distortions. However, the framework allows for more subtle signal manipulations that are not easily expressed in terms of PSNR distortion. These changes involve manipulations of contrast and/or saturation.

  4. Reversible DNA compaction.

    PubMed

    González-Pérez, Alfredo

    2014-01-01

    In this review we summarize and discuss the different methods we can use to achieve reversible DNA compaction in vitro. Reversible DNA compaction is a natural process that occurs in living cells and viruses. As a result these process long sequences of DNA can be concentrated in a small volume (compacted) to be decompacted only when the information carried by the DNA is needed. In the current work we review the main artificial compacting agents looking at their suitability for decompaction. The different approaches used for decompaction are strongly influenced by the nature of the compacting agent that determines the mechanism of compaction. We focus our discussion on two main artificial compacting agents: multivalent cations and cationic surfactants that are the best known compacting agents. The reversibility of the process can be achieved by adding chemicals like divalent cations, alcohols, anionic surfactants, cyclodextrins or by changing the chemical nature of the compacting agents via pH modifications, light induced conformation changes or by redox-reactions. We stress the relevance of electrostatic interactions and self-assembly as a main approach in order to tune up the DNA conformation in order to create an on-off switch allowing a transition between coil and compact states. The recent advances to control DNA conformation in vitro, by means of molecular self-assembly, result in a better understanding of the fundamental aspects involved in the DNA behavior in vivo and serve of invaluable inspiration for the development of potential biomedical applications. PMID:24444152

  5. Majorana bound states in magnetic skyrmions

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Stano, Peter; Klinovaja, Jelena; Loss, Daniel

    2016-06-01

    Magnetic skyrmions are highly mobile nanoscale topological spin textures. We show, both analytically and numerically, that a magnetic skyrmion of an even azimuthal winding number placed in proximity to an s -wave superconductor hosts a zero-energy Majorana bound state in its core, when the exchange coupling between the itinerant electrons and the skyrmion is strong. This Majorana bound state is stabilized by the presence of a spin-orbit interaction. We propose the use of a superconducting trijunction to realize non-Abelian statistics of such Majorana bound states.

  6. Lightweight Distance Bounding Protocol against Relay Attacks

    NASA Astrophysics Data System (ADS)

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  7. Bounds on dark matter in solar orbit

    SciTech Connect

    Anderson, J.D.; Lau, E.L.; Taylor, A.H.; Dicus, D.A.; Teplitz, D.C.; Texas Univ., Austin; Maryland Univ., College Park )

    1989-07-01

    The possibility is considered that a spherical distribution of dark matter (DM), matter not visible with current instruments, is trapped in the sun's gravitational field. Bounds are placed from the motion of Uranus and Neptune, on the amount of DM that could be so trapped within the radius of those planets' orbits, as follows: from the Voyager 2, Uranus-flyby data new, more accurate ephemeris values are generated. Trapped DM mass is bounded by noting that such a distribution would increase the effective mass of the sun as seen by the outer planets and by using the new ephemeris values to bound such an increase. 34 refs.

  8. Pattern Search Algorithms for Bound Constrained Minimization

    NASA Technical Reports Server (NTRS)

    Lewis, Robert Michael; Torczon, Virginia

    1996-01-01

    We present a convergence theory for pattern search methods for solving bound constrained nonlinear programs. The analysis relies on the abstract structure of pattern search methods and an understanding of how the pattern interacts with the bound constraints. This analysis makes it possible to develop pattern search methods for bound constrained problems while only slightly restricting the flexibility present in pattern search methods for unconstrained problems. We prove global convergence despite the fact that pattern search methods do not have explicit information concerning the gradient and its projection onto the feasible region and consequently are unable to enforce explicitly a notion of sufficient feasible decrease.

  9. Design and synthesis of novel bivalent ligands (MOR and DOR) by conjugation of enkephalin analogues with 4-anilidopiperidine derivatives.

    PubMed

    Deekonda, Srinivas; Wugalter, Lauren; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Wang, Yue; Bassirirad, Neemah M; Lai, Josephine; Kulkarni, Vinod; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

    2015-10-15

    We describe the design and synthesis of novel bivalent ligands based on the conjugation of 4-anilidopiperidine derivatives with enkephalin analogues. The design of non-peptide analogues is explored with 5-amino substituted (tetrahydronaphthalen-2yl) methyl containing 4-anilidopiperidine derivatives, while non-peptide-peptide ligands are explored by conjugating the C-terminus of enkephalin analogues (H-Xxx-DAla-Gly-Phe-OH) to the amino group of 4-anilidopiperidine small molecule derivatives with and without a linker. These novel bivalent ligands are evaluated for biological activities at μ and δ opioid receptors. They exhibit very good affinities at μ and δ opioid receptors, and potent agonist activities in MVD and GPI assays. Among these the lead bivalent ligand 17 showed excellent binding affinities (0.1 nM and 0.5 nM) at μ and δ opioid receptors respectively, and was found to have very potent agonist activities in MVD (56 ± 5.9 nM) and GPI (4.6 ± 1.9 nM) assays. In vivo the lead bivalent ligand 17 exhibited a short duration of action (<15 min) comparable to 4-anilidopiperidine derivatives, and moderate analgesic activity. The ligand 17 has limited application against acute pain but may have utility in settings where a highly reversible analgesic is required. PMID:26323872

  10. Effects of Pseudomonas species on the release of bound sup 14 C residues from soil treated with ( sup 14 C)atrazine

    SciTech Connect

    Khan, S.U.; Behki, R.M. )

    1990-11-01

    The release of bound (nonextractable) {sup 14}C residues from soil previously treated with ({sup 14}C)atrazine was investigated by incubation of the solvent-extracted soil with two species of Pseudomonas capable of metabolizing atrazine. The two species, 192 and 194, released bound {sup 14}C residues from the soil. Addition of glucose, known to increase microbiological activities, to the incubated soil appeared to enhance the release of soil-bound {sup 14}C residues, in particular in the presence of Pseudomonas species 192. The {sup 14}C bound residues in soil, mainly present as the parent compound and its hydroxy and monodealkylated analogues, were released into the incubation mixture and were subsequently metabolized by the two species involving dechlorination and dealkylation.

  11. Antioxidant activity of albumin-bound bilirubin.

    PubMed Central

    Stocker, R; Glazer, A N; Ames, B N

    1987-01-01

    Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space. PMID:3475708

  12. Slot antenna as a bound charge oscillator.

    PubMed

    Choe, Jong-Ho; Kang, Ji-Hun; Kim, Dai-Sik; Park, Q-Han

    2012-03-12

    We study the scattering properties of an optical slot antenna formed from a narrow rectangular hole in a metal film. We show that slot antennas can be modeled as bound charge oscillators mediating resonant light scattering. A simple closed-form expression for the scattering spectrum of a slot antenna is obtained that reveals the nature of a bound charge oscillator and also the effect of a substrate. We find that the spectral width of scattering resonance is dominated by a radiative damping caused by the Abraham-Lorentz force acting on a bound charge. The bound charge oscillator model provides not only an intuitive physical picture for the scattering of an optical slot antenna but also reasonable numerical agreements with rigorous calculations using the finite-difference time-domain method. PMID:22418535

  13. Bound phenolics in foods, a review.

    PubMed

    Acosta-Estrada, Beatriz A; Gutiérrez-Uribe, Janet A; Serna-Saldívar, Sergio O

    2014-01-01

    Among phytochemicals, phenolic compounds have been extensively researched due to their diverse health benefits. Phenolic compounds occur mostly as soluble conjugates and insoluble forms, covalently bound to sugar moieties or cell wall structural components. Absorption mechanisms for bound phenolic compounds in the gastrointestinal tract greatly depend on the liberation of sugar moieties. Food processes such as fermentation, malting, thermoplastic extrusion or enzymatic, alkaline and acid hydrolyses occasionally assisted with microwave or ultrasound have potential to release phenolics associated to cell walls. Different kinds of wet chemistry methodologies to release and detect bound phenolic have been developed. These include harsh heat treatments, chemical modifications or biocatalysis. New protocols for processing and determining phenolics in food matrices must be devised in order to release bound phenolics and for quality control in the growing functional food industry.

  14. Affirmative Action, or Reverse Discrimination?

    ERIC Educational Resources Information Center

    Dansby, Ike

    1996-01-01

    Determines the impact of affirmative action programs in response to charges that they are policies of reverse discrimination. Reviewing affirmative action programs submitted by Michigan State departments, researchers determined no reverse discrimination was apparent based on low numbers of reverse discrimination complaints filed by whites. (GR)

  15. Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives.

    PubMed

    Monte, A P; Waldman, S R; Marona-Lewicka, D; Wainscott, D B; Nelson, D L; Sanders-Bush, E; Nichols, D E

    1997-09-12

    hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.

  16. Terrestrial research in Mars analogue environments

    NASA Astrophysics Data System (ADS)

    Osipov, G.

    Fatty acids (FA) content was measured by GC-MS SIM technique in Sulfide ores of present day (Mid-Atlantic Ridge and others) and ancient (Ural Paleocene, Russia) black smokers; Early Proterozoic kerites of Volyn; Siberian, Canadian and Antarctic permafrosts and also in rocks of East-European platform Achaean crystalline basement. Analysis was shown presence those and only those fatty acids which are specific to microorganisms. FA with 12 up 19 of carbon atoms are thought to be a bacterial biomass sign. 3-Hydroxy fatty acids also found in samples and are strong specific markers of gram-negative bacteria. Cultivation yield living bacteria in some cases. The East-European platform Achaean crystalline basement rocks opened by Vorotilov Deep Well (VDW) drilled through Puchezh-Katunski impact structure were studied within depths 2575 - 2805 m. 34 microbial lipid markers were detected by GC-MS and 22 species were identified. Bacteria of g. Bacillus reached 6,8 % in subsurface communities. However, members of gg. Clostridium (37,1 - 33,2 %) and Rhodococcus (27,6 - 33,7 %) were absolute dominants within studied depth interval. Some lipid patterns of kerite samples could be assessed to definite genera or, in special cases, to species of contemporary microorganisms. For instance, 2-hydroxylauric acid is specific to Pseudomonas putida group or Acinetobacter spp., and hydroxymyristic together with hydroxypalmitic are specific to P.cepacea and cyanobacteria. 3-hydroxystearic acid was known as component of Acetobacter diazothrophycus and Gloebacter violaceous cyanobacterium. 10-hydroxystearic acid associated with Nocardia spp., which oxidizes oleic acid in organic substrates. 10-methylhexadecanoic (10Me16) acid together with 10Me14, 10Me15 and 10Me17 analogues are markers of actinomycetes. Significant part of Black Smokers organic matter is probably biogenic. Fatty acid features strongly assigns it to bacterial, microeucariotic and planta cells. Par example 3-hydroxy acids are

  17. Spectral analysis of lunar analogue samples

    NASA Astrophysics Data System (ADS)

    Offringa, Marloes; Foing, Bernard

    2016-04-01

    Analyses of samples derived from terrestrial analogue sites are used to study lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during field campaigns (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. Equipment used in the laboratory consists of a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer, a Raman laser spectrometer, as well as UV-VIS and NIR reflectance spectrometers. The Raman, UV-VIS and NIR are also used in combination with the EXoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011). Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Calibration of the devices by creating a new dark and reference spectra has to take place after every sample measurement. In this way we take into account changes that occur in the signal due to the eating of the devices during the measurements. Moreover, the integration time is adjusted to obtain a clear signal without leading to oversaturation in the reflectance spectrum. The typical integration times for the UV-VIS reflectance spectrometer vary between 1 - 18 s, depending on the amount of daylight during experiments. For the NIR reflectance spectrometer the integration time resulting in the best signals is approximately 150 ms in combination with a broad spectrum light

  18. Iron isotopes in an Archean ocean analogue

    NASA Astrophysics Data System (ADS)

    Busigny, Vincent; Planavsky, Noah J.; Jézéquel, Didier; Crowe, Sean; Louvat, Pascale; Moureau, Julien; Viollier, Eric; Lyons, Timothy W.

    2014-05-01

    Iron isotopes have been extensively used to trace the history of microbial metabolisms and the redox evolution of the oceans. Archean sedimentary rocks display greater variability in iron isotope ratios and more markedly negative values than those deposited in the Proterozoic and Phanerozoic. This increased variability has been linked to changes in either water column iron cycling or the extent of benthic microbial iron reduction through time. We tested these contrasting scenarios through a detailed study of anoxic and ferruginous Lac Pavin (France), which can serve as a modern analogue of the Archean ocean. A depth-profile in the water column of Lac Pavin shows a remarkable increase in dissolved Fe concentration (0.1-1200 μM) and δ56Fe values (-2.14‰ to +0.31‰) across the oxic-anoxic boundary to the lake bottom. The largest Fe isotope variability is found at the redox boundary and is related to partial oxidation of dissolved ferrous iron, leaving the residual Fe enriched in light isotopes. The analysis of four sediment cores collected along a lateral profile (one in the oxic layer, one at the redox boundary, one in the anoxic zone, and one at the bottom of the lake) indicates that bulk sediments, porewaters, and reactive Fe mostly have δ56Fe values near 0.0 ± 0.2‰, similar to detrital iron. In contrast, pyrite δ56Fe values in sub-chemocline cores (60, 65, and 92 m) are highly variable and show significant deviations from the detrital iron isotope composition (δ56Fepyrite between -1.51‰ and +0.09‰; average -0.93‰). Importantly, the pyrite δ56Fe values mirror the δ56Fe of dissolved iron at the redox boundary—where near quantitative sulfate and sulfide drawdown occurs—suggesting limited iron isotope fractionation during iron sulfide formation. This finding has important implications for the Archean environment. Specifically, this work suggests that in a ferruginous system, most of the Fe isotope variability observed in sedimentary pyrites can

  19. Performance bound for real OTEC heat engines

    SciTech Connect

    Wu, C.

    1987-01-01

    Maximum power and efficiency at the maximum power of an irreversible OTEC heat engine are treated. When time is explicitly considered in the energy exchanges between the heat engine and its surroundings, it is found that there is a bound on the efficiency of the real OTEC heat engine at the maximum power condition. This bound can guide the evaluation of existing OTEC systems or influence design of future OTEC heat engines.

  20. An upper bound on quantum entropy.

    SciTech Connect

    Zachos, C. K.; High Energy Physics

    2008-01-01

    Following ref [1], a classical upper bound for quantum entropy is identified and illustrated, 0 {le} S{sub q} {le} ln (e{sigma}{sup 2}/2{h_bar}), involving the variance {sigma}{sup 2} in phase space of the classical limit distribution of a given system. A fortiori, this further bounds the corresponding information-theoretical generalizations of the quantum entropy proposed by Renyi.

  1. New spectral features from bound dark matter

    NASA Astrophysics Data System (ADS)

    Catena, Riccardo; Kouvaris, Chris

    2016-07-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature that we predict can provide a complementary verification of dark matter discovery at experiments with positive signal but unclear background. The effect is generically expected, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section.

  2. Bound states in the Higgs model

    NASA Astrophysics Data System (ADS)

    di Leo, Leo; Darewych, Jurij W.

    1994-02-01

    We derive relativistic wave equations for the bound states of two Higgs bosons within the Higgs sector of the minimal standard model. The variational method and the Hamiltonian formalism of QFT are used to obtain the equations using a simple ||hh>+||hhh> Fock-space ansatz. We present approximate solutions of these equations for a range of Higgs boson masses, and explore the parameter space which corresponds to the existence of two-Higgs-boson bound states.

  3. Hamiltonian anomalies of bound states in QED

    SciTech Connect

    Shilin, V. I.; Pervushin, V. N.

    2013-10-15

    The Bound State in QED is described in systematic way by means of nonlocal irreducible representations of the nonhomogeneous Poincare group and Dirac's method of quantization. As an example of application of this method we calculate triangle diagram Para-Positronium {yields} {gamma}{gamma}. We show that the Hamiltonian approach to Bound State in QED leads to anomaly-type contribution to creation of pair of parapositronium by two photon.

  4. Reversible Thermal Stiffening in Polymer Nanocomposites.

    PubMed

    Senses, Erkan; Isherwood, Andrew; Akcora, Pinar

    2015-07-15

    Miscible polymer blends with different glass transition temperatures (Tg) are known to create confined interphases between glassy and mobile chains. Here, we show that nanoparticles adsorbed with a high-Tg polymer, poly(methyl methacrylate), and dispersed in a low-Tg matrix polymer, poly(ethylene oxide), exhibit a liquid-to-solid transition at temperatures above Tg's of both polymers. The mechanical adaptivity of nanocomposites to temperature underlies the existence of dynamically asymmetric bound layers on nanoparticles and more importantly reveals their impact on macroscopic mechanical response of composites. The unusual reversible stiffening behavior sets these materials apart from conventional polymer composites that soften upon heating. The presented stiffening mechanism in polymer nanocomposites can be used in applications for flexible electronics or mechanically induced actuators responding to environmental changes like temperature or magnetic fields.

  5. Reversal bending fatigue testing

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Tan, Ting

    2014-10-21

    Embodiments for apparatuses for testing reversal bending fatigue in an elongated beam are disclosed. Embodiments are configured to be coupled to first and second end portions of the beam and to apply a bending moment to the beam and create a pure bending condition in an intermediate portion of the beam. Embodiments are further configured to cyclically alternate the direction of the bending moment applied to the beam such that the intermediate portion of the beam cyclically bends in opposite directions in a pure bending condition.

  6. Synthesis and Evaluation of Eight- and Four-membered Iminosugar Analogues as Inhibitors of Testicular Ceramide-specific Glucosyltransferase, Testicular β-Glucosidase 2, and other Glycosidases

    PubMed Central

    Lee, Jae Chul; Francis, Subhashree; Dutta, Dinah; Gupta, Vijayalaxmi; Yang, Yan; Zhu, Jin-Yi; Tash, Joseph S.; Schönbrunn, Ernst

    2012-01-01

    Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve: ringclosing metathesis and Sharpless asymmetric dihydroxylation, and for the four-membered analogues: Sharpless epoxidation, epoxide ring opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6), was moderately active against rat-derived ceramide-specific glucosyltransferase and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3s,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25), displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonyl-azetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC50 of 600 nM and β-glucosidase (almond) with an IC50 of 20 µM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied. PMID:22432895

  7. Theoretical study on absorption and emission spectra of adenine analogues.

    PubMed

    Liu, Hongxia; Song, Qixia; Yang, Yan; Li, Yan; Wang, Haijun

    2014-04-01

    Fluorescent nucleoside analogues have attracted much attention in studying the structure and dynamics of nucleic acids in recent years. In the present work, we use theoretical calculations to investigate the structural and optical properties of four adenine analogues (termed as A1, A2, A3, and A4), and also consider the effects of aqueous solution and base pairing. The results show that the fluorescent adenine analogues can pair with thymine to form stable H-bonded WC base pairs. The excited geometries of both adenine analogues and WC base pairs are similar to the ground geometries. The absorption and emission maxima of adenine analogues are greatly red shifted compared with nature adenine, the oscillator strengths of A1 and A2 are stronger than A3 and A4 in both absorption and emission spectra. The calculated low-energy peaks in the absorption spectra are in good agreement with the experimental data. In general, the aqueous solution and base pairing can slightly red-shift both the absorption and emission maxima, and can increase the oscillator strengths of absorption spectra, but significantly decrease the oscillator strengths of A3 in emission spectra.

  8. Central effects of angiotensin II, its fragment and analogues.

    PubMed

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  9. Review of Insulin and its Analogues in Diabetes Mellitus

    PubMed Central

    Mane, Krishnappa; Chaluvaraju, KC; Niranjan, MS; Zaranappa, TR; Manjuthej, TR

    2012-01-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin’s, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  10. Error bounds from extra precise iterative refinement

    SciTech Connect

    Demmel, James; Hida, Yozo; Kahan, William; Li, Xiaoye S.; Mukherjee, Soni; Riedy, E. Jason

    2005-02-07

    We present the design and testing of an algorithm for iterative refinement of the solution of linear equations, where the residual is computed with extra precision. This algorithm was originally proposed in the 1960s [6, 22] as a means to compute very accurate solutions to all but the most ill-conditioned linear systems of equations. However two obstacles have until now prevented its adoption in standard subroutine libraries like LAPACK: (1) There was no standard way to access the higher precision arithmetic needed to compute residuals, and (2) it was unclear how to compute a reliable error bound for the computed solution. The completion of the new BLAS Technical Forum Standard [5] has recently removed the first obstacle. To overcome the second obstacle, we show how a single application of iterative refinement can be used to compute an error bound in any norm at small cost, and use this to compute both an error bound in the usual infinity norm, and a componentwise relative error bound. We report extensive test results on over 6.2 million matrices of dimension 5, 10, 100, and 1000. As long as a normwise (resp. componentwise) condition number computed by the algorithm is less than 1/max{l_brace}10,{radical}n{r_brace} {var_epsilon}{sub w}, the computed normwise (resp. componentwise) error bound is at most 2 max{l_brace}10,{radical}n{r_brace} {center_dot} {var_epsilon}{sub w}, and indeed bounds the true error. Here, n is the matrix dimension and w is single precision roundoff error. For worse conditioned problems, we get similarly small correct error bounds in over 89.4% of cases.

  11. Bounds Estimation Via Regression with Asymmetric Cost Functions

    NASA Technical Reports Server (NTRS)

    DeCoste, D.

    1997-01-01

    This paper addresses a significant but mostly-neglected class of problems that we call bounds estimation. This includes learning empirical best-case and worst-case algorithmic complexity bounds and red-line bounds on sensor data.

  12. Synthesis and Biological Evaluation of Carbocyclic Analogues of Pachastrissamine

    PubMed Central

    Kwon, Yongseok; Song, Jayoung; Bae, Hoon; Kim, Woo-Jung; Lee, Joo-Youn; Han, Geun-Hee; Lee, Sang Kook; Kim, Sanghee

    2015-01-01

    A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode of 4b in sphingosine kinase. In our docking model, pachastrissamine and 4b were able to effectively bind to the binding pocket of sphingosine kinase 1 as co-crystalized sphingosine. However, 4b showed a hydrophobic interaction with Phe192, which suggests that it contributes to its increased inhibitory activity against sphingosine kinase 1. PMID:25654428

  13. Migrastatin analogues target fascin to block tumour metastasis

    SciTech Connect

    Chen, L.; Jakoncic, J.; Yang, S.; Zhang, J.; Huang, X.Y.

    2010-04-15

    Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.

  14. New rubrolide analogues as inhibitors of photosynthesis light reactions.

    PubMed

    Varejão, Jodieh O S; Barbosa, Luiz C A; Ramos, Gabriela Álvarez; Varejão, Eduardo V V; King-Díaz, Beatriz; Lotina-Hennsen, Blas

    2015-04-01

    Natural products called rubrolides have been investigated as a model for the development of new herbicides that act on the photosynthesis apparatus. This study comprises a comprehensive analysis of the photosynthesis inhibitory ability of 27 new structurally diverse rubrolide analogues. In general, the results revealed that the compounds exhibited efficient inhibition of the photosynthetic process, but in some cases low water solubility may be a limiting factor. To elucidate their mode of action, the effects of the compounds on PSII and PSI, as well as their partial reaction on chloroplasts and the chlorophyll a fluorescence transients were measured. Our results showed that some of the most active rubrolide analogues act as a Hill reaction inhibitors at the QB level by interacting with the D1 protein at the reducing side of PSII. All of the active analogues follow Tice's rule of 5, which indicates that these compounds present physicochemical properties suitable for herbicides.

  15. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    PubMed

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.

  16. Conception, synthesis, and biological evaluation of original discodermolide analogues.

    PubMed

    de Lemos, Elsa; Agouridas, Evangelos; Sorin, Geoffroy; Guerreiro, Antonio; Commerçon, Alain; Pancrazi, Ange; Betzer, Jean-François; Lannou, Marie-Isabelle; Ardisson, Janick

    2011-08-29

    Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

  17. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    PubMed

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

  18. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors.

    PubMed

    Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F B; Menzies, Stefanie K; Morris, Joanne C; Tulloch, Lindsay B; Smith, Terry K

    2014-11-01

    Neglected tropical diseases remain a serious global health concern. Here, a series of novel bis-tetrahydropyran 1,4-triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure-activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti-HAT agents.

  19. The Object-analogue approach for probabilistic forecasting

    NASA Astrophysics Data System (ADS)

    Frediani, M. E.; Hopson, T. M.; Anagnostou, E. N.; Hacker, J.

    2015-12-01

    The object-analogue is a new method to estimate forecast uncertainty and to derive probabilistic predictions of gridded forecast fields over larger regions rather than point locations. The method has been developed for improving the forecast of 10-meter wind speed over the northeast US, and it can be extended to other forecast variables, vertical levels, and other regions. The object-analogue approach combines the analog post-processing technique (Hopson 2005; Hamill 2006; Delle Monache 2011) with the Method for Object-based Diagnostic Evaluation (MODE) for forecast verification (Davis et al 2006a, b). Originally, MODE is used to verify mainly precipitation forecasts using features of a forecast region represented by an object. The analog technique is used to reduce the NWP systematic and random errors of a gridded forecast field. In this study we use MODE-derived objects to characterize the wind fields forecasts into attributes such as object area, centroid location, and intensity percentiles, and apply the analogue concept to these objects. The object-analogue method uses a database of objects derived from reforecasts and their respective reanalysis. Given a real-time forecast field, it searches the database and selects the top-ranked objects with the most similar set of attributes using the MODE fuzzy logic algorithm for object matching. The attribute probabilities obtained with the set of selected object-analogues are used to derive a multi-layer probabilistic prediction. The attribute probabilities are combined into three uncertainty layers that address the main concerns of most applications: location, area, and magnitude. The multi-layer uncertainty can be weighted and combined or used independently in such that it provides a more accurate prediction, adjusted according to the application interest. In this study we present preliminary results of the object-analogue method. Using a database with one hundred storms we perform a leave-one-out cross-validation to

  20. Conformational phases of membrane bound cytoskeletal filaments

    NASA Astrophysics Data System (ADS)

    Quint, David A.; Grason, Gregory; Gopinathan, Ajay

    2013-03-01

    Membrane bound cytoskeletal filaments found in living cells are employed to carry out many types of activities including cellular division, rigidity and transport. When these biopolymers are bound to a membrane surface they may take on highly non-trivial conformations as compared to when they are not bound. This leads to the natural question; What are the important interactions which drive these polymers to particular conformations when they are bound to a surface? Assuming that there are binding domains along the polymer which follow a periodic helical structure set by the natural monomeric handedness, these bound conformations must arise from the interplay of the intrinsic monomeric helicity and membrane binding. To probe this question, we study a continuous model of an elastic filament with intrinsic helicity and map out the conformational phases of this filament for various mechanical and structural parameters in our model, such as elastic stiffness and intrinsic twist of the filament. Our model allows us to gain insight into the possible mechanisms which drive real biopolymers such as actin and tubulin in eukaryotes and their prokaryotic cousins MreB and FtsZ to take on their functional conformations within living cells.

  1. Revisiting cosmological bounds on radiative neutrino lifetime

    SciTech Connect

    Mirizzi, Alessandro; Montanino, Daniele; Serpico, Pasquale D.

    2007-09-01

    Neutrino oscillation experiments and direct bounds on absolute masses constrain neutrino mass differences to fall into the microwave energy range, for most of the allowed parameter space. As a consequence of these recent phenomenological advances, older constraints on radiative neutrino decays based on diffuse background radiations and assuming strongly hierarchical masses in the eV range are now outdated. We thus derive new bounds on the radiative neutrino lifetime using the high precision cosmic microwave background spectral data collected by the Far Infrared Absolute Spectrophotometer instrument on board the Cosmic Background Explorer. The lower bound on the lifetime is between a fewx10{sup 19} s and {approx}5x10{sup 20} s, depending on the neutrino mass ordering and on the absolute mass scale. However, due to phase space limitations, the upper bound in terms of the effective magnetic moment mediating the decay is not better than {approx}10{sup -8} Bohr magnetons. We also comment about possible improvements of these limits, by means of recent diffuse infrared photon background data. We compare these bounds with preexisting limits coming from laboratory or astrophysical arguments. We emphasize the complementarity of our results with others available in the literature.

  2. Computations of entropy bounds: Multidimensional geometric methods

    SciTech Connect

    Makaruk, H.E.

    1998-02-01

    The entropy bounds for constructive upper bound on the needed number-of-bits for solving a dichotomy is represented by the quotient of two multidimensional solid volumes. For minimization of this upper bound exact calculation of the volume of this quotient is needed. Three methods for exact computing of the volume of a given nD volume are presented: (1) general method for calculation any nD volume by slicing it into volumes of decreasing dimension is presented; (2) a method applying appropriate curvilinear coordinate system is described for volume bounded by symmetrical curvilinear hypersurfaces (spheres, cones, hyperboloids, ellipsoids, cylinders, etc.); and (3) an algorithm for dividing any nD complex into simplices and computing of the volume of the simplices is presented, supplemented by a general formula for calculation of volume of an nD simplex. These mathematical methods enable exact calculation of volume of any complicated multidimensional solids. The methods allow for the calculation of the minimal volume and lead to tighter bounds on the needed number-of-bits.

  3. Thermalization Time Bounds for Pauli Stabilizer Hamiltonians

    NASA Astrophysics Data System (ADS)

    Temme, Kristan

    2016-09-01

    We prove a general lower bound to the spectral gap of the Davies generator for Hamiltonians that can be written as the sum of commuting Pauli operators. These Hamiltonians, defined on the Hilbert space of N-qubits, serve as one of the most frequently considered candidates for a self-correcting quantum memory. A spectral gap bound on the Davies generator establishes an upper limit on the life time of such a quantum memory and can be used to estimate the time until the system relaxes to thermal equilibrium when brought into contact with a thermal heat bath. The bound can be shown to behave as {λ ≥ O(N^{-1} exp(-2β overline{ɛ}))} , where {overline{ɛ}} is a generalization of the well known energy barrier for logical operators. Particularly in the low temperature regime we expect this bound to provide the correct asymptotic scaling of the gap with the system size up to a factor of N -1. Furthermore, we discuss conditions and provide scenarios where this factor can be removed and a constant lower bound can be proven.

  4. Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues

    PubMed Central

    Shrivastava, Priyanka; Navratna, Vikas; Silla, Yumnam; Dewangan, Rikeshwer P.; Pramanik, Atreyi; Chaudhary, Sarika; Rayasam, GeethaVani; Kumar, Anuradha; Gopal, Balasubramanian; Ramachandran, Srinivasan

    2016-01-01

    The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L-aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate reductase (Mtb-rDapB). Alpha-ketopimelic acid (α-KPA) showed maximum inhibition of 88% and IC50 of 21 μM in the presence of pyruvate (500 μM) and ASA (400 μM). Competition experiments with pyruvate and ASA revealed competition of α-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data with multiple reaction monitoring (MRM) showed that the relative abundance peak of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal shift assays showed 1 °C Tm shift of Mtb-rDapA upon binding α-KPA. The 2.4 Å crystal structure of Mtb-rDapA-α-KPA complex showed the interaction of critical residues at the active site with α-KPA. Molecular dynamics simulations over 500 ns of pyruvate docked to Mtb-DapA and of α-KPA-bound Mtb-rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast to α-KPA. Molecular descriptors analysis showed that ligands with polar surface area of 91.7 Å2 are likely inhibitors. In summary, α-hydroxypimelic acid and other analogues could be explored further as inhibitors of Mtb-DapA. PMID:27501775

  5. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    PubMed Central

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-01-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  6. Five new discodermolide analogues from the marine sponge Discodermia species.

    PubMed

    Gunasekera, Sarath P; Paul, Gopal K; Longley, Ross E; Isbrucker, Richard A; Pomponi, Shirley A

    2002-11-01

    Discodermolide (1) and five new discodermolide analogues trivially named 2-epi-discodermolide (2), 2-des-methyldiscodermolide (3), 5-hydroxymethyldiscodermolate (4), 19-des-aminocarbonyldiscodermolide (5), and 9(13)-cyclodiscodermolide (6) have been isolated from marine sponges belonging to the genus Discodermia collected from the Caribbean Sea. The isolation, structure elucidation, and biological activities of 2-6 are described. The natural analogues, which were isolated in trace amounts, exhibited significant variation of cytotoxicity against the cultured murine P-388 leukemia and A-549 human adenocarcinoma cells and suggested the importance of the C(7) through C(17) moiety for potency against cultured tumor cell lines.

  7. Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

    PubMed Central

    2013-01-01

    The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure–activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A. PMID:24273633

  8. Tumor imaging and therapy using radiolabeled somatostatin analogues.

    PubMed

    de Jong, Marion; Breeman, Wout A P; Kwekkeboom, Dik J; Valkema, Roelf; Krenning, Eric P

    2009-07-21

    Molecular imaging plays an essential role in balancing the clinical benefits and risks of radionuclide-based cancer therapy. To effectively treat individual patients, careful assessment of biodistribution, dosimetry, and toxicity is essential. In this Account, we describe advances that combine features of molecular imaging and radionuclide therapy to provide new avenues toward individualized cancer treatment. Selective receptor-targeting radiopeptides have emerged as an important class of radiopharmaceuticals for molecular imaging and therapy of tumors that overexpress peptide receptors on the cell membrane. After such peptides labeled with gamma-emitting radionuclides bind to their receptors, they allow clinicians to visualize receptor-expressing tumors non-invasively. Peptides labeled with beta-particle emitters could also eradicate receptor-expressing tumors. The somatostatin receptors, which are overexpressed in a majority of neuroendocrine tumors, represent the first and best example of targets for radiopeptide-based imaging and radionuclide therapy. The somatostatin analogue (111)In-octreotide permits the localization and staging of neuroendocrine tumors that express the appropriate somatostatin receptors. Newer modified somatostatin analogues, including Tyr(3)-octreotide and Tyr(3)-octreotate, are successfully being used for tumor imaging and radionuclide therapy. Because there are few effective therapies for patients with inoperable or metastasized neuroendocrine tumors, this therapy is a promising novel treatment option for these patients. Peptide receptor imaging and radionuclide therapy can be combined in a single probe, called a "theranostic". To select patients who are likely to benefit from this type of intervention, we first use a peptide analogue labeled with a diagnostic radionuclide to obtain a scan. Selected patients will be treated using the same or a similar peptide analogue labeled with a therapeutic radionuclide. The development of such

  9. On slow light as a black hole analogue

    NASA Astrophysics Data System (ADS)

    Unruh, W. G.; Schützhold, R.

    2003-07-01

    Although slow light (electromagnetically induced transparency) would seem an ideal medium in which to institute a “dumb hole” (black hole analogue), it suffers from a number of problems. We show that the high phase velocity in the slow light regime ensures that the system cannot be used as an analogue displaying Hawking radiation. Even though an appropriately designed slow-light setup may simulate classical features of black holes—such as horizon, mode mixing, “Bogoliubov” coefficients, etc.—it does not reproduce the related quantum effects.

  10. Naturally occurring crystalline phases: analogues for radioactive waste forms

    SciTech Connect

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  11. Torsional stress in DNA limits collaboration among reverse gyrase molecules.

    PubMed

    Ogawa, Taisaku; Sutoh, Kazuo; Kikuchi, Akihiko; Kinosita, Kazuhiko

    2016-04-01

    Reverse gyrase is an enzyme that can overwind (introduce positive supercoils into) DNA using the energy obtained from ATP hydrolysis. The enzyme is found in hyperthermophiles, and the overwinding reaction generally requires a temperature above 70 °C. In a previous study using microscopy, we have shown that 30 consecutive mismatched base pairs (a bubble) in DNA serve as a well-defined substrate site for reverse gyrase, warranting the processive overwinding activity down to 50 °C. Here, we inquire how multiple reverse gyrase molecules may collaborate with each other in overwinding one DNA molecule. We introduced one, two, or four bubbles in a linear DNA that tethered a magnetic bead to a coverslip surface. At 40-71 °C in the presence of reverse gyrase, the bead rotated clockwise as viewed from above, to relax the DNA twisted by reverse gyrase. Dependence on the enzyme concentration indicated that each bubble binds reverse gyrase tightly (dissociation constant < 0.1 nm) and that bound enzyme continuously overwinds DNA for > 5 min. Rotation with two bubbles was significantly faster compared with one bubble, indicating that overwinding actions are basically additive, but four bubbles did not show further acceleration except at 40 °C where the activity was very low. The apparent saturation is due to the hydrodynamic friction against the rotating bead, as confirmed by increasing the medium viscosity. When torsional stress in the DNA, determined by the friction, approaches ~ 7 pN·nm (at 71 °C), the overwinding activity of reverse gyrase drops sharply. Multiple molecules of reverse gyrase collaborate additively within this limit.

  12. Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: core redesign.

    PubMed

    Schleicher, Kristin D; Sasaki, Yoshikazu; Tam, Annie; Kato, Daisuke; Duncan, Katharine K; Boger, Dale L

    2013-01-24

    The total synthesis of a systematic series of vinblastine analogues that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compounds with 5,5, 6,6, and the reversed 5,6 membered DE ring systems were prepared. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogues (81 and 44) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity.

  13. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  14. Reverse slapper detonator

    SciTech Connect

    Weingart, Richard C.

    1990-01-01

    A reverse slapper detonator (70), and methodology related thereto, are provided. The detonator (70) is adapted to be driven by a pulse of electric power from an external source (80). A conductor (20) is disposed along the top (14), side (18), and bottom (16) surfaces of a sheetlike insulator (12). Part of the conductor (20) comprises a bridge (28), and an aperture (30) is positioned within the conductor (20), with the bridge (28) and the aperture (30) located on opposite sides of the insulator (12). A barrel (40) and related explosive charge (50) are positioned adjacent to and in alignment with the aperture (30), and the bridge (28) is buttressed with a backing layer (60). When the electric power pulse vaporizes the bridge (28), a portion of the insulator (12) is propelled through the aperture (30) and barrel (40), and against the explosive charge (50), thereby detonating it.

  15. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2006-04-25

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  16. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2003-12-09

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  17. Reversed-polarity regions

    NASA Technical Reports Server (NTRS)

    Tang, F.

    1982-01-01

    It is found by a statistical study of 58 reversed-polarity regions (RPRs) covering the 11-year period 1969-1979 that RPRs (1) have a lifespan comparable to normal active regions, (2) do not show a tendency to rotate toward a more normal alignment, and (3) have stable configurations that do not suggest stress due to their anomalous magnetic alignment. As in normal regions, RPR magnetic complexity is found to be the primary factor in flare productivity. Weak-field RPRs produce no flares, and regions with complex spots produce more flares than regions with non-complex spots by a factor of five. The main difference between RPRs and normal regions lies in complex spot frequency, with less that 17% of normal active regions having such spots and fewer than 1.8% having long-lived complex ones, while 41% of RPRs have complex spots and 24% have long-lived complex spots.

  18. Properly apply reverse osmosis

    SciTech Connect

    Kucera, J.

    1997-02-01

    Reverse osmosis (RO) is a water purification technique used to reduce the loading of dissolved solids in solution. The popularity of RO for treating boiler feedwater is growing because of the rising cost of ion-exchange-based demineralization as well as safety concerns associated with handling acid and caustic. A properly designed and operated RO-based boiler-feedwater-treatment system can reduce the load to, and costs associated with, ion exchange demineralization. This article discusses RO feedwater quality recommendations, pretreatment techniques, and system monitoring necessary to achieve optimum RO system performance in the most cost-effective manner. Regardless of the application--whether it is the treatment of boiler feedwater, industrial wastewater, or process water--the approach to pretreatment and the other design and operating guidance offered here remains the same.

  19. Reverse Osmosis Optimization

    SciTech Connect

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  20. Reverse Osmosis Optimization

    SciTech Connect

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  1. Reverse photoacoustic standoff spectroscopy

    DOEpatents

    Van Neste, Charles W.; Senesac, Lawrence R.; Thundat, Thomas G.

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  2. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase

    SciTech Connect

    Vandevoorde, Severine; Saha, Bijali; Mahadevan, Anu; Razdan, Raj K.; Pertwee, Roger G.; Martin, Billy R.; Fowler, Christopher J. . E-mail: cf@pharm.umu.se

    2005-11-11

    Little is known as to the structural requirements of the acyl side chain for interaction of acylglycerols with monoacylglycerol lipase (MAGL), the enzyme chiefly responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. In the present study, a series of twelve analogues of 1-AG (the more stable regioisomer of 2-AG) were investigated with respect to their ability to inhibit the metabolism of 2-oleoylglycerol by cytosolic and membrane-bound MAGL. In addition, the ability of the compounds to inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) was investigated. For cytosolic MAGL, compounds with 20 carbon atoms in the acyl chain and 2-5 unsaturated bonds inhibited the hydrolysis of 2-oleoylglycerol with similar potencies (IC{sub 50} values in the range 5.1-8.2 {mu}M), whereas the two compounds with a single unsaturated bond were less potent (IC{sub 50} values 19 and 21 {mu}M). The fully saturated analogue 1-monoarachidin did not inhibit the enzyme, whereas the lower side chain analogues 1-monopalmitin and 1-monomyristin inhibited the enzyme with IC{sub 50} values of 12 and 32 {mu}M, respectively. The 22-carbon chain analogue of 1-AG was also potent (IC{sub 50} value 4.5 {mu}M). Introduction of an {alpha}-methyl group for the C20:4, C20:3, and C22:4 compounds did not affect potency in a consistent manner. For the FAAH and the membrane-bound MAGL, there was no obvious relationship between the degree of unsaturation of the acyl side chain and the ability to inhibit the enzymes. It is concluded that increasing the number of unsaturated bonds on the acyl side chain of 1-AG from 1 to 5 has little effect on the affinity of acylglycerols for cytosolic MAGL.

  3. Bound water in Kevlar 49 fibers

    SciTech Connect

    Garza, R.G.; Pruneda, C.O.; Morgan, R.J.

    1981-04-01

    From elemental analyses, thermogravimetric-mass spectroscopy studies and re-evaluation of previous water diffusion studies in Kevlar 49 fibers it is concluded that these fibers can contain two types of sorbed moisture. The fibers can absorb up to approx. 6 wt % loosely bound water with an activation energy for outgassing by desorption of 6 kcal/mole. This loosely bound water is a direct result of the presence of Na/sub 2/SO/sub 4/ impurities and the perturbations they induce on the packing of the rod-like poly (p-phenylene terephthalamide) macromolecules. Kevlar 49 fibers also inherently contain up to 30 wt % additional water which is tightly bound within the crystal lattice. This water exhibits an activation energy for outgassing by diffusion of approx. 40 kcal/mole and is only evolved from the fiber in significant quantities at t > 350/sup 0/C over a period of hours.

  4. Bounds on Neutrino Non-Standard Interactions

    SciTech Connect

    Fernandez-Martinez, Enrique

    2010-03-30

    We review the present model independent bounds on neutrino non-standard interactions both at neutrino production and detection and in its interactions with matter. For matter non-standard interactions the direct bounds are rather weak. However, matter non-standard interactions are related by gauge invariance to the production and detection ones as well as to flavour changing processes involving charged leptons. Taking into account these relations much stronger bounds of at least O(10{sup -2}) can be derived unless significant fine tunings are implemented. Testing non-standard interactions at this level at future neutrino oscillation facilities is challenging but still feasible at very ambitious proposals such as the Neutrino Factory.

  5. Weakly bound atomic trimers in ultracold traps

    SciTech Connect

    Yamashita, M. T.; Frederico, T.; Tomio, Lauro; Delfino, A.

    2003-09-01

    The experimental three-atom recombination coefficients of the atomic states {sup 23}Na|F=1,m{sub F}=-1>, {sup 87}Rb|F=1,m{sub F}=-1>, and {sup 85}Rb|F=2,m{sub F}=-2>, together with the corresponding two-body scattering lengths, allow predictions of the trimer bound-state energies for such systems in a trap. The recombination parameter is given as a function of the weakly bound trimer energies, which are in the interval 1bound state to our prediction, in the case of {sup 85}Rb|F=2,m{sub F}=-2>, for a particular trap, is shown to be relatively small.

  6. Experimental bound entanglement through a Pauli channel

    PubMed Central

    Amselem, Elias; Sadiq, Muhammad; Bourennane, Mohamed

    2013-01-01

    Understanding the characteristics of a quantum systems when affected by noise is one of the biggest challenges for quantum technologies. The general Pauli error channel is an important lossless channel for quantum communication. In this work we consider the effects of a Pauli channel on a pure four-qubit state and simulate the Pauli channel experimentally by studying the action on polarization encoded entangled photons. When the noise channel acting on the photons is correlated, a set spanned by four orthogonal bound entangled states can be generated. We study this interesting case experimentally and demonstrate that products of Bell states can be brought into a bound entangled regime. We find states in the set of bound entangled states which experimentally violate the CHSH inequality while still possessing a positive partial transpose. PMID:23752651

  7. Laboratory bounds on electron Lorentz violation

    SciTech Connect

    Altschul, Brett

    2010-07-01

    Violations of Lorentz boost symmetry in the electron and photon sectors can be constrained by studying several different high-energy phenomenon. Although they may not lead to the strongest bounds numerically, measurements made in terrestrial laboratories produce the most reliable results. Laboratory bounds can be based on observations of synchrotron radiation, as well as the observed absences of vacuum Cerenkov radiation (e{sup {+-}{yields}e{+-}+{gamma}}) and photon decay ({gamma}{yields}e{sup +}+e{sup -}). Using measurements of synchrotron energy losses at LEP and the survival of TeV photons, we place new bounds on the three electron Lorentz-violation coefficients c{sub (TJ)}, at the 3x10{sup -13} to 6x10{sup -15} levels.

  8. Convex Lower Bounds for Free Energy Minimization

    NASA Astrophysics Data System (ADS)

    Moussa, Jonathan

    We construct lower bounds on free energy with convex relaxations from the nonlinear minimization over probabilities to linear programs over expectation values. Finite-temperature expectation values are further resolved into distributions over energy. A superset of valid expectation values is delineated by an incomplete set of linear constraints. Free energy bounds can be improved systematically by adding constraints, which also increases their computational cost. We compute several free energy bounds of increasing accuracy for the triangular-lattice Ising model to assess the utility of this method. This work was supported by the Laboratory Directed Research and Development program at Sandia National Laboratories. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  9. Bound States in Boson Impurity Models

    NASA Astrophysics Data System (ADS)

    Shi, Tao; Wu, Ying-Hai; González-Tudela, A.; Cirac, J. I.

    2016-04-01

    The formation of bound states involving multiple particles underlies many interesting quantum physical phenomena, such as Efimov physics or superconductivity. In this work, we show the existence of an infinite number of such states for some boson impurity models. They describe free bosons coupled to an impurity and include some of the most representative models in quantum optics. We also propose a family of wave functions to describe the bound states and verify that it accurately characterizes all parameter regimes by comparing its predictions with exact numerical calculations for a one-dimensional tight-binding Hamiltonian. For that model, we also analyze the nature of the bound states by studying the scaling relations of physical quantities, such as the ground-state energy and localization length, and find a nonanalytical behavior as a function of the coupling strength. Finally, we discuss how to test our theoretical predictions in experimental platforms, such as photonic crystal structures and cold atoms in optical lattices.

  10. Bounded link prediction in very large networks

    NASA Astrophysics Data System (ADS)

    Cui, Wei; Pu, Cunlai; Xu, Zhongqi; Cai, Shimin; Yang, Jian; Michaelson, Andrew

    2016-09-01

    Evaluating link prediction methods is a hard task in very large complex networks due to the prohibitive computational cost. However, if we consider the lower bound of node pairs' similarity scores, this task can be greatly optimized. In this paper, we study CN index in the bounded link prediction framework, which is applicable to enormous heterogeneous networks. Specifically, we propose a fast algorithm based on the parallel computing scheme to obtain all node pairs with CN values larger than the lower bound. Furthermore, we propose a general measurement, called self-predictability, to quantify the performance of similarity indices in link prediction, which can also indicate the link predictability of networks with respect to given similarity indices.

  11. Defining the Polar Field Reversal

    NASA Technical Reports Server (NTRS)

    Upton, Lisa; Hathaway, David H.

    2013-01-01

    The polar fields on the Sun are directly related to solar cycle variability. Recently there has been interest in studying an important characteristic of the polar fields: the timing of the polar field reversals. However this characteristic has been poorly defined, mostly due to the limitations of early observations. In the past, the reversals have been calculated by averaging the flux above some latitude (i.e. 55deg or 75deg). Alternatively, the reversal could be defined by the time in which the previous polarity is completely canceled and replaced by the new polarity at 90de, precisely at the pole. We will use a surface flux transport model to illustrate the differences in the timing of the polar field reversal based on each of these definitions and propose standardization in the definition of the polar field reversal. The ability to predict the timing of the polar field reversal using a surface flux transport model will also be discussed.

  12. 77 FR 3751 - Extension of Deadlines; Upward Bound Program (Regular Upward Bound (UB))

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Regulations is available via the Federal Digital System at: www.gpo.gov/fdsys . At this site you can view this... Bound Program (Regular Upward Bound (UB)) notice on December 19, 2011 (76 FR 78621). DATES: Deadline for... notice in the Federal Register (76 FR 78621) inviting applications for new awards for fiscal year...

  13. Career Development and Personal Functioning Differences between Work-Bound and Non-Work Bound Students

    ERIC Educational Resources Information Center

    Creed, Peter A.; Patton, Wendy; Hood, Michelle

    2010-01-01

    We surveyed 506 Australian high school students on career development (exploration, planning, job-knowledge, decision-making, indecision), personal functioning (well-being, self-esteem, life satisfaction, school satisfaction) and control variables (parent education, school achievement), and tested differences among work-bound, college-bound and…

  14. Generalized mutual information and Tsirelson's bound

    SciTech Connect

    Wakakuwa, Eyuri; Murao, Mio

    2014-12-04

    We introduce a generalization of the quantum mutual information between a classical system and a quantum system into the mutual information between a classical system and a system described by general probabilistic theories. We apply this generalized mutual information (GMI) to a derivation of Tsirelson's bound from information causality, and prove that Tsirelson's bound can be derived from the chain rule of the GMI. By using the GMI, we formulate the 'no-supersignalling condition' (NSS), that the assistance of correlations does not enhance the capability of classical communication. We prove that NSS is never violated in any no-signalling theory.

  15. Proof of a quantum Bousso bound

    NASA Astrophysics Data System (ADS)

    Bousso, Raphael; Casini, Horacio; Fisher, Zachary; Maldacena, Juan

    2014-08-01

    We prove the generalized covariant entropy bound, ΔS≤(A-A')/4Gℏ, for light-sheets with initial area A and final area A'. The entropy ΔS is defined as a difference of von Neumann entropies of an arbitrary state and the vacuum, with both states restricted to the light-sheet under consideration. The proof applies to free fields, in the limit where gravitational backreaction is small. We do not assume the null energy condition. In regions where it is violated, we find that the bound is protected by the defining property of light-sheets: that their null generators are nowhere expanding.

  16. Upper bounds on the photon mass

    SciTech Connect

    Accioly, Antonio; Helayeel-Neto, Jose; Scatena, Eslley

    2010-09-15

    The effects of a nonzero photon rest mass can be incorporated into electromagnetism in a simple way using the Proca equations. In this vein, two interesting implications regarding the possible existence of a massive photon in nature, i.e., tiny alterations in the known values of both the anomalous magnetic moment of the electron and the gravitational deflection of electromagnetic radiation, are utilized to set upper limits on its mass. The bounds obtained are not as stringent as those recently found; nonetheless, they are comparable to other existing bounds and bring new elements to the issue of restricting the photon mass.

  17. NN*(1440) quasi-bound states

    SciTech Connect

    Zhao Lu; Zou Bingsong; Shen Pengnian; Zhang Yingjie

    2011-10-21

    Inspired by a recent observation of a narrow resonance-like structure around 2360 MeV in the pn {yields} d{pi}{sup 0}{pi}{sup 0} cross section, we investigate the possibility of forming NN*(1440) quasi-bound state by meson exchange potential. With parameters of the t-channel {pi}, {sigma}, {rho} and {omega} exchanges determined by relevant NN scattering and N*(1440) decay processes, it is found that a NN*(1440) quasi-bound state with the same quantum numbers as the deuteron can be formed with binding energy about 20 MeV.

  18. Learning within bounds and dream sleep

    NASA Astrophysics Data System (ADS)

    Geszti, T.; Pazmandi, F.

    1987-12-01

    In a bounded-synapses version of Hopfield's model (1984) for neural networks the quasienergy of a given memory, which is approximately equal to the depth of the corresponding energy well is calculated exactly by treating the change of a synaptic strength on learning as a random walk within bounds. Attractors corresponding to stored memories are found to be considerably flattened before serious retrieval errors arise. This allows dream sleep to be interpreted as random recall and relearning of fresh strong memories, in order to stack them on top of weak incidental memory imprints of a day.

  19. A note on BPS vortex bound states

    NASA Astrophysics Data System (ADS)

    Alonso-Izquierdo, A.; Garcia Fuertes, W.; Mateos Guilarte, J.

    2016-02-01

    In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

  20. J/{Psi}-nuclear bound states

    SciTech Connect

    Tsushima, K.; Thomas, A. W.; Lu, D. H.; Krein, G.

    2011-06-15

    J/{Psi}-nuclear bound state energies are calculated for a range of nuclei by solving the Proca (Klein-Gordon) equation. Critical input for the calculations, namely the medium-modified D and D* meson masses, as well as the nucleon density distributions in nuclei, are obtained from the quark-meson coupling model. The attractive potential originates from the D and D* meson loops in the J/{Psi} self-energy in the nuclear medium. It appears that J/{Psi}-nuclear bound states should produce a clear experimental signature provided that the J/{Psi} meson is produced in recoilless kinematics.

  1. Quantum Kolmogorov complexity and bounded quantum memory

    SciTech Connect

    Miyadera, Takayuki

    2011-04-15

    The effect of bounded quantum memory in a primitive information protocol has been examined using the quantum Kolmogorov complexity as a measure of information. We employed a toy two-party protocol in which Bob, by using a bounded quantum memory and an unbounded classical memory, estimates a message that was encoded in qubits by Alice in one of the bases X or Z. Our theorem gave a nontrivial effect of the memory boundedness. In addition, a generalization of the uncertainty principle in the presence of quantum memory has been obtained.

  2. Geomagnetic Reversals during the Phanerozoic.

    PubMed

    McElhinny, M W

    1971-04-01

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency. PMID:17735224

  3. Bounding the states of systems with unknown-but-bounded disturbances

    NASA Technical Reports Server (NTRS)

    Tsai, Wei K.; Parlos, Alexander G.; Verghese, George C.

    1990-01-01

    Control systems with hard constraints on certain variables are characterized, in an analytical review of recent investigations based on an unknown-but-bounded description of magnitude uncertainties. Hard-constraint problems typically arise in the design of controllers for potentially hazardous systems such as nuclear power plants. Consideration is given to norm bounds based on matrix measures, extensions of Schweppe's (1968) ellipsoid bounds, and set-theoretic regulator design. The performance of these approaches is evaluated by means of numerical simulations involving a third-order nonlinear steam-boiler model; the results are presented in graphs, and it is found that ellipsoid bounds are tightest in the general case, but that box bounds are even tighter for linear systems with Metzler system matrices.

  4. B-Ring-Aryl Substituted Luotonin A Analogues with a New Binding Mode to the Topoisomerase 1-DNA Complex Show Enhanced Cytotoxic Activity

    PubMed Central

    González-Ruiz, Víctor; Pascua, Irene; Fernández-Marcelo, Tamara; Ribelles, Pascual; Bianchini, Giulia; Sridharan, Vellaisamy; Iniesta, Pilar; Ramos, M. Teresa; Olives, Ana I.; Martín, M. Antonia; Menéndez, J. Carlos

    2014-01-01

    Topoisomerase 1 inhibition is an important strategy in targeted cancer chemotherapy. The drugs currently in use acting on this enzyme belong to the family of the camptothecins, and suffer severe limitations because of their low stability, which is associated with the hydrolysis of the δ-lactone moiety in their E ring. Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity. Therefore, the development of luotonin A analogues with an increased potency is important for progress in this area. In the present paper, a small library of luotonin A analogues modified at their A and B rings was generated by cerium(IV) ammonium nitrate-catalyzed Friedländer reactions. All analogues showed an activity similar or higher than the natural luotonin A in terms of topoisomerase 1 inhibition and some compounds had an activity comparable to that of camptothecin. Furthermore, most compounds showed a better activity than luotonin A in cell cytotoxicity assays. In order to rationalize these results, the first docking studies of luotonin-topoisomerase 1-DNA ternary complexes were undertaken. Most compounds bound in a manner similar to luotonin A and to standard topoisomerase poisons such as topotecan but, interestingly, the two most promising analogues, bearing a 3,5-dimethylphenyl substituent at ring B, docked in a different orientation. This binding mode allows the hydrophobic moiety to be shielded from the aqueous environment by being buried between the deoxyribose belonging to the G(+1) guanine and Arg364 in the scissile strand and the surface of the protein and a hydrogen bond between the D-ring carbonyl and the basic amino acid. The discovery of this new binding mode and its associated higher inhibitory potency is a significant advance in the design of new topoisomerase 1 inhibitors. PMID:24830682

  5. Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes.

    PubMed

    Tsyganov, Dmitry V; Krayushkin, Mikhail M; Konyushkin, Leonid D; Strelenko, Yuri A; Semenova, Marina N; Semenov, Victor V

    2016-04-22

    Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay. PMID:26910798

  6. Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes.

    PubMed

    Tsyganov, Dmitry V; Krayushkin, Mikhail M; Konyushkin, Leonid D; Strelenko, Yuri A; Semenova, Marina N; Semenov, Victor V

    2016-04-22

    Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay.

  7. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

  8. Synthesis of chlorins, bacteriochlorins and their tetraaza analogues

    NASA Astrophysics Data System (ADS)

    Dudkin, S. V.; Makarova, E. A.; Lukyanets, E. A.

    2016-07-01

    The currently known methods for the synthesis of hydrogenated derivatives of synthetic porphyrins — chlorins, bacteriochlorins, isobacteriochlorins and their tetraaza analogues — are considered. Reactions involving quasi-isolated double bonds including reduction, oxidative addition and cycloaddition are presented. Examples of direct synthesis of these macroheterocycles are given. The bibliography includes 168 references.

  9. A Macroscopic Analogue of the Nuclear Pairing Potential

    ERIC Educational Resources Information Center

    Dunlap, Richard A.

    2013-01-01

    A macroscopic system involving permanent magnets is used as an analogue to nucleons in a nucleus to illustrate the significance of the pairing interaction. This illustrates that the view of the total nuclear energy based only on the nucleon occupancy of the energy levels can yield erroneous results and it is only when the pairing interaction is…

  10. q-bosons and the q-analogue quantized field

    NASA Technical Reports Server (NTRS)

    Nelson, Charles A.

    1995-01-01

    The q-analogue coherent states are used to identify physical signatures for the presence of a 1-analogue quantized radiation field in the q-CS classical limits where the absolute value of z is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/absolute value of z) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H(sub N) = h(omega)(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (Delta N)(exp 2)/ (N) approaches 0 as the absolute value of z approaches infinity. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, phi(sub q), still exhibits normal classical behavior. The standard number-phase uncertainty-relation, Delta(N) Delta phi(sub q) = 1/2, and the approximate commutation relation, (N, phi(sub q)) = i, still hold for the single-mode q-analogue quantized field. So, N and phi(sub q) are almost canonically conjugate operators in the q-CS classical limit. The q-analogue CS's minimize this uncertainty relation for moderate (absolute value of z)(exp 2).

  11. Synthesis of 4” manipulated Lewis X trisaccharide analogues

    PubMed Central

    Moore, Christopher J

    2012-01-01

    Summary Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D-GlcNAcp) in which the galactosyl residue is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the desired protected Lex analogues. One-step global deprotection (Na/NH3) of the protected 4”-methoxy analogue, and two-step deprotections (removal of a p-methoxybenzyl with DDQ, then Zemplén deacylation) of the 4”-deoxychloro and 4”-deoxyfluoro protected Lex analogues gave the desired compounds in good yields. PMID:23019441

  12. An Analysis of an Autoclitic Analogue in Pigeons

    ERIC Educational Resources Information Center

    Kuroda, Toshikazu; Lattal, Kennon A.; García-Penagos, Andrés

    2014-01-01

    Using a conditional discrimination procedure, pigeons were exposed to a nonverbal analogue of qualifying autoclitics such as "definitely" and "maybe." It has been suggested that these autoclitics are similar to tacts except that they are under the control of private discriminative stimuli. Instead of the conventional assumption…

  13. A Laboratory Analogue for the Study of Peer Sexual Harassment

    ERIC Educational Resources Information Center

    Mitchell, Damon; Hirschman, Richard; Angelone, D. J.; Lilly, Roy S.

    2004-01-01

    The purpose of this study was to develop a laboratory analogue for the study of peer sexual harassment, and to examine person and situational factors associated with male on female peer sexual harassment. One hundred twenty-two male participants were given the opportunity to tell jokes to a female confederate from a joke list that included…

  14. New phosphorus analogues of nitrogen classics--no carbon copies.

    PubMed

    Gudat, Dietrich

    2014-05-01

    Getting heavy: The recently prepared phosphorus analogues of two old acquaintances, urea and dinitrogen tetroxide, bear some structural resemblance to their archetypes but are no carbon copies. Their syntheses and chemical properties reveal rather certain peculiarities, which back the doctrine that the electronic properties of the heavier elements in a group differ from those of the lightest congener. PMID:24718995

  15. The tubulin-bound conformation of paclitaxel: T-taxol vs "PTX-NY".

    PubMed

    Yang, Yutao; Alcaraz, Ana A; Snyder, James P

    2009-03-27

    Nearly 35 years after its discovery and 11 years after FDA approval of paclitaxel (PTX) as a breakthrough anticancer drug, the 3-D structure of the agent bound to its beta-tubulin target was proposed to be T-Taxol. The latter bioactive form has recently been challenged by the Ojima group with a structure, "PTX-NY" ("REDOR Taxol"), in which the C-13 side chain is proposed to adopt a different conformation and an alternative hydrogen-bonding pattern in the tubulin binding site. Previously, the two conformers were compared to show that only T-Taxol fits the PTX-derived electron crystallographic density. That work has been extended by molecular mechanics and quantum chemical methods to reveal that the PTX-NY conformation is relatively less stable, on average, by 10-11 kcal/mol. In agreement with NMR studies, an 11 ns molecular dynamics treatment for PTX in an explicit water pool locates T-Taxol along the trajectory, but not PTX-NY. Docking of various PTX conformers into the electron crystallographic binding site of tubulin demonstrates that PTX-NY cannot be accommodated unless the pocket is reorganized in violation of the experimental constraints. Finally, analysis of the structures of T-Taxol and PTX-NY for their capacity to predict the existence of superpotent PTX analogues discloses that only the former forecasts such analogues, as now established by the T-Taxol-inspired synthesis of bridged taxanes. In sum, all empirical criteria support T-Taxol as the bound conformation of PTX on beta-tubulin in microtubules.

  16. Spin Labeling ESR Investigation of Covalently Bound Residues in Soil

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Olga; Steinhoff, Heinz-Juergen; Klasmeier, Joerg; Schulz, Marcus; Matthies, Michael

    2013-04-01

    Organic xenobiotic chemicals, such as pesticides, biocides and veterinary pharmaceuticals, interact with soil, which results in the simultaneous formations of metabolites, mineralization products, and bound or non-extractable residues (NER). Substances or metabolites with reactive functional groups, such as aniline or phenol, have a tendency to give a larger proportion of NER. Despite numerous studies on NER, the majority of their chemical structures is still unknown. Reversible sequestration and irreversible formation of NER were also observed for veterinary antibiotic pharmaceuticals, after their application to soil with and without manure. For this purpose, we hypothesized a key role of specific functional groups of soil contaminants, via which contaminants are covalently bound to soil constituents, and advance a method of spin labeling ESR investigation of reaction products using a membrane method. Spin labels (SL) represent chemically stable paramagnetic molecules used as molecular labels and molecular probes for testing the covalent binding, structural properties, and molecular mobility of different physical, chemical, and biological systems. In the case of covalent binding of SL, their ESR spectra become broadened. We used stable nitroxide radicals (NR) as SL. These radicals modeled organic chemical contaminants and differed only in one functional group. The paramagnetic SL 4-Amino Tempo (4-amino-2,2,6,6-tetramethyl-1-piperidinylox) differed from Tempo (2,2,6,6-Tetramethylpiperidinooxy) in a substituent at the para-position of the piperidine ring, whereas Aniline Tempo (1-Piperidinyloxy, 2,2,6,-tetramethyl, 6-Aniline) differed from Tempo in an Aniline substituting one CH3 functional group. Before experimental analysis, we tested temporal changes in the concentration of both NR incubated with soil and found that the life-times of them in soil exceeded 3 days. We contaminated and labeled soil samples with NR, adding to soil the aqueous solution, which already

  17. Non-robust numerical simulations of analogue extension experiments

    NASA Astrophysics Data System (ADS)

    Naliboff, John; Buiter, Susanne

    2016-04-01

    Numerical and analogue models of lithospheric deformation provide significant insight into the tectonic processes that lead to specific structural and geophysical observations. As these two types of models contain distinct assumptions and tradeoffs, investigations drawing conclusions from both can reveal robust links between first-order processes and observations. Recent studies have focused on detailed comparisons between numerical and analogue experiments in both compressional and extensional tectonics, sometimes involving multiple lithospheric deformation codes and analogue setups. While such comparisons often show good agreement on first-order deformation styles, results frequently diverge on second-order structures, such as shear zone dip angles or spacing, and in certain cases even on first-order structures. Here, we present finite-element experiments that are designed to directly reproduce analogue "sandbox" extension experiments at the cm-scale. We use material properties and boundary conditions that are directly taken from analogue experiments and use a Drucker-Prager failure model to simulate shear zone formation in sand. We find that our numerical experiments are highly sensitive to numerous numerical parameters. For example, changes to the numerical resolution, velocity convergence parameters and elemental viscosity averaging commonly produce significant changes in first- and second-order structures accommodating deformation. The sensitivity of the numerical simulations to small parameter changes likely reflects a number of factors, including, but not limited to, high angles of internal friction assigned to sand, complex, unknown interactions between the brittle sand (used as an upper crust equivalent) and viscous silicone (lower crust), highly non-linear strain weakening processes and poor constraints on the cohesion of sand. Our numerical-analogue comparison is hampered by (a) an incomplete knowledge of the fine details of sand failure and sand

  18. Natural analogue studies: present status and performance assessment implications

    NASA Astrophysics Data System (ADS)

    Smellie, John A. T.; Karlsson, Fred; Alexander, W. Russell

    1997-04-01

    Studies of natural geological and archaeological systems as analogues to long-term processes, which are predicted to occur within a radioactive waste repository environment, have become increasingly popular over the last 10 years or so, to the extent that such studies form an integral part of many national programmes for radioactive waste disposal. There is now a common consensus that the natural analogue approach is a very useful scientific methodology to: (a) identify and understand processes and mechanisms analogous to those which could occur in the vicinity of a repository over realistic timescales, (b) derive input data which have been successfully used to test some of the laboratory-based models which form the basis of long-term repository performance assessment, and (c) to produce data which can be input directly to performance assessment models. Increasingly, analogues are playing an important role in public awareness, enabling the layman to understand better the concept of radioactive disposal and demonstrating the reliability of the disposal system over long periods of geological time. The complexity of geological systems means that it is very often difficult and sometimes impossible to quantify precisely the physico-chemical boundary conditions necessary to model a particular geochemical process or mechanism. Consequently, the availability of quantitative analogue data is limited when repository performance assessments are considered. However, this in no way detracts from their value in building confidence by demonstrating that important processes do exist and by showing qualitatively that they behave in a way predicted by models based on laboratory-derived data. The transfer of natural analogue data from the complexity of field studies to simplistic models which, by necessity, are used in performance assessments, is an area of activity which is presently being addressed. Field analogue studies are now being planned to interface with laboratory

  19. Transition States and transition state analogue interactions with enzymes.

    PubMed

    Schramm, Vern L

    2015-04-21

    Enzymatic transition states have lifetimes of a few femtoseconds (fs). Computational analysis of enzyme motions leading to transition state formation suggests that local catalytic site motions on the fs time scale provide the mechanism to locate transition states. An experimental test of protein fs motion and its relation to transition state formation can be provided by isotopically heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states without altered electrostatic properties, according to the Born-Oppenheimer approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent with altered protein bond frequencies slowing the search for the transition state. In other heavy enzymes, structural changes involved in reactant binding and release are also influenced. Slow protein motions associated with substrate binding and catalytic site preorganization are essential to allow the subsequent fs motions to locate the transition state and to facilitate the efficient release of products. In the catalytically competent geometry, local groups move in stochastic atomic motion on the fs time scale, within transition state-accessible conformations created by slower protein motions. The fs time scale for the transition state motions does not permit thermodynamic equilibrium between the transition state and stable enzyme states. Isotopically heavy enzymes provide a diagnostic tool for fast coupled protein motions to transition state formation and mass-dependent conformational changes. The binding of transition state analogue inhibitors is the opposite in catalytic time scale to formation of the transition state but is related by similar geometries of the enzyme-transition state and enzyme-inhibitor interactions. While enzymatic transition states have lifetimes as short as 10(-15) s, transition state analogues can bind tightly to enzymes with release rates greater than 10(3) s. Tight-binding transition state analogues stabilize the rare but

  20. Antifungal activity of eugenol analogues. Influence of different substituents and studies on mechanism of action.

    PubMed

    Carrasco, Héctor; Raimondi, Marcela; Svetaz, Laura; Di Liberto, Melina; Rodriguez, María V; Espinoza, Luis; Madrid, Alejandro; Zacchino, Susana

    2012-01-19

    Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH(3) at C-2 or the presence of one or two NO(2) groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL-1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.

  1. College Bound? Make the Right Choices

    ERIC Educational Resources Information Center

    Robinson, Jenna Ashley

    2009-01-01

    "College Bound? Make the Right Choices" is the Pope Center's latest tool for improving colleges and universities "from the bottom up" through better choices. Its purpose is to help high school students and their parents become smarter purchasers of higher education. This booklet by Jenna Ashley Robinson helps young people think through what they…

  2. Nondissipative decoherence bounds on quantum computation

    NASA Astrophysics Data System (ADS)

    Mancini, Stefano; Bonifacio, Rodolfo

    2001-03-01

    We investigate the capabilities of a quantum computer based on cold trapped ions in the presence of nondissipative decoherence. The latter is accounted by using the evolution time as a random variable and then averaging on a properly defined probability distribution. Severe bounds on computational performances are found.

  3. Interaction barriers for light, weakly bound projectiles

    SciTech Connect

    Kolata, J. J.; Aguilera, E. F.

    2009-02-15

    A parametrization of the interaction-barrier model of C. Y. Wong [Phys. Rev. Lett. 31, 766 (1973)] is given for light, weakly bound projectiles and also for the exotic 'halo' nuclei {sup 6}He and {sup 8}B. Comparisons are made with the original parametrization. The extremely anomalous behavior of the interaction radius and barrier curvature for halo nuclei is discussed.

  4. Bioactivity of albumins bound to silver nanoparticles.

    PubMed

    Mariam, Jessy; Sivakami, S; Kothari, D C; Dongre, P M

    2014-06-01

    The last decade has witnessed a tremendous rise in the proposed applications of nanomaterials in the field of medicine due to their very attractive physiochemical properties and novel actions such as the ability to reach previously inaccessible targets such as brain. However biological activity of functional molecules bound to nanoparticles and its physiological consequences is still unclear and hence this area requires immediate attention. The functional properties of Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) bound to silver nanoparticles (~60 nm) have been studied under physiological environment. Esterase activity, binding of drugs (warfarin and ibuprofen), antioxidant activity and copper binding by albumins was evaluated. The catalytic efficiencies of HSA and BSA diminished upon binding to silver nanoparticles. Perturbation in binding of warfarin and ibuprofen, loss of free sulphydryls, antioxidant activity and enhancement of copper binding were observed in albumins bound to nanoparticles. These alterations in functional activity of nanoparticle bound albumins which will have important consequences should be taken into consideration while using nanoparticles for diagnostic and therapeutic purposes.

  5. Bounds for the cumulative conditional expectation function

    SciTech Connect

    Fernández, M.; González-López, V. A.

    2015-03-10

    We introduce the concept of cumulative conditional expectation function. This is a quantity that provides statistical support for making decisions in applied problems. The goal of this paper is to find an analytical expression for upper and lower bounds of this function, assuming stochastic dependence types as being the underlying random structure.

  6. Opinion formation with upper and lower bounds

    NASA Astrophysics Data System (ADS)

    Yano, Ryosuke; Martin, Arnaud

    2015-12-01

    We investigate the opinion formation with upper and lower bounds. We formulate the binary exchange of opinions between two peoples under the second (or political) party using the relativistic inelastic-Boltzmann-Vlasov equation with randomly perturbed motion. In this paper, we discuss the relativistic effects on the opinion formation of peoples from the standpoint of the relativistic kinetic theory.

  7. Mentoring College Bound High School Seniors.

    ERIC Educational Resources Information Center

    Mowrer-Popiel, Elizabeth

    This article examines causes of the high rate of attrition of college freshmen during the first few weeks of school and describes a plan for mentorships between successful college students and college-bound secondary seniors prior to entrance into college. In discussing the challenges facing freshmen, the article suggests that they suffer stress…

  8. Book Selection, Collection Development, and Bounded Rationality.

    ERIC Educational Resources Information Center

    Schwartz, Charles A.

    1989-01-01

    Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

  9. Logistics Handbook, 1976. Colorado Outward Bound School.

    ERIC Educational Resources Information Center

    Colorado Outward Bound School, Denver.

    Logistics, a support mission, is vital to the successful operation of the Colorado Outward Bound School (COBS) courses. Logistics is responsible for purchasing, maintaining, transporting, and replenishing a wide variety of items, i.e., food, mountaineering and camping equipment, medical and other supplies, and vehicles. The Logistics coordinator…

  10. Ternary resin-bound Dynamic Combinatorial Chemistry.

    PubMed

    Gromova, Anna V; Ciszewski, Joseph M; Miller, Benjamin L

    2012-02-18

    The ability to carry out simultaneous orthogonal exchange chemistries has opened new opportunities for increasing the numerical and structural diversity accessible to Dynamic Combinatorial Chemistry. We present proof-of-concept experiments demonstrating this concept is transferrable to resin-bound DCC, facilitating the generation and analysis of libraries with greater structural diversity.

  11. Bound Indoleacetic Acid in Avena Coleoptiles 1

    PubMed Central

    Winter, Alan; Thimann, Kenneth V.

    1966-01-01

    When C14 carboxyl indoleacetic acid (IAA) is transported through Avena coleoptile sections a fraction of the activity becomes bound. The nature of this bound IAA has been investigated. Upon extraction with solvents and chromatography a substance having the RF of IAA in 4 solvents was detected. No evidence could be found for the formation of indoleacetyl conjugates. In pea stem sections subjected to a similar experimental regime good evidence was obtained for the occurrence of conjugates. When IAA was supplied exogenously to coleoptile sections floating in solutions the occurrence of conjugates was shown to be dependent on the presence of the primary leaf. In its absence no conjugates could be detected. On grinding coleoptile sections and subsequent centrifugation at 240 × g the radioactivity was found to be in the tissue fraction as opposed to the supernatant. The radioactivity cannot be removed from the tissue by extraction with water, buffer solution or treatment with ribonuclease. It is readily removed by 10% urea, crystalline trypsin and chymotrypsin. It is therefore concluded that IAA becomes bound to a protein. Bound IAA does not appear to be able to cause growth in Avena coleoptile sections. PMID:16656259

  12. Outward Bound as an Adjunct to Therapy.

    ERIC Educational Resources Information Center

    Chase, Nelson K.

    The Colorado Outward Bound School (COBS) provides successful adjunct programs for special populations undergoing therapy at the Adventure Home (Boulder, CO), the Juvenile Justice Program and the St. Luke's Hospital Alcoholism Recovery Unit (Denver, CO), and the Dartmouth-Hitchcock Medical Center Department of Psychiatry (Hanover, NH). The goals of…

  13. Theoretical Bounds of Direct Binary Search Halftoning.

    PubMed

    Liao, Jan-Ray

    2015-11-01

    Direct binary search (DBS) produces the images of the best quality among half-toning algorithms. The reason is that it minimizes the total squared perceived error instead of using heuristic approaches. The search for the optimal solution involves two operations: (1) toggle and (2) swap. Both operations try to find the binary states for each pixel to minimize the total squared perceived error. This error energy minimization leads to a conjecture that the absolute value of the filtered error after DBS converges is bounded by half of the peak value of the autocorrelation filter. However, a proof of the bound's existence has not yet been found. In this paper, we present a proof that shows the bound existed as conjectured under the condition that at least one swap occurs after toggle converges. The theoretical analysis also indicates that a swap with a pixel further away from the center of the autocorrelation filter results in a tighter bound. Therefore, we propose a new DBS algorithm which considers toggle and swap separately, and the swap operations are considered in the order from the edge to the center of the filter. Experimental results show that the new algorithm is more efficient than the previous algorithm and can produce half-toned images of the same quality as the previous algorithm.

  14. Lifetime of a Chemically Bound Helium Compound

    NASA Technical Reports Server (NTRS)

    Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Dochan (Technical Monitor)

    2001-01-01

    The rare-gas atoms are chemically inert, to an extent unique among all elements. This is due to the stable electronic structure of the atoms. Stable molecules with chemically bound rare-gas atoms are, however, known. A first such compound, XePtF6, W2S prepared in 1962 and since then a range of molecules containing radon, xenon and krypton have been obtained. Most recently, a first stable chemically bound compound of argon was prepared, leaving neon and helium as the only elements for which stable chemically bound molecules are not yet known. Electronic structure calculations predict that a metastable species HHeF exists, but significance of the result depends on the unknown lifetime. Here we report quantum dynamics calculations of the lifetime of HHeF, using accurate interactions computed from electronic structure theory. HHeF is shown to disintegrate by tunneling through energy barriers into He + HF and H + He + F the first channel greatly dominating. The lifetime of HHeF is more than 120 picoseconds, that of DHeF is 14 nanoseconds. The relatively long lifetimes are encouraging for the preparation prospects of this first chemically bound helium compound.

  15. Colorado Outward Bound School River Rafters' Manual.

    ERIC Educational Resources Information Center

    Leachman, Mark

    Instructional sequences, safety rules, duties of crew members, and procedures for Colorado Outward Bound School river rafting trips are summarized in this manual. Designed to acquaint instructors with the duties expected of them on the trips, the information in the manual is presented in outline form and is intended for those with prior river…

  16. College Bound Seniors, 1974-75.

    ERIC Educational Resources Information Center

    College Entrance Examination Board, New York, NY.

    Some one million college bound students, who were high school seniors during 1974-75 previously participated in the College Board's Admissions Testing Program (ATP), which included the Scholarship Aptitude Test (SAT), the Test of Standard Written English, the Student Descriptive Questionnaire, and the ATP Achievement Tests. These tests created a…

  17. Stability of carbonaceous dust analogues and glycine under UV irradiation and electron bombardment.

    PubMed

    Maté, Belén; Tanarro, Isabel; Moreno, Miguel A; Jiménez-Redondo, Miguel; Escribano, Rafael; Herrero, Víctor J

    2014-01-01

    The effect of UV photon (120-200 nm) and electron (2 keV) irradiation of analogues of interstellar carbonaceous dust and of glycine were investigated by means of IR spectroscopy. Films of hydrogenated amorphous carbon (HAC), taken as dust analogues, were found to be stable under UV photon and electron bombardment. High fluences of photons and electrons, of the order of 10(19) cm(-2), were needed for a film depletion of a few percent. UV photons were energetically more effective than electrons for depletion and led to a certain dehydrogenation of the HAC samples, whereas electrons led seemingly to a gradual erosion with no appreciable changes in the hydrocarbon structure. The rates of change observed may be relevant over the lifetime of a diffuse cloud, but cannot account for the rapid changes in hydrocarbon IR bands during the evolution of some proto-planetary nebulae. Glycine samples under the same photon and electron fluxes decay at a much faster rate, but tend usually to an equilibrium value different from zero, especially at low temperatures. Reversible reactions re-forming glycine, or the build-up of less transparent products, could explain this behavior. CO2 and methylamine were identified as UV photoproducts. Electron irradiation led to a gradual disappearance of the glycine layers, also with formation of CO2. No other reaction products were clearly identified. The thicker glycine layers (a few hundred nm) were not wholly depleted, but a film of the order of the electron penetration depth (80 nm), was totally destroyed with an electron fluence of -1 x 10(18) cm(-2). A 60 nm ice layer on top of glycine provided only partial shielding from the 2 keV electrons. From an energetic point of view, 2 keV electrons are less efficient than UV photons and, according to literature data, much less efficient than MeV protons for the destruction of glycine. The use of keV electrons to simulate effects of cosmic rays on analogues of interstellar grains should be taken with

  18. Biological evaluation of a novel sorafenib analogue, t-CUPM.

    PubMed

    Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I; Morisseau, Christophe; Wu, Jian; Weiss, Robert H; Hammock, Bruce D

    2015-01-01

    Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib.

  19. Cysteine analogues potentiate glucose-induced insulin release in vitro

    SciTech Connect

    Ammon, H.P.; Hehl, K.H.; Enz, G.; Setiadi-Ranti, A.; Verspohl, E.J.

    1986-12-01

    In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.

  20. Metric optimisation for analogue forecasting by simulated annealing

    NASA Astrophysics Data System (ADS)

    Bliefernicht, J.; Bárdossy, A.

    2009-04-01

    It is well known that weather patterns tend to recur from time to time. This property of the atmosphere is used by analogue forecasting techniques. They have a long history in weather forecasting and there are many applications predicting hydrological variables at the local scale for different lead times. The basic idea of the technique is to identify past weather situations which are similar (analogue) to the predicted one and to take the local conditions of the analogues as forecast. But the forecast performance of the analogue method depends on user-defined criteria like the choice of the distance function and the size of the predictor domain. In this study we propose a new methodology of optimising both criteria by minimising the forecast error with simulated annealing. The performance of the methodology is demonstrated for the probability forecast of daily areal precipitation. It is compared with a traditional analogue forecasting algorithm, which is used operational as an element of a hydrological forecasting system. The study is performed for several meso-scale catchments located in the Rhine basin in Germany. The methodology is validated by a jack-knife method in a perfect prognosis framework for a period of 48 years (1958-2005). The predictor variables are derived from the NCEP/NCAR reanalysis data set. The Brier skill score and the economic value are determined to evaluate the forecast skill and value of the technique. In this presentation we will present the concept of the optimisation algorithm and the outcome of the comparison. It will be also demonstrated how a decision maker should apply a probability forecast to maximise the economic benefit from it.

  1. Analogue Sites for Mars Missions - A report from two workshops

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Voytek, M. A.; Glamoclija, M.

    2014-12-01

    Fieldwork, at terrestrial sites that are analogous in some way to Mars, has a key role in defining questions addressed by Mars missions. For MSL, the question is whether its landing site was habitable, and for Mars 2020, the question is how do we search for and what are signs of life in ancient habitable environments. Implementing these investigations by means of a rover mission on a distant planetary surface has challenges due to a limited set of tools and period of operations. Using this context of planetary missions is important in shaping how analog research can be used to advance planetary science. Following a successful 2010 AGU fall meeting session entitled "Analogue Sites for Mars Missions", two community workshops were held at The Woodlands, TX March 2011 and the Carnegie Institute of Washington in July 2013. These activities represent an ongoing dialogue with the analogue and mission communities. The AGU session solicited presentations of current analogue research relevant to MSL, at which time the landing site selection process was still considering four final sites. The 2011 Woodlands workshop solicited details on representative science questions and analogue sites by means of an abstract template. The output from The Woodlands workshop was an initial metric to assess the utility of analogue sites against specific science questions, as well as recommendations for future activities. The 2013 Carnegie workshop, followed up on some of the recommendations from 2011. Both on-line interactive dialogue and in person discussions targeted broad topics, including 'the advantages and problems of using a great terrestrial analog for field testing', and 'knowing what we currently do about Mars, what would be the best place on the planet to collect the first suite of samples to be returned to Earth? What would be appropriate analog sites on Earth?'. The results and recommendations from both workshops are summarized to publicize and stimulate this ongoing discussion.

  2. Time-Reversal Violation

    NASA Astrophysics Data System (ADS)

    Bernabéu, José; Martínez-Vidal, Fernando

    2015-10-01

    The violation of CP symmetry between matter and antimatter in the neutral K and B meson systems is well established, with a high degree of consistency between all available experimental measurements and with the Standard Model of particle physics. On the basis of the up-to-now-unbroken CPT symmetry, the violation of CP symmetry strongly suggests that the behavior of these particles under weak interactions must also be asymmetric under time reversal T. Many searches for T violation have been performed and proposed using different observables and experimental approaches. These include T-odd observables, such as triple products in weak decays, and genuine observables, such as permanent electric dipole moments of nondegenerate stationary states and the breaking of the reciprocity relation. We discuss the conceptual basis of the required exchange of initial and final states with unstable particles, using quantum entanglement and the decay as a filtering measurement, for the case of neutral B and K mesons. Using this method, the BaBar experiment at SLAC has clearly observed T violation in B mesons.

  3. Reversible micromachining locator

    DOEpatents

    Salzer, Leander J.; Foreman, Larry R.

    1999-01-01

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved.

  4. Reversible micromachining locator

    DOEpatents

    Salzer, L.J.; Foreman, L.R.

    1999-08-31

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved. 7 figs.

  5. Time Reversal Violation

    SciTech Connect

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

  6. Reverse hierarchical PIV processing

    NASA Astrophysics Data System (ADS)

    Rohály, J.; Frigerio, F.; Hart, D. P.

    2002-07-01

    A novel hierarchical processing scheme is proposed to efficiently increase the spatial resolution and dynamic range of detecting particle image displacements in PIV images. The technique takes full advantage of the multi-resolution characteristic of the discrete correlation function by starting the processing at the smallest scale and, if necessary, gradually building correlation planes into larger interrogation areas based on the result of inter-level correlation correction and validation. It is shown that the algorithm can be implemented in both direct and FFT based correlation algorithms with greatly reduced computational complexity. The technique opens new perspectives for locally adaptive super-resolution processing taking flow field, seeding, and imaging anomalies into account. Processing at the lowest scale (e.g. pixel or particle image size) allows the combination of correlation planes on any shape. Hence the proposed reverse hierarchical processing represents interrogation area optimization both in size and shape in order to maximize the correlation plane signal-to-noise ratio. The method is successfully demonstrated on experimentally obtained images.

  7. New HiggsBounds from LEP and the Tevatron

    SciTech Connect

    Bechtle, P.; Brein, O.; Heinemeyer, S.; Weiglein, G.; Williams, K.

    2010-02-10

    We review the program HiggsBounds that tests theoretical predictions of models with arbitrary Higgs sectors against the exclusion bounds obtained from the Higgs searches at LEP and the Tevatron. We explicitly list the bounds that have been added after the first release of HiggsBounds.

  8. Sample Complexity Bounds for Differentially Private Learning

    PubMed Central

    Chaudhuri, Kamalika; Hsu, Daniel

    2013-01-01

    This work studies the problem of privacy-preserving classification – namely, learning a classifier from sensitive data while preserving the privacy of individuals in the training set. In particular, the learning algorithm is required in this problem to guarantee differential privacy, a very strong notion of privacy that has gained significant attention in recent years. A natural question to ask is: what is the sample requirement of a learning algorithm that guarantees a certain level of privacy and accuracy? We address this question in the context of learning with infinite hypothesis classes when the data is drawn from a continuous distribution. We first show that even for very simple hypothesis classes, any algorithm that uses a finite number of examples and guarantees differential privacy must fail to return an accurate classifier for at least some unlabeled data distributions. This result is unlike the case with either finite hypothesis classes or discrete data domains, in which distribution-free private learning is possible, as previously shown by Kasiviswanathan et al. (2008). We then consider two approaches to differentially private learning that get around this lower bound. The first approach is to use prior knowledge about the unlabeled data distribution in the form of a reference distribution chosen independently of the sensitive data. Given such a reference , we provide an upper bound on the sample requirement that depends (among other things) on a measure of closeness between and the unlabeled data distribution. Our upper bound applies to the non-realizable as well as the realizable case. The second approach is to relax the privacy requirement, by requiring only label-privacy – namely, that the only labels (and not the unlabeled parts of the examples) be considered sensitive information. An upper bound on the sample requirement of learning with label privacy was shown by Chaudhuri et al. (2006); in this work, we show a lower bound. PMID:25285183

  9. Insoluble-Bound Phenolics in Food.

    PubMed

    Shahidi, Fereidoon; Yeo, Ju-Dong

    2016-01-01

    This contribution provides a review of the topic of insoluble-bound phenolics, especially their localization, synthesis, transfer and formation in plant cells, as well as their metabolism in the human digestive system and corresponding bioactivities. In addition, their release from the food matrix during food processing and extraction methods are discussed. The synthesis of phenolics takes place mainly at the endoplasmic reticulum and they are then transferred to each organ through transport proteins such as the ATP-binding cassette (ABC) and multidrug and toxic compound extrusion (MATE) transporter at the organ's compartment membrane or via transport vesicles such as cytoplasmic and Golgi vesicles, leading to the formation of soluble and insoluble-bound phenolics at the vacuole and cell wall matrix, respectively. This part has not been adequately discussed in the food science literature, especially regarding the synthesis site and their transfer at the cellular level, thus this contribution provides valuable information to the involved scientists. The bound phenolics cannot be absorbed at the small intestine as the soluble phenolics do (5%-10%), thus passing into the large intestine and undergoing fermentation by a number of microorganisms, partially released from cell wall matrix of foods. Bound phenolics such as phenolic acids and flavonoids display strong bioactivities such as anticancer, anti-inflammation and cardiovascular disease ameliorating effects. They can be extracted by several methods such as acid, alkali and enzymatic hydrolysis to quantify their contents in foods. In addition, they can also be released from the cell wall matrix during food processing procedures such as fermentation, germination, roasting, extrusion cooking and boiling. This review provides critical information for better understanding the insoluble-bound phenolics in food and fills an existing gap in the literature. PMID:27626402

  10. Reverse Transfer Project, Summer 1986.

    ERIC Educational Resources Information Center

    Reis, Elizabeth

    In 1986, a Reverse Transfer Project was initiated at Moraine Valley Community College (MVCC) in order to promote the summer school attendance at MVCC of "reverse transfer" students (i.e., students who attended another institution during the regular academic year). A mailing, containing a cover letter, informational brochure, summer catalog, and…

  11. Preference Reversal in Multiattribute Choice

    ERIC Educational Resources Information Center

    Tsetsos, Konstantinos; Usher, Marius; Chater, Nick

    2010-01-01

    A central puzzle for theories of choice is that people's preferences between options can be reversed by the presence of decoy options (that are not chosen) or by the presence of other irrelevant options added to the choice set. Three types of reversal effect reported in the decision-making literature, the attraction, compromise, and similarity…

  12. Analogue modelling of inclined, brittle-ductile transpression: Testing analytical models through natural shear zones (external Betics)

    NASA Astrophysics Data System (ADS)

    Barcos, L.; Díaz-Azpiroz, M.; Balanyá, J. C.; Expósito, I.; Jiménez-Bonilla, A.; Faccenna, C.

    2016-07-01

    The combination of analytical and analogue models gives new opportunities to better understand the kinematic parameters controlling the evolution of transpression zones. In this work, we carried out a set of analogue models using the kinematic parameters of transpressional deformation obtained by applying a general triclinic transpression analytical model to a tabular-shaped shear zone in the external Betic Chain (Torcal de Antequera massif). According to the results of the analytical model, we used two oblique convergence angles to reproduce the main structural and kinematic features of structural domains observed within the Torcal de Antequera massif (α = 15° for the outer domains and α = 30° for the inner domain). Two parallel inclined backstops (one fixed and the other mobile) reproduce the geometry of the shear zone walls of the natural case. Additionally, we applied digital particle image velocimetry (PIV) method to calculate the velocity field of the incremental deformation. Our results suggest that the spatial distribution of the main structures observed in the Torcal de Antequera massif reflects different modes of strain partitioning and strain localization between two domain types, which are related to the variation in the oblique convergence angle and the presence of steep planar velocity - and rheological - discontinuities (the shear zone walls in the natural case). In the 15° model, strain partitioning is simple and strain localization is high: a single narrow shear zone is developed close and parallel to the fixed backstop, bounded by strike-slip faults and internally deformed by R and P shears. In the 30° model, strain partitioning is strong, generating regularly spaced oblique-to-the backstops thrusts and strike-slip faults. At final stages of the 30° experiment, deformation affects the entire model box. Our results show that the application of analytical modelling to natural transpressive zones related to upper crustal deformation

  13. Surface-Bound Casein Modulates the Adsorption and Activity of Kinesin on SiO2 Surfaces

    PubMed Central

    Ozeki, Tomomitsu; Verma, Vivek; Uppalapati, Maruti; Suzuki, Yukiko; Nakamura, Mikihiko; Catchmark, Jeffrey M.; Hancock, William O.

    2009-01-01

    Abstract Conventional kinesin is routinely adsorbed to hydrophilic surfaces such as SiO2. Pretreatment of surfaces with casein has become the standard protocol for achieving optimal kinesin activity, but the mechanism by which casein enhances kinesin surface adsorption and function is poorly understood. We used quartz crystal microbalance measurements and microtubule gliding assays to uncover the role that casein plays in enhancing the activity of surface-adsorbed kinesin. On SiO2 surfaces, casein adsorbs as both a tightly bound monolayer and a reversibly bound second layer that has a dissociation constant of 500 nM and can be desorbed by washing with casein-free buffer. Experiments using truncated kinesins demonstrate that in the presence of soluble casein, kinesin tails bind well to the surface, whereas kinesin head binding is blocked. Removing soluble casein reverses these binding profiles. Surprisingly, reversibly bound casein plays only a moderate role during kinesin adsorption, but it significantly enhances kinesin activity when surface-adsorbed motors are interacting with microtubules. These results point to a model in which a dynamic casein bilayer prevents reversible association of the heads with the surface and enhances association of the kinesin tail with the surface. Understanding protein-surface interactions in this model system should provide a framework for engineering surfaces for functional adsorption of other motor proteins and surface-active enzymes. PMID:19383474

  14. Influence of erosion and sedimentation on strike-slip fault systems: insights from analogue models

    NASA Astrophysics Data System (ADS)

    Le Guerroué, Erwan; Cobbold, Peter Robert

    2006-03-01

    We describe 18 experiments on the formation of strike-slip fault systems in sand. All models were in a rectangular box. A piston imparted strike-slip motion along a basal cut. In some experiments, uplifted areas underwent erosion. In others, all areas were subject to sedimentation. In experiments without erosion or sedimentation, first to develop were R-faults, at 16° to the basal cut. At later stages, P-faults and Y-faults took over. In section, faults splayed upward, forming flower structures. The splays had reverse components of slip. This was due to dilation, which reached 7% within fault splays. In experiments with erosion but no sedimentation, faults were less steep and accumulated greater amounts of reverse slip. In experiments with erosion and sedimentation, some faults propagated through their syn-kinematic cover, others became buried and inactive, whilst yet others were exposed by erosion. Therefore the average fault dip increased significantly. In experiments with sedimentation but no erosion, early faults propagated, whereas others became buried. Flower structures in nature have similar features. In areas of sedimentation, fault splays with gentle dips die out at depth, whereas steeper faults penetrate higher. In areas of erosion, strike-slip systems exhibit large amounts of reverse slip on steep bounding faults.

  15. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Fortescue, Ben; Hsieh, Min-Hsiu

    2015-08-01

    In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution pX Y Z and transform secret bits back into pX Y Z at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gács-Körner common information.

  16. Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core

    NASA Astrophysics Data System (ADS)

    da Fonseca, Paula C. A.; Morris, Edward P.

    2015-07-01

    The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 Å. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein-ligand interactions.

  17. Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core.

    PubMed

    da Fonseca, Paula C A; Morris, Edward P

    2015-07-02

    The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 Å. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein-ligand interactions.

  18. Entanglement bound for multipartite pure states based on local measurements

    SciTech Connect

    Jiang Lizhen; Chen Xiaoyu; Ye Tianyu

    2011-10-15

    An entanglement bound based on local measurements is introduced for multipartite pure states. It is the upper bound of the geometric measure and the relative entropy of entanglement. It is the lower bound of the minimal-measurement entropy. For pure bipartite states, the bound is equal to the entanglement entropy. The bound is applied to pure tripartite qubit states and the exact tripartite relative entropy of entanglement is obtained for a wide class of states.

  19. The Geomagnetic Field During a Reversal

    NASA Technical Reports Server (NTRS)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  20. Reverse osmosis reverses conventional wisdom with Superfund cleanup success

    SciTech Connect

    Collins, M. ); Miller, K. )

    1994-09-01

    Although widely recognized as the most efficient means of water purification, reverse osmosis has not been considered effective for remediating hazardous wastewater. Scaling and fouling, which can cause overruns and downtime, and require membrane replacement, have inhibited success in high-volume wastewater applications. Despite this background, a reverse osmosis technology developed in Europe recently was used successfully to treat large volumes of contaminated water at a major Superfund site in Texas. The technology's success there may increase the chances for reverse osmosis to find wider use in future cleanups and other waste treatment applications.

  1. Aerodynamics of intermittent bounds in flying birds

    NASA Astrophysics Data System (ADS)

    Tobalske, Bret W.; Hearn, Jason W. D.; Warrick, Douglas R.

    Flap-bounding is a common flight style in small birds in which flapping phases alternate with flexed-wing bounds. Body lift is predicted to be essential to making this flight style an aerodynamically attractive flight strategy. To elucidate the contributions of the body and tail to lift and drag during the flexed-wing bound phase, we used particle image velocimetry (PIV) and measured properties of the wake of zebra finch (Taeniopygia guttata, N = 5), flying at 6-10 m s- 1 in a variable speed wind tunnel as well as flow around taxidermically prepared specimens (N = 4) mounted on a sting instrumented with force transducers. For the specimens, we varied air velocity from 2 to 12 m s- 1 and body angle from -15∘ to 50∘. The wake of bounding birds and mounted specimens consisted of a pair of counterrotating vortices shed into the wake from the tail, with induced downwash in the sagittal plane and upwash in parasagittal planes lateral to the bird. This wake structure was present even when the tail was entirely removed. We observed good agreement between force measures derived from PIV and force transducers over the range of body angles typically used by zebra finch during forward flight. Body lift:drag (L:D) ratios averaged 1.4 in live birds and varied between 1 and 1.5 in specimens at body angles from 10∘ to 30∘. Peak (L:D) ratio was the same in live birds and specimens (1.5) and was exhibited in specimens at body angles of 15∘ or 20∘, consistent with the lower end of body angles utilized during bounds. Increasing flight velocity in live birds caused a decrease in CL and CD from maximum values of 1.19 and 0.95 during flight at 6 m s- 1 to minimum values of 0.70 and 0.54 during flight at 10 m s- 1. Consistent with delta-wing theory as applied to birds with a graduated-tail shape, trimming the tail to 0 and 50% of normal length reduced L:D ratios and extending tail length to 150% of normal increased L:D ratio. As downward induced velocity is present in the

  2. Aerodynamics of intermittent bounds in flying birds

    NASA Astrophysics Data System (ADS)

    Tobalske, Bret W.; Hearn, Jason W. D.; Warrick, Douglas R.

    2009-05-01

    Flap-bounding is a common flight style in small birds in which flapping phases alternate with flexed-wing bounds. Body lift is predicted to be essential to making this flight style an aerodynamically attractive flight strategy. To elucidate the contributions of the body and tail to lift and drag during the flexed-wing bound phase, we used particle image velocimetry (PIV) and measured properties of the wake of zebra finch ( Taeniopygia guttata, N = 5), flying at 6-10 m s-1 in a variable speed wind tunnel as well as flow around taxidermically prepared specimens ( N = 4) mounted on a sting instrumented with force transducers. For the specimens, we varied air velocity from 2 to 12 m s-1 and body angle from -15° to 50°. The wake of bounding birds and mounted specimens consisted of a pair of counter-rotating vortices shed into the wake from the tail, with induced downwash in the sagittal plane and upwash in parasagittal planes lateral to the bird. This wake structure was present even when the tail was entirely removed. We observed good agreement between force measures derived from PIV and force transducers over the range of body angles typically used by zebra finch during forward flight. Body lift:drag ( L: D) ratios averaged 1.4 in live birds and varied between 1 and 1.5 in specimens at body angles from 10° to 30°. Peak ( L: D) ratio was the same in live birds and specimens (1.5) and was exhibited in specimens at body angles of 15° or 20°, consistent with the lower end of body angles utilized during bounds. Increasing flight velocity in live birds caused a decrease in C L and C D from maximum values of 1.19 and 0.95 during flight at 6 m s-1 to minimum values of 0.70 and 0.54 during flight at 10 m s-1. Consistent with delta-wing theory as applied to birds with a graduated-tail shape, trimming the tail to 0 and 50% of normal length reduced L: D ratios and extending tail length to 150% of normal increased L: D ratio. As downward induced velocity is present in the

  3. A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site

    SciTech Connect

    Wu, J.C.; Warren, T.C.; Adams, J.; Proudfoot, J.; Skiles, J.; Raghavan, P.; Perry, C.; Potocki, I.; Farina, P.R.; Grob, P.M. )

    1991-02-26

    A novel dipyridodiazepinone, 6,11-dihydro-11-cyclopropyl-4-methyldipyrido(2,3-b:2{prime},3{prime}-e)-(1,4)diazepin-6-one (BI-RG-587), is a selective noncompetitive inhibitor of HIV-1 reverse transcriptase (RT-1). An azido photoaffinity analogue of BI-RG-587 was synthesized and found to irreversibly inhibit the enzyme upon UV irradiation. BI-RG-587 and close structural analogues competitively protected RT-1 from inactivation by the photoaffinity label. A thiobenzimidazolone (TIBO) derivative, a nonnucleoside inhibitor of RT-1, also protected the enzyme from photoinactivation, which suggests a common binding site for these compounds. Substrates dGTP, template-primer, and tRNA afforded no protection from enzyme inactivation. A tritiated photoaffinity probe was found to stoichiometrically and selectively label p66 such that 1 mol of probe inactivates 1 mol of RT-1.

  4. An analogue conceptual rainfall-runoff model for educational purposes

    NASA Astrophysics Data System (ADS)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

    Conceptual rainfall-runoff models, in which runoff processes are modelled with a series of connected linear and non-linear reservoirs, remain widely applied tools in science and practice. Additionally, the concept is appreciated in teaching due to its somewhat simplicity in explaining and exploring hydrological processes of catchments. However, when a series of reservoirs are used, the model system becomes highly parametrized and complex and the traceability of the model results becomes more difficult to explain to an audience not accustomed to numerical modelling. Since normally the simulations are performed with a not visible digital code, the results are also not easily comprehensible. This contribution therefore presents a liquid analogue model, in which a conceptual rainfall-runoff model is reproduced by a physical model. This consists of different acrylic glass containers representing different storage components within a catchment, e.g. soil water or groundwater storage. The containers are equipped and connected with pipes, in which water movement represents different flow processes, e.g. surface runoff, percolation or base flow. Water from a storage container is pumped to the upper part of the model and represents effective rainfall input. The water then flows by gravity through the different pipes and storages. Valves are used for controlling the flows within the analogue model, comparable to the parameterization procedure in numerical models. Additionally, an inexpensive microcontroller-based board and sensors are used to measure storage water levels, with online visualization of the states as time series data, building a bridge between the analogue and digital world. The ability to physically witness the different flows and water levels in the storages makes the analogue model attractive to the audience. Hands-on experiments can be performed with students, in which different scenarios or catchment types can be simulated, not only with the analogue but

  5. Design of peptoid analogue dimers and measure of their affinity for Grb2 SH3 domains.

    PubMed

    Vidal, M; Liu, W-Q; Lenoir, C; Salzmann, J; Gresh, N; Garbay, C

    2004-06-15

    This paper describes the design of the highest affinity ligands for Grb2 SH3 domains reported so far. These compounds were designed by combining N-alkyl amino acid incorporation in a proline-rich sequence with subsequent dimerization of the peptoid sequence based on structural data and molecular modeling. Optimization of the linker size is discussed, and the N-alkyl amino acid incorporation into both monomeric halves is reported. Because the affinity for Grb2 of the optimized compounds was too high to be measured using the fluorescent modifications that they induce on the Grb2 emission spectrum, a competition assay was developed. In this test, Grb2 is pulled down from a cellular extract by the initial VPPPVPPRRR peptide bound to Sepharose beads. In the presence of competitors, the test quantifies the amount of Grb2 displaced from the beads. It has enabled us to determine a K(i) value in the 10(-10) M range for the highest affinity Grb2 peptoid analogue dimer.

  6. A neurosteroid analogue photolabeling reagent labels the colchicine binding site on tubulin: A mass spectrometric analysis

    PubMed Central

    Chen, Zi-Wei; Chen, Li-Hai; Akentieva, Natalia; Lichti, Cheryl F.; Darbandi, Ramin; Hastings, Randy; Covey, Douglas F.; Reichert, David E.; Townsend, R. Reid; Evers, Alex S.

    2013-01-01

    Previous studies have shown that the neurosteroid analogue, 6-Azi-pregnanolone (6-AziP), photolabels voltage-dependent anion channels and proteins of approximately 55 kDa in rat brain membranes. The present study used two dimensional electrophoresis and nano-electrospray ionization ion trap mass spectrometry (nano-ESI-MS) to identify the 55 kDa proteins (pI 4.8) as isoforms of β-tubulin. This identification was confirmed by immuno-blot and immunoprecipitation of photolabeled protein with anti-β-tubulin antibody and by the demonstration that 6-AziP photolabels purified bovine brain tubulin in a concentration-dependent pattern. To identify the photolabeling sites, purified bovine brain tubulin was photolabeled with 6-AziP, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI). A 6-AziP adduct of TAVCDIPPR (m/z=1287.77), a β-tubulin specific peptide, was detected by MALDI. High resolution LC-MS/MS analysis identified that 6-AziP was covalently bound to cysteine 354 (Cys-354), previously identified as a colchicine binding site. 6-AziP photolabeling was inhibited by 2-methoxyestradiol, an endogenous derivative of estradiol thought to bind to the colchicine site. Structural modeling predicted that neurosteroids could dock in this colchicine site at the interface between α- and β-tubulin with the photolabeling group of 6-AziP positioned proximate to Cys-354. PMID:22451060

  7. Bounded excursion stable gravastars and black holes

    SciTech Connect

    Rocha, P; Da Silva, M F; Wang, Anzhong; Santos, N O E-mail: yasuda@on.br E-mail: mfasnic@gmail.com E-mail: anzhong_wang@baylor.edu

    2008-06-15

    Dynamical models of prototype gravastars were constructed in order to study their stability. The models are the Visser-Wiltshire three-layer gravastars, in which an infinitely thin spherical shell of stiff fluid divides the whole spacetime into two regions, where the internal region is de Sitter, and the external one is Schwarzschild. It is found that in some cases the models represent the 'bounded excursion' stable gravastars, where the thin shell is oscillating between two finite radii, while in other cases they collapse until the formation of black holes occurs. In the phase space, the region for the 'bounded excursion' gravastars is very small in comparison to that of black holes, but not empty. Therefore, although the possibility of the existence of gravastars cannot be excluded from such dynamical models, our results indicate that, even if gravastars do indeed exist, that does not exclude the possibility of the existence of black holes.

  8. An error bound for instantaneous coverage

    NASA Technical Reports Server (NTRS)

    White, Allan L.

    1991-01-01

    An error bound is derived for a reliability model approximation method. The approximation method is appropriate for the semi-Markov models of reconfigurable systems that are designed to achieve extremely high reliability. The semi-Markov models of these system are complex, and a significant amount of their complexity arises from the detailed descriptions of the reconfiguration processes. The reliability model approximation method consists of replacing a detailed description of a reconfiguration process with the probabilities of the possible outcomes of the reconfiguration process. These probabilities are included in the model as instantaneous jumps from the fault-occurrence state. Since little time is spent in the reconfiguration states, instantaneous jumps are a close approximation to the original model. This approximation procedure is shown to produce an overestimation for the probability of system failure, and an error bound is derived for this overestimation.

  9. Horizon ratio bound for inflationary fluctuations.

    PubMed

    Dodelson, Scott; Hui, Lam

    2003-09-26

    We demonstrate that the gravity wave background amplitude implies a robust upper bound on the wavelength-to-horizon ratio at the end of inflation: lambda/H(-1) less than or approximately equal e(60), as long as the cosmic energy density does not drop faster than radiation subsequent to inflation. This limit implies that N, the number of e-folds between horizon exit and the end of inflation for wave modes of interest, is less, similar 60 plus a model-dependent factor-for vast classes of slow-roll models, N less than or approximately equal 67. As an example, this bound solidifies the tension between observations of the cosmic microwave background anisotropies and chaotic inflation with a phi(4) potential by closing the escape hatch of large N (<62). PMID:14525296

  10. Extremum seeking with bounded update rates

    SciTech Connect

    Scheinker, Alexander; Krstić, Miroslav

    2013-11-16

    In this work, we present a form of extremum seeking (ES) in which the unknown function being minimized enters the system’s dynamics as the argument of a cosine or sine term, thereby guaranteeing known bounds on update rates and control efforts. We present general n-dimensional optimization and stabilization results as well as 2D vehicle control, with bounded velocity and control efforts. For application to autonomous vehicles, tracking a source in a GPS denied environment with unknown orientation, this ES approach allows for smooth heading angle actuation, with constant velocity, and in application to a unicycle-type vehicle results in control ability as if the vehicle is fully actuated. Our stability analysis is made possible by the classic results of Kurzweil, Jarnik, Sussmann, and Liu, regarding systems with highly oscillatory terms. In our stability analysis, we combine the averaging results with a semi-global practical stability result under small parametric perturbations developed by Moreau and Aeyels.

  11. Tsirelson's bound and supersymmetric entangled states

    PubMed Central

    Borsten, L.; Brádler, K.; Duff, M. J.

    2014-01-01

    A superqubit, belonging to a (2|1)-dimensional super-Hilbert space, constitutes the minimal supersymmetric extension of the conventional qubit. In order to see whether superqubits are more non-local than ordinary qubits, we construct a class of two-superqubit entangled states as a non-local resource in the CHSH game. Since super Hilbert space amplitudes are Grassmann numbers, the result depends on how we extract real probabilities and we examine three choices of map: (1) DeWitt (2) Trigonometric and (3) Modified Rogers. In cases (1) and (2), the winning probability reaches the Tsirelson bound pwin=cos2π/8≃0.8536 of standard quantum mechanics. Case (3) crosses Tsirelson's bound with pwin≃0.9265. Although all states used in the game involve probabilities lying between 0 and 1, case (3) permits other changes of basis inducing negative transition probabilities. PMID:25294964

  12. Is Fusion Inhibited for Weakly Bound Nuclei?

    SciTech Connect

    Takahashi, J.; Munhoz, M.; Szanto, E.M.; Carlin, N.; Added, N.; Suaide, A.A.; de Moura, M.M.; Liguori Neto, R.; Szanto de Toledo, A.; Canto, L.F.

    1997-01-01

    Complete fusion of light radioactive nuclei is predicted to be hindered at near-barrier energies. This feature is investigated in the case of the least bound stable nuclei. Evaporation residues resulting from the {sup 6,7}Li+{sup 9}Be and {sup 6,7}Li+{sup 12}C fusion reactions have been measured in order to study common features in reactions involving light weakly bound nuclei. The experimental excitation functions revealed that the fusion cross section is significantly smaller than the total reaction cross section and also smaller than the fusion cross section expected from the available systematics. A clear correlation between the fusion probability and nucleon (cluster) separation energy has been established.The results suggest that the breakup process has a strong influence on the hindrance of the fusion cross section. {copyright} {ital 1996} {ital The American Physical Society}

  13. Floquet bound states in the continuum

    NASA Astrophysics Data System (ADS)

    Longhi, Stefano; Della Valle, Giuseppe

    2013-07-01

    Quantum mechanics predicts that certain stationary potentials can sustain bound states with an energy buried in the continuous spectrum of scattered states, the so-called bound states in the continuum (BIC). Originally regarded as mathematical curiosities, BIC have found an increasing interest in recent years, particularly in quantum and classical transport of matter and optical waves in mesoscopic and photonic systems where the underlying potential can be judiciously tailored. Most of our knowledge of BIC is so far restricted to static potentials. Here we introduce a new kind of BIC, referred to as Floquet BIC, which corresponds to a normalizable Floquet state of a time-periodic Hamiltonian with a quasienergy embedded into the spectrum of Floquet scattered states. We discuss the appearance of Floquet BIC states in a tight-binding lattice model driven by an ac field in the proximity of the dynamic localization regime.

  14. Reinforcement Learning with Bounded Information Loss

    NASA Astrophysics Data System (ADS)

    Peters, Jan; Mülling, Katharina; Seldin, Yevgeny; Altun, Yasemin

    2011-03-01

    Policy search is a successful approach to reinforcement learning. However, policy improvements often result in the loss of information. Hence, it has been marred by premature convergence and implausible solutions. As first suggested in the context of covariant or natural policy gradients, many of these problems may be addressed by constraining the information loss. In this paper, we continue this path of reasoning and suggest two reinforcement learning methods, i.e., a model-based and a model free algorithm that bound the loss in relative entropy while maximizing their return. The resulting methods differ significantly from previous policy gradient approaches and yields an exact update step. It works well on typical reinforcement learning benchmark problems as well as novel evaluations in robotics. We also show a Bayesian bound motivation of this new approach [8].

  15. Floquet bound states in the continuum

    PubMed Central

    Longhi, Stefano; Valle, Giuseppe Della

    2013-01-01

    Quantum mechanics predicts that certain stationary potentials can sustain bound states with an energy buried in the continuous spectrum of scattered states, the so-called bound states in the continuum (BIC). Originally regarded as mathematical curiosities, BIC have found an increasing interest in recent years, particularly in quantum and classical transport of matter and optical waves in mesoscopic and photonic systems where the underlying potential can be judiciously tailored. Most of our knowledge of BIC is so far restricted to static potentials. Here we introduce a new kind of BIC, referred to as Floquet BIC, which corresponds to a normalizable Floquet state of a time-periodic Hamiltonian with a quasienergy embedded into the spectrum of Floquet scattered states. We discuss the appearance of Floquet BIC states in a tight-binding lattice model driven by an ac field in the proximity of the dynamic localization regime. PMID:23860625

  16. Mutual information rate and bounds for it.

    PubMed

    Baptista, Murilo S; Rubinger, Rero M; Viana, Emilson R; Sartorelli, José C; Parlitz, Ulrich; Grebogi, Celso

    2012-01-01

    The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two time series (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators. PMID:23112809

  17. Bounds for convection between rough boundaries

    NASA Astrophysics Data System (ADS)

    Goluskin, David; Doering, Charles R.

    2016-10-01

    We consider Rayleigh-B\\'enard convection in a layer of fluid between rough no-slip boundaries where the top and bottom boundary heights are functions of the horizontal coordinates with square-integrable gradients. We use the background method to derive an upper bound on mean heat flux across the layer for all admissible boundary geometries. This flux, normalized by the temperature difference between the boundaries, can grow with the Rayleigh number ($Ra$) no faster than ${\\cal O}(Ra^{1/2})$ as $Ra \\rightarrow \\infty$. Our analysis yields a family of similar bounds, depending on how various estimates are tuned, but every version depends explicitly on the boundary geometry. In one version the coefficient of the ${\\cal O}(Ra^{1/2})$ leading term is $0.242 + 2.925\\Vert\

  18. Horizon ratio bound for inflationary fluctuations.

    PubMed

    Dodelson, Scott; Hui, Lam

    2003-09-26

    We demonstrate that the gravity wave background amplitude implies a robust upper bound on the wavelength-to-horizon ratio at the end of inflation: lambda/H(-1) less than or approximately equal e(60), as long as the cosmic energy density does not drop faster than radiation subsequent to inflation. This limit implies that N, the number of e-folds between horizon exit and the end of inflation for wave modes of interest, is less, similar 60 plus a model-dependent factor-for vast classes of slow-roll models, N less than or approximately equal 67. As an example, this bound solidifies the tension between observations of the cosmic microwave background anisotropies and chaotic inflation with a phi(4) potential by closing the escape hatch of large N (<62).

  19. Are Proxima and α Centauri Gravitationally Bound?

    NASA Astrophysics Data System (ADS)

    Wertheimer, Jeremy G.; Laughlin, Gregory

    2006-11-01

    Using the most recent kinematic and radial velocity data in the literature, we calculate the binding energy of Proxima Centauri relative to the center of mass of the α Centauri system. When we adopt the centroids of the observed data, we find that the three stars constitute a bound system, albeit with a semimajor axis that is of order the same size as α Cen AB's Hill radius in the Galactic potential. We carry out a Monte Carlo simulation under the assumption that the errors in the observed quantities are uncorrelated. In this simulation, 44% of the trial systems are bound, and systems on the 1-3 σ tail of the radial velocity distribution can have Proxima currently located near the apastron position of its orbit. Our analysis shows that a further, very significant improvement in the characterization of the system can be gained by obtaining a more accurate measurement of the radial velocity of Proxima Cen.

  20. Scalable problems and memory bounded speedup

    NASA Technical Reports Server (NTRS)

    Sun, Xian-He; Ni, Lionel M.

    1992-01-01

    In this paper three models of parallel speedup are studied. They are fixed-size speedup, fixed-time speedup and memory-bounded speedup. The latter two consider the relationship between speedup and problem scalability. Two sets of speedup formulations are derived for these three models. One set considers uneven workload allocation and communication overhead and gives more accurate estimation. Another set considers a simplified case and provides a clear picture on the impact of the sequential portion of an application on the possible performance gain from parallel processing. The simplified fixed-size speedup is Amdahl's law. The simplified fixed-time speedup is Gustafson's scaled speedup. The simplified memory-bounded speedup contains both Amdahl's law and Gustafson's scaled speedup as special cases. This study leads to a better understanding of parallel processing.

  1. Structural Insight into Methyl-Coenzyme M Reductase Chemistry Using Coenzyme B Analogues

    SciTech Connect

    Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M.

    2010-09-07

    Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis: the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 {angstrom} long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 {angstrom} predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 {angstrom}. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues: pentanoyl, hexanoyl, octanoyl, and nonanoyl derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH, and CoB9SH, respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues

  2. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins.

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  3. Activation of factor IX bound to cultured bovine aortic endothelial cells.

    PubMed Central

    Stern, D M; Drillings, M; Kisiel, W; Nawroth, P; Nossel, H L; LaGamma, K S

    1984-01-01

    Previous studies have shown that factor IX and its activated form, factor IXa, bind to cultured vascular endothelial cells and that cell-bound factor IXa retains its procoagulant activity. The present studies provide evidence that factor IX bound to cultured bovine aortic endothelial cells can be activated. Factor IX activation was assessed by finding cleavage of the factor IX molecule on NaDodSO4/polyacrylamide gel electrophoresis and by the generation of procoagulant activity as assessed by thrombin-treated factor VIII-dependent generation of factor Xa activity. Cell-bound factor IX (0.8 micrograms per 4 X 10(8) cells per ml) could be activated by factor XIa (5 micrograms/ml) or by factor VIIa (0.1 micrograms/ml) without exogenous tissue factor when endothelial cells were treated with phorbol ester and acquired tissue factor-like procoagulant activity. Regardless of how factor IX was activated, the cell-bound factor IXa required thrombin-treated factor VIII and calcium, but not exogenous phospholipid, to activate factor X. In further experiments, factor X bound to endothelial cells specifically and reversibly with a dependence on calcium and with a lower affinity (half-maximal at 480 nM) than factor IX. At saturation, 9.1 X 10(6) factor X molecules were bound per cell. After activation of factor X by factor IXa, approximately 50% of the factor Xa formed could be eluted from the cells by 10 mM EDTA, suggesting that the factor Xa was cell associated. These observations indicate that endothelial cells can bind and promote the activation of factors IX and X in the absence of platelets or exogenous phospholipid. PMID:6608105

  4. Reductive mobilization of oxide-bound metals

    SciTech Connect

    Stone, A.T.

    1991-01-01

    We have completed a large number of experiments which examine the release of MnO{sub 2}-bound Co, Ni, and Cu. Our work has focused upon the following areas: (1) competitive adsorption among the three toxic metals and Mn(II); (2) toxic metal release upon addition of low MW organic reductants and complexants; and (3) toxic metal release upon addition of natural organic matter-rich surface waters and IHSS organic matter reference material.

  5. Upper and lower bounds on quantum codes

    NASA Astrophysics Data System (ADS)

    Smith, Graeme Stewart Baird

    This thesis provides bounds on the performance of quantum error correcting codes when used for quantum communication and quantum key distribution. The first two chapters provide a bare-bones introduction to classical and quantum error correcting codes, respectively. The next four chapters present achievable rates for quantum codes in various scenarios. The final chapter is dedicated to an upper bound on the quantum channel capacity. Chapter 3 studies coding for adversarial noise using quantum list codes, showing there exist quantum codes with high rates and short lists. These can be used, together with a very short secret key, to communicate with high fidelity at noise levels for which perfect fidelity is, impossible. Chapter 4 explores the performance of a family of degenerate codes when used to communicate over Pauli channels, showing they can be used to communicate over almost any Pauli channel at rates that are impossible for a nondegenerate code and that exceed those of previously known degenerate codes. By studying the scaling of the optimal block length as a function of the channel's parameters, we develop a heuristic for designing even better codes. Chapter 5 describes an equivalence between a family of noisy preprocessing protocols for quantum key distribution and entanglement distillation protocols whose target state belongs to a class of private states called "twisted states." In Chapter 6, the codes of Chapter 4 are combined with the protocols of Chapter 5 to provide higher key rates for one-way quantum key distribution than were previously thought possible. Finally, Chapter 7 presents a new upper bound on the quantum channel capacity that is both additive and convex, and which can be interpreted as the capacity of the channel for communication given access to side channels from a class of zero capacity "cloning" channels. This "clone assisted capacity" is equal to the unassisted capacity for channels that are degradable, which we use to find new upper

  6. Efficiency bounds for nonequilibrium heat engines

    SciTech Connect

    Mehta, Pankaj; Polkovnikov, Anatoli

    2013-05-15

    We analyze the efficiency of thermal engines (either quantum or classical) working with a single heat reservoir like an atmosphere. The engine first gets an energy intake, which can be done in an arbitrary nonequilibrium way e.g. combustion of fuel. Then the engine performs the work and returns to the initial state. We distinguish two general classes of engines where the working body first equilibrates within itself and then performs the work (ergodic engine) or when it performs the work before equilibrating (non-ergodic engine). We show that in both cases the second law of thermodynamics limits their efficiency. For ergodic engines we find a rigorous upper bound for the efficiency, which is strictly smaller than the equivalent Carnot efficiency. I.e. the Carnot efficiency can be never achieved in single reservoir heat engines. For non-ergodic engines the efficiency can be higher and can exceed the equilibrium Carnot bound. By extending the fundamental thermodynamic relation to nonequilibrium processes, we find a rigorous thermodynamic bound for the efficiency of both ergodic and non-ergodic engines and show that it is given by the relative entropy of the nonequilibrium and initial equilibrium distributions. These results suggest a new general strategy for designing more efficient engines. We illustrate our ideas by using simple examples. -- Highlights: ► Derived efficiency bounds for heat engines working with a single reservoir. ► Analyzed both ergodic and non-ergodic engines. ► Showed that non-ergodic engines can be more efficient. ► Extended fundamental thermodynamic relation to arbitrary nonequilibrium processes.

  7. Weakly bound states in heterogeneous waveguides

    NASA Astrophysics Data System (ADS)

    Amore, Paolo; Fernández, Francisco M.; Hofmann, Christoph P.

    2016-07-01

    We study the spectrum of the Helmholtz equation in a two-dimensional infinite waveguide, containing a weak heterogeneity localized at an internal point, and obeying Dirichlet boundary conditions at its border. We use the variational theorem to derive the condition for which the lowest eigenvalue of the spectrum falls below the continuum threshold and a bound state appears, localized at the heterogeneity. We devise a rigorous perturbation scheme and derive the exact expression for the energy to third order in the heterogeneity.

  8. Multipartite secret key distillation and bound entanglement

    SciTech Connect

    Augusiak, Remigiusz; Horodecki, Pawel

    2009-10-15

    Recently it has been shown that quantum cryptography beyond pure entanglement distillation is possible and a paradigm for the associated protocols has been established. Here we systematically generalize the whole paradigm to the multipartite scenario. We provide constructions of new classes of multipartite bound entangled states, i.e., those with underlying twisted Greenberger-Horne-Zeilinger (GHZ) structure and nonzero distillable cryptographic key. We quantitatively estimate the key from below with the help of the privacy squeezing technique.

  9. Detecting Lower Bounds to Quantum Channel Capacities.

    PubMed

    Macchiavello, Chiara; Sacchi, Massimiliano F

    2016-04-01

    We propose a method to detect lower bounds to quantum capacities of a noisy quantum communication channel by means of a few measurements. The method is easily implementable and does not require any knowledge about the channel. We test its efficiency by studying its performance for most well-known single-qubit noisy channels and for the generalized Pauli channel in an arbitrary finite dimension.

  10. {bar K}-NUCLEAR Deeply Bound States?

    NASA Astrophysics Data System (ADS)

    Gal, Avraham

    Following the prediction by Akaishi and Yamazaki of relatively narrow {bar K}-nuclear states, deeply bound by over 100 MeV where the main decay channel {bar K} N -> π Σ is closed, several experimental signals in stopped K- reactions on light nuclei have been interpreted recently as due to such states. In this talk I review (i) the evidence from K--atom data for a deep bar K-nucleus potential, as attractive as V{bar K}(ρ 0) ˜ -(150 - 200) MeV at nuclear matter density, that could support such states; and (ii) the theoretical arguments for a shallow potential, V{bar K}(ρ 0) ˜ -(40 - 60) MeV. I then review a recent work by Mareš, Friedman and Gal in which {bar K}-nuclear bound states are generated dynamically across the periodic table, using a RMF Lagrangian that couples the {bar K} to the scalar and vector meson fields mediating the nuclear interactions. The reduced phase space available for {bar K} absorption from these bound states is taken into account by adding a density- and energy-dependent imaginary term, underlying the corresponding {bar K}-nuclear level widths, with a strength constrained by K--atom fits. Substantial polarization of the core nucleus is found for light nuclei, with central nuclear densities enhanced by almost a factor of two. The binding energies and widths calculated in this dynamical model differ appreciably from those calculated for a static nucleus. These calculations provide a lower limit of Γ {bar K} ˜ 50 ± 10 MeV on the width of nuclear bound states for {bar K} binding energy in the range B{bar K} = 100 - 200 MeV.

  11. Exact BPS bound for noncommutative baby Skyrmions

    NASA Astrophysics Data System (ADS)

    Domrin, Andrei; Lechtenfeld, Olaf; Linares, Román; Maceda, Marco

    2013-11-01

    The noncommutative baby Skyrme model is a Moyal deformation of the two-dimensional sigma model plus a Skyrme term, with a group-valued or Grassmannian target. Exact abelian solitonic solutions have been identified analytically in this model, with a singular commutative limit. Inside any given Grassmannian, we establish a BPS bound for the energy functional, which is saturated by these baby Skyrmions. This asserts their stability for unit charge, as we also test in second-order perturbation theory.

  12. A simple, nondestructive assay for bound hyaluronan.

    PubMed

    Johnston, J B

    2000-01-01

    A simple, convenient, nondestructive method is described for the quantitative determination of bound hyaluronan. The method is based on the binding of the cationic dye Toluidine Blue O to the D-glucuronate component of the hyaluronan repeat disaccharide. Quantification is accomplished without interference by the dye's metachromatic properties. The method is easily adapted to hyaluronan coated medical devices and should be useful to developers and manufacturers of such devices and coatings.

  13. Experimental implementation of reverse time migration for nondestructive evaluation applications.

    PubMed

    Anderson, Brian E; Griffa, Michele; Bas, Pierre-Yves Le; Ulrich, Timothy J; Johnson, Paul A

    2011-01-01

    Reverse time migration (RTM) is a commonly employed imaging technique in seismic applications (e.g., to image reservoirs of oil). Its standard implementation cannot account for multiple scattering/reverberation. For this reason it has not yet found application in nondestructive evaluation (NDE). This paper applies RTM imaging to NDE applications in bounded samples, where reverberation is always present. This paper presents a fully experimental implementation of RTM, whereas in seismic applications, only part of the procedure is done experimentally. A modified RTM imaging condition is able to localize scatterers and locations of disbonding. Experiments are conducted on aluminum samples with controlled scatterers.

  14. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  15. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  16. Of Models and Machines: Implementing Bounded Rationality.

    PubMed

    Dick, Stephanie

    2015-09-01

    This essay explores the early history of Herbert Simon's principle of bounded rationality in the context of his Artificial Intelligence research in the mid 1950s. It focuses in particular on how Simon and his colleagues at the RAND Corporation translated a model of human reasoning into a computer program, the Logic Theory Machine. They were motivated by a belief that computers and minds were the same kind of thing--namely, information-processing systems. The Logic Theory Machine program was a model of how people solved problems in elementary mathematical logic. However, in making this model actually run on their 1950s computer, the JOHNNIAC, Simon and his colleagues had to navigate many obstacles and material constraints quite foreign to the human experience of logic. They crafted new tools and engaged in new practices that accommodated the affordances of their machine, rather than reflecting the character of human cognition and its bounds. The essay argues that tracking this implementation effort shows that "internal" cognitive practices and "external" tools and materials are not so easily separated as they are in Simon's principle of bounded rationality--the latter often shaping the dynamics of the former. PMID:26685521

  17. Of Models and Machines: Implementing Bounded Rationality.

    PubMed

    Dick, Stephanie

    2015-09-01

    This essay explores the early history of Herbert Simon's principle of bounded rationality in the context of his Artificial Intelligence research in the mid 1950s. It focuses in particular on how Simon and his colleagues at the RAND Corporation translated a model of human reasoning into a computer program, the Logic Theory Machine. They were motivated by a belief that computers and minds were the same kind of thing--namely, information-processing systems. The Logic Theory Machine program was a model of how people solved problems in elementary mathematical logic. However, in making this model actually run on their 1950s computer, the JOHNNIAC, Simon and his colleagues had to navigate many obstacles and material constraints quite foreign to the human experience of logic. They crafted new tools and engaged in new practices that accommodated the affordances of their machine, rather than reflecting the character of human cognition and its bounds. The essay argues that tracking this implementation effort shows that "internal" cognitive practices and "external" tools and materials are not so easily separated as they are in Simon's principle of bounded rationality--the latter often shaping the dynamics of the former.

  18. Lanczos iterated time-reversal.

    PubMed

    Oberai, Assad A; Feijóo, Gonzalo R; Barbone, Paul E

    2009-02-01

    A new iterative time-reversal algorithm capable of identifying and focusing on multiple scatterers in a relatively small number of iterations is developed. It is recognized that the traditional iterated time-reversal method is based on utilizing power iterations to determine the dominant eigenpairs of the time-reversal operator. The convergence properties of these iterations are known to be suboptimal. Motivated by this, a new method based on Lanczos iterations is developed. In several illustrative examples it is demonstrated that for the same number of transmitted and received signals, the Lanczos iterations based approach is substantially more accurate. PMID:19206835

  19. Reverse mortgage decision-making.

    PubMed

    Leviton, R

    2001-01-01

    Reverse mortgages have been suggested as a promising financial tool to help low-income older homeowners who want to remain in their houses. However, actual use of this option has been much below early estimates of potential demand. This study explored response to the new option through open-ended interviews of homeowners who had received reverse mortgage counseling. Decision-making was influenced by attachment to home, family input, and financial attitudes, including desire to leave a legacy. In general, homeowners took reverse mortgages only as a "last resort" that enabled them to maintain their independence.

  20. Reversible dilatancy in entangled single-wire materials.

    PubMed

    Rodney, David; Gadot, Benjamin; Martinez, Oriol Riu; du Roscoat, Sabine Rolland; Orgéas, Laurent

    2016-01-01

    Designing structures that dilate rapidly in both tension and compression would benefit devices such as smart filters, actuators or fasteners. This property however requires an unusual Poisson ratio, or Poisson function at finite strains, which has to vary with applied strain and exceed the familiar bounds: less than 0 in tension and above 1/2 in compression. Here, by combining mechanical tests and discrete element simulations, we show that a simple three-dimensional architected material, made of a self-entangled single long coiled wire, behaves in between discrete and continuum media, with a large and reversible dilatancy in both tension and compression. This unusual behaviour arises from an interplay between the elongation of the coiled wire and rearrangements due to steric effects, which, unlike in traditional discrete media, are hysteretically reversible when the architecture is made of an elastic fibre.

  1. Reversible dilatancy in entangled single-wire materials.

    PubMed

    Rodney, David; Gadot, Benjamin; Martinez, Oriol Riu; du Roscoat, Sabine Rolland; Orgéas, Laurent

    2016-01-01

    Designing structures that dilate rapidly in both tension and compression would benefit devices such as smart filters, actuators or fasteners. This property however requires an unusual Poisson ratio, or Poisson function at finite strains, which has to vary with applied strain and exceed the familiar bounds: less than 0 in tension and above 1/2 in compression. Here, by combining mechanical tests and discrete element simulations, we show that a simple three-dimensional architected material, made of a self-entangled single long coiled wire, behaves in between discrete and continuum media, with a large and reversible dilatancy in both tension and compression. This unusual behaviour arises from an interplay between the elongation of the coiled wire and rearrangements due to steric effects, which, unlike in traditional discrete media, are hysteretically reversible when the architecture is made of an elastic fibre. PMID:26413988

  2. Design and synthesis of analogues of natural products.

    PubMed

    Maier, Martin E

    2015-05-21

    In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error. PMID:25829247

  3. All-dielectric metasurface analogue of electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Yang, Yuanmu; Kravchenko, Ivan I.; Briggs, Dayrl P.; Valentine, Jason

    2014-12-01

    Metasurface analogues of electromagnetically induced transparency (EIT) have been a focus of the nanophotonics field in recent years, due to their ability to produce high-quality factor (Q-factor) resonances. Such resonances are expected to be useful for applications such as low-loss slow-light devices and highly sensitive optical sensors. However, ohmic losses limit the achievable Q-factors in conventional plasmonic EIT metasurfaces to values <~10, significantly hampering device performance. Here we experimentally demonstrate a classical analogue of EIT using all-dielectric silicon-based metasurfaces. Due to extremely low absorption loss and coherent interaction of neighbouring meta-atoms, a Q-factor of 483 is observed, leading to a refractive index sensor with a figure-of-merit of 103. Furthermore, we show that the dielectric metasurfaces can be engineered to confine the optical field in either the silicon resonator or the environment, allowing one to tailor light-matter interaction at the nanoscale.

  4. Analogue Transformations in Physics and their Application to Acoustics

    PubMed Central

    García-Meca, C.; Carloni, S.; Barceló, C.; Jannes, G.; Sánchez-Dehesa, J.; Martínez, A.

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an “analogue transformation acoustics” formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  5. Analogue transformations in physics and their application to acoustics.

    PubMed

    García-Meca, C; Carloni, S; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft.

  6. Neurological Effects of Bisphenol A and its Analogues

    PubMed Central

    Inadera, Hidekuni

    2015-01-01

    The endocrine disrupting chemical bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. The use of BPA-containing products in daily life makes exposure ubiquitous, and the potential human health risks of this chemical are a major public health concern. Although numerous in vitro and in vivo studies have been published on the effects of BPA on biological systems, there is controversy as to whether ordinary levels of exposure can have adverse effects in humans. However, the increasing incidence of developmental disorders is of concern, and accumulating evidence indicates that BPA has detrimental effects on neurological development. Other bisphenol analogues, used as substitutes for BPA, are also suspected of having a broad range of biological actions. The objective of this review is to summarize our current understanding of the neurobiological effects of BPA and its analogues, and to discuss preventive strategies from a public health perspective. PMID:26664253

  7. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents

    PubMed Central

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-01-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%–35% inhibition at the end of the experiment. PMID:27136567

  8. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  9. Neurological Effects of Bisphenol A and its Analogues.

    PubMed

    Inadera, Hidekuni

    2015-01-01

    The endocrine disrupting chemical bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. The use of BPA-containing products in daily life makes exposure ubiquitous, and the potential human health risks of this chemical are a major public health concern. Although numerous in vitro and in vivo studies have been published on the effects of BPA on biological systems, there is controversy as to whether ordinary levels of exposure can have adverse effects in humans. However, the increasing incidence of developmental disorders is of concern, and accumulating evidence indicates that BPA has detrimental effects on neurological development. Other bisphenol analogues, used as substitutes for BPA, are also suspected of having a broad range of biological actions. The objective of this review is to summarize our current understanding of the neurobiological effects of BPA and its analogues, and to discuss preventive strategies from a public health perspective. PMID:26664253

  10. Acoustic clouds: Standing sound waves around a black hole analogue

    NASA Astrophysics Data System (ADS)

    Benone, Carolina L.; Crispino, Luís C. B.; Herdeiro, Carlos; Radu, Eugen

    2015-05-01

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  11. Noncommutative analogue Aharonov-Bohm effect and superresonance

    NASA Astrophysics Data System (ADS)

    Anacleto, M. A.; Brito, F. A.; Passos, E.

    2013-06-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  12. Analogue transformations in physics and their application to acoustics.

    PubMed

    García-Meca, C; Carloni, S; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  13. Synthesis and antioxidant activities of Coenzyme Q analogues.

    PubMed

    Wang, Jin; Li, Shuo; Yang, Tao; Yang, Jian

    2014-10-30

    A series of 2,3-dimethoxy-5-methyl-1,4-benzoquinones (Coenzyme Q) substituted at the C-6 position with various groups were designed and synthesized based on the Coenzyme Q10 as potent antioxidant. In vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidant Coenzyme Q10 employing DPPH assay. All these synthesized Coenzyme Q analogues are found to exhibit good antioxidant activities. Of which Compound 8b bearing a N-benzoylpiperazine group at the C-6 position showed more potent inhibition of DPPH radical than Coenzyme Q10. All these results suggested the applicability of the Coenzyme Q analogues as potent antioxidants for combating oxidative stress.

  14. Millimeter and Submillimeter Studies of Interstellar Ice Analogues

    NASA Astrophysics Data System (ADS)

    Mesko, AJ; Wagner, Ian C.; Smith, Houston Hartwell; Milam, Stefanie N.; Widicus Weaver, Susanna L.

    2015-06-01

    The chemistry of interstellar ice analogues has been a topic of great interest to astrochemists over the last 20 years. Currently, the models of interstellar chemistry feature icy-grain reactions as a primary mechanism for the formation of many astrochemical species as well as potentially astrobiologically-relevant complex organic molecules. This talk presents new spectral results collected by a millimeter and submillimeter spectrometer coupled to a vacuum chamber designed to study the sublimation or sputtered products of icy-grain reactions initiated by thermal-processing or photo-processing of interstellar ice analogues. Initial results from thermal desorption and UV photoprocessing experiments of pure water ice and water + methanol ice mixtures will be presented.

  15. Alligator rivers analogue project an OECD/NEA international project

    SciTech Connect

    Duerden, P.; Airey, P.; Pescatore, C.

    1994-12-31

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained.

  16. Geoscience in Support of a Mars Methane Analogue Mission

    NASA Astrophysics Data System (ADS)

    Boivin, Alexandre

    The Mars Methane Analogue Mission, funded by the Canadian Space Agency through its Analogue Missions program, simulates a Mars rover mission whose purpose is to detect, analyse, and determine the source of methane emissions on the planet's surface. As part of this project, both an electromagnetic induction sounder (EMIS) and a high-resolution triangulation-based 3D laser scanner were tested in the field to demonstrate the benefit of including these instruments on future rover missions. EMIS data was inverted in order to derive information on the conductivity and magnetic susceptibility of the near subsurface. 3D laser scanner data was processed with fracture detection as a goal in order to simplify the search for areas of potential methane seepage. Both instruments were found to be very valuable for future rover missions of this type.

  17. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    SciTech Connect

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  18. Synthesis and biological activity of polyalthenol and pentacyclindole analogues.

    PubMed

    Marcos, Isidro S; Moro, Rosalina F; Costales, Isabel; Basabe, Pilar; Díez, David; Gil, Ana; Mollinedo, Faustino; Pérez-de la Rosa, Fátima; Pérez-Roth, Eduardo; Padrón, José M

    2014-02-12

    A series of indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid in order to test their biological activity. These analogues include diverse oxidation levels at the sesquiterpenyl moiety and different functionalization on the indole ring. All synthetic derivatives were tested against a representative panel of Gram positive and Gram negative bacterial strains, and the human solid tumour cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). Overall, the compounds presented activity against the cancer cell lines. The resulting lead, displaying a polyalthenol scaffold, showed GI50 values in the range 1.2-5.7 μM against all cell lines tested. PMID:24412720

  19. Bound states of Dirac fermions in monolayer gapped graphene in the presence of local perturbations

    NASA Astrophysics Data System (ADS)

    Mohsen, Yarmohammadi; Malek, Zareyan

    2016-06-01

    In graphene, conductance electrons behave as massless relativistic particles and obey an analogue of the Dirac equation in two dimensions with a chiral nature. For this reason, the bounding of electrons in graphene in the form of geometries of quantum dots is impossible. In gapless graphene, due to its unique electronic band structure, there is a minimal conductivity at Dirac points, that is, in the limit of zero doping. This creates a problem for using such a highly motivated new material in electronic devices. One of the ways to overcome this problem is the creation of a band gap in the graphene band structure, which is made by inversion symmetry breaking (symmetry of sublattices). We investigate the confined states of the massless Dirac fermions in an impured graphene by the short-range perturbations for “local chemical potential” and “local gap”. The calculated energy spectrum exhibits quite different features with and without the perturbations. A characteristic equation for bound states (BSs) has been obtained. It is surprisingly found that the relation between the radial functions of sublattices wave functions, i.e., , , and , , can be established by SO(2) group.

  20. OptZyme: Computational Enzyme Redesign Using Transition State Analogues

    PubMed Central

    Grisewood, Matthew J.; Gifford, Nathanael P.; Pantazes, Robert J.; Li, Ye; Cirino, Patrick C.; Janik, Michael J.; Maranas, Costas D.

    2013-01-01

    OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to use transition state analogue compounds, which are known for many reactions, as proxies for the typically unknown transition state structures. Mutations that minimize the interaction energy of the enzyme with its transition state analogue, rather than with its substrate, are identified that lower the transition state formation energy barrier. Using Escherichia coli β-glucuronidase as a benchmark system, we confirm that KM correlates (R2 = 0.960) with the computed interaction energy between the enzyme and the para-nitrophenyl- β, D-glucuronide substrate, kcat/KM correlates (R2 = 0.864) with the interaction energy of the transition state analogue, 1,5-glucarolactone, and kcat correlates (R2 = 0.854) with a weighted combination of interaction energies with the substrate and transition state analogue. OptZyme is subsequently used to identify mutants with improved KM, kcat, and kcat/KM for a new substrate, para-nitrophenyl- β, D-galactoside. Differences between the three libraries reveal structural differences that underpin improving KM, kcat, or kcat/KM. Mutants predicted to enhance the activity for para-nitrophenyl- β, D-galactoside directly or indirectly create hydrogen bonds with the altered sugar ring conformation or its substituents, namely H162S, L361G, W549R, and N550S. PMID:24116038