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Sample records for maximally bound ligand

  1. Finding Maximal Pairs with Bounded Gap

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Lyngsø, Rune B.; Pedersen, Christian N. S.

    1999-01-01

    . In this paper we present methods for finding all maximal pairs under various constraints on the gap. In a string of length n we can find all maximal pairs with gap in an upper and lower bounded interval in time O(n log n+z) where z is the number of reported pairs. If the upper bound is removed the time reduces...... to O(n+z). Since a tandem repeat is a pair where the gap is zero, our methods can be seen as a generalization of finding tandem repeats. The running time of our methods equals the running time of well known methods for finding tandem repeats....

  2. Ligand Depot: a data warehouse for ligands bound to macromolecules.

    Science.gov (United States)

    Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

    2004-09-01

    Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

  3. Maximal lens bounds on QSO-galaxy association

    International Nuclear Information System (INIS)

    Kovner, I.

    1989-01-01

    The maximal possible enhancement of QSO number counts that can be produced by any ensemble of lenses which conserve brightness and in which the magnification probability is negligibly correlated with the intrinsic QSO flux is obtained. Under the assumption of the Boyle et al. (1988) number-magnitude relation for the QSOs unaffected by lenses, the theory is applied to the QSO-galaxy association sample of Webster et al. (1988). The results suggest that the background QSOs of Webster et al. may be appreciably affected by lensing. 17 refs

  4. Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

    Science.gov (United States)

    Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

    2016-09-01

    We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

  5. Ligand-free, protein-bound technetium-99m. Evidence for tumour localisation

    International Nuclear Information System (INIS)

    Jakovljevic, A.C.; Pojer, P.M.

    1984-11-01

    An hypothesis that cations accumulate in tumours independent of ligand is tested. A preparation of technetium-99m known to be ligand-free (that is, the technetium is protein bound and no other ligand is injected) has been shown to accumulate in a T-cell lymphoma

  6. Bounds on absolutely maximally entangled states from shadow inequalities, and the quantum MacWilliams identity

    Science.gov (United States)

    Huber, Felix; Eltschka, Christopher; Siewert, Jens; Gühne, Otfried

    2018-04-01

    A pure multipartite quantum state is called absolutely maximally entangled (AME), if all reductions obtained by tracing out at least half of its parties are maximally mixed. Maximal entanglement is then present across every bipartition. The existence of such states is in many cases unclear. With the help of the weight enumerator machinery known from quantum error correction and the shadow inequalities, we obtain new bounds on the existence of AME states in dimensions larger than two. To complete the treatment on the weight enumerator machinery, the quantum MacWilliams identity is derived in the Bloch representation. Finally, we consider AME states whose subsystems have different local dimensions, and present an example for a 2×3×3×3 system that shows maximal entanglement across every bipartition.

  7. Tight upper bound for the maximal quantum value of the Svetlichny operators

    Science.gov (United States)

    Li, Ming; Shen, Shuqian; Jing, Naihuan; Fei, Shao-Ming; Li-Jost, Xianqing

    2017-10-01

    It is a challenging task to detect genuine multipartite nonlocality (GMNL). In this paper, the problem is considered via computing the maximal quantum value of Svetlichny operators for three-qubit systems and a tight upper bound is obtained. The constraints on the quantum states for the tightness of the bound are also presented. The approach enables us to give the necessary and sufficient conditions of violating the Svetlichny inequality (SI) for several quantum states, including the white and color noised Greenberger-Horne-Zeilinger (GHZ) states. The relation between the genuine multipartite entanglement concurrence and the maximal quantum value of the Svetlichny operators for mixed GHZ class states is also discussed. As the SI is useful for the investigation of GMNL, our results give an effective and operational method to detect the GMNL for three-qubit mixed states.

  8. A python-based docking program utilizing a receptor bound ligand shape: PythDock.

    Science.gov (United States)

    Chung, Jae Yoon; Cho, Seung Joo; Hah, Jung-Mi

    2011-09-01

    PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design.

  9. A Reward-Maximizing Spiking Neuron as a Bounded Rational Decision Maker.

    Science.gov (United States)

    Leibfried, Felix; Braun, Daniel A

    2015-08-01

    Rate distortion theory describes how to communicate relevant information most efficiently over a channel with limited capacity. One of the many applications of rate distortion theory is bounded rational decision making, where decision makers are modeled as information channels that transform sensory input into motor output under the constraint that their channel capacity is limited. Such a bounded rational decision maker can be thought to optimize an objective function that trades off the decision maker's utility or cumulative reward against the information processing cost measured by the mutual information between sensory input and motor output. In this study, we interpret a spiking neuron as a bounded rational decision maker that aims to maximize its expected reward under the computational constraint that the mutual information between the neuron's input and output is upper bounded. This abstract computational constraint translates into a penalization of the deviation between the neuron's instantaneous and average firing behavior. We derive a synaptic weight update rule for such a rate distortion optimizing neuron and show in simulations that the neuron efficiently extracts reward-relevant information from the input by trading off its synaptic strengths against the collected reward.

  10. Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans

    International Nuclear Information System (INIS)

    Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R.; Chiang, Janet; Gunsalus, Robert P.; Arbing, Mark A.; Perry, L. Jeanne

    2010-01-01

    Crystal structures of ModA from M. acetivorans in the apo and ligand-bound conformations confirm domain rotation upon ligand binding. The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 Å resolution and in the molybdate-bound conformation at 2.25 and 2.45 Å resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed α/β domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the ‘Venus flytrap’ model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins

  11. Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

    Science.gov (United States)

    Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

    2014-10-27

    The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

  12. Measuring binding of protein to gel-bound ligands using magnetic levitation.

    Science.gov (United States)

    Shapiro, Nathan D; Mirica, Katherine A; Soh, Siowling; Phillips, Scott T; Taran, Olga; Mace, Charles R; Shevkoplyas, Sergey S; Whitesides, George M

    2012-03-28

    This paper describes the use of magnetic levitation (MagLev) to measure the association of proteins and ligands. The method starts with diamagnetic gel beads that are functionalized covalently with small molecules (putative ligands). Binding of protein to the ligands within the bead causes a change in the density of the bead. When these beads are suspended in a paramagnetic aqueous buffer and placed between the poles of two NbFeB magnets with like poles facing, the changes in the density of the bead on binding of protein result in changes in the levitation height of the bead that can be used to quantify the amount of protein bound. This paper uses a reaction-diffusion model to examine the physical principles that determine the values of rate and equilibrium constants measured by this system, using the well-defined model system of carbonic anhydrase and aryl sulfonamides. By tuning the experimental protocol, the method is capable of quantifying either the concentration of protein in a solution, or the binding affinities of a protein to several resin-bound small molecules simultaneously. Since this method requires no electricity and only a single piece of inexpensive equipment, it may find use in situations where portability and low cost are important, such as in bioanalysis in resource-limited settings, point-of-care diagnosis, veterinary medicine, and plant pathology. It still has several practical disadvantages. Most notably, the method requires relatively long assay times and cannot be applied to large proteins (>70 kDa), including antibodies. The design and synthesis of beads with improved characteristics (e.g., larger pore size) has the potential to resolve these problems.

  13. pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins.

    Directory of Open Access Journals (Sweden)

    Priyanka Prakash

    2015-10-01

    Full Text Available Probe-based or mixed solvent molecular dynamics simulation is a useful approach for the identification and characterization of druggable sites in drug targets. However, thus far the method has been applied only to soluble proteins. A major reason for this is the potential effect of the probe molecules on membrane structure. We have developed a technique to overcome this limitation that entails modification of force field parameters to reduce a few pairwise non-bonded interactions between selected atoms of the probe molecules and bilayer lipids. We used the resulting technique, termed pMD-membrane, to identify allosteric ligand binding sites on the G12D and G13D oncogenic mutants of the K-Ras protein bound to a negatively charged lipid bilayer. In addition, we show that differences in probe occupancy can be used to quantify changes in the accessibility of druggable sites due to conformational changes induced by membrane binding or mutation.

  14. Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor.

    Science.gov (United States)

    Solt, Andras S; Bostock, Mark J; Shrestha, Binesh; Kumar, Prashant; Warne, Tony; Tate, Christopher G; Nietlispach, Daniel

    2017-11-27

    A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., G s and β-arrestin. Using 13 C methyl methionine NMR for the β 1 -adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with G s -mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody-receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamics are observed ranging from rigid nanobody-coupled states to extensive μs-to-ms timescale dynamics when bound to a full agonist. We suggest that the mobility of the full agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary complex, ligand efficacy determines the quality of the interaction between the rigidified receptor and an IBP and consequently the signalling level.

  15. Versatile gradients of chemistry, bound ligands and nanoparticles on alumina nanopore arrays

    International Nuclear Information System (INIS)

    Michelmore, Andrew; Poh, Zihan; Goreham, Renee V; Short, Robert D; Vasilev, Krasimir; Mierczynska, Agnieszka; Losic, Dusan

    2011-01-01

    Nanoporous alumina (PA) arrays produced by self-ordering growth, using electrochemical anodization, have been extensively explored for potential applications based upon the unique thermal, mechanical and structural properties, and high surface-to-volume ratio of these materials. However, the potential applications and functionality of these materials may be further extended by molecular-level engineering of the surface of the pore rims. In this paper we present a method for the generation of chemical gradients on the surface of PA arrays based upon plasma co-polymerization of two monomers. We further extend these chemical gradients, which are also gradients of surface charge, to those of bound ligands and number density gradients of nanoparticles. The latter represent a highly exotic new class of materials, comprising aligned PA, capped by gold nanoparticles around the rim of the pores. Gradients of chemistry, ligands and nanoparticles generated by our method retain the porous structure of the substrate, which is important in applications that take advantage of the inherent properties of these materials. This method can be readily extended to other porous materials.

  16. Versatile gradients of chemistry, bound ligands and nanoparticles on alumina nanopore arrays

    Energy Technology Data Exchange (ETDEWEB)

    Michelmore, Andrew; Poh, Zihan; Goreham, Renee V; Short, Robert D; Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes, SA 5095, Adelaide (Australia); Mierczynska, Agnieszka; Losic, Dusan, E-mail: Krasimir.vasilev@unisa.edu.au [Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Adelaide (Australia)

    2011-10-14

    Nanoporous alumina (PA) arrays produced by self-ordering growth, using electrochemical anodization, have been extensively explored for potential applications based upon the unique thermal, mechanical and structural properties, and high surface-to-volume ratio of these materials. However, the potential applications and functionality of these materials may be further extended by molecular-level engineering of the surface of the pore rims. In this paper we present a method for the generation of chemical gradients on the surface of PA arrays based upon plasma co-polymerization of two monomers. We further extend these chemical gradients, which are also gradients of surface charge, to those of bound ligands and number density gradients of nanoparticles. The latter represent a highly exotic new class of materials, comprising aligned PA, capped by gold nanoparticles around the rim of the pores. Gradients of chemistry, ligands and nanoparticles generated by our method retain the porous structure of the substrate, which is important in applications that take advantage of the inherent properties of these materials. This method can be readily extended to other porous materials.

  17. The exact LPT-bound for maximizing the minimum completion time

    NARCIS (Netherlands)

    Csirik, J.; Kellerer, H.; Woeginger, G.J.

    1992-01-01

    We consider the problem of assigning a set of jobs to a system of m identical processors in order to maximize the earliest processor completion time. It was known that the LPT-heuristic gives an approximation of worst case ratio at most 3/4. In this note we show that the exact worst case ratio of

  18. Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans.

    Science.gov (United States)

    Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R; Chiang, Janet; Gunsalus, Robert P; Arbing, Mark A; Perry, L Jeanne

    2010-03-01

    The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 A resolution and in the molybdate-bound conformation at 2.25 and 2.45 A resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed alpha/beta domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the 'Venus flytrap' model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins.

  19. Ligand-free, protein-bound technetium-99m iron-dextran enhancement of technetium pyrophosphate uptake in tumours

    International Nuclear Information System (INIS)

    Pojer, P.M.; Jakovljevic, A.C.; Wise, K.N.

    1985-01-01

    The biodistribution of technetium-99m was studied in T-cell lymphoma and selected organs of iron-dextran treated and control mice given technetium-99m pyrophosphate. The results showed that high serum iron levels increased tumour uptake of technetium pyrophosphate. This supports the hypothesis that technetium, in common with other metal-based tumour seeking radiopharmaceuticals, is transported to tumours as a ligand-free protein-bound cation. (U.K.)

  20. In vitro evaluation of biodegradable microspheres with surface-bound ligands.

    Science.gov (United States)

    Keegan, Mark E; Royce, Sara M; Fahmy, Tarek; Saltzman, W Mark

    2006-02-21

    Protein ligands were conjugated to the surface of biodegradable microspheres. These microsphere-ligand conjugates were then used in two in vitro model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the lectin Ulex europaeus agglutinin 1 to the microsphere surface increased microsphere adhesion to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of l-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complementary receptors.

  1. Surface-Bound Ligands Modulate Chemoselectivity and Activity of a Bimetallic Nanoparticle Catalyst

    KAUST Repository

    Vu, Khanh B.

    2015-04-03

    "Naked" metal nanoparticles (NPs) are thermodynamically and kinetically unstable in solution. Ligands, surfactants, or polymers, which adsorb at a particle\\'s surface, can be used to stabilize NPs; however, such a mode of stabilization is undesirable for catalytic applications because the adsorbates block the surface active sites. The catalytic activity and the stability of NPs are usually inversely correlated. Here, we describe an example of a bimetallic (PtFe) NP catalyst stabilized by carboxylate surface ligands that bind preferentially to one of the metals (Fe). NPs stabilized by fluorous ligands were found to be remarkably competent in catalyzing the hydrogenation of cinnamaldehyde; NPs stabilized by hydrocarbon ligands were significantly less active. The chain length of the fluorous ligands played a key role in determining the chemoselectivity of the FePt NP catalysts. (Chemical Presented). © 2015 American Chemical Society.

  2. A diketiminate-bound diiron complex with a bridging carbonate ligand

    Science.gov (United States)

    Sadique, Azwana R.; Brennessel, William W.; Holland, Patrick L.

    2009-01-01

    Reduction of carbon dioxide by a diiron(I) complex gives μ-carbonato-κ3 O:O′,O′′-bis­{[2,2,6,6-tetra­methyl-3,5-bis­(2,4,6-triisopropyl­phenyl)heptane-2,5-diiminate(1−)-κ2 N,N′]iron(II)} toluene disolvate, [Fe2(C41H65N)2(CO3)]·2C7H8, a diiron(II) species with a bridging carbonate ligand. The asymmetric unit contains one diiron complex and two cocrystallized toluene solvent mol­ecules that are distributed over three sites, one with atoms in general positions and two in crystallographic sites. Both FeII atoms are η2-coordinated to diketiminate ligands, but η1- and η2-coordinated to the bridging carbonate ligand. Thus, one FeII center is three-coordinate and the other is four-coordinate. The bridging carbonate ligand is nearly perpendicular to the iron–diketiminate plane of the four-coordinate FeII center and parallel to the plane of the three-coordinate FeII center. PMID:19407402

  3. Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.

    Science.gov (United States)

    Runge, Steffen; Thøgersen, Henning; Madsen, Kjeld; Lau, Jesper; Rudolph, Rainer

    2008-04-25

    The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.

  4. Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I).

    Science.gov (United States)

    Hanna, Jill R; Allan, Christopher; Lawrence, Charlotte; Meyer, Odile; Wilson, Neil D; Hulme, Alison N

    2017-05-14

    The CuAAC 'click' reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible 'turn-on' catalytic sensors for the detection of ligand-bound copper(I).

  5. Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I

    Directory of Open Access Journals (Sweden)

    Jill R. Hanna

    2017-05-01

    Full Text Available The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I. This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I.

  6. A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    Science.gov (United States)

    Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

    2017-07-01

    Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

  7. Blood Mixing Upregulates Platelet Membrane-Bound CD40 Ligand Expression in vitro Independent of Abo Compatibility.

    Science.gov (United States)

    Huang, Go-Shine; Hu, Mei-Hua; Lin, Tso-Chou; Lin, Yi-Chang; Tsai, Yi-Ting; Lin, Chih-Yuan; Ke, Hung-Yen; Zheng, Xu-Zhi; Tsai, Chien-Sung

    2017-11-30

    Platelets play a central role in the inflammation response via CD40 ligand (CD40L) expression, which may lead to transfusion reactions. The precise role of platelet CD40L-mediated inflammation in transfusion reactions is unclear. Therefore, we assessed the effects of in vitro blood mixing on platelet CD40L expression. In addition, we examined the effect of ABO compatibility on CD40L expression. Donor packed red blood cells were acquired from a blood bank, and recipient blood was obtained from patients undergoing cardiac surgery and prepared as washed platelets. Donor blood was mixed with suspended, washed recipient platelets to obtain a final mixing ratio of 1%, 5%, or 10% (vol/vol). The blood mixtures were divided into three groups: Group M, cross-matched blood-type mixing (n = 20); Group S, ABO type-specific uncross-matched blood (n = 20); and Group I, ABO incompatibility (not ABO type-specific blood and not process cross-matched) mixing (n = 20). The blood mixtures were used to detect platelet membrane-bound CD40L expression by flow cytometry. Blood mixing resulted in an increase in CD40L expression in Group M (P role in the induction of CD40L expression.

  8. Trans-ligand-dependent arrangement (bent or linear) of Pt II-bound dialkylcyanamide ligands: Molecular structure of trans-dichloro(dimethylcyanamide)(dimethyl sulfoxide)platinum(II)

    Science.gov (United States)

    Anisimova, Tatyana B.; Bokach, Nadezhda A.; Fritsky, Igor O.; Haukka, Matti

    2011-11-01

    The title compound, trans-[PtCl 2(NCNMe 2)(Me 2SO)], is the first example of the structurally characterized Pt II species having the nitrile and the sulfoxide ligands in the trans-position to each other. The most significant feature of this structure is the non-linear arrangement of the Pt sbnd N1 sbnd C1 fragment providing the rare case of the bent form of the dialkylcyanamide ligand.

  9. Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase (PDF) from Bacillus cereus in ligand-free and actinonin-bound forms

    International Nuclear Information System (INIS)

    Park, Joon Kyu; Moon, Jin Ho; Kim, Jae-Hong; Kim, Eunice EunKyeong

    2004-01-01

    Peptide deformylase (PDF) from B. cereus has been overexpressed, purified and crystallized in ligand-free and actinonin-bound forms. Diffraction data have been collected from these crystals to 1.7 and 2.0 Å resolution, respectively. In bacteria, protein expression initiates with an N-formyl group and this needs to be removed in order to ensure proper bacterial growth. These formylation and deformylation processes are unique to eubacteria; therefore, inhibition of these would provide a novel antibacterial therapy. Deformylation is carried out by peptide deformylase (PDF). PDF from Bacillus cereus, one of the major pathogenic bacteria, was cloned into expression plasmid pET-28a (Novagen), overexpressed in Escherichia coli BL21 (DE3) and purified to high quality. Crystals have been obtained of both ligand-free PDF and PDF to which actinonin, a highly potent naturally occurring inhibitor, is bound. Both crystals belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 42.72, b = 44.04, c = 85.19 Å and a = 41.31, b = 44.56, c = 84.47 Å, respectively. Diffraction data were collected to 1.7 Å resolution for the inhibitor-free crystals and to 2.0 Å resolution for the actinonin-bound crystals

  10. Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase (PDF) from Bacillus cereus in ligand-free and actinonin-bound forms.

    Science.gov (United States)

    Park, Joon Kyu; Moon, Jin Ho; Kim, Jae-Hong; Kim, Eunice EunKyeong

    2005-01-01

    In bacteria, protein expression initiates with an N-formyl group and this needs to be removed in order to ensure proper bacterial growth. These formylation and deformylation processes are unique to eubacteria; therefore, inhibition of these would provide a novel antibacterial therapy. Deformylation is carried out by peptide deformylase (PDF). PDF from Bacillus cereus, one of the major pathogenic bacteria, was cloned into expression plasmid pET-28a (Novagen), overexpressed in Escherichia coli BL21 (DE3) and purified to high quality. Crystals have been obtained of both ligand-free PDF and PDF to which actinonin, a highly potent naturally occurring inhibitor, is bound. Both crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 42.72, b = 44.04, c = 85.19 A and a = 41.31, b = 44.56, c = 84.47 A, respectively. Diffraction data were collected to 1.7 A resolution for the inhibitor-free crystals and to 2.0 A resolution for the actinonin-bound crystals.

  11. Cell surface-bound TIMP3 induces apoptosis in mesenchymal Cal78 cells through ligand-independent activation of death receptor signaling and blockade of survival pathways.

    Directory of Open Access Journals (Sweden)

    Christina Koers-Wunrau

    Full Text Available BACKGROUND: The matrix metalloproteinases (MMPs and their endogenous regulators, the tissue inhibitor of metalloproteinases (TIMPs 1-4 are responsible for the physiological remodeling of the extracellular matrix (ECM. Among all TIMPs, TIMP3 appears to play a unique role since TIMP3 is a secreted protein and, unlike the other TIMP family members, is tightly bound to the ECM. Moreover TIMP3 has been shown to be able to induce apoptotic cell death. As little is known about the underlying mechanisms, we set out to investigate the pro-apoptotic effect of TIMP3 in human mesenchymal cells. METHODOLOGY/PRINCIPAL FINDINGS: Lentiviral overexpression of TIMP3 in mesenchymal cells led to a strong dose-dependent induction of ligand-independent apoptosis as reflected by a five-fold increase in caspase 3 and 7 activity compared to control (pLenti6/V5-GW/lacZ or uninfected cells, whereas exogenous TIMP3 failed to induce apoptosis. Concordantly, increased cleavage of death substrate PARP and the caspases 3 and 7 was observed in TIMP3 overexpressing cultures. Notably, activation of caspase-8 but not caspase-9 was observed in TIMP3-overexpressing cells, indicating a death receptor-dependent mechanism. Moreover, overexpression of TIMP3 led to a further induction of apoptosis after stimulation with TNF-alpha, FasL and TRAIL. Most interestingly, TIMP3-overexpression was associated with a decrease in phosphorylation of cRaf, extracellular signal-regulated protein kinase (Erk1/2, ribosomal S6 kinase (RSK1 and Akt and serum deprivation of TIMP3-overexpressing cells resulted in a distinct enhancement of apoptosis, pointing to an impaired signaling of serum-derived survival factors. Finally, heparinase treatment of heparan sulfate proteoglycans led to the release of TIMP3 from the surface of overexpressing cells and to a significant decrease in apoptosis indicating that the binding of TIMP3 is necessary for apoptosis induction. CONCLUSION: The results demonstrate that

  12. Ligands in PSI structures

    International Nuclear Information System (INIS)

    Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

    2010-01-01

    A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

  13. The 2.1 Å resolution structure of cyanopindolol-bound β1-adrenoceptor identifies an intramembrane Na+ ion that stabilises the ligand-free receptor.

    Directory of Open Access Journals (Sweden)

    Jennifer L Miller-Gallacher

    Full Text Available The β1-adrenoceptor (β1AR is a G protein-coupled receptor (GPCR that is activated by the endogenous agonists adrenaline and noradrenaline. We have determined the structure of an ultra-thermostable β1AR mutant bound to the weak partial agonist cyanopindolol to 2.1 Å resolution. High-quality crystals (100 μm plates were grown in lipidic cubic phase without the assistance of a T4 lysozyme or BRIL fusion in cytoplasmic loop 3, which is commonly employed for GPCR crystallisation. An intramembrane Na+ ion was identified co-ordinated to Asp872.50, Ser1283.39 and 3 water molecules, which is part of a more extensive network of water molecules in a cavity formed between transmembrane helices 1, 2, 3, 6 and 7. Remarkably, this water network and Na+ ion is highly conserved between β1AR and the adenosine A2A receptor (rmsd of 0.3 Å, despite an overall rmsd of 2.4 Å for all Cα atoms and only 23% amino acid identity in the transmembrane regions. The affinity of agonist binding and nanobody Nb80 binding to β1AR is unaffected by Na+ ions, but the stability of the receptor is decreased by 7.5°C in the absence of Na+. Mutation of amino acid side chains that are involved in the co-ordination of either Na+ or water molecules in the network decreases the stability of β1AR by 5-10°C. The data suggest that the intramembrane Na+ and associated water network stabilise the ligand-free state of β1AR, but still permits the receptor to form the activated state which involves the collapse of the Na+ binding pocket on agonist binding.

  14. Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

    Science.gov (United States)

    Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

    2010-03-18

    Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

  15. Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface.

    Science.gov (United States)

    Cheng, Sara Y; Chou, George; Buie, Creighton; Vaughn, Mark W; Compton, Campbell; Cheng, Kwan H

    2016-03-01

    We used molecular dynamics simulations to explore the effects of asymmetric transbilayer distribution of anionic phosphatidylserine (PS) lipids on the structure of a protein on the membrane surface and subsequent protein-lipid interactions. Our simulation systems consisted of an amyloidogenic, beta-sheet rich dimeric protein (D42) absorbed to the phosphatidylcholine (PC) leaflet, or protein-contact PC leaflet, of two membrane systems: a single-component PC bilayer and double PC/PS bilayers. The latter comprised of a stable but asymmetric transbilayer distribution of PS in the presence of counterions, with a 1-component PC leaflet coupled to a 1-component PS leaflet in each bilayer. The maximally asymmetric PC/PS bilayer had a non-zero transmembrane potential (TMP) difference and higher lipid order packing, whereas the symmetric PC bilayer had a zero TMP difference and lower lipid order packing under physiologically relevant conditions. Analysis of the adsorbed protein structures revealed weaker protein binding, more folding in the N-terminal domain, more aggregation of the N- and C-terminal domains and larger tilt angle of D42 on the PC leaflet surface of the PC/PS bilayer versus the PC bilayer. Also, analysis of protein-induced membrane structural disruption revealed more localized bilayer thinning in the PC/PS versus PC bilayer. Although the electric field profile in the non-protein-contact PS leaflet of the PC/PS bilayer differed significantly from that in the non-protein-contact PC leaflet of the PC bilayer, no significant difference in the electric field profile in the protein-contact PC leaflet of either bilayer was evident. We speculate that lipid packing has a larger effect on the surface adsorbed protein structure than the electric field for a maximally asymmetric PC/PS bilayer. Our results support the mechanism that the higher lipid packing in a lipid leaflet promotes stronger protein-protein but weaker protein-lipid interactions for a dimeric protein on

  16. Pd-bound functionalized mesoporous silica as active catalyst for Suzuki coupling reaction: Effect of OAcˉ, PPh3 and Clˉ ligands on catalytic activity

    Science.gov (United States)

    Das, Trisha; Uyama, Hiroshi; Nandi, Mahasweta

    2018-04-01

    Three new palladium catalysts, PdCat-I, PdCat-II and PdCat-III, immobilized over heterogeneous silica support have been synthesized using different ligands attached to the palladium precursor. The ligands that have been used in this study are acetate, triphenylphosphine and chloride in PdCat-I, PdCat-II and PdCat-III, respectively. The ligands have different effect on stability of the compounds and impart different oxidation states to the metal center. The materials have been characterized by powder X-ray diffraction, nitrogen adsorption-desorption studies, transmission electron microscopy, thermal analysis, and different spectroscopic techniques. The Pd-content of the samples have been determined by ICP-AES analysis. The materials have been used as catalysts for Suzuki coupling reaction of aryl halides with phenylboronic acid under mild conditions. A comparative study has been carried out to ascertain the effect of the nature of different ligands on the outcome of the catalytic reactions. Products have been identified and estimated by 1H NMR and gas chromatography. The results show that the best yields are obtained with the catalyst containing triphenylphosphine as the ligand in methanol. Such type of work to study the effect of ligand on Suzuki coupling reaction over functionalized mesoporous silica heterogeneous catalysts have not been carried out so far.

  17. A new combined computational and NMR-spectroscopical strategy for the identification of additional conformational constraints of the bound ligand in an aprotic solvent

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Siebert, H.-C; André, S.; Asensio, J.l.; Cañada, F.J.; Dong, X.; Espinosa, M.; Frank, M.

    2000-01-01

    This study documents the feasibility of switching to an aprotic medium in sugar receptor research. The solvent change offers additional insights into mechanistic details of receptor-carbohydrate ligand interactions. If a receptor retained binding capacity in an aprotic medium, solvent-exchangeable

  18. On the maximal diphoton width

    CERN Document Server

    Salvio, Alberto; Strumia, Alessandro; Urbano, Alfredo

    2016-01-01

    Motivated by the 750 GeV diphoton excess found at LHC, we compute the maximal width into $\\gamma\\gamma$ that a neutral scalar can acquire through a loop of charged fermions or scalars as function of the maximal scale at which the theory holds, taking into account vacuum (meta)stability bounds. We show how an extra gauge symmetry can qualitatively weaken such bounds, and explore collider probes and connections with Dark Matter.

  19. Isolation, purification, and partial characterization of a membrane-bound Cl-/HCO3--activated ATPase complex from rat brain with sensitivity to GABAAergic ligands.

    Science.gov (United States)

    Menzikov, Sergey A

    2017-02-07

    This study describes the isolation and purification of a protein complex with [Formula: see text]-ATPase activity and sensitivity to GABA A ergic ligands from rat brain plasma membranes. The ATPase complex was enriched using size-exclusion, affinity, and ion-exchange chromatography. The fractions obtained at each purification step were subjected to SDS-polyacrylamide gel electrophoresis (SDS-PAGE), which revealed four subunits with molecular mass ∼48, 52, 56, and 59 kDa; these were retained at all stages of the purification process. Autoradiography revealed that the ∼52 and 56 kDa subunits could bind [ 3 H]muscimol. The [Formula: see text]-ATPase activity of this enriched protein complex was regulated by GABA A ergic ligands but was not sensitive to blockers of the NKCC or KCC cotransporters.

  20. Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization and antimalarial properties.

    Science.gov (United States)

    Ekengard, Erik; Kumar, Kamlesh; Fogeron, Thibault; de Kock, Carmen; Smith, Peter J; Haukka, Matti; Monari, Magda; Nordlander, Ebbe

    2016-03-07

    The synthesis and characterization of twenty new pentamethylcyclopentadienyl-rhodium and iridium complexes containing N^N and N^O-chelating chloroquine analogue ligands are described. The in vitro antimalarial activity of the new ligands as well as the complexes was evaluated against the chloroquine sensitive (CQS) NF54 and the chloroquine resistant (CQR) Dd2 strains of Plasmodium falciparum. The antimalarial activity was found to be good to moderate; although all complexes are less active than artesunate, some of the ligands and complexes showed better activity than chloroquine (CQ). In particular, rhodium complexes were found to be considerably more active than iridium complexes against the CQS NF54 strain. Salicylaldimine Schiff base ligands having electron-withdrawing groups (F, Cl, Br, I and NO2) in para position of the salicyl moiety and their rhodium complexes showed good antiplasmodial activity against both the CQS-NF54 and the CQR-Dd2 strains. The crystal structures of (η(5)-pentamethylcyclopentadienyl){N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)} chlororhodium(III) chloride and (η(5)-pentamethylcyclopentadienyl){(4-chloro-2-(((2-((7-chloroquinolin-4-yl)amino)ethyl)imino)methyl)phenolate)}chlororhodium(III) chloride are reported. The crystallization of the amino-pyridyl complex (η(5)-pentamethylcyclopentadienyl){(N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)}chloroiridium(III) chloride in acetone resulted in the formation of the imino-pyridyl derivative (η(5)-pentamethylcyclopentadienyl){(N1-(7-chloroquinolin-4-yl)-N2-(pyridin-2-ylmethylene)ethane-1,2-diamine)}chloroiridium(III) chloride, the crystal structure of which is also reported.

  1. Maximal quantum Fisher information matrix

    International Nuclear Information System (INIS)

    Chen, Yu; Yuan, Haidong

    2017-01-01

    We study the existence of the maximal quantum Fisher information matrix in the multi-parameter quantum estimation, which bounds the ultimate precision limit. We show that when the maximal quantum Fisher information matrix exists, it can be directly obtained from the underlying dynamics. Examples are then provided to demonstrate the usefulness of the maximal quantum Fisher information matrix by deriving various trade-off relations in multi-parameter quantum estimation and obtaining the bounds for the scalings of the precision limit. (paper)

  2. Entropy maximization

    Indian Academy of Sciences (India)

    Abstract. It is shown that (i) every probability density is the unique maximizer of relative entropy in an appropriate class and (ii) in the class of all pdf f that satisfy. ∫ fhi dμ = λi for i = 1, 2,...,...k the maximizer of entropy is an f0 that is pro- portional to exp(. ∑ ci hi ) for some choice of ci . An extension of this to a continuum of.

  3. Entropy Maximization

    Indian Academy of Sciences (India)

    It is shown that (i) every probability density is the unique maximizer of relative entropy in an appropriate class and (ii) in the class of all pdf that satisfy ∫ f h i d = i for i = 1 , 2 , … , … k the maximizer of entropy is an f 0 that is proportional to exp ⁡ ( ∑ c i h i ) for some choice of c i . An extension of this to a continuum of ...

  4. Modeling Equilibrium Fe Isotope Fractionation in Fe-Organic Complexes: Implications for the use of Fe Isotopes as a Biomarker and Trends Based on the Properties of Bound Ligands

    Science.gov (United States)

    Domagal-Goldman, S.; Kubicki, J. D.

    2006-05-01

    Fe Isotopes have been proposed as a useful tracer of biological and geochemical processes. Key to understanding the effects these various processes have on Fe isotopes is accurate modeling of the reactions responsible for the isotope fractionations. In this study, we examined the theoretical basis for the claims that Fe isotopes can be used as a biomarker. This was done by using molecular orbital/density functional theory (MO/DFT) calculations to predict the equilibrium fractionation of Fe isotopes due to changes in the redox state and the bonding environment of Fe. Specifically, we predicted vibrational frequencies for iron desferrioxamine (Fe-DFOB), iron triscatechol (Fe(cat)3), iron trisoxalate (Fe(ox)3), and hexaaquo iron (Fe(H2O)6) for complexes containing both ferrous (Fe2+) and ferric (Fe3+) iron. Using these vibrational frequencies, we then predicted fractionation factors between these six complexes. The predicted fractionation factors resulting from changes in the redox state of Fe fell in the range 2.5- 3.5‰. The fractionation factors resulting from changes in the bonding environment of Fe ranged from 0.2 to 1.4‰. These results indicate that changes in the bonding strength of Fe ligands are less important to Fe isotope fractionation processes than are changes to the redox state of Fe. The implications for use of Fe as a tracer of biological processes is clear: abiological redox changes must be ruled out in a sample before Fe isotopes are considered as a potential biomarker. Furthermore, the use of Fe isotopes to measure the redox state of the Earths surface environment through time is supported by this work, since changes in the redox state of Fe appear to be the more important driver of isotopic fractionations. In addition to the large differences between redox-driven fractionations and ligand-driven fractionations, we will also show general trends in the demand for heavy Fe isotopes as a function of properties of the bound ligand. This will help the

  5. Microassay for measurement of binding of radiolabelled ligands to cell surface molecules

    International Nuclear Information System (INIS)

    Woof, J.M.; Burton, D.R.

    1988-01-01

    An improved technique for measuring the binding of radiolabelled ligands to cell surface molecules has been developed by modification of a procedure using centrifugation through a water-immiscible oil to separate free and cell-bound ligand. It maximises the percentage of ligand bound since cell-bound and free ligand can be separated easily and reproducibly even when very small reaction volumes are used. This permits low levels of ligand radiolabelling and relatively low numbers of cells to be used

  6. Maximizing Entropy over Markov Processes

    DEFF Research Database (Denmark)

    Biondi, Fabrizio; Legay, Axel; Nielsen, Bo Friis

    2013-01-01

    The channel capacity of a deterministic system with confidential data is an upper bound on the amount of bits of data an attacker can learn from the system. We encode all possible attacks to a system using a probabilistic specification, an Interval Markov Chain. Then the channel capacity...... as a reward function, a polynomial algorithm to verify the existence of an system maximizing entropy among those respecting a specification, a procedure for the maximization of reward functions over Interval Markov Chains and its application to synthesize an implementation maximizing entropy. We show how...... to use Interval Markov Chains to model abstractions of deterministic systems with confidential data, and use the above results to compute their channel capacity. These results are a foundation for ongoing work on computing channel capacity for abstractions of programs derived from code....

  7. Maximizing entropy over Markov processes

    DEFF Research Database (Denmark)

    Biondi, Fabrizio; Legay, Axel; Nielsen, Bo Friis

    2014-01-01

    The channel capacity of a deterministic system with confidential data is an upper bound on the amount of bits of data an attacker can learn from the system. We encode all possible attacks to a system using a probabilistic specification, an Interval Markov Chain. Then the channel capacity...... as a reward function, a polynomial algorithm to verify the existence of a system maximizing entropy among those respecting a specification, a procedure for the maximization of reward functions over Interval Markov Chains and its application to synthesize an implementation maximizing entropy. We show how...... to use Interval Markov Chains to model abstractions of deterministic systems with confidential data, and use the above results to compute their channel capacity. These results are a foundation for ongoing work on computing channel capacity for abstractions of programs derived from code. © 2014 Elsevier...

  8. Profit maximization mitigates competition

    DEFF Research Database (Denmark)

    Dierker, Egbert; Grodal, Birgit

    1996-01-01

    We consider oligopolistic markets in which the notion of shareholders' utility is well-defined and compare the Bertrand-Nash equilibria in case of utility maximization with those under the usual profit maximization hypothesis. Our main result states that profit maximization leads to less price...... competition than utility maximization. Since profit maximization tends to raise prices, it may be regarded as beneficial for the owners as a whole. Moreover, if profit maximization is a good proxy for utility maximization, then there is no need for a general equilibrium analysis that takes the distribution...... of profits among consumers fully into account and partial equilibrium analysis suffices...

  9. Synthesis and reactivity of TADDOL-based chiral Fe(II) PNP pincer complexes-solution equilibria between κ(2)P,N- and κ(3)P,N,P-bound PNP pincer ligands.

    Science.gov (United States)

    Holzhacker, Christian; Stöger, Berthold; Carvalho, Maria Deus; Ferreira, Liliana P; Pittenauer, Ernst; Allmaier, Günter; Veiros, Luis F; Realista, Sara; Gil, Adrià; Calhorda, Maria José; Müller, Danny; Kirchner, Karl

    2015-08-07

    Treatment of anhydrous FeX2 (X = Cl, Br) with 1 equiv. of the asymmetric chiral PNP pincer ligands PNP-R,TAD (R = iPr, tBu) with an R,R-TADDOL (TAD) moiety afforded complexes of the general formula [Fe(PNP)X2]. In the solid state these complexes adopt a tetrahedral geometry with the PNP ligand coordinated in κ(2)P,N-fashion, as shown by X-ray crystallography and Mössbauer spectroscopy. Magnetization studies led to a magnetic moment very close to 4.9μB reflecting the expected four unpaired d-electrons (quintet ground state). In solution there are equilibria between [Fe(κ(3)P,N,P-PNP-R,TAD)X2] and [Fe(κ(2)P,N-PNP-R,TAD)X2] complexes, i.e., the PNP-R,TAD ligand is hemilabile. At -50 °C these equilibria are slow and signals of the non-coordinated P-TAD arm of the κ(2)P,N-PNP-R,TAD ligand can be detected by (31)P{(1)H} NMR spectroscopy. Addition of BH3 to a solution of [Fe(PNP-iPr,TAD)Cl2] leads to selective boronation of the pendant P-TAD arm shifting the equilibrium towards the four-coordinate complex [Fe(κ(2)P,N-PNP-iPr,TAD(BH3))Cl2]. DFT calculations corroborate the existence of equilibria between four- and five-coordinated complexes. Addition of CO to [Fe(PNP-iPr,TAD)X2] in solution yields the diamagnetic octahedral complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)X2], which react further with Ag(+) salts in the presence of CO to give the cationic complexes trans-[Fe(κ(3)P,N,P-PNP-iPr,TAD)(CO)2X](+). CO addition most likely takes place at the five coordinate complex [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. The mechanism for the CO addition was also investigated by DFT and the most favorable path obtained corresponds to the rearrangement of the pincer ligand first from a κ(2)P,N- to a κ(3)P,N,P-coordination mode followed by CO coordination to [Fe(κ(3)P,N,P-PNP-iPr,TAD)X2]. Complexes bearing tBu substituents do not react with CO. Moreover, in the solid state none of the tetrahedral complexes are able to bind CO.

  10. Maximally incompatible quantum observables

    Energy Technology Data Exchange (ETDEWEB)

    Heinosaari, Teiko, E-mail: teiko.heinosaari@utu.fi [Turku Centre for Quantum Physics, Department of Physics and Astronomy, University of Turku, FI-20014 Turku (Finland); Schultz, Jussi, E-mail: jussi.schultz@gmail.com [Dipartimento di Matematica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); Toigo, Alessandro, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Milano, Via Celoria 16, I-20133 Milano (Italy); Ziman, Mario, E-mail: ziman@savba.sk [RCQI, Institute of Physics, Slovak Academy of Sciences, Dúbravská cesta 9, 84511 Bratislava (Slovakia); Faculty of Informatics, Masaryk University, Botanická 68a, 60200 Brno (Czech Republic)

    2014-05-01

    The existence of maximally incompatible quantum observables in the sense of a minimal joint measurability region is investigated. Employing the universal quantum cloning device it is argued that only infinite dimensional quantum systems can accommodate maximal incompatibility. It is then shown that two of the most common pairs of complementary observables (position and momentum; number and phase) are maximally incompatible.

  11. Maximally incompatible quantum observables

    International Nuclear Information System (INIS)

    Heinosaari, Teiko; Schultz, Jussi; Toigo, Alessandro; Ziman, Mario

    2014-01-01

    The existence of maximally incompatible quantum observables in the sense of a minimal joint measurability region is investigated. Employing the universal quantum cloning device it is argued that only infinite dimensional quantum systems can accommodate maximal incompatibility. It is then shown that two of the most common pairs of complementary observables (position and momentum; number and phase) are maximally incompatible.

  12. Finding the Maximal Area of Bounded Polygons in a Circle

    Science.gov (United States)

    Rokach, Arie

    2005-01-01

    The article deals with the area of polygons that are inscribed in a given circle. Naturally, the following question arises: Among all n-polygons that are inscribed in a given circle, which one has the biggest area? Intuitively, it may be guessed that is suitable for secondary students, and without any use id calculus, but only using very…

  13. Maximizers versus satisficers

    OpenAIRE

    Andrew M. Parker; Wandi Bruine de Bruin; Baruch Fischhoff

    2007-01-01

    Our previous research suggests that people reporting a stronger desire to maximize obtain worse life outcomes (Bruine de Bruin et al., 2007). Here, we examine whether this finding may be explained by the decision-making styles of self-reported maximizers. Expanding on Schwartz et al. (2002), we find that self-reported maximizers are more likely to show problematic decision-making styles, as evidenced by self-reports of less behavioral coping, greater dependence on others when making decisions...

  14. Maximal combustion temperature estimation

    International Nuclear Information System (INIS)

    Golodova, E; Shchepakina, E

    2006-01-01

    This work is concerned with the phenomenon of delayed loss of stability and the estimation of the maximal temperature of safe combustion. Using the qualitative theory of singular perturbations and canard techniques we determine the maximal temperature on the trajectories located in the transition region between the slow combustion regime and the explosive one. This approach is used to estimate the maximal temperature of safe combustion in multi-phase combustion models

  15. Maximally multipartite entangled states

    Science.gov (United States)

    Facchi, Paolo; Florio, Giuseppe; Parisi, Giorgio; Pascazio, Saverio

    2008-06-01

    We introduce the notion of maximally multipartite entangled states of n qubits as a generalization of the bipartite case. These pure states have a bipartite entanglement that does not depend on the bipartition and is maximal for all possible bipartitions. They are solutions of a minimization problem. Examples for small n are investigated, both analytically and numerically.

  16. Ligand identification using electron-density map correlations

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2007-01-01

    An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

  17. Maximizers versus satisficers

    Directory of Open Access Journals (Sweden)

    Andrew M. Parker

    2007-12-01

    Full Text Available Our previous research suggests that people reporting a stronger desire to maximize obtain worse life outcomes (Bruine de Bruin et al., 2007. Here, we examine whether this finding may be explained by the decision-making styles of self-reported maximizers. Expanding on Schwartz et al. (2002, we find that self-reported maximizers are more likely to show problematic decision-making styles, as evidenced by self-reports of less behavioral coping, greater dependence on others when making decisions, more avoidance of decision making, and greater tendency to experience regret. Contrary to predictions, self-reported maximizers were more likely to report spontaneous decision making. However, the relationship between self-reported maximizing and worse life outcomes is largely unaffected by controls for measures of other decision-making styles, decision-making competence, and demographic variables.

  18. Is CP violation maximal

    International Nuclear Information System (INIS)

    Gronau, M.

    1984-01-01

    Two ambiguities are noted in the definition of the concept of maximal CP violation. The phase convention ambiguity is overcome by introducing a CP violating phase in the quark mixing matrix U which is invariant under rephasing transformations. The second ambiguity, related to the parametrization of U, is resolved by finding a single empirically viable definition of maximal CP violation when assuming that U does not single out one generation. Considerable improvement in the calculation of nonleptonic weak amplitudes is required to test the conjecture of maximal CP violation. 21 references

  19. Derivative pricing based on local utility maximization

    OpenAIRE

    Jan Kallsen

    2002-01-01

    This paper discusses a new approach to contingent claim valuation in general incomplete market models. We determine the neutral derivative price which occurs if investors maximize their local utility and if derivative demand and supply are balanced. We also introduce the sensitivity process of a contingent claim. This process quantifies the reliability of the neutral derivative price and it can be used to construct price bounds. Moreover, it allows to calibrate market models in order to be co...

  20. Perceptron Mistake Bounds

    OpenAIRE

    Mohri, Mehryar; Rostamizadeh, Afshin

    2013-01-01

    We present a brief survey of existing mistake bounds and introduce novel bounds for the Perceptron or the kernel Perceptron algorithm. Our novel bounds generalize beyond standard margin-loss type bounds, allow for any convex and Lipschitz loss function, and admit a very simple proof.

  1. Circuit lower bounds in bounded arithmetics

    Czech Academy of Sciences Publication Activity Database

    Pich, Ján

    2015-01-01

    Roč. 166, č. 1 (2015), s. 29-45 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902 Keywords : bounded arithmetic * circuit lower bounds Subject RIV: BA - General Mathematics Impact factor: 0.582, year: 2015 http://www.sciencedirect.com/science/article/pii/S0168007214000888

  2. Guinea pig maximization test

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner

    1985-01-01

    Guinea pig maximization tests (GPMT) with chlorocresol were performed to ascertain whether the sensitization rate was affected by minor changes in the Freund's complete adjuvant (FCA) emulsion used. Three types of emulsion were evaluated: the oil phase was mixed with propylene glycol, saline...

  3. Tri-maximal vs. bi-maximal neutrino mixing

    International Nuclear Information System (INIS)

    Scott, W.G

    2000-01-01

    It is argued that data from atmospheric and solar neutrino experiments point strongly to tri-maximal or bi-maximal lepton mixing. While ('optimised') bi-maximal mixing gives an excellent a posteriori fit to the data, tri-maximal mixing is an a priori hypothesis, which is not excluded, taking account of terrestrial matter effects

  4. Scattering by bound nucleons

    International Nuclear Information System (INIS)

    Tezuka, Hirokazu.

    1984-10-01

    Scattering of a particle by bound nucleons is discussed. Effects of nucleons that are bound in a nucleus are taken as a structure function. The way how to calculate the structure function is given. (author)

  5. Finite translation surfaces with maximal number of translations

    OpenAIRE

    Schlage-Puchta, Jan-Christoph; Weitze-Schmithuesen, Gabriela

    2013-01-01

    The natural automorphism group of a translation surface is its group of translations. For finite translation surfaces of genus g > 1 the order of this group is naturally bounded in terms of g due to a Riemann-Hurwitz formula argument. In analogy with classical Hurwitz surfaces, we call surfaces which achieve the maximal bound Hurwitz translation surfaces. We study for which g there exist Hurwitz translation surfaces of genus g.

  6. MAXIM: The Blackhole Imager

    Science.gov (United States)

    Gendreau, Keith; Cash, Webster; Gorenstein, Paul; Windt, David; Kaaret, Phil; Reynolds, Chris

    2004-01-01

    The Beyond Einstein Program in NASA's Office of Space Science Structure and Evolution of the Universe theme spells out the top level scientific requirements for a Black Hole Imager in its strategic plan. The MAXIM mission will provide better than one tenth of a microarcsecond imaging in the X-ray band in order to satisfy these requirements. We will overview the driving requirements to achieve these goals and ultimately resolve the event horizon of a supermassive black hole. We will present the current status of this effort that includes a study of a baseline design as well as two alternative approaches.

  7. Social group utility maximization

    CERN Document Server

    Gong, Xiaowen; Yang, Lei; Zhang, Junshan

    2014-01-01

    This SpringerBrief explains how to leverage mobile users' social relationships to improve the interactions of mobile devices in mobile networks. It develops a social group utility maximization (SGUM) framework that captures diverse social ties of mobile users and diverse physical coupling of mobile devices. Key topics include random access control, power control, spectrum access, and location privacy.This brief also investigates SGUM-based power control game and random access control game, for which it establishes the socially-aware Nash equilibrium (SNE). It then examines the critical SGUM-b

  8. New Maximal Two-distance Sets

    DEFF Research Database (Denmark)

    Lisonek, Petr

    1996-01-01

    A two-distance set in E^d is a point set X inthe d-dimensional Euclidean spacesuch that the distances between distinct points in Xassume only two different non-zero values. Based on results from classical distance geometry, we developan algorithm to classify, for a given dimension, all maximal...... (largest possible)two-distance sets in E^d.Using this algorithm we have completed the full classificationfor all dimensions less than or equal to 7, andwe have found one set in E^8 whosemaximality follows from Blokhuis' upper bound on sizes of s-distance sets.While in the dimensions less than or equal to 6...

  9. Pouliot type duality via a-maximization

    International Nuclear Information System (INIS)

    Kawano, Teruhiko; Ookouchi, Yutaka; Tachikawa, Yuji; Yagi, Futoshi

    2006-01-01

    We study four-dimensional N=1Spin(10) gauge theory with a single spinor and N Q vectors at the superconformal fixed point via the electric-magnetic duality and a-maximization. When gauge invariant chiral primary operators hit the unitarity bounds, we find that the theory with no superpotential is identical to the one with some superpotential at the infrared fixed point. The auxiliary field method in the electric theory offers a satisfying description of the infrared fixed point, which is consistent with the better picture in the magnetic theory. In particular, it gives a clear description of the emergence of new massless degrees of freedom in the electric theory

  10. Spectra of fluorinated rare earth. beta. -diketonates with added ligands

    Energy Technology Data Exchange (ETDEWEB)

    Khomenko, V.S.; Lozinskij, M.O.; Fialkov, Yu.A.; Rasshinina, T.A.; Krasovskaya, L.I. (AN Belorusskoj SSR, Minsk. Inst. Fiziki; AN Ukrainskoj SSR, Kiev. Inst. Organicheskoj Khimii)

    1984-01-01

    Different-ligand rare earth complexes are synthesized. Fluorated ..beta..-diketones, triethylphosphine oxide and trifluoracetic acid are used as active ligands. Mass-spectra of low and high resolution are taken at the energy of ionizing electrons of 70 eV, as well as luminescence spectra of complexes. Fragmentation ways of complexes decomposition under electron shock are studied. A series of changing the bound strength of additional ligands with europium in mixed complexes is determined. It is shown that the introduction of additional ligands can purposefully change physical and chemical properties of complexes.

  11. Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

    2016-11-15

    We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

  12. Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites

    Science.gov (United States)

    Vukovic, Sinisa; Brennan, Paul E.; Huggins, David J.

    2016-09-01

    The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

  13. Exploring the role of water in molecular recognition: predicting protein ligandability using a combinatorial search of surface hydration sites.

    Science.gov (United States)

    Vukovic, Sinisa; Brennan, Paul E; Huggins, David J

    2016-09-01

    The interaction between any two biological molecules must compete with their interaction with water molecules. This makes water the most important molecule in medicine, as it controls the interactions of every therapeutic with its target. A small molecule binding to a protein is able to recognize a unique binding site on a protein by displacing bound water molecules from specific hydration sites. Quantifying the interactions of these water molecules allows us to estimate the potential of the protein to bind a small molecule. This is referred to as ligandability. In the study, we describe a method to predict ligandability by performing a search of all possible combinations of hydration sites on protein surfaces. We predict ligandability as the summed binding free energy for each of the constituent hydration sites, computed using inhomogeneous fluid solvation theory. We compared the predicted ligandability with the maximum observed binding affinity for 20 proteins in the human bromodomain family. Based on this comparison, it was determined that effective inhibitors have been developed for the majority of bromodomains, in the range from 10 to 100 nM. However, we predict that more potent inhibitors can be developed for the bromodomains BPTF and BRD7 with relative ease, but that further efforts to develop inhibitors for ATAD2 will be extremely challenging. We have also made predictions for the 14 bromodomains with no reported small molecule K d values by isothermal titration calorimetry. The calculations predict that PBRM1(1) will be a challenging target, while others such as TAF1L(2), PBRM1(4) and TAF1(2), should be highly ligandable. As an outcome of this work, we assembled a database of experimental maximal K d that can serve as a community resource assisting medicinal chemistry efforts focused on BRDs. Effective prediction of ligandability would be a very useful tool in the drug discovery process.

  14. Physical Uncertainty Bounds (PUB)

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    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.

  15. Photon virtual bound state

    International Nuclear Information System (INIS)

    Inoue, J.; Ohtaka, K.

    2004-01-01

    We study virtual bound states in photonics, which are a vectorial extension of electron virtual bound states. The condition for these states is derived. It is found that the Mie resonant state which satisfies the condition that the size parameter is less than the angular momentum should be interpreted as a photon virtual bound state. In order to confirm the validity of the concept, we compare the photonic density of states, the width of which represents the lifetime of the photon virtual bound states, with numerical results

  16. The DMM Bound

    DEFF Research Database (Denmark)

    Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

    2010-01-01

    ) resultant by means of mixed volume, as well as recent advances on aggregate root bounds for univariate polynomials, and are applicable to arbitrary positive dimensional systems. We improve upon Canny's gap theorem [7] by a factor of O(dn-1), where d bounds the degree of the polynomials, and n is the number...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

  17. Reduction of dinitrogen ligands

    International Nuclear Information System (INIS)

    Richards, R.L.

    1983-01-01

    Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

  18. Bounded Gaussian process regression

    DEFF Research Database (Denmark)

    Jensen, Bjørn Sand; Nielsen, Jens Brehm; Larsen, Jan

    2013-01-01

    We extend the Gaussian process (GP) framework for bounded regression by introducing two bounded likelihood functions that model the noise on the dependent variable explicitly. This is fundamentally different from the implicit noise assumption in the previously suggested warped GP framework. We...... with the proposed explicit noise-model extension....

  19. Bounded Intention Planning Revisited

    OpenAIRE

    Sievers Silvan; Wehrle Martin; Helmert Malte

    2014-01-01

    Bounded intention planning provides a pruning technique for optimal planning that has been proposed several years ago. In addition partial order reduction techniques based on stubborn sets have recently been investigated for this purpose. In this paper we revisit bounded intention planning in the view of stubborn sets.

  20. MAXIMUM r-REGULAR INDUCED SUBGRAPH PROBLEM: FAST EXPONENTIAL ALGORITHMS AND COMBINATORIAL BOUNDS

    DEFF Research Database (Denmark)

    Gupta, S.; Raman, V.; Saurabh, S.

    2012-01-01

    We show that for a fixed r, the number of maximal r-regular induced subgraphs in any graph with n vertices is upper bounded by O(c(n)), where c is a positive constant strictly less than 2. This bound generalizes the well-known result of Moon and Moser, who showed an upper bound of 3(n/3) on the n...

  1. Bounding species distribution models

    Directory of Open Access Journals (Sweden)

    Thomas J. STOHLGREN, Catherine S. JARNEVICH, Wayne E. ESAIAS,Jeffrey T. MORISETTE

    2011-10-01

    Full Text Available 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].

  2. Bounding Species Distribution Models

    Science.gov (United States)

    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].

  3. Quantum bounds on Bell inequalities

    Science.gov (United States)

    Pál, Károly F.; Vértesi, Tamás

    2009-02-01

    We have determined the maximum quantum violation of 241 tight bipartite Bell inequalities with up to five two-outcome measurement settings per party by constructing the appropriate measurement operators in up to six-dimensional complex and eight-dimensional real-component Hilbert spaces using numerical optimization. Out of these inequalities 129 have been introduced here. In 43 cases higher-dimensional component spaces gave larger violation than qubits, and in three occasions the maximum was achieved with six-dimensional spaces. We have also calculated upper bounds on these Bell inequalities using a method proposed recently. For all but 20 inequalities the best solution found matched the upper bound. Surprisingly, the simplest inequality of the set examined, with only three measurement settings per party, was not among them, despite the high dimensionality of the Hilbert space considered. We also computed detection threshold efficiencies for the maximally entangled qubit pair. These could be lowered in several instances if degenerate measurements were also allowed.

  4. Maximal Bell's inequality violation for non-maximal entanglement

    International Nuclear Information System (INIS)

    Kobayashi, M.; Khanna, F.; Mann, A.; Revzen, M.; Santana, A.

    2004-01-01

    Bell's inequality violation (BIQV) for correlations of polarization is studied for a product state of two two-mode squeezed vacuum (TMSV) states. The violation allowed is shown to attain its maximal limit for all values of the squeezing parameter, ζ. We show via an explicit example that a state whose entanglement is not maximal allow maximal BIQV. The Wigner function of the state is non-negative and the average value of either polarization is nil

  5. Organically bound tritium

    International Nuclear Information System (INIS)

    Diabate, S.; Strack, S.

    1993-01-01

    Tritium released into the environment may be incorporated into organic matter. Organically bound tritium in that case will show retention times in organisms that are considerably longer than those of tritiated water which has significant consequences on dose estimates. This article reviews the most important processes of organically bound tritium production and transport through food networks. Metabolic reactions in plant and animal organisms with tritiated water as a reaction partner are of great importance in this respect. The most important production process, in quantitative terms, is photosynthesis in green plants. The translocation of organically bound tritium from the leaves to edible parts of crop plants should be considered in models of organically bound tritium behavior. Organically bound tritium enters the human body on several pathways, either from the primary producers (vegetable food) or at a higher tropic level (animal food). Animal experiments have shown that the dose due to ingestion of organically bound tritium can be up to twice as high as a comparable intake of tritiated water in gaseous or liquid form. In the environment, organically bound tritium in plants and animals is often found to have higher specific tritium concentrations than tissue water. This is not due to some tritium enrichment effects but to the fact that no equilibrium conditions are reached under natural conditions. 66 refs

  6. Deeply bound pionic atom

    International Nuclear Information System (INIS)

    Toki, Hiroshi; Yamazaki, Toshimitsu

    1989-01-01

    The standard method of pionic atom formation does not produce deeply bound pionic atoms. A study is made on the properties of deeply bound pionic atom states by using the standard pion-nucleus optical potential. Another study is made to estimate the cross sections of the formation of ls pionic atom states by various methods. The pion-nucleus optical potential is determined by weakly bound pionic atom states and pion nucleus scattering. Although this potential may not be valid for deeply bound pionic atoms, it should provide some hint on binding energies and level widths of deeply bound states. The width of the ls state comes out to be 0.3 MeV and is well separated from the rest. The charge dependence of the ls state is investigated. The binding energies and the widths increase linearly with Z azbove a Z of 30. The report then discusses various methods to populate deeply bound pionic atoms. In particular, 'pion exchange' reactions are proposed. (n, pπ) reaction is discussed first. The cross section is calculated by assuming the in- and out-going nucleons on-shell and the produced pion in (n1) pionic atom states. Then, (n, dπ - ) cross sections are estimated. (p, 2 Heπ - ) reaction would have cross sections similar to the cross section of (n, dπ - ) reaction. In conclusion, it seems best to do (n, p) experiment on heavy nuclei for deeply bound pionic atom. (Nogami, K.)

  7. Maximally Symmetric Composite Higgs Models.

    Science.gov (United States)

    Csáki, Csaba; Ma, Teng; Shu, Jing

    2017-09-29

    Maximal symmetry is a novel tool for composite pseudo Goldstone boson Higgs models: it is a remnant of an enhanced global symmetry of the composite fermion sector involving a twisting with the Higgs field. Maximal symmetry has far-reaching consequences: it ensures that the Higgs potential is finite and fully calculable, and also minimizes the tuning. We present a detailed analysis of the maximally symmetric SO(5)/SO(4) model and comment on its observational consequences.

  8. Principles of maximally classical and maximally realistic quantum ...

    Indian Academy of Sciences (India)

    Principles of maximally classical and maximally realistic quantum mechanics. S M ROY. Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India. Abstract. Recently Auberson, Mahoux, Roy and Singh have proved a long standing conjecture of Roy and Singh: In 2N-dimensional phase space, ...

  9. Bounded Rationality and Budgeting

    OpenAIRE

    Ibrahim, Mukdad

    2016-01-01

    This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

  10. Virial Expansion Bounds

    Science.gov (United States)

    Tate, Stephen James

    2013-10-01

    In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

  11. Bound and rebound states

    International Nuclear Information System (INIS)

    Orzalesi, C.A.

    1979-01-01

    In relativistic quantum theory, bound states generate forces in the crossed channel; such forces can affect the binding and self-consistent solutions should be sought for the bound-state problem. The author investigates how self-consistency can be achieved by successive approximations, in a simple scalar model and with successive relativistic eikonal approximations (EAs). Within the generalized ladder approximation, some exact properties of the resulting ''first generation'' bound states are discussed. The binding energies in this approximation are rather small even for rather large values of the primary coupling constant. The coupling of the constituent particles to the first-generation reggeon is determined by a suitable EA and a new generalized ladder amplitude is constructed with rungs given either by the primary gluons or by the first-generation reggeons. The resulting new (second-generation) bound states are found in a reggeized EA. The size of the corrections to the binding energies due to the rebinding effects is surprisingly large. The procedure is then iterated, so as to find - again in an EA - the third-generation bound states. The procedure is found to be self-consistent already at this stage: the third-generation bound states coincide with those of second generation, and no further rebinding takes place in the higher iterations of the approximation method. Features - good and bad - of the model are discussed, as well as the possible relevance of rebinding mechanisms in hadron dynamics. (author)

  12. Primordial two-component maximally symmetric inflation

    Science.gov (United States)

    Enqvist, K.; Nanopoulos, D. V.; Quirós, M.; Kounnas, C.

    1985-12-01

    We propose a two-component inflation model, based on maximally symmetric supergravity, where the scales of reheating and the inflation potential at the origin are decoupled. This is possible because of the second-order phase transition from SU(5) to SU(3)×SU(2)×U(1) that takes place when φ≅φcinflation at the global minimum, and leads to a reheating temperature TR≅(1015-1016) GeV. This makes it possible to generate baryon asymmetry in the conventional way without any conflict with experimental data on proton lifetime. The mass of the gravitinos is m3/2≅1012 GeV, thus avoiding the gravitino problem. Monopoles are diluted by residual inflation in the broken phase below the cosmological bounds if φcUSA.

  13. Maximal energy extraction under discrete diffusive exchange

    Energy Technology Data Exchange (ETDEWEB)

    Hay, M. J., E-mail: hay@princeton.edu [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States); Schiff, J. [Department of Mathematics, Bar-Ilan University, Ramat Gan 52900 (Israel); Fisch, N. J. [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States); Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543 (United States)

    2015-10-15

    Waves propagating through a bounded plasma can rearrange the densities of states in the six-dimensional velocity-configuration phase space. Depending on the rearrangement, the wave energy can either increase or decrease, with the difference taken up by the total plasma energy. In the case where the rearrangement is diffusive, only certain plasma states can be reached. It turns out that the set of reachable states through such diffusive rearrangements has been described in very different contexts. Building upon those descriptions, and making use of the fact that the plasma energy is a linear functional of the state densities, the maximal extractable energy under diffusive rearrangement can then be addressed through linear programming.

  14. Ligand Electron Density Shape Recognition Using 3D Zernike Descriptors

    Science.gov (United States)

    Gunasekaran, Prasad; Grandison, Scott; Cowtan, Kevin; Mak, Lora; Lawson, David M.; Morris, Richard J.

    We present a novel approach to crystallographic ligand density interpretation based on Zernike shape descriptors. Electron density for a bound ligand is expanded in an orthogonal polynomial series (3D Zernike polynomials) and the coefficients from this expansion are employed to construct rotation-invariant descriptors. These descriptors can be compared highly efficiently against large databases of descriptors computed from other molecules. In this manuscript we describe this process and show initial results from an electron density interpretation study on a dataset containing over a hundred OMIT maps. We could identify the correct ligand as the first hit in about 30 % of the cases, within the top five in a further 30 % of the cases, and giving rise to an 80 % probability of getting the correct ligand within the top ten matches. In all but a few examples, the top hit was highly similar to the correct ligand in both shape and chemistry. Further extensions and intrinsic limitations of the method are discussed.

  15. Crystallization of bi-functional ligand protein complexes.

    Science.gov (United States)

    Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

    2013-06-01

    Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Bounded Tamper Resilience

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Faust, Sebastian; Mukherjee, Pratyay

    2013-01-01

    Related key attacks (RKAs) are powerful cryptanalytic attacks where an adversary can change the secret key and observe the effect of such changes at the output. The state of the art in RKA security protects against an a-priori unbounded number of certain algebraic induced key relations, e.......g., affine functions or polynomials of bounded degree. In this work, we show that it is possible to go beyond the algebraic barrier and achieve security against arbitrary key relations, by restricting the number of tampering queries the adversary is allowed to ask for. The latter restriction is necessary......-protocols (including the Okamoto scheme, for instance) are secure even if the adversary can arbitrarily tamper with the prover’s state a bounded number of times and obtain some bounded amount of leakage. Interestingly, for the Okamoto scheme we can allow also independent tampering with the public parameters. We show...

  17. Massive Galileon positivity bounds

    Science.gov (United States)

    de Rham, Claudia; Melville, Scott; Tolley, Andrew J.; Zhou, Shuang-Yong

    2017-09-01

    The EFT coefficients in any gapped, scalar, Lorentz invariant field theory must satisfy positivity requirements if there is to exist a local, analytic Wilsonian UV completion. We apply these bounds to the tree level scattering amplitudes for a massive Galileon. The addition of a mass term, which does not spoil the non-renormalization theorem of the Galileon and preserves the Galileon symmetry at loop level, is necessary to satisfy the lowest order positivity bound. We further show that a careful choice of successively higher derivative corrections are necessary to satisfy the higher order positivity bounds. There is then no obstruction to a local UV completion from considerations of tree level 2-to-2 scattering alone. To demonstrate this we give an explicit example of such a UV completion.

  18. Maximizing and customer loyalty: Are maximizers less loyal?

    Directory of Open Access Journals (Sweden)

    Linda Lai

    2011-06-01

    Full Text Available Despite their efforts to choose the best of all available solutions, maximizers seem to be more inclined than satisficers to regret their choices and to experience post-decisional dissonance. Maximizers may therefore be expected to change their decisions more frequently and hence exhibit lower customer loyalty to providers of products and services compared to satisficers. Findings from the study reported here (N = 1978 support this prediction. Maximizers reported significantly higher intentions to switch to another service provider (television provider than satisficers. Maximizers' intentions to switch appear to be intensified and mediated by higher proneness to regret, increased desire to discuss relevant choices with others, higher levels of perceived knowledge of alternatives, and higher ego involvement in the end product, compared to satisficers. Opportunities for future research are suggested.

  19. Implications of maximal Jarlskog invariant and maximal CP violation

    International Nuclear Information System (INIS)

    Rodriguez-Jauregui, E.; Universidad Nacional Autonoma de Mexico

    2001-04-01

    We argue here why CP violating phase Φ in the quark mixing matrix is maximal, that is, Φ=90 . In the Standard Model CP violation is related to the Jarlskog invariant J, which can be obtained from non commuting Hermitian mass matrices. In this article we derive the conditions to have Hermitian mass matrices which give maximal Jarlskog invariant J and maximal CP violating phase Φ. We find that all squared moduli of the quark mixing elements have a singular point when the CP violation phase Φ takes the value Φ=90 . This special feature of the Jarlskog invariant J and the quark mixing matrix is a clear and precise indication that CP violating Phase Φ is maximal in order to let nature treat democratically all of the quark mixing matrix moduli. (orig.)

  20. Schiff base ligand

    Indian Academy of Sciences (India)

    Unknown

    Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

  1. Phenomenology of maximal and near-maximal lepton mixing

    International Nuclear Information System (INIS)

    Gonzalez-Garcia, M. C.; Pena-Garay, Carlos; Nir, Yosef; Smirnov, Alexei Yu.

    2001-01-01

    The possible existence of maximal or near-maximal lepton mixing constitutes an intriguing challenge for fundamental theories of flavor. We study the phenomenological consequences of maximal and near-maximal mixing of the electron neutrino with other (x=tau and/or muon) neutrinos. We describe the deviations from maximal mixing in terms of a parameter ε(equivalent to)1-2sin 2 θ ex and quantify the present experimental status for |ε| e mixing comes from solar neutrino experiments. We find that the global analysis of solar neutrino data allows maximal mixing with confidence level better than 99% for 10 -8 eV 2 ∼ 2 ∼ -7 eV 2 . In the mass ranges Δm 2 ∼>1.5x10 -5 eV 2 and 4x10 -10 eV 2 ∼ 2 ∼ -7 eV 2 the full interval |ε| e mixing in atmospheric neutrinos, supernova neutrinos, and neutrinoless double beta decay

  2. Maximize x(a - x)

    Science.gov (United States)

    Lange, L. H.

    1974-01-01

    Five different methods for determining the maximizing condition for x(a - x) are presented. Included is the ancient Greek version and a method attributed to Fermat. None of the proofs use calculus. (LS)

  3. Finding Maximal Quasiperiodicities in Strings

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Pedersen, Christian N. S.

    2000-01-01

    of length n in time O(n log n) and space O(n). Our algorithm uses the suffix tree as the fundamental data structure combined with efficient methods for merging and performing multiple searches in search trees. Besides finding all maximal quasiperiodic substrings, our algorithm also marks the nodes......Apostolico and Ehrenfeucht defined the notion of a maximal quasiperiodic substring and gave an algorithm that finds all maximal quasiperiodic substrings in a string of length n in time O(n log2 n). In this paper we give an algorithm that finds all maximal quasiperiodic substrings in a string...... in the suffix tree that have a superprimitive path-label....

  4. Bounded variation and around

    CERN Document Server

    Appell, Jürgen; Merentes Díaz, Nelson José

    2013-01-01

    This monographis a self-contained exposition of the definition and properties of functionsof bounded variation and their various generalizations; the analytical properties of nonlinear composition operators in spaces of such functions; applications to Fourier analysis, nonlinear integral equations, and boundary value problems. The book is written for non-specialists. Every chapter closes with a list of exercises and open problems.

  5. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  6. Natural products as tools for studies of ligand-gated ion channels

    DEFF Research Database (Denmark)

    Strømgaard, Kristian

    2005-01-01

    Ligand-gated ion channels, or ionotropic receptors, constitute a group of membrane-bound proteins that regulate the flux of ions across the cell membrane. In the brain, ligand-gated ion channels mediate fast neurotransmission. They are crucial for normal brain function and involved in many diseases...

  7. Maximization

    Directory of Open Access Journals (Sweden)

    A. Garmroodi Asil

    2017-09-01

    To further reduce the sulfur dioxide emission of the entire refining process, two scenarios of acid gas or air preheats are investigated when either of them is used simultaneously with the third enrichment scheme. The maximum overall sulfur recovery efficiency and highest combustion chamber temperature is slightly higher for acid gas preheats but air preheat is more favorable because it is more benign. To the best of our knowledge, optimization of the entire GTU + enrichment section and SRU processes has not been addressed previously.

  8. Maps of Bounded Rationality

    OpenAIRE

    Kahneman, Daniel

    2002-01-01

    The work cited by the Nobel committee was done jointly with the late Amos Tversky (1937-1996) during a long and unusually close collaboration. Together, we explored the psychology of intuitive beliefs and choices and examined their bounded rationality. This essay presents a current perspective on the three major topics of our joint work: heuristics of judgment, risky choice, and framing effects. In all three domains we studied intuitions - thoughts and preferences that come to mind quickly an...

  9. Bounded Satisfiability for PCTL

    OpenAIRE

    Bertrand, Nathalie; Fearnley, John; Schewe, Sven

    2012-01-01

    While model checking PCTL for Markov chains is decidable in polynomial-time, the decidability of PCTL satisfiability, as well as its finite model property, are long standing open problems. While general satisfiability is an intriguing challenge from a purely theoretical point of view, we argue that general solutions would not be of interest to practitioners: such solutions could be too big to be implementable or even infinite. Inspired by bounded synthesis techniques, we turn to the more appl...

  10. Group IV nanocrystals with ion-exchangeable surface ligands and methods of making the same

    Science.gov (United States)

    Wheeler, Lance M.; Nichols, Asa W.; Chernomordik, Boris D.; Anderson, Nicholas C.; Beard, Matthew C.; Neale, Nathan R.

    2018-01-09

    Methods are described that include reacting a starting nanocrystal that includes a starting nanocrystal core and a covalently bound surface species to create an ion-exchangeable (IE) nanocrystal that includes a surface charge and a first ion-exchangeable (IE) surface ligand ionically bound to the surface charge, where the starting nanocrystal core includes a group IV element.

  11. Universal bounds on current fluctuations.

    Science.gov (United States)

    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.

  12. Analytic quantum bounds on Bell inequalities

    International Nuclear Information System (INIS)

    Filipp, S.; Svozil, K.

    2005-01-01

    Full text: Can realism be combined with the quantum world? An important tool to investigate in this question are Bell's inequalities and violations thereof - they represent a cornerstone of our present understanding of quantum mechanics and therefore the description of nature. Here we present a simple algebraic method to calculate violations for any measurement arrangements that are maximal in the sense that quantum mechanics does not allow a stronger violation. Having two or more polarization analyzers available and a source producing photon-pairs in arbitrary polarization states Bell-type inequalities tell us which probabilities for measuring the polarization in particular directions are viable in a deterministic theory. Quantum mechanics does not obey these rules, but yields a violation of these inequalities. The questions is to what extent the inequalities are violated. Making use of a min-max principle analytical expressions can be found for the 'fine structure' of the maximal violations of arbitrary Bell-like inequalities, i. e. the upper bound reachable by any state when the analyzers measure in given directions. Knowing these bounds is useful for experimental tests of the validity of quantum mechanics and can serve as a prerequisite to answer the even more pressing question, why no stronger violation has been observed until now. (author)

  13. Chamaebatiaria millefolium (Torr.) Maxim.: fernbush

    Science.gov (United States)

    Nancy L. Shaw; Emerenciana G. Hurd

    2008-01-01

    Fernbush - Chamaebatiaria millefolium (Torr.) Maxim. - the only species in its genus, is endemic to the Great Basin, Colorado Plateau, and adjacent areas of the western United States. It is an upright, generally multistemmed, sweetly aromatic shrub 0.3 to 2 m tall. Bark of young branches is brown and becomes smooth and gray with age. Leaves are leathery, alternate,...

  14. Lower and Upper Bounds in Zone Based Abstractions of Timed Automata

    DEFF Research Database (Denmark)

    Behrmann, Gerd; Bouyer, Patricia; Larsen, Kim Guldstrand

    2004-01-01

    Timed automata have an infinite semantics. For verification purposes, one usually uses zone based abstractions w.r.t. the maximal constants to which clocks of the timed automaton are compared. We show that by distinguishing maximal lower and upper bounds, significantly coarser abstractions can...... dramatically increases the scalability of the real-time model checker Uppaal....

  15. Lower and Upper Bounds in Zone-Based Abstractions of Timed Automata

    DEFF Research Database (Denmark)

    Behrmann, Gerd; Bouyer, Patricia; Larsen, Kim Guldstrand

    2005-01-01

    The semantics of timed automata is defined using an infinite-state transition system. For verification purposes, one usually uses zone based abstractions w.r.t. the maximal constants to which clocks of the timed automaton are compared. We show that by distinguishing maximal lower and upper bounds...

  16. A bound on chaos

    Energy Technology Data Exchange (ETDEWEB)

    Maldacena, Juan [School of Natural Sciences, Institute for Advanced Study,1 Einstein Drive, Princeton, NJ (United States); Shenker, Stephen H. [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University,382 Via Pueblo Mall, Stanford, CA (United States); Stanford, Douglas [School of Natural Sciences, Institute for Advanced Study,1 Einstein Drive, Princeton, NJ (United States)

    2016-08-17

    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{sub L}≤2πk{sub B}T/ℏ. We give a precise mathematical argument, based on plausible physical assumptions, establishing this conjecture.

  17. Maximally reliable Markov chains under energy constraints.

    Science.gov (United States)

    Escola, Sean; Eisele, Michael; Miller, Kenneth; Paninski, Liam

    2009-07-01

    Signal-to-noise ratios in physical systems can be significantly degraded if the outputs of the systems are highly variable. Biological processes for which highly stereotyped signal generations are necessary features appear to have reduced their signal variabilities by employing multiple processing steps. To better understand why this multistep cascade structure might be desirable, we prove that the reliability of a signal generated by a multistate system with no memory (i.e., a Markov chain) is maximal if and only if the system topology is such that the process steps irreversibly through each state, with transition rates chosen such that an equal fraction of the total signal is generated in each state. Furthermore, our result indicates that by increasing the number of states, it is possible to arbitrarily increase the reliability of the system. In a physical system, however, an energy cost is associated with maintaining irreversible transitions, and this cost increases with the number of such transitions (i.e., the number of states). Thus, an infinite-length chain, which would be perfectly reliable, is infeasible. To model the effects of energy demands on the maximally reliable solution, we numerically optimize the topology under two distinct energy functions that penalize either irreversible transitions or incommunicability between states, respectively. In both cases, the solutions are essentially irreversible linear chains, but with upper bounds on the number of states set by the amount of available energy. We therefore conclude that a physical system for which signal reliability is important should employ a linear architecture, with the number of states (and thus the reliability) determined by the intrinsic energy constraints of the system.

  18. Using chemical shift perturbation to characterise ligand binding.

    Science.gov (United States)

    Williamson, Mike P

    2013-08-01

    Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced changes in chemical shift, CIS) follows changes in the chemical shifts of a protein when a ligand is added, and uses these to determine the location of the binding site, the affinity of the ligand, and/or possibly the structure of the complex. A key factor in determining the appearance of spectra during a titration is the exchange rate between free and bound, or more specifically the off-rate koff. When koff is greater than the chemical shift difference between free and bound, which typically equates to an affinity Kd weaker than about 3μM, then exchange is fast on the chemical shift timescale. Under these circumstances, the observed shift is the population-weighted average of free and bound, which allows Kd to be determined from measurement of peak positions, provided the measurements are made appropriately. (1)H shifts are influenced to a large extent by through-space interactions, whereas (13)Cα and (13)Cβ shifts are influenced more by through-bond effects. (15)N and (13)C' shifts are influenced both by through-bond and by through-space (hydrogen bonding) interactions. For determining the location of a bound ligand on the basis of shift change, the most appropriate method is therefore usually to measure (15)N HSQC spectra, calculate the geometrical distance moved by the peak, weighting (15)N shifts by a factor of about 0.14 compared to (1)H shifts, and select those residues for which the weighted shift change is larger than the standard deviation of the shift for all residues. Other methods are discussed, in particular the measurement of (13)CH3 signals. Slow to intermediate exchange rates lead to line broadening, and make Kd values very difficult to obtain. There is no good way to distinguish changes in chemical shift due to direct binding of the ligand from changes in chemical shift due to allosteric change. Ligand binding at multiple sites can often be characterised, by

  19. Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg²+ cation for phosphoryl ligands.

    Science.gov (United States)

    da Costa, Leonardo Moreira; de Mesquita Carneiro, José Walkimar; Paes, Lilian Weitzel Coelho

    2011-08-01

    DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

  20. Ultrafast dynamics of ligand and substrate interaction in endothelial nitric oxide synthase under Soret excitation.

    Science.gov (United States)

    Hung, Chih-Chang; Yabushita, Atsushi; Kobayashi, Takayoshi; Chen, Pei-Feng; Liang, Keng S

    2016-01-01

    Ultrafast transient absorption spectroscopy of endothelial NOS oxygenase domain (eNOS-oxy) was performed to study dynamics of ligand or substrate interaction under Soret band excitation. Photo-excitation dissociates imidazole ligand in 4ps. The eNOS-oxy without additive is partially bound with water molecule, thus its photoexcited dynamics also shows ligand dissociation in <800fs. Then it followed by vibrational cooling coupled with charge transfer in 4.8ps, and recombination of ligand to distal side of heme in 12ps. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Spectra of fluorinated rare earth β-diketonates with added ligands

    International Nuclear Information System (INIS)

    Khomenko, V.S.; Lozinskij, M.O.; Fialkov, Yu.A.; Rasshinina, T.A.; Krasovskaya, L.I.; AN Ukrainskoj SSR, Kiev. Inst. Organicheskoj Khimii)

    1984-01-01

    Different-ligand rare earth complexes are synthesized. Fluorated β-diketones, triethylphosphine oxide and trifluoracetic acid are used as active ligands. Mass-spectra of low and high resolution are taken at the energy of ionizing electrons of 70 eV, as well as luminescence spectra of complexes. Fragmentation ways of complexes decomposition under electron shock are studied. A series of changing the bound strength of additional ligands with europium in mixed complexes is determined. It is shown that the introduction of additional ligands can purposefully change physical and chemical properties of complexes

  2. IMNN: Information Maximizing Neural Networks

    Science.gov (United States)

    Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.

    2018-04-01

    This software trains artificial neural networks to find non-linear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). As compressing large data sets vastly simplifies both frequentist and Bayesian inference, important information may be inadvertently missed. Likelihood-free inference based on automatically derived IMNN summaries produces summaries that are good approximations to sufficient statistics. IMNNs are robustly capable of automatically finding optimal, non-linear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima.

  3. Is the β phase maximal?

    International Nuclear Information System (INIS)

    Ferrandis, Javier

    2005-01-01

    The current experimental determination of the absolute values of the CKM elements indicates that 2 vertical bar V ub /V cb V us vertical bar =(1-z), with z given by z=0.19+/-0.14. This fact implies that irrespective of the form of the quark Yukawa matrices, the measured value of the SM CP phase β is approximately the maximum allowed by the measured absolute values of the CKM elements. This is β=(π/6-z/3) for γ=(π/3+z/3), which implies α=π/2. Alternatively, assuming that β is exactly maximal and using the experimental measurement sin(2β)=0.726+/-0.037, the phase γ is predicted to be γ=(π/2-β)=66.3 o +/-1.7 o . The maximality of β, if confirmed by near-future experiments, may give us some clues as to the origin of CP violation

  4. Strategy to maximize maintenance operation

    OpenAIRE

    Espinoza, Michael

    2005-01-01

    This project presents a strategic analysis to maximize maintenance operations in Alcan Kitimat Works in British Columbia. The project studies the role of maintenance in improving its overall maintenance performance. It provides strategic alternatives and specific recommendations addressing Kitimat Works key strategic issues and problems. A comprehensive industry and competitive analysis identifies the industry structure and its competitive forces. In the mature aluminium industry, the bargain...

  5. Scalable Nonlinear AUC Maximization Methods

    OpenAIRE

    Khalid, Majdi; Ray, Indrakshi; Chitsaz, Hamidreza

    2017-01-01

    The area under the ROC curve (AUC) is a measure of interest in various machine learning and data mining applications. It has been widely used to evaluate classification performance on heavily imbalanced data. The kernelized AUC maximization machines have established a superior generalization ability compared to linear AUC machines because of their capability in modeling the complex nonlinear structure underlying most real world-data. However, the high training complexity renders the kernelize...

  6. Relativistic bound states

    International Nuclear Information System (INIS)

    Ritchie, Burke

    2006-01-01

    The Hamiltonian for Dirac's second-order equation depends nonlinearly on the potential V and the energy E. For this reason the magnetic contribution to the Hamiltonian for s-waves, which has a short range, is attractive for a repulsive Coulomb potential (V>0) and repulsive for an attractive Coulomb potential (V 2 . Usually solutions are found in the regime E=mc 2 +ε , where except for high Z, ε 2 . Here it is shown that for V>0 the attractive magnetic term and the linear repulsive term combine to support a bound state near E=0.5mc 2 corresponding to a binding energy E b =-ε =0.5mc 2

  7. A Maximal Element Theorem in FWC-Spaces and Its Applications

    Science.gov (United States)

    Hu, Qingwen; Miao, Yulin

    2014-01-01

    A maximal element theorem is proved in finite weakly convex spaces (FWC-spaces, in short) which have no linear, convex, and topological structure. Using the maximal element theorem, we develop new existence theorems of solutions to variational relation problem, generalized equilibrium problem, equilibrium problem with lower and upper bounds, and minimax problem in FWC-spaces. The results represented in this paper unify and extend some known results in the literature. PMID:24782672

  8. FLOUTING MAXIMS IN INDONESIA LAWAK KLUB CONVERSATION

    Directory of Open Access Journals (Sweden)

    Rahmawati Sukmaningrum

    2017-04-01

    Full Text Available This study aims to identify the types of maxims flouted in the conversation in famous comedy show, Indonesia Lawak Club. Likewise, it also tries to reveal the speakers‘ intention of flouting the maxim in the conversation during the show. The writers use descriptive qualitative method in conducting this research. The data is taken from the dialogue of Indonesia Lawak club and then analyzed based on Grice‘s cooperative principles. The researchers read the dialogue‘s transcripts, identify the maxims, and interpret the data to find the speakers‘ intention for flouting the maxims in the communication. The results show that there are four types of maxims flouted in the dialogue. Those are maxim of quality (23%, maxim of quantity (11%, maxim of manner (31%, and maxim of relevance (35. Flouting the maxims in the conversations is intended to make the speakers feel uncomfortable with the conversation, show arrogances, show disagreement or agreement, and ridicule other speakers.

  9. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  10. Specific ability of sulfur-ligands on removal of 203Hg-labeled organomercury from hemoglobin in comparison with nitrogen-ligands

    International Nuclear Information System (INIS)

    Hojo, Yasuji; Sugiura, Yukio; Tanaka, Hisashi

    1975-01-01

    Removal of 203 Hg-labeled organomercurials, bound to sulfhydryl groups of hemoglobin, by various chelating agents was investigated by the use of equilibrium dialysis. Organomercurials employed were chlormerodrin, methylmercury, ethylmercury and phenylmercury compounds. Higher and more specific effects of the sulfur-ligands, such as penicillamine and glutathione, on removal of organomercurial were found as compared with those of the nitrogen-ligands such as EDTA, glycine and polymethylenediamines. Linear correlation was observed between the degree of organomercury elimination from hemoglobin and the stability constant (log K 1 ) of 1:1 organomercury complex in both the sulfur- and nitrogen-ligand systems and at the same value of log K 1 , the elimination-effect of sulfur-ligands was extremely greater than that of the nitrogen-ligands. The relationship between the average percentage of removal and the Taft's polar substituent constant of organic moiety of the metal was also linear among the organomercury compounds other than chlormerodrin. The average removal percentage by sulfur-ligands increased in the order, ethylmercury>methylmercury>phenylmercury, while that of the nitrogen-ligands was not different among the organomercurials investigated. In addition, direct ligand-exchange reaction between hemoglobin-SH and the ligand coordinating-atom (S or N) against organomercurials rather than Ssub(N2) reaction via the ternary complex, hemoglobin-S-RHg-ligand, is postulated. (auth.)

  11. Bounding approaches to system identification

    CERN Document Server

    Norton, John; Piet-Lahanier, Hélène; Walter, Éric

    1996-01-01

    In response to the growing interest in bounding error approaches, the editors of this volume offer the first collection of papers to describe advances in techniques and applications of bounding of the parameters, or state variables, of uncertain dynamical systems. Contributors explore the application of the bounding approach as an alternative to the probabilistic analysis of such systems, relating its importance to robust control-system design.

  12. Market access through bound tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Yalcin, Erdal; Schröder, Philipp

    2010-01-01

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and longterm...

  13. Market Access through Bound Tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and long...

  14. Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

    KAUST Repository

    Choi, Joshua J.; Bealing, Clive R.; Bian, Kaifu; Hughes, Kevin J.; Zhang, Wenyu; Smilgies, Detlef-M.; Hennig, Richard G.; Engstrom, James R.; Hanrath, Tobias

    2011-01-01

    The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

  15. Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

    KAUST Repository

    Choi, Joshua J.

    2011-03-09

    The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

  16. Quivers of Bound Path Algebras and Bound Path Coalgebras

    Directory of Open Access Journals (Sweden)

    Dr. Intan Muchtadi

    2010-09-01

    Full Text Available bras and coalgebras can be represented as quiver (directed graph, and from quiver we can construct algebras and coalgebras called path algebras and path coalgebras. In this paper we show that the quiver of a bound path coalgebra (resp. algebra is the dual quiver of its bound path algebra (resp. coalgebra.

  17. Outer measures and weak type estimates of Hardy-Littlewood maximal operators

    Directory of Open Access Journals (Sweden)

    Terasawa Yutaka

    2006-01-01

    Full Text Available We will introduce the times modified centered and uncentered Hardy-Littlewood maximal operators on nonhomogeneous spaces for . We will prove that the times modified centered Hardy-Littlewood maximal operator is weak type bounded with constant when if the Radon measure of the space has "continuity" in some sense. In the proof, we will use the outer measure associated with the Radon measure. We will also prove other results of Hardy-Littlewood maximal operators on homogeneous spaces and on the real line by using outer measures.

  18. Maximal Abelian sets of roots

    CERN Document Server

    Lawther, R

    2018-01-01

    In this work the author lets \\Phi be an irreducible root system, with Coxeter group W. He considers subsets of \\Phi which are abelian, meaning that no two roots in the set have sum in \\Phi \\cup \\{ 0 \\}. He classifies all maximal abelian sets (i.e., abelian sets properly contained in no other) up to the action of W: for each W-orbit of maximal abelian sets we provide an explicit representative X, identify the (setwise) stabilizer W_X of X in W, and decompose X into W_X-orbits. Abelian sets of roots are closely related to abelian unipotent subgroups of simple algebraic groups, and thus to abelian p-subgroups of finite groups of Lie type over fields of characteristic p. Parts of the work presented here have been used to confirm the p-rank of E_8(p^n), and (somewhat unexpectedly) to obtain for the first time the 2-ranks of the Monster and Baby Monster sporadic groups, together with the double cover of the latter. Root systems of classical type are dealt with quickly here; the vast majority of the present work con...

  19. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  20. Competition Law and the Bounded Rationality of Firms

    OpenAIRE

    Bhattacharya, Shilpi

    2016-01-01

    Firm rationality plays a role in several aspects of competition law. Yet, the conception of the firm as a rational, profit maximizing entity has been disputed in different disciplines. This literature shows that neoclassical economic assumptions on which competition law is based can fall short of explaining the full range of observed firm behaviour. Accordingly, an alternative conception of the firm as boundedly rational can impact the understanding of firm conduct in competition law. Be...

  1. Radiobiology with DNA ligands

    International Nuclear Information System (INIS)

    Weinreich, R.; Argentini, M.; Guenther, I.; Koziorowski, J.; Larsson, B.; Nievergelt-Egido, M.C.; Salt, C.; Wyer, L.; Dos Santos, D.F.; Hansen, H.J.

    1997-01-01

    The paper deals with the following topics: labelling of DNA ligands and other tumour-affinic compounds with 4.15-d 124 I, radiotoxicity of Hoechst 33258 and 33342 and of iodinated Hoechst 33258 in cell cultures, preparation of 76 Br-, 123 I-, and 221 At-labelled 5-halo-2'-deoxyuridine, chemical syntheses of boron derivatives of Hoechst 33258.III., Gadolinium neutron capture therapy

  2. Bounds for Asian basket options

    Science.gov (United States)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  3. Product differentiation under bounded rationality

    NARCIS (Netherlands)

    Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

    2015-01-01

    We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

  4. A feasibility study of unconventional planar ligand spacers in chalcogenide nanocrystals.

    Science.gov (United States)

    Lukose, Binit; Clancy, Paulette

    2016-05-18

    The solar cell efficiency of chalcogenide nanocrystals (quantum dots) has been limited in the past by the insulation between neighboring quantum dots caused by intervening, often long-chain, aliphatic ligands. We have conducted a computationally based feasibility study to investigate the use of ultra-thin, planar, charge-conducting ligands as an alternative to traditional long passive ligands. Not only might these radically unconventional ligands decrease the mean distance between adjacent quantum dots, but, since they are charge-conducting, they have the potential to actively enhance charge migration. Our ab initio studies compare the binding energies, electronic energy gaps, and absorption characteristics for both conventional and unconventional ligands, such as phthalocyanines, porphyrins and coronene. This comparison identified these unconventional ligands with the exception of titanyl phthalocyanine, that bind to themselves more strongly than to the surface of the quantum dot, which is likely to be less desirable for enhancing charge transport. The distribution of finite energy levels of the bound system is sensitive to the ligand's binding site and the levels correspond to delocalized states. We also observed a trap state localized on a single Pb atom when a sulfur-containing phenyldithiocarbamate (PTC) ligand is attached to a slightly off-stoichiometric dot in a manner that the sulfur of the ligand completes stoichiometry of the bound system. Hence, this is indicative of the source of trap state when thio-based ligands are bound to chalcogenide nanocrystals. We also predict that titanyl phthalocyanine in a mix with chalcogenide dots of diameter ∼1.5 Å can form a donor-acceptor system.

  5. Metabolism of organically bound tritium

    International Nuclear Information System (INIS)

    Travis, C.C.

    1984-01-01

    The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables

  6. Maximizing benefits from resource development

    International Nuclear Information System (INIS)

    Skjelbred, B.

    2002-01-01

    The main objectives of Norwegian petroleum policy are to maximize the value creation for the country, develop a national oil and gas industry, and to be at the environmental forefront of long term resource management and coexistence with other industries. The paper presents a graph depicting production and net export of crude oil for countries around the world for 2002. Norway produced 3.41 mill b/d and exported 3.22 mill b/d. Norwegian petroleum policy measures include effective regulation and government ownership, research and technology development, and internationalisation. Research and development has been in five priority areas, including enhanced recovery, environmental protection, deep water recovery, small fields, and the gas value chain. The benefits of internationalisation includes capitalizing on Norwegian competency, exploiting emerging markets and the assurance of long-term value creation and employment. 5 figs

  7. Maximizing synchronizability of duplex networks

    Science.gov (United States)

    Wei, Xiang; Emenheiser, Jeffrey; Wu, Xiaoqun; Lu, Jun-an; D'Souza, Raissa M.

    2018-01-01

    We study the synchronizability of duplex networks formed by two randomly generated network layers with different patterns of interlayer node connections. According to the master stability function, we use the smallest nonzero eigenvalue and the eigenratio between the largest and the second smallest eigenvalues of supra-Laplacian matrices to characterize synchronizability on various duplexes. We find that the interlayer linking weight and linking fraction have a profound impact on synchronizability of duplex networks. The increasingly large inter-layer coupling weight is found to cause either decreasing or constant synchronizability for different classes of network dynamics. In addition, negative node degree correlation across interlayer links outperforms positive degree correlation when most interlayer links are present. The reverse is true when a few interlayer links are present. The numerical results and understanding based on these representative duplex networks are illustrative and instructive for building insights into maximizing synchronizability of more realistic multiplex networks.

  8. On Maximal Surfaces in Certain Non-Flat 3-Dimensional Robertson-Walker Spacetimes

    Energy Technology Data Exchange (ETDEWEB)

    Romero, Alfonso, E-mail: aromero@ugr.es [Universidad de Granada, Departamento de Geometria y Topologia (Spain); Rubio, Rafael M., E-mail: rmrubio@uco.es [Universidad de Cordoba, Departamento de Matematicas, Campus de Rabanales (Spain)

    2012-09-15

    An upper bound for the integral, on a geodesic disc, of the squared length of the gradient of a distinguished function on any maximal surface in certain non-flat 3-dimensional Robertson-Walker spacetimes is obtained. As an application, a new proof of a known Calabi-Bernstein's theorem is given.

  9. VIOLATION OF CONVERSATION MAXIM ON TV ADVERTISEMENTS

    Directory of Open Access Journals (Sweden)

    Desak Putu Eka Pratiwi

    2015-07-01

    Full Text Available Maxim is a principle that must be obeyed by all participants textually and interpersonally in order to have a smooth communication process. Conversation maxim is divided into four namely maxim of quality, maxim of quantity, maxim of relevance, and maxim of manner of speaking. Violation of the maxim may occur in a conversation in which the information the speaker has is not delivered well to his speaking partner. Violation of the maxim in a conversation will result in an awkward impression. The example of violation is the given information that is redundant, untrue, irrelevant, or convoluted. Advertisers often deliberately violate the maxim to create unique and controversial advertisements. This study aims to examine the violation of maxims in conversations of TV ads. The source of data in this research is food advertisements aired on TV media. Documentation and observation methods are applied to obtain qualitative data. The theory used in this study is a maxim theory proposed by Grice (1975. The results of the data analysis are presented with informal method. The results of this study show an interesting fact that the violation of maxim in a conversation found in the advertisement exactly makes the advertisements very attractive and have a high value.

  10. Fluorescent ligands for studying neuropeptide receptors by confocal microscopy

    Directory of Open Access Journals (Sweden)

    A. Beaudet

    1998-11-01

    Full Text Available This paper reviews the use of confocal microscopy as it pertains to the identification of G-protein coupled receptors and the study of their dynamic properties in cell cultures and in mammalian brain following their tagging with specific fluorescent ligands. Principles that should guide the choice of suitable ligands and fluorophores are discussed. Examples are provided from the work carried out in the authors' laboratory using custom synthetized fluoresceinylated or BODIPY-tagged bioactive peptides. The results show that confocal microscopic detection of specifically bound fluorescent ligands permits high resolution appraisal of neuropeptide receptor distribution both in cell culture and in brain sections. Within the framework of time course experiments, it also allows for a dynamic assessment of the internalization and subsequent intracellular trafficking of bound fluorescent molecules. Thus, it was found that neurotensin, somatostatin and mu- and delta-selective opioid peptides are internalized in a receptor-dependent fashion and according to receptor-specific patterns into their target cells. In the case of neurotensin, this internalization process was found to be clathrin-mediated, to proceed through classical endosomal pathways and, in neurons, to result in a mobilization of newly formed endosomes from neural processes to nerve cell bodies and from the periphery of cell bodies towards the perinuclear zone. These mechanisms are likely to play an important role for ligand inactivation, receptor regulation and perhaps also transmembrane signaling.

  11. Bexarotene ligand pharmaceuticals.

    Science.gov (United States)

    Hurst, R E

    2000-12-01

    Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

  12. Curvature bound from gravitational catalysis

    Science.gov (United States)

    Gies, Holger; Martini, Riccardo

    2018-04-01

    We determine bounds on the curvature of local patches of spacetime from the requirement of intact long-range chiral symmetry. The bounds arise from a scale-dependent analysis of gravitational catalysis and its influence on the effective potential for the chiral order parameter, as induced by fermionic fluctuations on a curved spacetime with local hyperbolic properties. The bound is expressed in terms of the local curvature scalar measured in units of a gauge-invariant coarse-graining scale. We argue that any effective field theory of quantum gravity obeying this curvature bound is safe from chiral symmetry breaking through gravitational catalysis and thus compatible with the simultaneous existence of chiral fermions in the low-energy spectrum. With increasing number of dimensions, the curvature bound in terms of the hyperbolic scale parameter becomes stronger. Applying the curvature bound to the asymptotic safety scenario for quantum gravity in four spacetime dimensions translates into bounds on the matter content of particle physics models.

  13. Maximal Repetitions in Written Texts: Finite Energy Hypothesis vs. Strong Hilberg Conjecture

    Directory of Open Access Journals (Sweden)

    Łukasz Dębowski

    2015-08-01

    Full Text Available The article discusses two mutually-incompatible hypotheses about the stochastic mechanism of the generation of texts in natural language, which could be related to entropy. The first hypothesis, the finite energy hypothesis, assumes that texts are generated by a process with exponentially-decaying probabilities. This hypothesis implies a logarithmic upper bound for maximal repetition, as a function of the text length. The second hypothesis, the strong Hilberg conjecture, assumes that the topological entropy grows as a power law. This hypothesis leads to a hyperlogarithmic lower bound for maximal repetition. By a study of 35 written texts in German, English and French, it is found that the hyperlogarithmic growth of maximal repetition holds for natural language. In this way, the finite energy hypothesis is rejected, and the strong Hilberg conjecture is partly corroborated.

  14. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  15. Improved Range Searching Lower Bounds

    DEFF Research Database (Denmark)

    Larsen, Kasper Green; Nguyen, Huy L.

    2012-01-01

    by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...... and Rosenberg's theorem), are also hard for dynamic range searching in the group model. This theorem allows us to reuse decades of research on range reporting lower bounds to immediately obtain a range of new group model lower bounds. Amongst others, this includes an improved lower bound for the fundamental...

  16. Outcome of the first wwPDB/CCDC/D3R Ligand Validation Workshop

    Science.gov (United States)

    Adams, Paul D.; Aertgeerts, Kathleen; Bauer, Cary; Bell, Jeffrey A.; Berman, Helen M.; Bhat, Talapady N.; Blaney, Jeff; Bolton, Evan; Bricogne, Gerard; Brown, David; Burley, Stephen K.; Case, David A.; Clark, Kirk L.; Darden, Tom; Emsley, Paul; Feher, Victoria A.; Feng, Zukang; Groom, Colin R.; Harris, Seth F.; Hendle, Jorg; Holder, Thomas; Joachimiak, Andrzej; Kleywegt, Gerard J.; Krojer, Tobias; Marcotrigiano, Joseph; Mark, Alan E.; Markley, John L.; Miller, Matthew; Minor, Wladek; Montelione, Gaetano T.; Murshudov, Garib; Nakagawa, Atsushi; Nakamura, Haruki; Nicholls, Anthony; Nicklaus, Marc; Nolte, Robert T.; Padyana, Anil K.; Peishoff, Catherine E.; Pieniazek, Susan; Read, Randy J.; Shao, Chenghua; Sheriff, Steven; Smart, Oliver; Soisson, Stephen; Spurlino, John; Stouch, Terry; Svobodova, Radka; Tempel, Wolfram; Terwilliger, Thomas C.; Tronrud, Dale; Velankar, Sameer; Ward, Suzanna; Warren, Gregory L.; Westbrook, John D.; Williams, Pamela; Yang, Huanwang; Young, Jasmine

    2016-01-01

    Summary Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery/design, and the goodness-of-fit of ligand models to electron density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide Protein Data Bank/Cambridge Crystallographic Data Centre/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30–31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the Protein Data Bank? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated. PMID:27050687

  17. Maximizing ROI (return on information)

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, B.

    2000-05-01

    The role and importance of managing information are discussed, underscoring the importance by quoting from the report of the International Data Corporation, according to which Fortune 500 companies lost $ 12 billion in 1999 due to inefficiencies resulting from intellectual re-work, substandard performance , and inability to find knowledge resources. The report predicts that this figure will rise to $ 31.5 billion by 2003. Key impediments to implementing knowledge management systems are identified as : the cost and human resources requirement of deployment; inflexibility of historical systems to adapt to change; and the difficulty of achieving corporate acceptance of inflexible software products that require changes in 'normal' ways of doing business. The author recommends the use of model, document and rule-independent systems with a document centered interface (DCI), employing rapid application development (RAD) and object technologies and visual model development, which eliminate these problems, making it possible for companies to maximize their return on information (ROI), and achieve substantial savings in implementation costs.

  18. Maximizing the optical network capacity.

    Science.gov (United States)

    Bayvel, Polina; Maher, Robert; Xu, Tianhua; Liga, Gabriele; Shevchenko, Nikita A; Lavery, Domaniç; Alvarado, Alex; Killey, Robert I

    2016-03-06

    Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available. But as the volume of data continues to increase, is there a limit to the capacity of an optical fibre communication channel? The optical fibre channel is nonlinear, and the intensity-dependent Kerr nonlinearity limit has been suggested as a fundamental limit to optical fibre capacity. Current research is focused on whether this is the case, and on linear and nonlinear techniques, both optical and electronic, to understand, unlock and maximize the capacity of optical communications in the nonlinear regime. This paper describes some of them and discusses future prospects for success in the quest for capacity. © 2016 The Authors.

  19. Bound states in string nets

    Science.gov (United States)

    Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

    2016-11-01

    We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

  20. On functions of bounded semivariation

    Czech Academy of Sciences Publication Activity Database

    Monteiro, Giselle Antunes

    2015-01-01

    Roč. 40, č. 2 (2015), s. 233-276 ISSN 0147-1937 Institutional support: RVO:67985840 Keywords : semivariation * functions of bounded variation * regulated functions Subject RIV: BA - General Mathematics http://projecteuclid.org/euclid.rae/1491271216

  1. Computational Lower Bounds Using Diagonalization

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 7. Computational Lower Bounds Using Diagonalization - Languages, Turing Machines and Complexity Classes. M V Panduranga Rao. General Article Volume 14 Issue 7 July 2009 pp 682-690 ...

  2. Maximal hypersurfaces and foliations of constant mean curvature in general relativity

    International Nuclear Information System (INIS)

    Marsden, J.E.; Tipler, F.J.; Texas Univ., Austin

    1980-01-01

    We prove theorems on existence, uniqueness and smoothness of maximal and constant mean curvature compact spacelike hypersurfaces in globally hyperbolic spacetimes. The uniqueness theorem for maximal hypersurfaces of Brill and Flaherty, which assumed matter everywhere, is extended to specetimes that are vacuum and non-flat or that satisfy a generic-type condition. In this connection we show that under general hypotheses, a spatially closed universe with a maximal hypersurface must be Wheeler universe; i.e. be closed in time as well. The existence of Lipschitz achronal maximal volume hypersurfaces under the hypothesis that candidate hypersurfaces are bounded away from the singularity is proved. This hypothesis is shown to be valid in two cases of interest: when the singularities are of strong curvature type, and when the singularity is a single ideal point. Some properties of these maximal volume hypersurfaces and difficulties with Avez' original arguments are discussed. The difficulties involve the possibility that the maximal volume hypersurface can be null on certain portions; we present an incomplete argument which suggests that these hypersurfaces are always smooth, but prove that an a priori bound on the second fundamental form does imply smoothness. An extension of the perturbation theorem of Choquet-Bruhat, Fischer and Marsden is given and conditions under which local foliantions by constant mean curvature hypersurfaces can be extended to global ones is obtained. (orig.)

  3. Moessbauer spectroscopic study of polymer-bound heme complexes

    International Nuclear Information System (INIS)

    Tsuchida, Eishun; Nishide, Hiroyuki; Yokoyama, Hiroyuki; Inoue, Hidenari; Shirai, Tsuneo.

    1984-01-01

    Moessbauer spectra were measured on the heme complexes of poly(1-vinyl- and 1-vinyl-2-methylimidazole)(PVI and PMI) and heme derivatives with covalently bound imidazoleligand (IH) and 2-methylimidazole-ligand (MIH) embedded in poly(1-vinyl-2-pyrrolidone) film. Quadrupole splitting (ΔE sub(Q)) for the carbon monoxide adduct of PMI-heme indicated large electronic field gradient at the iron nucleus, probably due to steric hindrance of the polymer chain, and this behavior agreed with its low affinity with carbon monoxide. PMI-heme formed an oxygen adduct and its isomer shift and ΔE sub(Q) values were obtained. (author)

  4. Receptor-ligand binding sites and virtual screening.

    Science.gov (United States)

    Hattotuwagama, Channa K; Davies, Matthew N; Flower, Darren R

    2006-01-01

    Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified by a haphazard and empirical process, it is now increasingly driven by both knowledge of the receptor-mediated basis of disease and how drug molecules interact with receptors and the wider physiome. Medicinal chemistry postulates that to understand a congeneric ligand series, or set thereof, is to understand the nature and requirements of a ligand binding site. Likewise, structural molecular biology posits that to understand a binding site is to understand the nature of ligands bound therein. Reality sits somewhere between these extremes, yet subsumes them both. Complementary to rules of ligand design, arising through decades of medicinal chemistry, structural biology and computational chemistry are able to elucidate the nature of binding site-ligand interactions, facilitating, at both pragmatic and conceptual levels, the drug discovery process.

  5. Tuning Confinement in Colloidal Silicon Nanocrystals with Saturated Surface Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Neale, Nathan R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Carroll, Gerard [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Limpens, Rens [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-04-16

    The optical properties of silicon nanocrystals (Si NCs) are a subject of intense study and continued debate. In particular, Si NC photoluminescence (PL) properties are known to depend strongly on the surface chemistry, resulting in electron-hole recombination pathways derived from the Si NC band-edge, surface-state defects, or combined NC-conjugated ligand hybrid states. In this Letter, we perform a comparison of three different saturated surface functional groups - alkyls, amides, and alkoxides - on nonthermal plasma-synthesized Si NCs. We find a systematic and size-dependent high-energy (blue) shift in the PL spectrum of Si NCs with amide and alkoxy functionalization relative to alkyl. Time-resolved photoluminescence and transient absorption spectroscopies reveal no change in the excited-state dynamics between Si NCs functionalized with alkyl, amide, or alkoxide ligands, showing for the first time that saturated ligands - not only surface-derived charge-transfer states or hybridization between NC and low-lying ligand orbitals - are responsible for tuning the Si NC optical properties. To explain these PL shifts we propose that the atom bound to the Si NC surface strongly interacts with the Si NC electronic wave function and modulates the Si NC quantum confinement. These results reveal a potentially broadly applicable correlation between the optoelectronic properties of Si NCs and related quantum-confined structures based on the interaction between NC surfaces and the ligand binding group.

  6. Tuning Confinement in Colloidal Silicon Nanocrystals with Saturated Surface Ligands.

    Science.gov (United States)

    Carroll, Gerard M; Limpens, Rens; Neale, Nathan R

    2018-05-09

    The optical properties of silicon nanocrystals (Si NCs) are a subject of intense study and continued debate. In particular, Si NC photoluminescence (PL) properties are known to depend strongly on the surface chemistry, resulting in electron-hole recombination pathways derived from the Si NC band-edge, surface-state defects, or combined NC-conjugated ligand hybrid states. In this Letter, we perform a comparison of three different saturated surface functional groups-alkyls, amides, and alkoxides-on nonthermal plasma-synthesized Si NCs. We find a systematic and size-dependent high-energy (blue) shift in the PL spectrum of Si NCs with amide and alkoxy functionalization relative to alkyl. Time-resolved photoluminescence and transient absorption spectroscopies reveal no change in the excited-state dynamics between Si NCs functionalized with alkyl, amide, or alkoxide ligands, showing for the first time that saturated ligands-not only surface-derived charge-transfer states or hybridization between NC and low-lying ligand orbitals-are responsible for tuning the Si NC optical properties. To explain these PL shifts we propose that the atom bound to the Si NC surface strongly interacts with the Si NC electronic wave function and modulates the Si NC quantum confinement. These results reveal a potentially broadly applicable correlation between the optoelectronic properties of Si NCs and related quantum-confined structures based on the interaction between NC surfaces and the ligand binding group.

  7. Singular Value Decomposition and Ligand Binding Analysis

    Directory of Open Access Journals (Sweden)

    André Luiz Galo

    2013-01-01

    Full Text Available Singular values decomposition (SVD is one of the most important computations in linear algebra because of its vast application for data analysis. It is particularly useful for resolving problems involving least-squares minimization, the determination of matrix rank, and the solution of certain problems involving Euclidean norms. Such problems arise in the spectral analysis of ligand binding to macromolecule. Here, we present a spectral data analysis method using SVD (SVD analysis and nonlinear fitting to determine the binding characteristics of intercalating drugs to DNA. This methodology reduces noise and identifies distinct spectral species similar to traditional principal component analysis as well as fitting nonlinear binding parameters. We applied SVD analysis to investigate the interaction of actinomycin D and daunomycin with native DNA. This methodology does not require prior knowledge of ligand molar extinction coefficients (free and bound, which potentially limits binding analysis. Data are acquired simply by reconstructing the experimental data and by adjusting the product of deconvoluted matrices and the matrix of model coefficients determined by the Scatchard and McGee and von Hippel equation.

  8. Does mental exertion alter maximal muscle activation?

    Directory of Open Access Journals (Sweden)

    Vianney eRozand

    2014-09-01

    Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

  9. AUC-Maximizing Ensembles through Metalearning.

    Science.gov (United States)

    LeDell, Erin; van der Laan, Mark J; Petersen, Maya

    2016-05-01

    Area Under the ROC Curve (AUC) is often used to measure the performance of an estimator in binary classification problems. An AUC-maximizing classifier can have significant advantages in cases where ranking correctness is valued or if the outcome is rare. In a Super Learner ensemble, maximization of the AUC can be achieved by the use of an AUC-maximining metalearning algorithm. We discuss an implementation of an AUC-maximization technique that is formulated as a nonlinear optimization problem. We also evaluate the effectiveness of a large number of different nonlinear optimization algorithms to maximize the cross-validated AUC of the ensemble fit. The results provide evidence that AUC-maximizing metalearners can, and often do, out-perform non-AUC-maximizing metalearning methods, with respect to ensemble AUC. The results also demonstrate that as the level of imbalance in the training data increases, the Super Learner ensemble outperforms the top base algorithm by a larger degree.

  10. Metal-ligand interactions

    Science.gov (United States)

    Ervin, Kent M.

    Experimental studies of the interactions of small transition-metal cluster anions with carbonyl ligands are reviewed and compared with neutral and cationic clusters. Under thermal conditions, the reaction rates of transition-metal clusters with carbon monoxide are measured as a function of cluster size. Saturation limits for carbon monoxide addition can be related to the geometric structures of the clusters. Both energy-resolved threshold collision-induced dissociation experiments and time-resolved photodissociation experiments are used to measure metal-carbonyl binding energies. For platinum and palladium trimer anions, the carbonyl binding energies are assigned to different geometric binding sites. Platinum and palladium cluster anions catalyse the oxidation of carbon monoxide to carbon dioxide in a full catalytic cycle at thermal energies.

  11. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. On maximal massive 3D supergravity

    OpenAIRE

    Bergshoeff , Eric A; Hohm , Olaf; Rosseel , Jan; Townsend , Paul K

    2010-01-01

    ABSTRACT We construct, at the linearized level, the three-dimensional (3D) N = 4 supersymmetric " general massive supergravity " and the maximally supersymmetric N = 8 " new massive supergravity ". We also construct the maximally supersymmetric linearized N = 7 topologically massive supergravity, although we expect N = 6 to be maximal at the non-linear level. (Bergshoeff, Eric A) (Hohm, Olaf) (Rosseel, Jan) P.K.Townsend@da...

  13. Inclusive Fitness Maximization:An Axiomatic Approach

    OpenAIRE

    Okasha, Samir; Weymark, John; Bossert, Walter

    2014-01-01

    Kin selection theorists argue that evolution in social contexts will lead organisms to behave as if maximizing their inclusive, as opposed to personal, fitness. The inclusive fitness concept allows biologists to treat organisms as akin to rational agents seeking to maximize a utility function. Here we develop this idea and place it on a firm footing by employing a standard decision-theoretic methodology. We show how the principle of inclusive fitness maximization and a related principle of qu...

  14. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

  15. Activity versus outcome maximization in time management.

    Science.gov (United States)

    Malkoc, Selin A; Tonietto, Gabriela N

    2018-04-30

    Feeling time-pressed has become ubiquitous. Time management strategies have emerged to help individuals fit in more of their desired and necessary activities. We provide a review of these strategies. In doing so, we distinguish between two, often competing, motives people have in managing their time: activity maximization and outcome maximization. The emerging literature points to an important dilemma: a given strategy that maximizes the number of activities might be detrimental to outcome maximization. We discuss such factors that might hinder performance in work tasks and enjoyment in leisure tasks. Finally, we provide theoretically grounded recommendations that can help balance these two important goals in time management. Published by Elsevier Ltd.

  16. On the maximal superalgebras of supersymmetric backgrounds

    International Nuclear Information System (INIS)

    Figueroa-O'Farrill, Jose; Hackett-Jones, Emily; Moutsopoulos, George; Simon, Joan

    2009-01-01

    In this paper we give a precise definition of the notion of a maximal superalgebra of certain types of supersymmetric supergravity backgrounds, including the Freund-Rubin backgrounds, and propose a geometric construction extending the well-known construction of its Killing superalgebra. We determine the structure of maximal Lie superalgebras and show that there is a finite number of isomorphism classes, all related via contractions from an orthosymplectic Lie superalgebra. We use the structure theory to show that maximally supersymmetric waves do not possess such a maximal superalgebra, but that the maximally supersymmetric Freund-Rubin backgrounds do. We perform the explicit geometric construction of the maximal superalgebra of AdS 4 X S 7 and find that it is isomorphic to osp(1|32). We propose an algebraic construction of the maximal superalgebra of any background asymptotic to AdS 4 X S 7 and we test this proposal by computing the maximal superalgebra of the M2-brane in its two maximally supersymmetric limits, finding agreement.

  17. Task-oriented maximally entangled states

    International Nuclear Information System (INIS)

    Agrawal, Pankaj; Pradhan, B

    2010-01-01

    We introduce the notion of a task-oriented maximally entangled state (TMES). This notion depends on the task for which a quantum state is used as the resource. TMESs are the states that can be used to carry out the task maximally. This concept may be more useful than that of a general maximally entangled state in the case of a multipartite system. We illustrate this idea by giving an operational definition of maximally entangled states on the basis of communication tasks of teleportation and superdense coding. We also give examples and a procedure to obtain such TMESs for n-qubit systems.

  18. Quantitative analysis of protein-ligand interactions by NMR.

    Science.gov (United States)

    Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

    2016-08-01

    Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

  19. Simulation bounds for system availability

    International Nuclear Information System (INIS)

    Tietjen, G.L.; Waller, R.A.

    1976-01-01

    System availability is a dominant factor in the practicality of nuclear power electrical generating plants. A proposed model for obtaining either lower bounds or interval estimates on availability uses observed data on ''n'' failure-to-repair cycles of the system to estimate the parameters in the time-to-failure and time-to-repair models. These estimates are then used in simulating failure/repair cycles of the system. The availability estimate is obtained for each of 5000 samples of ''n'' failure/repair cycles to form a distribution of estimates. Specific percentile points of those simulated distributions are selected as lower simulation bounds or simulation interval bounds for the system availability. The method is illustrated with operational data from two nuclear plants for which an exponential time-to-failure and a lognormal time-to-repair are assumed

  20. Selenolate complexes of CYP101 and the heme-bound hHO-1/H25A proximal cavity mutant.

    Science.gov (United States)

    Jiang, Yongying; Ortiz de Montellano, Paul R

    2008-05-05

    Thiolate and selenolate complexes of CYP101 (P450cam) and the H25A proximal cavity mutant of heme-bound human heme oxygenase-1 (hHO-1) have been examined by UV-vis spectroscopy. Both thiolate and selenolate ligands bound to the heme distal side in CYP101 and gave rise to characteristic hyperporphyrin spectra. Thiolate ligands also bound to the proximal side of the heme in the cavity created by the H25A mutation in hHO-1, giving a Soret absorption similar to that of the H25C hHO-1 mutant. Selenolate ligands also bound to this cavity mutant under anaerobic conditions but reduced the heme iron to the ferrous state, as shown by the formation of a ferrous CO complex. Under aerobic conditions, the selenolate ligand but not the thiolate ligand was rapidly oxidized. These results indicate that selenocysteine-coordinated heme proteins will not be stable species in the absence of a redox potential stabilizing effect.

  1. Relativistic bound state wave functions

    International Nuclear Information System (INIS)

    Micu, L.

    2005-01-01

    A particular method of writing the bound state wave functions in relativistic form is applied to the solutions of the Dirac equation with confining potentials in order to obtain a relativistic description of a quark antiquark bound system representing a given meson. Concerning the role of the effective constituent in the present approach we first observe that without this additional constituent we couldn't expand the bound state wave function in terms of products of free states. Indeed, we notice that if the wave function depends on the relative coordinates only, all the expansion coefficients would be infinite. Secondly we remark that the effective constituent enabled us to give a Lorentz covariant meaning to the potential energy of the bound system which is now seen as the 4th component of a 4-momentum. On the other side, by relating the effective constituent to the quantum fluctuations of the background field which generate the binding, we provided a justification for the existence of some spatial degrees of freedom accompanying the interaction potential. These ones, which are quite unusual in quantum mechanics, in our model are the natural consequence of the the independence of the quarks and can be seen as the effect of the imperfect cancellation of the vector momenta during the quantum fluctuations. Related with all these we remark that the adequate representation for the relativistic description of a bound system is the momentum representation, because of the transparent and easy way of writing the conservation laws and the transformation properties of the wave functions. The only condition to be fulfilled is to find a suitable way to take into account the potential energy of the bound system. A particular feature of the present approach is that the confining forces are due to a kind of glue where both quarks are embedded. This recalls other bound state models where the wave function is factorized in terms of constituent wave functions and the confinement is

  2. Four-quark bound states

    International Nuclear Information System (INIS)

    Zouzou, S.

    1986-01-01

    In the framework of simple non-relativistic potential models, we examine the system consisting of two quarks and two antiquarks with equal or unequal masses. We search for possible bound states below the threshold for the spontaneous dissociation into two mesons. We solve the four body problem by empirical or systematic variational methods and we include the virtual meson-meson components of the wave function. With standard two-body potentials, there is no proliferation of multiquarks. With unequal quark masses, we obtain however exotic (anti Qanti Qqq) bound states with a baryonic antidiquark-quark-quark structure very analogous to the heavy flavoured (Q'qq) baryons. (orig.)

  3. Bound entanglement and local realism

    International Nuclear Information System (INIS)

    Kaszlikowski, Dagomir; Zukowski, Marek; Gnacinski, Piotr

    2002-01-01

    We show using a numerical approach, which gives necessary and sufficient conditions for the existence of local realism, that the bound entangled state presented in Bennett et al. [Phys. Rev. Lett. 82, 5385 (1999)] admits a local and realistic description. We also find the lowest possible amount of some appropriate entangled state that must be ad-mixed to the bound entangled state so that the resulting density operator has no local and realistic description and as such can be useful in quantum communication and quantum computation

  4. Maximally Entangled Multipartite States: A Brief Survey

    International Nuclear Information System (INIS)

    Enríquez, M; Wintrowicz, I; Życzkowski, K

    2016-01-01

    The problem of identifying maximally entangled quantum states of a composite quantum systems is analyzed. We review some states of multipartite systems distinguished with respect to certain measures of quantum entanglement. Numerical results obtained for 4-qubit pure states illustrate the fact that the notion of maximally entangled state depends on the measure used. (paper)

  5. Utility maximization and mode of payment

    NARCIS (Netherlands)

    Koning, R.H.; Ridder, G.; Heijmans, R.D.H.; Pollock, D.S.G.; Satorra, A.

    2000-01-01

    The implications of stochastic utility maximization in a model of choice of payment are examined. Three types of compatibility with utility maximization are distinguished: global compatibility, local compatibility on an interval, and local compatibility on a finite set of points. Keywords:

  6. Corporate Social Responsibility and Profit Maximizing Behaviour

    OpenAIRE

    Becchetti, Leonardo; Giallonardo, Luisa; Tessitore, Maria Elisabetta

    2005-01-01

    We examine the behavior of a profit maximizing monopolist in a horizontal differentiation model in which consumers differ in their degree of social responsibility (SR) and consumers SR is dynamically influenced by habit persistence. The model outlines parametric conditions under which (consumer driven) corporate social responsibility is an optimal choice compatible with profit maximizing behavior.

  7. Quantum Bocce: Magnon–magnon collisions between propagating and bound states in 1D spin chains

    International Nuclear Information System (INIS)

    Longo, Paolo; Greentree, Andrew D.; Busch, Kurt; Cole, Jared H.

    2013-01-01

    The dynamics of two magnons in a Heisenberg spin chain under the influence of a non-uniform magnetic field is investigated by means of a numerical wave-function-based approach using a Holstein–Primakoff transformation. The magnetic field is localized in space such that it supports exactly one single-particle bound state. We study the interaction of this bound mode with an incoming spin wave and the interplay between transmittance, energy and momentum matching. We find analytic criteria for maximizing the interconversion between propagating single-magnon modes and true propagating two-magnon states. The manipulation of bound and propagating magnons is an essential step towards quantum magnonics.

  8. Behavior of the maximal solution of the Cauchy problem for some nonlinear pseudoparabolic equation as $|x|oinfty$

    Directory of Open Access Journals (Sweden)

    Tatiana Kavitova

    2012-08-01

    Full Text Available We prove a comparison principle for solutions of the Cauchy problem of the nonlinear pseudoparabolic equation $u_t=Delta u_t+ Deltavarphi(u +h(t,u$ with nonnegative bounded initial data. We show stabilization of a maximal solution to a maximal solution of the Cauchy problem for the corresponding ordinary differential equation $vartheta'(t=h(t,vartheta$ as $|x|oinfty$ under certain conditions on an initial datum.

  9. Inclusive fitness maximization: An axiomatic approach.

    Science.gov (United States)

    Okasha, Samir; Weymark, John A; Bossert, Walter

    2014-06-07

    Kin selection theorists argue that evolution in social contexts will lead organisms to behave as if maximizing their inclusive, as opposed to personal, fitness. The inclusive fitness concept allows biologists to treat organisms as akin to rational agents seeking to maximize a utility function. Here we develop this idea and place it on a firm footing by employing a standard decision-theoretic methodology. We show how the principle of inclusive fitness maximization and a related principle of quasi-inclusive fitness maximization can be derived from axioms on an individual׳s 'as if preferences' (binary choices) for the case in which phenotypic effects are additive. Our results help integrate evolutionary theory and rational choice theory, help draw out the behavioural implications of inclusive fitness maximization, and point to a possible way in which evolution could lead organisms to implement it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Maximal Entanglement in High Energy Physics

    Directory of Open Access Journals (Sweden)

    Alba Cervera-Lierta, José I. Latorre, Juan Rojo, Luca Rottoli

    2017-11-01

    Full Text Available We analyze how maximal entanglement is generated at the fundamental level in QED by studying correlations between helicity states in tree-level scattering processes at high energy. We demonstrate that two mechanisms for the generation of maximal entanglement are at work: i $s$-channel processes where the virtual photon carries equal overlaps of the helicities of the final state particles, and ii the indistinguishable superposition between $t$- and $u$-channels. We then study whether requiring maximal entanglement constrains the coupling structure of QED and the weak interactions. In the case of photon-electron interactions unconstrained by gauge symmetry, we show how this requirement allows reproducing QED. For $Z$-mediated weak scattering, the maximal entanglement principle leads to non-trivial predictions for the value of the weak mixing angle $\\theta_W$. Our results are a first step towards understanding the connections between maximal entanglement and the fundamental symmetries of high-energy physics.

  11. An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe

    International Nuclear Information System (INIS)

    Saio, Tomohide; Ogura, Kenji; Shimizu, Kazumi; Yokochi, Masashi; Burke, Terrence R.; Inagaki, Fuyuhiko

    2011-01-01

    A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation enhancement (PRE) can be observed for both the target protein and its bound ligand. Based on PRE and PCS information, the bound ligand is then screened from the compound library and the structure of the ligand–protein complex is determined. PRE is an isotropic paramagnetic effect observed within 30 Å from the lanthanide ion, and is utilized for the ligand screening in the present study. PCS is an anisotropic paramagnetic effect providing long-range (∼40 Å) distance and angular information on the observed nuclei relative to the paramagnetic lanthanide ion, and utilized for the structure determination of the ligand–protein complex. Since a two-point anchored lanthanide-binding peptide tag is utilized for fixing the lanthanide ion to the target protein, this screening method can be generally applied to non-metal-binding proteins. The usefulness of this strategy was demonstrated in the case of the growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain and its low- and high-affinity ligands.

  12. Two novel mixed-ligand complexes containing organosulfonate ligands.

    Science.gov (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

    2008-07-01

    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  13. Bounding Radionuclide Inventory and Accident Consequence Calculation for the 1L Target

    International Nuclear Information System (INIS)

    Kelsey, Charles T. IV

    2011-01-01

    A bounding radionuclide inventory for the tungsten of the Los Alamos Neutron Science Center (LANSCE) IL Target is calculated. Based on the bounding inventory, the dose resulting from the maximum credible incident (MCI) is calculated for the maximally exposed offsite individual (MEOl). The design basis accident involves tungsten target oxidation following a loss of cooling accident. Also calculated for the bounding radionuclide inventory is the ratio to the LANSCE inventory threshold for purposes of inventory control as described in the target inventory control policy. A bounding radionuclide inventory calculation for the lL Target was completed using the MCNPX and CINDER'90 codes. Continuous beam delivery at 200 (micro)A to 2500 mA·h was assumed. The total calculated activity following this irradiation period is 205,000 Ci. The dose to the MEOI from the MCI is 213 mrem for the bounding inventory. The LANSCE inventory control threshold ratio is 132.

  14. Semiclassical bounds in magnetic bottles

    Czech Academy of Sciences Publication Activity Database

    Barseghyan, Diana; Exner, Pavel; Kovařík, H.; Weidl, T.

    2016-01-01

    Roč. 28, č. 1 (2016), s. 1650002 ISSN 0129-055X R&D Projects: GA ČR(CZ) GA14-06818S Institutional support: RVO:61389005 Keywords : magnetic Laplacian * discrete spectrum * eigenvalue bounds Subject RIV: BE - Theoretical Physics Impact factor: 1.426, year: 2016

  15. Positivity bounds for Sivers functions

    International Nuclear Information System (INIS)

    Kang Zhongbo; Soffer, Jacques

    2011-01-01

    We generalize a positivity constraint derived initially for parity-conserving processes to the parity-violating ones, and use it to derive non-trivial bounds on several Sivers functions, entering in the theoretical description of single spin asymmetry for various processes.

  16. Bound states of 'dressed' particles

    International Nuclear Information System (INIS)

    Shirokov, M.I.

    1994-01-01

    A new approach to the problem of bound states in relativistic quantum field theories is suggested. It uses the creation - destruction operators of 'dresses' particles which have been granted by Faddeev's (1963) 'dressing' formalism. Peculiarities of the proposed approach as compared to the known ones are discussed. 8 refs. (author)

  17. Quantum lower bound for sorting

    OpenAIRE

    Shi, Yaoyun

    2000-01-01

    We prove that \\Omega(n log(n)) comparisons are necessary for any quantum algorithm that sorts n numbers with high success probability and uses only comparisons. If no error is allowed, at least 0.110nlog_2(n) - 0.067n + O(1) comparisons must be made. The previous known lower bound is \\Omega(n).

  18. Unconditional lower bounds against advice

    NARCIS (Netherlands)

    Buhrman, H.; Fortnow, L.; Santhanam, R.

    2009-01-01

    We show several unconditional lower bounds for exponential time classes against polynomial time classes with advice, including: (1) For any constant c, NEXP not in P^{NP[n^c]} (2) For any constant c, MAEXP not in MA/n^c (3) BPEXP not in BPP/n^{o(1)}. It was previously unknown even whether NEXP in

  19. Binding energies of two deltas bound states

    International Nuclear Information System (INIS)

    Sato, Hiroshi; Saito, Koichi.

    1982-06-01

    Bound states of the two-deltas system are investigated by employing the realistic one boson exchange potential. It is found that there exist many bound states in each isospin channel and also found that the tensor interaction plays important role in producing these bound states. Relationship between these bound states and dibaryon resonances is discussed. (J.P.N.)

  20. Heterogeneity and dynamics of the ligand recognition mode in purine-sensing riboswitches.

    Science.gov (United States)

    Jain, Niyati; Zhao, Liang; Liu, John D; Xia, Tianbing

    2010-05-04

    High-resolution crystal structures and biophysical analyses of purine-sensing riboswitches have revealed that a network of hydrogen bonding interactions appear to be largey responsible for discrimination of cognate ligands against structurally related compounds. Here we report that by using femtosecond time-resolved fluorescence spectroscopy to capture the ultrafast decay dynamics of the 2-aminopurine base as the ligand, we have detected the presence of multiple conformations of the ligand within the binding pockets of one guanine-sensing and two adenine-sensing riboswitches. All three riboswitches have similar conformational distributions of the ligand-bound state. The known crystal structures represent the global minimum that accounts for 50-60% of the population, where there is no significant stacking interaction between the ligand and bases of the binding pocket, but the hydrogen-bonding cage collectively provides an electronic environment that promotes an ultrafast ( approximately 1 ps) charge transfer pathway. The ligand also samples multiple conformations in which it significantly stacks with either the adenine or the uracil bases of the A21-U75 and A52-U22 base pairs that form the ceiling and floor of the binding pocket, respectively, but favors the larger adenine bases. These alternative conformations with well-defined base stacking interactions are approximately 1-1.5 kcal/mol higher in DeltaG degrees than the global minimum and have distinct charge transfer dynamics within the picosecond to nanosecond time regime. Inside the pocket, the purine ligand undergoes dynamic motion on the low nanosecond time scale, sampling the multiple conformations based on time-resolved anisotropy decay dynamics. These results allowed a description of the energy landscape of the bound ligand with intricate details and demonstrated the elastic nature of the ligand recognition mode by the purine-sensing riboswitches, where there is a dynamic balance between hydrogen bonding

  1. Dissecting Orthosteric Contacts for a Reverse-Fragment-Based Ligand Design.

    Science.gov (United States)

    Chandramohan, Arun; Tulsian, Nikhil K; Anand, Ganesh S

    2017-08-01

    Orthosteric sites on proteins are formed typically from noncontiguous interacting sites in three-dimensional space where the composite binding interaction of a biological ligand is mediated by multiple synergistic interactions of its constituent functional groups. Through these multiple interactions, ligands stabilize both the ligand binding site and the local secondary structure. However, relative energetic contributions of the individual contacts in these protein-ligand interactions are difficult to resolve. Deconvolution of the contributions of these various functional groups in natural inhibitors/ligand would greatly aid in iterative fragment-based drug discovery (FBDD). In this study, we describe an approach of progressive unfolding of a target protein using a gradient of denaturant urea to reveal the individual energetic contributions of various ligand-functional groups to the affinity of the entire ligand. Through calibrated unfolding of two protein-ligand systems: cAMP-bound regulatory subunit of Protein Kinase A (RIα) and IBMX-bound phosphodiesterase8 (PDE8), monitored by amide hydrogen-deuterium exchange mass spectrometry, we show progressive disruption of individual orthosteric contacts in the ligand binding sites, allowing us to rank the energetic contributions of these individual interactions. In the two cAMP-binding sites of RIα, exocyclic phosphate oxygens of cAMP were identified to mediate stronger interactions than ribose 2'-OH in both the RIα-cAMP binding interfaces. Further, we have also ranked the relative contributions of the different functional groups of IBMX based on their interactions with the orthosteric residues of PDE8. This strategy for deconstruction of individual binding sites and identification of the strongest functional group interaction in enzyme orthosteric sites offers a rational starting point for FBDD.

  2. Maximum and minimum entropy states yielding local continuity bounds

    Science.gov (United States)

    Hanson, Eric P.; Datta, Nilanjana

    2018-04-01

    Given an arbitrary quantum state (σ), we obtain an explicit construction of a state ρɛ * ( σ ) [respectively, ρ * , ɛ ( σ ) ] which has the maximum (respectively, minimum) entropy among all states which lie in a specified neighborhood (ɛ-ball) of σ. Computing the entropy of these states leads to a local strengthening of the continuity bound of the von Neumann entropy, i.e., the Audenaert-Fannes inequality. Our bound is local in the sense that it depends on the spectrum of σ. The states ρɛ * ( σ ) and ρ * , ɛ (σ) depend only on the geometry of the ɛ-ball and are in fact optimizers for a larger class of entropies. These include the Rényi entropy and the minimum- and maximum-entropies, providing explicit formulas for certain smoothed quantities. This allows us to obtain local continuity bounds for these quantities as well. In obtaining this bound, we first derive a more general result which may be of independent interest, namely, a necessary and sufficient condition under which a state maximizes a concave and Gâteaux-differentiable function in an ɛ-ball around a given state σ. Examples of such a function include the von Neumann entropy and the conditional entropy of bipartite states. Our proofs employ tools from the theory of convex optimization under non-differentiable constraints, in particular Fermat's rule, and majorization theory.

  3. Correcting ligands, metabolites, and pathways

    NARCIS (Netherlands)

    Ott, M.A.; Vriend, G.

    2006-01-01

    BACKGROUND: A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases,

  4. A symmetric Roos bound for linear codes

    NARCIS (Netherlands)

    Duursma, I.M.; Pellikaan, G.R.

    2006-01-01

    The van Lint–Wilson AB-method yields a short proof of the Roos bound for the minimum distance of a cyclic code. We use the AB-method to obtain a different bound for the weights of a linear code. In contrast to the Roos bound, the role of the codes A and B in our bound is symmetric. We use the bound

  5. Trapping of palindromic ligands within native transthyretin prevents amyloid formation

    Science.gov (United States)

    Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.; Robinson, Carol V.; Wood, Stephen P.; Pepys, Mark B.

    2010-01-01

    Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. PMID:21059958

  6. Proof of the insecurity of quantum secret sharing based on the Smolin bound entangled states

    International Nuclear Information System (INIS)

    Ya-Fei, Yu; Zhi-Ming, Zhang

    2009-01-01

    This paper reconsiders carefully the possibility of using the Smolin bound entangled states as the carrier for sharing quantum secret. It finds that the process of quantum secret sharing based on Smolin states has insecurity though the Smolin state was reported to violate maximally the two-setting Bell-inequality. The general proof is given. (general)

  7. Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domain

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    , and by the antagonist, strychnine. Voltage-clamp fluorometry involves labeling introduced cysteines with environmentally sensitive fluorophores and inferring structural rearrangements from ligand-induced fluorescence changes. In the inner beta-sheet, we labeled residues in loop 2 and in binding domain loops D and E....... At each position, strychnine and glycine induced distinct maximal fluorescence responses. The pre-M1 domain responded similarly; at each of four labeled positions glycine produced a strong fluorescence signal, whereas strychnine did not. This suggests that glycine induces conformational changes...... in the inner beta-sheet and pre-M1 domain that may be important for activation, desensitization, or both. In contrast, most labeled residues in loops C and F yielded fluorescence changes identical in magnitude for glycine and strychnine. A notable exception was H201C in loop C. This labeled residue responded...

  8. Shared temptations: An fMRI study of dishonest profit maximization.

    Science.gov (United States)

    Simmank, Fabian

    2017-12-01

    A single case of a tempting-decision task involving financial gain is reported. The subject showed a prosocial Social Value Orientation and applied a profit-maximizing strategy. Differential brain activation patterns for self-serving and other-serving decisions were observed. Results provide new insight into the design of paradigms on bounded ethicality and self- and group-serving behavior. © 2017 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  9. Bipartite Bell Inequality and Maximal Violation

    International Nuclear Information System (INIS)

    Li Ming; Fei Shaoming; Li-Jost Xian-Qing

    2011-01-01

    We present new bell inequalities for arbitrary dimensional bipartite quantum systems. The maximal violation of the inequalities is computed. The Bell inequality is capable of detecting quantum entanglement of both pure and mixed quantum states more effectively. (general)

  10. HEALTH INSURANCE: CONTRIBUTIONS AND REIMBURSEMENT MAXIMAL

    CERN Document Server

    HR Division

    2000-01-01

    Affected by both the salary adjustment index on 1.1.2000 and the evolution of the staff members and fellows population, the average reference salary, which is used as an index for fixed contributions and reimbursement maximal, has changed significantly. An adjustment of the amounts of the reimbursement maximal and the fixed contributions is therefore necessary, as from 1 January 2000.Reimbursement maximalThe revised reimbursement maximal will appear on the leaflet summarising the benefits for the year 2000, which will soon be available from the divisional secretariats and from the AUSTRIA office at CERN.Fixed contributionsThe fixed contributions, applicable to some categories of voluntarily insured persons, are set as follows (amounts in CHF for monthly contributions):voluntarily insured member of the personnel, with complete coverage:815,- (was 803,- in 1999)voluntarily insured member of the personnel, with reduced coverage:407,- (was 402,- in 1999)voluntarily insured no longer dependent child:326,- (was 321...

  11. Maximal Inequalities for Dependent Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jorgensen, Jorgen

    2016-01-01

    Maximal inequalities play a crucial role in many probabilistic limit theorem; for instance, the law of large numbers, the law of the iterated logarithm, the martingale limit theorem and the central limit theorem. Let X-1, X-2,... be random variables with partial sums S-k = X-1 + ... + X-k. Then a......Maximal inequalities play a crucial role in many probabilistic limit theorem; for instance, the law of large numbers, the law of the iterated logarithm, the martingale limit theorem and the central limit theorem. Let X-1, X-2,... be random variables with partial sums S-k = X-1 + ... + X......-k. Then a maximal inequality gives conditions ensuring that the maximal partial sum M-n = max(1) (...

  12. Maximizing Function through Intelligent Robot Actuator Control

    Data.gov (United States)

    National Aeronautics and Space Administration — Maximizing Function through Intelligent Robot Actuator Control Successful missions to Mars and beyond will only be possible with the support of high-performance...

  13. An ethical justification of profit maximization

    DEFF Research Database (Denmark)

    Koch, Carsten Allan

    2010-01-01

    In much of the literature on business ethics and corporate social responsibility, it is more or less taken for granted that attempts to maximize profits are inherently unethical. The purpose of this paper is to investigate whether an ethical argument can be given in support of profit maximizing...... behaviour. It is argued that some form of consequential ethics must be applied, and that both profit seeking and profit maximization can be defended from a rule-consequential point of view. It is noted, however, that the result does not apply unconditionally, but requires that certain form of profit (and...... utility) maximizing actions are ruled out, e.g., by behavioural norms or formal institutions....

  14. A definition of maximal CP-violation

    International Nuclear Information System (INIS)

    Roos, M.

    1985-01-01

    The unitary matrix of quark flavour mixing is parametrized in a general way, permitting a mathematically natural definition of maximal CP violation. Present data turn out to violate this definition by 2-3 standard deviations. (orig.)

  15. A cosmological problem for maximally symmetric supergravity

    International Nuclear Information System (INIS)

    German, G.; Ross, G.G.

    1986-01-01

    Under very general considerations it is shown that inflationary models of the universe based on maximally symmetric supergravity with flat potentials are unable to resolve the cosmological energy density (Polonyi) problem. (orig.)

  16. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

    2003-01-01

    BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake......, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS......: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION...

  17. Maximal supergravities and the E10 model

    International Nuclear Information System (INIS)

    Kleinschmidt, Axel; Nicolai, Hermann

    2006-01-01

    The maximal rank hyperbolic Kac-Moody algebra e 10 has been conjectured to play a prominent role in the unification of duality symmetries in string and M theory. We review some recent developments supporting this conjecture

  18. Structure of the [delta]-opioid receptor bound to naltrindole

    Energy Technology Data Exchange (ETDEWEB)

    Granier, Sébastien; Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I.; Kobilka, Brian K. (Stanford-MED)

    2012-07-11

    The opioid receptor family comprises three members, the {mu}-, {delta}- and {kappa}-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The {delta}-opioid receptor ({delta}-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the {mu}-OR and {kappa}-OR have recently been solved. Here we report the crystal structure of the mouse {delta}-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the {mu}-OR and {kappa}-OR, the {delta}-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the {delta}-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

  19. Computer simulation of bounded plasmas

    International Nuclear Information System (INIS)

    Lawson, W.S.

    1987-01-01

    The problems of simulating a one-dimensional bounded plasma system using particles in a gridded space are systematically explored and solutions to them are given. Such problems include the injection of particles at the boundaries, the solution of Poisson's equation, and the inclusion of an external circuit between the confining boundaries. A recently discovered artificial cooling effect is explained as being a side-effect of quiet injection, and its potential for causing serious but subtle errors in bounded simulation is noted. The methods described in the first part of the thesis are then applied to the simulation of an extension of the Pierce diode problem, specifically a Pierce diode modified by an external circuit between the electrodes. The results of these simulations agree to high accuracy with theory when a theory exists, and also show some interesting chaotic behavior in certain parameter regimes. The chaotic behavior is described in detail

  20. Bounded Rationality in Transposition Processes

    DEFF Research Database (Denmark)

    Vollaard, Hans; Martinsen, Dorte Sindbjerg

    2014-01-01

    Studies explaining the timeliness and correctness of the transposition of EU directives into national legislation have provided rather inconclusive findings. They do not offer a clear-cut prediction concerning the transposition of the patients’ rights directive, which is one of the first that con......Studies explaining the timeliness and correctness of the transposition of EU directives into national legislation have provided rather inconclusive findings. They do not offer a clear-cut prediction concerning the transposition of the patients’ rights directive, which is one of the first...... that concerns the organisation and financing of national healthcare systems. This article applies the perspective of bounded rationality to explain (irregularities in) the timely and correct transposition of EU directives. The cognitive and organisational constraints long posited by the bounded rationality...

  1. Maximal stochastic transport in the Lorenz equations

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Sahil, E-mail: sahil.agarwal@yale.edu [Program in Applied Mathematics, Yale University, New Haven (United States); Wettlaufer, J.S., E-mail: john.wettlaufer@yale.edu [Program in Applied Mathematics, Yale University, New Haven (United States); Departments of Geology & Geophysics, Mathematics and Physics, Yale University, New Haven (United States); Mathematical Institute, University of Oxford, Oxford (United Kingdom); Nordita, Royal Institute of Technology and Stockholm University, Stockholm (Sweden)

    2016-01-08

    We calculate the stochastic upper bounds for the Lorenz equations using an extension of the background method. In analogy with Rayleigh–Bénard convection the upper bounds are for heat transport versus Rayleigh number. As might be expected, the stochastic upper bounds are larger than the deterministic counterpart of Souza and Doering [1], but their variation with noise amplitude exhibits interesting behavior. Below the transition to chaotic dynamics the upper bounds increase monotonically with noise amplitude. However, in the chaotic regime this monotonicity depends on the number of realizations in the ensemble; at a particular Rayleigh number the bound may increase or decrease with noise amplitude. The origin of this behavior is the coupling between the noise and unstable periodic orbits, the degree of which depends on the degree to which the ensemble represents the ergodic set. This is confirmed by examining the close returns plots of the full solutions to the stochastic equations and the numerical convergence of the noise correlations. The numerical convergence of both the ensemble and time averages of the noise correlations is sufficiently slow that it is the limiting aspect of the realization of these bounds. Finally, we note that the full solutions of the stochastic equations demonstrate that the effect of noise is equivalent to the effect of chaos.

  2. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Science.gov (United States)

    2013-03-26

    ...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

  3. Gaussian maximally multipartite-entangled states

    Science.gov (United States)

    Facchi, Paolo; Florio, Giuseppe; Lupo, Cosmo; Mancini, Stefano; Pascazio, Saverio

    2009-12-01

    We study maximally multipartite-entangled states in the context of Gaussian continuous variable quantum systems. By considering multimode Gaussian states with constrained energy, we show that perfect maximally multipartite-entangled states, which exhibit the maximum amount of bipartite entanglement for all bipartitions, only exist for systems containing n=2 or 3 modes. We further numerically investigate the structure of these states and their frustration for n≤7 .

  4. Gaussian maximally multipartite-entangled states

    International Nuclear Information System (INIS)

    Facchi, Paolo; Florio, Giuseppe; Pascazio, Saverio; Lupo, Cosmo; Mancini, Stefano

    2009-01-01

    We study maximally multipartite-entangled states in the context of Gaussian continuous variable quantum systems. By considering multimode Gaussian states with constrained energy, we show that perfect maximally multipartite-entangled states, which exhibit the maximum amount of bipartite entanglement for all bipartitions, only exist for systems containing n=2 or 3 modes. We further numerically investigate the structure of these states and their frustration for n≤7.

  5. Neutrino mass textures with maximal CP violation

    International Nuclear Information System (INIS)

    Aizawa, Ichiro; Kitabayashi, Teruyuki; Yasue, Masaki

    2005-01-01

    We show three types of neutrino mass textures, which give maximal CP violation as well as maximal atmospheric neutrino mixing. These textures are described by six real mass parameters: one specified by two complex flavor neutrino masses and two constrained ones and the others specified by three complex flavor neutrino masses. In each texture, we calculate mixing angles and masses, which are consistent with observed data, as well as Majorana CP phases

  6. Why firms should not always maximize profits

    OpenAIRE

    Kolstad, Ivar

    2006-01-01

    Though corporate social responsibility (CSR) is on the agenda of most major corporations, corporate executives still largely support the view that corporations should maximize the returns to their owners. There are two lines of defence for this position. One is the Friedmanian view that maximizing owner returns is the corporate social responsibility of corporations. The other is a position voiced by many executives, that CSR and profits go together. This paper argues that the first position i...

  7. Maximally Informative Observables and Categorical Perception

    OpenAIRE

    Tsiang, Elaine

    2012-01-01

    We formulate the problem of perception in the framework of information theory, and prove that categorical perception is equivalent to the existence of an observable that has the maximum possible information on the target of perception. We call such an observable maximally informative. Regardless whether categorical perception is real, maximally informative observables can form the basis of a theory of perception. We conclude with the implications of such a theory for the problem of speech per...

  8. Spectrum of gluino bound states

    International Nuclear Information System (INIS)

    Chanowitz, M.; Sharpe, S.; California Univ., Berkeley

    1983-01-01

    Using the bag model to first order in αsub(s) we find that if light gluinos exist they will appear as constituents of electrically charged bound states which are stable against strong interaction decay. We review the present experimental constraints and conclude that light, long-lived charged hadrons containing gluinos might exist with lifetimes between 2x10 - 8 and 10 - 14 s. (orig.)

  9. Cyclotron transitions of bound ions

    Science.gov (United States)

    Bezchastnov, Victor G.; Pavlov, George G.

    2017-06-01

    A charged particle in a magnetic field possesses discrete energy levels associated with particle rotation around the field lines. The radiative transitions between these levels are the well-known cyclotron transitions. We show that a bound complex of particles with a nonzero net charge displays analogous transitions between the states of confined motion of the entire complex in the field. The latter bound-ion cyclotron transitions are affected by a coupling between the collective and internal motions of the complex and, as a result, differ from the transitions of a "reference" bare ion with the same mass and charge. We analyze the cyclotron transitions for complex ions by including the coupling within a rigorous quantum approach. Particular attention is paid to comparison of the transition energies and oscillator strengths to those of the bare ion. Selection rules based on integrals of collective motion are derived for the bound-ion cyclotron transitions analytically, and the perturbation and coupled-channel approaches are developed to study the transitions quantitatively. Representative examples are considered and discussed for positive and negative atomic and cluster ions.

  10. Trapping of palindromic ligands within native transthyretin prevents amyloid formation

    OpenAIRE

    Kolstoe, Simon E.; Mangione, Palma P.; Bellotti, Vittorio; Taylor, Graham W.; Tennent, Glenys A.; Deroo, Stéphanie; Morrison, Angus J.; Cobb, Alexander J. A.; Coyne, Anthony; McCammon, Margaret G.; Warner, Timothy D.; Mitchell, Jane; Gill, Raj; Smith, Martin D.; Ley, Steven V.

    2010-01-01

    Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one...

  11. Structural studies of Ca2+-ATPase ligand and regulatory complexes

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring

    2015-01-01

    , the surrounding membrane itself has a huge influence on SERCA structure and function. Changes in the membrane thickness can alter the activity of the ATPase significantly, and even cause changes in the stoichiometry of ion transport. Structural studies on SERCA in the presence of four different phosphatidyl...... choline lipids with different aliphatic chain length and saturation show three specific lipid binding sites. The four different lipids analysed bind to the same binding sites with varying degrees of disorder. The study contributes to understanding the complex interplay between the surrounding membrane...... to explore the possibilities for an efficient screening of ligand-bound SERCA structures, serial femtosecond crystallography experiments of microcrystals of SERCA1a in the Ca2+ bound state and in a vanadate stabilised E2 state was conducted. A structure obtained at 2.8 Å maximum resolution of the proof...

  12. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

    International Nuclear Information System (INIS)

    Poór, Miklós; Li, Yin; Matisz, Gergely; Kiss, László; Kunsági-Máté, Sándor; Kőszegi, Tamás

    2014-01-01

    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin

  13. Labeling schemes for bounded degree graphs

    DEFF Research Database (Denmark)

    Adjiashvili, David; Rotbart, Noy Galil

    2014-01-01

    We investigate adjacency labeling schemes for graphs of bounded degree Δ = O(1). In particular, we present an optimal (up to an additive constant) log n + O(1) adjacency labeling scheme for bounded degree trees. The latter scheme is derived from a labeling scheme for bounded degree outerplanar...... graphs. Our results complement a similar bound recently obtained for bounded depth trees [Fraigniaud and Korman, SODA 2010], and may provide new insights for closing the long standing gap for adjacency in trees [Alstrup and Rauhe, FOCS 2002]. We also provide improved labeling schemes for bounded degree...

  14. Shareholder, stakeholder-owner or broad stakeholder maximization

    OpenAIRE

    Mygind, Niels

    2004-01-01

    With reference to the discussion about shareholder versus stakeholder maximization it is argued that the normal type of maximization is in fact stakeholder-owner maxi-mization. This means maximization of the sum of the value of the shares and stake-holder benefits belonging to the dominating stakeholder-owner. Maximization of shareholder value is a special case of owner-maximization, and only under quite re-strictive assumptions shareholder maximization is larger or equal to stakeholder-owner...

  15. Evaluating risk using bounding calculations and limited data; TOPICAL

    International Nuclear Information System (INIS)

    COWLEY, W.L.

    1999-01-01

    This paper describes a methodology for estimating the potential risk to workers and the public from igniting organic solvents in any of the 177 underground waste storage tanks at the Hanford Site in southeastern Washington state. The Hanford Site is one of the U.S. Department of Energy's former production facilities for nuclear materials. The tanks contain mixed radioactive wastes. Risk is measured by calculating toxicological and radiological accident consequences and frequencies and comparing the results to established regulatory guidelines. Available sample data is insufficient to adequately characterize the waste and solvent, so a model that maximizes releases from the tanks (bounding case) is used. Maximizing releases (and thus consequences) is a standard technique used in safety analysis to compensate for lack of information. The model predicts bounding values of fire duration, the time at which the fire extinguishes because of lack of oxygen, and a pressure history of a fire in a tank. The model output is used to calculate mass and volume release rates of material from the tanks. The mass and volume release rates permit calculation of radiological and toxicological consequences. The resulting consequence calculations demonstrate that risk from an organic solvent fire in the tanks is within regulatory guidelines

  16. Estimating risk using bounding calculations and limited data

    International Nuclear Information System (INIS)

    COWLEY, W.L.

    1999-01-01

    This paper describes a methodology for estimating the potential risk to workers and the public from igniting organic solvents in any of the 177 underground waste storage tanks at the Hanford Site in southeastern Washington state. The Hanford Site is one of the U.S. Department of Energy's former production facilities for nuclear materials. The tanks contain mixed radioactive wastes. Risk is measured by calculating toxicological and radiological accident consequences and frequencies and comparing the results to established regulatory guidelines. Available sample data is insufficient to adequately characterize the waste and solvent, so a model that maximizes releases from the tanks (bounding case) is used. Maximizing releases (and thus consequences) is a standard technique used in safety analysis to compensate for lack of information. The model predicts bounding values of fire duration, the time at which the fire extinguishes because of lack of oxygen, and a pressure history of a fire in a tank. The model output is used to calculate mass and volume release rates of material from the tanks. The mass and volume release rates permit calculation of radiological and toxicological consequences. The resulting consequence calculations demonstrate that risk from an organic solvent fire in the tanks is within regulatory guidelines

  17. The algebras of bounded and essentially bounded Lebesgue measurable functions

    Directory of Open Access Journals (Sweden)

    Mortini Raymond

    2017-04-01

    Full Text Available Let X be a set in ℝn with positive Lebesgue measure. It is well known that the spectrum of the algebra L∞(X of (equivalence classes of essentially bounded, complex-valued, measurable functions on X is an extremely disconnected compact Hausdorff space.We show, by elementary methods, that the spectrum M of the algebra ℒb(X, ℂ of all bounded measurable functions on X is not extremely disconnected, though totally disconnected. Let ∆ = { δx : x ∈ X} be the set of point evaluations and let g be the Gelfand topology on M. Then (∆, g is homeomorphic to (X, Τdis,where Tdis is the discrete topology. Moreover, ∆ is a dense subset of the spectrum M of ℒb(X, ℂ. Finally, the hull h(I, (which is homeomorphic to M(L∞(X, of the ideal of all functions in ℒb(X, ℂ vanishing almost everywhere on X is a nowhere dense and extremely disconnected subset of the Corona M \\ ∆ of ℒb(X, ℂ.

  18. A Fluid Membrane-Based Soluble Ligand Display System for Live CellAssays

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jwa-Min; Nair, Pradeep N.; Neve, Richard M.; Gray, Joe W.; Groves, Jay T.

    2005-10-14

    Cell communication modulates numerous biological processes including proliferation, apoptosis, motility, invasion and differentiation. Correspondingly, there has been significant interest in the development of surface display strategies for the presentation of signaling molecules to living cells. This effort has primarily focused on naturally surface-bound ligands, such as extracellular matrix components and cell membranes. Soluble ligands (e.g. growth factors and cytokines) play an important role in intercellular communications, and their display in a surface-bound format would be of great utility in the design of array-based live cell assays. Recently, several cell microarray systems that display cDNA, RNAi, or small molecules in a surface array format were proven to be useful in accelerating high-throughput functional genetic studies and screening therapeutic agents. These surface display methods provide a flexible platform for the systematic, combinatorial investigation of genes and small molecules affecting cellular processes and phenotypes of interest. In an analogous sense, it would be an important advance if one could display soluble signaling ligands in a surface assay format that allows for systematic, patterned presentation of soluble ligands to live cells. Such a technique would make it possible to examine cellular phenotypes of interest in a parallel format with soluble signaling ligands as one of the display parameters. Herein we report a ligand-modified fluid supported lipid bilayer (SLB) assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined. The method reported herein benefits from the naturally fluid state of the supported membrane, which allows

  19. Vacua of maximal gauged D=3 supergravities

    International Nuclear Information System (INIS)

    Fischbacher, T; Nicolai, H; Samtleben, H

    2002-01-01

    We analyse the scalar potentials of maximal gauged three-dimensional supergravities which reveal a surprisingly rich structure. In contrast to maximal supergravities in dimensions D≥4, all these theories possess a maximally supersymmetric (N=16) ground state with negative cosmological constant Λ 2 gauged theory, whose maximally supersymmetric groundstate has Λ = 0. We compute the mass spectra of bosonic and fermionic fluctuations around these vacua and identify the unitary irreducible representations of the relevant background (super)isometry groups to which they belong. In addition, we find several stationary points which are not maximally supersymmetric, and determine their complete mass spectra as well. In particular, we show that there are analogues of all stationary points found in higher dimensions, among them are de Sitter (dS) vacua in the theories with noncompact gauge groups SO(5, 3) 2 and SO(4, 4) 2 , as well as anti-de Sitter (AdS) vacua in the compact gauged theory preserving 1/4 and 1/8 of the supersymmetries. All the dS vacua have tachyonic instabilities, whereas there do exist nonsupersymmetric AdS vacua which are stable, again in contrast to the D≥4 theories

  20. PANP is a novel O-glycosylated PILR{alpha} ligand expressed in neural tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kogure, Amane [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Shiratori, Ikuo [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Wang, Jing [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); Lanier, Lewis L. [Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 (United States); Arase, Hisashi, E-mail: arase@biken.osaka-u.ac.jp [Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan); Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871 (Japan); JST CREST, Saitama 332-0012 (Japan)

    2011-02-18

    Research highlights: {yields} A Novel molecule, PANP, was identified to be a PILR{alpha} ligand. {yields} Sialylated O-glycan structures on PANP were required for PILR{alpha} recognition. {yields} Transcription of PANP was mainly observed in neural tissues. {yields} PANP seems to be involved in immune regulation as a ligand for PILR{alpha}. -- Abstract: PILR{alpha} is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR{alpha} to its ligand CD99 is involved in immune regulation; however, whether there are other PILR{alpha} ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR{alpha}. Transcription of PANP was mainly observed in neural tissues. PILR{alpha}-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR{alpha} reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR{alpha}.

  1. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  2. Synthesis and Isotope Effects on the Excited State Properties of NN Bound Complexes

    NARCIS (Netherlands)

    Soman, Suraj; Younis, Hamid M.; Browne, Wesley R.; Vos, Johannes G.; Pryce, Mary T.

    2017-01-01

    A versatile approach to the preparation of [Ir(LL)(2)Cl-2](PF6) type complexes is reported, in which LL is an (NN)-N- bound polypyridyl ligand [X(2)bpy, X(2)phen, where X = H-, CH3-, (CH3)(3)C-, or phenyl-, and bpy = 2,2-bipyridyl, phen = 1,10-phenanthroline] as well as their deuterated analogues.

  3. Voronoi Diagrams Without Bounding Boxes

    Science.gov (United States)

    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).

  4. Sensitivity analysis using probability bounding

    International Nuclear Information System (INIS)

    Ferson, Scott; Troy Tucker, W.

    2006-01-01

    Probability bounds analysis (PBA) provides analysts a convenient means to characterize the neighborhood of possible results that would be obtained from plausible alternative inputs in probabilistic calculations. We show the relationship between PBA and the methods of interval analysis and probabilistic uncertainty analysis from which it is jointly derived, and indicate how the method can be used to assess the quality of probabilistic models such as those developed in Monte Carlo simulations for risk analyses. We also illustrate how a sensitivity analysis can be conducted within a PBA by pinching inputs to precise distributions or real values

  5. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing ...... quantities of interest. To be able to utilise the evidence about the derivative it is suggested to adapt the ‘conventional’ problem statement to variational calculus and the way to do so is demonstrated. A number of examples are given throughout the paper....

  6. Removal of bound metal fasteners

    Science.gov (United States)

    Kramer, R. F.

    1981-04-01

    This project explored the removal of bound metal fasteners through the use of ultrasonically assisted wrenches. Two wrenches were designed, fabricated and tested. Previous studies had indicated an increase in thread tension for a given torque application under the influence of ultrasonics. Based on this, the loosening of seized and corroded fasteners with the aid of ultrasonics was explored. Experimental data confirmed our prior analysis of the torque-tension relationship under the influence of ultrasonics; however, our progress did not satisfy the requirements necessary to loosen seized studs in a shipyard environment.

  7. Space mappings with bounded distortion

    CERN Document Server

    Reshetnyak, Yu G

    1989-01-01

    This book is intended for researchers and students concerned with questions in analysis and function theory. The author provides an exposition of the main results obtained in recent years by Soviet and other mathematicians in the theory of mappings with bounded distortion, an active direction in contemporary mathematics. The mathematical tools presented can be applied to a broad spectrum of problems that go beyond the context of the main topic of investigation. For a number of questions in the theory of partial differential equations and the theory of functions with generalized derivatives, this is the first time they have appeared in an internationally distributed monograph.

  8. An information maximization model of eye movements

    Science.gov (United States)

    Renninger, Laura Walker; Coughlan, James; Verghese, Preeti; Malik, Jitendra

    2005-01-01

    We propose a sequential information maximization model as a general strategy for programming eye movements. The model reconstructs high-resolution visual information from a sequence of fixations, taking into account the fall-off in resolution from the fovea to the periphery. From this framework we get a simple rule for predicting fixation sequences: after each fixation, fixate next at the location that minimizes uncertainty (maximizes information) about the stimulus. By comparing our model performance to human eye movement data and to predictions from a saliency and random model, we demonstrate that our model is best at predicting fixation locations. Modeling additional biological constraints will improve the prediction of fixation sequences. Our results suggest that information maximization is a useful principle for programming eye movements.

  9. Utility Maximization in Nonconvex Wireless Systems

    CERN Document Server

    Brehmer, Johannes

    2012-01-01

    This monograph formulates a framework for modeling and solving utility maximization problems in nonconvex wireless systems. First, a model for utility optimization in wireless systems is defined. The model is general enough to encompass a wide array of system configurations and performance objectives. Based on the general model, a set of methods for solving utility maximization problems is developed. The development is based on a careful examination of the properties that are required for the application of each method. The focus is on problems whose initial formulation does not allow for a solution by standard convex methods. Solution approaches that take into account the nonconvexities inherent to wireless systems are discussed in detail. The monograph concludes with two case studies that demonstrate the application of the proposed framework to utility maximization in multi-antenna broadcast channels.

  10. Determining Normal-Distribution Tolerance Bounds Graphically

    Science.gov (United States)

    Mezzacappa, M. A.

    1983-01-01

    Graphical method requires calculations and table lookup. Distribution established from only three points: mean upper and lower confidence bounds and lower confidence bound of standard deviation. Method requires only few calculations with simple equations. Graphical procedure establishes best-fit line for measured data and bounds for selected confidence level and any distribution percentile.

  11. On semidefinite programming bounds for graph bandwidth

    NARCIS (Netherlands)

    de Klerk, E.; Nagy, M.; Sotirov, R.

    2013-01-01

    In this paper, we propose two new lower bounds on graph bandwidth and cyclic bandwidth based on semidefinite programming (SDP) relaxations of the quadratic assignment problem. We compare the new bounds with two other SDP bounds reported in [A. Blum, G. Konjevod, R. Ravi, and S. Vempala,

  12. Observational Bounds on Cosmic Doomsday

    Energy Technology Data Exchange (ETDEWEB)

    Shmakova, Marina

    2003-07-11

    Recently it was found, in a broad class of models, that the dark energy density may change its sign during the evolution of the universe. This may lead to a global collapse of the universe within the time t{sub c} {approx} 10{sup 10}-10{sup 11} years. Our goal is to find what bounds on the future lifetime of the universe can be placed by the next generation of cosmological observations. As an example, we investigate the simplest model of dark energy with a linear potential V({phi}) = V{sub 0}(1 + {alpha}{phi}). This model can describe the present stage of acceleration of the universe if {alpha} is small enough. However, eventually the field {phi} rolls down, V({phi}) becomes negative, and the universe collapses. The existing observational data indicate that the universe described by this model will collapse not earlier than t{sub c} {approx_equal} 10 billion years from the present moment. We show that the data from SNAP and Planck satellites may extend the bound on the ''doomsday'' time to tc 40 billion years at the 95% confidence level.

  13. Maximizing band gaps in plate structures

    DEFF Research Database (Denmark)

    Halkjær, Søren; Sigmund, Ole; Jensen, Jakob Søndergaard

    2006-01-01

    periodic plate using Bloch theory, which conveniently reduces the maximization problem to that of a single base cell. Secondly, we construct a finite periodic plate using a number of the optimized base cells in a postprocessed version. The dynamic properties of the finite plate are investigated......Band gaps, i.e., frequency ranges in which waves cannot propagate, can be found in elastic structures for which there is a certain periodic modulation of the material properties or structure. In this paper, we maximize the band gap size for bending waves in a Mindlin plate. We analyze an infinite...... theoretically and experimentally and the issue of finite size effects is addressed....

  14. Singularity Structure of Maximally Supersymmetric Scattering Amplitudes

    DEFF Research Database (Denmark)

    Arkani-Hamed, Nima; Bourjaily, Jacob L.; Cachazo, Freddy

    2014-01-01

    We present evidence that loop amplitudes in maximally supersymmetric (N=4) Yang-Mills theory (SYM) beyond the planar limit share some of the remarkable structures of the planar theory. In particular, we show that through two loops, the four-particle amplitude in full N=4 SYM has only logarithmic ...... singularities and is free of any poles at infinity—properties closely related to uniform transcendentality and the UV finiteness of the theory. We also briefly comment on implications for maximal (N=8) supergravity theory (SUGRA)....

  15. Learning curves for mutual information maximization

    International Nuclear Information System (INIS)

    Urbanczik, R.

    2003-01-01

    An unsupervised learning procedure based on maximizing the mutual information between the outputs of two networks receiving different but statistically dependent inputs is analyzed [S. Becker and G. Hinton, Nature (London) 355, 161 (1992)]. For a generic data model, I show that in the large sample limit the structure in the data is recognized by mutual information maximization. For a more restricted model, where the networks are similar to perceptrons, I calculate the learning curves for zero-temperature Gibbs learning. These show that convergence can be rather slow, and a way of regularizing the procedure is considered

  16. The ultimate security bounds of quantum key distribution protocols

    International Nuclear Information System (INIS)

    Nikolopoulos, G.M.; Alber, G.

    2005-01-01

    Full text: Quantum key distribution (QKD) protocols exploit quantum correlations in order to establish a secure key between two legitimate users. Recent work on QKD has revealed a remarkable link between quantum and secret correlations. In this talk we report on recent results concerning the ultimate upper security bounds of various QKD schemes (i.e., the maximal disturbance up to which the two legitimate users share quantum correlations) under the assumption of general coherent attacks. In particular, we derive an analytic expression for the ultimate upper security bound of QKD schemes that use two mutually unbiased bases. As long as the two legitimate users focus on the sifted key and treat each pair of data independently during the post processing, our results are valid for arbitrary dimensions of the information carriers. The bound we have derived is well below the predictions of optimal cloning machines. The possibility of extraction of a secret key beyond entanglement distillation is also discussed. In the case of qutrits we argue that any eavesdropping strategy is equivalent to a symmetric one. For higher dimensions, however, such equivalence is generally no longer valid. (author)

  17. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  18. Statistical removal of background signals from high-throughput 1H NMR line-broadening ligand-affinity screens

    International Nuclear Information System (INIS)

    Worley, Bradley; Sisco, Nicholas J.; Powers, Robert

    2015-01-01

    NMR ligand-affinity screens are vital to drug discovery, are routinely used to screen fragment-based libraries, and used to verify chemical leads from high-throughput assays and virtual screens. NMR ligand-affinity screens are also a highly informative first step towards identifying functional epitopes of unknown proteins, as well as elucidating the biochemical functions of protein–ligand interaction at their binding interfaces. While simple one-dimensional 1 H NMR experiments are capable of indicating binding through a change in ligand line shape, they are plagued by broad, ill-defined background signals from protein 1 H resonances. We present an uncomplicated method for subtraction of protein background in high-throughput ligand-based affinity screens, and show that its performance is maximized when phase-scatter correction is applied prior to subtraction

  19. UV-Visible Spectroscopy-Based Quantification of Unlabeled DNA Bound to Gold Nanoparticles.

    Science.gov (United States)

    Baldock, Brandi L; Hutchison, James E

    2016-12-20

    DNA-functionalized gold nanoparticles have been increasingly applied as sensitive and selective analytical probes and biosensors. The DNA ligands bound to a nanoparticle dictate its reactivity, making it essential to know the type and number of DNA strands bound to the nanoparticle surface. Existing methods used to determine the number of DNA strands per gold nanoparticle (AuNP) require that the sequences be fluorophore-labeled, which may affect the DNA surface coverage and reactivity of the nanoparticle and/or require specialized equipment and other fluorophore-containing reagents. We report a UV-visible-based method to conveniently and inexpensively determine the number of DNA strands attached to AuNPs of different core sizes. When this method is used in tandem with a fluorescence dye assay, it is possible to determine the ratio of two unlabeled sequences of different lengths bound to AuNPs. Two sizes of citrate-stabilized AuNPs (5 and 12 nm) were functionalized with mixtures of short (5 base) and long (32 base) disulfide-terminated DNA sequences, and the ratios of sequences bound to the AuNPs were determined using the new method. The long DNA sequence was present as a lower proportion of the ligand shell than in the ligand exchange mixture, suggesting it had a lower propensity to bind the AuNPs than the short DNA sequence. The ratio of DNA sequences bound to the AuNPs was not the same for the large and small AuNPs, which suggests that the radius of curvature had a significant influence on the assembly of DNA strands onto the AuNPs.

  20. Bounding Averages Rigorously Using Semidefinite Programming: Mean Moments of the Lorenz System

    Science.gov (United States)

    Goluskin, David

    2018-04-01

    We describe methods for proving bounds on infinite-time averages in differential dynamical systems. The methods rely on the construction of nonnegative polynomials with certain properties, similarly to the way nonlinear stability can be proved using Lyapunov functions. Nonnegativity is enforced by requiring the polynomials to be sums of squares, a condition which is then formulated as a semidefinite program (SDP) that can be solved computationally. Although such computations are subject to numerical error, we demonstrate two ways to obtain rigorous results: using interval arithmetic to control the error of an approximate SDP solution, and finding exact analytical solutions to relatively small SDPs. Previous formulations are extended to allow for bounds depending analytically on parametric variables. These methods are illustrated using the Lorenz equations, a system with three state variables ( x, y, z) and three parameters (β ,σ ,r). Bounds are reported for infinite-time averages of all eighteen moments x^ly^mz^n up to quartic degree that are symmetric under (x,y)\\mapsto (-x,-y). These bounds apply to all solutions regardless of stability, including chaotic trajectories, periodic orbits, and equilibrium points. The analytical approach yields two novel bounds that are sharp: the mean of z^3 can be no larger than its value of (r-1)^3 at the nonzero equilibria, and the mean of xy^3 must be nonnegative. The interval arithmetic approach is applied at the standard chaotic parameters to bound eleven average moments that all appear to be maximized on the shortest periodic orbit. Our best upper bound on each such average exceeds its value on the maximizing orbit by less than 1%. Many bounds reported here are much tighter than would be possible without computer assistance.

  1. Electron transfer. 88. Cobalt(III)-bound phosphite and hypophosphite

    International Nuclear Information System (INIS)

    Linn, D.E. Jr.; Gould, E.S.

    1987-01-01

    Phosphite and hypophosphite coordinate to cobalt(III) in (NH 3 ) 5 Co/sup III/ through oxygen, rather than through phosphorus. The resulting complexes undergo electron-transfer reactions with Ru(NH 3 ) 6 2+ much more slowly than with Eu 2+ or V 2+ , indicating that the latter two reactants preferentially utilize ligand bridging. Reductions with Cr 2+ are shown to accompanied by transfer of the phosphorus-containing ligands, and reaction of the protonated phosphito (biphosphito) derivative (pK/sub A/ = 3.06 at 23 0 C) proceeds through a combination of acid-independent and inverse-acid paths, both routes yielding the same phosphito-bound Cr(III) product. The hypophosphito, but not the biphosphito, complex reacts with Ce(IV), producing Co 2+ in an induced electron-transfer process. The yield of Co 2+ falls off progressively as [Ce/sup IV/] is increased, pointing to a sequence in which a Co(III)-bound P(II) radical is formed in initial attack by Ce(IV) but subsequently undergoes partition between competing reaction paths, i.e. internal electron transfer to Co(III) vs external oxidation by a second Ce(IV) center. The hypophosphito complex, but not the biphosphito complex, smoothly decomposes in basic media via an internal redox reaction, yielding Co(II) quantitatively, along with a 1:1 mixture of phosphite, and hypophosphite. This transformation, which fails with mixtures of (NH 3 ) 5 Co(H 2 O) 3+ and H 2 PO 2 - appears to be catalyzed specifically by OH - . Deuterium-labeling experiments disclose a solvent isotope effect. Reaction mechanisms are suggested for all the observed results. 54 references, 5 tables

  2. Sulfur ligand mediated electrochemistry of gold surfaces and nanoparticles: what, how, and why

    DEFF Research Database (Denmark)

    Chi, Qijin; Ford, Michael J.; Halder, Arnab

    2017-01-01

    Gold surfaces are widely used in electrochemistry whilst gold nanoparticles have very many uses, with both the surfaces and the particles often being protected by sulfur-bound organic ligands. The ligands not only provide chemical stability but also directly participate in many desired processes....... This review considers the diversity of known atomic structures for gold-sulfur interfaces, how these structures facilitate a diversity of mechanisms in electrochemical applications, and why this is possible based on recent advances in the basic understanding of the electronic structure of gold-sulfur bonds...

  3. Capacity Bounds for Parallel Optical Wireless Channels

    KAUST Repository

    Chaaban, Anas; Rezki, Zouheir; Alouini, Mohamed-Slim

    2016-01-01

    A system consisting of parallel optical wireless channels with a total average intensity constraint is studied. Capacity upper and lower bounds for this system are derived. Under perfect channel-state information at the transmitter (CSIT), the bounds have to be optimized with respect to the power allocation over the parallel channels. The optimization of the lower bound is non-convex, however, the KKT conditions can be used to find a list of possible solutions one of which is optimal. The optimal solution can then be found by an exhaustive search algorithm, which is computationally expensive. To overcome this, we propose low-complexity power allocation algorithms which are nearly optimal. The optimized capacity lower bound nearly coincides with the capacity at high SNR. Without CSIT, our capacity bounds lead to upper and lower bounds on the outage probability. The outage probability bounds meet at high SNR. The system with average and peak intensity constraints is also discussed.

  4. Maximizing the Range of a Projectile.

    Science.gov (United States)

    Brown, Ronald A.

    1992-01-01

    Discusses solutions to the problem of maximizing the range of a projectile. Presents three references that solve the problem with and without the use of calculus. Offers a fourth solution suitable for introductory physics courses that relies more on trigonometry and the geometry of the problem. (MDH)

  5. Robust Utility Maximization Under Convex Portfolio Constraints

    International Nuclear Information System (INIS)

    Matoussi, Anis; Mezghani, Hanen; Mnif, Mohamed

    2015-01-01

    We study a robust maximization problem from terminal wealth and consumption under a convex constraints on the portfolio. We state the existence and the uniqueness of the consumption–investment strategy by studying the associated quadratic backward stochastic differential equation. We characterize the optimal control by using the duality method and deriving a dynamic maximum principle

  6. Ehrenfest's Lottery--Time and Entropy Maximization

    Science.gov (United States)

    Ashbaugh, Henry S.

    2010-01-01

    Successful teaching of the Second Law of Thermodynamics suffers from limited simple examples linking equilibrium to entropy maximization. I describe a thought experiment connecting entropy to a lottery that mixes marbles amongst a collection of urns. This mixing obeys diffusion-like dynamics. Equilibrium is achieved when the marble distribution is…

  7. Reserve design to maximize species persistence

    Science.gov (United States)

    Robert G. Haight; Laurel E. Travis

    2008-01-01

    We develop a reserve design strategy to maximize the probability of species persistence predicted by a stochastic, individual-based, metapopulation model. Because the population model does not fit exact optimization procedures, our strategy involves deriving promising solutions from theory, obtaining promising solutions from a simulation optimization heuristic, and...

  8. Maximal indecomposable past sets and event horizons

    International Nuclear Information System (INIS)

    Krolak, A.

    1984-01-01

    The existence of maximal indecomposable past sets MIPs is demonstrated using the Kuratowski-Zorn lemma. A criterion for the existence of an absolute event horizon in space-time is given in terms of MIPs and a relation to black hole event horizon is shown. (author)

  9. Maximization of eigenvalues using topology optimization

    DEFF Research Database (Denmark)

    Pedersen, Niels Leergaard

    2000-01-01

    to localized modes in low density areas. The topology optimization problem is formulated using the SIMP method. Special attention is paid to a numerical method for removing localized eigenmodes in low density areas. The method is applied to numerical examples of maximizing the first eigenfrequency, One example...

  10. Maximizing Resource Utilization in Video Streaming Systems

    Science.gov (United States)

    Alsmirat, Mohammad Abdullah

    2013-01-01

    Video streaming has recently grown dramatically in popularity over the Internet, Cable TV, and wire-less networks. Because of the resource demanding nature of video streaming applications, maximizing resource utilization in any video streaming system is a key factor to increase the scalability and decrease the cost of the system. Resources to…

  11. A THEORY OF MAXIMIZING SENSORY INFORMATION

    NARCIS (Netherlands)

    Hateren, J.H. van

    1992-01-01

    A theory is developed on the assumption that early sensory processing aims at maximizing the information rate in the channels connecting the sensory system to more central parts of the brain, where it is assumed that these channels are noisy and have a limited dynamic range. Given a stimulus power

  12. Maximizing scientific knowledge from randomized clinical trials

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Atar, Dan; Pitt, Bertram

    2010-01-01

    Trialists have an ethical and financial responsibility to plan and conduct clinical trials in a manner that will maximize the scientific knowledge gained from the trial. However, the amount of scientific information generated by randomized clinical trials in cardiovascular medicine is highly vari...

  13. A Model of College Tuition Maximization

    Science.gov (United States)

    Bosshardt, Donald I.; Lichtenstein, Larry; Zaporowski, Mark P.

    2009-01-01

    This paper develops a series of models for optimal tuition pricing for private colleges and universities. The university is assumed to be a profit maximizing, price discriminating monopolist. The enrollment decision of student's is stochastic in nature. The university offers an effective tuition rate, comprised of stipulated tuition less financial…

  14. Logit Analysis for Profit Maximizing Loan Classification

    OpenAIRE

    Watt, David L.; Mortensen, Timothy L.; Leistritz, F. Larry

    1988-01-01

    Lending criteria and loan classification methods are developed. Rating system breaking points are analyzed to present a method to maximize loan revenues. Financial characteristics of farmers are used as determinants of delinquency in a multivariate logistic model. Results indicate that debt-to-asset and operating ration are most indicative of default.

  15. Developing maximal neuromuscular power: Part 1--biological basis of maximal power production.

    Science.gov (United States)

    Cormie, Prue; McGuigan, Michael R; Newton, Robert U

    2011-01-01

    This series of reviews focuses on the most important neuromuscular function in many sport performances, the ability to generate maximal muscular power. Part 1 focuses on the factors that affect maximal power production, while part 2, which will follow in a forthcoming edition of Sports Medicine, explores the practical application of these findings by reviewing the scientific literature relevant to the development of training programmes that most effectively enhance maximal power production. The ability of the neuromuscular system to generate maximal power is affected by a range of interrelated factors. Maximal muscular power is defined and limited by the force-velocity relationship and affected by the length-tension relationship. The ability to generate maximal power is influenced by the type of muscle action involved and, in particular, the time available to develop force, storage and utilization of elastic energy, interactions of contractile and elastic elements, potentiation of contractile and elastic filaments as well as stretch reflexes. Furthermore, maximal power production is influenced by morphological factors including fibre type contribution to whole muscle area, muscle architectural features and tendon properties as well as neural factors including motor unit recruitment, firing frequency, synchronization and inter-muscular coordination. In addition, acute changes in the muscle environment (i.e. alterations resulting from fatigue, changes in hormone milieu and muscle temperature) impact the ability to generate maximal power. Resistance training has been shown to impact each of these neuromuscular factors in quite specific ways. Therefore, an understanding of the biological basis of maximal power production is essential for developing training programmes that effectively enhance maximal power production in the human.

  16. Understanding Violations of Gricean Maxims in Preschoolers and Adults

    Directory of Open Access Journals (Sweden)

    Mako eOkanda

    2015-07-01

    Full Text Available This study used a revised Conversational Violations Test to examine Gricean maxim violations in 4- to 6-year-old Japanese children and adults. Participants’ understanding of the following maxims was assessed: be informative (first maxim of quantity, avoid redundancy (second maxim of quantity, be truthful (maxim of quality, be relevant (maxim of relation, avoid ambiguity (second maxim of manner, and be polite (maxim of politeness. Sensitivity to violations of Gricean maxims increased with age: 4-year-olds’ understanding of maxims was near chance, 5-year-olds understood some maxims (first maxim of quantity and maxims of quality, relation, and manner, and 6-year-olds and adults understood all maxims. Preschoolers acquired the maxim of relation first and had the greatest difficulty understanding the second maxim of quantity. Children and adults differed in their comprehension of the maxim of politeness. The development of the pragmatic understanding of Gricean maxims and implications for the construction of developmental tasks from early childhood to adulthood are discussed.

  17. Influence of ligand structure on anticancer and antioxidant properties of rhenium cluster compounds

    Directory of Open Access Journals (Sweden)

    I. V. Leus

    2009-11-01

    Full Text Available Under the model growth of T8 Guerin’s carcinoma in rats we studied the anticancer activity of the system rhenium-platinum, which includes cis-dicarboxylates of rhenium (III with different alkyl ligands, erythrocytes number and its morphological structure, erythrocytic stability, blood haemoglobin concentration, catalase activity and concentration of TBA-active products in the rats blood plasma. The renium-platinum system had considerable antioxidat effect and prevented the growth of tumour, that was maximal for a compound with the pivalate ligand.

  18. VORONOI DIAGRAMS WITHOUT BOUNDING BOXES

    Directory of Open Access Journals (Sweden)

    E. T. K. Sang

    2015-10-01

    Full Text Available 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.

  19. Spectral computations for bounded operators

    CERN Document Server

    Ahues, Mario; Limaye, Balmohan

    2001-01-01

    Exact eigenvalues, eigenvectors, and principal vectors of operators with infinite dimensional ranges can rarely be found. Therefore, one must approximate such operators by finite rank operators, then solve the original eigenvalue problem approximately. Serving as both an outstanding text for graduate students and as a source of current results for research scientists, Spectral Computations for Bounded Operators addresses the issue of solving eigenvalue problems for operators on infinite dimensional spaces. From a review of classical spectral theory through concrete approximation techniques to finite dimensional situations that can be implemented on a computer, this volume illustrates the marriage of pure and applied mathematics. It contains a variety of recent developments, including a new type of approximation that encompasses a variety of approximation methods but is simple to verify in practice. It also suggests a new stopping criterion for the QR Method and outlines advances in both the iterative refineme...

  20. Crystallization of protein–ligand complexes

    International Nuclear Information System (INIS)

    Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

    2007-01-01

    Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

  1. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

    2017-01-01

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  2. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui

    2017-10-02

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  3. Reactivity of halide and pseudohalide ligands

    International Nuclear Information System (INIS)

    Kukushkin, Yu.N.

    1987-01-01

    Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

  4. The upper bound on the lightest Higgs mass in the NMSSM revisited

    International Nuclear Information System (INIS)

    Ellwanger, Ulrich; Hugonie, Cyril

    2007-04-01

    We update the upper bound on the lightest CP even Higgs mass in the NMSSM, which is given as a function of tanβ and λ. We include the available one and two loop corrections to the NMSSM Higgs masses, and constraints from the absence of Landau singularities below the GUT scale as well as from the stability of the NMSSM Higgs potential. For m top varying between 171.4 and 178 GeV, squark masses of 1 TeV and maximal mixing the upper bound is assumed near tanβ ∼ 2 and varies between 139.9 and 141.4 GeV

  5. Universal localizing bounds for compact invariant sets of natural polynomial Hamiltonian systems

    International Nuclear Information System (INIS)

    Starkov, Konstantin E.

    2008-01-01

    In this Letter we study the localization problem of compact invariant sets of natural Hamiltonian systems with a polynomial Hamiltonian. Our results are based on applying the first order extremum conditions. We compute universal localizing bounds for some domain containing all compact invariant sets of a Hamiltonian system by using one quadratic function of a simple form. These bounds depend on the value of the total energy of the system, degree and some coefficients of a potential and, in addition, some positive number got as a result of a solution of one maximization problem. Besides, under some quasihomogeneity condition(s) we generalize our construction of the localization set

  6. Universal localizing bounds for compact invariant sets of natural polynomial Hamiltonian systems

    Energy Technology Data Exchange (ETDEWEB)

    Starkov, Konstantin E. [CITEDI-IPN, Av. del Parque 1310, Mesa de Otay, Tijuana, BC (Mexico)], E-mail: konst@citedi.mx

    2008-10-06

    In this Letter we study the localization problem of compact invariant sets of natural Hamiltonian systems with a polynomial Hamiltonian. Our results are based on applying the first order extremum conditions. We compute universal localizing bounds for some domain containing all compact invariant sets of a Hamiltonian system by using one quadratic function of a simple form. These bounds depend on the value of the total energy of the system, degree and some coefficients of a potential and, in addition, some positive number got as a result of a solution of one maximization problem. Besides, under some quasihomogeneity condition(s) we generalize our construction of the localization set.

  7. Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin.

    Science.gov (United States)

    Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck

    2015-09-11

    Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Detection of site-specific binding and co-binding of ligands to macromolecules using 19F NMR

    International Nuclear Information System (INIS)

    Jenkins, B.G.

    1991-01-01

    Study of ligand-macromolecular interactions by 19 F nuclear magnetic resonance (NMR) spectroscopy affords many opportunities for obtaining molecular biochemical and pharmaceutical information. This is due to the absence of a background fluorine signal, as well as the relatively high sensitivity of 19 F NMR. Use of fluorine-labeled ligands enables one to probe not only binding and co-binding phenomena to macromolecules, but also can provide data on binding constants, stoichiometries, kinetics, and conformational properties of these complexes. Under conditions of slow exchange and macromolecule-induced chemical shifts, multiple 19 F NMR resonances can be observed for free and bound ligands. These shifted resonances are a direct correlate of the concentration of ligand bound in a specific state rather than the global concentrations of bound or free ligand which are usually determined using other techniques such as absorption spectroscopy or equilibrium dialysis. Examples of these interactions are demonstrated both from the literature and from interactions of 5-fluorotryptophan, 5-fluorosalicylic acid, flurbiprofen, and sulindac sulfide with human serum albumin. Other applications of 19 F NMR to study of these interactions in vivo, as well for receptor binding and metabolic tracing of fluorinated drugs and proteins are discussed

  9. Upper bounds on the relative energy difference of pure and mixed Gaussian states with a fixed fidelity

    International Nuclear Information System (INIS)

    Dodonov, V V

    2012-01-01

    Exact and approximate formulas for the upper bound of the relative energy difference of two Gaussian states with a fixed fidelity between them are derived. The reciprocal formulas for the upper bound of the fidelity for the fixed value of the relative energy difference are also obtained. The bounds appear higher for pure states than for mixed ones, and their maximal values correspond to squeezed vacuum states. In particular, to guarantee the relative energy difference less than 10%, for quite arbitrary Gaussian states, the fidelity between them must exceed the level 0.998866. (fast track communication)

  10. MHC-I Ligand Discovery Using Targeted Database Searches of Mass Spectrometry Data: Implications for T-Cell Immunotherapies

    DEFF Research Database (Denmark)

    Murphy, J. Patrick; Konda, Prathyusha; Kowalewski, Daniel J.

    2017-01-01

    Class I major histocompatibility complex (MHC-I)-bound peptide ligands dictate the activation and specificity of CD8+ T cells and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these MHC-I pept...

  11. Sampling and energy evaluation challenges in ligand binding protein design.

    Science.gov (United States)

    Dou, Jiayi; Doyle, Lindsey; Jr Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L; Baker, David

    2017-12-01

    The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17-OHP with micromolar affinity. A co-crystal structure of one of the designs revealed that 17-OHP is rotated 180° around a pseudo-two-fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same "flipped" orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two-fold symmetry of the molecule. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  12. Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology

    Directory of Open Access Journals (Sweden)

    Kotaro Sakamoto

    2017-09-01

    Full Text Available ActRIIB (activin receptor type-2B is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN, growth differentiation factor 11 (GDF11, and bone morphogenetic protein 9 (BMP9. Notably, the protein-protein interaction (PPI between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9, AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

  13. Refined reservoir description to maximize oil recovery

    International Nuclear Information System (INIS)

    Flewitt, W.E.

    1975-01-01

    To assure maximized oil recovery from older pools, reservoir description has been advanced by fully integrating original open-hole logs and the recently introduced interpretive techniques made available through cased-hole wireline saturation logs. A refined reservoir description utilizing normalized original wireline porosity logs has been completed in the Judy Creek Beaverhill Lake ''A'' Pool, a reefal carbonate pool with current potential productivity of 100,000 BOPD and 188 active wells. Continuous porosity was documented within a reef rim and cap while discontinuous porous lenses characterized an interior lagoon. With the use of pulsed neutron logs and production data a separate water front and pressure response was recognized within discrete environmental units. The refined reservoir description aided in reservoir simulation model studies and quantifying pool performance. A pattern water flood has now replaced the original peripheral bottom water drive to maximize oil recovery

  14. Maximal frustration as an immunological principle.

    Science.gov (United States)

    de Abreu, F Vistulo; Mostardinha, P

    2009-03-06

    A fundamental problem in immunology is that of understanding how the immune system selects promptly which cells to kill without harming the body. This problem poses an apparent paradox. Strong reactivity against pathogens seems incompatible with perfect tolerance towards self. We propose a different view on cellular reactivity to overcome this paradox: effector functions should be seen as the outcome of cellular decisions which can be in conflict with other cells' decisions. We argue that if cellular systems are frustrated, then extensive cross-reactivity among the elements in the system can decrease the reactivity of the system as a whole and induce perfect tolerance. Using numerical and mathematical analyses, we discuss two simple models that perform optimal pathogenic detection with no autoimmunity if cells are maximally frustrated. This study strongly suggests that a principle of maximal frustration could be used to build artificial immune systems. It would be interesting to test this principle in the real adaptive immune system.

  15. O{sup -} bound small polarons in oxide materials

    Energy Technology Data Exchange (ETDEWEB)

    Schirmer, O F [Department of Physics, University of Osnabrueck, D-49076 Osnabrueck (Germany)

    2006-11-01

    Holes bound to acceptor defects in oxide crystals are often localized by lattice distortion at just one of the equivalent oxygen ligands of the defect. Such holes thus form small polarons in symmetric clusters of a few oxygen ions. An overview on mainly the optical manifestations of those clusters is given. The article is essentially divided into two parts: the first one covers the basic features of the phenomena and their explanations, exemplified by several paradigmatic defects; in the second part numerous oxide materials are presented which exhibit bound small polaron optical properties. The first part starts with summaries on the production of bound hole polarons and the identification of their structure. It is demonstrated why they show strong, wide absorption bands, usually visible, based on polaron stabilization energies of typically 1 eV. The basic absorption process is detailed with a fictitious two-well system. Clusters with four, six and twelve equivalent ions are realized in various oxide compounds. In these cases several degenerate optically excited polaron states occur, leading to characteristic final state resonance splittings. The peak energies of the absorption bands as well as the sign of the transfer energy depend on the topology of the clusters. A special section is devoted to the distinction between interpolaron and intrapolaron optical transitions. The latter are usually comparatively weak. The oxide compounds exhibiting bound hole small polaron absorptions include the alkaline earth oxides (e.g. MgO), BeO and ZnO, the perovskites BaTiO{sub 3} and KTaO{sub 3}, quartz, the sillenites (e.g. Bi{sub 12}TiO{sub 20}), Al{sub 2}O{sub 3}, LiNbO{sub 3}, topaz and various other materials. There are indications that the magnetic crystals NiO, doped with Li, and LaMnO{sub 3}, doped with Sr, also show optical features caused by bound hole polarons. Beyond being elementary paradigms for the properties of small polarons in general, the defect species treated

  16. Ligand-regulated peptide aptamers.

    Science.gov (United States)

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  17. Terminal altitude maximization for Mars entry considering uncertainties

    Science.gov (United States)

    Cui, Pingyuan; Zhao, Zeduan; Yu, Zhengshi; Dai, Juan

    2018-04-01

    Uncertainties present in the Mars atmospheric entry process may cause state deviations from the nominal designed values, which will lead to unexpected performance degradation if the trajectory is designed merely based on the deterministic dynamic model. In this paper, a linear covariance based entry trajectory optimization method is proposed considering the uncertainties presenting in the initial states and parameters. By extending the elements of the state covariance matrix as augmented states, the statistical behavior of the trajectory is captured to reformulate the performance metrics and path constraints. The optimization problem is solved by the GPOPS-II toolbox in MATLAB environment. Monte Carlo simulations are also conducted to demonstrate the capability of the proposed method. Primary trading performances between the nominal deployment altitude and its dispersion can be observed by modulating the weights on the dispersion penalty, and a compromised result referring to maximizing the 3σ lower bound of the terminal altitude is achieved. The resulting path constraints also show better satisfaction in a disturbed environment compared with the nominal situation.

  18. Instanton bound states in ABJM theory

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [DESY Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

    2013-06-15

    The partition function of the ABJM theory receives non-perturbative corrections due to instanton effects. We study these non-perturbative corrections, including bound states of worldsheet instantons and membrane instantons, in the Fermi-gas approach. We require that the total non-perturbative correction should be always finite for arbitrary Chern-Simons level. This finiteness is realized quite non-trivially because each bound state contribution naively diverges at some levels. The poles of each contribution should be canceled out in total. We use this pole cancellation mechanism to find unknown bound state corrections from known ones. We conjecture a general expression of the bound state contribution. Summing up all the bound state contributions, we find that the effect of bound states is simply incorporated into the worldsheet instanton correction by a redefinition of the chemical potential in the Fermi-gas system. Analytic expressions of the 3- and 4-membrane instanton corrections are also proposed.

  19. Control of Shareholders’ Wealth Maximization in Nigeria

    OpenAIRE

    A. O. Oladipupo; C. O. Okafor

    2014-01-01

    This research focuses on who controls shareholder’s wealth maximization and how does this affect firm’s performance in publicly quoted non-financial companies in Nigeria. The shareholder fund was the dependent while explanatory variables were firm size (proxied by log of turnover), retained earning (representing management control) and dividend payment (representing measure of shareholders control). The data used for this study were obtained from the Nigerian Stock Exchange [NSE] fact book an...

  20. Definable maximal discrete sets in forcing extensions

    DEFF Research Database (Denmark)

    Törnquist, Asger Dag; Schrittesser, David

    2018-01-01

    Let  be a Σ11 binary relation, and recall that a set A is -discrete if no two elements of A are related by . We show that in the Sacks and Miller forcing extensions of L there is a Δ12 maximal -discrete set. We use this to answer in the negative the main question posed in [5] by showing...

  1. Dynamic Convex Duality in Constrained Utility Maximization

    OpenAIRE

    Li, Yusong; Zheng, Harry

    2016-01-01

    In this paper, we study a constrained utility maximization problem following the convex duality approach. After formulating the primal and dual problems, we construct the necessary and sufficient conditions for both the primal and dual problems in terms of FBSDEs plus additional conditions. Such formulation then allows us to explicitly characterize the primal optimal control as a function of the adjoint process coming from the dual FBSDEs in a dynamic fashion and vice versa. Moreover, we also...

  2. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  3. Beyond Helper Phage: Using "Helper Cells" to Select Peptide Affinity Ligands.

    Directory of Open Access Journals (Sweden)

    M Lisa Phipps

    Full Text Available Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1 ensure efficient display; 2 maximize the ability to select high affinity ligands; and 3 minimize the effect of the display context on binding. The "helper cell" packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report on the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.

  4. Single maximal versus combination punch kinematics.

    Science.gov (United States)

    Piorkowski, Barry A; Lees, Adrian; Barton, Gabor J

    2011-03-01

    The aim of this study was to determine the influence of punch type (Jab, Cross, Lead Hook and Reverse Hook) and punch modality (Single maximal, 'In-synch' and 'Out of synch' combination) on punch speed and delivery time. Ten competition-standard volunteers performed punches with markers placed on their anatomical landmarks for 3D motion capture with an eight-camera optoelectronic system. Speed and duration between key moments were computed. There were significant differences in contact speed between punch types (F(2,18,84.87) = 105.76, p = 0.001) with Lead and Reverse Hooks developing greater speed than Jab and Cross. There were significant differences in contact speed between punch modalities (F(2,64,102.87) = 23.52, p = 0.001) with the Single maximal (M+/- SD: 9.26 +/- 2.09 m/s) higher than 'Out of synch' (7.49 +/- 2.32 m/s), 'In-synch' left (8.01 +/- 2.35 m/s) or right lead (7.97 +/- 2.53 m/s). Delivery times were significantly lower for Jab and Cross than Hook. Times were significantly lower 'In-synch' than a Single maximal or 'Out of synch' combination mode. It is concluded that a defender may have more evasion-time than previously reported. This research could be of use to performers and coaches when considering training preparations.

  5. Formation Control for the MAXIM Mission

    Science.gov (United States)

    Luquette, Richard J.; Leitner, Jesse; Gendreau, Keith; Sanner, Robert M.

    2004-01-01

    Over the next twenty years, a wave of change is occurring in the space-based scientific remote sensing community. While the fundamental limits in the spatial and angular resolution achievable in spacecraft have been reached, based on today s technology, an expansive new technology base has appeared over the past decade in the area of Distributed Space Systems (DSS). A key subset of the DSS technology area is that which covers precision formation flying of space vehicles. Through precision formation flying, the baselines, previously defined by the largest monolithic structure which could fit in the largest launch vehicle fairing, are now virtually unlimited. Several missions including the Micro-Arcsecond X-ray Imaging Mission (MAXIM), and the Stellar Imager will drive the formation flying challenges to achieve unprecedented baselines for high resolution, extended-scene, interferometry in the ultraviolet and X-ray regimes. This paper focuses on establishing the feasibility for the formation control of the MAXIM mission. MAXIM formation flying requirements are on the order of microns, while Stellar Imager mission requirements are on the order of nanometers. This paper specifically addresses: (1) high-level science requirements for these missions and how they evolve into engineering requirements; and (2) the development of linearized equations of relative motion for a formation operating in an n-body gravitational field. Linearized equations of motion provide the ground work for linear formation control designs.

  6. Gradient Dynamics and Entropy Production Maximization

    Science.gov (United States)

    Janečka, Adam; Pavelka, Michal

    2018-01-01

    We compare two methods for modeling dissipative processes, namely gradient dynamics and entropy production maximization. Both methods require similar physical inputs-how energy (or entropy) is stored and how it is dissipated. Gradient dynamics describes irreversible evolution by means of dissipation potential and entropy, it automatically satisfies Onsager reciprocal relations as well as their nonlinear generalization (Maxwell-Onsager relations), and it has statistical interpretation. Entropy production maximization is based on knowledge of free energy (or another thermodynamic potential) and entropy production. It also leads to the linear Onsager reciprocal relations and it has proven successful in thermodynamics of complex materials. Both methods are thermodynamically sound as they ensure approach to equilibrium, and we compare them and discuss their advantages and shortcomings. In particular, conditions under which the two approaches coincide and are capable of providing the same constitutive relations are identified. Besides, a commonly used but not often mentioned step in the entropy production maximization is pinpointed and the condition of incompressibility is incorporated into gradient dynamics.

  7. Interaction between alkaline earth cations and oxo-ligands. DFT study of the affinity of the Ca2+ cation for carbonyl ligands.

    Science.gov (United States)

    da Costa, Leonardo Moreira; Carneiro, José Walkimar de Mesquita; Romeiro, Gilberto Alves; Paes, Lilian Weitzel Coelho

    2011-02-01

    The affinity of the Ca(2+) ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods. Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)(2)] (R=H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca(2+) cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less negative (destabilizing the complex formed).

  8. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  9. Bounded elements in Locally C*-algebras

    International Nuclear Information System (INIS)

    El Harti, Rachid

    2001-09-01

    In order to get more useful information about Locally C*-algebras, we introduce in this paper the notion of bounded elements. First, we study the connection between bounded elements and spectrally bounded elements. Some structural results of Locally C*-algebras are established in Theorems 1 , 2 and 3. As an immediate consequence of Theorem 3, we give a characterization of the connected component of the identity in the group of unitary elements for a Locally C*-algebra. (author)

  10. Fuzzy upper bounds and their applications

    Energy Technology Data Exchange (ETDEWEB)

    Soleimani-damaneh, M. [Department of Mathematics, Faculty of Mathematical Science and Computer Engineering, Teacher Training University, 599 Taleghani Avenue, Tehran 15618 (Iran, Islamic Republic of)], E-mail: soleimani_d@yahoo.com

    2008-04-15

    This paper considers the concept of fuzzy upper bounds and provides some relevant applications. Considering a fuzzy DEA model, the existence of a fuzzy upper bound for the objective function of the model is shown and an effective approach to solve that model is introduced. Some dual interpretations are provided, which are useful for practical purposes. Applications of the concept of fuzzy upper bounds in two physical problems are pointed out.

  11. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  12. Bounded cohomology of discrete groups

    CERN Document Server

    Frigerio, Roberto

    2017-01-01

    The author manages a near perfect equilibrium between necessary technicalities (always well motivated) and geometric intuition, leading the readers from the first simple definition to the most striking applications of the theory in 13 very pleasant chapters. This book can serve as an ideal textbook for a graduate topics course on the subject and become the much-needed standard reference on Gromov's beautiful theory. -Michelle Bucher The theory of bounded cohomology, introduced by Gromov in the late 1980s, has had powerful applications in geometric group theory and the geometry and topology of manifolds, and has been the topic of active research continuing to this day. This monograph provides a unified, self-contained introduction to the theory and its applications, making it accessible to a student who has completed a first course in algebraic topology and manifold theory. The book can be used as a source for research projects for master's students, as a thorough introduction to the field for graduate student...

  13. Some Improved Nonperturbative Bounds for Fermionic Expansions

    Energy Technology Data Exchange (ETDEWEB)

    Lohmann, Martin, E-mail: marlohmann@gmail.com [Universita di Roma Tre, Dipartimento di Matematica (Italy)

    2016-06-15

    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.

  14. Cardiorespiratory Coordination in Repeated Maximal Exercise

    Directory of Open Access Journals (Sweden)

    Sergi Garcia-Retortillo

    2017-06-01

    Full Text Available Increases in cardiorespiratory coordination (CRC after training with no differences in performance and physiological variables have recently been reported using a principal component analysis approach. However, no research has yet evaluated the short-term effects of exercise on CRC. The aim of this study was to delineate the behavior of CRC under different physiological initial conditions produced by repeated maximal exercises. Fifteen participants performed 2 consecutive graded and maximal cycling tests. Test 1 was performed without any previous exercise, and Test 2 6 min after Test 1. Both tests started at 0 W and the workload was increased by 25 W/min in males and 20 W/min in females, until they were not able to maintain the prescribed cycling frequency of 70 rpm for more than 5 consecutive seconds. A principal component (PC analysis of selected cardiovascular and cardiorespiratory variables (expired fraction of O2, expired fraction of CO2, ventilation, systolic blood pressure, diastolic blood pressure, and heart rate was performed to evaluate the CRC defined by the number of PCs in both tests. In order to quantify the degree of coordination, the information entropy was calculated and the eigenvalues of the first PC (PC1 were compared between tests. Although no significant differences were found between the tests with respect to the performed maximal workload (Wmax, maximal oxygen consumption (VO2 max, or ventilatory threshold (VT, an increase in the number of PCs and/or a decrease of eigenvalues of PC1 (t = 2.95; p = 0.01; d = 1.08 was found in Test 2 compared to Test 1. Moreover, entropy was significantly higher (Z = 2.33; p = 0.02; d = 1.43 in the last test. In conclusion, despite the fact that no significant differences were observed in the conventionally explored maximal performance and physiological variables (Wmax, VO2 max, and VT between tests, a reduction of CRC was observed in Test 2. These results emphasize the interest of CRC

  15. Optimal bounds and extremal trajectories for time averages in nonlinear dynamical systems

    Science.gov (United States)

    Tobasco, Ian; Goluskin, David; Doering, Charles R.

    2018-02-01

    For any quantity of interest in a system governed by ordinary differential equations, it is natural to seek the largest (or smallest) long-time average among solution trajectories, as well as the extremal trajectories themselves. Upper bounds on time averages can be proved a priori using auxiliary functions, the optimal choice of which is a convex optimization problem. We prove that the problems of finding maximal trajectories and minimal auxiliary functions are strongly dual. Thus, auxiliary functions provide arbitrarily sharp upper bounds on time averages. Moreover, any nearly minimal auxiliary function provides phase space volumes in which all nearly maximal trajectories are guaranteed to lie. For polynomial equations, auxiliary functions can be constructed by semidefinite programming, which we illustrate using the Lorenz system.

  16. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    International Nuclear Information System (INIS)

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian; Roitberg, Adrian E.

    2015-01-01

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data

  17. On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

    Energy Technology Data Exchange (ETDEWEB)

    Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Fernandez-Alberti, Sebastian, E-mail: sfalberti@gmail.com [Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal (Argentina); Roitberg, Adrian E. [Departments of Physics and Chemistry, University of Florida, Gainesville, Florida 32611 (United States)

    2015-06-28

    The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

  18. Thermodynamics of Ligand Binding to a Heterogeneous RNA Population in the Malachite Green Aptamer

    Science.gov (United States)

    Sokoloski, Joshua E.; Dombrowski, Sarah E.; Bevilacqua, Philip C.

    2011-01-01

    The malachite green aptamer binds two closely related ligands, malachite green (MG) and tetramethylrosamine (TMR), with near equal affinity. The MG ligand consists of three phenyl rings emanating from a central carbon, while TMR has two of the three rings connected by an ether linkage. The binding pockets for MG and TMR in the aptamer, known from high-resolution structure, differ only in the conformation of a few nucleotides. Herein, we applied isothermal titration calorimetry (ITC) to compare the thermodynamics for binding of MG and TMR to the aptamer. Binding heat capacities were obtained from ITC titrations over the temperature range of 15 to 60 °C. Two temperature regimes were found for MG binding: one from 15 to 45 °C where MG bound with a large negative heat capacity and an apparent stoichiometry (n) of ~0.4, and another from 50 to 60 °C where MG bound with positive heat capacity and n~1.1. The binding of TMR, on the other hand, revealed only one temperature regime for binding, with a more modest negative heat capacity and n~1.2. The large difference in heat capacity between the two ligands suggests that significantly more conformational rearrangement occurs upon the binding of MG than TMR, which is consistent with differences in solvent accessible surface area calculated for available ligand-bound structures. Lastly, we note that binding stoichiometry of MG was improved not only by raising the temperature, but also by lowering the concentration of Mg2+ or increasing the time between ITC injections. These studies suggest that binding of a dynamical ligand to a functional RNA requires the RNA itself to have significant dynamics. PMID:22192051

  19. Moral satisficing: rethinking moral behavior as bounded rationality.

    Science.gov (United States)

    Gigerenzer, Gerd

    2010-07-01

    What is the nature of moral behavior? According to the study of bounded rationality, it results not from character traits or rational deliberation alone, but from the interplay between mind and environment. In this view, moral behavior is based on pragmatic social heuristics rather than moral rules or maximization principles. These social heuristics are not good or bad per se, but solely in relation to the environments in which they are used. This has methodological implications for the study of morality: Behavior needs to be studied in social groups as well as in isolation, in natural environments as well as in labs. It also has implications for moral policy: Only by accepting the fact that behavior is a function of both mind and environmental structures can realistic prescriptive means of achieving moral goals be developed. Copyright © 2010 Cognitive Science Society, Inc.

  20. Upper bound for the length of commutative algebras

    International Nuclear Information System (INIS)

    Markova, Ol'ga V

    2009-01-01

    By the length of a finite system of generators for a finite-dimensional associative algebra over an arbitrary field one means the least positive integer k such that the words of length not exceeding k span this algebra (as a vector space). The maximum length for the systems of generators of an algebra is referred to as the length of the algebra. In the present paper, an upper bound for the length of a commutative algebra in terms of a function of two invariants of the algebra, the dimension and the maximal degree of the minimal polynomial for the elements of the algebra, is obtained. As a corollary, a formula for the length of the algebra of diagonal matrices over an arbitrary field is obtained. Bibliography: 8 titles.

  1. NKG2D Ligands in Tumor Immunity: Two Sides of a Coin

    Directory of Open Access Journals (Sweden)

    Jennifer eWu

    2015-03-01

    Full Text Available The activating/co-stimulatory receptor NKG2D (natural-killer group 2, member D is expressed on the surface of all human NK, NKT, CD8+ T and subsets of γδ+ T cells. The significance of NKG2D function in tumor immunity has been well demonstrated in experimental animal models. However, the role of human NKG2D ligands in regulating tumor immunity and cancer prognosis had been controversial in the literature. In this review, we summarize the latest advancement, discuss the controversies, and present evidence that membrane-bound and soluble NKG2D ligands oppositely regulate tumor immunity. We also discuss new perspectives of targeting NKG2D ligands for cancer immunotherapy.

  2. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.

    Science.gov (United States)

    Amato, Anastasia; Lucas, Xavier; Bortoluzzi, Alessio; Wright, David; Ciulli, Alessio

    2018-04-20

    Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers.

  3. Automating crystallographic structure solution and refinement of protein–ligand complexes

    International Nuclear Information System (INIS)

    Echols, Nathaniel; Moriarty, Nigel W.; Klei, Herbert E.; Afonine, Pavel V.; Bunkóczi, Gábor; Headd, Jeffrey J.; McCoy, Airlie J.; Oeffner, Robert D.; Read, Randy J.; Terwilliger, Thomas C.; Adams, Paul D.

    2013-01-01

    A software system for automated protein–ligand crystallography has been implemented in the Phenix suite. This significantly reduces the manual effort required in high-throughput crystallographic studies. High-throughput drug-discovery and mechanistic studies often require the determination of multiple related crystal structures that only differ in the bound ligands, point mutations in the protein sequence and minor conformational changes. If performed manually, solution and refinement requires extensive repetition of the same tasks for each structure. To accelerate this process and minimize manual effort, a pipeline encompassing all stages of ligand building and refinement, starting from integrated and scaled diffraction intensities, has been implemented in Phenix. The resulting system is able to successfully solve and refine large collections of structures in parallel without extensive user intervention prior to the final stages of model completion and validation

  4. Variational lower bound on the scattering length

    International Nuclear Information System (INIS)

    Rosenberg, L.; Spruch, L.

    1975-01-01

    The scattering length A characterizes the zero-energy scattering of one system by another. It was shown some time ago that a variational upper bound on A could be obtained using methods, of the Rayleigh-Ritz type, which are commonly employed to obtain upper bounds on energy eigenvalues. Here we formulate a method for obtaining a variational lower bound on A. Once again the essential idea is to express the scattering length as a variational estimate plus an error term and then to reduce the problem of bounding the error term to one involving bounds on energy eigenvalues. In particular, the variational lower bound on A is rigorously established provided a certin modified Hamiltonian can be shown to have no discrete states lying below the level of the continuum threshold. It is unfortunately true that necessary conditions for the existence of bound states are not available for multiparticle systems in general. However, in the case of positron-atom scattering the adiabatic approximation can be introduced as an (essentially) solvable comparison problem to rigorously establish the nonexistence of bound states of the modified Hamiltonian. It has recently been shown how the validity of the variational upper bound on A can be maintained when the target ground-state wave function is imprecisely known. Similar methods can be used to maintain the variational lower bound on A. Since the bound is variational, the error in the calculated scattering length will be of second order in the error in the wave function. The use of the adiabatic approximation in the present context places no limitation in principle on the accuracy achievable

  5. Strong solutions for the Navier-Stokes equations on bounded and unbounded domains with a moving boundary

    Directory of Open Access Journals (Sweden)

    Juergen Saal

    2007-02-01

    Full Text Available It is proved under mild regularity assumptions on the data that the Navier-Stokes equations in bounded and unbounded noncylindrical regions admit a unique local-in-time strong solution. The result is based on maximal regularity estimates for the in spatial regions with a moving boundary obtained in [16] and the contraction mapping principle.

  6. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  7. Elucidation of Ligand-Dependent Modulation of Disorder-Order Transitions in the Oncoprotein MDM2.

    Directory of Open Access Journals (Sweden)

    Juan A Bueren-Calabuig

    2015-06-01

    Full Text Available Numerous biomolecular interactions involve unstructured protein regions, but how to exploit such interactions to enhance the affinity of a lead molecule in the context of rational drug design remains uncertain. Here clarification was sought for cases where interactions of different ligands with the same disordered protein region yield qualitatively different results. Specifically, conformational ensembles for the disordered lid region of the N-terminal domain of the oncoprotein MDM2 in the presence of different ligands were computed by means of a novel combination of accelerated molecular dynamics, umbrella sampling, and variational free energy profile methodologies. The resulting conformational ensembles for MDM2, free and bound to p53 TAD (17-29 peptide identify lid states compatible with previous NMR measurements. Remarkably, the MDM2 lid region is shown to adopt distinct conformational states in the presence of different small-molecule ligands. Detailed analyses of small-molecule bound ensembles reveal that the ca. 25-fold affinity improvement of the piperidinone family of inhibitors for MDM2 constructs that include the full lid correlates with interactions between ligand hydrophobic groups and the C-terminal lid region that is already partially ordered in apo MDM2. By contrast, Nutlin or benzodiazepinedione inhibitors, that bind with similar affinity to full lid and lid-truncated MDM2 constructs, interact additionally through their solubilizing groups with N-terminal lid residues that are more disordered in apo MDM2.

  8. General linear-optical quantum state generation scheme: Applications to maximally path-entangled states

    International Nuclear Information System (INIS)

    VanMeter, N. M.; Lougovski, P.; Dowling, Jonathan P.; Uskov, D. B.; Kieling, K.; Eisert, J.

    2007-01-01

    We introduce schemes for linear-optical quantum state generation. A quantum state generator is a device that prepares a desired quantum state using product inputs from photon sources, linear-optical networks, and postselection using photon counters. We show that this device can be concisely described in terms of polynomial equations and unitary constraints. We illustrate the power of this language by applying the Groebner-basis technique along with the notion of vacuum extensions to solve the problem of how to construct a quantum state generator analytically for any desired state, and use methods of convex optimization to identify bounds to success probabilities. In particular, we disprove a conjecture concerning the preparation of the maximally path-entangled |n,0>+|0,n> (NOON) state by providing a counterexample using these methods, and we derive a new upper bound on the resources required for NOON-state generation

  9. Optimal bounds and extremal trajectories for time averages in dynamical systems

    Science.gov (United States)

    Tobasco, Ian; Goluskin, David; Doering, Charles

    2017-11-01

    For systems governed by differential equations it is natural to seek extremal solution trajectories, maximizing or minimizing the long-time average of a given quantity of interest. A priori bounds on optima can be proved by constructing auxiliary functions satisfying certain point-wise inequalities, the verification of which does not require solving the underlying equations. We prove that for any bounded autonomous ODE, the problems of finding extremal trajectories on the one hand and optimal auxiliary functions on the other are strongly dual in the sense of convex duality. As a result, auxiliary functions provide arbitrarily sharp bounds on optimal time averages. Furthermore, nearly optimal auxiliary functions provide volumes in phase space where maximal and nearly maximal trajectories must lie. For polynomial systems, such functions can be constructed by semidefinite programming. We illustrate these ideas using the Lorenz system, producing explicit volumes in phase space where extremal trajectories are guaranteed to reside. Supported by NSF Award DMS-1515161, Van Loo Postdoctoral Fellowships, and the John Simon Guggenheim Foundation.

  10. Titration ELISA as a Method to Determine the Dissociation Constant of Receptor Ligand Interaction.

    Science.gov (United States)

    Eble, Johannes A

    2018-02-15

    The dissociation constant describes the interaction between two partners in the binding equilibrium and is a measure of their affinity. It is a crucial parameter to compare different ligands, e.g., competitive inhibitors, protein isoforms and mutants, for their binding strength to a binding partner. Dissociation constants are determined by plotting concentrations of bound versus free ligand as binding curves. In contrast, titration curves, in which a signal that is proportional to the concentration of bound ligand is plotted against the total concentration of added ligand, are much easier to record. The signal can be detected spectroscopically and by enzyme-linked immunosorbent assay (ELISA). This is exemplified in a protocol for a titration ELISA that measures the binding of the snake venom-derived rhodocetin to its immobilized target domain of α2β1 integrin. Titration ELISAs are versatile and widely used. Any pair of interacting proteins can be used as immobilized receptor and soluble ligand, provided that both proteins are pure, and their concentrations are known. The difficulty so far has been to determine the dissociation constant from a titration curve. In this study, a mathematical function underlying titration curves is introduced. Without any error-prone graphical estimation of a saturation yield, this algorithm allows processing of the raw data (signal intensities at different concentrations of added ligand) directly by mathematical evaluation via non-linear regression. Thus, several titration curves can be recorded simultaneously and transformed into a set of characteristic parameters, among them the dissociation constant and the concentration of binding-active receptor, and they can be evaluated statistically. When combined with this algorithm, titration ELISAs gain the advantage of directly presenting the dissociation constant. Therefore, they may be used more efficiently in the future.

  11. Ligand and Metal Based Multielectron Redox Chemistry of Cobalt Supported by Tetradentate Schiff Bases.

    Science.gov (United States)

    Andrez, Julie; Guidal, Valentin; Scopelliti, Rosario; Pécaut, Jacques; Gambarelli, Serge; Mazzanti, Marinella

    2017-06-28

    We have investigated the influence of bound cations on the reduction of cobalt complexes of redox active ligands and explored the reactivity of reduced species with CO 2 . The one electron reduction of [Co II ( R salophen)] with alkali metals (M = Li, Na, K) leads to either ligand-centered or metal-centered reduction depending on the alkali ion. It affords either the [Co I ( R salophen)K] complexes or the [Co II 2 (bis-salophen)M 2 ] (M = Li, Na) dimers that are present in solution in equilibrium with the respective [Co I (salophen)M] complexes. The two electron reduction of [Co II ( OMe salophen)] results in both ligand centered and metal centered reduction affording the Co(I)-Co(II)-Co(I) [Co 3 (tris- OMe salophen)Na 6 (THF) 6 ], 6 complex supported by a bridging deca-anionic tris- OMe salophen 10- ligand where three OMe salophen units are connected by two C-C bonds. Removal of the Na ion from 6 leads to a redistribution of the electrons affording the complex [(Co( OMe salophen)) 2 Na][Na(cryptand)] 3 , 7. The EPR spectrum of 7 suggests the presence of a Co(I) bound to a radical anionic ligand. Dissolution of 7 in pyridine leads to the isolation of [Co I 2 (bis- OMe salophen)Na 2 Py 4 ][Na(cryptand)] 2 , 8. Complex 6 reacts with ambient CO 2 leading to multiple CO 2 reduction products. The product of CO 2 addition to the OMe salophen ligand, [Co( OMe salophen-CO 2 )Na] 2 [Na(cryptand)] 2 , 9, was isolated but CO 3 2- formation in 53% yield was also detected. Thus, the electrons stored in the reversible C-C bonds may be used for the transformation of carbon dioxide.

  12. Stacked spheres and lower bound theorem

    Indian Academy of Sciences (India)

    BASUDEB DATTA

    2011-11-20

    Nov 20, 2011 ... Preliminaries. Lower bound theorem. On going work. Definitions. An n-simplex is a convex hull of n + 1 affinely independent points. (called vertices) in some Euclidean space R. N . Stacked spheres and lower bound theorem. Basudeb Datta. Indian Institute of Science. 2 / 27 ...

  13. A strongly quasiconvex PAC-Bayesian bound

    DEFF Research Database (Denmark)

    Thiemann, Niklas; Igel, Christian; Wintenberger, Olivier

    2017-01-01

    We propose a new PAC-Bayesian bound and a way of constructing a hypothesis space, so that the bound is convex in the posterior distribution and also convex in a trade-off parameter between empirical performance of the posterior distribution and its complexity. The complexity is measured by the Ku...

  14. On the range of completely bounded maps

    Directory of Open Access Journals (Sweden)

    Richard I. Loebl

    1978-01-01

    Full Text Available It is shown that if every bounded linear map from a C*-algebra α to a von Neumann algebra β is completely bounded, then either α is finite-dimensional or β⫅⊗Mn, where is a commutative von Neumann algebra and Mn is the algebra of n×n complex matrices.

  15. Bounds in the location-allocation problem

    DEFF Research Database (Denmark)

    Juel, Henrik

    1981-01-01

    Develops a family of stronger lower bounds on the objective function value of the location-allocation problem. Solution methods proposed to solve problems in location-allocation; Efforts to develop a more efficient bound solution procedure; Determination of the locations of the sources....

  16. Experimental evidence for bounds on quantum correlations.

    Science.gov (United States)

    Bovino, F A; Castagnoli, G; Degiovanni, I P; Castelletto, S

    2004-02-13

    We implemented the experiment proposed by Cabello in the preceding Letter to test the bounds of quantum correlation. As expected from the theory we found that, for certain choices of local observables, Tsirelson's bound of the Clauser-Horne-Shimony-Holt inequality (2 x square root of 2) is not reached by any quantum states.

  17. Exponential Lower Bounds For Policy Iteration

    OpenAIRE

    Fearnley, John

    2010-01-01

    We study policy iteration for infinite-horizon Markov decision processes. It has recently been shown policy iteration style algorithms have exponential lower bounds in a two player game setting. We extend these lower bounds to Markov decision processes with the total reward and average-reward optimality criteria.

  18. Conductivity bound from dirty black holes

    Energy Technology Data Exchange (ETDEWEB)

    Bitaghsir Fadafan, Kazem, E-mail: bitaghsir@shahroodut.ac.ir

    2016-11-10

    We propose a lower bound of the dc electrical conductivity in strongly disordered, strongly interacting quantum field theories using holography. We study linear response of black holes with broken translational symmetry in Einstein–Maxwell-dilaton theories of gravity. Using the generalized Stokes equations at the horizon, we derive the lower bound of the electrical conductivity for the dual two dimensional disordered field theory.

  19. No-arbitrage bounds for financial scenarios

    DEFF Research Database (Denmark)

    Geyer, Alois; Hanke, Michael; Weissensteiner, Alex

    2014-01-01

    We derive no-arbitrage bounds for expected excess returns to generate scenarios used in financial applications. The bounds allow to distinguish three regions: one where arbitrage opportunities will never exist, a second where arbitrage may be present, and a third, where arbitrage opportunities...

  20. Postactivation potentiation biases maximal isometric strength assessment.

    Science.gov (United States)

    Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Oliveira, Thiago Pires; Assumpção, Claudio de Oliveira; Greco, Camila Coelho; Cardozo, Adalgiso Croscato; Denadai, Benedito Sérgio

    2014-01-01

    Postactivation potentiation (PAP) is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs). The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers (n = 23) performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI), contractile impulse (CI), root mean square of the electromyographic signal during PTI (RMS), and rate of torque development (RTD), in different intervals, were measured. Significant increases in IPT (240.6 ± 55.7 N·m versus 248.9 ± 55.1 N·m), RTD (746 ± 152 N·m·s(-1) versus 727 ± 158 N·m·s(-1)), and RMS (59.1 ± 12.2% RMSMAX  versus 54.8 ± 9.4% RMSMAX) were found on the second MVC. tPTI decreased significantly on the second MVC (2373 ± 1200 ms versus 2784 ± 1226 ms). We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables.

  1. Gain maximization in a probabilistic entanglement protocol

    Science.gov (United States)

    di Lorenzo, Antonio; Esteves de Queiroz, Johnny Hebert

    Entanglement is a resource. We can therefore define gain as a monotonic function of entanglement G (E) . If a pair with entanglement E is produced with probability P, the net gain is N = PG (E) - (1 - P) C , where C is the cost of a failed attempt. We study a protocol where a pair of quantum systems is produced in a maximally entangled state ρm with probability Pm, while it is produced in a partially entangled state ρp with the complementary probability 1 -Pm . We mix a fraction w of the partially entangled pairs with the maximally entangled ones, i.e. we take the state to be ρ = (ρm + wUlocρpUloc+) / (1 + w) , where Uloc is an appropriate unitary local operation designed to maximize the entanglement of ρ. This procedure on one hand reduces the entanglement E, and hence the gain, but on the other hand it increases the probability of success to P =Pm + w (1 -Pm) , therefore the net gain N may increase. There may be hence, a priori, an optimal value for w, the fraction of failed attempts that we mix in. We show that, in the hypothesis of a linear gain G (E) = E , even assuming a vanishing cost C -> 0 , the net gain N is increasing with w, therefore the best strategy is to always mix the partially entangled states. Work supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico, proc. 311288/2014-6, and by FAPEMIG, Fundação de Amparo à Pesquisa de Minas Gerais, proc. IC-FAPEMIG2016-0269 and PPM-00607-16.

  2. Maximizing percentage depletion in solid minerals

    International Nuclear Information System (INIS)

    Tripp, J.; Grove, H.D.; McGrath, M.

    1982-01-01

    This article develops a strategy for maximizing percentage depletion deductions when extracting uranium or other solid minerals. The goal is to avoid losing percentage depletion deductions by staying below the 50% limitation on taxable income from the property. The article is divided into two major sections. The first section is comprised of depletion calculations that illustrate the problem and corresponding solutions. The last section deals with the feasibility of applying the strategy and complying with the Internal Revenue Code and appropriate regulations. Three separate strategies or appropriate situations are developed and illustrated. 13 references, 3 figures, 7 tables

  3. What currency do bumble bees maximize?

    Directory of Open Access Journals (Sweden)

    Nicholas L Charlton

    2010-08-01

    Full Text Available In modelling bumble bee foraging, net rate of energetic intake has been suggested as the appropriate currency. The foraging behaviour of honey bees is better predicted by using efficiency, the ratio of energetic gain to expenditure, as the currency. We re-analyse several studies of bumble bee foraging and show that efficiency is as good a currency as net rate in terms of predicting behaviour. We suggest that future studies of the foraging of bumble bees should be designed to distinguish between net rate and efficiency maximizing behaviour in an attempt to discover which is the more appropriate currency.

  4. Maximizing policy learning in international committees

    DEFF Research Database (Denmark)

    Nedergaard, Peter

    2007-01-01

    , this article demonstrates that valuable lessons can be learned about policy learning, in practice and theoretically, by analysing the cooperation in the OMC committees. Using the Advocacy Coalition Framework as the starting point of analysis, 15 hypotheses on policy learning are tested. Among other things......, it is concluded that in order to maximize policy learning in international committees, empirical data should be made available to committees and provided by sources close to the participants (i.e. the Commission). In addition, the work in the committees should be made prestigious in order to attract well...

  5. SHARP ENTRYWISE PERTURBATION BOUNDS FOR MARKOV CHAINS.

    Science.gov (United States)

    Thiede, Erik; VAN Koten, Brian; Weare, Jonathan

    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.

  6. New bounds on isotropic Lorentz violation

    International Nuclear Information System (INIS)

    Carone, Christopher D.; Sher, Marc; Vanderhaeghen, Marc

    2006-01-01

    Violations of Lorentz invariance that appear via operators of dimension four or less are completely parametrized in the Standard Model Extension (SME). In the pure photonic sector of the SME, there are 19 dimensionless, Lorentz-violating parameters. Eighteen of these have experimental upper bounds ranging between 10 -11 and 10 -32 ; the remaining parameter, k-tilde tr , is isotropic and has a much weaker bound of order 10 -4 . In this Brief Report, we point out that k-tilde tr gives a significant contribution to the anomalous magnetic moment of the electron and find a new upper bound of order 10 -8 . With reasonable assumptions, we further show that this bound may be improved to 10 -14 by considering the renormalization of other Lorentz-violating parameters that are more tightly constrained. Using similar renormalization arguments, we also estimate bounds on Lorentz-violating parameters in the pure gluonic sector of QCD

  7. Covariant entropy bound and loop quantum cosmology

    International Nuclear Information System (INIS)

    Ashtekar, Abhay; Wilson-Ewing, Edward

    2008-01-01

    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.

  8. Developing maximal neuromuscular power: part 2 - training considerations for improving maximal power production.

    Science.gov (United States)

    Cormie, Prue; McGuigan, Michael R; Newton, Robert U

    2011-02-01

    This series of reviews focuses on the most important neuromuscular function in many sport performances: the ability to generate maximal muscular power. Part 1, published in an earlier issue of Sports Medicine, focused on the factors that affect maximal power production while part 2 explores the practical application of these findings by reviewing the scientific literature relevant to the development of training programmes that most effectively enhance maximal power production. The ability to generate maximal power during complex motor skills is of paramount importance to successful athletic performance across many sports. A crucial issue faced by scientists and coaches is the development of effective and efficient training programmes that improve maximal power production in dynamic, multi-joint movements. Such training is referred to as 'power training' for the purposes of this review. Although further research is required in order to gain a deeper understanding of the optimal training techniques for maximizing power in complex, sports-specific movements and the precise mechanisms underlying adaptation, several key conclusions can be drawn from this review. First, a fundamental relationship exists between strength and power, which dictates that an individual cannot possess a high level of power without first being relatively strong. Thus, enhancing and maintaining maximal strength is essential when considering the long-term development of power. Second, consideration of movement pattern, load and velocity specificity is essential when designing power training programmes. Ballistic, plyometric and weightlifting exercises can be used effectively as primary exercises within a power training programme that enhances maximal power. The loads applied to these exercises will depend on the specific requirements of each particular sport and the type of movement being trained. The use of ballistic exercises with loads ranging from 0% to 50% of one-repetition maximum (1RM) and

  9. Bounds on the entanglement entropy of droplet states in the XXZ spin chain

    Science.gov (United States)

    Beaud, V.; Warzel, S.

    2018-01-01

    We consider a class of one-dimensional quantum spin systems on the finite lattice Λ ⊂Z , related to the XXZ spin chain in its Ising phase. It includes in particular the so-called droplet Hamiltonian. The entanglement entropy of energetically low-lying states over a bipartition Λ = B ∪ Bc is investigated and proven to satisfy a logarithmic bound in terms of min{n, |B|, |Bc|}, where n denotes the maximal number of down spins in the considered state. Upon addition of any (positive) random potential, the bound becomes uniformly constant on average, thereby establishing an area law. The proof is based on spectral methods: a deterministic bound on the local (many-body integrated) density of states is derived from an energetically motivated Combes-Thomas estimate.

  10. Maximization techniques for oilfield development profits

    International Nuclear Information System (INIS)

    Lerche, I.

    1999-01-01

    In 1981 Nind provided a quantitative procedure for estimating the optimum number of development wells to emplace on an oilfield to maximize profit. Nind's treatment assumed that there was a steady selling price, that all wells were placed in production simultaneously, and that each well's production profile was identical and a simple exponential decline with time. This paper lifts these restrictions to allow for price fluctuations, variable with time emplacement of wells, and production rates that are more in line with actual production records than is a simple exponential decline curve. As a consequence, it is possible to design production rate strategies, correlated with price fluctuations, so as to maximize the present-day worth of a field. For price fluctuations that occur on a time-scale rapid compared to inflation rates it is appropriate to have production rates correlate directly with such price fluctuations. The same strategy does not apply for price fluctuations occurring on a time-scale long compared to inflation rates where, for small amplitudes in the price fluctuations, it is best to sell as much product as early as possible to overcome inflation factors, while for large amplitude fluctuations the best strategy is to sell product as early as possible but to do so mainly on price upswings. Examples are provided to show how these generalizations of Nind's (1981) formula change the complexion of oilfield development optimization. (author)

  11. Crystal structures of carbamate kinase from Giardia lamblia bound with citric acid and AMP-PNP.

    Directory of Open Access Journals (Sweden)

    Kap Lim

    Full Text Available The parasite Giardia lamblia utilizes the L-arginine dihydrolase pathway to generate ATP from L-arginine. Carbamate kinase (CK catalyzes the last step in this pathway, converting ADP and carbamoyl phosphate to ATP and ammonium carbamate. Because the L-arginine pathway is essential for G. lamblia survival and absent in high eukaryotes including humans, the enzyme is a potential target for drug development. We have determined two crystal structures of G. lamblia CK (glCK with bound ligands. One structure, in complex with a nonhydrolyzable ATP analog, adenosine 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP, was determined at 2.6 Å resolution. The second structure, in complex with citric acid bound in the postulated carbamoyl phosphate binding site, was determined in two slightly different states at 2.1 and 2.4 Å resolution. These structures reveal conformational flexibility of an auxiliary domain (amino acid residues 123-170, which exhibits open or closed conformations or structural disorder, depending on the bound ligand. The structures also reveal a smaller conformational change in a region associated the AMP-PNP adenine binding site. The protein residues involved in binding, together with a model of the transition state, suggest that catalysis follows an in-line, predominantly dissociative, phosphotransfer reaction mechanism, and that closure of the flexible auxiliary domain is required to protect the transition state from bulk solvent.

  12. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  13. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  14. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  15. Cooperation between bound waters and hydroxyls in controlling isotope-exchange rates

    Science.gov (United States)

    Panasci, Adele F.; McAlpin, J. Gregory; Ohlin, C. André; Christensen, Shauna; Fettinger, James C.; Britt, R. David; Rustad, James R.; Casey, William H.

    2012-02-01

    Mineral oxides differ from aqueous ions in that the bound water molecules are usually attached to different metal centers, or vicinal, and thus separated from one another. In contrast, for most monomeric ions used to establish kinetic reactivity trends, such as octahedral aquo ions (e.g., Al(H 2O) 63+), the bound waters are closely packed, or geminal. Because of this structural difference, the existing literature about ligand substitution in monomer ions may be a poor guide to the reactions of geochemical interest. To understand how coordination of the reactive functional groups might affect the rates of simple water-exchange reactions, we synthesized two structurally similar Rh(III) complexes, [Rh(phen) 2(H 2O) 2] 3+ [ 1] and [Rh(phen) 2(H 2O)Cl] 2+ [ 2] where (phen) = 1,10-phenanthroline. Complex [ 1] has two adjacent, geminal, bound waters in the inner-coordination sphere and [ 2] has a single bound water adjacent to a bound chloride ion. We employed Rh(III) as a trivalent metal rather than a more geochemically relevant metal like Fe(III) or Al(III) to slow the rate of reaction, which makes possible measurement of the rates of isotopic substitution by simple mass spectrometry. We prepared isotopically pure versions of the molecules, dissolved them into isotopically dissimilar water, and measured the rates of exchange from the extents of 18O and 16O exchange at the bound waters. The pH dependency of rates differ enormously between the two complexes. Pseudo-first-order rate coefficients at 298 K for water exchanges from the fully protonated molecules are close: k0298 = 5 × 10 -8(±0.5 × 10 -8) s -1 for [ 1] and k0298 = 2.5 × 10 -9(±1 × 10 -9) for [ 2]. Enthalpy and entropy activation parameters (Δ H‡ and Δ S‡) were measured to be 119(±3) kJ mol -1, and 14(±1) J mol -1 K -1, respectively for [ 1]. The corresponding parameters for the mono-aquo complex, [ 2], are 132(±3) kJ mol -1 and 41.5(±2) J mol -1 K -1. Rates increase by many orders of magnitude

  16. An evolutionary model of bounded rationality and intelligence.

    Directory of Open Access Journals (Sweden)

    Thomas J Brennan

    Full Text Available BACKGROUND: Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia-it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. METHODS AND FINDINGS: Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. CONCLUSIONS: Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that

  17. An evolutionary model of bounded rationality and intelligence.

    Science.gov (United States)

    Brennan, Thomas J; Lo, Andrew W

    2012-01-01

    Most economic theories are based on the premise that individuals maximize their own self-interest and correctly incorporate the structure of their environment into all decisions, thanks to human intelligence. The influence of this paradigm goes far beyond academia-it underlies current macroeconomic and monetary policies, and is also an integral part of existing financial regulations. However, there is mounting empirical and experimental evidence, including the recent financial crisis, suggesting that humans do not always behave rationally, but often make seemingly random and suboptimal decisions. Here we propose to reconcile these contradictory perspectives by developing a simple binary-choice model that takes evolutionary consequences of decisions into account as well as the role of intelligence, which we define as any ability of an individual to increase its genetic success. If no intelligence is present, our model produces results consistent with prior literature and shows that risks that are independent across individuals in a generation generally lead to risk-neutral behaviors, but that risks that are correlated across a generation can lead to behaviors such as risk aversion, loss aversion, probability matching, and randomization. When intelligence is present the nature of risk also matters, and we show that even when risks are independent, either risk-neutral behavior or probability matching will occur depending upon the cost of intelligence in terms of reproductive success. In the case of correlated risks, we derive an implicit formula that shows how intelligence can emerge via selection, why it may be bounded, and how such bounds typically imply the coexistence of multiple levels and types of intelligence as a reflection of varying environmental conditions. Rational economic behavior in which individuals maximize their own self interest is only one of many possible types of behavior that arise from natural selection. The key to understanding which types of

  18. Development of immobilized ligands for actinide separations

    International Nuclear Information System (INIS)

    Paine, R.T.

    1994-01-01

    Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

  19. A new probe of solvent accessibility of bound photosensitizers. 1. Ruthenium(II) and osmium(II) photosensitizers in sodium lauryl sulfate micelles

    International Nuclear Information System (INIS)

    Hauenstein, B.L. Jr.; Dressick, W.J.; Buell, S.L.; Demas, J.N.; DeGraff, B.A.

    1983-01-01

    A new method of measuring solvent accessibility of photosensitizers bound to organized media is presented. In particular, the solvent accessibility of a series of ruthenium(II) and osmium(II) photosensitizers bound to sodium lauryl sulfate micelles has been determined. The method takes advantage of the large solvent deuterium effect on the excited-state lifetimes of these complexes. The solvent accessibility of the bound complexes correlates with the hydrophobicity of the ligands. The potential application of this method to a variety of other systems is mentioned

  20. Structural characterization of natural nickel and copper binding ligands along the US GEOTRACES Eastern Pacific Zonal transect

    Directory of Open Access Journals (Sweden)

    Rene M Boiteau

    2016-11-01

    Full Text Available Organic ligands form strong complexes with many trace elements in seawater. Various metals can compete for the same ligand chelation sites, and the final speciation of bound metals is determined by relative binding affinities, concentrations of binding sites, uncomplexed metal concentrations, and association/dissociation kinetics. Different ligands have a wide range of metal affinities and specificities. However, the chemical composition of these ligands in the marine environment remains poorly constrained, which has hindered progress in modeling marine metal speciation. In this study, we detected and characterized natural ligands that bind copper (Cu and nickel (Ni in the eastern South Pacific Ocean with liquid chromatography tandem inductively coupled plasma mass spectrometry (LC-ICPMS, and high resolution electrospray ionization mass spectrometry (ESIMS. Dissolved Cu, Ni, and ligand concentrations were highest near the coast. Chromatographically unresolved polar compounds dominated ligands isolated near the coast by solid phase extraction. Offshore, metal and ligand concentrations decreased, but several new ligands appeared. One major ligand was detected that bound both Cu2+ and Ni2+. Based on accurate mass and fragmentation measurements, this compound has a molecular formula of C20H21N4O8S2 + M+ (M = metal isotope and contains several azole-like metal binding groups. Additional lipophilic Ni complexes were also present only in oligotrophic waters, with masses of 649, 698, and 712 m/z (corresponding to the 58Ni metal complex. Molecular formulae of C32H54N3O6S2Ni+ and C33H56N3O6S2Ni+ were determined for two of these compounds. Addition of Cu and Ni to the samples also revealed the presence of additional compounds that can bind both Ni and Cu. Although these specific compounds represent a small fraction of the total dissolved Cu and Ni pool, they highlight the compositional diversity and spatial heterogeneity of marine Ni and Cu ligands, as

  1. Continuous bounded cohomology of locally compact groups

    CERN Document Server

    2001-01-01

    Recent research has repeatedly led to connections between important rigidity questions and bounded cohomology. However, the latter has remained by and large intractable. This monograph introduces the functorial study of the continuous bounded cohomology for topological groups, with coefficients in Banach modules. The powerful techniques of this more general theory have successfully solved a number of the original problems in bounded cohomology. As applications, one obtains, in particular, rigidity results for actions on the circle, for representations on complex hyperbolic spaces and on Teichmüller spaces. A special effort has been made to provide detailed proofs or references in quite some generality.

  2. Positivity bounds on double parton distributions

    International Nuclear Information System (INIS)

    Diehl, Markus; Kasemets, Tomas

    2013-03-01

    Double hard scattering in proton-proton collisions is described in terms of double parton distributions. We derive bounds on these distributions that follow from their interpretation as probability densities, taking into account all possible spin correlations between two partons in an unpolarized proton. These bounds constrain the size of the polarized distributions and can for instance be used to set upper limits on the effects of spin correlations in double hard scattering. We show that the bounds are stable under leading-order DGLAP evolution to higher scales.

  3. Remarks on Bousso's covariant entropy bound

    CERN Document Server

    Mayo, A E

    2002-01-01

    Bousso's covariant entropy bound is put to the test in the context of a non-singular cosmological solution of general relativity found by Bekenstein. Although the model complies with every assumption made in Bousso's original conjecture, the entropy bound is violated due to the occurrence of negative energy density associated with the interaction of some the matter components in the model. We demonstrate how this property allows for the test model to 'elude' a proof of Bousso's conjecture which was given recently by Flanagan, Marolf and Wald. This corroborates the view that the covariant entropy bound should be applied only to stable systems for which every matter component carries positive energy density.

  4. The bound state problem and quark confinement

    International Nuclear Information System (INIS)

    Chaichian, M.; Demichev, A.P.; Nelipa, N.F.

    1980-01-01

    A quantum field-theoretic model in which quark is confined is considered. System of equations for the Green functions of colour singlet and octet bound states is obtained. The method is based on the nonperturbative Schwinger-Dyson equations with the use of Slavnov-Taylor identities. It is shown that in the framework of the model if there exist singlet, then also exist octet bound states of the quark-antiquark system. Thus in general, confinement of free quarks does not mean absence of their coloured bound states. (author)

  5. Quasi-bound states in continuum

    International Nuclear Information System (INIS)

    Nakamura, Hiroaki; Hatano, Naomichi; Garmon, Sterling; Petrosky, Tomio

    2007-08-01

    We report the prediction of quasi-bound states (resonant states with very long lifetimes) that occur in the eigenvalue continuum of propagating states for a wide region of parameter space. These quasi-bound states are generated in a quantum wire with two channels and an adatom, when the energy bands of the two channels overlap. A would-be bound state that lays just below the upper energy band is slightly destabilized by the lower energy band and thereby becomes a resonant state with a very long lifetime (a second QBIC lays above the lower energy band). (author)

  6. Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages

    International Nuclear Information System (INIS)

    Schlepper-Schaefer, J.; Huelsmann, D.; Djovkar, A.; Meyer, H.E.; Herbertz, L.; Kolb, H.; Kolb-Bachofen, V.

    1986-01-01

    The intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues is rat liver was followed. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au 5 ), 17 nm (Au 17 ), 50 nm (Au 50 ) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au 5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc

  7. Shareholder, stakeholder-owner or broad stakeholder maximization

    DEFF Research Database (Denmark)

    Mygind, Niels

    2004-01-01

    With reference to the discussion about shareholder versus stakeholder maximization it is argued that the normal type of maximization is in fact stakeholder-owner maxi-mization. This means maximization of the sum of the value of the shares and stake-holder benefits belonging to the dominating...... including the shareholders of a company. Although it may be the ultimate goal for Corporate Social Responsibility to achieve this kind of maximization, broad stakeholder maximization is quite difficult to give a precise definition. There is no one-dimensional measure to add different stakeholder benefits...... not traded on the mar-ket, and therefore there is no possibility for practical application. Broad stakeholder maximization instead in practical applications becomes satisfying certain stakeholder demands, so that the practical application will be stakeholder-owner maximization un-der constraints defined...

  8. Maximizing Lumen Gain With Directional Atherectomy.

    Science.gov (United States)

    Stanley, Gregory A; Winscott, John G

    2016-08-01

    To describe the use of a low-pressure balloon inflation (LPBI) technique to delineate intraluminal plaque and guide directional atherectomy in order to maximize lumen gain and achieve procedure success. The technique is illustrated in a 77-year-old man with claudication who underwent superficial femoral artery revascularization using a HawkOne directional atherectomy catheter. A standard angioplasty balloon was inflated to 1 to 2 atm during live fluoroscopy to create a 3-dimensional "lumenogram" of the target lesion. Directional atherectomy was performed only where plaque impinged on the balloon at a specific fluoroscopic orientation. The results of the LPBI technique were corroborated with multimodality diagnostic imaging, including digital subtraction angiography, intravascular ultrasound, and intra-arterial pressure measurements. With the LPBI technique, directional atherectomy can routinely achieve <10% residual stenosis, as illustrated in this case, thereby broadly supporting a no-stent approach to lower extremity endovascular revascularization. © The Author(s) 2016.

  9. Distributed-Memory Fast Maximal Independent Set

    Energy Technology Data Exchange (ETDEWEB)

    Kanewala Appuhamilage, Thejaka Amila J.; Zalewski, Marcin J.; Lumsdaine, Andrew

    2017-09-13

    The Maximal Independent Set (MIS) graph problem arises in many applications such as computer vision, information theory, molecular biology, and process scheduling. The growing scale of MIS problems suggests the use of distributed-memory hardware as a cost-effective approach to providing necessary compute and memory resources. Luby proposed four randomized algorithms to solve the MIS problem. All those algorithms are designed focusing on shared-memory machines and are analyzed using the PRAM model. These algorithms do not have direct efficient distributed-memory implementations. In this paper, we extend two of Luby’s seminal MIS algorithms, “Luby(A)” and “Luby(B),” to distributed-memory execution, and we evaluate their performance. We compare our results with the “Filtered MIS” implementation in the Combinatorial BLAS library for two types of synthetic graph inputs.

  10. Quench dynamics of topological maximally entangled states.

    Science.gov (United States)

    Chung, Ming-Chiang; Jhu, Yi-Hao; Chen, Pochung; Mou, Chung-Yu

    2013-07-17

    We investigate the quench dynamics of the one-particle entanglement spectra (OPES) for systems with topologically nontrivial phases. By using dimerized chains as an example, it is demonstrated that the evolution of OPES for the quenched bipartite systems is governed by an effective Hamiltonian which is characterized by a pseudospin in a time-dependent pseudomagnetic field S(k,t). The existence and evolution of the topological maximally entangled states (tMESs) are determined by the winding number of S(k,t) in the k-space. In particular, the tMESs survive only if nontrivial Berry phases are induced by the winding of S(k,t). In the infinite-time limit the equilibrium OPES can be determined by an effective time-independent pseudomagnetic field Seff(k). Furthermore, when tMESs are unstable, they are destroyed by quasiparticles within a characteristic timescale in proportion to the system size.

  11. Maximizing policy learning in international committees

    DEFF Research Database (Denmark)

    Nedergaard, Peter

    2007-01-01

    , this article demonstrates that valuable lessons can be learned about policy learning, in practice and theoretically, by analysing the cooperation in the OMC committees. Using the Advocacy Coalition Framework as the starting point of analysis, 15 hypotheses on policy learning are tested. Among other things......In the voluminous literature on the European Union's open method of coordination (OMC), no one has hitherto analysed on the basis of scholarly examination the question of what contributes to the learning processes in the OMC committees. On the basis of a questionnaire sent to all participants......, it is concluded that in order to maximize policy learning in international committees, empirical data should be made available to committees and provided by sources close to the participants (i.e. the Commission). In addition, the work in the committees should be made prestigious in order to attract well...

  12. Lovelock black holes with maximally symmetric horizons

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hideki; Willison, Steven; Ray, Sourya, E-mail: hideki@cecs.cl, E-mail: willison@cecs.cl, E-mail: ray@cecs.cl [Centro de Estudios CientIficos (CECs), Casilla 1469, Valdivia (Chile)

    2011-08-21

    We investigate some properties of n( {>=} 4)-dimensional spacetimes having symmetries corresponding to the isometries of an (n - 2)-dimensional maximally symmetric space in Lovelock gravity under the null or dominant energy condition. The well-posedness of the generalized Misner-Sharp quasi-local mass proposed in the past study is shown. Using this quasi-local mass, we clarify the basic properties of the dynamical black holes defined by a future outer trapping horizon under certain assumptions on the Lovelock coupling constants. The C{sup 2} vacuum solutions are classified into four types: (i) Schwarzschild-Tangherlini-type solution; (ii) Nariai-type solution; (iii) special degenerate vacuum solution; and (iv) exceptional vacuum solution. The conditions for the realization of the last two solutions are clarified. The Schwarzschild-Tangherlini-type solution is studied in detail. We prove the first law of black-hole thermodynamics and present the expressions for the heat capacity and the free energy.

  13. MAXIMIZING THE BENEFITS OF ERP SYSTEMS

    Directory of Open Access Journals (Sweden)

    Paulo André da Conceição Menezes

    2010-04-01

    Full Text Available The ERP (Enterprise Resource Planning systems have been consolidated in companies with different sizes and sectors, allowing their real benefits to be definitively evaluated. In this study, several interactions have been studied in different phases, such as the strategic priorities and strategic planning defined as ERP Strategy; business processes review and the ERP selection in the pre-implementation phase, the project management and ERP adaptation in the implementation phase, as well as the ERP revision and integration efforts in the post-implementation phase. Through rigorous use of case study methodology, this research led to developing and to testing a framework for maximizing the benefits of the ERP systems, and seeks to contribute for the generation of ERP initiatives to optimize their performance.

  14. Maximizing profitability in a hospital outpatient pharmacy.

    Science.gov (United States)

    Jorgenson, J A; Kilarski, J W; Malatestinic, W N; Rudy, T A

    1989-07-01

    This paper describes the strategies employed to increase the profitability of an existing ambulatory pharmacy operated by the hospital. Methods to generate new revenue including implementation of a home parenteral therapy program, a home enteral therapy program, a durable medical equipment service, and home care disposable sales are described. Programs to maximize existing revenue sources such as increasing the capture rate on discharge prescriptions, increasing "walk-in" prescription traffic and increasing HMO prescription volumes are discussed. A method utilized to reduce drug expenditures is also presented. By minimizing expenses and increasing the revenues for the ambulatory pharmacy operation, net profit increased from +26,000 to over +140,000 in one year.

  15. Maximizing the benefits of a dewatering system

    International Nuclear Information System (INIS)

    Matthews, P.; Iverson, T.S.

    1999-01-01

    The use of dewatering systems in the mining, industrial sludge and sewage waste treatment industries is discussed, also describing some of the problems that have been encountered while using drilling fluid dewatering technology. The technology is an acceptable drilling waste handling alternative but it has had problems associated with recycled fluid incompatibility, high chemical costs and system inefficiencies. This paper discussed the following five action areas that can maximize the benefits and help reduce costs of a dewatering project: (1) co-ordinate all services, (2) choose equipment that fits the drilling program, (3) match the chemical treatment with the drilling fluid types, (4) determine recycled fluid compatibility requirements, and (5) determine the disposal requirements before project start-up. 2 refs., 5 figs

  16. Mixtures of maximally entangled pure states

    Energy Technology Data Exchange (ETDEWEB)

    Flores, M.M., E-mail: mflores@nip.up.edu.ph; Galapon, E.A., E-mail: eric.galapon@gmail.com

    2016-09-15

    We study the conditions when mixtures of maximally entangled pure states remain entangled. We found that the resulting mixed state remains entangled when the number of entangled pure states to be mixed is less than or equal to the dimension of the pure states. For the latter case of mixing a number of pure states equal to their dimension, we found that the mixed state is entangled provided that the entangled pure states to be mixed are not equally weighted. We also found that one can restrict the set of pure states that one can mix from in order to ensure that the resulting mixed state is genuinely entangled. Also, we demonstrate how these results could be applied as a way to detect entanglement in mixtures of the entangled pure states with noise.

  17. Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators

    Science.gov (United States)

    Lazennec, Gwendal; Canaple, Laurence; Saugy, Damien; Wahli, Walter

    2000-01-01

    The nuclear peroxisome proliferator-activated receptors (PPARs) α, β and γ activate the transcription of multiple genes involved in lipid metabolism. Several natural and synthetic ligands have been identified for each PPAR isotype but little is known about the phosphorylation state of these receptors. We show here that activators of protein kinase A (PKA) can enhance mouse PPAR activity in the absence and the presence of exogenous ligands in transient transfection experiments. The activation function 1 (AF-1) of PPARs was dispensable for transcriptional enhancement, whereas the activation function 2 (AF-2) was required for this effect. We also show that several domains of PPAR can be phosphorylated by PKA in vitro. Moreover, gel experiments suggest that PKA stabilizes binding of the liganded PPAR to DNA. PKA inhibitors decreased not only the kinase dependent induction of PPARs but also their ligand-dependent induction, suggesting that the ligands may also mobilize the PKA pathway to lead to maximal transcriptional induction by PPARs. Moreover, comparing PPARα KO with PPARα wild-type mice, we show that the expression of the ACO gene can be regulated by PKA-activated PPARα in liver. These data demonstrate that the PKA pathway is an important modulator of PPAR activity and we propose a model associating this pathway in the control of fatty acid β-oxidation under conditions of fasting, stress and exercise. PMID:11117527

  18. REDOR NMR Reveals Multiple Conformers for a Protein Kinase C Ligand in a Membrane Environment

    Directory of Open Access Journals (Sweden)

    Hao Yang

    2018-01-01

    Full Text Available Bryostatin 1 (henceforth bryostatin is in clinical trials for the treatment of Alzheimer’s disease and for HIV/AIDS eradication. It is also a preclinical lead for cancer immunotherapy and other therapeutic indications. Yet nothing is known about the conformation of bryostatin bound to its protein kinase C (PKC target in a membrane microenvironment. As a result, efforts to design more efficacious, better tolerated, or more synthetically accessible ligands have been limited to structures that do not include PKC or membrane effects known to influence PKC–ligand binding. This problem extends more generally to many membrane-associated proteins in the human proteome. Here, we use rotational-echo double-resonance (REDOR solid-state NMR to determine the conformations of PKC modulators bound to the PKCδ-C1b domain in the presence of phospholipid vesicles. The conformationally limited PKC modulator phorbol diacetate (PDAc is used as an initial test substrate. While unanticipated partitioning of PDAc between an immobilized protein-bound state and a mobile state in the phospholipid assembly was observed, a single conformation in the bound state was identified. In striking contrast, a bryostatin analogue (bryolog was found to exist exclusively in a protein-bound state, but adopts a distribution of conformations as defined by three independent distance measurements. The detection of multiple PKCδ-C1b-bound bryolog conformers in a functionally relevant phospholipid complex reveals the inherent dynamic nature of cellular systems that is not captured with single-conformation static structures. These results indicate that binding, selectivity, and function of PKC modulators, as well as the design of new modulators, are best addressed using a dynamic multistate model, an analysis potentially applicable to other membrane-associated proteins.

  19. A Criterion to Identify Maximally Entangled Four-Qubit State

    International Nuclear Information System (INIS)

    Zha Xinwei; Song Haiyang; Feng Feng

    2011-01-01

    Paolo Facchi, et al. [Phys. Rev. A 77 (2008) 060304(R)] presented a maximally multipartite entangled state (MMES). Here, we give a criterion for the identification of maximally entangled four-qubit states. Using this criterion, we not only identify some existing maximally entangled four-qubit states in the literature, but also find several new maximally entangled four-qubit states as well. (general)

  20. Maximal lattice free bodies, test sets and the Frobenius problem

    DEFF Research Database (Denmark)

    Jensen, Anders Nedergaard; Lauritzen, Niels; Roune, Bjarke Hammersholt

    Maximal lattice free bodies are maximal polytopes without interior integral points. Scarf initiated the study of maximal lattice free bodies relative to the facet normals in a fixed matrix. In this paper we give an efficient algorithm for computing the maximal lattice free bodies of an integral m...... method is inspired by the novel algorithm by Einstein, Lichtblau, Strzebonski and Wagon and the Groebner basis approach by Roune....

  1. Exploring the composition of protein-ligand binding sites on a large scale.

    Directory of Open Access Journals (Sweden)

    Nickolay A Khazanov

    Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

  2. Tight Bounds for Distributed Functional Monitoring

    DEFF Research Database (Denmark)

    Woodruff, David P.; Zhang, Qin

    2011-01-01

    $, our bound resolves their main open question. Our lower bounds are based on new direct sum theorems for approximate majority, and yield significant improvements to problems in the data stream model, improving the bound for estimating $F_p, p > 2,$ in $t$ passes from $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{2/p......} t))$ to $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{4/p} t))$, giving the first bound for estimating $F_0$ in $t$ passes of $\\Omega(1/(\\eps^2 t))$ bits of space that does not use the gap-hamming problem, and showing a distribution for the gap-hamming problem with high external information cost or super...

  3. Redshift-space limits of bound structures

    NARCIS (Netherlands)

    Duenner, Rolando; Reisenegger, Andreas; Meza, Andres; Araya, Pablo A.; Quintana, Hernan

    2007-01-01

    An exponentially expanding Universe, possibly governed by a cosmological constant, forces gravitationally bound structures to become more and more isolated, eventually becoming causally disconnected from each other and forming so-called 'island universes'. This new scenario reformulates the question

  4. Error Bounds: Necessary and Sufficient Conditions

    Czech Academy of Sciences Publication Activity Database

    Outrata, Jiří; Kruger, A.Y.; Fabian, Marián; Henrion, R.

    2010-01-01

    Roč. 18, č. 2 (2010), s. 121-149 ISSN 1877-0533 R&D Projects: GA AV ČR IAA100750802 Institutional research plan: CEZ:AV0Z10750506; CEZ:AV0Z10190503 Keywords : Error bounds * Calmness * Subdifferential * Slope Subject RIV: BA - General Mathematics Impact factor: 0.333, year: 2010 http://library.utia.cas.cz/separaty/2010/MTR/outrata-error bounds necessary and sufficient conditions.pdf

  5. Malabsorption of protein bound vitamin B12.

    OpenAIRE

    Dawson, D W; Sawers, A H; Sharma, R K

    1984-01-01

    Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, ...

  6. New Spectral Features from Bound Dark Matter

    DEFF Research Database (Denmark)

    Catena, Riccardo; Kouvaris, Chris

    2016-01-01

    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 we predict can provide the ultimate smoking gun for dark matter discovery for experiments...... with positive signal but unclear background. The new feature is universal, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section....

  7. Automatic bounding estimation in modified NLMS algorithm

    International Nuclear Information System (INIS)

    Shahtalebi, K.; Doost-Hoseini, A.M.

    2002-01-01

    Modified Normalized Least Mean Square algorithm, which is a sign form of Nlm based on set-membership (S M) theory in the class of optimal bounding ellipsoid (OBE) algorithms, requires a priori knowledge of error bounds that is unknown in most applications. In a special but popular case of measurement noise, a simple algorithm has been proposed. With some simulation examples the performance of algorithm is compared with Modified Normalized Least Mean Square

  8. Effect of Ligand Exchange on the Photoluminescence Properties of Cu-Doped Zn-In-Se Quantum Dots

    Science.gov (United States)

    Dong, Xiaofei; Xu, Jianping; Yang, Hui; Zhang, Xiaosong; Mo, Zhaojun; Shi, Shaobo; Li, Lan; Yin, Shougen

    2018-04-01

    The surface-bound ligands of a semiconductor nanocrystal can affect its electron transition behavior. We investigate the photoluminescence (PL) properties of Cu-doped Zn-In-Se quantum dots (QDs) through the exchange of oleylamine with 6-mercaptohexanol (MCH). Fourier transform infrared and 1H nuclear magnetic resonance spectroscopies, and mass spectrometry reveal that the short-chain MCH molecules are bound to the QD surface. The emission peaks remain unchanged after ligand exchange, and the PL quantum yield is reduced from 49% to 38%. The effects of particle size and defect type on the change in PL behavior upon ligand substitution are excluded through high-resolution transmission electron microscopy, UV-Vis absorption, and PL spectroscopies. The origin of the decreased PL intensity is associated with increased ligand density and the stronger ligand electron-donating abilities of MCH-capped QDs that induce an increase in the nonradiative transition probability. A lower PL quenching transition temperature is observed for MCH-capped QDs and is associated with increasing electron-acoustic phonon coupling due to the lower melting temperature of MCH.

  9. Determination, at equilibrium, of association constants of labelled or unlabelled ligands by a non-graphical method

    International Nuclear Information System (INIS)

    Goertz, G.; Longchampt, J.; Crepy, O.; Judas, O.; Jayle, M.-F.

    1976-01-01

    Determination, at equilibrium of association constants of labelled or unlabelled ligands by a non-graphical method are described. This work deals with the determination of association constants at equilibrium by a non-graphical method in binding systems containing one specific receptor. Equations have been derived from that originally described by Lea (Biochim. Biophys. Acta, 322, 68-74), the terms of which are obtained from the data of simple displacement curves of a bound radioactive ligand by unlabelled competitors identical or different in nature. By knowing the function relating the variations of the bound ligand (B) to the affinity constant (Ksub(i)) and the quantity (Msub(i)) of competitor for a given system, it is possible to calculate any of these parameters when the two others are measured. Thus, it becomes easy to compare the relative affinities of different receptors for the same ligand or that of one receptor for various labelled or unlabelled ligands. Furthermore, theoretical displacement curves can be drawn and compared to experimental data, only when knowing the affinity constant of a specific binding system in given conditions. These modes of calculation have been tested in a study of interactions between various steroids and a fraction of human serum proteins precipitated by ammonium sulfate (30-45%) and containing the sex hormone-binding globulin. Association constants thus obtained agree well with those reported in the literature and determined by graphical procedures

  10. Macrocyclic ligands for uranium complexation

    International Nuclear Information System (INIS)

    Potts, K.T.

    1991-04-01

    A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd 0 chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs

  11. Absolute Lower Bound on the Bounce Action

    Science.gov (United States)

    Sato, Ryosuke; Takimoto, Masahiro

    2018-03-01

    The decay rate of a false vacuum is determined by the minimal action solution of the tunneling field: bounce. In this Letter, we focus on models with scalar fields which have a canonical kinetic term in N (>2 ) dimensional Euclidean space, and derive an absolute lower bound on the bounce action. In the case of four-dimensional space, we show the bounce action is generically larger than 24 /λcr, where λcr≡max [-4 V (ϕ )/|ϕ |4] with the false vacuum being at ϕ =0 and V (0 )=0 . We derive this bound on the bounce action without solving the equation of motion explicitly. Our bound is derived by a quite simple discussion, and it provides useful information even if it is difficult to obtain the explicit form of the bounce solution. Our bound offers a sufficient condition for the stability of a false vacuum, and it is useful as a quick check on the vacuum stability for given models. Our bound can be applied to a broad class of scalar potential with any number of scalar fields. We also discuss a necessary condition for the bounce action taking a value close to this lower bound.

  12. Generalized surface tension bounds in vacuum decay

    Science.gov (United States)

    Masoumi, Ali; Paban, Sonia; Weinberg, Erick J.

    2018-02-01

    Coleman and De Luccia (CDL) showed that gravitational effects can prevent the decay by bubble nucleation of a Minkowski or AdS false vacuum. In their thin-wall approximation this happens whenever the surface tension in the bubble wall exceeds an upper bound proportional to the difference of the square roots of the true and false vacuum energy densities. Recently it was shown that there is another type of thin-wall regime that differs from that of CDL in that the radius of curvature grows substantially as one moves through the wall. Not only does the CDL derivation of the bound fail in this case, but also its very formulation becomes ambiguous because the surface tension is not well defined. We propose a definition of the surface tension and show that it obeys a bound similar in form to that of the CDL case. We then show that both thin-wall bounds are special cases of a more general bound that is satisfied for all bounce solutions with Minkowski or AdS false vacua. We discuss the limit where the parameters of the theory attain critical values and the bound is saturated. The bounce solution then disappears and a static planar domain wall solution appears in its stead. The scalar field potential then is of the form expected in supergravity, but this is only guaranteed along the trajectory in field space traced out by the bounce.

  13. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

    2017-01-01

    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  14. Ligand-receptor Interactions by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Novak. P.

    2008-04-01

    Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

  15. Autocrine signal transmission with extracellular ligand degradation

    Science.gov (United States)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-03-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

  16. Organotellurium ligands – designing and complexation reactions

    Indian Academy of Sciences (India)

    Unknown

    membered rings it is negative and ~30 ppm only. Keywords. Organotellurium ligands; hybrid telluroether; platinum metal complexes; tellurium-125 NMR. 1. Introduction. Tellurium is the noblest metalloid which may act as a Lewis acid as well as Lewis base. The ligand chemistry of tellurium, which acts as a 'soft' donor, was ...

  17. Virtual screening using the ligand ZINC database for novel lipoxygenase-3 inhibitors.

    Science.gov (United States)

    Monika; Kour, Janmeet; Singh, Kulwinder

    2013-01-01

    The leukotrienes constitute a group of arachidonic acid-derived compounds with biologic activities suggesting important roles in inflammation and immediate hypersensitivity. Epidermis-type lipoxygenase-3 (ALOXE3), a distinct subclass within the multigene family of mammalian lipoxygenases, is a novel isoenzyme involved in the metabolism of leukotrienes and plays a very important role in skin barrier functions. Lipoxygenase selective inhibitors such as azelastine and zileuton are currently used to reduce inflammatory response. Nausea, pharyngolaryngeal pain, headache, nasal burning and somnolence are the most frequently reported adverse effects of these drugs. Therefore, there is still a need to develop more potent lipoxygenase inhibitors. In this paper, we report the screening of various compounds from the ZINC database (contains over 21 million compounds) using the Molegro Virtual Docker software against the ALOXE3 protein. Screening was performed using molecular constraints tool to filter compounds with physico-chemical properties similar to the 1N8Q bound ligand protocatechuic acid. The analysis resulted in 4319 Lipinski compliant hits which are docked and scored to identify structurally novel ligands that make similar interactions to those of known ligands or may have different interactions with other parts of the binding site. Our screening approach identified four molecules ZINC84299674; ZINC76643455; ZINC84299122 & ZINC75626957 with MolDock score of -128.901, -120.22, -116.873 & - 102.116 kcal/mol, respectively. Their energy scores were better than the 1N8Q bound co-crystallized ligand protocatechuic acid (with MolDock score of -77.225 kcal/mol). All the ligands were docked within the binding pocket forming interactions with amino acid residues.

  18. Structural analysis of protein-ligand interactions: the binding of endogenous compounds and of synthetic drugs.

    Science.gov (United States)

    Gallina, Anna M; Bork, Peer; Bordo, Domenico

    2014-02-01

    The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.

  19. On maximal surfaces in asymptotically flat space-times

    International Nuclear Information System (INIS)

    Bartnik, R.; Chrusciel, P.T.; O Murchadha, N.

    1990-01-01

    Existence of maximal and 'almost maximal' hypersurfaces in asymptotically flat space-times is established under boundary conditions weaker than those considered previously. We show in particular that every vacuum evolution of asymptotically flat data for Einstein equations can be foliated by slices maximal outside a spatially compact set and that every (strictly) stationary asymptotically flat space-time can be foliated by maximal hypersurfaces. Amongst other uniqueness results, we show that maximal hypersurface can be used to 'partially fix' an asymptotic Poincare group. (orig.)

  20. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary); Li, Yin; Matisz, Gergely [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kiss, László [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary)

    2014-01-15

    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin.

  1. A Note of Caution on Maximizing Entropy

    Directory of Open Access Journals (Sweden)

    Richard E. Neapolitan

    2014-07-01

    Full Text Available The Principle of Maximum Entropy is often used to update probabilities due to evidence instead of performing Bayesian updating using Bayes’ Theorem, and its use often has efficacious results. However, in some circumstances the results seem unacceptable and unintuitive. This paper discusses some of these cases, and discusses how to identify some of the situations in which this principle should not be used. The paper starts by reviewing three approaches to probability, namely the classical approach, the limiting frequency approach, and the Bayesian approach. It then introduces maximum entropy and shows its relationship to the three approaches. Next, through examples, it shows that maximizing entropy sometimes can stand in direct opposition to Bayesian updating based on reasonable prior beliefs. The paper concludes that if we take the Bayesian approach that probability is about reasonable belief based on all available information, then we can resolve the conflict between the maximum entropy approach and the Bayesian approach that is demonstrated in the examples.

  2. Optimal topologies for maximizing network transmission capacity

    Science.gov (United States)

    Chen, Zhenhao; Wu, Jiajing; Rong, Zhihai; Tse, Chi K.

    2018-04-01

    It has been widely demonstrated that the structure of a network is a major factor that affects its traffic dynamics. In this work, we try to identify the optimal topologies for maximizing the network transmission capacity, as well as to build a clear relationship between structural features of a network and the transmission performance in terms of traffic delivery. We propose an approach for designing optimal network topologies against traffic congestion by link rewiring and apply them on the Barabási-Albert scale-free, static scale-free and Internet Autonomous System-level networks. Furthermore, we analyze the optimized networks using complex network parameters that characterize the structure of networks, and our simulation results suggest that an optimal network for traffic transmission is more likely to have a core-periphery structure. However, assortative mixing and the rich-club phenomenon may have negative impacts on network performance. Based on the observations of the optimized networks, we propose an efficient method to improve the transmission capacity of large-scale networks.

  3. New features of the maximal abelian projection

    International Nuclear Information System (INIS)

    Bornyakov, V.G.; Polikarpov, M.I.; Syritsyn, S.N.; Schierholz, G.; Suzuki, T.

    2005-12-01

    After fixing the Maximal Abelian gauge in SU(2) lattice gauge theory we decompose the nonabelian gauge field into the so called monopole field and the modified nonabelian field with monopoles removed. We then calculate respective static potentials and find that the potential due to the modified nonabelian field is nonconfining while, as is well known, the monopole field potential is linear. Furthermore, we show that the sum of these potentials approximates the nonabelian static potential with 5% or higher precision at all distances considered. We conclude that at large distances the monopole field potential describes the classical energy of the hadronic string while the modified nonabelian field potential describes the string fluctuations. Similar decomposition was observed to work for the adjoint static potential. A check was also made of the center projection in the direct center gauge. Two static potentials, determined by projected Z 2 and by modified nonabelian field without Z 2 component were calculated. It was found that their sum is a substantially worse approximation of the SU(2) static potential than that found in the monopole case. It is further demonstrated that similar decomposition can be made for the flux tube action/energy density. (orig.)

  4. The Cramér-Rao Bounds and Sensor Selection for Nonlinear Systems with Uncertain Observations.

    Science.gov (United States)

    Wang, Zhiguo; Shen, Xiaojing; Wang, Ping; Zhu, Yunmin

    2018-04-05

    This paper considers the problems of the posterior Cramér-Rao bound and sensor selection for multi-sensor nonlinear systems with uncertain observations. In order to effectively overcome the difficulties caused by uncertainty, we investigate two methods to derive the posterior Cramér-Rao bound. The first method is based on the recursive formula of the Cramér-Rao bound and the Gaussian mixture model. Nevertheless, it needs to compute a complex integral based on the joint probability density function of the sensor measurements and the target state. The computation burden of this method is relatively high, especially in large sensor networks. Inspired by the idea of the expectation maximization algorithm, the second method is to introduce some 0-1 latent variables to deal with the Gaussian mixture model. Since the regular condition of the posterior Cramér-Rao bound is unsatisfied for the discrete uncertain system, we use some continuous variables to approximate the discrete latent variables. Then, a new Cramér-Rao bound can be achieved by a limiting process of the Cramér-Rao bound of the continuous system. It avoids the complex integral, which can reduce the computation burden. Based on the new posterior Cramér-Rao bound, the optimal solution of the sensor selection problem can be derived analytically. Thus, it can be used to deal with the sensor selection of a large-scale sensor networks. Two typical numerical examples verify the effectiveness of the proposed methods.

  5. Upper bounds on superpartner masses from upper bounds on the Higgs boson mass.

    Science.gov (United States)

    Cabrera, M E; Casas, J A; Delgado, A

    2012-01-13

    The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanβ, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11)  GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass.

  6. Bounds on poloidal kinetic energy in plane layer convection

    Science.gov (United States)

    Tilgner, A.

    2017-12-01

    A numerical method is presented that conveniently computes upper bounds on heat transport and poloidal energy in plane layer convection for infinite and finite Prandtl numbers. The bounds obtained for the heat transport coincide with earlier results. These bounds imply upper bounds for the poloidal energy, which follow directly from the definitions of dissipation and energy. The same constraints used for computing upper bounds on the heat transport lead to improved bounds for the poloidal energy.

  7. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  8. Bounds for nonlinear composites via iterated homogenization

    Science.gov (United States)

    Ponte Castañeda, P.

    2012-09-01

    Improved estimates of the Hashin-Shtrikman-Willis type are generated for the class of nonlinear composites consisting of two well-ordered, isotropic phases distributed randomly with prescribed two-point correlations, as determined by the H-measure of the microstructure. For this purpose, a novel strategy for generating bounds has been developed utilizing iterated homogenization. The general idea is to make use of bounds that may be available for composite materials in the limit when the concentration of one of the phases (say phase 1) is small. It then follows from the theory of iterated homogenization that it is possible, under certain conditions, to obtain bounds for more general values of the concentration, by gradually adding small amounts of phase 1 in incremental fashion, and sequentially using the available dilute-concentration estimate, up to the final (finite) value of the concentration (of phase 1). Such an approach can also be useful when available bounds are expected to be tighter for certain ranges of the phase volume fractions. This is the case, for example, for the "linear comparison" bounds for porous viscoplastic materials, which are known to be comparatively tighter for large values of the porosity. In this case, the new bounds obtained by the above-mentioned "iterated" procedure can be shown to be much improved relative to the earlier "linear comparison" bounds, especially at low values of the porosity and high triaxialities. Consistent with the way in which they have been derived, the new estimates are, strictly, bounds only for the class of multi-scale, nonlinear composites consisting of two well-ordered, isotropic phases that are distributed with prescribed H-measure at each stage in the incremental process. However, given the facts that the H-measure of the sequential microstructures is conserved (so that the final microstructures can be shown to have the same H-measure), and that H-measures are insensitive to length scales, it is conjectured

  9. Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Sakthivel

    2018-03-01

    Full Text Available Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11 and galectin-14 (LGALS-14 has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4 and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins when compared to the larval stage (two proteins. Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13, which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS-14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.

  10. Conformational changes and allosteric communications in human serum albumin due to ligand binding.

    Science.gov (United States)

    Ahalawat, Navjeet; Murarka, Rajesh K

    2015-01-01

    It is well recognized that knowledge of structure alone is not sufficient to understand the fundamental mechanism of biomolecular recognition. Information of dynamics is necessary to describe motions involving relevant conformational states of functional importance. We carried out principal component analysis (PCA) of structural ensemble, derived from 84 crystal structures of human serum albumin (HSA) with different ligands and/or different conditions, to identify the functionally important collective motions, and compared with the motions along the low-frequency modes obtained from normal mode analysis of the elastic network model (ENM) of unliganded HSA. Significant overlap is observed in the collective motions derived from PCA and ENM. PCA and ENM analysis revealed that ligand selects the most favored conformation from accessible equilibrium structures of unliganded HSA. Further, we analyzed dynamic network obtained from molecular dynamics simulations of unliganded HSA and fatty acids- bound HSA. Our results show that fatty acids-bound HSA has more robust community network with several routes to communicate among different parts of the protein. Critical nodes (residues) identified from dynamic network analysis are in good agreement with allosteric residues obtained from sequence-based statistical coupling analysis method. This work underscores the importance of intrinsic structural dynamics of proteins in ligand recognition and can be utilized for the development of novel drugs with optimum activity.

  11. Structural Studies of Bcl-xL/ligand Complexes using {sup 19}F NMR

    Energy Technology Data Exchange (ETDEWEB)

    Yu Liping; Hajduk, Philip J.; Mack, Jamey; Olejniczak, Edward T. [GPRD, Abbott Laboratories, Pharmaceutical Discovery Division (United States)], E-mail: Edward.olejniczak@abbott.com

    2006-04-15

    Fluorine atoms are often incorporated into drug molecules as part of the lead optimization process in order to improve affinity or modify undesirable metabolic and pharmacokinetic profiles. From an NMR perspective, the abundance of fluorinated drug leads provides an exploitable niche for structural studies using {sup 19}F NMR in the drug discovery process. As {sup 19}F has no interfering background signal from biological sources, {sup 19}F NMR studies of fluorinated drugs bound to their protein receptors can yield easily interpretable and unambiguous structural constraints. {sup 19}F can also be selectively incorporated into proteins to obtain additional constraints for structural studies. Despite these advantages, {sup 19}F NMR has rarely been exploited for structural studies due to its broad lines in macromolecules and their ligand complexes, leading to weak signals in {sup 1}H/{sup 19}F heteronuclear NOE experiments. Here we demonstrate several different experimental strategies that use {sup 19}F NMR to obtain ligand-protein structural constraints for ligands bound to the anti-apoptotic protein Bcl-xL, a drug target for anti-cancer therapy. These examples indicate the applicability of these methods to typical structural problems encountered in the drug development process.

  12. Thermalization Time Bounds for Pauli Stabilizer Hamiltonians

    Science.gov (United States)

    Temme, Kristan

    2017-03-01

    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.

  13. Universal bounds in even-spin CFTs

    Energy Technology Data Exchange (ETDEWEB)

    Qualls, Joshua D. [Department of Physics, National Taiwan University,Taipei, Taiwan (China)

    2015-12-01

    We prove using invariance under the modular S− and ST−transformations that every unitary two-dimensional conformal field theory (CFT) having only even-spin primary operators (with no extended chiral algebra and with right- and left-central charges c,c̃>1) contains a primary operator with dimension Δ{sub 1} satisfying 0<Δ{sub 1}<((c+c̃)/24)+0.09280…. After deriving both analytical and numerical bounds, we discuss how to extend our methods to bound higher conformal dimensions before deriving lower and upper bounds on the number of primary operators in a given energy range. Using the AdS{sub 3}/CFT{sub 2} dictionary, the bound on Δ{sub 1} proves the lightest massive excitation in appropriate theories of 3D matter and gravity with cosmological constant Λ<0 can be no heavier than 1/8G{sub N}+O(√(−Λ)); the bounds on the number of operators are related via AdS/CFT to the entropy of states in the dual gravitational theory. In the flat-space approximation, the limiting mass is exactly that of the lightest BTZ black hole.

  14. Setting Optimal Bounds on Risk in Asset Allocation - a Convex Program

    Directory of Open Access Journals (Sweden)

    James E. Falk

    2002-10-01

    Full Text Available The 'Portfolio Selection Problem' is traditionally viewed as selecting a mix of investment opportunities that maximizes the expected return subject to a bound on risk. However, in reality, portfolios are made up of a few 'asset classes' that consist of similar opportunities. The asset classes are managed by individual `sub-managers', under guidelines set by an overall portfolio manager. Once a benchmark (the `strategic' allocation has been set, an overall manager may choose to allow the sub-managers some latitude in which opportunities make up the classes. He may choose some overall bound on risk (as measured by the variance and wish to set bounds that constrain the submanagers. Mathematically we show that the problem is equivalent to finding a hyper-rectangle of maximal volume within an ellipsoid. It is a convex program, albeit with potentially a large number of constraints. We suggest a cutting plane algorithm to solve the problem and include computational results on a set of randomly generated problems as well as a real-world problem taken from the literature.

  15. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  16. Value maximizing maintenance policies under general repair

    International Nuclear Information System (INIS)

    Marais, Karen B.

    2013-01-01

    One class of maintenance optimization problems considers the notion of general repair maintenance policies where systems are repaired or replaced on failure. In each case the optimality is based on minimizing the total maintenance cost of the system. These cost-centric optimizations ignore the value dimension of maintenance and can lead to maintenance strategies that do not maximize system value. This paper applies these ideas to the general repair optimization problem using a semi-Markov decision process, discounted cash flow techniques, and dynamic programming to identify the value-optimal actions for any given time and system condition. The impact of several parameters on maintenance strategy, such as operating cost and revenue, system failure characteristics, repair and replacement costs, and the planning time horizon, is explored. This approach provides a quantitative basis on which to base maintenance strategy decisions that contribute to system value. These decisions are different from those suggested by traditional cost-based approaches. The results show (1) how the optimal action for a given time and condition changes as replacement and repair costs change, and identifies the point at which these costs become too high for profitable system operation; (2) that for shorter planning horizons it is better to repair, since there is no time to reap the benefits of increased operating profit and reliability; (3) how the value-optimal maintenance policy is affected by the system's failure characteristics, and hence whether it is worthwhile to invest in higher reliability; and (4) the impact of the repair level on the optimal maintenance policy. -- Highlights: •Provides a quantitative basis for maintenance strategy decisions that contribute to system value. •Shows how the optimal action for a given condition changes as replacement and repair costs change. •Shows how the optimal policy is affected by the system's failure characteristics. •Shows when it is

  17. Radiation induced ligand loss from cobalt complexes

    International Nuclear Information System (INIS)

    Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

    2000-01-01

    Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

  18. Amide proton exchange rates of a bound pepsin inhibitor determined by isotope-edited proton NMR experiments

    International Nuclear Information System (INIS)

    Fesik, S.W.; Luly, J.R.; Stein, H.H.; BaMaung, N.

    1987-01-01

    From a series of isotope-edited proton NMR spectra, amide proton exchange rates were measured at 20 C, 30 C, and 40 0 C for a tightly bound 15 N-labeled tripeptide inhibitor of porcine pepsin (IC50 = 1.7 X 10(-) M). Markedly different NH exchange rates were observed for the three amide protons of the bound inhibitor. The P1 NH exchanged much more slowly than the P2 NH and P3 NH. These results are discussed in terms of the relative solvent accessibility in the active site and the role of the NH protons of the inhibitor for hydrogen bonding to the enzyme. In this study a useful approach is demonstrated for obtaining NH exchange rates on ligands bound to biomacromolecules, the knowledge of which could be of potential utility in the design of therapeutically useful nonpeptide enzyme inhibitors from peptide leads

  19. Prospect balancing theory: Bounded rationality of drivers' speed choice.

    Science.gov (United States)

    Schmidt-Daffy, Martin

    2014-02-01

    This paper introduces a new approach to model the psychological determinants of drivers' speed choice: prospect-balancing theory. The theory transfers psychological insight into the bounded rationality of human decision-making to the field of driving behaviour. Speed choice is conceptualized as a trade-off between two options for action: the option to drive slower and the option to drive faster. Each option is weighted according to a subjective value and a subjectively weighted probability attributed to the achievement of the associated action goal; e.g. to avoid an accident by driving more slowly. The theory proposes that the subjective values and weightings of probability differ systematically from the objective conditions and thereby usually favour a cautious speed choice. A driving simulation study with 24 male participants supports this assumption. In a conflict between a monetary gain in case of fast arrival and a monetary loss in case of a collision with a deer, participants chose a velocity lower than that which would maximize their pay-out. Participants' subjective certainty of arriving in time and of avoiding a deer collision assessed at different driving speeds diverged from the respective objective probabilities in accordance with the observed bias in choice of speed. Results suggest that the bounded rationality of drivers' speed choice might be used to support attempts to improve road safety. Thus, understanding the motivational and perceptual determinants of this intuitive mode of decision-making might be a worthwhile focus of future research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  1. Scalability under a Power Bound using the GREMLINs Framework

    International Nuclear Information System (INIS)

    Maiterth, Matthias

    2015-01-01

    With the move towards exascale, system and software developers will have to deal with issues of extreme parallelism. The system properties affected most by the increase in node and core count are the shared resources on node and across the system. The increase in parallelism leads to reduced memory and bandwidth when regarding individual cores. Since power is a limiting factor for supercomputers, and power is not fully utilized in current systems, overprovisioning compute resources is a viable approach to maximized power utilization. To maximize system performance in regard to these changing conditions, it is necessary to understand how resource restrictions impact performance and system behavior. For the purpose of understanding anticipated system properties the GREMLINs Framework was developed. The framework gives the opportunity to add power restrictions, hinder memory properties and introduce faults to study resilience, among others. These features give the opportunity to use current petascale technology to study problems system designers and software developers will have to face when moving towards exascale and beyond. This work describes the initial release of the GREMLINs Framework, developed for this work, and shows how it can be used to study the scaling behavior of proxy applications. These proxy applications represent a selection of HPC workloads important to the scientific community. The proxy applications studied are AMG2013, an algebraic multi-grid linear system solver, CoMD, a classical molecular dynamics proxy application and NEKBONE, an application that uses a high order spectral element method to solve the Navier-Stokes equations. The main interest of these studies lies in analysis regarding their power behavior at scale under a power bound. These findings show how the GREMLINs Framework can help systems and software designers to attain better application performance and can also be used as basis for CPU power balancing tools to use power more

  2. Scalability under a Power Bound using the GREMLINs Framework

    Energy Technology Data Exchange (ETDEWEB)

    Maiterth, Matthias [Ludwig Maximilian Univ., Munich (Germany)

    2015-02-16

    With the move towards exascale, system and software developers will have to deal with issues of extreme parallelism. The system properties affected most by the increase in node and core count are the shared resources on node and across the system. The increase in parallelism leads to reduced memory and bandwidth when regarding individual cores. Since power is a limiting factor for supercomputers, and power is not fully utilized in current systems, overprovisioning compute resources is a viable approach to maximized power utilization. To maximize system performance in regard to these changing conditions, it is necessary to understand how resource restrictions impact performance and system behavior. For the purpose of understanding anticipated system properties the GREMLINs Framework was developed. The framework gives the opportunity to add power restrictions, hinder memory properties and introduce faults to study resilience, among others. These features give the opportunity to use current petascale technology to study problems system designers and software developers will have to face when moving towards exascale and beyond. This work describes the initial release of the GREMLINs Framework, developed for this work, and shows how it can be used to study the scaling behavior of proxy applications. These proxy applications represent a selection of HPC workloads important to the scientific community. The proxy applications studied are AMG2013, an algebraic multi-grid linear system solver, CoMD, a classical molecular dynamics proxy application and NEKBONE, an application that uses a high order spectral element method to solve the Navier-Stokes equations. The main interest of these studies lies in analysis regarding their power behavior at scale under a power bound. These findings show how the GREMLINs Framework can help systems and software designers to attain better application performance and can also be used as basis for CPU power balancing tools to use power more

  3. Yukawa Bound States and Their LHC Phenomenology

    Directory of Open Access Journals (Sweden)

    Enkhbat Tsedenbaljir

    2013-01-01

    Full Text Available We present the current status on the possible bound states of extra generation quarks. These include phenomenology and search strategy at the LHC. If chiral fourth-generation quarks do exist their strong Yukawa couplings, implied by current experimental lower bound on their masses, may lead to formation of bound states. Due to nearly degenerate 4G masses suggested by Precision Electroweak Test one can employ “heavy isospin” symmetry to classify possible spectrum. Among these states, the color-octet isosinglet vector ω 8 is the easiest to be produced at the LHC. The discovery potential and corresponding decay channels are covered in this paper. With possible light Higgs at ~125 GeV two-Higgs doublet version is briefly discussed.

  4. Bounded Gaps between Products of Special Primes

    Directory of Open Access Journals (Sweden)

    Ping Ngai Chung

    2014-03-01

    Full Text Available In their breakthrough paper in 2006, Goldston, Graham, Pintz and Yıldırım proved several results about bounded gaps between products of two distinct primes. Frank Thorne expanded on this result, proving bounded gaps in the set of square-free numbers with r prime factors for any r ≥ 2, all of which are in a given set of primes. His results yield applications to the divisibility of class numbers and the triviality of ranks of elliptic curves. In this paper, we relax the condition on the number of prime factors and prove an analogous result using a modified approach. We then revisit Thorne’s applications and give a better bound in each case.

  5. Braneworld black holes and entropy bounds

    Directory of Open Access Journals (Sweden)

    Y. Heydarzade

    2018-01-01

    Full Text Available The Bousso's D-bound entropy for the various possible black hole solutions on a 4-dimensional brane is checked. It is found that the D-bound entropy here is apparently different from that of obtained for the 4-dimensional black hole solutions. This difference is interpreted as the extra loss of information, associated to the extra dimension, when an extra-dimensional black hole is moved outward the observer's cosmological horizon. Also, it is discussed that N-bound entropy is hold for the possible solutions here. Finally, by adopting the recent Bohr-like approach to black hole quantum physics for the excited black holes, the obtained results are written also in terms of the black hole excited states.

  6. Energy conditions bounds and supernovae data

    International Nuclear Information System (INIS)

    Lima, M.P.; Vitenti, S.D.P.; Reboucas, M.J.

    2008-01-01

    The energy conditions play an important role in the description of some important properties of the Universe, including the current accelerating expansion phase and the possible recent phase of super-acceleration. In a recent work we have provided a detailed study of the energy conditions for the recent past by deriving bounds from energy conditions and by making the confrontation of the bounds with supernovae data. Here, we extend and update these results in two different ways. First, by carrying out a new statistical analysis for q(z) estimates needed for the confrontation between the bounds and supernovae data. Second, by providing a new picture of the energy conditions fulfillment and violation in the light of the recently compiled Union set of 307 type Ia supernovae and by using two different statistical approaches

  7. Bound water in Kevlar 49 fibers

    International Nuclear Information System (INIS)

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

    1981-01-01

    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 2 SO 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 0 C over a period of hours

  8. Cosmological implications of Dark Matter bound states

    Energy Technology Data Exchange (ETDEWEB)

    Mitridate, Andrea [Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa (Italy); Redi, Michele; Smirnov, Juri [INFN, Sezione di Firenze, and Dipartimento di Fisica e Astronomia, Università di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino (Italy); Strumia, Alessandro, E-mail: andrea.mitridate@gmail.com, E-mail: michele.redi@fi.infn.it, E-mail: juri.smirnov@mpi-hd.mpg.de, E-mail: alessandro.strumia@cern.ch [Dipartimento di Fisica dell' Università di Pisa and INFN, Pisa (Italy)

    2017-05-01

    We present generic formulæ for computing how Sommerfeld corrections together with bound-state formation affects the thermal abundance of Dark Matter with non-abelian gauge interactions. We consider DM as a fermion 3plet (wino) or 5plet under SU(2) {sub L} . In the latter case bound states raise to 11.5 TeV the DM mass required to reproduce the cosmological DM abundance and give indirect detection signals such as (for this mass) a dominant γ-line around 70 GeV. Furthermore, we consider DM co-annihilating with a colored particle, such as a squark or a gluino, finding that bound state effects are especially relevant in the latter case.

  9. A Versatile Dinucleating Ligand Containing Sulfonamide Groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

  10. X-ray structures of progesterone receptor ligand binding domain in its agonist state reveal differing mechanisms for mixed profiles of 11beta-substituted steroids.

    NARCIS (Netherlands)

    Lusher, S.J.; Raaijmakers, H.C.A.; Vu-Pham, D.; Kazemier, B.; Bosch, R.; McGuire, R.; Azevedo, R.; Hamersma, H.; Dechering, K.; Oubrie, A.; Duin, M. van; Vlieg, J. de

    2012-01-01

    We present here the x-ray structures of the progesterone receptor (PR) in complex with two mixed profile PR modulators whose functional activity results from two differing molecular mechanisms. The structure of Asoprisnil bound to the agonist state of PR demonstrates the contribution of the ligand

  11. Deprotonation induced ligand-to-metal electron transfer: Synthesis of a mixed-valence Rh(-I,I) dinuclear compound and its reaction with dioxygen

    NARCIS (Netherlands)

    Tejel, C.; Ciriano, M.A.; del Río, M.P.; van den Bruele, F.J.; Hetterscheid, D.G.H.; Tsichlis i Spithas, N.; de Bruin, B.

    2008-01-01

    Treatment of bis(2-picolyl)amine (bpa) with [{Rh(nbd)(mu-OMe))(2)] leads to unexpected and unique redox asymmetric dinuclear Rh-I, Rh+I complex [{Rh(ndb)}(2)(bpa-2H)] (2) with a pi-coordinating imine bound to a tetrahedral low valent rhodate(-I). Mono-oxygenation of the deprotonated bpa ligand in 2

  12. D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies

    Science.gov (United States)

    Gaieb, Zied; Liu, Shuai; Gathiaka, Symon; Chiu, Michael; Yang, Huanwang; Shao, Chenghua; Feher, Victoria A.; Walters, W. Patrick; Kuhn, Bernd; Rudolph, Markus G.; Burley, Stephen K.; Gilson, Michael K.; Amaro, Rommie E.

    2018-01-01

    The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.

  13. Comparison of Lasserre's Measure-based Bounds for Polynomial Optimization to Bounds Obtained by Simulated Annealing

    NARCIS (Netherlands)

    de Klerk, Etienne; Laurent, Monique

    We consider the problem of minimizing a continuous function f over a compact set K. We compare the hierarchy of upper bounds proposed by Lasserre in [SIAM J. Optim. 21(3) (2011), pp. 864-885] to bounds that may be obtained from simulated annealing. We show that, when f is a polynomial and K a convex

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

    Science.gov (United States)

    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…

  15. A note on BPS vortex bound states

    Directory of Open Access Journals (Sweden)

    A. Alonso-Izquierdo

    2016-02-01

    Full Text Available 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.

  16. A note on BPS vortex bound states

    Energy Technology Data Exchange (ETDEWEB)

    Alonso-Izquierdo, A., E-mail: alonsoiz@usal.es [Departamento de Matematica Aplicada, Universidad de Salamanca (Spain); Garcia Fuertes, W., E-mail: wifredo@uniovi.es [Departamento de Fisica, Universidad de Oviedo (Spain); Mateos Guilarte, J., E-mail: guilarte@usal.es [Departamento de Fisica Fundamental, Universidad de Salamanca (Spain)

    2016-02-10

    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.

  17. [Membrane-bound cytokine and feedforward regulation].

    Science.gov (United States)

    Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua

    2013-10-01

    Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

  18. The covariant entropy bound in gravitational collapse

    International Nuclear Information System (INIS)

    Gao, Sijie; Lemos, Jose P. S.

    2004-01-01

    We study the covariant entropy bound in the context of gravitational collapse. First, we discuss critically the heuristic arguments advanced by Bousso. Then we solve the problem through an exact model: a Tolman-Bondi dust shell collapsing into a Schwarzschild black hole. After the collapse, a new black hole with a larger mass is formed. The horizon, L, of the old black hole then terminates at the singularity. We show that the entropy crossing L does not exceed a quarter of the area of the old horizon. Therefore, the covariant entropy bound is satisfied in this process. (author)

  19. Bound states in curved quantum waveguides

    International Nuclear Information System (INIS)

    Exner, P.; Seba, P.

    1987-01-01

    We study free quantum particle living on a curved planar strip Ω of a fixed width d with Dirichlet boundary conditions. It can serve as a model for electrons in thin films on a cylindrical-type substrate, or in a curved quantum wire. Assuming that the boundary of Ω is infinitely smooth and its curvature decays fast enough at infinity, we prove that a bound state with energy below the first transversal mode exists for all sufficiently small d. A lower bound on the critical width is obtained using the Birman-Schwinger technique. (orig.)

  20. Lower Bounds for External Memory Dictionaries

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf

    2003-01-01

    We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N < M insertions perform at most δ · N/B I/Os, then......We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N

  1. Bound constrained quadratic programming via piecewise

    DEFF Research Database (Denmark)

    Madsen, Kaj; Nielsen, Hans Bruun; Pinar, M. C.

    1999-01-01

    of a symmetric, positive definite matrix, and is solved by Newton iteration with line search. The paper describes the algorithm and its implementation including estimation of lambda/sub 1/ , how to get a good starting point for the iteration, and up- and downdating of Cholesky factorization. Results of extensive......We consider the strictly convex quadratic programming problem with bounded variables. A dual problem is derived using Lagrange duality. The dual problem is the minimization of an unconstrained, piecewise quadratic function. It involves a lower bound of lambda/sub 1/ , the smallest eigenvalue...

  2. Quantum Kolmogorov complexity and bounded quantum memory

    International Nuclear Information System (INIS)

    Miyadera, Takayuki

    2011-01-01

    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.

  3. Cell surface receptors for signal transduction and ligand transport: a design principles study.

    Directory of Open Access Journals (Sweden)

    Harish Shankaran

    2007-06-01

    Full Text Available Receptors constitute the interface of cells to their external environment. These molecules bind specific ligands involved in multiple processes, such as signal transduction and nutrient transport. Although a variety of cell surface receptors undergo endocytosis, the systems-level design principles that govern the evolution of receptor trafficking dynamics are far from fully understood. We have constructed a generalized mathematical model of receptor-ligand binding and internalization to understand how receptor internalization dynamics encodes receptor function and regulation. A given signaling or transport receptor system represents a particular implementation of this module with a specific set of kinetic parameters. Parametric analysis of the response of receptor systems to ligand inputs reveals that receptor systems can be characterized as being: i avidity-controlled where the response control depends primarily on the extracellular ligand capture efficiency, ii consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii dual-sensitivity where both the avidity and consumption parameters are important. We show that the transferrin and low-density lipoprotein receptors are avidity-controlled, the vitellogenin receptor is consumption-controlled, and the epidermal growth factor receptor is a dual-sensitivity receptor. Significantly, we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of signaling receptors rather than merely serving to attenuate signaling. Our analysis reveals that the location of a receptor system in the avidity-consumption parameter space can be used to understand both its function and its regulation.

  4. Protonation of Ferrous Dinitrogen Complexes Containing a Diphosphine Ligand with a Pendant Amine

    Energy Technology Data Exchange (ETDEWEB)

    Heiden, Zachariah M.; Chen, Shentan; Mock, Michael T.; Dougherty, William G.; Kassel, W. S.; Rousseau, Roger J.; Bullock, R. Morris

    2013-04-01

    The addition of protons to pendant amine containing ferrous dinitrogen complexes, of the type [FeX(N2)(PEtNMePEt)(dmpm)]+ (X = H, Cl, or Br; PEtNMePEt = Et2PCH2N(Me)CH2PEt2 and dmpm = Me2PCH2PMe2), was found to protonate at the pendant amine as opposed to the dinitrogen ligand. This protonation increased the νN2 of the complex by about 25 cm-1, shifting the Fe(II/I) couple 330 mV to a more positive potential. A similar shift was observed in the case of [FeX(CO)(PEtNMePEt)(dmpm)]+ (X = H, Cl, or Br). Computational analysis verified these experimental results and showed the coordination of N2 to Fe(II) centers increases the basicity of N2 (vs. free N2) by 13 and 20 pKa units for the trans halides and hydrides, respectively. Although the iron center was found to increase the basicity of the bound N2 ligand, coordinated N2 is not sufficiently basic to be protonated. In the case of ferrous dinitrogen complexes containing a basic pendant methylamine, the amine site was determined to be the most basic site by 30 pKa units compared to protonation at the N2 ligand. To increase the basicity of the N2 ligand in order to promote proton transfer from the pendant amine to the N2 ligand, chemical reduction of these ferrous dinitrogen complexes was performed and found to result in oxidative addition of the methylene C-H bond of the PEtNMePEt ligand to Fe, preventing isolation of a reduced Fe(0) N2 complex. This work was supported as part of 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.

  5. POLITENESS MAXIM OF MAIN CHARACTER IN SECRET FORGIVEN

    Directory of Open Access Journals (Sweden)

    Sang Ayu Isnu Maharani

    2017-06-01

    Full Text Available Maxim of Politeness is an interesting subject to be discussed, since politeness has been criticized from our childhood. We are obliques to be polite to anyone either in speaking or in acting. Somehow we are manage to show politeness in our spoken expression though our intention might be not so polite. For example we must appriciate others opinion although we feel objection toward the opinion. In this article the analysis of politeness is based on maxim proposes by Leech. He proposed six types of politeness maxim. The discussion shows that the main character (Kristen and Kami use all types of maxim in their conversation. The most commonly used are approbation maxim and agreement maxim

  6. Improving binding mode and binding affinity predictions of docking by ligand-based search of protein conformations: evaluation in D3R grand challenge 2015

    Science.gov (United States)

    Xu, Xianjin; Yan, Chengfei; Zou, Xiaoqin

    2017-08-01

    The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by using the information embedded in the known protein-ligand complex structures to improve both binding mode and binding affinity predictions. Specifically, a ligand similarity calculation method was employed to search a receptor structure with a bound ligand sharing high similarity with the query ligand for the docking use. The strategy was applied to the two datasets (HSP90 and MAP4K4) in recent D3R Grand Challenge 2015. In addition, for the HSP90 dataset, a system-specific scoring function (ITScore2_hsp90) was generated by recalibrating our statistical potential-based scoring function (ITScore2) using the known protein-ligand complex structures and the statistical mechanics-based iterative method. For the HSP90 dataset, better performances were achieved for both binding mode and binding affinity predictions comparing with the original ITScore2 and with ensemble docking. For the MAP4K4 dataset, although there were only eight known protein-ligand complex structures, our docking strategy achieved a comparable performance with ensemble docking. Our method for receptor conformational selection and iterative method for the development of system-specific statistical potential-based scoring functions can be easily applied to other protein targets that have a number of protein-ligand complex structures available to improve predictions on binding.

  7. Maximizers versus satisficers: Decision-making styles, competence, and outcomes

    OpenAIRE

    Andrew M. Parker; Wändi Bruine de Bruin; Baruch Fischhoff

    2007-01-01

    Our previous research suggests that people reporting a stronger desire to maximize obtain worse life outcomes (Bruine de Bruin et al., 2007). Here, we examine whether this finding may be explained by the decision-making styles of self-reported maximizers. Expanding on Schwartz et al.\\ (2002), we find that self-reported maximizers are more likely to show problematic decision-making styles, as evidenced by self-reports of less behavioral coping, greater dependence on others when making decision...

  8. Natural maximal νμ-ντ mixing

    International Nuclear Information System (INIS)

    Wetterich, C.

    1999-01-01

    The naturalness of maximal mixing between myon- and tau-neutrinos is investigated. A spontaneously broken nonabelian generation symmetry can explain a small parameter which governs the deviation from maximal mixing. In many cases all three neutrino masses are almost degenerate. Maximal ν μ -ν τ -mixing suggests that the leading contribution to the light neutrino masses arises from the expectation value of a heavy weak triplet rather than from the seesaw mechanism. In this scenario the deviation from maximal mixing is predicted to be less than about 1%. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. On the way towards a generalized entropy maximization procedure

    International Nuclear Information System (INIS)

    Bagci, G. Baris; Tirnakli, Ugur

    2009-01-01

    We propose a generalized entropy maximization procedure, which takes into account the generalized averaging procedures and information gain definitions underlying the generalized entropies. This novel generalized procedure is then applied to Renyi and Tsallis entropies. The generalized entropy maximization procedure for Renyi entropies results in the exponential stationary distribution asymptotically for q element of (0,1] in contrast to the stationary distribution of the inverse power law obtained through the ordinary entropy maximization procedure. Another result of the generalized entropy maximization procedure is that one can naturally obtain all the possible stationary distributions associated with the Tsallis entropies by employing either ordinary or q-generalized Fourier transforms in the averaging procedure.

  10. Violating Bell inequalities maximally for two d-dimensional systems

    International Nuclear Information System (INIS)

    Chen Jingling; Wu Chunfeng; Oh, C. H.; Kwek, L. C.; Ge Molin

    2006-01-01

    We show the maximal violation of Bell inequalities for two d-dimensional systems by using the method of the Bell operator. The maximal violation corresponds to the maximal eigenvalue of the Bell operator matrix. The eigenvectors corresponding to these eigenvalues are described by asymmetric entangled states. We estimate the maximum value of the eigenvalue for large dimension. A family of elegant entangled states |Ψ> app that violate Bell inequality more strongly than the maximally entangled state but are somewhat close to these eigenvectors is presented. These approximate states can potentially be useful for quantum cryptography as well as many other important fields of quantum information

  11. Photoaffinity labeling of [3H]flunitrazepam- and [3H]Ro15-4513-bound pellets in rat cerebral cortex and cerebellum

    International Nuclear Information System (INIS)

    Chiu, T.H.; Yu, Onnfoh; Rosenberg, H.C.

    1989-01-01

    Irreversible incorporation of [ 3 H]flunitrazepam and [ 3 H]Ro15-4513 into GABA/benzodiazepine receptor subunits was studied by UV/irradiation using ligand-bound membrane pellets from rat cerebral cortical and cerebellar synaptic membranes. Specific incorporation for [ 3 H]flunitrazepam was greater in the pellet than in the suspension. The incorporation was identical for [ 3 H]Ro15-4513 in both pellet and suspension. With the ligand-bound pellets, 50% of the available binding sites were photolabeled by both ligands in cortex and cerebellum. SDS polyacrylamide gel electrophoresis and fluorography of [ 3 H]flunitrazepam photo-labeled receptor revealed the same number of major sites in both brain regions. In contrast, [ 3 H]Ro15-4513 appears to label fewer sites in cortex and cerebellum. Photoaffinity labeling with [ 3 H]flunitrazepam in ligand-bound membrane pellet provides a more selective and reliable method for studying the subunit structure of GABA/benzodiazepine receptor complex

  12. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... The study was carried out using the software Ligand Scout (version .... Computer Science, for his great help and support. We are also grateful to Faculty of Engineering and applied. Sciences, Mohammad .... Aided Mol. Design ...

  13. Synthesis and characterization β-ketoamine ligands

    Science.gov (United States)

    Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

    2018-04-01

    β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

  14. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  15. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  16. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  17. Models of bounded rationality under certainty

    NARCIS (Netherlands)

    Rasouli, S.; Timmermans, H.J.P.; Rasouli, S.; Timmermans, H.J.P.

    2015-01-01

    Purpose This chapter reviews models of decision-making and choice under conditions of certainty. It allows readers to position the contribution of the other chapters in this book in the historical development of the topic area. Theory Bounded rationality is defined in terms of a strategy to simplify

  18. Sobolev spaces on bounded symmetric domains

    Czech Academy of Sciences Publication Activity Database

    Engliš, Miroslav

    Roč. 60, č. 12 ( 2015 ), s. 1712-1726 ISSN 1747-6933 Institutional support: RVO:67985840 Keywords : bounded symmetric domain * Sobolev space * Bergman space Subject RIV: BA - General Mathematics Impact factor: 0.466, year: 2015 http://www.tandfonline.com/doi/abs/10.1080/17476933. 2015 .1043910

  19. Properties of Excitons Bound to Ionized Donors

    DEFF Research Database (Denmark)

    Skettrup, Torben; Suffczynski, M.; Gorzkowski, W.

    1971-01-01

    Binding energies, interparticle distances, oscillator strengths, and exchange corrections are calculated for the three-particle complex corresponding to an exciton bound to an ionized donor. The results are given as functions of the mass ratio of the electron and hole. Binding of the complex is o...

  20. Bogomol'nyi bounds for cosmic strings

    International Nuclear Information System (INIS)

    Comtet, A.; Gibbons, G.W.; Cambridge Univ.

    1987-09-01

    We establish Bogomol'nyi inequalities for the deficit angle of some cylindrically symmetric asymptotically local flat (CALF) spacetimes containing cosmic strings. These results prove the stability against arbitrary cylindrical deformations of those configurations which saturate the bound. Such configurations satisfy first order equations which can, in some cases, be solved exactly

  1. Bounding the bias of contrastive divergence learning

    DEFF Research Database (Denmark)

    Fischer, Anja; Igel, Christian

    2011-01-01

    Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k...

  2. Bound States in the Mirror TBA

    NARCIS (Netherlands)

    Arutyunov, G.E.; Frolov, S.; van Tongeren, S.J.

    2012-01-01

    The spectrum of the light-cone AdS_5 \\times S^5 superstring contains states composed of particles with complex momenta including in particular those which turn into bound states in the decompactification limit. We propose the mirror TBA description for these states. We focus on a three-particle

  3. Harmonic maps of the bounded symmetric domains

    International Nuclear Information System (INIS)

    Xin, Y.L.

    1994-06-01

    A shrinking property of harmonic maps into R IV (2) is proved which is used to classify complete spacelike surfaces of the parallel mean curvature in R 4 2 with a reasonable condition on the Gauss image. Liouville-type theorems of harmonic maps from the higher dimensional bounded symmetric domains are also established. (author). 25 refs

  4. Scattering theory methods for bound state problems

    International Nuclear Information System (INIS)

    Raphael, R.B.; Tobocman, W.

    1978-01-01

    For the analysis of the properties of a bound state system one may use in place of the Schroedinger equation the Lippmann-Schwinger (LS) equation for the wave function or the LS equation for the reactance operator. Use of the LS equation for the reactance operator constrains the solution to have correct asymptotic behaviour, so this approach would appear to be desirable when the bound state wave function is to be used to calculate particle transfer form factors. The Schroedinger equation based N-level analysis of the s-wave bound states of a square well is compared to the ones based on the LS equation. It is found that the LS equation methods work better than the Schroedinger equation method. The method that uses the LS equation for the wave function gives the best results for the wave functions while the method that uses the LS equation for the reactance operator gives the best results for the binding energies. The accuracy of the reactance operator based method is remarkably insensitive to changes in the oscillator constant used for the harmonic oscillator function basis set. It is also remarkably insensitive to the number of nodes in the bound state wave function. (Auth.)

  5. Lower bounds on scintillation detector timing performance

    International Nuclear Information System (INIS)

    Clinthorne, N.H.; Rogers, W.L.; Hero, A.O. III.; Petrick, N.A.

    1990-01-01

    Fundamental method-independent limits on the timing performance of scintillation detectors are useful for identifying regimes in which either present timing methods are nearly optimal or where a considerable performance gain might be realized using better pulse processing techniques. Several types of lower bounds on mean-squared timing error (MSE) performance have been developed and applied to scintillation detectors. The simple Cramer-Rao (CR) bound can be useful in determining the limiting MSE for scintillators having a relatively high rate of photon problction such as BaF 2 and NaI(Tl); however, it tends to overestimate the achievalbe performance for scintillators with lower rates such as BGO. For this reason, alternative bounds have been developed using rate-distortion theory or by assuming that the conversion of energy to scintillation light must pass through excited states which have exponential lifetime densities. The bounds are functions of the mean scintillation pulse shape, the scintillation intensity, and photodetector characteristics; they are simple to evaluate and can be used to conveniently assess the limiting timing performance of scintillation detectors. (orig.)

  6. Efficiency gains, bounds, and risk in finance

    NARCIS (Netherlands)

    Sarisoy, Cisil

    2015-01-01

    This thesis consists of three chapters. The first chapter analyzes efficiency gains in the estimation of expected returns based on asset pricing models and examines the economic implications of such gains in portfolio allocation exercises. The second chapter provides nonparametric efficiency bounds

  7. Book Selection, Collection Development, and Bounded Rationality.

    Science.gov (United States)

    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)…

  8. Monotonicity and bounds on Bessel functions

    Directory of Open Access Journals (Sweden)

    Larry Landau

    2000-07-01

    Full Text Available survey my recent results on monotonicity with respect to order of general Bessel functions, which follow from a new identity and lead to best possible uniform bounds. Application may be made to the "spreading of the wave packet" for a free quantum particle on a lattice and to estimates for perturbative expansions.

  9. Collisional properties of weakly bound heteronuclear dimers

    NARCIS (Netherlands)

    Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

    2008-01-01

    We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

  10. Bounded Rationality of Generalized Abstract Fuzzy Economies

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2014-01-01

    Full Text Available By using a nonlinear scalarization technique, the bounded rationality model M for generalized abstract fuzzy economies in finite continuous spaces is established. Furthermore, by using the model M, some new theorems for structural stability and robustness to (λ,ϵ-equilibria of generalized abstract fuzzy economies are proved.

  11. Bounded Rationality in Individual Decision Making

    OpenAIRE

    Camerer, Colin F.

    1998-01-01

    The main objectives of this paper are: (i) To give a pithy, opinionated summary of what has been learned about bounded rationality in individual decision making from experiments in economics and psychology (drawing on my 1995 Handbook of Experimental Economics chapter); and (ii) mention some promising new directions for research which would be included if that chapter were written today.

  12. Crystal structures of the ligand-binding region of uPARAP

    DEFF Research Database (Denmark)

    Yuan, Cai; Jürgensen, Henrik J; Engelholm, Lars H

    2016-01-01

    The proteins of the mannose receptor (MR) family share a common domain organization and have a broad range of biological functions. Urokinase plasminogen activator receptor-associated protein (uPARAP) (or Endo180) is a member of this family and plays an important role in extracellular matrix...... remodelling through interaction with its ligands, including collagens and urokinase plasminogen activator receptor (uPAR). We report the crystal structures of the first four domains of uPARAP (also named the ligand-binding region, LBR) at pH 7.4 in Ca(2+)-bound and Ca(2+)-free forms. The first domain....... These LLRs undergo a Ca(2+)-dependent conformational change, and this is likely to be the key structural determinant affecting the overall conformation of uPARAP. Our results provide a molecular mechanism to support the structural flexibility of uPARAP, and shed light on the structural flexibility of other...

  13. Semiconductor Quantum Dots with Photoresponsive Ligands.

    Science.gov (United States)

    Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

    2016-10-01

    Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

  14. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  15. How Diverse are the Protein-Bound Conformations of Small-Molecule Drugs and Cofactors?

    Science.gov (United States)

    Friedrich, Nils-Ole; Simsir, Méliné; Kirchmair, Johannes

    2018-03-01

    Knowledge of the bioactive conformations of small molecules or the ability to predict them with theoretical methods is of key importance to the design of bioactive compounds such as drugs, agrochemicals and cosmetics. Using an elaborate cheminformatics pipeline, which also evaluates the support of individual atom coordinates by the measured electron density, we compiled a complete set (“Sperrylite Dataset”) of high-quality structures of protein-bound ligand conformations from the PDB. The Sperrylite Dataset consists of a total of 10,936 high-quality structures of 4548 unique ligands. Based on this dataset, we assessed the variability of the bioactive conformations of 91 small molecules—each represented by a minimum of ten structures—and found it to be largely independent of the number of rotatable bonds. Sixty-nine molecules had at least two distinct conformations (defined by an RMSD greater than 1 Å). For a representative subset of 17 approved drugs and cofactors we observed a clear trend for the formation of few clusters of highly similar conformers. Even for proteins that share a very low sequence identity, ligands were regularly found to adopt similar conformations. For cofactors, a clear trend for extended conformations was measured, although in few cases also coiled conformers were observed. The Sperrylite Dataset is available for download from http://www.zbh.uni-hamburg.de/sperrylite_dataset.

  16. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  17. Sharp Bounds for Symmetric and Asymmetric Diophantine Approximation

    Institute of Scientific and Technical Information of China (English)

    Cornelis KRAAIKAMP; Ionica SMEETS

    2011-01-01

    In 2004,Tong found bounds for the approximation quality of a regular continued fraction convergent to a rational number,expressed in bounds for both the previous and next approximation.The authors sharpen his results with a geometric method and give both sharp upper and lower bounds.The asymptotic frequencies that these bounds occur are also calculated.

  18. Concurrent coordination of ligand in metal chloride complexes with 1-vinyl-2-(2-pyridyl)benzimidazole

    International Nuclear Information System (INIS)

    Bajkalov, L.V.; Domnina, E.S.

    1996-01-01

    The properties and structure of bivalent cadmium and 1-vinyl-2-(2-pyridyl)benzimidazole chloride complexes, which have been prepared for the first time, have been studied by the methods of potentiometric titration and PMR, 35 Cl NQR, UV and IR spectroscopy. For the complexes above di- and polymeric structures in crystal phase are suggested, where ligand plays the role of a bridge. N,N-bidentate ligand. In solution the complexes dissociate with formation of monomeric coordination compounds, their metal being bound by different ways, stemming from participation of N benzimidazole or pyridine fragment of the ligand. Adducts of ionic type with second sphere 1-vinyl-2-(2-pyridyl)benzimidazole cation have been obtained in the course of hydrochlorination of the complexes prepared

  19. Bounds on isocurvature perturbations from cosmic microwave background and large scale structure data.

    Science.gov (United States)

    Crotty, Patrick; García-Bellido, Juan; Lesgourgues, Julien; Riazuelo, Alain

    2003-10-24

    We obtain very stringent bounds on the possible cold dark matter, baryon, and neutrino isocurvature contributions to the primordial fluctuations in the Universe, using recent cosmic microwave background and large scale structure data. Neglecting the possible effects of spatial curvature, tensor perturbations, and reionization, we perform a Bayesian likelihood analysis with nine free parameters, and find that the amplitude of the isocurvature component cannot be larger than about 31% for the cold dark matter mode, 91% for the baryon mode, 76% for the neutrino density mode, and 60% for the neutrino velocity mode, at 2sigma, for uncorrelated models. For correlated adiabatic and isocurvature components, the fraction could be slightly larger. However, the cross-correlation coefficient is strongly constrained, and maximally correlated/anticorrelated models are disfavored. This puts strong bounds on the curvaton model.

  20. Differential Privacy for Relational Algebra: Improving the Sensitivity Bounds via Constraint Systems

    Directory of Open Access Journals (Sweden)

    Catuscia Palamidessi

    2012-07-01

    Full Text Available Differential privacy is a modern approach in privacy-preserving data analysis to control the amount of information that can be inferred about an individual by querying a database. The most common techniques are based on the introduction of probabilistic noise, often defined as a Laplacian parametric on the sensitivity of the query. In order to maximize the utility of the query, it is crucial to estimate the sensitivity as precisely as possible. In this paper we consider relational algebra, the classical language for queries in relational databases, and we propose a method for computing a bound on the sensitivity of queries in an intuitive and compositional way. We use constraint-based techniques to accumulate the information on the possible values for attributes provided by the various components of the query, thus making it possible to compute tight bounds on the sensitivity.

  1. Hadamard States for the Klein-Gordon Equation on Lorentzian Manifolds of Bounded Geometry

    Science.gov (United States)

    Gérard, Christian; Oulghazi, Omar; Wrochna, Michał

    2017-06-01

    We consider the Klein-Gordon equation on a class of Lorentzian manifolds with Cauchy surface of bounded geometry, which is shown to include examples such as exterior Kerr, Kerr-de Sitter spacetime and the maximal globally hyperbolic extension of the Kerr outer region. In this setup, we give an approximate diagonalization and a microlocal decomposition of the Cauchy evolution using a time-dependent version of the pseudodifferential calculus on Riemannian manifolds of bounded geometry. We apply this result to construct all pure regular Hadamard states (and associated Feynman inverses), where regular refers to the state's two-point function having Cauchy data given by pseudodifferential operators. This allows us to conclude that there is a one-parameter family of elliptic pseudodifferential operators that encodes both the choice of (pure, regular) Hadamard state and the underlying spacetime metric.

  2. Evaluation of anti-hyperglycemic effect of Actinidia kolomikta (Maxim. etRur.) Maxim. root extract.

    Science.gov (United States)

    Hu, Xuansheng; Cheng, Delin; Wang, Linbo; Li, Shuhong; Wang, Yuepeng; Li, Kejuan; Yang, Yingnan; Zhang, Zhenya

    2015-05-01

    This study aimed to evaluate the anti-hyperglycemic effect of ethanol extract from Actinidia kolomikta (Maxim. etRur.) Maxim. root (AKE).An in vitro evaluation was performed by using rat intestinal α-glucosidase (maltase and sucrase), the key enzymes linked with type 2 diabetes. And an in vivo evaluation was also performed by loading maltose, sucrose, glucose to normal rats. As a result, AKE showed concentration-dependent inhibition effects on rat intestinal maltase and rat intestinal sucrase with IC(50) values of 1.83 and 1.03mg/mL, respectively. In normal rats, after loaded with maltose, sucrose and glucose, administration of AKE significantly reduced postprandial hyperglycemia, which is similar to acarbose used as an anti-diabetic drug. High contents of total phenolics (80.49 ± 0.05mg GAE/g extract) and total flavonoids (430.69 ± 0.91mg RE/g extract) were detected in AKE. In conclusion, AKE possessed anti-hyperglycemic effects and the possible mechanisms were associated with its inhibition on α-glucosidase and the improvement on insulin release and/or insulin sensitivity as well. The anti-hyperglycemic activity possessed by AKE maybe attributable to its high contents of phenolic and flavonoid compounds.

  3. Bioavailability of organically bound Fe to model phytoplankton of the Southern Ocean

    Directory of Open Access Journals (Sweden)

    C. S. Hassler

    2009-10-01

    Full Text Available Iron (Fe is known to be mostly bound to organic ligands and to limit primary productivity in the Southern Ocean. It is thus important to investigate the bioavailability of organically bound Fe. In this study, we used four phytoplankton species of the Southern Ocean (Phaeocystis sp., Chaetoceros sp., Fragilariopsis kerguelensis and Thalassiosira antarctica Comber to measure the influence of various organic ligands on Fe solubility and bioavailability. Short-term uptake Fe:C ratios were inversely related to the surface area to volume ratios of the phytoplankton. The ratio of extracellular to intracellular Fe is used to discuss the relative importance of diffusive supply and uptake to control Fe bioavailability. The effect of excess organic ligands on Fe bioavailability cannot be solely explained by their effect on Fe solubility. For most strains studied, the bioavailability of Fe can be enhanced relative to inorganic Fe in the presence of porphyrin, catecholate siderophore and saccharides whereas it was decreased in presence of hydroxamate siderophore and organic amine. For Thalassiosira, iron bioavailability was not affected by the presence of porphyrin, catecholate siderophore and saccharides. The enhancement of Fe bioavailability in presence of saccharides is presented as the result from both the formation of bioavailable (or chemically labile organic form of Fe and the stabilisation of Fe within the dissolved phase. Given the ubiquitous presence of saccharides in the ocean, these compounds might represent an important factor to control the basal level of soluble and bioavailable Fe. Results show that the use of model phytoplankton is promising to improve mechanistic understanding of Fe bioavailability and primary productivity in HNLC regions of the ocean.

  4. Violations of Bell inequalities as lower bounds on the communication cost of nonlocal correlations

    International Nuclear Information System (INIS)

    Pironio, Stefano

    2003-01-01

    To reproduce in a local hidden variables theory correlations that violate Bell inequalities, communication must occur between the parties. We show that the amount of violation of a Bell inequality imposes a lower bound on the average communication needed to produce these correlations. Moreover, for every probability distribution there exists an optimal inequality for which the degree of violation gives the minimal average communication. As an example, to produce using classical resources the correlations that maximally violate the Clauser-Horne-Shimony-Holt inequality, (√2)-1≅0.4142 bits of communication are necessary and sufficient. For Bell tests performed on two entangled states of dimension d≥3 where each party has the choice between two measurements, our results suggest that more communication is needed to simulate outcomes obtained from certain nonmaximally entangled states than maximally entangled ones

  5. Alternative approaches to maximally supersymmetric field theories

    International Nuclear Information System (INIS)

    Broedel, Johannes

    2010-01-01

    The central objective of this work is the exploration and application of alternative possibilities to describe maximally supersymmetric field theories in four dimensions: N=4 super Yang-Mills theory and N=8 supergravity. While twistor string theory has been proven very useful in the context of N=4 SYM, no analogous formulation for N=8 supergravity is available. In addition to the part describing N=4 SYM theory, twistor string theory contains vertex operators corresponding to the states of N=4 conformal supergravity. Those vertex operators have to be altered in order to describe (non-conformal) Einstein supergravity. A modified version of the known open twistor string theory, including a term which breaks the conformal symmetry for the gravitational vertex operators, has been proposed recently. In a first part of the thesis structural aspects and consistency of the modified theory are discussed. Unfortunately, the majority of amplitudes can not be constructed, which can be traced back to the fact that the dimension of the moduli space of algebraic curves in twistor space is reduced in an inconsistent manner. The issue of a possible finiteness of N=8 supergravity is closely related to the question of the existence of valid counterterms in the perturbation expansion of the theory. In particular, the coefficient in front of the so-called R 4 counterterm candidate has been shown to vanish by explicit calculation. This behavior points into the direction of a symmetry not taken into account, for which the hidden on-shell E 7(7) symmetry is the prime candidate. The validity of the so-called double-soft scalar limit relation is a necessary condition for a theory exhibiting E 7(7) symmetry. By calculating the double-soft scalar limit for amplitudes derived from an N=8 supergravity action modified by an additional R 4 counterterm, one can test for possible constraints originating in the E 7(7) symmetry. In a second part of the thesis, the appropriate amplitudes are calculated

  6. Molecular dynamics simulation of S100B protein to explore ligand blockage of the interaction with p53 protein

    Science.gov (United States)

    Zhou, Zhigang; Li, Yumin

    2009-10-01

    As a tumor suppressor, p53 plays an important role in cancer suppression. The biological function of p53 as a tumor suppressor is disabled when it binds to S100B. Developing the ligands to block the S100B-p53 interaction has been proposed as one of the most important approaches to the development of anti-cancer agents. We screened a small compound library against the binding interface of S100B and p53 to identify potential compounds to interfere with the interaction. The ligand-binding effect on the S100B-p53 interaction was explored by molecular dynamics at the atomic level. The results show that the ligand bound between S100B and p53 propels the two proteins apart by about 2 Å compared to the unligated S100B-p53 complex. The binding affinity of S100B and p53 decreases by 8.5-14.6 kcal/mol after a ligand binds to the interface from the original unligated state of the S100B-p53 complex. Ligand-binding interferes with the interaction of S100B and p53. Such interference could impact the association of S100B and p53, which would free more p53 protein from the pairing with S100B and restore the biological function of p53 as a tumor suppressor. The analysis of the binding mode and ligand structural features would facilitate our effort to identify and design ligands to block S100B-p53 interaction effectively. The results from the work suggest that developing ligands targeting the interface of S100B and p53 could be a promising approach to recover the normal function of p53 as a tumor suppressor.

  7. Space-Bounded Church-Turing Thesis and Computational Tractability of Closed Systems.

    Science.gov (United States)

    Braverman, Mark; Schneider, Jonathan; Rojas, Cristóbal

    2015-08-28

    We report a new limitation on the ability of physical systems to perform computation-one that is based on generalizing the notion of memory, or storage space, available to the system to perform the computation. Roughly, we define memory as the maximal amount of information that the evolving system can carry from one instant to the next. We show that memory is a limiting factor in computation even in lieu of any time limitations on the evolving system-such as when considering its equilibrium regime. We call this limitation the space-bounded Church-Turing thesis (SBCT). The SBCT is supported by a simulation assertion (SA), which states that predicting the long-term behavior of bounded-memory systems is computationally tractable. In particular, one corollary of SA is an explicit bound on the computational hardness of the long-term behavior of a discrete-time finite-dimensional dynamical system that is affected by noise. We prove such a bound explicitly.

  8. Quantum Cramer–Rao Bound for a Massless Scalar Field in de Sitter Space

    Directory of Open Access Journals (Sweden)

    Marcello Rotondo

    2017-10-01

    Full Text Available How precisely can we estimate cosmological parameters by performing a quantum measurement on a cosmological quantum state? In quantum estimation theory, the variance of an unbiased parameter estimator is bounded from below by the inverse of measurement-dependent Fisher information and ultimately by quantum Fisher information, which is the maximization of the former over all positive operator-valued measurements. Such bound is known as the quantum Cramer –Rao bound. We consider the evolution of a massless scalar field with Bunch–Davies vacuum in a spatially flat FLRW spacetime, which results in a two-mode squeezed vacuum out-state for each field wave number mode. We obtain the expressions of the quantum Fisher information as well as the Fisher informations associated to occupation number measurement and power spectrum measurement, and show the specific results of their evolution for pure de Sitter expansion and de Sitter expansion followed by a radiation-dominated phase as examples. We will discuss these results from the point of view of the quantum-to-classical transition of cosmological perturbations and show quantitatively how this transition and the residual quantum correlations affect the bound on the precision.

  9. Bounds on fluid permeability for viscous flow through porous media

    International Nuclear Information System (INIS)

    Berryman, J.G.

    1985-01-01

    General properties of variational bounds on Darcy's constant for slow viscous flow through porous media are studied. The bounds are also evaluated numerically for the penetrable sphere model. The bound of Doi depending on two-point correlations and the analytical bound of Weissberg and Prager give comparable results in the low density limit but the analytical bound is superior for higher densities. Prager's bound depending on three-point correlation functions is worse than the analytical bound at low densities but better (although comparable to it) at high densities. A procedure for methodically improving Prager's three point bound is presented. By introducing a Gaussian trial function, the three-point bound is improved by an order of magnitude for moderate values of porosity. The new bounds are comparable in magnitude to the Kozeny--Carman empirical relation for porous materials

  10. Characterization of chicken thrombocyte responses to Toll-like receptor ligands.

    Directory of Open Access Journals (Sweden)

    Michael St Paul

    Full Text Available Thrombocytes are the avian equivalent to mammalian platelets. In addition to their hemostatic effects, mammalian platelets rely in part on pattern recognition receptors, such as the Toll-like receptors (TLR, to detect the presence of pathogens and signal the release of certain cytokines. Ligands for TLRs include lipopolysaccharide (LPS, which is bound by TLR4, as well as unmethylated CpG DNA motifs, which are bound by TLR9 in mammals and TLR21 in chickens. Similar to mammalian platelets, avian thrombocytes have been shown to express TLR4 and secrete some pro-inflammatory cytokines in response to LPS treatment. However, the full extent of the contributions made by thrombocytes to host immunity has yet to be elucidated. Importantly, the mechanisms by which TLR stimulation may modulate thrombocyte effector functions have not been well characterized. As such, the objective of the present study was to gain further insight into the immunological role of thrombocytes by analyzing their responses to treatment with ligands for TLR4 and TLR21. To this end, we quantified the relative expression of several immune system genes at 1, 3, 8 and 18 hours post-treatment using real-time RT-PCR. Furthermore, production of nitric oxide and phagocytic activity of thrombocytes was measured after their activation with TLR ligands. We found that thrombocytes constitutively express transcripts for both pro- and anti-inflammatory cytokines, in addition to those associated with anti-viral responses and antigen presentation. Moreover, we found that both LPS and CpG oligodeoxynucleotides (ODN induced robust pro-inflammatory responses in thrombocytes, as characterized by more than 100 fold increase in interleukin (IL-1β, IL-6 and IL-8 transcripts, while only LPS enhanced nitric oxide production and phagocytic capabilities. Future studies may be aimed at examining the responses of thrombocytes to other TLR ligands.

  11. An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

    Science.gov (United States)

    Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon

    2014-05-27

    Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.

  12. Quantum localization and bound-state formation in Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Franzosi, Roberto; Giampaolo, Salvatore M.; Illuminati, Fabrizio

    2010-01-01

    We discuss the possibility of exponential quantum localization in systems of ultracold bosonic atoms with repulsive interactions in open optical lattices without disorder. We show that exponential localization occurs in the maximally excited state of the lowest energy band. We establish the conditions under which the presence of the upper energy bands can be neglected, determine the successive stages and the quantum phase boundaries at which localization occurs, and discuss schemes to detect it experimentally by visibility measurements. The discussed mechanism is a particular type of quantum localization that is intuitively understood in terms of the interplay between nonlinearity and a bounded energy spectrum.

  13. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.

    2016-06-22

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  14. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

    2016-01-01

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  15. Upper bounds for reversible circuits based on Young subgroups

    DEFF Research Database (Denmark)

    Abdessaied, Nabila; Soeken, Mathias; Thomsen, Michael Kirkedal

    2014-01-01

    We present tighter upper bounds on the number of Toffoli gates needed in reversible circuits. Both multiple controlled Toffoli gates and mixed polarity Toffoli gates have been considered for this purpose. The calculation of the bounds is based on a synthesis approach based on Young subgroups...... that results in circuits using a more generalized gate library. Starting from an upper bound for this library we derive new bounds which improve the existing bound by around 77%....

  16. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  17. Kinetic theory in maximal-acceleration invariant phase space

    International Nuclear Information System (INIS)

    Brandt, H.E.

    1989-01-01

    A vanishing directional derivative of a scalar field along particle trajectories in maximal acceleration invariant phase space is identical in form to the ordinary covariant Vlasov equation in curved spacetime in the presence of both gravitational and nongravitational forces. A natural foundation is thereby provided for a covariant kinetic theory of particles in maximal-acceleration invariant phase space. (orig.)

  18. IIB solutions with N>28 Killing spinors are maximally supersymmetric

    International Nuclear Information System (INIS)

    Gran, U.; Gutowski, J.; Papadopoulos, G.; Roest, D.

    2007-01-01

    We show that all IIB supergravity backgrounds which admit more than 28 Killing spinors are maximally supersymmetric. In particular, we find that for all N>28 backgrounds the supercovariant curvature vanishes, and that the quotients of maximally supersymmetric backgrounds either preserve all 32 or N<29 supersymmetries

  19. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Gnaiger, Erich; Calbet, Jose A L

    2011-01-01

    Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial respira...

  20. Pace's Maxims for Homegrown Library Projects. Coming Full Circle

    Science.gov (United States)

    Pace, Andrew K.

    2005-01-01

    This article discusses six maxims by which to run library automation. The following maxims are discussed: (1) Solve only known problems; (2) Avoid changing data to fix display problems; (3) Aut viam inveniam aut faciam; (4) If you cannot make it yourself, buy something; (5) Kill the alligator closest to the boat; and (6) Just because yours is…