WorldWideScience

Sample records for cation-pi interactions stabilize

  1. Cation-pi interactions stabilize the structure of the antimicrobial peptide indolicidin near membranes: molecular dynamics simulations

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Kaznessis, Yiannis N

    2007-01-01

    We implemented molecular dynamics simulations of the 13-residue antimicrobial peptide indolicidin (ILPWKWPWWPWRR-NH2) in dodecylphosphocholine (DPC) and sodium dodecyl sulfate (SDS) micelles. In DPC, a persistent cation-pi interaction between TRP11 and ARG13 defined the structure of the peptide...... near the interface. A transient cation-pi interaction was also observed between TRP4 and the choline group on DPC lipids. We also implemented simulation of a mutant of indolicidin in the DPC micelle where TRP11 was replaced by ALA11. As a result of the mutation, the boat-shaped conformation is lost...

  2. The geometry and efficacy of cation-pi interactions in a diagonal position of a designed beta-hairpin.

    Science.gov (United States)

    Tatko, Chad D; Waters, Marcey L

    2003-11-01

    Cation-pi interactions are common in proteins, but their contribution to the stability and specificity of protein structure has not been well established. In this study, we examined the impact of cation-pi interactions in a diagonal position of a beta-hairpin peptide through comparison of the interaction of Phe or Trp with Lys or Arg. The diagonal interactions ranged from -0.20 to -0.48 kcal/mole. Our experimental values for the diagonal cation-pi interactions are similar to those found in alpha-helical studies. Upfield shifting of the Lys and Arg side chains indicates that the geometries of cation-pi interactions adopted in the 12-residue beta-hairpin are comparable to those found in protein structures. The Lys was found to interact through the polarized Cepsilon, and the Arg is stacked against the aromatic ring of Phe or Trp. Folding of these peptides was found to be enthalpically favorable (DeltaH degrees equals approximately -3 kcal/mole) and entropically unfavorable (DeltaS degrees equals approximately -8 cal mole(-1) K(-1)).

  3. Cation-{pi}-interaction promoted aggregation of aromatic molecules and energy transfer within Y zeolites

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, K.J.; Sunoj, R.B.; Chandrasekhar, J.; Ramamurthy, V.

    2000-05-30

    Photophysical studies of naphthalene confirm that aromatic molecules tend to aggregate within cation exchanged Y zeolites. Ground-state aggregation is traced to the presence of cation-aromatic {pi}-interaction. Solvents that can coordinate to the cation turn off the cation-aromatic interaction, and consequently aggregation does not occur in zeolites that are impregnated with the above solvents. The solvent that exhibits a maximum in such an effect is water. MP2 calculations on cation-benzene dimer indicate that cation-{pi}-interaction results in stabilization of the {pi}-stacked benzene dimer. Results of MP2 calculations are consistent with the formation of ground-state {pi}-stacked aggregates of naphthalene molecules within Y zeolites.

  4. Compensation of steric demand by cation-pi interactions, cobaltocenium cations as guests in tetraurea calix[4]arene dimers.

    Science.gov (United States)

    Frish, Limor; Vysotsky, Myroslav O; Böhmer, Volker; Cohen, Yoram

    2003-06-07

    The affinities of ferrocene (2) and the cobaltocenium cation (3+), which have roughly the same size and differ in their charge, towards the inner cavity of the dimeric capsule formed by tetraurea calix[4]arene (1) were studied in C2D4Cl2 solutions. While 3+, which occupies more than 75% of the internal volume of the dimer, is readily encapsulated this is not the case for 2. This is probably due to cation-pi interactions, which operate only between 3+ and the aromatic rings of the calix[4]arene dimer. We found that the affinity of the cobaltocenium cation is higher than that of the tropylium cation (4+) and is only 2-3 times less than that of the tetraethylammoniun cation (5+). From the variable temperature 1H NMR spectra of this capsule, the free energy of activation at 298 K (deltaGdouble dagger(298K)) for the reorientation of the hydrogen bonded belt between the two parts of the dimer could be determined by total line shape analysis for the aromatic protons of the calixarene. The value of 14.3 +/- 0.2 kcal mol(-1) for the dimeric capsules of 3+ PF6- is very similar to the free activation energy found for dimeric capsules of 1 with 4+ PF6- and 5+ PF6- in C2D4Cl2. It becomes significantly lower, if PF6- is replaced by BF4-. We also found that ten times more DMSO is needed to disrupt the capsule 1 x 3+ x 1 than the corresponding 1 x 1 dimer containing benzene as guest. This demonstrates again the importance of the cation-pi interactions for the stability of such hydrogen-bonded dimeric capsules.

  5. A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Millen, Kat S; Hanek, Ariele P;

    2008-01-01

    Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains pr...

  6. Enhanced sorption of polycyclic aromatic hydrocarbons to tetra-alkyl ammonium modified smectites via cation-pi interactions.

    Science.gov (United States)

    Qu, Xiaolei; Liu, Ping; Zhu, Dongqiang

    2008-02-15

    The objective of this study was to characterize molecular sorptive interactions of polycyclic aromatic hydrocarbons (PAHs) by organoclays modified with quaternary ammonium cations. Three PAHs, naphthalene (NAPH), phenanthrene (PHEN), and pyrene (PYR), and three chlorobenzenes, 1,2-dichlorobenzene (DCB), 1,2,4,5-tetrachlorobenzene (TeCB), and pentachlorobenzene (PtCB), were sorbed from aqueous solution to reference montmorillonite clays (SWy-2) exchanged respectively with tetramethyl ammonium (TMA), tetraethyl ammonium (TEA), tetra-n-butyl ammonium (TBA), and hexadecyltrimethyl ammonium (HDTMA) cations. Solute hydrophobicities are compared between PAHs and chlorobenzenes using the solute n-octanol-water partition coefficient, n-hexadecane-water partition coefficient, and polyethylene-water distribution coefficient. The PAHs show several- to more than 10-fold greater sorption than the chlorobenzenes having close hydrophobicities but fewer delocalized pi electrons (NAPH/DCB, PHEN/TeCB, and PYR/ PtCB) by TEA-, TBA-, and HDTMA-clays. Furthermore, the PAHs show greater trends of solubility enhancement than the compared chlorobenzenes by TMA, TEA, and TBA in aqueous solution. The enhanced sorption and aqueous solubility of PAHs are best described by cation-pi interactions between ammonium cations and PAHs relative to chlorobenzenes that are incapable of such interactions. Cation-pi complexation between PAHs and tetra-alkyl ammonium cations in chloroform was verified by ring-current-induced upfield chemical shifts of the alkyl groups of cations in the 1H NMR spectrum.

  7. Improving the Force Field Description of Tyrosine-Choline Cation-pi Interactions : QM Investigation of Phenol-N(Me)(4)(+) Interactions

    NARCIS (Netherlands)

    Khan, Hanif M.; Grauffel, Cedric; Broer, Ria; MacKerell, Alexander D.; Havenith, Remco W. A.; Reuter, Nathalie

    2016-01-01

    Cation-pi interactions between tyrosine amino acids and compounds containing N,N,N-trimethylethanolammonium (N(CH3)(3)) are involved in the recognition of histone tails by chromodomains and in the recognition of phosphatidylcholine (PC) phospholipids by membrane-binding proteins. Yet, the lack of ex

  8. A multinuclear solid-state NMR study of alkali metal ions in tetraphenylborate salts, M[BPh4] (M = Na, K, Rb and Cs): what is the NMR signature of cation-pi interactions?

    Science.gov (United States)

    Wu, Gang; Terskikh, Victor

    2008-10-16

    We report a multinuclear solid-state ( (23)Na, (39)K, (87)Rb, (133)Cs) NMR study of tetraphenylborate salts, M[BPh 4] (M = Na, K, Rb, Cs). These compounds are isostructural in the solid state with the alkali metal ion surrounded by four phenyl groups resulting in strong cation-pi interactions. From analyses of solid-state NMR spectra obtained under stationary and magic-angle spinning (MAS) conditions at 11.75 and 21.15 T, we have obtained the quadrupole coupling constants, C Q, and the chemical shift tensor parameters for the alkali metal ions in these compounds. We found that the observed quadrupole coupling constant for M (+) in M[BPh 4] is determined by a combination of nuclear quadrupole moment, Sternheimer antishielding factor, and unit cell dimensions. On the basis of a comparison between computed paramagnetic and diamagnetic contributions to the total chemical shielding values for commonly found cation-ligand interactions, we conclude that cation-pi interactions give rise to significantly lower paramagnetic shielding contributions than other cation-ligand interactions. As a result, highly negative chemical shifts are expected to be the NMR signature for cations interacting exclusively with pi systems.

  9. Fibrinogen stability under surfactant interaction.

    Science.gov (United States)

    Hassan, Natalia; Barbosa, Leandro R S; Itri, Rosangela; Ruso, Juan M

    2011-10-01

    Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen's secondary structure is affected by all three studied surfactants (decrease in α-helix and an increase in β-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. PIC: Protein Interactions Calculator.

    Science.gov (United States)

    Tina, K G; Bhadra, R; Srinivasan, N

    2007-07-01

    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bonds, interactions between hydrophobic residues, ionic interactions, hydrogen bonds, aromatic-aromatic interactions, aromatic-sulphur interactions and cation-pi interactions within a protein or between proteins in a complex. Interactions are calculated on the basis of standard, published criteria. The identified interactions between residues can be visualized using a RasMol and Jmol interface. The advantage with PIC server is the easy availability of inter-residue interaction calculations in a single site. It also determines the accessible surface area and residue-depth, which is the distance of a residue from the surface of the protein. User can also recognize specific kind of interactions, such as apolar-apolar residue interactions or ionic interactions, that are formed between buried or exposed residues or near the surface or deep inside.

  11. Phase transformations, stability, and materials interactions

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J.W. Jr.; Brewer, L.; Cost, J.R.; Shewmon, P.

    1977-07-01

    The proceedings of the Materials Sciences Workshop on Phase Transformations, Stability, and Materials Interactions are divided into sections according to the following topics: (I) workshop scope and priorities; (II) study group reports--ERDA mission needs; (III) study group reports--technical area research priorities. (SDF)

  12. Stability of Horndeski vector-tensor interactions

    Energy Technology Data Exchange (ETDEWEB)

    Jiménez, Jose Beltrán [Centre for Cosmology, Particle Physics and Phenomenology, Institute of Mathematics and Physics, Louvain University, 2 Chemin du Cyclotron, Louvain-la-Neuve, 1348 (Belgium); Durrer, Ruth; Heisenberg, Lavinia [Département de Physique Théorique and Center for Astroparticle Physics, Université de Genève, 24 quai Ansermet, Genève 4, CH-1211 (Switzerland); Thorsrud, Mikjel, E-mail: jose.beltran@uclouvain.be, E-mail: ruth.durrer@unige.ch, E-mail: lavinia.heisenberg@unige.ch, E-mail: mikjel.thorsrud@astro.uio.no [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, Oslo, N-0315 (Norway)

    2013-10-01

    We study the Horndeski vector-tensor theory that leads to second order equations of motion and contains a non-minimally coupled abelian gauge vector field. This theory is remarkably simple and consists of only 2 terms for the vector field, namely: the standard Maxwell kinetic term and a coupling to the dual Riemann tensor. Furthermore, the vector sector respects the U(1) gauge symmetry and the theory contains only one free parameter, M{sup 2}, that controls the strength of the non-minimal coupling. We explore the theory in a de Sitter spacetime and study the presence of instabilities and show that it corresponds to an attractor solution in the presence of the vector field. We also investigate the cosmological evolution and stability of perturbations in a general FLRW spacetime. We find that a sufficient condition for the absence of ghosts is M{sup 2} > 0. Moreover, we study further constraints coming from imposing the absence of Laplacian instabilities. Finally, we study the stability of the theory in static and spherically symmetric backgrounds (in particular, Schwarzschild and Reissner-Nordström-de Sitter). We find that the theory, quite generally, do have ghosts or Laplacian instabilities in regions of spacetime where the non-minimal interaction dominates over the Maxwell term. We also calculate the propagation speed in these spacetimes and show that superluminality is a quite generic phenomenon in this theory.

  13. Stability of Horndeski vector-tensor interactions

    Science.gov (United States)

    Beltrán Jiménez, Jose; Durrer, Ruth; Heisenberg, Lavinia; Thorsrud, Mikjel

    2013-10-01

    We study the Horndeski vector-tensor theory that leads to second order equations of motion and contains a non-minimally coupled abelian gauge vector field. This theory is remarkably simple and consists of only 2 terms for the vector field, namely: the standard Maxwell kinetic term and a coupling to the dual Riemann tensor. Furthermore, the vector sector respects the U(1) gauge symmetry and the theory contains only one free parameter, M2, that controls the strength of the non-minimal coupling. We explore the theory in a de Sitter spacetime and study the presence of instabilities and show that it corresponds to an attractor solution in the presence of the vector field. We also investigate the cosmological evolution and stability of perturbations in a general FLRW spacetime. We find that a sufficient condition for the absence of ghosts is M2 > 0. Moreover, we study further constraints coming from imposing the absence of Laplacian instabilities. Finally, we study the stability of the theory in static and spherically symmetric backgrounds (in particular, Schwarzschild and Reissner-Nordström-de Sitter). We find that the theory, quite generally, do have ghosts or Laplacian instabilities in regions of spacetime where the non-minimal interaction dominates over the Maxwell term. We also calculate the propagation speed in these spacetimes and show that superluminality is a quite generic phenomenon in this theory.

  14. Stability and dynamics of magnetocapillary interactions

    CERN Document Server

    Chinomona, Rujeko; Mitchell, William H; Yao, Yao; Spagnolie, Saverio E

    2014-01-01

    Recent experiments have shown that floating ferromagnetic beads, under the influence of an oscillating background magnetic field, can move along a liquid-air interface in a sustained periodic locomotion [Lumay et al., Soft Matter, 2013, 9, 2420]. Dynamic activity arises from a periodically induced dipole-dipole repulsion between the beads acting in concert with capillary attraction. We investigate analytically and numerically the stability and dynamics of this magnetocapillary swimming, and explore other related topics including the steady and periodic equilibrium configurations of two and three beads. The swimming speed and system stability depend on a dimensionless measure of the relative repulsive and attractive forces which we term the magnetocapillary number. An oscillatory magnetic field may stabilize an otherwise unstable collinear configuration, and striking behaviors are observed in fast transitions to and from locomotory states, offering insight into the behavior and self-assembly of interface-bound...

  15. Dispersion Interactions and the Stability of Amine Dimers

    Science.gov (United States)

    Guttmann, Robin

    2017-01-01

    Abstract Weak, intermolecular interactions in amine dimers were studied by using the combination of a dispersionless density functional and a function that describes the dispersion contribution to the interaction energy. The validity of this method was shown by comparison of structural and energetic properties with data obtained with a conventional density functional and the coupled cluster method. The stability of amine dimers was shown to depend on the size, the shape, and the relative orientation of the alkyl substituents, and it was shown that the stabilization energy for large substituents is dominated by dispersion interactions. In contrast to traditional chemical explanations that attribute stability and condensed matter properties solely to hydrogen bonding and, thus, to the properties of the atoms forming the hydrogen bridge, we show that without dispersion interactions not even the stability and structure of the ammonia dimer can be correctly described. The stability of amine dimers depends crucially on the interaction between the non‐polar alkyl groups, which is dominated by dispersion interactions. This interaction is also responsible for the energetic part of the free energy interaction used to describe hydrophobic interactions in liquid alkanes. The entropic part has its origin in the high degeneracy of the interaction energy for complexes of alkane molecules, which exist in a great variety of conformers, having their origin in internal rotations of the alkane chains. PMID:28794953

  16. Monetary and fiscal policy interaction and government debt stabilization

    NARCIS (Netherlands)

    van Aarle, B.; Bovenberg, A.L.; Raith, M.

    1995-01-01

    In many developing and developed countries, government debt stabilization is an important policy issue. This paper models the strategic interaction between the monetary authorities who control monetization and the fiscal authorities who control primary fiscal deficits. Government debt dynamics are

  17. Predicting Marital Happiness and Stability from Newlywed Interactions.

    Science.gov (United States)

    Gottman, John M.; Coan, James; Carrere, Sybil; Swanson, Catherine

    1998-01-01

    Marital interaction processes that are predictive of divorce or marital stability and processes that discriminate between happily and unhappily married stable couples are explored (N=130). Seven types of process models are examined, and results are discussed. Divorce and stability were predicted with 83% accuracy, and satisfaction with 80%…

  18. Stabilization of 2D quantum gravity by branching interactions

    CERN Document Server

    Diego, O

    1995-01-01

    In this paper the stabilization of 2D quantum Gravity by branching interactions is considered. The perturbative expansion and the first nonperturbative term of the stabilized model are the same than the unbounded matrix model which define pure Gravity, but it has new nonperturbative effects that survives in the continuum limit.

  19. Stability of Horndeski vector-tensor interactions

    CERN Document Server

    Jiménez, Jose Beltrán; Heisenberg, Lavinia; Thorsrud, Mikjel

    2013-01-01

    We study the Horndeski vector-tensor theory that leads to second order equations of motion and contains a non-minimally coupled abelian gauge vector field. This theory is remarkably simple and consists of only 2 terms for the vector field, namely: the standard Maxwell kinetic term and a coupling to the dual Riemann tensor. Furthermore, the vector sector respects the U(1) gauge symmetry and the theory contains only one free parameter, M^2, that controls the strength of the non-minimal coupling. We explore the theory in a de Sitter spacetime and study the presence of instabilities and show that it corresponds to an attractor solution in the presence of the vector field. We also investigate the cosmological evolution and stability of perturbations in a general FLRW spacetime. We find that a sufficient condition for the absence of ghosts is M^2>0. Moreover, we study further constraints coming from imposing the absence of Laplacian instabilities. Finally, we study the stability of the theory in static and spherica...

  20. The effects of interaction compartments on stability for competitive systems.

    Science.gov (United States)

    Rozdilsky, Ian D; Stone, Lewi; Solow, Andrew

    2004-03-21

    The interactions between species are unlikely to be randomly arranged, and there is increasing evidence that most interactions occur within small species sub-groups, or compartments, that do not strongly interact with one another. We examine whether arranging the interactions of a competitive system into compartments influences the system properties of linear stability, feasibility, reactivity, and biomass stability, thereby altering the likelihood of species persistence. Model Lotka-Volterra systems of diffuse competition were analysed with interactions arranged randomly and in compartments. It was found, using a variety of dynamical measures, that arranging interactions into compartments enhances the likelihood of species persistence. Since many natural competitive systems appear to have interactions arranged within compartments, this may be an outcome of the positive attributes that this form of organization offers.

  1. Stability of family interaction from ages 6 to 18.

    Science.gov (United States)

    Loeber, R; Drinkwater, M; Yin, Y; Anderson, S J; Schmidt, L C; Crawford, A

    2000-08-01

    Research has demonstrated the stability of juvenile offending during childhood and adolescence but generally has not focused on the continuity of family interactions associated with juvenile offending. The present report focused on the stability of several family interaction events and attributes (i.e., physical punishment, communication, supervision, positive parenting, and parent-child relationship) for a large sample of male adolescents and their primary caretakers, drawn from a multiyear longitudinal study that represented middle childhood through late adolescence (ages 6-18). We also assessed the impact of ethnicity, family composition, teenage motherhood, and youth delinquency on these interactions. Test-retest correlations and growth-curve analyses were used to assess relative and absolute stability of the interactions, respectively. As predicted, relative stability of family interaction was high. There was an absolute change in scores of physical punishment (decreased) compared to poor supervision and low positive parenting (both increased), whereas poor communication and bad relationship with the caretaker did not measurably change with age. Single-parent families and families with teenage mothers experienced significantly worse interactions over time than did families consisting of two biological parents present in the household. These findings are discussed in relation to the development of juvenile offending.

  2. Monetary and fiscal policy interaction and government debt stabilization

    NARCIS (Netherlands)

    van Aarle, B.; Bovenberg, A.L.; Raith, M.

    1995-01-01

    In many developing and developed countries, government debt stabilization is an important policy issue. This paper models the strategic interaction between the monetary authorities who control monetization and the fiscal authorities who control primary fiscal deficits. Government debt dynamics are d

  3. Stability and modal analysis of shock/boundary layer interactions

    Science.gov (United States)

    Nichols, Joseph W.; Larsson, Johan; Bernardini, Matteo; Pirozzoli, Sergio

    2016-06-01

    The dynamics of oblique shock wave/turbulent boundary layer interactions is analyzed by mining a large-eddy simulation (LES) database for various strengths of the incoming shock. The flow dynamics is first analyzed by means of dynamic mode decomposition (DMD), which highlights the simultaneous occurrence of two types of flow modes, namely a low-frequency type associated with breathing motion of the separation bubble, accompanied by flapping motion of the reflected shock, and a high-frequency type associated with the propagation of instability waves past the interaction zone. Global linear stability analysis performed on the mean LES flow fields yields a single unstable zero-frequency mode, plus a variety of marginally stable low-frequency modes whose stability margin decreases with the strength of the interaction. The least stable linear modes are grouped into two classes, one of which bears striking resemblance to the breathing mode recovered from DMD and another class associated with revolving motion within the separation bubble. The results of the modal and linear stability analysis support the notion that low-frequency dynamics is intrinsic to the interaction zone, but some continuous forcing from the upstream boundary layer may be required to keep the system near a limit cycle. This can be modeled as a weakly damped oscillator with forcing, as in the early empirical model by Plotkin (AIAA J 13:1036-1040, 1975).

  4. Stability and modal analysis of shock/boundary layer interactions

    Science.gov (United States)

    Nichols, Joseph W.; Larsson, Johan; Bernardini, Matteo; Pirozzoli, Sergio

    2017-02-01

    The dynamics of oblique shock wave/turbulent boundary layer interactions is analyzed by mining a large-eddy simulation (LES) database for various strengths of the incoming shock. The flow dynamics is first analyzed by means of dynamic mode decomposition (DMD), which highlights the simultaneous occurrence of two types of flow modes, namely a low-frequency type associated with breathing motion of the separation bubble, accompanied by flapping motion of the reflected shock, and a high-frequency type associated with the propagation of instability waves past the interaction zone. Global linear stability analysis performed on the mean LES flow fields yields a single unstable zero-frequency mode, plus a variety of marginally stable low-frequency modes whose stability margin decreases with the strength of the interaction. The least stable linear modes are grouped into two classes, one of which bears striking resemblance to the breathing mode recovered from DMD and another class associated with revolving motion within the separation bubble. The results of the modal and linear stability analysis support the notion that low-frequency dynamics is intrinsic to the interaction zone, but some continuous forcing from the upstream boundary layer may be required to keep the system near a limit cycle. This can be modeled as a weakly damped oscillator with forcing, as in the early empirical model by Plotkin (AIAA J 13:1036-1040, 1975).

  5. Stabilization of protein-protein interactions by small molecules.

    Science.gov (United States)

    Giordanetto, Fabrizio; Schäfer, Anja; Ottmann, Christian

    2014-11-01

    Protein-protein interactions (PPIs) are implicated in every disease and mastering the ability to influence PPIs with small molecules would considerably enlarge the druggable genome. Whereas inhibition of PPIs has repeatedly been shown to work successfully, targeted stabilization of PPIs is underrepresented in the literature. This is all the more surprising because natural products like FK506, rapamycin, brefeldin, forskolin and fusicoccin confer their physiological activity by stabilizing specific PPIs. However, recently a number of very interesting synthetic molecules have been reported from drug discovery projects that indeed achieve their desired activities by stabilizing either homo- or hetero-oligomeric complexes of their target proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Graph theory and stability analysis of protein complex interaction networks.

    Science.gov (United States)

    Huang, Chien-Hung; Chen, Teng-Hung; Ng, Ka-Lok

    2016-04-01

    Protein complexes play an essential role in many biological processes. Complexes can interact with other complexes to form protein complex interaction network (PCIN) that involves in important cellular processes. There are relatively few studies on examining the interaction topology among protein complexes; and little is known about the stability of PCIN under perturbations. We employed graph theoretical approach to reveal hidden properties and features of four species PCINs. Two main issues are addressed, (i) the global and local network topological properties, and (ii) the stability of the networks under 12 types of perturbations. According to the topological parameter classification, we identified some critical protein complexes and validated that the topological analysis approach could provide meaningful biological interpretations of the protein complex systems. Through the Kolmogorov-Smimov test, we showed that local topological parameters are good indicators to characterise the structure of PCINs. We further demonstrated the effectiveness of the current approach by performing the scalability and data normalization tests. To measure the robustness of PCINs, we proposed to consider eight topological-based perturbations, which are specifically applicable in scenarios of targeted, sustained attacks. We found that the degree-based, betweenness-based and brokering-coefficient-based perturbations have the largest effect on network stability.

  7. Improved physical stability of amorphous state through acid base interactions.

    Science.gov (United States)

    Telang, Chitra; Mujumdar, Siddharthya; Mathew, Michael

    2009-06-01

    To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically.

  8. Stabilizer-Guided Inhibition of Protein-Protein Interactions.

    Science.gov (United States)

    Milroy, Lech-Gustav; Bartel, Maria; Henen, Morkos A; Leysen, Seppe; Adriaans, Joris M C; Brunsveld, Luc; Landrieu, Isabelle; Ottmann, Christian

    2015-12-21

    The discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Stability as a natural selection mechanism on interacting networks

    Directory of Open Access Journals (Sweden)

    Francisco A. Tamarit

    2010-02-01

    Full Text Available Biological networks of interacting agents exhibit similar topological properties for a wide range of scales, from cellular to ecological levels, suggesting the existence of a common evolutionary origin. A general evolutionary mechanism based on global stability has been proposed recently  [J I Perotti, et al., Phys. Rev. Lett. 103, 108701 (2009]. This mechanism was incorporated into a  model of a growing network of interacting agents in which each new agent's membership in the network is determined by the agent's effect on the network's global stability. In this work, we analyze different quantities that characterize the topology of the emerging networks, such as global connectivity, clustering and average nearest neighbors degree, showing that they reproduce scaling behaviors frequently observed in several biological systems. The influence of the stability selection  mechanism on the dynamics associated to the resulting network, as well as  the interplay  between some topological and functional features are also analyzed.Received: 17 July 2010; Accepted: 27 September 2010; Edited by: D. H. Zanette; Reviewed by: V. M. Eguiluz, Inst. Fisica Interdisciplinar y Sist. Complejos, Palma de Mallorca, Spain; DOI: 10.4279/PIP.020005

  10. Structure, Stability and Interaction Studies on Nucleotide Analogue Systems

    Directory of Open Access Journals (Sweden)

    R. Kanakaraju

    2003-08-01

    Full Text Available Abstract: Most of the biological molecules have a good interaction with water molecules. The hydrogen bonding interactions with the structural analogues of nucleic acid phosphate group namely dimethyl phosphate anion (DMP and diethyl phosphate anion (DEP are studied employing the ab initio and density functional theory methods. Inspections have been made to locate the reactive sites for the interactions of isomeric forms of mono, di and tri hydrates of alkyl phosphate anion using the above theories. It reveals, water molecules have a very strong interaction with the phosphate group in both the molecules and their interactions induce the changes in the structural parameters of the PO4 group for both the DMP and DEP anions. The optimized structural parameters, total energy, dipole moment and rotational constants are calculated and are compared with the available experimental values. The chemical hardness and chemical potential for these complexes have been calculated at HF/6-31G* level of theory and discussed the conformational stability of these complexes.

  11. Static interactions and stability of matter in Rindler space

    CERN Document Server

    Lenz, F; Yazaki, K

    2010-01-01

    Dynamical issues associated with quantum fields in Rindler space are addressed in a study of the interaction between two sources at rest generated by the exchange of scalar particles, photons and gravitons. These static interaction energies in Rindler space are shown to be scale invariant, complex quantities. The imaginary part will be seen to have its quantum mechanical origin in the presence of an infinity of zero modes in uniformly accelerated frames which in turn are related to the radiation observed in inertial frames. The impact of a uniform acceleration on the stability of matter and the properties of particles is discussed and estimates are presented of the instability of hydrogen atoms when approaching the horizon.

  12. Stabilization of perturbed Boolean network attractors through compensatory interactions

    Science.gov (United States)

    2014-01-01

    Background Understanding and ameliorating the effects of network damage are of significant interest, due in part to the variety of applications in which network damage is relevant. For example, the effects of genetic mutations can cascade through within-cell signaling and regulatory networks and alter the behavior of cells, possibly leading to a wide variety of diseases. The typical approach to mitigating network perturbations is to consider the compensatory activation or deactivation of system components. Here, we propose a complementary approach wherein interactions are instead modified to alter key regulatory functions and prevent the network damage from triggering a deregulatory cascade. Results We implement this approach in a Boolean dynamic framework, which has been shown to effectively model the behavior of biological regulatory and signaling networks. We show that the method can stabilize any single state (e.g., fixed point attractors or time-averaged representations of multi-state attractors) to be an attractor of the repaired network. We show that the approach is minimalistic in that few modifications are required to provide stability to a chosen attractor and specific in that interventions do not have undesired effects on the attractor. We apply the approach to random Boolean networks, and further show that the method can in some cases successfully repair synchronous limit cycles. We also apply the methodology to case studies from drought-induced signaling in plants and T-LGL leukemia and find that it is successful in both stabilizing desired behavior and in eliminating undesired outcomes. Code is made freely available through the software package BooleanNet. Conclusions The methodology introduced in this report offers a complementary way to manipulating node expression levels. A comprehensive approach to evaluating network manipulation should take an "all of the above" perspective; we anticipate that theoretical studies of interaction modification

  13. Normal and friction stabilization techniques for interactive rigid body constraint-based contact force computations

    DEFF Research Database (Denmark)

    2010-01-01

    We present a novel, yet simple, method for stabilization of normal forces. A normal stabilization term, carefully designed from hypotheses about interactive usability, is added to the contact force problem. Further, we propose friction stabilization as a completely new stabilization paradigm in i...

  14. The Stability of Icosahedral Cluster and the Range of Interaction Potential

    Institute of Scientific and Technical Information of China (English)

    DING Feng; WANG Jin-Lan; SHEN Wei-Feng; WANG Bao-Lin; LI Hui; WANG Guang-Hou

    2001-01-01

    The relation between the stability of icosahedral clusters and the range of interaction potential is discussed.We found that the stability of icosahedral clusters nay decrease with decreasing range of interaction potential. A simple formula about the critical number of icosahedral clusters and the range of interaction potential (M1/3c = A1 + A2r2eff)was proposed. The calculation of the stability of icosahedral fullerence molecular clusters shows that our idea is right.``

  15. Stability of a skyrmion and interaction of magnons

    Science.gov (United States)

    Aristov, D. N.; Matveeva, P. G.

    2016-12-01

    The stability of a single Belavin-Polyakov (BP) skyrmion in an isotropic Heisenberg ferromagnet is studied. Such a skyrmion is higher in energy than the uniform ferromagnetic state and is thus metastable. Starting from the lattice model in two spatial dimensions and using Maleyev-Dyson representation for spin operators, we examine the effects of magnon-magnon interaction for two quantities at T =0 . First, we discuss self-energy corrections to the magnon energy. Second, we analyze the two-particle Green's function and possible bound states of two magnons. The simplicity of the model makes possible full analytic treatment of all relevant processes. We found that the magnons remain well-defined quasiparticles with a finite lifetime. The bound states of two magnons are suppressed near the skyrmion, although they are not excluded far away from it. A resonance for magnons of the dilational mode in the vicinity of the BP skyrmion is also found, which leads to a redistribution of the spectral weight. We conclude that the BP skyrmion as the classical topological object is not destroyed by quantum fluctuations.

  16. Thermal stability conditions of a weakly interacting Fermi gas in a weak magnetic field

    Institute of Scientific and Technical Information of China (English)

    Fudian Men; Hui Liu; Houyu Zhu

    2009-01-01

    On the basis of the results derived from pseudopotential method and ensemble theory,thermal stability of a weakly interacting Fermi gas in a weak magnetic field is studied by using analytical method of thermodynamics.The exact analytical expressions of stability conditions at different temperatures are given,and the effects of interactions as well as magnetic field on the stability of the system are discussed.It is shown that there is an upper-limit magnetic field for the stability of the system at low temperatures,and there is an attractive dividing value at high temperatures.If attractive interaction is lower than the critical value,the stability of the system has no request for magnetic field,but if attractive interaction is higher than the dividing value,a lower-limit magnetic field exists for the stability of the system.

  17. Stability analysis of interacting queues in the ALOHA system

    Science.gov (United States)

    Rao, Ramesh

    The author considers the finite-user, infinite-buffer slotted ALOHA system and analytically extends the known bounds for its stability region. The technique used consists of expressing the stability region in terms of certain status probabilities and then solving for the status probabilities by using results from the analysis of dependent queues and that of Markov chains.

  18. Stabilization of protein-protein interactions in drug discovery.

    Science.gov (United States)

    Andrei, Sebastian A; Sijbesma, Eline; Hann, Michael; Davis, Jeremy; O'Mahony, Gavin; Perry, Matthew W D; Karawajczyk, Anna; Eickhoff, Jan; Brunsveld, Luc; Doveston, Richard G; Milroy, Lech-Gustav; Ottmann, Christian

    2017-09-01

    PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.

  19. Interaction of NiO with yttria-stabilized zirconia

    DEFF Research Database (Denmark)

    Kuzjukevics, A.; Linderoth, Søren

    1997-01-01

    As-prepared and heat treated plasma-produced 8 and 10 mol% yttria-stabilized zirconia (YSZ) powders doped with 0, 5, 10 and 75 mol% NiO have been investigated by XRD. The as-prepared powders are mixtures of metastable tetragonal and cubic phases but they transform to a single YSZ phase upon heat...... treatment above 1200 degrees C. The solubility of NiO in yttria-stabilized zirconia is less than 2 mol% at 1600 degrees C and varies little within the investigated yttria concentration range. The solubility increases with increasing temperature and the total NiO concentration. The activation energy...

  20. Genotype by environment interactions and yield stability of stem ...

    African Journals Online (AJOL)

    GREGORY

    2011-06-01

    Jun 1, 2011 ... stability of stem borer resistant maize hybrids in Kenya. Yoseph .... additive model with environments as the only main effects. A two- ..... silage dry matter content of 18 Dutch maize varieties. However .... Genetic components of yield ... modification, and protein quality of hybrid and open-pollinated quality.

  1. Thermodynamic stability of a weakly interacting Fermi gas trapped in a harmonic potential

    Institute of Scientific and Technical Information of China (English)

    Men Fu-Dian; Liu Hui; Zhu Hou-Yu

    2008-01-01

    Based on the theoretical results derived from pseudopotential method and local approximation,this paper studies the thermodynamic stability of a weakly interacting Fermi gas trapped in a harmonic potential by using analytical method of thermodynamics.The effects of the interparticle interactions as well as external potential on the thermodynamic stability of the system are discussed.It is shown that the system is stable as for the complete average,but as for local parts,the system is unstable anywhere.This instability shows that the stability conditions of mechanics cannot be satisfied anywhere,and the stability conditions of thermostatics cannot be satisfied somewhere.In addition,the interactions and external potential have direct effects on the local stability of the system.

  2. Kekulene: Structure, stability and nature of H•••H interactions in large PAHs

    Science.gov (United States)

    Poater, J.; Paauwe, J.; Pan, S.; Merino, G.; Guerra, C. Fonseca; Bickelhaupt, F. M.

    2017-09-01

    We have quantum chemically analyzed how the stability of small and larger polycyclic aromatic hydrocarbons (PAHs) is determined by characteristic patterns in their structure using density functional theory at the BLYP/TZ2P level. In particular, we focus on the effect of the nonbonded H•••H interactions that occur in the bay region of kinked (or armchair) PAHs, but not in straight (or zigzag) PAHs. Model systems comprise anthracene, phenanthrene, and kekulene as well as derivatives thereof. Our main goals are: (1) to explore how nonbonded H•••H interactions in armchair configurations of kinked PAHs affect the geometry and stability of PAHs and how their effect changes as the number of such interactions in a PAH increases; (2) to understand the extent of stabilization upon the substitution of a bay Csbnd H fragment by either C• or N; and (3) to examine the origin of such stabilizing/destabilizing interactions.

  3. genotype by environment interaction and grain yield stability ...

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT: Genotypes by environment (GXE) interactions are almost unanimously considered to be ... important tool in plant breeding and this has to be ..... Pakistan Journal of Biological Sci- ... mosome Engineering and Crop Improvement.

  4. Stabilized helical peptides: a strategy to target protein-protein interactions.

    Science.gov (United States)

    Klein, Mark A

    2014-08-14

    Protein-protein interactions are critical for cell proliferation, differentiation, and function. Peptides hold great promise for clinical applications focused on targeting protein-protein interactions. Advantages of peptides include a large chemical space and potential diversity of sequences and structures. However, peptides do present well-known challenges for drug development. Progress has been made in the development of stabilizing alpha helices for potential therapeutic applications. Advantages and disadvantages of different methods of helical peptide stabilization are discussed.

  5. Regulation of PCNA-protein interactions for genome stability

    DEFF Research Database (Denmark)

    Mailand, Niels; Gibbs-Seymour, Ian; Bekker-Jensen, Simon

    2013-01-01

    Proliferating cell nuclear antigen (PCNA) has a central role in promoting faithful DNA replication, providing a molecular platform that facilitates the myriad protein-protein and protein-DNA interactions that occur at the replication fork. Numerous PCNA-associated proteins compete for binding...... to a common surface on PCNA; hence these interactions need to be tightly regulated and coordinated to ensure proper chromosome replication and integrity. Control of PCNA-protein interactions is multilayered and involves post-translational modifications, in particular ubiquitylation, accessory factors...... and regulated degradation of PCNA-associated proteins. This regulatory framework allows cells to maintain a fine-tuned balance between replication fidelity and processivity in response to DNA damage....

  6. Stabilization of quinapril by incorporating hydrogen bonding interactions

    Directory of Open Access Journals (Sweden)

    Roy B

    2009-01-01

    Full Text Available In the present study stability of various known solvates of quinapril hydrochloride has been compared with nitromethane solvate. Nitromethane solvate was found to be more stable compared to other known solvates. Single crystal X-ray diffraction analysis of quinapril nitromethane solvate shows intermolecular hydrogen bonding between quinapril molecule and nitromethane. Stabilization of quinapril by forming strong hydrogen bonding network as in case of co-crystals was further studied by forming co-crystal with tris(hydroxymethylamino methane. Quinapril free base forms a stable salt with tris(hydroxymethylamino methane not reported earlier. Quinapril tris(hydroxymethylamino methane salt found to be stable even at 80° for 72 h i.e. hardly any formation of diketopiperazine and diacid impurity. As expected single crystal X-ray diffraction analysis reveals tris(hydroxymethylamino methane salt of quinapril shows complex hydrogen bonding network between the two entities along with ionic bond. The properties of this stable salt - stable in solid as well as solution phase, might lead to an alternate highly stable formulation.

  7. Patterns in intraspecific interaction strengths and the stability of food webs

    NARCIS (Netherlands)

    Altena, van C.; Hemerik, L.; Heesterbeek, J.A.P.; Ruiter, de P.C.

    2016-01-01

    A common approach to analyse stability of biological communities is to calculate the interaction strength matrix. Problematic in this approach is defining intraspecific interaction strengths, represented by diagonal elements in the matrix, due to a lack of empirical data for these strengths. Theoret

  8. Stability of stationary states of non-local equations with singular interaction potentials

    KAUST Repository

    Fellner, Klemens

    2011-04-01

    We study the large-time behaviour of a non-local evolution equation for the density of particles or individuals subject to an external and an interaction potential. In particular, we consider interaction potentials which are singular in the sense that their first derivative is discontinuous at the origin.For locally attractive singular interaction potentials we prove under a linear stability condition local non-linear stability of stationary states consisting of a finite sum of Dirac masses. For singular repulsive interaction potentials we show the stability of stationary states of uniformly bounded solutions under a convexity condition.Finally, we present numerical simulations to illustrate our results. © 2010 Elsevier Ltd.

  9. High Stability Metal-Protein Interactions Evaluated by Microcalorimetry

    Science.gov (United States)

    2016-04-29

    SECURITY CLASSIFICATION OF: Isothermal titration calorimetry (ITC) is a microcalorimetry technique used to study interactions between biomolecules...took place on July 8, 2015. A third site visit occurred on August 24, 2015 in which the entire wash module including the vacuum pump was replaced...determined that the concentration of MES buffer needs to be no lower than 100 mM (i.e. a 50:1 molar ratio relative to BeSO4) in order to avoid pH

  10. Stability of Numerical Interface Conditions for Fluid/Structure Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Banks, J W; Sjogreen, B

    2009-08-13

    In multi physics computations, where a compressible fluid is coupled with a linearly elastic solid, it is standard to enforce continuity of the normal velocities and of the normal stresses at the interface between the fluid and the solid. In a numerical scheme, there are many ways that the velocity- and stress-continuity can be enforced in the discrete approximation. This paper performs a normal mode analysis to investigate the stability of different numerical interface conditions for a model problem approximated by upwind type of finite difference schemes. The analysis shows that depending on the ratio of densities between the solid and the fluid, some numerical interface conditions are stable up to the maximal CFL-limit, while other numerical interface conditions suffer from a severe reduction of the stable CFL-limit. The paper also presents a new interface condition, obtained as a simplified charcteristic boundary condition, that is proved to not suffer from any reduction of the stable CFL-limit. Numerical experiments in one space dimension show that the new interface condition is stable also for computations with the non-linear Euler equations of compressible fluid flow coupled with a linearly elastic solid.

  11. Quaternary climate - Terrestrial Biosphere Interaction: amplifying or stabilizing?

    Science.gov (United States)

    Claussen, Martin

    2016-04-01

    According to the Gaia hypothesis, interaction between climate and biological processes tend to homeostatically maintain, on a global scale, conditions favourable for life. Does the idea of homeostatic interaction between terrestrial biosphere and climate hold for the Quaternary glacial - interglacial changes? Interpretation of palaeoclimate and palaeobotanic evidence by using climate and Earth system models yields an interesting picture. The synergy between the sea-ice albedo - climate feedback and the taiga-tundra - climate feedback is suggested to amplify the orbitally forced climatic precession. This effect seems to be strong at regional scale, but small at global scale. Various simulations indicate that biogeophysical processes amplify the difference of some 4 to 6 K in global mean temperature between glacial and interglacial climate by some 10 percent. The combined effect of biogeophysical and biogeochemical processes, i.e. processes with involve carbon stored in biomass and soil, is less clear. Theoretical studies suggest that in pre-industrial, interglacial climate, a reduction in boreal and extratropical forests tend to cool the climate and a reduction in tropical forest, to warm the climate. Recent estimates in changes in organic carbon stored under ice sheets and in permafrost point at the possibility that the sum of all terrestrial biogeochemical processes might almost "carbon neutral" to the climate system. If corroborated, this observation would favour the assumption of a dominance of biogeophysical processes amplifying orbitally forced Quaternary climate variations.

  12. Contribution of dipole-dipole interactions to the stability of the collagen triple helix.

    Science.gov (United States)

    Improta, Roberto; Berisio, Rita; Vitagliano, Luigi

    2008-05-01

    Unveiling sequence-stability and structure-stability relationships is a major goal of protein chemistry and structural biology. Despite the enormous efforts devoted, answers to these issues remain elusive. In principle, collagen represents an ideal system for such investigations due to its simplified sequence and regular structure. However, the definition of the molecular basis of collagen triple helix stability has hitherto proved to be a difficult task. Particularly puzzling is the decoding of the mechanism of triple helix stabilization/destabilization induced by imino acids. Although the propensity-based model, which correlates the propensities of the individual imino acids with the structural requirements of the triple helix, is able to explicate most of the experimental data, it is unable to predict the rather high stability of peptides embedding Gly-Hyp-Hyp triplets. Starting from the available X-ray structures of this polypeptide, we carried out an extensive quantum chemistry analysis of the mutual interactions established by hydroxyproline residues located at the X and Y positions of the Gly-X-Y motif. Our data clearly indicate that the opposing rings of these residues establish significant van der Waals and dipole-dipole interactions that play an important role in triple helix stabilization. These findings suggest that triple helix stabilization can be achieved by distinct structural mechanisms. The interplay of these subtle but recurrent effects dictates the overall stability of this widespread structural motif.

  13. Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction.

    Science.gov (United States)

    Doveston, Richard G; Kuusk, Ave; Andrei, Sebastian A; Leysen, Seppe; Cao, Qing; Castaldi, Maria P; Hendricks, Adam; Brunsveld, Luc; Chen, Hongming; Boyd, Helen; Ottmann, Christian

    2017-08-01

    14-3-3 proteins are positive regulators of the tumor suppressor p53, the mutation of which is implicated in many human cancers. Current strategies for targeting of p53 involve restoration of wild-type function or inhibition of the interaction with MDM2, its key negative regulator. Despite the efficacy of these strategies, the alternate approach of stabilizing the interaction of p53 with positive regulators and, thus, enhancing tumor suppressor activity, has not been explored. Here, we report the first example of small-molecule stabilization of the 14-3-3 - p53 protein-protein interaction (PPI) and demonstrate the potential of this approach as a therapeutic modality. We also observed a disconnect between biophysical and crystallographic data in the presence of a stabilizing molecule, which is unusual in 14-3-3 PPIs. © 2017 Federation of European Biochemical Societies.

  14. Stabilization and enhancement of traffic flow by the next-nearest-neighbor interaction.

    Science.gov (United States)

    Nagatani, T

    1999-12-01

    The car-following model of traffic is extended to take into account the car interaction before the next car ahead (the next-nearest-neighbor interaction). The traffic behavior of the extended car-following model is investigated numerically and analytically. It is shown that the next-nearest-neighbor interaction stabilizes the traffic flow. The jamming transition between the freely moving and jammed phases occurs at a higher density than the threshold of the original car-following model. By increasing the maximal velocity, the traffic current is enhanced without jam by the stabilization effect. The jamming transition is analyzed with the use of the linear stability and nonlinear perturbation methods. The traffic jam is described by the kink solution of the modified Korteweg-de Vries equation. The theoretical coexisting curve is in good agreement with the simulation result.

  15. Role of interaction forces in controlling the stability and polishing performance of CMP slurries.

    Science.gov (United States)

    Basim, G Bahar; Vakarelski, Ivan U; Moudgil, Brij M

    2003-07-15

    Chemical mechanical polishing (CMP) is an essential step in metal and dielectric planarization in multilayer microelectronic device fabrication. In the CMP process it is necessary to minimize the extent of surface defect formation while maintaining good planarity and optimal material removal rates. These requirements are met through the control of chemical and mechanical interactions during the polishing process by engineering the slurry chemistry, particulate properties, and stability. In this study, the performance of surfactant-stabilized silica CMP slurries at high pH and high ionic strengths are investigated with particular emphasis on the particle-particle and particle-substrate interactions. It is shown that for the design of consistently high performing slurries, stability of abrasive particles must be achieved under the dynamic processing conditions of CMP while maintaining sufficient pad-particle-wafer interactions.

  16. Probing Bio-Nano Interactions between Blood Proteins and Monolayer-Stabilized Graphene Sheets

    DEFF Research Database (Denmark)

    Gan, Shiyu; Zhong, Lijie; Han, Dongxue

    2015-01-01

    to significant improvement in their resistance to electrolyte salts and long-term stability, but retain their core structural characteristics. Five types of model human blood proteins including human fibrinogen, γ-globulin, bovine serum albumin (BSA), insulin, and histone are tested. The main drving forces...... stability in biological environments is limited. Systematic probing on the binding of proteins to CCG is currently lacking. Herein, we report a comprehensive study on the interactions between blood proteins and stabilized CCG (sCCG). CCG nanosheets are functionalized by monolayers of perylene leading...

  17. Relation between stabilization energy, crystal field coefficient and themagnetic exchange interaction for Tb3+ ion

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiangmu; MA Wenjuan; CUI Shuwen; WANG Lihua

    2006-01-01

    Based on a single ion model, Hamiltonian of the simplest form about magnetocrystalline anisotropy for Tb3+ ion was solved by using the numerical method. The relation between the stabilization energy, crystal field coefficient B20 and the magnetic exchange interaction was studied as temperature approaches to 0K. The results show that the stabilization energy contributed by Tb3+ is linear with crystal field coefficient B20 approximately, but it is insensitive to the change of magnetic exchange interaction for the strong magnetic substancessuch as TbCo5, Tb2Co17 and Tb2Fe14B compounds.

  18. Nonlinear Model of the Specificity of DNA-Protein Interactions and Its Stability

    Science.gov (United States)

    Dwiputra, D.; Hidayat, W.; Khairani, R.; Zen, F. P.

    2016-08-01

    Specific DNA-protein interactions are fundamental processes of living cells. We propose a new model of DNA-protein interactions to explain the site specificity of the interactions. The hydrogen bonds between DNA base pairs and between DNA-protein peptide groups play a significant role in determination of the specific binding site. We adopt the Morse potential with coupling terms to construct the Hamiltonian of coupled oscillators representing the hydrogen bonds in which the depth of the potentials vary in the DNA chain. In this paper we investigate the stability of the model to determine the conditions satisfying the biological circumstances of the DNA-protein interactions.

  19. Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery?

    Science.gov (United States)

    Thiel, Philipp; Kaiser, Markus; Ottmann, Christian

    2012-02-27

    The modulation of protein-protein interactions (PPIs) has been recognized as one of the most challenging tasks in drug discovery. While their systematic development has long been considered as intractable, this view has changed over the last years, with the first drug candidates undergoing clinical studies. To date, the vast majority of PPI modulators are interaction inhibitors. However, in many biological contexts a prolonged lifespan of a PPI might be desirable, calling for the complementary approach of PPI stabilization. In fact, nature offers impressive examples of this concept and some PPI-stabilizing natural products have already found application as important drugs. Moreover, directed small-molecule stabilization has recently been demonstrated. Therefore, it is time to take a closer look at the constructive side of modulating PPIs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Electronic metal-support interaction enhanced oxygen reduction activity and stability of boron carbide supported platinum

    Science.gov (United States)

    Jackson, Colleen; Smith, Graham T.; Inwood, David W.; Leach, Andrew S.; Whalley, Penny S.; Callisti, Mauro; Polcar, Tomas; Russell, Andrea E.; Levecque, Pieter; Kramer, Denis

    2017-06-01

    Catalysing the reduction of oxygen in acidic media is a standing challenge. Although activity of platinum, the most active metal, can be substantially improved by alloying, alloy stability remains a concern. Here we report that platinum nanoparticles supported on graphite-rich boron carbide show a 50-100% increase in activity in acidic media and improved cycle stability compared to commercial carbon supported platinum nanoparticles. Transmission electron microscopy and x-ray absorption fine structure analysis confirm similar platinum nanoparticle shapes, sizes, lattice parameters, and cluster packing on both supports, while x-ray photoelectron and absorption spectroscopy demonstrate a change in electronic structure. This shows that purely electronic metal-support interactions can significantly improve oxygen reduction activity without inducing shape, alloying or strain effects and without compromising stability. Optimizing the electronic interaction between the catalyst and support is, therefore, a promising approach for advanced electrocatalysts where optimizing the catalytic nanoparticles themselves is constrained by other concerns.

  1. The interaction of postural and voluntary strategies for stability in Parkinson's disease

    NARCIS (Netherlands)

    de Lima-Pardini, Andrea C.; Papegaaij, Selma; Cohen, Rajal G.; Teixeira, Luis A.; Smith, Beth A.; Horak, Fay B.

    2012-01-01

    de Lima-Pardini AC, Papegaaij S, Cohen RG, Teixeira LA, Smith BA, Horak FB. The interaction of postural and voluntary strategies for stability in Parkinson's disease. J Neurophysiol 108: 1244-1252, 2012. First published June 6, 2012; doi:10.1152/jn.00118.2012.-This study assessed the effects of stab

  2. Stability of Solitary Waves for Three Coupled Long Wave - Short Wave Interaction Equations

    OpenAIRE

    Borluk, H.; Erbay, S.

    2009-01-01

    In this paper we consider a three-component system of one dimensional long wave-short wave interaction equations. The system has two-parameter family of solitary wave solutions. We prove orbital stability of the solitary wave solutions using variational methods.

  3. Macroeconomic policy interaction: State dependency and implications for financial stability in UK: A systemic review

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Nasir

    2016-12-01

    Full Text Available The association between economic and financial stabilities and influence of macroeconomic policies on the financial sector creates scope of active policy role in financial stability. As a contribution to the existing body of knowledge, this study has analysed the implications of macroeconomic policy interaction/coordination for financial stability, proxied by financial assets, i.e. equity and bonds price oscillation. The critical review and analysis of the existing literature on the subject suggests that there is also ample evidence of interdependence between monetary and fiscal policies and this interrelation necessitates coordination between them for the sake of financial stability. There is also a case for analysing the symmetry of financial markets responses to macroeconomic policy interaction. On methodological and empirical grounds, it is vital to test the robustness of policy recommendations to overcome the limitation of a single empirical approach (Jeffrey–Lindley’s paradox. Hence, the Frequentist and Bayesian approaches should be used in commentary manner. The policy interaction and optimal policy combination should also be analysed in the context of institutional design and major financial events to gain insight into the implications of policy interaction in the periods of stable economic and financial environments as well as period of financial and economic distress.

  4. Intersubunit ionic interactions stabilize the nucleoside diphosphate kinase of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Georgescauld, Florian; Moynie, Lucile; Habersetzer, Johann;

    2013-01-01

    Most nucleoside diphosphate kinases (NDPKs) are hexamers. The C-terminal tail interacting with the neighboring subunits is crucial for hexamer stability. In the NDPK from Mycobacterium tuberculosis (Mt) this tail is missing. The quaternary structure of Mt-NDPK is essential for full enzymatic acti...

  5. Contributions of cation-π interactions to the collagen triple helix stability.

    Science.gov (United States)

    Chen, Chia-Ching; Hsu, Wei; Hwang, Kuo-Chu; Hwu, Jih Ru; Lin, Chun-Cheng; Horng, Jia-Cherng

    2011-04-01

    Cation-π interactions are found to be an important noncovalent force in proteins. Collagen is a right-handed triple helix composed of three left-handed PPII helices, in which (X-Y-Gly) repeats dominate in the sequence. Molecular modeling indicates that cation-π interactions could be formed between the X and Y positions in adjacent collagen strands. Here, we used a host-guest peptide system: (Pro-Hyp-Gly)(3)-(Pro-Y-Gly-X-Hyp-Gly)-(Pro-Hyp-Gly)(3), where X is an aromatic residue and Y is a cationic residue, to study the cation-π interaction in the collagen triple helix. Circular dichroism (CD) measurements and Tm data analysis show that the cation-π interactions involving Arg have a larger contribution to the conformational stability than do those involving Lys, and Trp forms a weaker cation-π interaction with cationic residues than expected as a result of steric effects. The results also show that the formation of cation-π interactions between Arg and Phe depends on their relative positions in the strand. Moreover, the fluorinated and methylated Phe substitutions show that an electron-withdrawing or electron-donating substituent on the aromatic ring can modulate its π-electron density and the cation-π interaction in collagen. Our data demonstrate that the cation-π interaction could play an important role in stabilizing the collagen triple helix.

  6. Analysis of protein stability and ligand interactions by thermal shift assay.

    Science.gov (United States)

    Huynh, Kathy; Partch, Carrie L

    2015-02-02

    Purification of recombinant proteins for biochemical assays and structural studies is time-consuming and presents inherent difficulties that depend on the optimization of protein stability. The use of dyes to monitor thermal denaturation of proteins with sensitive fluorescence detection enables rapid and inexpensive determination of protein stability using real-time PCR instruments. By screening a wide range of solution conditions and additives in a 96-well format, the thermal shift assay easily identifies conditions that significantly enhance the stability of recombinant proteins. The same approach can be used as an initial low-cost screen to discover new protein-ligand interactions by capitalizing on increases in protein stability that typically occur upon ligand binding. This unit presents a methodological workflow for small-scale, high-throughput thermal denaturation of recombinant proteins in the presence of SYPRO Orange dye.

  7. Microfluidic EDGE emulsification: the importance of interface interactions on droplet formation and pressure stability

    Science.gov (United States)

    Sahin, Sami; Bliznyuk, Olesya; Rovalino Cordova, Ana; Schroën, Karin

    2016-05-01

    The fact that interactions of components with interfaces can influence processes is well-known; e.g. deposit accumulation on heat exchangers and membrane fouling lead to additional resistances against heat and mass transfer, respectively. In microfluidic emulsification, the situation is even more complex. Component accumulation at the liquid/liquid interface is necessary for emulsion stability, while undesired at the solid/liquid interface where it may change wettability. For successful emulsification both aspects need to be controlled, and that is investigated in this paper for o/w emulsification with microfluidic EDGE devices. These devices were characterised previously, and can be used to detect small wettability changes through e.g. the pressure stability of the device. We used various oil/emulsifier combinations (alkanes, vegetable oil, surfactants and proteins) and related droplet size and operational pressure stability to component interactions with the solid surface and liquid interface. Surfactants with a strong interaction with glass always favour emulsification, while surfactants that have week interactions with the surface can be replaced by vegetable oil that interacts strongly with glass, resulting in loss of emulsification. Our findings clearly show that an appropriate combination of construction material and emulsion components is needed to achieve successful emulsification in microfluidic EDGE devices.

  8. Pressure perturbation calorimetry, heat capacity and the role of water in protein stability and interactions.

    Science.gov (United States)

    Cooper, A; Cameron, D; Jakus, J; Pettigrew, G W

    2007-12-01

    It is widely acknowledged, and usually self-evident, that solvent water plays a crucial role in the overall thermodynamics of protein stabilization and biomolecular interactions. Yet we lack experimental techniques that can probe unambiguously the nature of protein-water or ligand-water interactions and how they might change during protein folding or ligand binding. PPC (pressure perturbation calorimetry) is a relatively new technique based on detection of the heat effects arising from application of relatively small pressure perturbations (+/-5 atm; 1 atm=101.325 kPa) to dilute aqueous solutions of proteins or other biomolecules. We show here how this can be related to changes in solvation/hydration during protein-protein and protein-ligand interactions. Measurements of 'anomalous' heat capacity effects in a wide variety of biomolecular interactions can also be related to solvation effects as part of a quite fundamental principle that is emerging, showing how the apparently unusual thermodynamics of interactions in water can be rationalized as an inevitable consequence of processes involving the co-operative interaction of multiple weak interactions. This leads to a generic picture of the thermodynamics of protein folding stabilization in which hydrogen-bonding plays a much more prominent role than has been hitherto supposed.

  9. The role of C-H$\\ldots$ interaction in the stabilization of benzene and adamantane clusters

    Indian Academy of Sciences (India)

    R Mahesh Kumar; M Elango; R Parthasarathi; Dolly Vijay; V Subramanian

    2012-01-01

    In this investigation, a systematic attempt has been made to understand the interaction between adamantane and benzene using both ab initio and density functional theory methods. C-H$\\ldots$ type of interaction between C-H groups of adamantane and cloud of benzene is found as the important attraction for complex formation. The study also reveals that the methylene (-CH2) and methine (-CH) groups of adamantane interact with benzene resulting in different geometrical structures. And it is found that the former complex is stronger than the later. The diamondoid structure of adamantane enables it to interact with a maximum of four benzene molecules, each one along the four faces. The stability of the complex increases with increase in the number of benzene molecules. The energy decomposition analysis of adamantane-benzene complexes using DMA approach shows that the origin of the stability primarily arises from the dispersive interaction. The theory of atoms in molecules (AIM) supports the existence of weak interaction between the two systems. The electrostatic topography features provide clues for the mode of interaction of adamantane with benzene.

  10. Linking computation and experiments to study the role of charge-charge interactions in protein folding and stability

    Science.gov (United States)

    Makhatadze, George I.

    2017-02-01

    Over the past two decades there has been an increase in appreciation for the role of surface charge-charge interactions in protein folding and stability. The perception shifted from the belief that charge-charge interactions are not important for protein folding and stability to the near quantitative understanding of how these interactions shape the folding energy landscape. This led to the ability of computational approaches to rationally redesign surface charge-charge interactions to modulate thermodynamic properties of proteins. Here we summarize our progress in understanding the role of charge-charge interactions for protein stability using examples drawn from my own laboratory and touch upon unanswered questions.

  11. Stabilization of collagen through bioconversion: An insight in protein-protein interaction.

    Science.gov (United States)

    Usharani, Nagarajan; Jayakumar, Gladstone Christopher; Kanth, Swarna Vinodh; Rao, Jonnalagadda Raghava

    2014-08-01

    Collagen is a natural protein, which is used as a vital biomaterial in tissue engineering. The major concern about native collagen is lack of its thermal stability and weak resistance to proteolytic degradation. In this scenario, the crosslinking compounds used for stabilization of collagen are mostly of chemical nature and exhibit toxicity. The enzyme mediated crosslinking of collagen provides a novel alternative, nontoxic method for stabilization. In this study, aldehyde forming enzyme (AFE) is used in the bioconversion of hydroxylmethyl groups of collagen to formyl groups that results in the formation of peptidyl aldehyde. The resulted peptidyl aldehyde interacts with bipolar ions of basic amino acid residues of collagen. Further interaction leads to the formation of conjugated double bonds (aldol condensation involving the aldehyde group of peptidyl aldehyde) within the collagen. The enzyme modified collagen matrices have shown an increase in the denaturation temperature, when compared with native collagen. Enzyme modified collagen membranes exhibit resistance toward collagenolytic activity. Moreover, they exhibited a nontoxic nature. The catalytic activity of AFE on collagen as a substrate establishes an efficient modification, which enhances the structural stability of collagen. This finds new avenues in the context of protein-protein stabilization and discovers paramount application in tissue engineering.

  12. Interaction and UV-Stability of Various Organic Capping Agents on the Surface of Anatase Nanoparticles

    Directory of Open Access Journals (Sweden)

    Mohsin Raza

    2014-04-01

    Full Text Available Anatase nanoparticles synthesized by the sol-gel method were surface-functionalized with long alkyl chain coupling agents as compatibilizers for a nonpolar environment, containing different anchor groups for surface interaction namely phosphonate (dodecyl phosphonate, carboxylate (dodecanoic acid, sulfate (sodium dodecyl sulphate, and amine (dodecyl amine. It was shown that the surface of the nanoparticles can be functionalized with the various surface groups applying similar reaction conditions. The kind of surface interaction was analyzed applying FTIR spectroscopy. The phosphonate and the carboxylate groups interact with the surface via quite strong covalent or coordinative interactions, respectively. The sulfate and amine based coupling agents on the other hand exhibit electrostatic interactions. UV stability studies of the surface bound groups revealed different degradation mechanisms for the various functionalities and moreover showed that phosphonates are the most stable among the investigated surface capping groups.

  13. Dynamical stabilization by phonon-phonon interaction exemplified in cubic zirconia

    Energy Technology Data Exchange (ETDEWEB)

    Souvatsos, [etrps G [Los Alamos National Laboratory; Rudin, Sven P [Los Alamos National Laboratory

    2008-01-01

    Cubic zirconia exhibits a soft phonon mode (X{sup -}{sub 2}), which becomes dynamically unstable at low temperatures. Previous ab initio invest.igations into the temperature-induced stabilization of the soft mode treated it as an independent anharmonic oscillator. Calculations presented here, using the self consistent ab initio lattice dynamical (SCAILD) method to evaluate the phonons at 2570 K, show that the soft mode should not be treated independently of other phonon modes. Phonon-phonon interactions stabilize the X{sup -}{sub 2} mode. Furthermore, the effective potential experienced by the mode takes on a quadratic form.

  14. Stabilizing G-quadruplex DNA by methylazacalix[n]pyridine through shape-complementary interaction.

    Science.gov (United States)

    Guan, Ai-Jiao; Shen, Meng-Jie; Zhang, En-Xuan; Li, Qian; Wang, Li-Xia; Xu, Li-Jin; Xiang, Jun-Feng; Tang, Ya-Lin

    2016-01-15

    It is found that G-quadruplexes have important functions in biological systems, such as gene expression. Molecules which can stabilize the G-quadruplex structure may have potential application in regulating the expression of gene. A series of methylazacalix[n]pyridine (n=4, 6, 7, 8, 9) has been tested to stabilize the intermolecular human telomeric G-quadruplex (T12 and H12), intramolecular TBA, c-kit and bcl-2 G-quadruplex by CD denaturation experiments. The results showed that only methylazacalix[6]pyridine (MACP6) can stabilize the intermolecular G-quadruplex formed from the 12bp human telomere. Further studies evidenced that the shape-complementary binding mode was what contributed to the interaction between MACP6 and T12 G-quadruplex.

  15. Modulated growth, stability and interactions of liquid-like coacervate assemblies of elastin.

    Science.gov (United States)

    Muiznieks, Lisa D; Cirulis, Judith T; van der Horst, Astrid; Reinhardt, Dieter P; Wuite, Gijs J L; Pomès, Régis; Keeley, Fred W

    2014-06-01

    Elastin self-assembles from monomers into polymer networks that display elasticity and resilience. The first major step in assembly is a liquid-liquid phase separation known as coacervation. This process represents a continuum of stages from initial phase separation to early growth of droplets by coalescence and later "maturation" leading to fiber formation. Assembly of tropoelastin-rich globules is on pathway for fiber formation in vivo. However, little is known about these intermediates beyond their size distribution. Here we investigate the contribution of sequence and structural motifs from full-length tropoelastin and a set of elastin-like polypeptides to the maturation of coacervate assemblies, observing their growth, stability and interaction behavior, and polypeptide alignment within matured globules. We conclude that maturation is driven by surface properties, leading to stabilization of the interface between the hydrophobic interior and aqueous solvent, potentially through structural motifs, and discuss implications for droplet interactions in fiber formation.

  16. Effects of three-body interaction on collective excitation and stability of Bose-Einstein condensate

    Institute of Scientific and Technical Information of China (English)

    Peng Ping; Li Guan-Qiang

    2009-01-01

    This paper investigates the collective excitation and stability of low-dimensional Bose-Einstein condensates with two-and three-body interactions by the variational analysis of the time-dependent Gross-Pitaevskii-Ginzburg equation.The spectrum of the low-energy excitation and the effective potential for the width of the condensate are obtained.The results show that:(i) the repulsive two-body interaction among atoms makes the frequency red-shifted for the internal excitation and the repulsive or attractive three-body interaction always makes it blue-shifted; (ii) the region for the existence of the stable bound states is obtained by identifying the critical value of the two-and three-body interactions.

  17. Stability on Adaptive NN Formation Control with Variant Formation Patterns and Interaction Topologies

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2008-03-01

    Full Text Available The formation task achieved by multiple robots is a tough issue in practice, because of the limitations of the sensing abilities and communicating functions among them. This paper investigates the decentralized formation control in case of parameter uncertainties, bounded disturbances, and variant interactions among robots. To design decentralized controller, a formation description is firstly proposed, which consists of two aspects in terms of formation pattern and interaction topology. Then the formation control using adaptive neural network (ANN is proposed based on the relative error derived from formation description. From the analysis on stability of the formation control under invariant/variant formation pattern and interaction topology, it is concluded that if formation pattern is of class Ck, k ≥1, and interaction graph is connected and changed with finite times, the convergence of the formation control is guaranteed, so that robots must form the formation described by the formation pattern.

  18. Stability on Adaptive NN Formation Control with Variant Formation Patterns and Interaction Topologies

    Directory of Open Access Journals (Sweden)

    Yangmin Li

    2008-11-01

    Full Text Available The formation task achieved by multiple robots is a tough issue in practice, because of the limitations of the sensing abilities and communicating functions among them. This paper investigates the decentralized formation control in case of parameter uncertainties, bounded disturbances, and variant interactions among robots. To design decentralized controller, a formation description is firstly proposed, which consists of two aspects in terms of formation pattern and interaction topology. Then the formation control using adaptive neural network (ANN is proposed based on the relative error derived from formation description. From the analysis on stability of the formation control under invariant/variant formation pattern and interaction topology, it is concluded that if formation pattern is of class kC, 1k≥ , and interaction graph is connected and changed with finite times, the convergence of the formation control is guaranteed, so that robots must form the formation described by the formation pattern.

  19. 'Trophic whales' as biotic buffers: weak interactions stabilize ecosystems against nutrient enrichment.

    Science.gov (United States)

    Schwarzmüller, Florian; Eisenhauer, Nico; Brose, Ulrich

    2015-05-01

    Human activities may compromise biodiversity if external stressors such as nutrient enrichment endanger overall network stability by inducing unstable dynamics. However, some ecosystems maintain relatively high diversity levels despite experiencing continuing disturbances. This indicates that some intrinsic properties prevent unstable dynamics and resulting extinctions. Identifying these 'ecosystem buffers' is crucial for our understanding of the stability of ecosystems and an important tool for environmental and conservation biologists. In this vein, weak interactions have been suggested as stabilizing elements of complex systems, but their relevance has rarely been tested experimentally. Here, using network and allometric theory, we present a novel concept for a priori identification of species that buffer against externally induced instability of increased population oscillations via weak interactions. We tested our model in a microcosm experiment using a soil food-web motif. Our results show that large-bodied species feeding at the food web's base, so called 'trophic whales', can buffer ecosystems against unstable dynamics induced by nutrient enrichment. Similar to the functionality of chemical or mechanical buffers, they serve as 'biotic buffers' that take up stressor effects and thus protect fragile systems from instability. We discuss trophic whales as common functional building blocks across ecosystems. Considering increasing stressor effects under anthropogenic global change, conservation of these network-intrinsic biotic buffers may help maintain the stability and diversity of natural ecosystems.

  20. Self-propelled particles with soft-core interactions: patterns, stability, and collapse.

    Science.gov (United States)

    D' Orsogna, M R; Chuang, Y L; Bertozzi, A L; Chayes, L S

    2006-03-17

    Understanding collective properties of driven particle systems is significant for naturally occurring aggregates and because the knowledge gained can be used as building blocks for the design of artificial ones. We model self-propelling biological or artificial individuals interacting through pairwise attractive and repulsive forces. For the first time, we are able to predict stability and morphology of organization starting from the shape of the two-body interaction. We present a coherent theory, based on fundamental statistical mechanics, for all possible phases of collective motion.

  1. Stability and Chaos of Two Coupled Bose-Einstein Condensates with Three-Body Interaction

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    We study the dynamics of two Bose-Einstein condensates (BECs) tunnel-coupled by a double-well potential.A real three-body interaction term is considered and a two-mode approximation is used to derive two coupled equations,which describe the relative population and relative phase. By solving the equations and analyzing the stability of the system, we find the stable stationary solutions for a constant atomic scattering length. When a periodically time-varying scattering length is applied, Melnikov analysis and numerical calculation demonstrate the existence of chaotic behavior and the dependence of chaos on the three-body interaction parameters.

  2. Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study.

    Science.gov (United States)

    Milroy, Lech-Gustav; Brunsveld, Luc; Ottmann, Christian

    2013-01-18

    Small-molecule modulation of protein-protein interactions (PPIs) is one of the most exciting but also difficult fields in chemical biology and drug development. As one of the most important "hub" proteins with at least 200-300 interaction partners, the 14-3-3 proteins are an especially fruitful case for PPI intervention. Here, we summarize recent success stories in small-molecule modulation, both inhibition and stabilization, of 14-3-3 PPIs. The chemical breath of modulators includes natural products such as fusicoccin A and derivatives but also compounds identified via high-throughput and in silico screening, which has yielded a toolbox of useful inhibitors and stabilizers for this interesting class of adapter proteins. Protein-protein interactions (PPIs) are involved in almost all biological processes, with any given protein typically engaged in complexes with other proteins for the majority of its lifetime. Hence, proteins function not simply as single, isolated entities but display their roles by interacting with other cellular components. These different interaction patterns are presumably as important as the intrinsic biochemical activity status of the protein itself. The biological role of a protein is therefore decisively dependent on the underlying PPI network that furthermore can show great spatial and temporal variations. A thorough appreciation and understanding of this concept and its regulation mechanisms could help to develop new therapeutic agents and concepts.

  3. Triethanolamine Stabilization of Methotrexate-β-Cyclodextrin Interactions in Ternary Complexes

    Directory of Open Access Journals (Sweden)

    Jahamunna A. A. Barbosa

    2014-09-01

    Full Text Available The interaction of methotrexate (MTX with beta-cyclodextrin (β-CD in the presence of triethanolamine (TEA was investigated with the aim to elucidate the mechanism whereby self-assembly cyclodextrin systems work in association with this third component. Solubility diagram studies showed synergic increment of the MTX solubility to be about thirty-fold. Experiments using 2D ROESY and molecular modeling studies revealed the inclusion of aromatic ring III of the drug into β-CD cavity, in which TEA contributes by intensifying MTX interaction with β-CD and stabilizes MTX:β-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:β-CD:TEA and comparisons were made with freeze dried binary MTX:β-CD and physical mixtures. FTIR studies evidenced that MTX–β-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (DSC, thermogravimetric analysis (TG/first derivative of TG analysis (DTG and C,N,H elementary analysis and structural (X-ray diffraction analysis, (XRD studies, mainly regarding the increment of drug stability. The efficient in vitro drug dissolution studies successfully demonstrated the contribution of ternary complexes, which highlights the importance of this possible new raw material for further applications in drug delivery systems.

  4. Triethanolamine Stabilization of Methotrexate-β-Cyclodextrin Interactions in Ternary Complexes

    Science.gov (United States)

    Barbosa, Jahamunna A. A.; Zoppi, Ariana; Quevedo, Mario A.; de Melo, Polyanne N.; de Medeiros, Arthur S. A.; Streck, Letícia; de Oliveira, Alice R.; Fernandes-Pedrosa, Matheus F.; Longhi, Marcela R.; da Silva-Júnior, Arnóbio A.

    2014-01-01

    The interaction of methotrexate (MTX) with beta-cyclodextrin (β-CD) in the presence of triethanolamine (TEA) was investigated with the aim to elucidate the mechanism whereby self-assembly cyclodextrin systems work in association with this third component. Solubility diagram studies showed synergic increment of the MTX solubility to be about thirty-fold. Experiments using 2D ROESY and molecular modeling studies revealed the inclusion of aromatic ring III of the drug into β-CD cavity, in which TEA contributes by intensifying MTX interaction with β-CD and stabilizes MTX:β-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:β-CD:TEA and comparisons were made with freeze dried binary MTX:β-CD and physical mixtures. FTIR studies evidenced that MTX–β-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TG)/first derivative of TG analysis (DTG) and C,N,H elementary analysis) and structural (X-ray diffraction analysis, (XRD)) studies, mainly regarding the increment of drug stability. The efficient in vitro drug dissolution studies successfully demonstrated the contribution of ternary complexes, which highlights the importance of this possible new raw material for further applications in drug delivery systems. PMID:25257529

  5. Role of van der Waals interactions for the intrinsic stability of polyalanine helices

    Science.gov (United States)

    Tkatchenko, Alexandre; Blum, Volker; Ireta, Joel; Scheffler, Matthias

    2009-03-01

    The helical motif is an ubiquitous conformation adopted by aminoacid residues in a protein structure and helix formation is the simplest example of the protein folding process. How stable is the folded peptide helix in comparison to a random coil structure? What are the interactions responsible for stabilizing the helical conformation? Answering these questions has thus a direct implication for understanding protein folding. In this work we use density functional theory (DFT) augmented with a non-empirical correction for van der Waals (vdW) forces to study the stability of alanine polypeptide helices in vacuo. We find a large stabilization of the native helical forms when vdW correction is used. It amounts to 121%, 157% and 83% on top of the Perdew-Burke-Ernzerhof (PBE) functional in the case of infinite α, π and 310 helices, respectively. Thus, the experimentally observed α helix is significantly stabilized by vdW forces both over the fully extended and the 310 conformations. Our findings also suggest an explanation to the remarkable stability of gas-phase alanine helices up to high temperatures [M. Kohtani et al. JACS 126, 7420 (2004)].

  6. Fetal bovine serum influences the stability and bioactivity of resveratrol analogues: A polyphenol-protein interaction approach.

    Science.gov (United States)

    Tang, Fen; Xie, Yixi; Cao, Hui; Yang, Hua; Chen, Xiaoqing; Xiao, Jianbo

    2017-03-15

    Fetal bovine serum (FBS) is a universal growth supplement of cell and tissue culture media. Herein, the influences of FBS on the stability and antioxidant activity of 21 resveratrol analogues were investigated using a polyphenol-protein interaction approach. The structure-stability relationships of resveratrol analogues in FBS showed a clear decrease in the stability of hydroxylated resveratrol analogues in the order: resorcinol-type>pyrogallol-type>catechol-type. The glycosylation and methoxylation of resveratrol analogues enhanced their stability. A linear relationship between the stability of resveratrol analogues in FBS and the affinity of resveratrol analogues-FBS interaction was found. The oxidation process is not the only factor governing the stability of resveratrol analogues in FBS. These results facilitated the insightful investigation of the role of polyphenol-protein interactions in serum, thereby providing some fundamental clues for future clinical research and pharmacological studies on natural small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Spectroscopic investigations of novel pharmaceuticals: Stability and resonant interaction with laser beam

    Science.gov (United States)

    Smarandache, Adriana; Boni, Mihai; Andrei, Ionut Relu; Handzlik, Jadwiga; Kiec-Kononowicz, Katarzyna; Staicu, Angela; Pascu, Mihail-Lucian

    2017-09-01

    This paper presents data about photophysics of two novel thio-hydantoins that exhibit promising pharmaceutical properties in multidrug resistance control. Time stability studies are necessary to establish the proper use of these compounds in different applications. As for their administration as drugs, it is imperative to know their shelf life, as well as storage conditions. At the same time, laser induced modified properties of the two new compounds are valuable to further investigate their specific interactions with other materials, including biological targets. The two new thio-hydantoins under generic names SZ-2 and SZ-7 were prepared as solutions in dimethyl sulfoxide at different concentrations, as well as in deionised water. For the stability assay they were kept in various light/temperature conditions up to 60 days. The stability was estimates based on UV-vis absorption measurements. The samples in bulk shape were exposed different time intervals to laser radiation emitted at 266 nm as the fourth harmonic of a Nd:YAG laser. The resonant interaction of the studied compounds with laser beams was analysed through spectroscopic methods UV-vis and FTIR absorption, as well as laser induced fluorescence spectroscopy. As for stability assay, only solutions kept in dark at 4 °C have preserved the absorption characteristics, considering the cumulated measuring errors, less than one week. The vibrational changes that occur in their FTIR and modified fluorescence spectra upon laser beam exposure are also discussed. A result of the experimental analysis is that modifications are induced in molecular structures of the investigated compounds by resonant interaction with laser radiation. This fact evidences that the molecules are photoreactive and their characteristics might be shaped through controlled laser radiation exposure using appropriate protocols. This conclusion opens many opportunities both in the biomedical field, but also in other industrial activities

  8. Stability of maternal discipline practices and the quality of mother-child interaction during toddlerhood.

    Science.gov (United States)

    Huang, Keng-Yen; Caughy, Margaret O'Brien; Lee, Li-Ching; Miller, Therese; Genevro, Janice

    2009-07-01

    This study examined the stability of maternal punitive/high-power discipline (PD) and inductive/authoritative discipline (ID) over the second and third years of life and the effect of maternal discipline on quality of mother-child interactions. Data from a longitudinal sample with 179 mother-toddler dyads were analyzed, and selected factors (i.e., child sex, temperament) that might moderate the association between maternal discipline and quality of mother-child interactions were also examined. Maternal discipline, quality of mother-child interactions, and temperamental moderators were measured at 16-18 months (Time 1) and 34-37 months (Time 2). Results showed that the stability of maternal use of discipline strategies over the toddler years was moderate. Lower maternal use of PD, higher maternal use of ID, and higher preference/reliance on ID (relative to PD) were associated with higher quality of mother-child interactions. Moderation effects of child temperament were also found. High ID and PD were associated with low quality of mother-child relationships in non-temperamentally difficult children but not in temperamentally difficult children.

  9. Effect of shock interactions on the attitude stability of a toroidal ballute for reentry vehicles

    Science.gov (United States)

    Otsu, Hirotaka; Abe, Takashi

    2016-11-01

    The effect of shock interactions on the attitude stability of a reentry vehicle system with a toroidal ballute was investigated. The hypersonic wind tunnel experimental results showed that when the shock interaction occurred near or outside the ballute, an unstable oscillation of the ballute was observed. This was caused by the local high-pressure region on the ballute surface created by the shock interaction between the shock from the reentry capsule and the shock from the ballute. To avoid this unstable oscillation, the radius of the ballute should be designed to be large enough so that the shock from the capsule will be located inside the ballute, which can avoid the local high-pressure region on the ballute surface.

  10. Relative stability of the FCC and HCP polymorphs with interacting polymers.

    Science.gov (United States)

    Mahynski, Nathan A; Kumar, Sanat K; Panagiotopoulos, Athanassios Z

    2015-01-14

    Recent work [Mahynski et al., Nat. Commun., 2014, 5, 4472] has demonstrated that the addition of long linear homopolymers thermodynamically biases crystallizing hard-sphere colloids to produce the hexagonal close-packed (HCP) polymorph over the closely related face-centered cubic (FCC) structure when the polymers and colloids are purely repulsive. In this report, we investigate the effects of thermal interactions on each crystal polymorph to explore the possibility of stabilizing the FCC crystal structure over the HCP. We find that the HCP polymorph remains at least as stable as its FCC counterpart across the entire range of interactions we explored, where interactions were quantified by the reduced second virial coefficient, -1.50 0, its tetrahedral voids produce a similar effect when B FCC crystals are elusive in these binary mixtures.

  11. Hearing (Rivaling Lips and Seeing Voices: How Audiovisual Interactions Modulate Perceptual Stabilization in Binocular Rivalry

    Directory of Open Access Journals (Sweden)

    Manuel eVidal

    2014-09-01

    Full Text Available In binocular rivalry (BR, sensory input remains the same yet subjective experience fluctuates irremediably between two mutually exclusive representations. We investigated the perceptual stabilization effect of an additional sound on the BR dynamics using speech stimuli known to involve robust audiovisual (AV interactions at several cortical levels. Subjects sensitive to the McGurk effect were presented looping videos of rivaling faces uttering /aba/ and /aga/ respectively, while synchronously hearing the voice /aba/. They reported continuously the dominant percept, either observing passively or trying actively to promote one of the faces. The few studies that investigated the influence of information from an external modality on perceptual competition reported results that seem at first sight inconsistent. Since these differences could stem from how well the modalities matched, we addressed this by comparing two levels of AV congruence: real (/aba/ viseme vs. illusory (/aga/ viseme producing the /ada/ McGurk fusion. First, adding the voice /aba/ stabilized both real and illusory congruent lips percept. Second, real congruence of the added voice improved volitional control whereas illusory congruence did not, suggesting a graded contribution to the top-down sensitivity control of selective attention. In conclusion, a congruent sound enhanced considerably attentional control over the perceptual outcome selection; however, differences between passive stabilization and active control according to AV congruency suggest these are governed by two distinct mechanisms. Based on existing theoretical models of BR, selective attention and AV interaction in speech perception, we provide a general interpretation of our findings.

  12. Stabilization of Protein-Protein Interactions in chemical biology and drug discovery.

    Science.gov (United States)

    Bier, David; Thiel, Philipp; Briels, Jeroen; Ottmann, Christian

    2015-10-01

    More than 300,000 Protein-Protein Interactions (PPIs) can be found in human cells. This number is significantly larger than the number of single proteins, which are the classical targets for pharmacological intervention. Hence, specific and potent modulation of PPIs by small, drug-like molecules would tremendously enlarge the "druggable genome" enabling novel ways of drug discovery for essentially every human disease. This strategy is especially promising in diseases with difficult targets like intrinsically disordered proteins or transcription factors, for example neurodegeneration or metabolic diseases. Whereas the potential of PPI modulation has been recognized in terms of the development of inhibitors that disrupt or prevent a binary protein complex, the opposite (or complementary) strategy to stabilize PPIs has not yet been realized in a systematic manner. This fact is rather surprising given the number of impressive natural product examples that confer their activity by stabilizing specific PPIs. In addition, in recent years more and more examples of synthetic molecules are being published that work as PPI stabilizers, despite the fact that in the majority they initially have not been designed as such. Here, we describe examples from both the natural products as well as the synthetic molecules advocating for a stronger consideration of the PPI stabilization approach in chemical biology and drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  14. Sequence, Stability, Structure of G-Quadruplexes and Their Drug Interactions

    Science.gov (United States)

    Chen, Yuwei; Yang, Danzhou

    2012-01-01

    Although DNA is most widely known to store and pass along genetic information, the discovery of G-quadruplex structures has illuminated a new role of DNA in biology. DNA G-quadruplexes are four-stranded globular nucleic acid secondary structures formed in specific G-rich sequences with biological significance, such as human telomeres and oncogene promoters. This review focuses on the unimolecular DNA G-quadruplexes, which can readily form in solution under physiological conditions and are considered to be most biologically relevant. Available structural data show a great conformational diversity of unimolecular G-quadruplexes, amenable to small molecule drug targeting. The relationship of sequence, structure, and stability of unimolecular DNA G-quadruplexes, as well as the recent progress on interactions with small molecule compounds and insights into rational design of G-quadruplex-interactive molecules, will be discussed. PMID:22956454

  15. Interaction of environmental moisture with powdered green tea formulations: effect on catechin chemical stability.

    Science.gov (United States)

    Ortiz, J; Ferruzzi, M G; Taylor, L S; Mauer, L J

    2008-06-11

    Green tea and tea catechins must be stable in finished products to deliver health benefits; however, they may be adversely affected by tea processing/storage conditions and the presence of other components. The objective of this study was to determine the effects of storage relative humidity (RH) and addition of other ingredients on catechin stability in simulated dry beverage mixtures. Samples of green tea powder alone and mixed with sucrose, citric acid, and/or ascorbic acid were prepared and stored in desiccators at 22 degrees C and 0-85% RH for up to 3 months. Epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate were determined by high-performance liquid chromatography (HPLC). Formulation and the interaction of formulation and RH significantly promoted catechin degradation ( P or = 58% RH by the presence of powdered citric acid and at > or = 75% RH by the presence of ascorbic acid. Catechins degraded the most in formulations containing both acids. Although catechin chemical stability was maintained at < or = 43% RH in all samples stored at 22 degrees C for 3 months, caking was observed in samples at these relative humidities. These results are the first to demonstrate that addition of other dry components to tea powders may affect catechin stability in finished dry blends and highlight the importance of considering the complex interplay between a multicomponent system and its environment for developing stable products.

  16. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Nathan J. [National Inst. of Health (NIH), Bethesda, MD (United States); Inglese, James [National Inst. of Health (NIH), Bethesda, MD (United States); Ferré-D’Amaré, Adrian R. [National Inst. of Health (NIH), Bethesda, MD (United States)

    2015-12-07

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. This method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. Our research demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  17. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Science.gov (United States)

    Baird, Nathan J.; Inglese, James; Ferré-D'Amaré, Adrian R.

    2015-12-01

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. The method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. This demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  18. Interactions between Carotenoids from Marine Bacteria and Other Micronutrients: Impact on Stability and Antioxidant Activity.

    Science.gov (United States)

    Sy, Charlotte; Dangles, Olivier; Borel, Patrick; Caris-Veyrat, Catherine

    2015-11-19

    Recently isolated spore-forming pigmented marine bacteria Bacillus indicus HU36 are sources of oxygenated carotenoids with original structures (about fifteen distinct yellow and orange pigments with acylated d-glucosyl groups). In this study, we evaluated the stability (sensitivity to iron-induced autoxidation) and antioxidant activity (inhibition of iron-induced lipid peroxidation) of combinations of bacterial HU36 carotenoids with the bacterial vitamin menaquinone MQ-7 and with phenolic antioxidants (vitamin E, chlorogenic acid, rutin). Unexpectedly, MQ-7 strongly improves the ability of HU36 carotenoids to inhibit Fe(II)-induced lipid peroxidation, although MQ-7 was not consumed in the medium. We propose that their interaction modifies the carotenoid antioxidant mechanism(s), possibly by allowing carotenoids to scavenge the initiating radicals. For comparison, β-carotene and lycopene in combination were shown to exhibit a slightly higher stability toward iron-induced autoxidation, as well as an additive antioxidant activity as compared to the carotenoids, individually. HU36 carotenoids and phenolic antioxidants displayed synergistic activities in the inhibition of linoleic acid peroxidation induced by heme iron, but not by free iron. Synergism could arise from antioxidants interacting via electron transfer through the porphyrin nucleus of heme iron. Overall, combining antioxidants acting via complementary mechanisms could be the key for optimizing the activity of this bacterial carotenoid cocktail.

  19. Magnetic interactions as a stabilizing factor of semiquinone species of lawsone by metal complexation

    Energy Technology Data Exchange (ETDEWEB)

    Valle-Bourrouet, Grettel [Universidad de Costa Rica, Escuela de Quimica, San Jose (Costa Rica); Ugalde-Saldivar, Victor M. [Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, C.P. 04510, Mexico, D.F. (Mexico); Gomez, Martin [Departamento de Sistemas Biologicos, Universidad Autonoma Metropolitana-Xochimilco, C.P. 04960, Mexico, D.F. (Mexico); Ortiz-Frade, Luis A. [Centro de Investigacion y Desarrollo Tecnologico en Electroquimica, Parque Tecnologico Queretaro, Sanfandila, 76703, Pedro Escobedo, Queretaro (Mexico); Gonzalez, Ignacio [Universidad Autonoma Metropolitana - Iztapalapa, Departamento de Quimica, Area de Electroquimica, Apartado postal 55-534, 09340, Mexico, D.F. (Mexico); Frontana, Carlos, E-mail: ultrabuho@yahoo.com.m [Departamento de Quimica, Centro de Investigacion y Estudios Avanzados, Av. Instituto Politecnico Nacional No. 2508 Col. San Pedro Zacatenco, C.P. 07360, Mexico, D.F. (Mexico)

    2010-12-01

    Changes in electrochemical reactivity for lawsone anions (lawsone, 2-hydroxy-1,4-naphthoquinone, HLw) being coordinated to a series of metallic ions in dimethylsulfoxide solution were evaluated. Upon performing cyclic voltammetry experiments for metal complexes of this quinone with pyridine (Py) - structural formula M(II)(Lw{sup -}){sub 2}(Py){sub 2}; M: Co(II), Ni(II), Zn(II) - it was found that the reduction of coordinated Lw{sup -} units occurs during the first and second electron uptake in the analyzed compounds. The stability of the electrogenerated intermediates for each complex depends on the d electron configuration in each metal center and is determined by magnetic interactions with the available spins considering an octahedral conformation for all the compounds. This was evidenced by in situ spectroelectrochemical-ESR measurements in the Zn(II) complex in which due to the lack of magnetic interaction owing to its electron configuration, the structure of the coordinated anion radical species was determined. Successive reduction of the associated Lw{sup -} units leads to partial dissociation of the complex, determined by the identification of free radical dianion structures in solution. These results show some insights on how metal-lawsone complexation can modify the solution reactivity and stability of the electrogenerated radical species.

  20. Interaction analysis of back-to-back mechanically stabilized earth walls

    Institute of Scientific and Technical Information of China (English)

    Sadok Benmebarek; Samir Attallaoui; Naïma Benmebarek

    2016-01-01

    Back-to-back mechanically stabilized earth walls (BBMSEWs) are encountered in bridge approaches, ramp ways, rockfall protection systems, earth dams, levees and noise barriers. However, available design guidelines for BBMSEWs are limited and not applicable to numerical modeling when back-to-back walls interact with each other. The objective of this paper is to investigate, using PLAXIS code, the effects of the reduction in the distance between BBMSEW, the reinforcement length, the quality of backfill material and the connection of reinforcements in the middle, when the back-to-back walls are close. The results indicate that each of the BBMSEWs behaves independently if the width of the embankment between mechanically stabilized earth walls is greater than that of the active zone. This is in good agreement with the result of FHWA design guideline. However, the results show that the FHWA design guideline un-derestimates the lateral earth pressure when back-to-back walls interact with each other. Moreover, for closer BBMSEWs, FHWA design guideline strongly overestimates the maximum tensile force in the reinforcement. The investigation of the quality of backfill material shows that the minor increase in embankment cohesion can lead to significant reductions in both the lateral earth pressure and the maximum tensile force in geosynthetic. When the distance between the two earth walls is close to zero, the connection of reinforcement between back-to-back walls significantly improves the factor of safety.

  1. TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.

    Science.gov (United States)

    Konishi, Akimitsu; Izumi, Takashi; Shimizu, Shigeomi

    2016-09-23

    Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Interactions between Carotenoids from Marine Bacteria and Other Micronutrients: Impact on Stability and Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Charlotte Sy

    2015-11-01

    Full Text Available Recently isolated spore-forming pigmented marine bacteria Bacillus indicus HU36 are sources of oxygenated carotenoids with original structures (about fifteen distinct yellow and orange pigments with acylated d-glucosyl groups. In this study, we evaluated the stability (sensitivity to iron-induced autoxidation and antioxidant activity (inhibition of iron-induced lipid peroxidation of combinations of bacterial HU36 carotenoids with the bacterial vitamin menaquinone MQ-7 and with phenolic antioxidants (vitamin E, chlorogenic acid, rutin. Unexpectedly, MQ-7 strongly improves the ability of HU36 carotenoids to inhibit FeII-induced lipid peroxidation, although MQ-7 was not consumed in the medium. We propose that their interaction modifies the carotenoid antioxidant mechanism(s, possibly by allowing carotenoids to scavenge the initiating radicals. For comparison, β-carotene and lycopene in combination were shown to exhibit a slightly higher stability toward iron-induced autoxidation, as well as an additive antioxidant activity as compared to the carotenoids, individually. HU36 carotenoids and phenolic antioxidants displayed synergistic activities in the inhibition of linoleic acid peroxidation induced by heme iron, but not by free iron. Synergism could arise from antioxidants interacting via electron transfer through the porphyrin nucleus of heme iron. Overall, combining antioxidants acting via complementary mechanisms could be the key for optimizing the activity of this bacterial carotenoid cocktail.

  3. Interaction analysis of back-to-back mechanically stabilized earth walls

    Directory of Open Access Journals (Sweden)

    Sadok Benmebarek

    2016-10-01

    Full Text Available Back-to-back mechanically stabilized earth walls (BBMSEWs are encountered in bridge approaches, ramp ways, rockfall protection systems, earth dams, levees and noise barriers. However, available design guidelines for BBMSEWs are limited and not applicable to numerical modeling when back-to-back walls interact with each other. The objective of this paper is to investigate, using PLAXIS code, the effects of the reduction in the distance between BBMSEW, the reinforcement length, the quality of backfill material and the connection of reinforcements in the middle, when the back-to-back walls are close. The results indicate that each of the BBMSEWs behaves independently if the width of the embankment between mechanically stabilized earth walls is greater than that of the active zone. This is in good agreement with the result of FHWA design guideline. However, the results show that the FHWA design guideline underestimates the lateral earth pressure when back-to-back walls interact with each other. Moreover, for closer BBMSEWs, FHWA design guideline strongly overestimates the maximum tensile force in the reinforcement. The investigation of the quality of backfill material shows that the minor increase in embankment cohesion can lead to significant reductions in both the lateral earth pressure and the maximum tensile force in geosynthetic. When the distance between the two earth walls is close to zero, the connection of reinforcement between back-to-back walls significantly improves the factor of safety.

  4. Pursuing Financial Stability: A Resource Dependence Perspective on Interactions between Pro-Vice Chancellors in a Network of Universities

    Science.gov (United States)

    Pilbeam, Colin

    2012-01-01

    In resource-constrained environments universities increasingly must interact collaboratively and competitively to ensure financial stability. Such interactions are supported by the actions of senior university managers. This study investigated the extent and purpose of the interconnections between members of two groups of pro-vice chancellors…

  5. Parabolized Stability Equations analysis of nonlinear interactions with forced eigenmodes to control subsonic jet instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Itasse, Maxime, E-mail: Maxime.Itasse@onera.fr; Brazier, Jean-Philippe, E-mail: Jean-Philippe.Brazier@onera.fr; Léon, Olivier, E-mail: Olivier.Leon@onera.fr; Casalis, Grégoire, E-mail: Gregoire.Casalis@onera.fr [Onera - The French Aerospace Lab, F-31055 Toulouse (France)

    2015-08-15

    Nonlinear evolution of disturbances in an axisymmetric, high subsonic, high Reynolds number hot jet with forced eigenmodes is studied using the Parabolized Stability Equations (PSE) approach to understand how modes interact with one another. Both frequency and azimuthal harmonic interactions are analyzed by setting up one or two modes at higher initial amplitudes and various phases. While single mode excitation leads to harmonic growth and jet noise amplification, controlling the evolution of a specific mode has been made possible by forcing two modes (m{sub 1}, n{sub 1}), (m{sub 2}, n{sub 2}), such that the difference in azimuth and in frequency matches the desired “target” mode (m{sub 1} − m{sub 2}, n{sub 1} − n{sub 2}). A careful setup of the initial amplitudes and phases of the forced modes, defined as the “killer” modes, has allowed the minimizing of the initially dominant instability in the near pressure field, as well as its estimated radiated noise with a 15 dB loss. Although an increase of the overall sound pressure has been found in the range of azimuth and frequency analyzed, the present paper reveals the possibility to make the initially dominant instability ineffective acoustically using nonlinear interactions with forced eigenmodes.

  6. Protein-silver nanoparticle interactions to colloidal stability in acidic environments.

    Science.gov (United States)

    Tai, Jui-Ting; Lai, Chao-Shun; Ho, Hsin-Chia; Yeh, Yu-Shan; Wang, Hsiao-Fang; Ho, Rong-Ming; Tsai, De-Hao

    2014-11-04

    We report a kinetic study of Ag nanoparticles (AgNPs) under acidic environments (i.e., pH 2.3 to pH ≈7) and systematically investigate the impact of protein interactions [i.e., bovine serum albumin (BSA) as representative] to the colloidal stability of AgNPs. Electrospray-differential mobility analysis (ES-DMA) was used to characterize the particle size distributions and the number concentrations of AgNPs. Transmission electron microscopy was employed orthogonally to provide visualization of AgNPs. For unconjugated AgNPs, the extent of aggregation, or the average particle size, was shown to be increased significantly with an increase of acidity, where a partial coalescence was found between the primary particles of unconjugated AgNP clusters. Aggregation rate constant, kD, was also shown to be proportional to acidity, following a correlation of log(kD) = -1.627(pH)-9.3715. Using ES-DMA, we observe BSA had a strong binding affinity (equilibrium binding constant, ≈ 1.1 × 10(6) L/mol) to the surface of AgNPs, with an estimated maximum molecular surface density of ≈0.012 nm(-2). BSA-functionalized AgNPs exhibited highly-improved colloidal stability compared to the unconjugated AgNPs under acidic environments, where both the acid-induced interfacial dissolution and the particle aggregation became negligible. Results confirm a complex mechanism of colloidal stability of AgNPs: the aggregation process was shown to be dominant, and the formation of BSA corona on AgNPs suppressed both particle aggregation and interfacial dissolution of AgNP samples under acidic environments.

  7. Decavanadate interactions with actin: inhibition of G-actin polymerization and stabilization of decameric vanadate.

    Science.gov (United States)

    Ramos, Susana; Manuel, Miguel; Tiago, Teresa; Duarte, Rui; Martins, Jorge; Gutiérrez-Merino, Carlos; Moura, José J G; Aureliano, Manuel

    2006-11-01

    Decameric vanadate species (V10) inhibit the rate and the extent of G-actin polymerization with an IC50 of 68+/-22 microM and 17+/-2 microM, respectively, whilst they induce F-actin depolymerization at a lower extent. On contrary, no effect on actin polymerization and depolymerization was detected for 2mM concentration of "metavanadate" solution that contains ortho and metavanadate species, as observed by combining kinetic with (51)V NMR spectroscopy studies. Although at 25 degrees C, decameric vanadate (10 microM) is unstable in the assay medium, and decomposes following a first-order kinetic, in the presence of G-actin (up to 8 microM), the half-life increases 5-fold (from 5 to 27 h). However, the addition of ATP (0.2mM) in the medium not only prevents the inhibition of G-actin polymerization by V10 but it also decreases the half-life of decomposition of decameric vanadate species from 27 to 10h. Decameric vanadate is also stabilized by the sarcoplasmic reticulum vesicles, which raise the half-life time from 5 to 18h whereas no effects were observed in the presence of phosphatidylcholine liposomes, myosin or G-actin alone. It is proposed that the "decavanadate" interaction with G-actin, favored by the G-actin polymerization, stabilizes decameric vanadate species and induces inhibition of G-actin polymerization. Decameric vanadate stabilization by cytoskeletal and transmembrane proteins can account, at least in part, for decavanadate toxicity reported in the evaluation of vanadium (V) effects in biological systems.

  8. Role of Dispersion Interactions in the Polymorphism and Entropic Stabilization of the Aspirin Crystal

    Science.gov (United States)

    Reilly, Anthony M.; Tkatchenko, Alexandre

    2014-08-01

    Aspirin has been used and studied for over a century but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable.

  9. Dissipatively Stabilized Quantum Sensor Based on Indirect Nuclear-Nuclear Interactions

    Science.gov (United States)

    Chen, Q.; Schwarz, I.; Plenio, M. B.

    2017-07-01

    We propose to use a dissipatively stabilized nitrogen vacancy (NV) center as a mediator of interaction between two nuclear spins that are protected from decoherence and relaxation of the NV due to the periodical resets of the NV center. Under ambient conditions this scheme achieves highly selective high-fidelity quantum gates between nuclear spins in a quantum register even at large NV-nuclear distances. Importantly, this method allows for the use of nuclear spins as a sensor rather than a memory, while the NV spin acts as an ancillary system for the initialization and readout of the sensor. The immunity to the decoherence and relaxation of the NV center leads to a tunable sharp frequency filter while allowing at the same time the continuous collection of the signal to achieve simultaneously high spectral selectivity and high signal-to-noise ratio.

  10. Simulating open quantum systems: from many-body interactions to stabilizer pumping

    CERN Document Server

    Mueller, M; Zhou, Y L; Roos, C F; Zoller, P

    2011-01-01

    In a recent experiment, Barreiro et al. demonstrated the fundamental building blocks of an open-system quantum simulator with trapped ions [Nature 470, 486 (2011)]. Using up to five ions, single- and multi-qubit entangling gate operations were combined with optical pumping in stroboscopic sequences. This enabled the implementation of both coherent many-body dynamics as well as dissipative processes by controlling the coupling of the system to an artificial, suitably tailored environment. This engineering was illustrated by the dissipative preparation of entangled two- and four-qubit states, the simulation of coherent four-body spin interactions and the quantum non-demolition measurement of a multi-qubit stabilizer operator. In the present paper, we present the theoretical framework of this gate-based ("digital") simulation approach for open-system dynamics with trapped ions. In addition, we discuss how within this simulation approach minimal instances of spin models of interest in the context of topological q...

  11. Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation

    Science.gov (United States)

    Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

    2016-11-01

    Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD+-dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some “loose-binding” substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

  12. Stability

    Directory of Open Access Journals (Sweden)

    Nada S. Abdelwahab

    2017-05-01

    Full Text Available The present work concerns with the development of stability indicating the RP-HPLC method for simultaneous determination of guaifenesin (GUF and pseudoephedrine hydrochloride (PSH in the presence of guaifenesin related substance (Guaiacol. GUC, and in the presence of syrup excepients with minimum sample pre-treatment. In the developed RP-HPLC method efficient chromatographic separation was achieved for GUF, PSH, GUC and syrup excepients using ODS column as a stationary phase and methanol: water (50:50, v/v, pH = 4 with orthophosphoric acid as a mobile phase with a flow rate of 1 mL min−1 and UV detection at 210 nm. The chromatographic run time was approximately 10 min. Calibration curves were drawn relating the integrated area under peak to the corresponding concentrations of PSH, GUF and GUC in the range of 1–8, 1–20, 0.4–8 μg mL−1, respectively. The developed method has been validated and met the requirements delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. The validated method was successfully applied for determination of the studied drugs in triaminic chest congestion® syrup; moreover its results were statistically compared with those obtained by the official method and no significant difference was found between them.

  13. Genotype × environmental interactions for analyzing adaptability and stability in different clones of Dalbergia sissoo Roxb.

    Institute of Scientific and Technical Information of China (English)

    A.Kumar; A.Bhatt; S.Ravichandran; V.Kumar; S.Dobhal

    2012-01-01

    In total 36 superior clones of Dalbergia sissoo Roxb.,screened from 300 selections conducted in natural and growing range of India and Nepal,were multiplied using single nodal cuttings and established to evaluate genotype×environmental interactions for adaptability and stability at the age of 30 months in three geographical locations in the state of Punjab,India.Clone 124 had maximum adaptability and stability (bi =1.04) to perform exceedingly well over the locations.Clones 36 and 1 were stable with mean regression coefficient of 0.84 and 1.22,respectively.Nonetheless,clone 41 performed exceedingly well for all the characters to attain maximum population mean,and the performance varied substantially across the locations.Therefore,clone 41 was eonsidered as productive but non-adaptive clone.Though some of the clones were sensitive to sites,14 clones for height,16 for collar diameter,12 for DBH and 7 for volume were relatively un-sensitive with higher regression coefficient.Nonetheless,clone 124 was the most stable with average bi value of 1.04 and productive,which could play an important role in future breeding and commercial deployment of stable and productive planting stock of Dalbergia sissoo.

  14. Complete structure of the bacterial flagellar hook reveals extensive set of stabilizing interactions

    Science.gov (United States)

    Matsunami, Hideyuki; Barker, Clive S.; Yoon, Young-Ho; Wolf, Matthias; Samatey, Fadel A.

    2016-01-01

    The bacterial flagellar hook is a tubular helical structure made by the polymerization of multiple copies of a protein, FlgE. Here we report the structure of the hook from Campylobacter jejuni by cryo-electron microscopy at a resolution of 3.5 Å. On the basis of this structure, we show that the hook is stabilized by intricate inter-molecular interactions between FlgE molecules. Extra domains in FlgE, found only in Campylobacter and in related bacteria, bring more stability and robustness to the hook. Functional experiments suggest that Campylobacter requires an unusually strong hook to swim without its flagella being torn off. This structure reveals details of the quaternary organization of the hook that consists of 11 protofilaments. Previous study of the flagellar filament of Campylobacter by electron microscopy showed its quaternary structure made of seven protofilaments. Therefore, this study puts in evidence the difference between the quaternary structures of a bacterial filament and its hook. PMID:27811912

  15. Solid phase stability of a double-minimum interaction potential system

    Energy Technology Data Exchange (ETDEWEB)

    Suematsu, Ayumi; Yoshimori, Akira, E-mail: a.yoshimori@cmt.phys.kyushu-u.ac.jp; Saiki, Masafumi; Matsui, Jun [Department of Physics, Kyushu University, Fukuoka 812-8581 (Japan); Odagaki, Takashi [School of Science and Engineering, Tokyo Denki University, Hatoyama, Saitama 350-0394 (Japan)

    2014-06-28

    We study phase stability of a system with double-minimum interaction potential in a wide range of parameters by a thermodynamic perturbation theory. The present double-minimum potential is the Lennard-Jones-Gauss potential, which has a Gaussian pocket as well as a standard Lennard-Jones minimum. As a function of the depth and position of the Gaussian pocket in the potential, we determine the coexistence pressure of crystals (fcc and bcc). We show that the fcc crystallizes even at zero pressure when the position of the Gaussian pocket is coincident with the first or third nearest neighbor site of the fcc crystal. The bcc crystal is more stable than the fcc crystal when the position of the Gaussian pocket is coincident with the second nearest neighbor sites of the bcc crystal. The stable crystal structure is determined by the position of the Gaussian pocket. These results show that we can control the stability of the solid phase by tuning the potential function.

  16. Interaction of bilirubin with Ag and Au ions: green synthesis of bilirubin-stabilized nanoparticles

    Science.gov (United States)

    Shukla, Shashi P.; Roy, Mainak; Mukherjee, Poulomi; Tyagi, A. K.; Mukherjee, Tulsi; Adhikari, Soumyakanti

    2012-07-01

    We report a simple green chemistry to synthesize and stabilize monodispersed silver and gold nanoparticles sols by reducing aqueous solution of the respective metal salts in the presence of bilirubin (BR). No additional capping agent was used in the process of stabilization of the nanoparticles. As a completely new finding, we have observed that BR known to be toxic at higher concentration in one hand and conversely an antioxidant at physiological concentration reduces these metal ions to form the respective metal nanoparticles. Moreover, BR and its oxidized products also serve as capping agents to the nanoparticles. The particles were characterized by transmission electron microscopy. BR and its oxidized products capped nanoparticles are stable for months. The UV-Vis absorption spectra of the silver sol show the plasmon peak of symmetric spherical particles which was further reflected in the TEM images. The sizes of the silver particles were about 5 nm. These silver particles showed reasonably high antibacterial activity in Gram negative wild type E. coli. In the case of interaction of BR with gold ions, we could obtain cubic gold nanoparticles of average sizes 20-25 nm. Possible modes of anchorage of BR and/its oxidized products to silver nanoparticles were demonstrated by surface-enhanced resonance Raman spectroscopy (SERS) that in turn demonstrated the feasibility of using these nanoparticles as SERS substrates.

  17. Interaction of bilirubin with Ag and Au ions: green synthesis of bilirubin-stabilized nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Shashi P. [Bhabha Atomic Research Centre, Radiation and Photochemistry Division (India); Roy, Mainak [Bhabha Atomic Research Centre, Chemistry Division (India); Mukherjee, Poulomi [Bhabha Atomic Research Centre, Nuclear Agriculture and Biotechnology Division (India); Tyagi, A. K. [Bhabha Atomic Research Centre, Chemistry Division (India); Mukherjee, Tulsi [Bhabha Atomic Research Centre, Chemistry Group (India); Adhikari, Soumyakanti, E-mail: asoumya@barc.gov.in [Bhabha Atomic Research Centre, Radiation and Photochemistry Division (India)

    2012-07-15

    We report a simple green chemistry to synthesize and stabilize monodispersed silver and gold nanoparticles sols by reducing aqueous solution of the respective metal salts in the presence of bilirubin (BR). No additional capping agent was used in the process of stabilization of the nanoparticles. As a completely new finding, we have observed that BR known to be toxic at higher concentration in one hand and conversely an antioxidant at physiological concentration reduces these metal ions to form the respective metal nanoparticles. Moreover, BR and its oxidized products also serve as capping agents to the nanoparticles. The particles were characterized by transmission electron microscopy. BR and its oxidized products capped nanoparticles are stable for months. The UV-Vis absorption spectra of the silver sol show the plasmon peak of symmetric spherical particles which was further reflected in the TEM images. The sizes of the silver particles were about 5 nm. These silver particles showed reasonably high antibacterial activity in Gram negative wild type E. coli. In the case of interaction of BR with gold ions, we could obtain cubic gold nanoparticles of average sizes 20-25 nm. Possible modes of anchorage of BR and/its oxidized products to silver nanoparticles were demonstrated by surface-enhanced resonance Raman spectroscopy (SERS) that in turn demonstrated the feasibility of using these nanoparticles as SERS substrates.

  18. Interstrand dipole-dipole interactions can stabilize the collagen triple helix.

    Science.gov (United States)

    Shoulders, Matthew D; Raines, Ronald T

    2011-07-01

    The amino acid sequence of collagen is composed of GlyXaaYaa repeats. A prevailing paradigm maintains that stable collagen triple helices form when (2S)-proline (Pro) or Pro derivatives that prefer the C(γ)-endo ring pucker are in the Xaa position and Pro derivatives that prefer the C(γ)-exo ring pucker are in the Yaa position. Anomalously, an amino acid sequence in an invertebrate collagen has (2S,4R)-4-hydroxyproline (Hyp), a C(γ)-exo-puckered Pro derivative, in the Xaa position. In certain contexts, triple helices with Hyp in the Xaa position are now known to be hyperstable. Most intriguingly, the sequence (GlyHypHyp)(n) forms a more stable triple helix than does the sequence (GlyProHyp)(n). Competing theories exist for the physicochemical basis of the hyperstability of (GlyHypHyp)(n) triple helices. By synthesizing and analyzing triple helices with different C(γ)-exo-puckered proline derivatives in the Xaa and Yaa positions, we conclude that interstrand dipole-dipole interactions are the primary determinant of their additional stability. These findings provide a new framework for understanding collagen stability.

  19. The Supply Chain Triangle: How Synchronisation, Stability, and Productivity of Material Flows Interact

    Directory of Open Access Journals (Sweden)

    Florian Klug

    2013-01-01

    Full Text Available Empirical evidence created a commonly accepted understanding that synchronisation and stability of material flows impact its productivity. This crucial link between synchronous and stable material flows by time and quantity to create a supply chain with the highest throughput rates is at the heart of lean thinking. Although this supply chain triangle has generally been acknowledged over many years, it is necessary to reach a finer understanding of these dynamics. Therefore, we will develop and study supply chains with the help of fluid dynamics. A multistage, continuous material flow is modelled through a conservation law for material density. Unlike similar approaches, our model is not based on some quasi steady-state assumptions about the stochastic behaviour of the involved supply chain but rather on a simple deterministic rule for material flow density. These models allow us to take into account the nonlinear, dynamical interactions of different supply chain echelons and to test synchronised and stable flow with respect to its potential impacts. Numerical simulations verify that the model is able to simulate transient supply chain phenomena. Moreover, a quantification method relating to the fundamental link between synchronisation, stability, and productivity of supply chains has been found.

  20. Stabilization of the angiotensin-(1-7) receptor Mas through interaction with PSD95.

    Science.gov (United States)

    Bian, Weihua; Sun, Licui; Yang, Longyan; Li, Ji-Feng; Hu, Jia; Zheng, Shuai; Guo, Ruihan; Feng, Duiping; Ma, Qian; Shi, Xiaocui; Xiong, Ying; Yang, Xiaomei; Song, Ran; Xu, Jianguo; Wang, Songlin; He, Junqi

    2013-08-01

    The functions and signalling mechanisms of the Ang-(1-7) [angiotensin-(1-7)] receptor Mas have been studied extensively. However, less attention has been paid to the intracellular regulation of Mas protein. In the present study, PSD95 (postsynaptic density 95), a novel binding protein of Mas receptor, was identified, and their association was characterized further. Mas specifically interacts with PDZ1-2, but not the PDZ3, domain of PSD95 via Mas-CT (Mas C-terminus), and the last four amino acids [ETVV (Glu-Thr-Val-Val)] of Mas-CT were determined to be essential for this interaction, as shown by GST pull-down, co-immunoprecipitation and confocal co-localization experiments. Gain-of-function and loss-of-function studies indicated that PSD95 enhanced Mas protein expression by increasing the stabilization of the receptor. Mas degradation was robustly inhibited by the proteasome inhibitor MG132 in time- and dose-dependent manners, and the expression of PSD95 impaired Mas ubiquitination, indicating that the PSD95-Mas association inhibits Mas receptor degradation via the ubiquitin-proteasome proteolytic pathway. These findings reveal a novel mechanism of Mas receptor regulation by which its expression is modulated at the post-translational level by ubiquitination, and clarify the role of PSD95, which binds directly to Mas, blocking the ubiquitination and subsequent degradation of the receptor via the ubiquitin-proteasome proteolytic pathway.

  1. A direct proofreader-clamp interaction stabilizes the Pol III replicase in the polymerization mode

    KAUST Repository

    Jergic, Slobodan

    2013-02-22

    Processive DNA synthesis by the αÉ"θ core of the Escherichia coli Pol III replicase requires it to be bound to the β 2 clamp via a site in the α polymerase subunit. How the É" proofreading exonuclease subunit influences DNA synthesis by α was not previously understood. In this work, bulk assays of DNA replication were used to uncover a non-proofreading activity of É". Combination of mutagenesis with biophysical studies and single-molecule leading-strand replication assays traced this activity to a novel β-binding site in É" that, in conjunction with the site in α, maintains a closed state of the αÉ"θ-β 2 replicase in the polymerization mode of DNA synthesis. The É"-β interaction, selected during evolution to be weak and thus suited for transient disruption to enable access of alternate polymerases and other clamp binding proteins, therefore makes an important contribution to the network of protein-protein interactions that finely tune stability of the replicase on the DNA template in its various conformational states. © 2013 European Molecular Biology Organization.

  2. Sulfatide-Hsp70 Interaction Promotes Hsp70 Clustering and Stabilizes Binding to Unfolded Protein

    Directory of Open Access Journals (Sweden)

    Yoichiro Harada

    2015-05-01

    Full Text Available The 70-kDa heat shock protein (Hsp70, one of the major stress-inducible molecular chaperones, is localized not only in the cytosol, but also in extracellular milieu in mammals. Hsp70 interacts with various cell surface glycolipids including sulfatide (3'-sulfogalactosphingolipid. However, the molecular mechanism, as well as the biological relevance, underlying the glycolipid-Hsp70 interaction is unknown. Here we report that sulfatide promotes Hsp70 oligomerization through the N-terminal ATPase domain, which stabilizes the binding of Hsp70 to unfolded protein in vitro. We find that the Hsp70 oligomer has apparent molecular masses ranging from 440 kDa to greater than 669 kDa. The C-terminal peptide-binding domain is dispensable for the sulfatide-induced oligomer formation. The oligomer formation is impaired in the presence of ATP, while the Hsp70 oligomer, once formed, is unable to bind to ATP. These results suggest that sulfatide locks Hsp70 in a high-affinity state to unfolded proteins by clustering the peptide-binding domain and blocking the binding to ATP that induces the dissociation of Hsp70 from protein substrates.

  3. Communication: Many-body stabilization of non-covalent interactions: Structure, stability, and mechanics of Ag3Co(CN)6 framework

    Science.gov (United States)

    Liu, Xiaofei; Hermann, Jan; Tkatchenko, Alexandre

    2016-12-01

    Stimuli-responsive metal-organic frameworks (MOFs) and other framework materials exhibit a broad variety of useful properties, which mainly stem from an interplay of strong covalent bonds within the organic linkers with presumably weak van der Waals (vdW) interactions which determine the overall packing of the framework constituents. Using Ag3Co(CN)6 as a fundamental test case—a system with a colossal positive and negative thermal expansion [A. L. Goodwin et al., Science 319, 794 (2008)]—we demonstrate that its structure, stability, dielectric, vibrational, and mechanical properties are critically influenced by many-body electronic correlation contributions to non-covalent vdW interactions. The Ag3Co(CN)6 framework is a remarkable molecular crystal, being visibly stabilized, rather than destabilized, by many-body vdW correlations. A detailed comparison with H3Co(CN)6 highlights the crucial role of strongly polarized metallophilic interactions in dictating the exceptional properties of denser MOFs. Beyond MOFs, our findings indicate that many-body electronic correlations can substantially stabilize polarizable materials, providing a novel mechanism for tuning the properties of nanomaterials with intricate structural motifs.

  4. Integrating plant-microbe interactions to understand soil C stabilization with the MIcrobial-MIneral Carbon Stabilization model (MIMICS)

    Science.gov (United States)

    Grandy, Stuart; Wieder, Will; Kallenbach, Cynthia; Tiemann, Lisa

    2014-05-01

    If soil organic matter is predominantly microbial biomass, plant inputs that build biomass should also increase SOM. This seems obvious, but the implications fundamentally change how we think about the relationships between plants, microbes and SOM. Plant residues that build microbial biomass are typically characterized by low C/N ratios and high lignin contents. However, plants with high lignin contents and high C/N ratios are believed to increase SOM, an entrenched idea that still strongly motivates agricultural soil management practices. Here we use a combination of meta-analysis with a new microbial-explicit soil biogeochemistry model to explore the relationships between plant litter chemistry, microbial communities, and SOM stabilization in different soil types. We use the MIcrobial-MIneral Carbon Stabilization (MIMICS) model, newly built upon the Community Land Model (CLM) platform, to enhance our understanding of biology in earth system processes. The turnover of litter and SOM in MIMICS are governed by the activity of r- and k-selected microbial groups and temperature sensitive Michaelis-Menten kinetics. Plant and microbial residues are stabilized short-term by chemical recalcitrance or long-term by physical protection. Fast-turnover litter inputs increase SOM by >10% depending on temperature in clay soils, and it's only in sandy soils devoid of physical protection mechanisms that recalcitrant inputs build SOM. These results challenge centuries of lay knowledge as well as conventional ideas of SOM formation, but are they realistic? To test this, we conducted a meta-analysis of the relationships between the chemistry of plant liter inputs and SOM concentrations. We find globally that the highest SOM concentrations are associated with plant inputs containing low C/N ratios. These results are confirmed by individual tracer studies pointing to greater stabilization of low C/N ratio inputs, particularly in clay soils. Our model and meta-analysis results suggest

  5. Surface-supported Ag islands stabilized by a quantum size effect: Their interaction with small molecules relevant to ethylene epoxidation

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dahai [Iowa State Univ., Ames, IA (United States)

    2013-05-15

    This dissertation focuses on how QSE-stabilized, surface-supported Ag nanoclusters will interact with ethylene or oxygen. Experiments are performed to determine whether the QSE-mediated Ag islands react differently toward adsorption of ethylene or oxygen, or whether the adsorption of these small molecules will affect the QSE-mediated stability of Ag islands. Studies of the interaction of oxygen with Ag/Si(111)-7×7 were previously reported, but these studies were performed at a low Ag coverage where 3D Ag islands were not formed. So the study of such a system at a higher Ag coverage will be a subject of this work. The interaction of ethylene with Ag/Si(111)-7×7, as well as the interaction of oxygen with Ag/NiAl(110) are also important parts of this study.

  6. Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

    Directory of Open Access Journals (Sweden)

    Christian B. Winiger

    2014-07-01

    Full Text Available Aromatic π–π stacking interactions are ubiquitous in nature, medicinal chemistry and materials sciences. They play a crucial role in the stacking of nucleobases, thus stabilising the DNA double helix. The following paper describes a series of chimeric DNA–polycyclic aromatic hydrocarbon (PAH hybrids. The PAH building blocks are electron-rich pyrene and electron-poor perylenediimide (PDI, and were incorporated into complementary DNA strands. The hybrids contain different numbers of pyrene–PDI interactions that were found to directly influence duplex stability. As the pyrene–PDI ratio approaches 1:1, the stability of the duplexes increases with an average value of 7.5 °C per pyrene–PDI supramolecular interaction indicating the importance of electrostatic complementarity for aromatic π–π stacking interactions.

  7. Stability of metal organic frameworks and interaction of small gas molecules in these materials

    Science.gov (United States)

    Tan, Kui

    The work in this dissertation combines spectroscopy ( in-situ infrared absorption and Raman), powder X-ray diffraction and DFT calculations to study the stability of metal organic frameworks materials (MOFs) in the presence of water vapor and other corrosive gases (e.g., SO 2, NO2 NO), and the interaction and competitive co-adsorption of several gases within MOFs by considering two types of prototypical MOFs: 1) a MOF with saturated metal centers based on paddlewheel secondary building units: M(bdc)(ted)0.5 [M=Cu, Zn, Ni, Co, bdc = 1,4-benzenedicarboxylate, ted = triethylenediamine], and 2) a MOF with unsaturated metal centers: M2(dobdc) [M=Mg2+, Zn2+, Ni2+, Co2+ and dobdc = 2,5-dihydroxybenzenedicarboxylate]. We find that the stability of MOFs to water vapor critically depends on their structure and the specific metal cation in the building units. For M(bdc)(ted)0.5, the metal-bdc bond is the most vulnerable for Cu(bdc)(ted)0.5, while the metal-ted bond is first attacked for the Zn and Co analogs. In contrast, Ni(bdc)(ted)0.5 remains stable under the same conditions. For M2(dobdc), or MOF-74, the weak link is the dobdc-metal bond. The water molecule is dissociatively adsorbed at the metal-oxygen group with OH adsorption directly on the metal center and H adsorption on the bridging O of the phenolate group in the dobdc linker. Other technologically important molecules besides water, such as NO, NO2, SO2, tend to poison M2(dobdc) through dissociative or molecular adsorption onto the open metal sites. A high uptake SO2 capacity was measured in M(bdc)(ted)0.5, attributed to multipoint interactions between the guest SO2 molecule and the MOF host. In the case of competitive co-adsorption between CO2 and other small molecules, we find that binding energy alone is not a good indicator of molecular site occupation within the MOF (i.e., it cannot successfully predict and evaluate the displacement of CO2 by other molecules). Instead, we show that the kinetic barrier for the

  8. Intergroup structure and identity management among ethnic minority and majority groups : The interactive effects of perceived stability, legitimacy, and permeability

    NARCIS (Netherlands)

    Verkuyten, Maykel; Reijerse, Arjan

    2008-01-01

    This paper is an examination, in a natural setting, of the interactive effects of perceived stability, legitimacy, and group permeability on group identification, stereotypes, and group feelings among Turkish-Dutch and ethnically Dutch participants. The findings strongly support predictions derived

  9. The Thermal Stability and Domain Interactions of the Mannitol Permease of Escherichia coli. A Differential Scanning Calorimetry Study

    NARCIS (Netherlands)

    Meijberg, Wim; Schuurman-Wolters, Gea K.; Scheek, Ruud M.; Robillard, George T.

    1998-01-01

    The thermal stability and domain interactions in the mannitol transporter from Escherichia coli, enzyme IImtl, have been studied by differential scanning calorimetry. To this end, the wild type enzyme, IICBAmtl, as well as IICBmtl and IICmtl, were reconstituted into a dimyristoylphosphatidylcholine

  10. The thermal stability and domain interactions of the mannitol permease of Escherichia coli - A differential scanning calorimetry study

    NARCIS (Netherlands)

    Meijberg, W.; Schuurman-Wolters, G.K.; Scheek, R.M.; Robillard, G.T.

    1998-01-01

    The thermal stability and domain interactions in the mannitol transporter from Escherichia coli, enzyme IImtl, have been studied by differential scanning calorimetry. To this end, the wild type enzyme, IICBAmtl, as well as IICBmtl and IICmtl, were reconstituted into a dimyristoylphosphatidylcholine

  11. Exploring the Stability of Gold Nanoparticles by Experimenting with Adsorption Interactions of Nanomaterials in an Undergraduate Lab

    Science.gov (United States)

    Lee, Chi-Feng; You, Pei-Yun; Lin, Ying-Chiao; Hsu, Tsai-Ling; Cheng, Pi-Yun; Wu, Yu-Xuan; Tseng, Chi-Shun; Chen, Sheng-Wen; Chang, Huey-Por; Lin, Yang-Wei

    2015-01-01

    The proposed experiment can help students to understand the factors involved in the stability of gold nanoparticles (Au NPs) by exploring the adsorption interaction between Au NPs and various substances. The students in this study found that the surface plasmon resonance band of Au NP solutions underwent a red shift (i.e., from 520 to 650 nm)…

  12. Molecular Control of Vascular Tube Morphogenesis and Stabilization: Regulation by Extracellular Matrix, Matrix Metalloproteinases, and Endothelial Cell-Pericyte Interactions

    Science.gov (United States)

    Davis, George E.; Stratman, Amber N.; Sacharidou, Anastasia

    Recent studies have revealed a critical role for both extracellular matrices and matrix metalloproteinases in the molecular control of vascular morphogenesis and stabilization in three-dimensional (3D) tissue environments. Key interactions involve endothelial cells (ECs) and pericytes, which coassemble to affect vessel formation, remodeling, and stabilization events during development and postnatal life. EC-pericyte interactions control extracellular matrix remodeling events including vascular basement membrane matrix assembly, a necessary step for endothelial tube maturation and stabilization. ECs form tube networks in 3D extracellular matrices in a manner dependent on integrins, membrane-type metalloproteinases, and the Rho GTPases, Cdc42 and Rac1. Recent work has defined an EC lumen signaling complex of proteins composed of these proteins that controls 3D matrix-specific signaling events required for these processes. The EC tube formation process results in the creation of a network of proteolytically generated vascular guidance tunnels. These tunnels are physical matrix spaces that regulate vascular tube remodeling and represent matrix conduits into which pericytes are recruited to allow dynamic cell-cell interactions with ECs. These dynamic EC-pericyte interactions induce vascular basement membrane matrix deposition, leading to vessel maturation and stabilization.

  13. Stability of resonant configurations during the migration of planets and constraints on disk-planet interactions

    CERN Document Server

    Delisle, J -B; Laskar, J

    2015-01-01

    We study the stability of mean-motion resonances (MMR) between two planets during their migration in a protoplanetary disk. We use an analytical model of resonances, and describe the effect of the disk by a migration timescale (T_{m,i}) and an eccentricity damping timescale (T_{e,i}) for each planet (i=1,2 respectively for the inner and outer planet). We show that the resonant configuration is stable if T_{e,1}/T_{e,2} > (e_1/e_2)^2. This general result can be used to put constraints on specific models of disk-planet interactions. For instance, using classical prescriptions for type I migration, we show that when the angular momentum deficit (AMD) of the inner orbit is larger than the outer's orbit AMD, resonant systems must have a locally inverted disk density profile to stay locked in resonance during the migration. This inversion is very untypical of type I migration and our criterion can thus provide an evidence against classical type I migration. That is indeed the case for the Jupiter-mass resonant syst...

  14. Contrasting the beam interaction characteristics of selected lasers with a partially stabilized zirconia bio-ceramic

    Science.gov (United States)

    Lawrence, J.

    2002-08-01

    Differences in the beam interaction characteristics of a CO2 laser, a Nd : YAG laser, a high power diode laser (HPDL) and an excimer laser with a partially stabilized zirconia bio-ceramic have been studied. A derivative of Beer-Lambert's law was applied and the laser beam absorption lengths of the four lasers were calculated as 33.55×10-3 cm for the CO2 laser, 18.22×10-3 cm for the Nd : YAG laser, 17.17×10-3 cm for the HPDL and 8.41×10-6 cm for the excimer laser. It was determined graphically that the fluence threshold values at which significant material removal was effected by the CO2 laser, the Nd : YAG laser, the HPDL and the excimer laser were 52 J cm-2, 97 J cm-2, 115 J cm-2 and 0.48 J cm-2, respectively. The thermal loading value for the CO2 laser, the Nd : YAG laser, the HPDL and the excimer laser were calculated as being 1.55 kJ cm-3, 5.32 kJ cm3, 6.69 kJ cm-3 and 57.04 kJ cm-3, respectively.

  15. Additive interfacial chiral interaction in multilayers for stabilization of small individual skyrmions at room temperature

    Science.gov (United States)

    Moreau-Luchaire, C.; Moutafis, C.; Reyren, N.; Sampaio, J.; Vaz, C. A. F.; van Horne, N.; Bouzehouane, K.; Garcia, K.; Deranlot, C.; Warnicke, P.; Wohlhüter, P.; George, J.-M.; Weigand, M.; Raabe, J.; Cros, V.; Fert, A.

    2016-05-01

    Facing the ever-growing demand for data storage will most probably require a new paradigm. Nanoscale magnetic skyrmions are anticipated to solve this issue as they are arguably the smallest spin textures in magnetic thin films in nature. We designed cobalt-based multilayered thin films in which the cobalt layer is sandwiched between two heavy metals and so provides additive interfacial Dzyaloshinskii-Moriya interactions (DMIs), which reach a value close to 2 mJ m-2 in the case of the Ir|Co|Pt asymmetric multilayers. Using a magnetization-sensitive scanning X-ray transmission microscopy technique, we imaged small magnetic domains at very low fields in these multilayers. The study of their behaviour in a perpendicular magnetic field allows us to conclude that they are actually magnetic skyrmions stabilized by the large DMI. This discovery of stable sub-100 nm individual skyrmions at room temperature in a technologically relevant material opens the way for device applications in the near future.

  16. Cat-state generation and stabilization for a nuclear spin through electric quadrupole interaction

    Science.gov (United States)

    Bulutay, Ceyhun

    2017-07-01

    Spin cat states are superpositions of two or more coherent spin states (CSSs) that are distinctly separated over the Bloch sphere. Additionally, the nuclei with angular momenta greater than 1/2 possess a quadrupolar charge distribution. At the intersection of these two phenomena, we devise a simple scheme for generating various types of nuclear-spin cat states. The native biaxial electric quadrupole interaction that is readily available in strained solid-state systems plays a key role here. However, the fact that built-in strain cannot be switched off poses a challenge for the stabilization of target cat states once they are prepared. We remedy this by abruptly diverting via a single rotation pulse the state evolution to the neighborhood of the fixed points of the underlying classical Hamiltonian flow. Optimal process parameters are obtained as a function of electric field gradient biaxiality and nuclear-spin angular momentum. The overall procedure is seen to be robust under 5% deviations from optimal values. We show that higher-level cat states with four superposed CSS can also be formed using three rotation pulses. Finally, for open systems subject to decoherence we extract the scaling of cat-state fidelity damping with respect to the spin quantum number. This reveals rates greater than the dephasing of individual CSSs. Yet, our results affirm that these cat states can preserve their fidelities for practically useful durations under the currently attainable decoherence levels.

  17. Bianchi type I anisotropic universe and stability interacting ghost dark energy in Brans-Dicke theories

    CERN Document Server

    Hossienkhani, Hossien

    2016-01-01

    A spatially homogeneous and anisotropic Bianchi type I universe has been studied with the ghost dark energy (GDE) in the framework of Brans-Dicke theory. For this purpose, we use the squared sound speed $v_s^2$ whose sign determines the stability of the model. At first, we obtain the equation of state parameter, $\\omega_\\Lambda$, the deceleration parameter $q$ and the evolution equation of the ghost dark energy. Then, we extend our study to the case of ghost dark energy in a non-isotropic and Brans-Dicke framework and find out that the transition of $\\omega_\\Lambda$ to the phantom regime can be more easily accounted for than when it is restored into the Einstein field equations. Our numerical result show the effects of the interaction and anisotropic on the evolutionary behaviour the ghost dark energy models. In conclusion, we find evidence that the ghost dark energy in BD theory can lead to a stable universe favored by observations at the present time.

  18. Spectroscopic Characterization of Stability and Interaction of Pd-Ag Complexes

    Directory of Open Access Journals (Sweden)

    Sharad V. Lande

    2014-01-01

    Full Text Available Colloidal metal nanoparticles are of great interest because of their use as catalysts, photocatalysts, adsorbents, and sensors as well as their application in optical, electronic, and magnetic devices. Supported bimetallic systems represent a large part of heterogeneous catalysts which have been used in various reactions important in the chemical, petrochemical, and oil industry. Pd-Ag bimetallic nanocatalysts have become vitally important in some of the petrochemical industry’s processes like hydrogenation of C2–C5 olefins. A heat-treatment method for the preparation of well-stable Pd-Ag complexes is demonstrated using water, concentrated HCl and concentrated nitric acid as media. The stability and interaction of Pd-Ag complexes were characterized by UV-vis absorption spectroscopy. Pd-Ag bimetallic nanoparticles of spherical cubic and octahedral shape in the range of average particle size of 20–60 nm have been prepared and characterized by transmission electron microscopy (TEM.

  19. Manipulation of the magnetic exchange interaction in SmCo films with high thermal stability by controlling phase transformation

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Chun; Li, Ning; Li, Shuai; Huo, Qianming; Li, Minghua; Zhan, Qian; Jiang, Yong; Yu, Guanghua [University of Science and Technology Beijing, Department of Materials Physics and Chemistry, Beijing (China); Li, Baohe H. [Beijing Technology and Business University, Department of Physics, School of Sciences, Beijing (China); Yin, Jinhua [University of Science and Technology Beijing, Department of Physics, Beijing (China)

    2012-01-15

    High thermal stability and tunable magnetic exchange interaction (MEI) in SmCo materials have been the critical problem in applications to magnetic recording media and nanocomposite permanent magnets. We constructed SmCo films with a high thermal stability and tunable MEI by controlling the phase transformation through properly increasing the Sm concentration (20.5-37.7 at.%) and controlling the annealing process. Microstructure studies show that the SmCo{sub 5} phases ensure that the film has a high thermal stability. Moreover, we manipulated the MEI in the film with non-magnetic precipitated SmCo{sub 2} particles in the vicinity of SmCo{sub 5} particles. These results provide a novel way to tune the MEI in SmCo materials while maintaining a high thermal stability. (orig.)

  20. Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

    Science.gov (United States)

    DeFeo, Christopher J.; Alvarado-Facundo, Esmeralda; Vassell, Russell

    2015-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well

  1. Stability and phase transition of localized modes in Bose–Einstein condensates with both two- and three-body interactions

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xiao-Dong; Ai, Qing; Zhang, Mei; Xiong, Jun, E-mail: junxiong@bnu.edu.cn; Yang, Guo-Jian; Deng, Fu-Guo

    2015-09-15

    We investigate the stability and phase transition of localized modes in Bose–Einstein Condensates (BECs) in an optical lattice with the discrete nonlinear Schrödinger model by considering both two- and three-body interactions. We find that there are three types of localized modes, bright discrete breather (DB), discrete kink (DK), and multi-breather (MUB). Moreover, both two- and three-body on-site repulsive interactions can stabilize DB, while on-site attractive three-body interactions destabilize it. There is a critical value for the three-body interaction with which both DK and MUB become the most stable ones. We give analytically the energy thresholds for the destabilization of localized states and find that they are unstable (stable) when the total energy of the system is higher (lower) than the thresholds. The stability and dynamics characters of DB and MUB are general for extended lattice systems. Our result is useful for the blocking, filtering, and transfer of the norm in nonlinear lattices for BECs with both two- and three-body interactions.

  2. Biomass Reallocation between Juveniles and Adults Mediates Food Web Stability by Distributing Energy Away from Strong Interactions.

    Science.gov (United States)

    Caskenette, Amanda L; McCann, Kevin S

    2017-01-01

    Ecological theory has uncovered dynamical differences between food web modules (i.e. low species food web configurations) with only species-level links and food web modules that include within-species links (e.g. non-feeding links between mature and immature individuals) and has argued that these differences ought to cause food web theory that includes within-species links to contrast with classical food web theory. It is unclear, however, if life-history will affect the observed connection between interaction strength and stability in species-level theory. We show that when the predator in a species-level food chain is split into juvenile and adult stages using a simple nested approach, stage-structure can mute potentially strong interactions through the transfer of biomass within a species. Within-species biomass transfer distributes energy away from strong interactions promoting increased system stability consistent with classical food web theory.

  3. Small-Molecule Stabilization of the 14-3-3/Gab2 Protein-Protein Interaction (PPI) Interface.

    Science.gov (United States)

    Bier, David; Bartel, Maria; Sies, Katharina; Halbach, Sebastian; Higuchi, Yusuke; Haranosono, Yu; Brummer, Tilman; Kato, Nobuo; Ottmann, Christian

    2016-04-19

    Small-molecule modulation of protein-protein interactions (PPIs) is one of the most promising new areas in drug discovery. In the vast majority of cases only inhibition or disruption of PPIs is realized, whereas the complementary strategy of targeted stabilization of PPIs is clearly under-represented. Here, we report the example of a semi-synthetic natural product derivative--ISIR-005--that stabilizes the cancer-relevant interaction of the adaptor protein 14-3-3 and Gab2. The crystal structure of ISIR-005 in complex with 14-3-3 and the binding motif of Gab2 comprising two phosphorylation sites (Gab2pS210pT391) showed how the stabilizing molecule binds to the rim-of-the-interface of the protein complex. Only in the direct vicinity of 14-3-3/Gab2pT391 site is a pre-formed pocket occupied by ISIR-005; binding of the Gab2pS210 motif to 14-3-3 does not create an interface pocket suitable for the molecule. Accordingly, ISIR-005 only stabilizes the binding of the Gab2pT391 but not the Gab2pS210 site. This study represents structural and biochemical proof of the druggability of the 14-3-3/Gab2 PPI interface with important implications for the development of PPI stabilizers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. The Interplay of Disulfide Bonds, α-Helicity, and Hydrophobic Interactions Leads to Ultrahigh Proteolytic Stability of Peptides.

    Science.gov (United States)

    Chen, Yaqi; Yang, Chaoqiong; Li, Tao; Zhang, Miao; Liu, Yang; Gauthier, Marc A; Zhao, Yibing; Wu, Chuanliu

    2015-08-10

    The contribution of noncovalent interactions to the stability of naturally occurring peptides and proteins has been generally acknowledged, though how these can be rationally manipulated to improve the proteolytic stability of synthetic peptides remains to be explored. In this study, a platform to enhance the proteolytic stability of peptides was developed by controllably dimerizing them into α-helical dimers, connected by two disulfide bonds. This platform not only directs peptides toward an α-helical conformation but permits control of the interfacial hydrophobic interactions between the peptides of the dimer. Using two model dimeric systems constructed from the N-terminal α-helix of RNase A and known inhibitors for the E3 ubiquitin ligase MDM2 (and its homologue MDMX), a deeper understanding into the interplay of disulfide bonds, α-helicity, and hydrophobic interactions on enhanced proteolytic stability was sought out. Results reveal that all three parameters play an important role on attaining ultrahigh proteolytic resistance, a concept that can be exploited for the development of future peptide therapeutics. The understanding gained through this study will enable this strategy to be tailored to new peptides because the proposed strategy displays substantial tolerance to sequence permutation. It thus appears promising for conveniently creating prodrugs composed entirely of the therapeutic peptide itself (i.e., in the form of a dimer).

  5. AOCS Performance and Stability Validation for a 160-m Solar Sail with Control-Structure Interactions

    Science.gov (United States)

    Wie, Bong; Murphy, David

    2005-01-01

    Future solar sail missions, such as NASA's Solar Polar Imager Vision, will require sails with dimensions on the order of 50-500 m. We are examining a square sail design with moving mass (trim control mass, TCM) and quadrant rotation primary actuators plus pulsed plasma thrusters (PPTs) at the mast tips for backup attitude control. Quadrant rotation is achieved via roll stabilizer bars (RSB) at the mast tips. At these sizes, given the gossamer nature of the sail supporting structures, flexible modes may be low enough to interact with the control system, especially as these actuators are located on the flexible structure itself and not on the rigid core. This paper develops a practical analysis of the flexible interactions using state-space systems and modal data from finite element models of the system. Torsion and bending of the masts during maneuvers could significantly affect the function of the actuators while activation of the membrane modes could adversely affect the thrust vector direction and magnitude. Analysis of the RSB and TCM dynamics for developing high-fidelity simulations is included. For control analysis of the flexible system, standard finite-element models of the flexible sail body are loaded and the modal data is used to create a modal coordinate state-space system. Key parameters include which modes to include, which nodes are of interest for force inputs and displacement outputs, connecting nodes through which external forces and torques are applied from the flex body to the core, any nominal momentum in the system, and any steady rates. The system is linearized about the nominal attitude and rate. The state-space plant can then be analyzed with a state-space controller, and Bode, Nyquist, step and impulse responses generated. The approach is general for any rigid core with a flexible appendage. This paper develops a compensator for a simple two-mass flex system and extrapolates the results to the solar sail. A finite element model of the 20 m

  6. Protor-2 interacts with tristetraprolin to regulate mRNA stability during stress

    Science.gov (United States)

    Holmes, Brent; Artinian, Nicholas; Anderson, Lauren; Martin, Jheralyn; Masri, Janine; Cloninger, Cheri; Bernath, Andrew; Bashir, Tariq; Benavides-Serrato, Angelica; Gera, Joseph

    2011-01-01

    The A/U-rich RNA binding protein tristetraprolin (TTP) is an mRNA destabilizing factor which plays a role in the regulated turnover of many transcripts encoding proteins involved in immune function and cell growth control. TTP also plays a role in stress-induced destabilization of mRNAs. Here we report the interaction of TTP with a component of the mTORC2 kinase, Protor-2 (PRR5-L, protein Q6MZQ0/FLJ14213/CAE45978). Protor-2 is structurally similar to human PRR5 and has been demonstrated to bind mTORC2 via Rictor and/or Sin1 and may signal downstream events promoting apoptosis. Protor-2 dissociates from mTORC2 upon hyperactivation of the kinase and is not required for mTORC2 integrity or activity. We identified Protor-2 in a yeast two-hybrid screen as a TTP interactor using the C-terminal mRNA decay domain of TTP as bait. The interaction of Protor-2 with TTP was also confirmed in vivo in co-immunoprecipitation experiments and Protor-2 was also detected in immunoprecipitates of rictor. Protor-2 was shown to stimulate TTP-mediated mRNA turnover of several TTP-associated mRNAs (TNF-α, GM-CSF, IL-3 and COX-2) in Jurkat cells when overexpressed while the half-lives of transcripts which do not decay via a TTP-mediated mechanism were unaffected. Knockdown of Protor-2 via RNAi inhibited TTP-mediated mRNA turnover of these TTP-associated mRNAs and inhibited association of TTP with cytoplasmic stress granules (SG) or mRNA processing bodies (P-bodies) following induction of the integrated stress response. These results suggest that Protor-2 associates with TTP to accelerate TTP-mediated mRNA turnover and functionally links the control of TTP regulated mRNA stability to mTORC2 activity. PMID:21964062

  7. Magnetic Radial Vortex Stabilization and Efficient Manipulation Driven by the Dzyaloshinskii-Moriya Interaction and Spin-Transfer Torque

    Science.gov (United States)

    Siracusano, G.; Tomasello, R.; Giordano, A.; Puliafito, V.; Azzerboni, B.; Ozatay, O.; Carpentieri, M.; Finocchio, G.

    2016-08-01

    Solitons are very promising for the design of the next generation of ultralow power devices for storage and computation. The key ingredient to achieving this goal is the fundamental understanding of their stabilization and manipulation. Here, we show how the interfacial Dzyaloshinskii-Moriya Interaction (IDMI) is able to lift the energy degeneracy of a magnetic vortex state by stabilizing a topological soliton with radial chirality, hereafter called radial vortex. It has a noninteger Skyrmion number S (0.5 wave emissions due to vortex-antivortex annihilations.

  8. Interactions between laponite and microbial biofilms in porous media: implications for colloid transport and biofilm stability.

    Science.gov (United States)

    Leon-Morales, C Felipe; Leis, Andrew P; Strathmann, Martin; Flemming, Hans-Curt

    2004-09-01

    Quartz sand columns and sand-filled microscope flow cells were used to investigate the transport characteristics of the clay colloid laponite, and a biofilm-forming bacterium, Pseudomonas aeruginosa SG81. Separate experiments were performed with each particle to determine their individual transport characteristics in clean sand columns. In a second set of experiments, bacterial biofilms were formed prior to introduction of the clay colloids. In the independent transport experiments, bacteria and laponite each conformed to known physicochemical principles. A sodium chloride concentration of 7 x 10(-2) M caused complete retention of the laponite within the sand columns. P. aeruginosa SG81 was generally less influenced by ionic strength effects; it showed relatively low mobility at all ionic strengths tested and some (albeit reduced) mobility when introduced to the columns in 1M NaCl, the highest concentration tested, but nevertheless showed reproducible trends. Under conditions favourable to laponite retention and biofilm stability (7 x 10(-2) MNaCl), laponite suspensions were able to remobilise a portion of the attached bacterial biomass. At low ionic strength, the profile of laponite elution was also altered in the presence of a P. aeruginosa biofilm. These observations suggest that while a reduction in ionic strength has a dominant influence on the mobilisation of biological and inorganic colloids, the presence of laponite and biomass can have a distinct influence on the mobility of both types of colloids. Since these events are likely to occur in subsurface environments, our results suggest that colloid-biofilm interactions will have implications for colloid-bound contaminant transport and the remobilisation of pathogens.

  9. Numerical analysis for the evaluation of the stability of underground cavities in calcarenite interacting with buildings

    Science.gov (United States)

    Castellanza, Riccardo; Lollino, Piernicola; Oryem Ciantia, Matteo; di Prisco, Claudio; Crosta, Giovanni; Frigerio, Gabriele

    2013-04-01

    Soft and highly porous rocks such as tuffs and calcarenites are very common rocks. Due to their porous calcareous structure they are quite prone to water induced weathering mechanisms. Onshore and inland natural underground cavities are evident signs of these phenomena and of the effects in terms of failure. These materials have been largely employed in the past as building and ornamental stones and as sites to excavate underground cavities for different uses. The world famous Unesco site of "Sassi di Matera", the underground cavities in Canosa di Puglia and Gravina di Puglia , or the calcarenite cliff and natural caves of Polignano a Mare are the most representative cases. Nowadays, many of these are deteriorating because of weathering due to humidity, water infiltration, environmental pollution, and direct exposure to marine aerosols and meteoric water precipitations. In all these cases, a careful assessment of the safety of the built environment and a conscious identification of the safety measures cannot be separated from the analysis of the interaction between the cavities and the overlying buildings, and of the evolution and spatial distribution of the weathering processes. This contribute summarizes the authors' experience on the subject and suggests a methodological approach to quantitatively assess the stability of underground cavities. Starting from experimental evidences at micro and macroscale, the main debonding mechanisms have been taken into account in numerical models. The time-evolution scenarios of the weathering processes is introduced in three-dimensional numerical modelling. The intention is to provide a potentially useful tool for risk assessment in similar complex geomechanical situations.

  10. Conical quarl swirl stabilized non-premixed flames: flame and flow field interaction

    KAUST Repository

    Elbaz, Ayman M.

    2017-09-19

    The flame-flow field interaction is studied in non-premixed methane swirl flames stabilized in quartz quarl via simultaneous measurements of the flow field using a stereo PIV and OH-PLIF at 5 KHz repetition rate. Under the same swirl intensity, two flames with different fuel jet velocity were investigated. The time-averaged flow field shows a unique flow pattern at the quarl exit, where two recirculation vortices are formed; a strong recirculation zone formed far from the quarl exit and a larger recirculation zone extending inside the quarl. However, the instantaneous images show that, the flow pattern near the quarl exit plays a vital role in the spatial location and structure of the reaction zone. In the low fuel jet velocity flame, a pair of vortical structures, located precisely at the corners of the quarl exit, cause the flame to roll up into the central region of low speed flow, where the flame sheet then tracks the axial velocity fluctuations. The vorticity field reveals a vortical structure surrounding the reaction zones, which reside on a layer of low compressive strain adjacent to that vortical structure. In the high fuel jet velocity flame, initially a laminar flame sheet resides at the inner shear layer of the main jet, along the interface between incoming fresh gas and high temperature recirculating gas. Further downstream, vortex breakdown alters the flame sheet path toward the central flame region. The lower reaction zones show good correlation to the regions of maximum vorticity and track the regions of low compressive strain associated with the inner shear layer of the jet flow. In both flames the reactions zones conform the passage of the large structure while remaining inside the low speed regions or at the inner shear layer.

  11. Protein denaturation with guanidine hydrochloride or urea provides a different estimate of stability depending on the contributions of electrostatic interactions.

    Science.gov (United States)

    Monera, O. D.; Kay, C. M.; Hodges, R. S.

    1994-01-01

    The objective of this study was to address the question of whether or not urea and guanidine hydrochloride (GdnHCl) give the same estimates of the stability of a particular protein. We previously suspected that the estimates of protein stability from GdnHCl and urea denaturation data might differ depending on the electrostatic interactions stabilizing the proteins. Therefore, 4 coiled-coil analogs were designed, where the number of intrachain and interchain electrostatic attractions (A) were systematically changed to repulsions (R): 20A, 15A5R, 10A10R, and 20R. The GdnHCl denaturation data showed that the 4 coiled-coil analogs, which had electrostatic interactions ranging from 20 attractions to 20 repulsions, had very similar [GdnHCl]1/2 values (average of congruent to 3.5 M) and, as well, their delta delta Gu values were very close to 0 (0.2 kcal/mol). In contrast, urea denaturation showed that the [urea]1/2 values proportionately decreased with the stepwise change from 20 electrostatic attractions to 20 repulsions (20A, 7.4 M; 15A5R, 5.4 M; 10A10R, 3.2 M; and 20R, 1.4 M), and the delta delta Gu values correspondingly increased with the increasing differences in electrostatic interactions (20A-15A5R, 1.5 kcal/mol; 20A-10A10R, 3.7 kcal/mol; and 20A-20R, 5.8 kcal/mol). These results indicate that the ionic nature of GdnHCl masks electrostatic interactions in these model proteins, a phenomenon that was absent when the unchanged urea was used. Thus, GdnHCl and urea denaturations may give vastly different estimates of protein stability, depending on how important electrostatic interactions are to the protein. PMID:7703845

  12. Thermodynamic Stability and Structure of Oxidized Cu(110) Surfaces: The Critical Role of non-Local Interactions

    Science.gov (United States)

    Bamidele, Joseph; Brndiar, Jan; Stich, Ivan; Kantorovitch, Lev

    2013-03-01

    Thermodynamic stability of oxidized Cu(110) surface is studied using DFT techniques. At high oxygen exposures standard techniques predict more phases to be quasi-isoenergetic, whereas experiments observe only the c(6 × 2) phase at high oxygen exposures clearly indicating this phase to be the ground-state separated by considerable energy differences from other candidates. We show that this surface system is stabilized by a delicate coexistence and balance of chemi- and physi-sorption. Agreement with experiments is only achieved if the van der Waals interaction between the surface templates is accounted for in DFT thermodynamics. Moreover, van der Waals stabilization of the surface structure is anticipated to be a general feature present also in the cases of other related surfaces.

  13. Fe-C interactions and soil organic matter stability in two tropical soils of contrasting parent materials

    Science.gov (United States)

    Coward, E.; Thompson, A.; Plante, A. F.

    2014-12-01

    The long residence time of soil organic matter (SOM) is a dynamic property, reflecting the diversity of stabilization mechanisms active within the soil matrix. Climate and ecosystem properties act at the broadest scale, while biochemical recalcitrance, physical occlusion and mineral association drive stability at the microscale. Increasing evidence suggests that the stability of SOM is dominated by organo-mineral interactions. However, the 2:1 clays that provide much of the stabilization capacity in temperate soils are typically absent in tropical soils due to weathering. In contrast, these soils may contain an abundance of iron and aluminium oxides and oxyhydroxides, known as short-range-order (SRO) minerals. These SRO minerals are capable of SOM stabilization through adsorption or co-precipitation, a faculty largely enabled by their high specific surface area (SSA). As such, despite their relatively small mass, SRO minerals may contribute substantially to the SOM stabilization capacity of tropical soils. The objective of this work is to characterize and quantify these Fe-C interactions. Surface (0-20 cm) soil samples were taken from 20 quantitative soil pits dug within the Luquillo Critical Zone Observatory in northeast Puerto Rico. Soils were stratified across granodiorite and volcaniclastic parent materials. Four extraction procedures were used to isolate three different forms of Fe-C interactions: sodium pyrophosphate to isolate organo-metallic complexes, hydroxylamine and oxalate to isolate SRO Fe- and Al-hydroxides, and dithionite to isolate crystalline Fe-oxyhydroxides. Extracts were analysed for DOC and Fe and Al concentrations to estimate the amount of SOM associated with each mineral type. Soils were subjected to SSA and solid-phase C analyses before and after extraction to determine the contribution of the various Fe mineral types to soil SSA, and therefore to potential stabilization capacity through organo-mineral complexation. Preliminary results

  14. Controlling the size and morphology of griseofulvin nanoparticles using polymeric stabilizers by evaporation-assisted solvent-antisolvent interaction method

    Science.gov (United States)

    Kumar, Raj; Siril, Prem Felix

    2015-06-01

    Griseofulvin (GF) is a potential drug for cancer therapy. However, its application is limited by its poor water solubility. Ultrafine GF nanoparticles were prepared through evaporation-assisted solvent-antisolvent interaction method for improving its solubility. Acetone was used as the solvent and water was used as the antisolvent. It was observed that particle size could be controlled by varying the concentration of GF in acetone. Average particle size was very low, 16 ± 4 and 28 ± 8 nm, when the concentration of GF was 5 and 25 mM, respectively, in acetone. However, the particle size increased drastically to more than 3 µm, when the concentration was increased to 50 mM. Interestingly, the presence of optimized concentration of polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) as stabilizers in the antisolvent resulted in significant reduction of particle size. Particle size decreased to less than 40 nm in the presence of the polymeric stabilizers, even when the concentration was 50 mM. Field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy imaging revealed that the polymeric stabilizers encapsulated very small GF particles and thus stabilized them. The solubility of GF-HPMC, GF-PVP, and the bare GF particles that were prepared from 50 mM solution (micro-GF) was nearly 24, 19, and 11 times, respectively, higher than that of raw-GF. In vitro dissolution studies revealed that almost 100 % of the drug was released in 60 min from GF-PVP and GF-HPMC. Fourier transform infrared spectroscopy did not detect any strong interaction between GF and the stabilizers. X-ray diffraction showed that the prepared GF nanoparticles and the micro-GF were in polymorphic form I. Differential scanning calorimetric studies showed that the crystallinity of the nanoformulated GF was only slightly lower than that of raw-GF. Thus, particle size reduction and the presence of stabilizers led to significant enhancement in

  15. Amino acids as co-amorphous stabilizers for poorly water-soluble drugs--Part 2: molecular interactions.

    Science.gov (United States)

    Löbmann, Korbinian; Laitinen, Riikka; Strachan, Clare; Rades, Thomas; Grohganz, Holger

    2013-11-01

    The formation of co-amorphous drug-drug mixtures has proved to be a powerful approach to stabilize the amorphous form and at the same time increase the dissolution of poorly water-soluble drugs. Molecular interactions in these co-amorphous formulations can play a crucial role in stabilization and dissolution enhancement. In this regard, Fourier-transform infrared spectroscopy (FTIR) is a valuable tool to analyze the molecular near range order of the compounds in the co-amorphous mixtures. In this study, several co-amorphous drugs--low molecular weight excipient blends--have been analyzed with FTIR spectroscopy. Molecular interactions of the drugs carbamazepine and indomethacin with the amino acids arginine, phenylalanine, and tryptophan were investigated. The amino acids were chosen from the biological target site of both drugs and prepared as co-amorphous formulations together with the drugs by vibrational ball milling. A detailed analysis of the FTIR spectra of these formulations revealed specific peak shifts in the vibrational modes of functional groups of drug and amino acid, as long as one amino acid from the biological target site was present in the blends. These peak shifts indicate that the drugs formed specific molecular interactions (hydrogen bonding and π-π interactions) with the amino acids. In the drug-amino acid mixtures that contained amino acids which were not present at the biological target site, no such interactions were identified. This study shows the potential of amino acids as small molecular weight excipients in co-amorphous formulations to stabilize the amorphous form of a poorly water-soluble drug through strong and specific molecular interactions with the drug.

  16. Molecular insights into the stabilization of protein-protein interactions with small molecule: The FKBP12-rapamycin-FRB case study

    Science.gov (United States)

    Chaurasia, Shilpi; Pieraccini, Stefano; De Gonda, Riccardo; Conti, Simone; Sironi, Maurizio

    2013-11-01

    Targetting protein-protein interactions is a challenging task in drug discovery process. Despite the challenges, several studies provided evidences for the development of small molecules modulating protein-protein interactions. Here we consider a typical case of protein-protein interaction stabilization: the complex between FKBP12 and FRB with rapamycin. We have analyzed the stability of the complex and characterized its interactions at the atomic level by performing free energy calculations and computational alanine scanning. It is shown that rapamycin stabilizes the complex by acting as a bridge between the two proteins; and the complex is stable only in the presence of rapamycin.

  17. Stability and magnetic interactions between magnetite nanoparticles dispersed in zeolite as studied using Mössbauer spectroscopy

    Science.gov (United States)

    Herojit singh, L.; Govindaraj, R.; Mythili, R.; Amarendra, G.

    2016-11-01

    Stability of superparamagnetic magnetite nanoparticles as formed in Zeolite has been addressed in a detailed manner based on isochronal annealing studies using Mössbauer spectroscopy. A strong binding of these nanoparticles in Zeolite has been deduced as the coarsening of the nanoparticles is observed following annealing treatments beyond 825 K. In addition, the magnetic interactions between these superparamagnetic magnetite nanoparticles in the as dispersed condition in Zeolite have been elucidated by means of low temperature Mössbauer studies. A strong dependence of the dipole-dipole interactions between superparamagnetic particles of cubic iron oxides is deduced based on this study.

  18. Dynamical stabilization of the body centered cubic phase in lanthanum and thorium by phonon-phonon interaction

    Energy Technology Data Exchange (ETDEWEB)

    Souvatzis, P; Rudin, S P [Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Bjoerkman, T; Eriksson, O [Department of Physics, Uppsala University, Box 530, SE-75121, Uppsala (Sweden); Andersson, P [FOI, Swedish Defence Research Agency, SE-164 90 Stockholm (Sweden); Katsnelson, M I [Institute for Molecules and Materials, Radboud University Nijmegen, NL-6525 ED, Nijmegen (Netherlands)], E-mail: petros.souvatzis@gmail.com

    2009-04-29

    A recently developed self-consistent ab initio lattice dynamical method has been applied to the high temperature body centered cubic (bcc) phase of La and Th, which are dynamically unstable at low temperatures. The bcc phase of these metals is found to be stabilized by phonon-phonon interactions. The calculated high temperature phonon frequencies for La are found to be in good agreement with the corresponding experimental data.

  19. Effects of interactive metronome training on postural stability and upper extremity function in Parkinson’s disease: a case study

    Science.gov (United States)

    Kim, Arim; Lee, Hye-Sun; Song, Chiang-Soon

    2017-01-01

    [Purpose] The purpose of this study was to examine the effects of interactive metronome training on the postural stability and upper extremity function of an individual with Parkinson’s disease. [Subject and Methods] The participant of this case study was a 75-year-old female with Parkinson’s disease diagnosed 7 years prior. This study was a single-subject research with an A-B-A design. She received IM training during the treatment phase (B phase) for 40 minutes per session. She was assessed pretest and posttest using the Berg balance scale and Wolf motor function test, and at baseline and the treatment phase using the measured box-and-block test and a Tetrax system. [Results] After training, the patient’s static and dynamic balance, functional activity, and performance time of the upper extremity improved. Interactive metronome therapy improved the manual dexterity of both hands. Interactive metronome therapy also improved the limit of stability of the Parkinson’s disease. [Conclusion] Though a case study, the results of this study suggest that IM therapy is effective at restoring the postural stability and upper extremity function of patients with Parkinson’s disease. PMID:28210066

  20. Hot melt extrusion for amorphous solid dispersions: temperature and moisture activated drug-polymer interactions for enhanced stability.

    Science.gov (United States)

    Sarode, Ashish L; Sandhu, Harpreet; Shah, Navnit; Malick, Waseem; Zia, Hossein

    2013-10-07

    Hot melt extrudates (HMEs) of indomethacin (IND) with Eudragit EPO and Kollidon VA 64 and those of itraconazole (ITZ) with HPMCAS-LF and Kollidon VA 64 were manufactured using a Leistritz twin screw extruder. The milled HMEs were stored at controlled temperature and humidity conditions. The samples were collected after specified time periods for 3 months. The stability of amorphous HMEs was assessed using moisture analysis, thermal evaluation, powder X-ray diffraction, FTIR, HPLC, and dissolution study. In general, the moisture content increased with time, temperature, and humidity levels. Amorphous ITZ was physically unstable at very high temperature and humidity levels, and its recrystallization was detected in the HMEs manufactured using Kollidon VA 64. Although physical stability of IND was better sustained by both Eudragit EPO and Kollidon VA 64, chemical degradation of the drug was identified in the stability samples of HMEs with Eudragit EPO stored at 50 °C. The dissolution rates and the supersaturation levels were significantly decreased for the stability samples in which crystallization was detected. Interestingly, the supersaturation was improved for the stability samples of IND:Eudragit EPO and ITZ:HPMCAS-LF, in which no physical or chemical instability was observed. This enhancement in supersaturation was attributed to the temperature and moisture activated electrostatic interactions between the drugs and their counterionic polymers.

  1. On the stabilization of modulus in Randall–Sundrum model by R$\\Phi^2$ interaction

    Indian Academy of Sciences (India)

    Tofighi A

    2016-03-01

    A solution to the problem of modulus stabilization is to couple a massless bulk scalar field non-minimally to five-dimensional curvature. We present an exact treatment of the stabilization condition. Our results show that the square of effective mass of this scalar field is necessarily negative. We also find the existence of a closely spaced maximum near the minimum of the effective potential

  2. Substituent effect on the molecular stability, group interaction, detonation performance, and thermolysis mechanism of nitroamino-substituted cyclopentanes and cyclohexanes

    Institute of Scientific and Technical Information of China (English)

    QIU Ling; GONG XueDong; JU XueHai; XIAO HeMing

    2008-01-01

    Density functional theory (DFT) method has been employed to study the effect of nitroamino group as a substituent in cyclopentane and cyclohexane, which usually construct the polycyclic or caged nitra-mines. Molecular structures were investigated at the B3LYP/6-31G** level, and isodesmic reactions were designed for calculating the group interactions. The results show that the group interactions ac-cord with the group additivity, increasing with the increasing number of nitroamino groups. The distance between substituents influences the interactions. Detonation performances were evaluated by the Kamlet-Jacobs equations based on the predicted densities and heats of formation, while thermal stability and pyrolysis mechanism were studied by the computations of bond dissociation energy (BDE). It is found that the contributions of nitroamino groups to the detonation heat, detonation velocity, detonation pressure, and stability all deviate from the group additivity. Only 3a, 3b, and 9a-9c may be novel potential candidates of high energy density materials (HEDMs) according to the quantitative cri-teria of HEDM (ρ≈1.9 g/cm3, D≈9.0 km/s, P≈40.0 GPa). Stability decreases with the increasing number of N-NO2 groups, and homolysis of N-NO2 bond is the initial step in the thermolysis of the title com-pounds. Coupled with the demand of thermal stability (BDE > 20 kcal/mol), only 1,2,4-trinitrotriazacy-clohexane and 1,2,4,5-tetranitrotetraazacyclohexane are suggested as feasible energetic materials.These results may provide basic information for the molecular design of HEDMs.

  3. Interactions of cullin3/KCTD5 complexes with both cytoplasmic and nuclear proteins: Evidence for a role in protein stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, Natalja; Heilbronn, Regine; Weger, Stefan, E-mail: stefan.weger@charite.de

    2015-08-28

    Based on its specific interaction with cullin3 mediated by an N-terminal BTB/POZ homologous domain, KCTD5 has been proposed to function as substrate adapter for cullin3 based ubiquitin E3 ligases. In the present study we tried to validate this hypothesis through identification and characterization of additional KCTD5 interaction partners. For the replication protein MCM7, the zinc finger protein ZNF711 and FAM193B, a yet poorly characterized cytoplasmic protein, we could demonstrate specific interaction with KCTD5 both in yeast two-hybrid and co-precipitation studies in mammalian cells. Whereas trimeric complexes of cullin3 and KCTD5 with the respective KCTD5 binding partner were formed, KCTD5/cullin3 induced polyubiquitylation and/or proteasome-dependent degradation of these binding partners could not be demonstrated. On the contrary, KCTD5 or Cullin3 overexpression increased ZNF711 protein stability. - Highlights: • KCTD5 nuclear translocation depends upon M phase and protein oligomerization. • Identification of MCM7, ZNF711 and FAM193 as KCTD5 interaction partners. • Formation of trimeric complexes of KCTD5/cullin3 with MCM7, ZNF711 and FAM193B. • KCTD5 is not involved in polyubiquitylation of MCM7 replication factor. • The KCTD5/cullin3 complex stabilizes ZNF711 transcription factor.

  4. Enzyme-polysaccharide interaction: a method for improved stability of horseradish peroxidase.

    Science.gov (United States)

    Kagliwal, Lalit D; Singhal, Rekha S

    2014-08-01

    With the advent of green technology, use of enzymes as biocatalyst has become increasingly popular. However, in doing so, enzymes can lose their structure and catalytic activity under conditions that might be necessary for other components of processes. Compared to other strategies, chemical modification is a simple and effective technique for generating stable enzyme. Horseradish peroxidase (HRP; EC 1.11.1.7) was chemically modified by conjugating with 10 different polysaccharides. All polysaccharides were found to increase the thermal and pH stability of HRP with starch being most promising. Further, different parameters were evaluated for effective conjugation and thus stability of HRP conjugate. The degradation kinetics and storage stability of HRP proved the conjugate to be 6.4 times more stable than free enzyme. The starch conjugated HRP and free HRP were further evaluated for its application in decolorization of bromophenol blue dye. Both the enzymes were able to efficiently (>90%) decolorize the dye within minutes.

  5. Stability and magnetic interactions between magnetite nanoparticles dispersed in zeolite as studied using Mössbauer spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Herojit singh, L. [Materials Science Group Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Govindaraj, R., E-mail: govind@igcar.gov.in [Materials Science Group Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Mythili, R. [Physical Metallurgy Group Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Amarendra, G. [Materials Science Group Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India)

    2016-11-15

    Stability of superparamagnetic magnetite nanoparticles as formed in Zeolite has been addressed in a detailed manner based on isochronal annealing studies using Mössbauer spectroscopy. A strong binding of these nanoparticles in Zeolite has been deduced as the coarsening of the nanoparticles is observed following annealing treatments beyond 825 K. In addition, the magnetic interactions between these superparamagnetic magnetite nanoparticles in the as dispersed condition in Zeolite have been elucidated by means of low temperature Mössbauer studies. A strong dependence of the dipole–dipole interactions between superparamagnetic particles of cubic iron oxides is deduced based on this study. - Highlights: • Dispersion of superparamagnetic magnetite particles in zeolite. • A strong binding of magnetite particles in zeolite deduced using Mössbauer studies. • Difference in spin relaxation behavior of bare and zeolite dispersed magnetite particles. • A strong dipole–dipole interactions between magnetite particles.

  6. Mechanism of Amido-Thiourea Catalyzed Enantioselective Imine Hydrocyanation: Transition State Stabilization via Multiple Non-Covalent Interactions

    Science.gov (United States)

    Zuend, Stephan J.

    2009-01-01

    An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple non-covalent interactions; these ion pairs collapse to form the enantiomeric α-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P ≪ 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions. PMID:19778044

  7. The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations.

    Science.gov (United States)

    Djordjević Filijović, Nataša; Antonijević, Milan D; Pavlović, Aleksandar; Vučković, Ivan; Nikolić, Katarina; Agbaba, Danica

    2015-03-01

    Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.

  8. On critical stability of three quantum charges interacting through delta potentials

    DEFF Research Database (Denmark)

    Cornean, Horia; Duclos, Pierre; Ricaud, Benjamin

    We consider three one dimensional quantum, charged and spinless particles interacting through delta potentials. We derive sufficient conditions which guarantee the existence of at least one bound state.......We consider three one dimensional quantum, charged and spinless particles interacting through delta potentials. We derive sufficient conditions which guarantee the existence of at least one bound state....

  9. Stability and anomalous compressibility of Bose gases near resonance: The scale-dependent interactions and thermal effects

    Science.gov (United States)

    Jiang, Shao-Jian; Zhou, Fei

    2015-07-01

    The stability of Bose gases near resonance has been a puzzling problem in recent years. In this article, we demonstrate that in addition to generating thermal pressure, thermal atoms enhance the repulsiveness of the scale-dependent interactions between condensed atoms due to a renormalization effect and further stabilize the Bose gases. Consequently, we find that, as a precursor of instability, the compressibility develops an anomalous structure as a function of scattering length and is drastically reduced compared with the mean-field value. Furthermore, the density profile of a Bose gas in a harmonic trap is found to develop a flat top near the center. This is due to the anomalous behavior of compressibility and can be a potential smoking gun for probing such an effect.

  10. Compensatory interactions to stabilize multiple steady states or mitigate the effects of multiple deregulations in biological networks

    Science.gov (United States)

    Yang, Gang; Campbell, Colin; Albert, Réka

    2016-12-01

    Complex diseases can be modeled as damage to intracellular networks that results in abnormal cell behaviors. Network-based dynamic models such as Boolean models have been employed to model a variety of biological systems including those corresponding to disease. Previous work designed compensatory interactions to stabilize an attractor of a Boolean network after single node damage. We generalize this method to a multinode damage scenario and to the simultaneous stabilization of multiple steady state attractors. We classify the emergent situations, with a special focus on combinatorial effects, and characterize each class through simulation. We explore how the structural and functional properties of the network affect its resilience and its possible repair scenarios. We demonstrate the method's applicability to two intracellular network models relevant to cancer. This work has implications in designing prevention strategies for complex disease.

  11. The role of weakly polar and H-bonding interactions in the stabilization of the conformers of FGG, WGG, and YGG: an aqueous phase computational study.

    Science.gov (United States)

    Csontos, József; Murphy, Richard F; Lovas, Sándor

    2008-11-01

    The energetics of intramolecular interactions on the conformational potential energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp-Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated. To identify the representative conformations, simulated annealing molecular dynamics (MD) and density functional theory (DFT) methods were used. The interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar interactions account for 15%, 34%, and 9% of the stabilization energies of the FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can make an important energetic contribution to protein structure and function.

  12. Influence of salt bridge interactions on the gas-phase stability of DNA/peptide complexes

    Science.gov (United States)

    Alves, Sandra; Woods, Amina; Delvolvé, Alice; Tabet, Jean Claude

    2008-12-01

    Negative ion mode electrospray ionization mass spectrometry was used to study DNA duplexes-peptide interaction. In the present study, we show that peptides that contain two adjacent basic residues interact noncovalently with DNA single strand or duplex. Fragmentation of the complexes between peptides containing basic residues and DNA were studied under collisions and showed unexpected dissociation pathways, as previously reported for peptide-peptide interactions. The binary complexes are dissociated either along fragmentation of the covalent bonds of the peptide backbone and/or along the single DNA strand backbone cleavage without disruption of noncovalent interaction, which demonstrates the strong binding of peptide to the DNA strand. Sequential MS/MS and MSn were further performed on ternary complexes formed between duplexes and peptides to investigate the nature of interaction. The CID spectra showed as major pathway the disruption of the noncovalent interactions and the formation of binary complexes and single-strand ions, directed by the nucleic acid gas-phase acidity. Indeed, a preferential formation of complexes with thymidine containing single strands is observed. An alternative pathway is also detected, in which complexes are dissociated along the covalent bond of the peptide and/or DNA according to the basicity. Our experimental data suggest the presence of strong salt bridge interactions between DNA and peptides containing basic residues.

  13. Controlling the size and morphology of griseofulvin nanoparticles using polymeric stabilizers by evaporation-assisted solvent–antisolvent interaction method

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Raj, E-mail: rk7410@gmail.com; Siril, Prem Felix, E-mail: prem@iitmandi.ac.in [Indian Institute of Technology Mandi, School of Basic Sciences and Advanced Material Research Centre (India)

    2015-06-15

    Griseofulvin (GF) is a potential drug for cancer therapy. However, its application is limited by its poor water solubility. Ultrafine GF nanoparticles were prepared through evaporation-assisted solvent–antisolvent interaction method for improving its solubility. Acetone was used as the solvent and water was used as the antisolvent. It was observed that particle size could be controlled by varying the concentration of GF in acetone. Average particle size was very low, 16 ± 4 and 28 ± 8 nm, when the concentration of GF was 5 and 25 mM, respectively, in acetone. However, the particle size increased drastically to more than 3 µm, when the concentration was increased to 50 mM. Interestingly, the presence of optimized concentration of polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) as stabilizers in the antisolvent resulted in significant reduction of particle size. Particle size decreased to less than 40 nm in the presence of the polymeric stabilizers, even when the concentration was 50 mM. Field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy imaging revealed that the polymeric stabilizers encapsulated very small GF particles and thus stabilized them. The solubility of GF-HPMC, GF-PVP, and the bare GF particles that were prepared from 50 mM solution (micro-GF) was nearly 24, 19, and 11 times, respectively, higher than that of raw-GF. In vitro dissolution studies revealed that almost 100 % of the drug was released in 60 min from GF-PVP and GF-HPMC. Fourier transform infrared spectroscopy did not detect any strong interaction between GF and the stabilizers. X-ray diffraction showed that the prepared GF nanoparticles and the micro-GF were in polymorphic form I. Differential scanning calorimetric studies showed that the crystallinity of the nanoformulated GF was only slightly lower than that of raw-GF. Thus, particle size reduction and the presence of stabilizers led to significant

  14. Interaction of age and mechanical stability on bone defect healing: an early transcriptional analysis of fracture hematoma in rat.

    Directory of Open Access Journals (Sweden)

    Andrea Ode

    Full Text Available Among other stressors, age and mechanical constraints significantly influence regeneration cascades in bone healing. Here, our aim was to identify genes and, through their functional annotation, related biological processes that are influenced by an interaction between the effects of mechanical fixation stability and age. Therefore, at day three post-osteotomy, chip-based whole-genome gene expression analyses of fracture hematoma tissue were performed for four groups of Sprague-Dawley rats with a 1.5-mm osteotomy gap in the femora with varying age (12 vs. 52 weeks - biologically challenging and external fixator stiffness (mechanically challenging. From 31099 analysed genes, 1103 genes were differentially expressed between the six possible combinations of the four groups and from those 144 genes were identified as statistically significantly influenced by the interaction between age and fixation stability. Functional annotation of these differentially expressed genes revealed an association with extracellular space, cell migration or vasculature development. The chip-based whole-genome gene expression data was validated by q-RT-PCR at days three and seven post-osteotomy for MMP-9 and MMP-13, members of the mechanosensitive matrix metalloproteinase family and key players in cell migration and angiogenesis. Furthermore, we observed an interaction of age and mechanical stimuli in vitro on cell migration of mesenchymal stromal cells. These cells are a subpopulation of the fracture hematoma and are known to be key players in bone regeneration. In summary, these data correspond to and might explain our previously described biomechanical healing outcome after six weeks in response to fixation stiffness variation. In conclusion, our data highlight the importance of analysing the influence of risk factors of fracture healing (e.g. advanced age, suboptimal fixator stability in combination rather than alone.

  15. Conserved interaction of Ctf18-RFC with DNA polymerase ε is critical for maintenance of genome stability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Okimoto, Hiroko; Tanaka, Seiji; Araki, Hiroyuki; Ohashi, Eiji; Tsurimoto, Toshiki

    2016-05-01

    Human Ctf18-RFC, a PCNA loader complex, interacts with DNA polymerase ε (Polε) through a structure formed by the Ctf18, Dcc1 and Ctf8 subunits. The C-terminal stretch of Ctf18, which is highly conserved from yeast to human, is necessary to form the Polε-capturing structure. We found that in the budding yeast Saccharomyces cerevisiae, Ctf18, Dcc1 and Ctf8 formed the same structure through the conserved C-terminus and interacted specifically with Polε. Thus, the specific interaction of Ctf18-RFC with Polε is a conserved feature between these proteins. A C-terminal deletion mutant of Ctf18 (ctf18(ΔC) ) exhibited the same high sensitivity to hydroxyurea as the complete deletion strain (ctf18Δ) or ATPase-deficient mutant (ctf18(K189A) ), but was somewhat less sensitive to methyl methanesulfonate than either of them. These phenotypes were also observed in dcc1Δ and ctf8Δ, predicted to be deficient in the interaction with Polε. Furthermore, both plasmid loss and gross chromosomal rearrangement (GCR) rates were increased in ctf18(ΔC) cells to the same extent as in ctf18Δ cells. These results indicate that the Ctf18-RFC/Polε interaction plays a crucial role in maintaining genome stability in budding yeast, probably through recruitment of this PCNA loader to the replication fork.

  16. Probing the Interfacial Interaction in Layered-Carbon-Stabilized Iron Oxide Nanostructures: A Soft X-ray Spectroscopic Study.

    Science.gov (United States)

    Zhang, Hui; Liu, Jinyin; Zhao, Guanqi; Gao, Yongjun; Tyliszczak, Tolek; Glans, Per-Anders; Guo, Jinghua; Ma, Ding; Sun, Xu-Hui; Zhong, Jun

    2015-04-22

    We have stabilized the iron oxide nanoparticles (NPs) of various sizes on layered carbon materials (Fe-oxide/C) that show excellent catalytic performance. From the characterization of X-ray absorption spectroscopy (XAS), X-ray emission spectroscopy (XES), scanning transmission X-ray microscopy (STXM) and X-ray magnetic circular dichroism spectroscopy (XMCD), a strong interfacial interaction in the Fe-oxide/C hybrids has been observed between the small iron oxide NPs and layered carbon in contrast to the weak interaction in the large iron oxide NPs. The interfacial interaction between the NPs and layered carbon is found to link with the improved catalytic performance. In addition, the Fe L-edge XMCD spectra show that the large iron oxide NPs are mainly γ-Fe2O3 with a strong ferromagnetic property, whereas the small iron oxide NPs with strong interfacial interaction are mainly α-Fe2O3 or amorphous Fe2O3 with a nonmagnetic property. The results strongly suggest that the interfacial interaction plays a key role for the catalytic performance, and the experimental findings may provide guidance toward rational design of high-performance catalysts.

  17. Influence of Different Y-Y Interactions on the Stability of Strange Hadronic Matter

    Institute of Scientific and Technical Information of China (English)

    SONG Hong-Qiu; SU Ru-Keng; QIAN Wei-Liang

    2004-01-01

    @@ An effective model is used to study the equation of state (EOS) of strange hadronic matter with nucleons, Ahyperons and -hyperons. In the calculation, a newest weak hyperon-hyperon (Y-Y) interaction deduced from the recent observation [Phys. Rev. Lett. 87 (2001)212502-1] of a 6AAHe double hypernucleus is adopted. The calculated results are compared to those calculated with the strong Y-Y interaction used in previous studies.

  18. Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling.

    Science.gov (United States)

    Huber, Kilian V M; Olek, Karin M; Müller, André C; Tan, Chris Soon Heng; Bennett, Keiryn L; Colinge, Jacques; Superti-Furga, Giulio

    2015-11-01

    Thermal stabilization of proteins after ligand binding provides an efficient means to assess the binding of small molecules to proteins. We show here that in combination with quantitative mass spectrometry, the approach allows for the systematic survey of protein engagement by cellular metabolites and drugs. We profiled the targets of the drugs methotrexate and (S)-crizotinib and the metabolite 2'3'-cGAMP in intact cells and identified the 2'3'-cGAMP cognate transmembrane receptor STING, involved in immune signaling.

  19. The effect of intertube van der Waals interaction on the stability of pristine and functionalized carbon nanotubes under compression.

    Science.gov (United States)

    Kuang, Y D; Shi, S Q; Chan, P K L; Chen, C Y

    2010-03-26

    This paper investigates the effect of intertube van der Waals interaction on the stability of pristine and covalently functionalized carbon nanotubes under axial compression, using molecular mechanics simulations. After regulating the number of inner layers of the armchair four-walled (5, 5)@(10, 10)@(15, 15)@(20, 20) and zigzag four-walled (6, 0)@(15, 0)@(24, 0)@(33, 0) carbon nanotubes, the critical buckling strains of the corresponding tubes are calculated. The results show that each of the three inner layers in the functionalized armchair nanotube noticeably contributes to the stability of the outermost tube, and together increase the critical strain amplitude by 155%. However, the three inner layers in the corresponding pristine nanotube, taken together, increase the critical strain of the outermost tube by only 23%. In addition, for both the pristine and functionalized zigzag nanotubes, only the (24, 0) layer, among the three inner layers, contributes to the critical strain of the corresponding outermost tube, by 11% and 29%, respectively. The underlying mechanism of the enhanced stability related to nanotube chirality and functionalization is analyzed in detail.

  20. Id1 interacts and stabilizes the Epstein-Barr virus latent membrane protein 1 (LMP1 in nasopharyngeal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Pok Man Hau

    Full Text Available The EBV-encoded latent membrane protein 1 (LMP1 functions as a constitutive active form of tumor necrosis factor receptor (TNFR and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC cell line (C666-1 and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells.

  1. Temperature Dependence of the Stability of Ion Pair Interactions, and its Implications on the Thermostability of Proteins from Thermophiles

    Indian Academy of Sciences (India)

    SWETHA BIKKINA; AGASTYA P BHATI; SILADITYA PADHI; U DEVA PRIYAKUMAR

    2017-03-01

    An understanding of the determinants of the thermal stability of thermostable proteins is expected to enable design of enzymes that can be employed in industrial biocatalytic processes carried out at high temperatures. A major factor that has been proposed to stabilize thermostable proteins is the high occurrenceof salt bridges. The current study employs free energy calculations to elucidate the thermodynamics of the formation of salt bridge interactions and the temperature dependence, using acetate and methylguanidium ionsas model systems. Three different orientations of the methylguanidinium approaching the carboxylate grouphave been considered for obtaining the free energy profiles. The association of the two ions becomes more favorable with an increase in temperature. The desolvation penalty corresponding to the association of the ionpair is the lowest at high temperatures. The occurrence of bridging water molecules between the ions ensures that the ions are not fully desolvated, and this could provide an explanation for the existence of internal watermolecules in thermostable proteins reported recently. The findings provide a detailed picture of the interactions that make ion pair association at high temperatures a favorable process, and reaffirm the importance of saltbridges in the design of thermostable proteins.

  2. Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: stability and interaction with ligands.

    Directory of Open Access Journals (Sweden)

    Silvana A Rosú

    Full Text Available A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.

  3. The effect of asphaltene-paraffin interactions on crude oil stability

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, M.C. del; Carbogani, L. [PDVSA, Caracas (Venezuela)

    2000-08-01

    The effect of asphaltene-paraffin complexes on crude oil stability, in terms of wax crystallization and asphaltene deposits solubility, was studied. The influence of flocculated asphaltenes on the wax crystallization tendency of a paraffinic crude oil was evaluated by means of Polarized Light Microscopy. Heavy linear paraffins (nC24+ paraffins) were added to the crude oil in a controlled fashion in order to evaluate its effect on the cloud point and the effectiveness of a maleic anhydride copolymer derivative paraffin inhibitor. Experiments done in the presence and absence of asphaltene fraction allowed to demonstrate that flocculated asphaltenes provide wax crystallization sites whose presence increases the cloud point of crude oil and also interferes with crystal inhibition mechanism. The existence of asphaltene-paraffins complexes and some structural effects were further assessed by HPLC kinetic dissolution studies of composite materials formed by combinations of such hydrocarbon types. Commercial macrocrystalline and microcrystalline waxes were used in these experiments. Different types of asphaltenes were probed as well, covering varying ranges of aromaticities and stability. (au)

  4. Stabilization of membranes upon interaction of amphipathic polymers with membrane proteins.

    Science.gov (United States)

    Picard, Martin; Duval-Terrié, Caroline; Dé, Emmanuelle; Champeil, Philippe

    2004-11-01

    Amphipathic polymers derived from polysaccharides, namely hydrophobically modified pullulans, were previously suggested to be useful as polymeric substitutes of ordinary surfactants for efficient and structure-conserving solubilization of membrane proteins, and one such polymer, 18C(10), was optimized for solubilization of proteins derived from bacterial outer membranes (Duval-Terrie et al. 2003). We asked whether a similar ability to solubilize proteins could also be demonstrated in eukaryotic membranes, namely sarcoplasmic reticulum (SR) fragments, the major protein of which is SERCA1a, an integral membrane protein with Ca(2+)-dependent ATPase and Ca(2+)-pumping activity. We found that 18C(10)-mediated solubilization of these SR membranes did not occur. Simultaneously, however, we found that low amounts of this hydrophobically modified pullulan were very efficient at preventing long-term aggregation of these SR membranes. This presumably occurred because the negatively charged polymer coated the membranous vesicles with a hydrophilic corona (a property shared by many other amphipathic polymers), and thus minimized their flocculation. Reminiscent of the old Arabic gum, which stabilizes Indian ink by coating charcoal particles, the newly designed amphipathic polymers might therefore unintentionally prove useful also for stabilization of membrane suspensions.

  5. Stabilization variation of organic conductor surfaces induced by π-π stacking interactions

    Institute of Scientific and Technical Information of China (English)

    Dou Rui-Fen; Lin Feng; Liu Fu-Wei; Sun Yi; Yang Ji-Yong; Lin Bing-Fa; He Lin; Xiong Chang-Min; Nie Jia-Cai

    2012-01-01

    The structures and stabilization of three crystal surfaces of TCNQ-based charge transfer complexes(CTCs)including PrQ(TCNQ)2,MPM(TCNQ)2,and MEM(TCNQ)2,have been investigated by scanning tunneling microscopy(STM).The three bulk-truncated surfaces are all ac-surface,which are terminated with TCNQ molecular arrays.On the ac-surface of PrQ(TCNQ)2,the TCNQ molecules form a tetramer structure with a wavelike row behavior and a γ angle of about 18° between adjacent molecules.Moreover,the dimer structures are resolved on both ac-surfaces of MPM(TCNQ)2 and MEM(TCNQ)2.In addition,the tetramer structure is the most stable structure,while the dimer structures are unstable and easily subject to the STM tip disturbance,which results in changeable unit cells.The main reasous for the surface stabilization variation among the three ac-surfaces are provided by using the ‘π-atom model'.

  6. Lateral Reaction Jet Flow Interaction Effects on a Generic Fin-Stabilized Munition in Supersonic Crossflows

    Science.gov (United States)

    2013-11-01

    269–275. 9. Stahl, B.; Edmunds , H.; Gulhan, A. Experimental Investigation of Hot and Cold Side Jet Interaction With a Supersonic Cross Flow...LICHTENBERG-SCANLAN G MALEJKO T RECCHIA C STOUT W TOLEDO J TRAVAILLE E VAZQUEZ C WILSON 4 PM CAS (PDF) M BURKE R KIEBLER

  7. Financial Stability and Interacting Networks of Financial Institutions and Market Infrastructures

    NARCIS (Netherlands)

    Léon, C.; Berndsen, R.J.; Renneboog, L.D.R.

    2014-01-01

    An interacting network coupling financial institutions’ multiplex (i.e. multi-layer) and financial market infrastructures’ single-layer networks gives an accurate picture of a financial system’s true connective architecture. We examine and compare the main properties of Colombian multiplex and inter

  8. Financial Stability and Interacting Networks of Financial Institutions and Market Infrastructures

    NARCIS (Netherlands)

    Léon, C.; Berndsen, R.J.; Renneboog, L.D.R.

    2014-01-01

    An interacting network coupling financial institutions’ multiplex (i.e. multi-layer) and financial market infrastructures’ single-layer networks gives an accurate picture of a financial system’s true connective architecture. We examine and compare the main properties of Colombian multiplex and

  9. Effects of solute-solute interactions on protein stability studied using various counterions and dendrimers.

    Directory of Open Access Journals (Sweden)

    Curtiss P Schneider

    Full Text Available Much work has been performed on understanding the effects of additives on protein thermodynamics and degradation kinetics, in particular addressing the Hofmeister series and other broad empirical phenomena. Little attention, however, has been paid to the effect of additive-additive interactions on proteins. Our group and others have recently shown that such interactions can actually govern protein events, such as aggregation. Here we use dendrimers, which have the advantage that both size and surface chemical groups can be changed and therein studied independently. Dendrimers are a relatively new and broad class of materials which have been demonstrated useful in biological and therapeutic applications, such as drug delivery, perturbing amyloid formation, etc. Guanidinium modified dendrimers pose an interesting case given that guanidinium can form multiple attractive hydrogen bonds with either a protein surface or other components in solution, such as hydrogen bond accepting counterions. Here we present a study which shows that the behavior of such macromolecule species (modified PAMAM dendrimers is governed by intra-solvent interactions. Attractive guanidinium-anion interactions seem to cause clustering in solution, which inhibits cooperative binding to the protein surface but at the same time, significantly suppresses nonnative aggregation.

  10. Interaction between soil mineralogy and the application of crop residues on aggregate stability and hydraulic conductivity of the soil

    Science.gov (United States)

    Lado, M.; Kiptoon, R.; Bar-Tal, A.; Wakindiki, I. I. C.; Ben-Hur, M.

    2012-04-01

    One of the main goals of modern agriculture is to achieve sustainability by maintaining crop productivity while avoiding soil degradation. Intensive cultivation could lead to a reduction in soil organic matter that could affect the structure stability and hydraulic conductivity of the soil. Moreover, crops extract nutrients from the soil that are taken away from the field when harvested, and as a consequence, the addition of fertilizers to the soil is necessary to maintain crop productivity. One way to deal with these problems is to incorporate crop residues into the soil after harvest. Crop residues are a source of organic matter that could improve soil physical properties, such as aggregate stability and soil hydraulic conductivity. However, this effect could vary according to other soil properties, such as clay content, clay mineralogy, and the presence of other cementing materials in the soil (mainly carbonates and aluminum and iron oxides). In the present work, the interaction between the addition of chickpea crop residues to the soil and clay mineralogy on aggregate stability and saturated hydraulic conductivity were studied. Chickpea plant residues were added at a rate of 0.5% (w/w) to smectitic, kaolinitic, illitic and non-phyllosilicate soils from different regions. The soils without (control) and with chickpea residues were incubated for 0, 3, 7 and 30 days, and the saturated hydraulic conductivity of the soils was measured in columns after each incubation time. The response of hydraulic conductivity to the addition of residues and incubation time was different in the soils with various mineralogies, although in general, the addition of chickpea residues increased the saturated hydraulic conductivity as compared with the control soils. This positive effect of crop residues on hydraulic conductivity was mainly a result of improved aggregate stability and resistance to slaking during wetting.

  11. Influence of degree correlations on network structure and stability in protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    Zimmer Ralf

    2007-08-01

    Full Text Available Abstract Background The existence of negative correlations between degrees of interacting proteins is being discussed since such negative degree correlations were found for the large-scale yeast protein-protein interaction (PPI network of Ito et al. More recent studies observed no such negative correlations for high-confidence interaction sets. In this article, we analyzed a range of experimentally derived interaction networks to understand the role and prevalence of degree correlations in PPI networks. We investigated how degree correlations influence the structure of networks and their tolerance against perturbations such as the targeted deletion of hubs. Results For each PPI network, we simulated uncorrelated, positively and negatively correlated reference networks. Here, a simple model was developed which can create different types of degree correlations in a network without changing the degree distribution. Differences in static properties associated with degree correlations were compared by analyzing the network characteristics of the original PPI and reference networks. Dynamics were compared by simulating the effect of a selective deletion of hubs in all networks. Conclusion Considerable differences between the network types were found for the number of components in the original networks. Negatively correlated networks are fragmented into significantly less components than observed for positively correlated networks. On the other hand, the selective deletion of hubs showed an increased structural tolerance to these deletions for the positively correlated networks. This results in a lower rate of interaction loss in these networks compared to the negatively correlated networks and a decreased disintegration rate. Interestingly, real PPI networks are most similar to the randomly correlated references with respect to all properties analyzed. Thus, although structural properties of networks can be modified considerably by degree

  12. Genotype × environment interactions and phenotypic stability for wheat grown in stressful conditions

    Directory of Open Access Journals (Sweden)

    Banjac Borislav

    2014-01-01

    Full Text Available The objective of this study was to present the results of experiment conducted on 11 cultivars of wheat (Triticum aestivum L. and 1 cultivar of triticale (Triticosecale W on stressful conditions of halomorphic solonetz in Kumane, Banat, Serbia. Across three growing seasons genotypic variability, monitoring of phenotypic variation and genotype by environment interaction (GEI for number of grains per spike and yield was studied. The cultivar were grown in field trails of control treatment and treatments with measures repairs solonetz using phosphogypsum in the amount of 25 t•ha-1 and 50 t•ha-1. GEI was tested using AMMI (Additive Main Effects and Multiplicative Interaction model. The expression of tested traits were statistically significant and showed additive and non-additive sources of variation. The first source of variation, quantified IPCA1 axis explained most of the structure of GEI.

  13. Stability properties of vector solitons in two-component Bose-Einstein condensates with tunable interactions

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiao-Fei; Zhang Pei; He Wan-Quan; Liu Xun-Xu

    2011-01-01

    By using a unified theory of the formation of various types of vector-solitons in two-component Bose-Einstein condensates with tunable interactions, we obtain a family of exact vector-soliton solutions for the coupled nonlinear Schr(o)dinger equations. Moreover, the Bogoliubov equation shows that there exists stable dark soliton in specific situations. Our results open up new ways in considerable experimental interest for the quantum control of multi-component Bose-Einstein condensates.

  14. Ant aggression and evolutionary stability in plant-ant and plant-pollinator mutualistic interactions.

    Science.gov (United States)

    Oña, L; Lachmann, M

    2011-03-01

    Mutualistic partners derive a benefit from their interaction, but this benefit can come at a cost. This is the case for plant-ant and plant-pollinator mutualistic associations. In exchange for protection from herbivores provided by the resident ants, plants supply various kinds of resources or nests to the ants. Most ant-myrmecophyte mutualisms are horizontally transmitted, and therefore, partners share an interest in growth but not in reproduction. This lack of alignment in fitness interests between plants and ants drives a conflict between them: ants can attack pollinators that cross-fertilize the host plants. Using a mathematical model, we define a threshold in ant aggressiveness determining pollinator survival or elimination on the host plant. In our model we observed that, all else being equal, facultative interactions result in pollinator extinction for lower levels of ant aggressiveness than obligatory interactions. We propose that the capacity to discriminate pollinators from herbivores should not often evolve in ants, and when it does it will be when the plants exhibit limited dispersal in an environment that is not seed saturated so that each seed produced can effectively generate a new offspring or if ants acquire an extra benefit from pollination (e.g. if ants eat fruit). We suggest specific mutualism examples where these hypotheses can be tested empirically. © 2010 The Authors. Journal of Evolutionary Biology © 2010 European Society For Evolutionary Biology.

  15. Environmental influences on pigeonpea-Fusarium udum interactions and stability of genotypes to Fusarium wilt.

    Directory of Open Access Journals (Sweden)

    Mamta eSharma

    2016-03-01

    Full Text Available Fusarium wilt (Fusarium udum Butler is an important biotic constraint to pigeonpea (Cajanus cajan L. production worldwide. Breeding for fusarium wilt resistance continues to be an integral part of genetic improvement of pigeonpea. Therefore, the study was aimed to identify and validate resistant genotypes to fusarium wilt and determine the magnitude of genotype × environment (G × E interactions through multi-environment and multi-year screening. Total 976 genotypes including germplasm and breeding lines were screened against wilt in wilt sick plot at Patancheru, India. Ninety two genotypes found resistant to wilt were tested further for two more years in wilt sick plot at Patancheru and Pigeonpea Wilt Nursery (PWN comprising of 29 genotypes was constituted. PWN was evaluated at nine locations representing different agro-climatic zones of India for wilt resistance during two crop seasons 2007/08 and 2008/09. Genotypes (G, environment (E and G × E interactions biplot partitioned main effect into G, E and G × E interactions and significant effects (p≤0.001 were obtained for wilt incidence. Genotype contributed 36.51% of resistance variation followed by environment (29.32%. GGE biplot in integration with boxplot and multiple comparison tests enabled us to identify seven stable genotypes (ICPL 20109, ICPL 20096, ICPL 20115, ICPL 20116, ICPL 20102, ICPL 20106 and ICPL 20094 based on their performance across diverse environments. These genotypes have broad based resistance and can be exploited in pigeonpea breeding program.

  16. Environmental Influences on Pigeonpea-Fusarium udum Interactions and Stability of Genotypes to Fusarium Wilt.

    Science.gov (United States)

    Sharma, Mamta; Ghosh, Raju; Telangre, Rameshwar; Rathore, Abhishek; Saifulla, Muhammad; Mahalinga, Dayananda M; Saxena, Deep R; Jain, Yogendra K

    2016-01-01

    Fusarium wilt (Fusarium udum Butler) is an important biotic constraint to pigeonpea (Cajanus cajan L.) production worldwide. Breeding for fusarium wilt resistance continues to be an integral part of genetic improvement of pigeonpea. Therefore, the study was aimed at identifying and validating resistant genotypes to fusarium wilt and determining the magnitude of genotype × environment (G × E) interactions through multi-environment and multi-year screening. A total of 976 genotypes including germplasm and breeding lines were screened against wilt using wilt sick plot at Patancheru, India. Ninety two genotypes resistant to wilt were tested for a further two years using wilt sick plot at Patancheru. A Pigeonpea Wilt Nursery (PWN) comprising of 29 genotypes was then established. PWN was evaluated at nine locations representing different agro-climatic zones of India for wilt resistance during two crop seasons 2007/08 and 2008/09. Genotypes (G), environment (E), and G × E interactions were examined by biplot which partitioned the main effect into G, E, and G × E interactions with significant levels (p ≤ 0.001) being obtained for wilt incidence. The genotype contributed 36.51% of resistance variation followed by the environment (29.32%). A GGE biplot integrated with a boxplot and multiple comparison tests enabled us to identify seven stable genotypes (ICPL 20109, ICPL 20096, ICPL 20115, ICPL 20116, ICPL 20102, ICPL 20106, and ICPL 20094) based on their performance across diverse environments. These genotypes have broad based resistance and can be exploited in pigeonpea breeding programs.

  17. A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface.

    Science.gov (United States)

    Anders, Carolin; Higuchi, Yusuke; Koschinsky, Kristin; Bartel, Maria; Schumacher, Benjamin; Thiel, Philipp; Nitta, Hajime; Preisig-Müller, Regina; Schlichthörl, Günter; Renigunta, Vijay; Ohkanda, Junko; Daut, Jürgen; Kato, Nobuo; Ottmann, Christian

    2013-04-18

    Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 μM FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Stabilization of physical RAF/14-3-3 interaction by cotylenin A as treatment strategy for RAS mutant cancers.

    Science.gov (United States)

    Molzan, Manuela; Kasper, Stefan; Röglin, Lars; Skwarczynska, Malgorzata; Sassa, Takeshi; Inoue, Takatsugu; Breitenbuecher, Frank; Ohkanda, Junko; Kato, Nobuo; Schuler, Martin; Ottmann, Christian

    2013-09-20

    One-third of all human cancers harbor somatic RAS mutations. This leads to aberrant activation of downstream signaling pathways involving the RAF kinases. Current ATP-competitive RAF inhibitors are active in cancers with somatic RAF mutations, such as BRAF(V600) mutant melanomas. However, they paradoxically promote the growth of RAS mutant tumors, partly due to the complex interplay between different homo- and heterodimers of A-RAF, B-RAF, and C-RAF. Based on pathway analysis and structure-guided compound identification, we describe the natural product cotylenin-A (CN-A) as stabilizer of the physical interaction of C-RAF with 14-3-3 proteins. CN-A binds to inhibitory 14-3-3 interaction sites of C-RAF, pSer233, and pSer259, but not to the activating interaction site, pSer621. While CN-A alone is inactive in RAS mutant cancer models, combined treatment with CN-A and an anti-EGFR antibody synergistically suppresses tumor growth in vitro and in vivo. This defines a novel pharmacologic strategy for treatment of RAS mutant cancers.

  19. Interactions of cubilin with megalin and the product of the amnionless gene (AMN): effect on its stability.

    Science.gov (United States)

    Ahuja, Rajiv; Yammani, Raghunatha; Bauer, Joseph A; Kalra, Seema; Seetharam, Shakuntla; Seetharam, Bellur

    2008-03-01

    Cubilin, a 456 kDa multipurpose receptor lacking in both transmembrane and cytoplasmic domains is expressed in the apical BBMs (brush border membranes) of polarized epithelia. Cubilin interacts with two transmembrane proteins, AMN, a 45-50 kDa protein product of the amnionless gene, and megalin, a 600 kDa giant endocytic receptor. In vitro, three fragments of cubilin, the 113-residue N-terminus and CUB domains 12-17 and 22-27, demonstrated Ca2+-dependent binding to megalin. Immunoprecipitation and immunoblotting studies using detergent extracts of rat kidney BBMs revealed that cubilin interacts with both megalin and AMN. Ligand (intrinsic factor-cobalamin)-affinity chromatography showed that in renal BBMs, functional cubilin exists as a complex with both AMN and megalin. Cubilin and AMN levels were reduced by 80% and 55-60% respectively in total membranes and BBMs obtained from kidney of megalin antibody-producing rabbits. Immunohistochemical analysis and turnover studies for cubilin in megalin or AMN gene-silenced opossum kidney cells showed a significant reduction (85-90%) in cubilin staining and a 2-fold decrease in its half-life. Taken together, these results indicate that three distinct regions of cubilin bind to megalin and its interactions with both megalin and AMN are essential for its intracellular stability.

  20. EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1.

    Science.gov (United States)

    Lobo, Miguel J; Amaral, Margarida D; Zaccolo, Manuela; Farinha, Carlos M

    2016-07-01

    Cyclic AMP (cAMP) activates protein kinase A (PKA) but also the guanine nucleotide exchange factor 'exchange protein directly activated by cAMP' (EPAC1; also known as RAPGEF3). Although phosphorylation by PKA is known to regulate CFTR channel gating - the protein defective in cystic fibrosis - the contribution of EPAC1 to CFTR regulation remains largely undefined. Here, we demonstrate that in human airway epithelial cells, cAMP signaling through EPAC1 promotes CFTR stabilization at the plasma membrane by attenuating its endocytosis, independently of PKA activation. EPAC1 and CFTR colocalize and interact through protein adaptor NHERF1 (also known as SLC9A3R1). This interaction is promoted by EPAC1 activation, triggering its translocation to the plasma membrane and binding to NHERF1. Our findings identify a new CFTR-interacting protein and demonstrate that cAMP activates CFTR through two different but complementary pathways - the well-known PKA-dependent channel gating pathway and a new mechanism regulating endocytosis that involves EPAC1. The latter might constitute a novel therapeutic target for treatment of cystic fibrosis.

  1. A simple model for the interaction between vertical eddy heat fluxes and static stability

    Science.gov (United States)

    Gutowski, W. J., Jr.

    1985-01-01

    A numerical model for studying the interaction of vertical eddy heat fluxes and vertical temperature structure in midlatitude regions is described. The temperature profile for the model was derived from calculations of the equilibrium among heating rates in simplified representations of large-scale vertical eddy heat flux, moist convection and radiation. An eddy flux profile is calculated based on the quasi-geostrophic, liner baroclinic instability of a single wave. Model equilibrium states for summer and winter conditions are compared with observations, and the results are discussed in detail.

  2. Heparin stability by determining unsubstituted amino groups using hydrophilic interaction chromatography mass spectrometry.

    Science.gov (United States)

    Fu, Li; Li, Lingyun; Cai, Chao; Li, Guoyun; Zhang, Fuming; Linhardt, Robert J

    2014-09-15

    The thermal instability of the anticoagulant heparin is associated, in part, with the solvolytic loss of N-sulfo groups. This study describes a new method to assess the increased content of unsubstituted amino groups present in thermally stressed and autoclave-sterilized heparin formulations. N-Acetylation of heparin samples with acetic anhydride-d6 is followed by exhaustive heparinase treatment and disaccharide analysis by hydrophilic interaction chromatography mass spectrometry (HILIC-MS). The introduction of a stable isotopic label provides a sensitive probe for the detection and localization of the lost N-sulfo groups, potentially providing valuable insights into the degradation mechanism and the reasons for anticoagulant potency loss.

  3. CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation

    Energy Technology Data Exchange (ETDEWEB)

    Draheim, Kyle M.; Li, Xiaofeng; Zhang, Rong; Fisher, Oriana S.; Villari, Giulia; Boggon, Titus J.; Calderwood, David A. [Yale

    2015-04-21

    Mutations in the essential adaptor proteins CCM2 or CCM3 lead to cerebral cavernous malformations (CCM), vascular lesions that most frequently occur in the brain and are strongly associated with hemorrhagic stroke, seizures, and other neurological disorders. CCM2 binds CCM3, but the molecular basis of this interaction, and its functional significance, have not been elucidated. Here, we used x-ray crystallography and structure-guided mutagenesis to show that an α-helical LD-like motif within CCM2 binds the highly conserved “HP1” pocket of the CCM3 focal adhesion targeting (FAT) homology domain. By knocking down CCM2 or CCM3 and rescuing with binding-deficient mutants, we establish that CCM2–CCM3 interactions protect CCM2 and CCM3 proteins from proteasomal degradation and show that both CCM2 and CCM3 are required for normal endothelial cell network formation. However, CCM3 expression in the absence of CCM2 is sufficient to support normal cell growth, revealing complex-independent roles for CCM3.

  4. Climate change alters stability and species potential interactions in a large marine ecosystem.

    Science.gov (United States)

    Griffith, Gary P; Strutton, Peter G; Semmens, Jayson M

    2017-09-04

    We have little empirical evidence of how large-scale overlaps between large numbers of marine species may have altered in response to human impacts. Here, we synthesized all available distribution data (>1 million records) since 1992 for 61 species of the East Australian marine ecosystem, a global hot spot of ocean warming and continuing fisheries exploitation. Using a novel approach, we constructed networks of the annual changes in geographical overlaps between species. Using indices of changes in species overlap, we quantified changes in the ecosystem stability, species robustness, species sensitivity and structural keystone species. We then compared the species overlap indices with environmental and fisheries data to identify potential factors leading to the changes in distributional overlaps between species. We found that the structure of the ecosystem has changed with a decrease in asymmetrical geographical overlaps between species. This suggests that the ecosystem has become less stable and potentially more susceptible to environmental perturbations. Most species have shown a decrease in overlaps with other species. The greatest decrease in species overlap robustness and sensitivity to the loss of other species has occurred in the pelagic community. Some demersal species have become more robust and less sensitive. Pelagic structural keystone species, predominately the tunas and billfish, have been replaced by demersal fish species. The changes in species overlap were strongly correlated with regional oceanographic changes, in particular increasing ocean warming and the southward transport of warmer and saltier water with the East Australian Current (EAC), but less correlated with fisheries catch. Our study illustrates how large-scale multispecies distribution changes can help identify structural changes in marine ecosystems associated with climate change. This article is protected by copyright. All rights reserved. This article is protected by copyright. All

  5. Stabilization of cancer-specific gene carrier via hydrophobic interaction for a clear-cut response to cancer signaling.

    Science.gov (United States)

    Kim, Chan Woo; Toita, Riki; Kang, Jeong-Hun; Li, Kai; Lee, Eun Kyung; Zhao, Guo Xi; Funamoto, Daiki; Nobori, Takanobu; Nakamura, Yuta; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki

    2013-09-28

    Here, we developed a new gene carrier, comprising a linear polyethylenimine (LPEI) grafted with a hydrophobically modified cationic peptide containing a long alkyl chain, for use in cancer-specific gene delivery. The cationic peptide is a substrate of protein kinase Cα (PKCα), which is known to be activated specifically in cancer cells. The hydrophobically modified LPEI-peptide conjugate (LPEI-C10-peptide) could form a polyplex with DNA through electrostatic and hydrophobic interactions between the anionic DNA strands and the cationic peptide substrate. The hydrophobic modification of the peptide did not affect the reactivity of the peptide toward PKCα, while the polyplex showed improved intracellular uptake. Because of the efficient endosomal escape and enhanced stability, the polyplex significantly improved the transgene regulation responding to intracellular PKCα activity.

  6. Optimization of Cyanine Dye Stability and Analysis of FRET Interaction on DNA Microarrays.

    Science.gov (United States)

    von der Haar, Marcel; Heuer, Christopher; Pähler, Martin; von der Haar, Kathrin; Lindner, Patrick; Scheper, Thomas; Stahl, Frank

    2016-11-30

    The application of DNA microarrays for high throughput analysis of genetic regulation is often limited by the fluorophores used as markers. The implementation of multi-scan techniques is limited by the fluorophores' susceptibility to photobleaching when exposed to the scanner laser light. This paper presents combined mechanical and chemical strategies which enhance the photostability of cyanine 3 and cyanine 5 as part of solid state DNA microarrays. These strategies are based on scanning the microarrays while the hybridized DNA is still in an aqueous solution with the presence of a reductive/oxidative system (ROXS). Furthermore, the experimental setup allows for the analysis and eventual normalization of Förster-resonance-energy-transfer (FRET) interaction of cyanine-3/cyanine-5 dye combinations on the microarray. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the comparability of microarray experiment results between labs.

  7. Optimization of Cyanine Dye Stability and Analysis of FRET Interaction on DNA Microarrays

    Directory of Open Access Journals (Sweden)

    Marcel von der Haar

    2016-11-01

    Full Text Available The application of DNA microarrays for high throughput analysis of genetic regulation is often limited by the fluorophores used as markers. The implementation of multi-scan techniques is limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner laser light. This paper presents combined mechanical and chemical strategies which enhance the photostability of cyanine 3 and cyanine 5 as part of solid state DNA microarrays. These strategies are based on scanning the microarrays while the hybridized DNA is still in an aqueous solution with the presence of a reductive/oxidative system (ROXS. Furthermore, the experimental setup allows for the analysis and eventual normalization of Förster-resonance-energy-transfer (FRET interaction of cyanine-3/cyanine-5 dye combinations on the microarray. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the comparability of microarray experiment results between labs.

  8. Influence of Fluid, Solid, and Geometric Parameters on the Fluid-Structure Interaction Response and Stability of Flexible Lifting Surfaces

    Science.gov (United States)

    Chae, Eun Jung; Akcabay, Deniz Tolga; Young, Yin Lu

    2013-11-01

    There is an increasing interest to use innovative passive/active flexible lifting surfaces to take advantage of the fluid-structure interaction (FSI) response to improve performance or harvest energy. However, design and testing of flexible lifting surfaces are quite complicated, particularly for lightweight structures in a dense, viscous fluid. The objectives of this work are to (1) investigate the influence of varying fluid, material, and geometric parameters on the FSI response and stability boundaries, and (2) to develop generic parametric maps to facilitate the design of flexible lifting surfaces In particular, the focus is on the influence of solid-to-fluid density ratio, Reynolds number, relative stiffness ratio, and relative excitation frequency ratio on the FSI response and static/dynamic divergence and flutter stability boundaries. The results show that the governing failure mode transitions from flutter to dynamic divergence to static divergence when the solid-to-fluid added mass ratio decreases. In addition, classic linear potential theory is severely under-conservative in predicting the flutter boundary, and cannot predict the transition to dynamic divergence for cases in the low mass ratio regimes due to the strong nonlinear, viscous FSI response that develops when the fluid forces are comparable or greater than the solid forces. The Office of Naval Research (Grant no. N00014-11-1-0833); the National Research Foundation of Korea (GCRC-SOP Grant no. 2012-0004783).

  9. The First Residue of the PWWP Motif Modulates HATH Domain Binding, Stability, and Protein-Protein Interaction.

    Science.gov (United States)

    Hung, Yi-Lin; Lee, Hsia-Ju; Jiang, Ingjye; Lin, Shang-Chi; Lo, Wei-Cheng; Lin, Yi-Jan; Sue, Shih-Che

    2015-07-01

    Hepatoma-derived growth factor (hHDGF) and HDGF-related proteins (HRPs) contain conserved N-terminal HATH domains with a characteristic structural motif, namely the PWWP motif. The HATH domain has attracted attention because of its ability to bind with heparin/heparan sulfate, DNA, and methylated histone peptide. Depending on the sequence of the PWWP motif, HRP HATHs are classified into P-type (Pro-His-Trp-Pro) and A-type (Ala-His-Trp-Pro) forms. A-type HATH is highly unstable and tends to precipitate in solution. We replaced the Pro residue in P-type HATHHDGF with Ala and evaluated the influence on structure, dynamics, and ligand binding. Nuclear magnetic resonance (NMR) hydrogen/deuterium exchange and circular dichroism (CD) measurements revealed reduced stability. Analysis of NMR backbone (15)N relaxations (R1, R2, and nuclear Overhauser effect) revealed additional backbone dynamics in the interface between the β-barrel and the C-terminal helix bundle. The β1-β2 loop, where the AHWP sequence is located, has great structural flexibility, which aids HATH-HATH interaction through the loop. A-type HATH, therefore, shows a stronger tendency to aggregate when binding with heparin and DNA oligomers. This study defines the role of the first residue of the PWWP motif in modulating HATH domain stability and oligomer formation in binding.

  10. Rapid binding of electrostatically stabilized iron oxide nanoparticles to THP-1 monocytic cells via interaction with glycosaminoglycans.

    Science.gov (United States)

    Ludwig, Antje; Poller, Wolfram C; Westphal, Kera; Minkwitz, Susann; Lättig-Tünnemann, Gisela; Metzkow, Susanne; Stangl, Karl; Baumann, Gert; Taupitz, Matthias; Wagner, Susanne; Schnorr, Jörg; Stangl, Verena

    2013-03-01

    Magnetic resonance imaging (MRI) with contrast agents that target specific inflammatory components of atherosclerotic lesions has the potential to emerge as promising diagnostic modality for detecting unstable plaques. Since a high content of macrophages and alterations of the extracellular matrix are hallmarks of plaque instability, these structures represent attractive targets for new imaging modalities. In this study, we compared in vitro uptake and binding of electrostatically stabilized citrate-coated very small superparamagnetic iron oxide particles (VSOP) to THP-1 cells with sterically stabilized carboxydextran-coated Resovist(®). Uptake of VSOP in both THP-1 monocytic cells and THP-derived macrophages (THP-MΦ) was more efficient compared to Resovist(®) without inducing cytotoxicity or modifying normal cellular functions (no changes in levels of reactive oxygen species, caspase-3 activity, proliferation, cytokine production). Importantly, VSOP bound with high affinity to the cell surface and to apoptotic membrane vesicles. Inhibition of glycosaminoglycan (GAG) synthesis by glucose deprivation in THP-MΦ was associated with a significant reduction of VSOP attachment suggesting that the strong interaction of VSOP with the membranes of cells and apoptotic vesicles occurs via binding to negatively charged GAGs. These in vitro experiments show that VSOP-enhanced MRI may represent a new imaging approach for visualizing high-risk plaques on the basis of targeting pathologically increased GAGs or apoptotic membrane vesicles in atherosclerotic lesions. VSOP should be investigated further in appropriate in vivo experiments to characterize accumulation in unstable plaque.

  11. Highly Dynamic Interactions Maintain Kinetic Stability of the ClpXP Protease During the ATP-Fueled Mechanical Cycle.

    Science.gov (United States)

    Amor, Alvaro J; Schmitz, Karl R; Sello, Jason K; Baker, Tania A; Sauer, Robert T

    2016-06-17

    The ClpXP protease assembles in a reaction in which an ATP-bound ring hexamer of ClpX binds to one or both heptameric rings of the ClpP peptidase. Contacts between ClpX IGF-loops and clefts on a ClpP ring stabilize the complex. How ClpXP stability is maintained during the ATP-hydrolysis cycle that powers mechanical unfolding and translocation of protein substrates is poorly understood. Here, we use a real-time kinetic assay to monitor the effects of nucleotides on the assembly and disassembly of ClpXP. When ATP is present, complexes containing single-chain ClpX assemble via an intermediate and remain intact until transferred into buffers containing ADP or no nucleotides. ATP binding to high-affinity subunits of the ClpX hexamer prevents rapid dissociation, but additional subunits must be occupied to promote assembly. Small-molecule acyldepsipeptides, which compete with the IGF loops of ClpX for ClpP-cleft binding, cause exceptionally rapid dissociation of otherwise stable ClpXP complexes, suggesting that the IGF-loop interactions with ClpP must be highly dynamic. Our results indicate that the ClpX hexamer spends almost no time in an ATP-free state during the ATPase cycle, allowing highly processive degradation of protein substrates.

  12. Spontaneous nucleation and topological stabilization of skyrmions in magnetic nanodisks with the interfacial Dzyaloshinskii-Moriya interaction

    Science.gov (United States)

    Kolesnikov, A. G.; Samardak, A. S.; Stebliy, M. E.; Ognev, A. V.; Chebotkevich, L. A.; Sadovnikov, A. V.; Nikitov, S. A.; Kim, Yong Jin; Cha, In Ho; Kim, Young Keun

    2017-05-01

    One of the major societal challenges is reducing the power consumption of information technology (IT) devices and numerous data centers. Distinct from the current approaches based on switching of magnetic single-domain nanostructures or on movement of domain walls under high currents, an original magnetic skyrmion technology offers ultra-low power, fast, high-density, and scalable spintronic devices, including non-volatile random access memory. Using data-driven micromagnetic simulations, we demonstrate the possibility of spontaneous nucleation and stabilization of different skyrmionic states, such as skyrmions, merons, and meron-like configurations, in heavy metal/ferromagnetic nanodisks with the interfacial Dzyaloshinskii-Moriya interaction (iDMI) as a result of quasi-static magnetization reversal only. Since iDMI is not easily modulated in real systems, we show that skyrmion stabilization is easily achievable by manipulating magnetic anisotropy, saturation magnetization, and the diameters of nanodisks. The state diagrams, presented in terms of the topological charge, allow to explicitly distinguish the intermediate states between skyrmions and merons and can be used for developing a skyrmionic medium, which has been recently proposed to be a building block for future spin-orbitronic devices.

  13. Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

    Science.gov (United States)

    Prasad, Dev; Chauhan, Harsh; Atef, Eman

    2014-11-01

    The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions.

  14. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

    Science.gov (United States)

    Shakeel, Shabih; Westerhuis, Brenda M.; Domanska, Ausra; Koning, Roman I.; Matadeen, Rishi; Koster, Abraham J.; Bakker, Arjen Q.; Beaumont, Tim; Wolthers, Katja C.; Butcher, Sarah J.

    2016-07-01

    The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation.

  15. Nudel is crucial for the WAVE complex assembly in vivo by selectively promoting subcomplex stability and formation through direct interactions

    Institute of Scientific and Technical Information of China (English)

    Shuang Wu; Li Ma; Yibo Wu; Rong Zeng; Xueliang Zhu

    2012-01-01

    The WAVE regulatory complex (WRC),consisting of WAVE,Sra,Nap,Abi,and HSPC300,activates the Arp2/3 complex to control branched actin polymerization in response to Rac activation.How the WRC is assembled in vivo is not clear.Here we show that Nudel,a protein critical for lamellipodia formation,dramatically stabilized the Sra1-Nap1-Abi1 complex against degradation in cells through a dynamic binding to Sra1,whereas its physical interaction with HSPC300 protected free HSPC300 from the proteasome-mediated degradation and stimulated the HSPC300-WAVE2 complex formation.By contrast,Nudel showed little or no interactions with the Sra1-Nap1-Abi1-WAVE2 and the Sra1-Nap1-Abi1-HSPC300 complexes as well as the mature WRC.Depletion of Nudel by RNAi led to general subunit degradation and markedly attenuated the levels of mature WRC.It also abolished the WRC-dependent actin polymerization in vitro and the Rac1-induced lamellipodial actin network formation during cell spreading.Therefore,Nudel is important for the early steps of the WRC assembly in vivo by antagonizing the instability of certain WRC subunits and subcomplexes.

  16. Combining long term field experiments and nanoscale analysis to enhance process understanding of root litter stabilization by mineral interactions

    Science.gov (United States)

    Chabbi, Abad; Baumann, Karen; Remusat, Laurent; Barre, Pierre; Dignac, Marie-France; Rumpel, Cornelia

    2015-04-01

    stabilised OM may consist primarily of microbial cells. Thus our study is consistent with the microbial efficiency-matrix stabilisation (MEMS) hypothesis (Cotrufo et al., 2013), which says that microbial use efficiency determines stabilisation through interaction with the mineral phase. It also shows the importance of using long term field observations in addition to short term laboratory studies. Reference Cotrufo, M.F., Wallenstein, M.D., Boot, C., Denef, K., Paul, E., 2013. The microbial efficiency-matrix stabilisation (MEMS) framework integrates plant litter decomposition with soil organic matter stabilization: do labile plant inputs form stable organic matter? Global Change Biology, 19, 988-995.

  17. The Interaction Between FX and Credit Risk as an Example of Intersection of Monetary and Financial Stability Policy Goals – The Case of Serbia

    Directory of Open Access Journals (Sweden)

    Jović Željko

    2016-05-01

    Full Text Available The financial system of Serbia is highly bank-centric and euroised, which is a common specific feature of financial systems in developing countries. High level of euroisation represents an adequate environment for the development of emphasized interaction of foreign exchange and credit risks; therefore, creation of the spillover mechanism of foreign exchange risk to credit risk is immanent for euroised systems. Although maintaining the stability of the dinar exchange rate is a secondary goal of the National Bank of Serbia in relation to price and financial stability as the primary goals, in terms of existence of the aforesaid spillover mechanism, maintaining stability of the dinar exchange rate represents the area where there is an interaction between the goals of monetary policy (price stability and those of financial stability policy (maintaining and strengthening the financial system’s stability. In order to explore whether the spillover mechanism of foreign exchange risk to credit risk exists in Serbia’s financial system, the vector autoregressive (VAR model is applied on data from the Serbian banking sector to quantify the impact of changes in the dinar exchange rates on the rate of non-performing loans (NPLs; the sample was formed in the period of increased instability of the dinar exchange rate, from 31 January 2008 to 31 December 2010. As we have quantitatively confirmed the impact of increase in the dinar exchange rate on the increase of 90-120 days past due NPLs, we can conclude that the existence of expressed interaction between foreign exchange risk and credit risk in the Serbian financial system represents a paradigm of the regulator’s need to achieve contemporary goals of monetary and financial stability policy by maintaining relative stability of the dinar exchange rates. Depreciation of the local currency has inflationary pressure on price stability and simultaneously influences the achievement of financial stability goals

  18. Mode stability analysis in the beam-wave interaction process for a three-gap Hughes-type coupled cavity chain

    Institute of Scientific and Technical Information of China (English)

    Luo Ji-Run; Cui Jian; Zhu Min; Guo Wei

    2013-01-01

    Based on space-charge wave theory,the formulae of the beam-wave coupling coefficient and the beam-loaded conductance are given for the beam-wave interaction in an N-gap Hughes-type coupled cavity chain.The ratio of the nonbeam-loaded quality factor of the coupled cavity chain to the beam quality factor is used to determine the stability of the beam-wave interaction.As an example,the stabilities of the beam-wave interaction in a three-gap Hughes-type coupled cavity chain are discussed with the formulae and the CST code for the operations of the 2π,π,and π/2 modes,respectively.The results show that stable operation of the 2π,π,and π/2 modes may all be realized in an extended-interaction klystron with the three-gap Hughes-type coupled cavity chain.

  19. Organo-mineral interactions promote greater soil organic carbon stability under aspen in semi-arid montane forests in Utah

    Science.gov (United States)

    Van Miegroet, H.; Roman Dobarco, M.

    2014-12-01

    Forest species influence soil organic carbon (SOC) storage through litter input, which in interaction with soil microclimate, texture and mineralogy, lead to different SOC stabilization and storage patterns. We sampled mineral soil (0-15 cm) across the ecotone between aspen (Populus tremuloides) and mixed conifers stands (Abies lasiocarpa and Pseudotsuga menziesii) in semi-arid montane forests from Utah, to investigate the influence of vegetation vs. site characteristics on SOC stabilization, storage and chemistry. SOC was divided into light fraction (LF), mineral-associated SOC in the silt and clay fraction (MoM), and a dense subfraction > 53 μm (SMoM) using wet sieving and electrostatic attraction. SOC decomposability and solubility was derived from long term laboratory incubations and hot water extractions (HWE). Fourier transform infrared spectroscopy (FTIR) was used to study differences in chemical functional groups in LF and MoM. Vegetation cover did not affect SOC storage (47.0 ± 16.5 Mg C ha-1), SOC decomposability (cumulative CO2-C release of 93.2 ± 65.4 g C g-1 C), or SOC solubility (9.8 ± 7.2 mg C g-1 C), but MoM content increased with presence of aspen [pure aspen (31.2 ± 15.1 Mg C ha-1) > mixed (25.7 ± 8.8 Mg C ha-1) > conifer (22.8 ± 9.0 Mg C ha-1)]. Organo-mineral complexes reduced biological availability of SOC, indicated by the negative correlation between silt+clay (%) and decomposable SOC per gram of C (r = -0.48, p = 0.001) or soluble SOC (r = -0.59, p < 0.0001). FTIR spectral analysis indicated that higher MoM content under aspen was not due to higher concentration of recalcitrant compounds (e.g., aliphatic and aromatic C), but rather to stabilization of simple molecules (e.g., polysaccharides) of plant or microbial origin. FTIR spectra clustered by sites with similar parent material rather than by vegetation cover. This suggests that initial differences in litter chemistry between aspen and conifers converged into similar MoM chemistry

  20. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation.

    Directory of Open Access Journals (Sweden)

    Matteo eLambrughi

    2012-11-01

    Full Text Available Cyclin-dependent kinase inhibitors (CKIs are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs, which lack a well-defined and organized three-dimensional structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs and collapsed conformations. These structural features can be relevant to protein function in vivo.The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models of the compact conformations of the Sic1 kinase-inhibitory domain (KID by all-atom molecular-dynamics simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of hub residues and electrostatic interactions which are likely to be involved in the stabilization of globular states.

  1. Something to lose and nothing to gain : The role of stress in the interactive effect of power and stability on risk taking

    NARCIS (Netherlands)

    Jordan, Jennifer; Sivanathan, Niro; Galinsky, Adam D.

    2011-01-01

    The current investigation explores how power and stability within a social hierarchy interact to affect risk taking. Building on a diverse, interdisciplinary body of research, including work on non-human primates, intergroup status, and childhood social hierarchies, we predicted that the unstable po

  2. The thermal stability and domain interactions of the mannitol permease of Escherichia coli. A differential scanning calorimetry study.

    Science.gov (United States)

    Meijberg, W; Schuurman-Wolters, G K; Boer, H; Scheek, R M; Robillard, G T

    1998-08-14

    The thermal stability and domain interactions in the mannitol transporter from Escherichia coli, enzyme IImtl, have been studied by differential scanning calorimetry. To this end, the wild type enzyme, IICBAmtl, as well as IICBmtl and IICmtl, were reconstituted into a dimyristoylphosphatidylcholine lipid bilayer. The changes in the gel to liquid crystalline transition of the lipid indicated that the protein was inserted into the membrane, disturbing a total of approximately 40 lipid molecules/protein molecule. The thermal unfolding profile of EIImtl exhibited three separate transitions, two of which were overlapping, that could be assigned to structural domains in the protein. Treatment with trypsin, resulting in the degradation of the water-soluble part of the enzyme while leaving the binding and translocation capability of the enzyme intact, resulted in a decrease of the Tm and enthalpy of unfolding of the membrane-embedded C domain. This effect was much more apparent in the presence of the substrate but only partly so in the presence of the substrate analog perseitol. These results are consistent with a recently proposed model (Meijberg, W., Schuurman-Wolters, G. K., and Robillard, G. T. (1998) J. Biol. Chem. 273, 7949-7946), in which the B domain takes part in the conformational changes during the substrate binding process.

  3. Stabilization of neutral polyfluorene in aqueous solution through their interaction with phospholipids and sol-gel encapsulation.

    Science.gov (United States)

    Mallavia, Ricardo; Martínez-Tomé, Maria José; Vázquez-Guilló, Rebeca; Kahveci, Zehra; Estepa, Amparo; Mateo, C Reyes

    2013-04-24

    Interaction between poly[9,9-bis(6'-bromohexyl)-2,7-fluorene-co-alt-1,4-phenylene] (PFPBr2), a neutral conjugated polyfluorene which is completely insoluble in water, and zwitterionic phospholipids has been investigated in order to generate new fluorescent structures which are stable in aqueous media as a means of extending the biological applications of these kinds of polymers. Two types of differently shaped and composed fluorescent structures were identified and then isolated and characterized separately using different biophysical techniques. The first structure type, corresponding to liposomal complexes, showed a fluorescence band centered around 405 nm and maximum absorption at 345 nm, while the second, corresponding to polymer-phospholipid aggregates of variable sizes with lower lipid content, absorbed at longer wavelengths and displayed a well resolved fluorescence spectrum with a maximum centered at 424 nm. Both structures were stable in a large range of pH, and their fluorescence intensity remained practically unaltered for 10 days; it then began to decrease, which was probably because of aggregation. Encapsulation of these structures within the pores of a sol-gel matrix did not affect their fluorescent properties but increased their stability, avoiding further aggregation and subsequent precipitation.

  4. Cellular interactions and photoprotective effects of idebenone-loaded nanostructured lipid carriers stabilized using PEG-free surfactant.

    Science.gov (United States)

    Kyadarkunte, Abhay Y; Patole, Milind S; Pokharkar, Varsha B

    2015-02-01

    In past years, nanostructured lipid carriers (NLCs) have emerged as novel topical antioxidant delivery systems because of combined positive features of liposomes and polymeric nanoparticles. Here, we seek to unlock the possibility of idebenone (IDB; an antioxidant)-loaded NLCs (IDB-NLCs) cellular interactions such as, viability and uptake, and its photoprotective effects against Ultraviolet-B (UVB)-mediated oxidative stress in immortal human keratinocyte cell line (HaCaT). The two-step preformulation strategy followed by three-level, three-variable, L9 (3(3)) Taguchi robust orthogonal design employed was important in improving IDB-NLCs key physicochemical aspects such as, entrapment efficiency, drug release (sustained), occlusion, skin deposition and physical stability. UV crosslinker, confocal microscopy and flow cytometry techniques were used to (1) mediate oxidative stress in HaCaT cells, (2) study a qualitative cellular uptake, (3) measure intracellular reactive oxygen species (ROS), and mitochondrial membrane potential, respectively. NLCs markedly improved biocompatibility of IDB under normal as well as stress conditions. Quantitative and qualitative cell uptake studies demonstrated a significant uptake of IDB-NLCs (3-fold increase) and nile red-labeled IDB-NLCs (NR-IDB-NLCs) at 2 h, respectively, hence exerted improved photoprotective effects.

  5. Size-Dependent Protein-Nanoparticle Interactions in Citrate-Stabilized Gold Nanoparticles: The Emergence of the Protein Corona.

    Science.gov (United States)

    Piella, Jordi; Bastús, Neus G; Puntes, Víctor

    2017-01-18

    Surface modifications of highly monodisperse citrate-stabilized gold nanoparticles (AuNPs) with sizes ranging from 3.5 to 150 nm after their exposure to cell culture media supplemented with fetal bovine serum were studied and characterized by the combined use of UV-vis spectroscopy, dynamic light scattering, and zeta potential measurements. In all the tested AuNPs, a dynamic process of protein adsorption was observed, evolving toward the formation of an irreversible hard protein coating known as Protein Corona. Interestingly, the thickness and density of this protein coating were strongly dependent on the particle size, making it possible to identify different transition regimes as the size of the particles increased: (i) NP-protein complexes (or incomplete corona), (ii) the formation of a near-single dense protein corona layer, and (iii) the formation of a multilayer corona. In addition, the different temporal patterns in the evolution of the protein coating came about more quickly for small particles than for the larger ones, further revealing the significant role that size plays in the kinetics of this process. Since the biological identity of the NPs is ultimately determined by the protein corona and different NP-biological interactions take place at different time scales, these results are relevant to biological and toxicological studies.

  6. Investigation and correlation of physical stability, dissolution behaviour and interaction parameter of amorphous solid dispersions of telmisartan: a drug development perspective.

    Science.gov (United States)

    Dukeck, R; Sieger, P; Karmwar, P

    2013-07-16

    The aim of this study was to investigate if amorphous solid dispersions of telmisartan, prepared in presence of different polymers, exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their physical stability (time to crystallisation) and dissolution behaviour. Amorphous samples were prepared by melt quenching. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and differential scanning calorimetry. All freshly prepared samples were completely X-ray amorphous (with a halo being the only feature in the diffractograms). The shape of the halos in the diffractograms varied suggesting structural variations in the near order of the molecules between the different amorphous solid dispersions (ASDs). Principal component analysis of the Raman spectra of the various ASD revealed that the samples clustered in the scores plot, again suggesting structural differences due to the presence of different drug-polymer interaction. The ranking of the samples with respect to physical stability and interaction parameter was: ASD of telmisartan:eudragit>ASD of telmisartan:soluplus>ASD of telmisartan:HPMC>ASD of telmisartan:PVP>amorphous telmisartan. The interaction parameter, calculated by using the Flory Huggins theory, showed a good correlation with the experimentally determined stability whereas a weak correlation was found with dissolution behaviour of different ASD. This study showed that correlation of physical stability and dissolution behaviour with calculated interaction parameter is possible for the same amorphous systems prepared by using different polymers. This could aid in selecting the most appropriate polymer for the development of optimised formulations containing amorphous drugs. It can be concluded that ASD prepared by using different polymers have different structural and thermal properties. These differences affect the physical stability and dissolution

  7. Analysis of the stabilization process of indomethacin crystals via π-π and CH-π interactions measured by Raman spectroscopy and X-ray diffraction

    Science.gov (United States)

    Hattori, Yusuke; Otsuka, Makoto

    2016-09-01

    In this study, formations of π-π and CH-π interactions in the crystallization of amorphous indomethacin (IMC) were investigated by simultaneous Raman spectroscopy and X-ray diffraction (XRD) measurements. The activation energy obtained from the change in the peak at 1616 cm-1 corresponded to the energy obtained from the XRD diffraction peak at 21.6°. We suggest that the stable IMC crystal forms by carboxyl-carboxyl interactions, which is followed by CH-π and π-π interactions supporting stabilization in the indole and chlorophenyl rings.

  8. Genotype-environment interaction and phenotypic stability for girth growth and rubber yield of Hevea clones in São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Gonçalves Paulo de Souza

    2003-01-01

    Full Text Available The best-yielding, best vigour and most stable Hevea clones are identified by growing clones in different environments. However, research on the stability in Hevea brasiliensis (Willd. Adr. ex Juss. Muell.-Arg. is scarce. The objectives of this work were to assess genotype-environment interaction and determine stable genotypes. Stability analysis were performed on results for girth growth and rubber yield of seven clones from five comparative trials conducted over 10 years (girth growth and four years (rubber yield in São Paulo State, Brazil. Stability was estimated using the Eberhart and Russell (1966 method. Year by location and location variability were the dominant sources of interactions. The stability analysis identified GT 1 and IAN 873 as the most stable clones for girth growth and rubber yield respectively since their regression coefficients were almost the unity (b = 1 and they had one of the lowest deviations from regressions (S2di. Their coefficient of determination (R² was as high as 89.5% and 89.8% confirming their stability. In contrast, clones such as PB 235, PR 261, and RRIM 701 for girth growth and clones such as GT 1 for rubber yield with regression coefficients greater than one were regarded as sensitive to environment changes.

  9. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Science.gov (United States)

    Sharma, Reetu; Sastry, G Narahari

    2015-01-01

    Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  10. Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Reetu Sharma

    Full Text Available Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

  11. EMERGING ROLE OF N- AND C-TERMINAL INTERACTIONS IN STABILIZING (β;/α8 FOLD WITH SPECIAL EMPHASIS ON FAMILY 10 XYLANASES

    Directory of Open Access Journals (Sweden)

    Amit Bhardwaj

    2012-09-01

    Full Text Available Xylanases belong to an important class of industrial enzymes. Various xylanases have been purified and characterized from a plethora of organisms including bacteria, marine algae, plants, protozoans, insects, snails and crustaceans. Depending on the source, the enzymatic activity of xylanases varies considerably under various physico-chemical conditions such as temperature, pH, high salt and in the presence of proteases. Family 10 or glycosyl hydrolase 10 (GH10 xylanases are one of the well characterized and thoroughly studied classes of industrial enzymes. The TIM-barrel fold structure which is ubiquitous in nature is one of the characteristics of family 10 xylanases. Family 10 xylanases have been used as a “model system” due to their TIM-barrel fold to dissect and understand protein stability under various conditions. A better understanding of structure-stability-function relationships of family 10 xylanases allows one to apply these governing molecular rules to engineer other TIM-barrel fold proteins to improve their stability and retain function(s under adverse conditions. In this review, we discuss the implications of N-and C-terminal interactions, observed in family 10 xylanases on protein stability under extreme conditions. The role of metal binding and aromatic clusters in protein stability is also discussed. Studying and understanding family 10 xylanase structure and function, can contribute to our protein engineering knowledge.

  12. Emerging role of N- and C-terminal interactions in stabilizing (β/α8 fold with special emphasis on Family 10 xylanases

    Directory of Open Access Journals (Sweden)

    Amit Bhardwaj

    2012-09-01

    Full Text Available Xylanases belong to an important class of industrial enzymes. Various xylanases have been purified and characterized from a plethora of organisms including bacteria, marine algae, plants, protozoans, insects, snails and crustaceans. Depending on the source, the enzymatic activity of xylanases varies considerably under various physico-chemical conditions such as temperature, pH, high salt and in the presence of proteases. Family 10 or glycosyl hydrolase 10 (GH10 xylanases are one of the well characterized and thoroughly studied classes of industrial enzymes. The TIM-barrel fold structure which is ubiquitous in nature is one of the characteristics of family 10 xylanases. Family 10 xylanases have been used as a “model system” due to their TIM-barrel fold to dissect and understand protein stability under various conditions. A better understanding of structure-stability-function relationships of family 10 xylanases allows one to apply these governing molecular rules to engineer other TIM-barrel fold proteins to improve their stability and retain function(s under adverse conditions. In this review, we discuss the implications of N-and C-terminal interactions, observed in family 10 xylanases on protein stability under extreme conditions. The role of metal binding and aromatic clusters in protein stability is also discussed. Studying and understanding family 10 xylanase structure and function, can contribute to our protein engineering knowledge.

  13. HVDC-System-Interaction Assessment through Line-Flow Change-Distribution Factor and Transient-Stability Analysis at Planning Stage

    Directory of Open Access Journals (Sweden)

    Sungchul Hwang

    2016-12-01

    Full Text Available Many of the recent projects for new transmission line have considered the high-voltage direct current (HVDC system, owing to the many advantages of the direct current (DC system. The most noteworthy advantage is that a cable can serve as a substitute for the overhead transmission line in residential areas; therefore, the HVDC system application is increasing, and as the number of DC systems in the power system increases, the interaction assessment regarding the HVDC system gains importance. An index named multi-infeed interaction factor (MIIF is commonly used to estimate the interaction between power converters; however, the HVDC system is composed of two converters and a transmission line. The MIIF represents the interaction between the rectifiers and inverters, but not for the whole system. In this work, a method to assess the interaction of the whole system was therefore studied. To decide on the location of the new HVDC transmission system at the planning stage, in consideration of the interaction of the existing DC system, the line flow change distribution factor, according to the HVDC-transmission capacity change, was examined. Also, a power system transient -stability analysis was performed with different HVDC system locations, depending on the distribution factor. The simulation results indicate that when the factor is higher, two HVDC systems have a stronger interaction and are less stable in the transient state.

  14. Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1.

    Science.gov (United States)

    Blees, Johanna S; Bokesch, Heidi R; Rübsamen, Daniela; Schulz, Kathrin; Milke, Larissa; Bajer, Magdalena M; Gustafson, Kirk R; Henrich, Curtis J; McMahon, James B; Colburn, Nancy H; Schmid, Tobias; Brüne, Bernhard

    2012-01-01

    Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70(S6K1)-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin), it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target) and HIF-1α (a pVHL-target), implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition.

  15. Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1.

    Directory of Open Access Journals (Sweden)

    Johanna S Blees

    Full Text Available Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70(S6K1-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin, it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target and HIF-1α (a pVHL-target, implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition.

  16. Substituent effect on the molecular stability,group interaction,detonation performance,and thermolysis mechanism of nitroamino-substituted cyclopentanes and cyclohexanes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Density functional theory (DFT) method has been employed to study the effect of nitroamino group as a substituent in cyclopentane and cyclohexane, which usually construct the polycyclic or caged nitra-mines. Molecular structures were investigated at the B3LYP/6-31G** level, and isodesmic reactions were designed for calculating the group interactions. The results show that the group interactions ac-cord with the group additivity, increasing with the increasing number of nitroamino groups. The dis-tance between substituents influences the interactions. Detonation performances were evaluated by the Kamlet-Jacobs equations based on the predicted densities and heats of formation, while thermal stability and pyrolysis mechanism were studied by the computations of bond dissociation energy (BDE). It is found that the contributions of nitroamino groups to the detonation heat, detonation velocity, detonation pressure, and stability all deviate from the group additivity. Only 3a, 3b, and 9a-9c may be novel potential candidates of high energy density materials (HEDMs) according to the quantitative cri-teria of HEDM (ρ≈ 1.9 g/cm3, D ≈ 9.0 km/s, P ≈ 40.0 GPa). Stability decreases with the increasing number of N-NO2 groups, and homolysis of N-NO2 bond is the initial step in the thermolysis of the title com-pounds. Coupled with the demand of thermal stability (BDE > 20 kcal/mol), only 1,2,4-trinitrotriazacy-clohexane and 1,2,4,5-tetranitrotetraazacyclohexane are suggested as feasible energetic materials. These results may provide basic information for the molecular design of HEDMs.

  17. Yeast frataxin is stabilized by low salt concentrations: cold denaturation disentangles ionic strength effects from specific interactions.

    Science.gov (United States)

    Sanfelice, Domenico; Puglisi, Rita; Martin, Stephen R; Di Bari, Lorenzo; Pastore, Annalisa; Temussi, Piero Andrea

    2014-01-01

    Frataxins are a family of metal binding proteins associated with the human Friedreich's ataxia disease. Here, we have addressed the effect of non-specifically binding salts on the stability of the yeast ortholog Yfh1. This protein is a sensitive model since its stability is strongly dependent on the environment, in particular on ionic strength. Yfh1 also offers the unique advantage that its cold denaturation can be observed above the freezing point of water, thus allowing the facile construction of the whole protein stability curve and hence the measurement of accurate thermodynamic parameters for unfolding. We systematically measured the effect of several cations and, as a control, of different anions. We show that, while strongly susceptible to ionic strength, as it would be in the cellular environment, Yfh1 stability is sensitive not only to divalent cations, which bind specifically, but also to monovalent cations. We pinpoint the structural bases of the stability and hypothesize that the destabilization induced by an unusual cluster of negatively charged residues favours the entrance of water molecules into the hydrophobic core, consistent with the generally accepted mechanism of cold denaturation.

  18. Quantifying the Impact of Background Atmospheric Stability on Air-Ice-Ocean Interactions the Arctic Ocean During the Fall Freeze-Up

    Science.gov (United States)

    Guest, P. S.; Persson, O. P. G.; Blomquist, B.; Fairall, C. W.

    2016-02-01

    "Background" stability refers to the effect of vertical virtual temperature variations above the surface layer on fluxes within the surface layer. This is different from the classical surface layer stability quantified by the Obhukhov length scale. In most locations, changes in the background stability do not have a significant direct impact on surface fluxes. However in polar regions, where there is usually a strong low-level temperature inversion capping the boundary layer, changes in background stability can have big impacts on surface fluxes. Therefore, in the Arctic, there is potential for a positive feedback effect between ice cover and surface wind speed (and momentum flux) due to the background stability effects. As the surface becomes more ice free, heat fluxes from the surface weaken the temperature inversion which in turn increases the surface wind speed which further increases the surface turbulent heat fluxes and removes more sea ice by melting or advection. It is not clear how important feedbacks involving the background stability are during the fall freeze up of the Arctic Ocean; that will be the focus of this study. As part of an ONR-sponsored cruise in the fall of 2015 to examine sea state and boundary layer processes in the Beaufort Sea on the R/V Sikuliaq, the authors will perform a variety of surface layer and upper level atmospheric measurements of temperature, humidity and wind vector using ship platform instruments, radiosonde weather balloons, tethered balloons, kites, and miniature quad-rotor unmanned aerial vehicles. In addition, the authors will deploy a full suite of turbulent and radiational flux measurements from the vessel. These measurements will be used to quantify the impact of changing surface conditions on atmospheric structure and vice-versa. The goal is to directly observe how the surface and atmosphere above the surface layer interact and feedback with each other through radiational and turbulent fluxes.

  19. Electronic structure and relative stability of 1:1 Cu-O2 adducts from difference-dedicated configuration interaction calculations.

    Science.gov (United States)

    Zapata-Rivera, Jhon; Caballol, Rosa; Calzado, Carmen J

    2011-04-30

    A computational strategy to analyze Cu-O(2) adducts based on the use of difference-dedicated configuration interaction (DDCI) calculations is presented. The electronic structure, vertical gaps and nature of the metal-O(2) interaction, and the extension of the charge transfer between both fragments have been investigated. Relative stabilities between isomers are determined from triplet states CCSD(T) calculations. The key point of the here proposed strategy rests on the use of a rationally designed active space, containing only those orbitals, which optimize the interaction pathways between LCu and O(2) fragments. The procedure has been tested on a broad set of model and synthetic biomimetic systems, the results compared with previous theoretical evaluations and/or available experimental data. Our study indicates that this strategy can be considered as an alternative approach to multireference second-order perturbation theory methods to deal with this type of systems with remarkable biradical nature.

  20. Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I

    Directory of Open Access Journals (Sweden)

    Hagen Thilo

    2011-04-01

    Full Text Available Abstract The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein. We found that Compound C functions as an inhibitor of complex I of the mitochondrial electron transport chain as demonstrated by its effect on mitochondrial respiration. It also prevents hypoxia-induced Hypoxia-Inducible Factor-1α stabilization in a dose dependent manner. In addition, Compound C does not have significant effects on reactive oxygen species production from complex I via both forward and reverse electron flux. This study provides evidence that similar to other mitochondrial electron transport chain inhibitors, Compound C regulates Hypoxia-Inducible Factor-1α stability by controlling the cellular oxygen concentration.

  1. Investigating Mutations to Reduce Huntingtin Aggregation by Increasing Htt-N-Terminal Stability and Weakening Interactions with PolyQ Domain

    Science.gov (United States)

    Mazza-Anthony, Cody; Waldispühl, Jérôme

    2016-01-01

    Huntington's disease is a fatal autosomal genetic disorder characterized by an expanded glutamine-coding CAG repeat sequence in the huntingtin (Htt) exon 1 gene. The Htt protein associated with the disease misfolds into toxic oligomers and aggregate fibril structures. Competing models for the misfolding and aggregation phenomena have suggested the role of the Htt-N-terminal region and the CAG trinucleotide repeats (polyQ domain) in affecting aggregation propensities and misfolding. In particular, one model suggests a correlation between structural stability and the emergence of toxic oligomers, whereas a second model proposes that molecular interactions with the extended polyQ domain increase aggregation propensity. In this paper, we computationally explore the potential to reduce Htt aggregation by addressing the aggregation causes outlined in both models. We investigate the mutation landscape of the Htt-N-terminal region and explore amino acid residue mutations that affect its structural stability and hydrophobic interactions with the polyQ domain. Out of the millions of 3-point mutation combinations that we explored, the (L4K E12K K15E) was the most promising mutation combination that addressed aggregation causes in both models. The mutant structure exhibited extreme alpha-helical stability, low amyloidogenicity potential, a hydrophobic residue replacement, and removal of a solvent-inaccessible intermolecular side chain that assists oligomerization. PMID:28096892

  2. Stabilization of species coexistence in spatial models through the aggregation-segregation effect generated by local dispersal and nonspecific local interactions.

    Science.gov (United States)

    Detto, Matteo; Muller-Landau, Helene C

    2016-12-01

    Spatial interactions are widely acknowledged to play a significant role in sustaining diversity in ecological communities. However, theoretical work on this topic has focused on how spatial processes affect coexistence of species that differ in their strategies, with less attention to how spatial processes matter when competitors are equivalent. Furthermore, though it is recognized that models with local dispersal and local competition may sustain higher diversities of equivalent competitors than models in which these are not both localized, there is debate as to whether this reflects merely equalizing effects or whether there is also a stabilizing component. In this study, we explore how dispersal limitation and nonspecific local competition influence the outcome of species coexistence in communities driven by stochastic drift. We demonstrate that space alone acts as a stabilizing factor in a continuous space model with local dispersal and competition, as individuals of rare species on average experience lower total neighborhood densities, causing per capita reproductive rates to decrease systematically with increasing abundance. These effects prolong time to extinction in a closed system and enhance species diversity in an open system with constant immigration. Fundamentally, these stabilizing effects are obtained when dispersal limitation interacts with local competition to generate fluctuations in population growth rates. Thus this effect can be considered a fluctuating mechanism similar to spatial or temporal storage effects, but generated purely endogenously without requiring any exogenous environmental variability or species dissimilarities.

  3. C-H…pi interactions in proteins: prevalence, pattern of occurrence, residue propensities, location, and contribution to protein stability.

    Science.gov (United States)

    Kumar, Manjeet; Balaji, Petety V

    2014-02-01

    C-H…pi interactions are a class of non-covalent interactions found in different molecular systems including organic crystals, proteins and nucleic acids. High-resolution protein structures have been analyzed in the present study to delineate various aspects of C-H…pi interactions. Additionally, to determine the extent to which redundancy of a database biases the outcome, two datasets differing from each other in the level of redundancy have been analyzed. On average, only one out of six {with C-H(Aro) group} or eight {with C-H(Ali) group} residues in a protein participate as C-H group donors. Neither the frequency of occurrence in proteins nor the number of C-H groups present in it is correlated to the propensity of an amino acid to participate in C-H…pi interactions. Most of the residues that participate in C-H…pi interactions are solvent-shielded. Solvent shielded nature of most of the C-H…pi interactions and prevalence of intra- as well as inter-secondary structural element C-H…pi interactions suggest that the contribution of these interactions to the enthalpy of folded form will be significant. The separation in the primary structure between donor and acceptor residues is found to be correlated to secondary structure type. Other insights obtained from this study include the presence of networks of C-H…pi interactions spanning multiple secondary structural elements. To our knowledge this has not been reported so far. A substantial number of residues involved in C-H…pi interactions are found in catalytic and ligand binding sites suggesting their possible role in maintaining active site geometry. No significant differences of C-H…pi interactions in the two datasets are found for any of the parameters/features analyzed.

  4. Structure of soybean seed coat peroxidase: a plant peroxidase with unusual stability and haem-apoprotein interactions

    DEFF Research Database (Denmark)

    Henriksen, A; Mirza, O; Indiani, C

    2001-01-01

    Soybean seed coat peroxidase (SBP) is a peroxidase with extraordinary stability and catalytic properties. It belongs to the family of class III plant peroxidases that can oxidize a wide variety of organic and inorganic substrates using hydrogen peroxide. Because the plant enzyme is a heterogeneous...

  5. Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network.

    Science.gov (United States)

    Podder, Avijit; Jatana, Nidhi; Latha, N

    2014-09-21

    Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders. Taking into consideration that proteins function collectively in a network for most of the biological processes, the present study is aimed to depict the interactions between all dopamine receptors following a systems biology approach. To capture comprehensive interactions of candidate proteins associated with human dopamine receptors, we performed a protein-protein interaction network (PPIN) analysis of all five receptors and their protein partners by mapping them into human interactome and constructed a human Dopamine Receptors Interaction Network (DRIN). We explored the topology of dopamine receptors as molecular network, revealing their characteristics and the role of central network elements. More to the point, a sub-network analysis was done to determine major functional clusters in human DRIN that govern key neurological pathways. Besides, interacting proteins in a pathway were characterized and prioritized based on their affinity for utmost drug molecules. The vulnerability of different networks to the dysfunction of diverse combination of components was estimated under random and direct attack scenarios. To the best of our knowledge, the current study is unique to put all five dopamine receptors together in a common interaction network and to understand the functionality of interacting proteins collectively. Our study pinpointed distinctive topological and functional properties of human dopamine receptors that have helped in identifying potential therapeutic drug targets in the dopamine interaction network.

  6. Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

    Science.gov (United States)

    Ratnaparkhi, Aditi; Muthu, Shivani A; Shiriskar, Sonali M; Pissurlenkar, Raghuvir R S; Choudhary, Sinjan; Ahmad, Basir

    2015-09-01

    Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.

  7. Stability of the transthyretin molecule as a key factor in the interaction with a-beta peptide--relevance in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Carlos A Ribeiro

    Full Text Available Transthyretin (TTR protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenylamino] (DCPA and [4-(3,5-difluorophenyl] (DFPB were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this

  8. Introduction of an electron push-pull system yields a planar Red Kaede fluorescence protein chromophore analogue stabilized by a C = O… interaction

    Indian Academy of Sciences (India)

    Ashish Singh; Basanta Kumar Rajbongshi; Gurunath Ramanathan

    2015-05-01

    Crystal structures of four red kaede fluorescence protein chromophore analogues are reported here. Molecules I-III adopt a non-planar geometry stabilized by … stacking and hydrogen bonding. Introduction of an electron push-pull system induces molecule IV to be planar and a C = O… supramolecular interaction is observed as well. Strong electron withdrawing and donating groups also ensure formation of a higher order two and three dimensional supramolecular architecture through hydrogen bonds in molecules I and IV. All the analogues exhibit good photoluminescence properties and emit in the red region with excellent quantum yields.

  9. Occurrence and stability of lone pair–π stacking interactions between ribose and nucleobases in functional RNAs

    KAUST Repository

    Chawla, Mohit

    2017-08-18

    The specific folding pattern and function of RNA molecules lies in various weak interactions, in addition to the strong base-base pairing and stacking. One of these relatively weak interactions, characterized by the stacking of the O4′ atom of a ribose on top of the heterocycle ring of a nucleobase, has been known to occur but has largely been ignored in the description of RNA structures. We identified 2015 ribose–base stacking interactions in a high-resolution set of non-redundant RNA crystal structures. They are widespread in structured RNA molecules and are located in structural motifs other than regular stems. Over 50% of them involve an adenine, as we found ribose-adenine contacts to be recurring elements in A-minor motifs. Fewer than 50% of the interactions involve a ribose and a base of neighboring residues, while approximately 30% of them involve a ribose and a nucleobase at least four residues apart. Some of them establish inter-domain or inter-molecular contacts and often implicate functionally relevant nucleotides. In vacuo ribose-nucleobase stacking interaction energies were calculated by quantum mechanics methods. Finally, we found that lone pair–π stacking interactions also occur between ribose and aromatic amino acids in RNA–protein complexes.

  10. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  11. [small beta]-Turn mimetic-based stabilizers of protein-protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase

    DEFF Research Database (Denmark)

    Kim, Chanwoo; Jung, Jinjoo; Thanh Tung, Truong

    2016-01-01

    For the systematic perturbation of protein-protein interactions, we designed and synthesized tetra-substituted hexahydro-4H-pyrazino[2,1-c][1,2,4]triazine-4,7(6H)-diones as [small beta]-turn mimetics. We then devised a new synthetic route to obtain [small beta]-turn mimetic scaffolds via tandem N...... in the nutrient-dependent mTORC1 signalling pathway. Western blot analysis of phosphorylated S6K1 as well as FRET-based imaging confirmed that 5c3,9 stabilizes the direct interaction between LRS and RagD and activates mTORC1 in live cells under leucine-deprived conditions. Thus, 5c3,9 can be used as a new...

  12. Predicting important residues and interaction pathways in proteins using Gaussian Network Model: binding and stability of HLA proteins.

    Directory of Open Access Journals (Sweden)

    Turkan Haliloglu

    Full Text Available A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed.

  13. Synthesis and characterization of the first 2 d neptunyl structure stabilized by side-on cation-cation interactions

    Energy Technology Data Exchange (ETDEWEB)

    Vlaisavljevich, Bess; Miro, Pere; Ma, Dongxia; Cramer, Christopher J.; Gagliardi, Laura [Department of Chemistry, Supercomputing Institute and Chemical Theory Center, University of Minnesota, Minneapolis, MN (United States); Sigmon, Ginger E.; Burns, Peter C. [Department of Civil and Environmental Engineering and Earth Sciences, and Department of Chemistry and Biochemistry, University of Notre Dame, IN (United States)

    2013-02-25

    A new 2 D sheet structure containing a side-on cation-cation interaction (CCI) has been synthesized and characterized. Unprecedentedly, no chelating ligands between the cations are present. The nature of the side-on interaction and ligand effects has been explored by using a variety of quantum chemical methods. The spin-orbit-coupled ground state mixes singlet, triplet, and quintet-pure spin states. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. INTERACTIONS OF NATURAL ANTIOXIDANTS WITH RED GRAPE POMACE ANTHOCYANINS IN A LIQUID MODEL MATRIX: STABILITY AND COPIGMENTATION EFFECTS

    Directory of Open Access Journals (Sweden)

    BADHERDINE SIDANI

    2011-03-01

    Full Text Available The purpose of this study was an examination of the stability and colour en-hancement of red grape pomace anthocyanins in a juice model matrix, and the effect of the addition of natural antioxidants. The approach was based on a juice-like liquid medium (10.1 °Bx, pH 3.48, which was used as the model matrix to test the effect of the addition of natural antioxidants (L-cysteine, as-corbic acid, catechin and quercetin on the degradability of anthocyanin pigments, extracted from grape pomace. It was found that treatment of the model solutions at 80 °C induced anthocyanin decomposition, which obeyed first order kinetics. Addition of increasing amounts of antioxidants, including L-cysteine, ascorbic acid, catechin and quercetin, did not provoke a proportional impact, either positive or negative, with regard to anthocyanin stability. The best stabilising effect was seen after addition of ascorbic acid and catechin at con¬centrations of 4 and 2 mg L-1, respectively (P < 0.001. Quercetin, however, was demonstrated a very efficient copigment, inducing an increase in A520 by 63%, at pH 5.6 and a copigment-to-pigment ratio of 10.

  15. Transgene-host cell interactions mediate significant influences on the production, stability, and function of recombinant canine FVIII

    Directory of Open Access Journals (Sweden)

    Bredon Crawford

    2015-01-01

    Full Text Available Recombinant FVIII manufacturing is characterized by poor product stability and low yields. Codon-optimization of transgenes accelerates translation by exploiting the synonymous codon usage bias of a species. However, this can alter the performance of the final product. Additionally, the effects of transgene design across diverse cell types are not well understood and are of interest for next-generation protein and gene therapies. To investigate the effects of transgene design across different host cells, B-domain-deleted (BDD and modified codon-optimized (CO-N6 transgenes were inserted via lentiviral delivery into cBOECs, HEK293T, and MDCK cells. The CO-N6 cFVIII transgene produced threefold more protein per transgene in HEK293T cells, and sixfold more protein in the two canine cell lines. However, pharmacokinetic analysis in hemophilia A dogs demonstrated that cFVIII produced from cBOECs transduced with the CO-N6 transgene had significantly reduced in vivo recovery. Furthermore, this product showed reduced in vitro stability and activity on thrombin activation versus the BDD product. This trend was reversed in HEK293T lines. Overall, our results demonstrate the need for an integrated approach that not only assesses protein expression levels but also considers the influence that host-cells have on preserving the molecular and biochemical properties of the naturally occurring FVIII.

  16. Soft interactions and volume exclusion by polymeric crowders can stabilize or destabilize transient structure in disordered proteins depending on polymer concentration.

    Science.gov (United States)

    Rusinga, Farai I; Weis, David D

    2017-08-01

    The effects of macromolecular crowding on the transient structure of intrinsically disordered proteins is not well-understood. Crowding by biological molecules inside cells could modulate transient structure and alter IDP function. Volume exclusion theory and observations of structured proteins suggest that IDP transient structure would be stabilized by macromolecular crowding. Amide hydrogen exchange (HX) of IDPs in highly concentrated polymer solutions would provide valuable insights into IDP transient structure under crowded conditions. Here, we have used mass spectrometry to measure HX by a transiently helical random coil domain of the activator of thyroid and retinoid receptor (ACTR) in solutions containing 300 g L(-1) and 400 g L(-1) of Ficoll, a synthetic polysaccharide, using a recently-developed strong cation exchange-based cleanup method [Rusinga, et al., Anal Chem 2017;89:1275-1282]. Transiently helical regions of ACTR exchanged faster in 300 g L(-1) Ficoll than in dilute buffer. In contrast, one transient helix exchanged more slowly in 400 g L(-1) Ficoll. Nonspecific interactions destabilize ACTR helicity in 300 g L(-1) Ficoll because ACTR engages with the Ficoll polymer mesh. In contrast, 400 g L(-1) Ficoll is a semi-dilute solution where ACTR cannot engage the Ficoll mesh. At this higher concentration, volume exclusion stabilizes ACTR helicity because ACTR is compacted in interstitial spaces between Ficoll molecules. Our results suggest that the interplay between nonspecific interactions and volume exclusion in different cellular compartments could modulate IDP function by altering the stability of IDP transient structures. Proteins 2017; 85:1468-1479. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. A novel interaction between DNA ligase III and DNA polymerase gamma plays an essential role in mitochondrial DNA stability.

    Science.gov (United States)

    De, Ananya; Campbell, Colin

    2007-02-15

    The data in the present study show that DNA polymerase gamma and DNA ligase III interact in mitochondrial protein extracts from cultured HT1080 cells. An interaction was also observed between the two recombinant proteins in vitro. Expression of catalytically inert versions of DNA ligase III that bind DNA polymerase gamma was associated with reduced mitochondrial DNA copy number and integrity. In contrast, overexpression of wild-type DNA ligase III had no effect on mitochondrial DNA copy number or integrity. Experiments revealed that wild-type DNA ligase III facilitates the interaction of DNA polymerase gamma with a nicked DNA substrate in vitro, and that the zinc finger domain of DNA ligase III is required for this activity. Mitochondrial protein extracts prepared from cells overexpressing a DNA ligase III protein that lacked the zinc finger domain had reduced base excision repair activity compared with extracts from cells overexpressing the wild-type protein. These data support the interpretation that the interaction of DNA ligase III and DNA polymerase gamma is required for proper maintenance of the mammalian mitochondrial genome.

  18. The transcription elongation factor Bur1-Bur2 interacts with replication protein A and maintains genome stability during replication stress

    DEFF Research Database (Denmark)

    Clausing, Emanuel; Mayer, Andreas; Chanarat, Sittinan

    2010-01-01

    foci. Interestingly, the DNA damage sensitivity of an rfa1 mutant was suppressed by bur1 mutation, further underscoring a functional link between these two protein complexes. The transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress....

  19. 稳定剂对ADN和NC初期相互作用的影响%Influences of Stabilizers on the Nascent Interaction between ADN and NC

    Institute of Scientific and Technical Information of China (English)

    李吉祯; 王祎; 刘芳莉; 付小龙; 樊学忠; 张腊莹; 王琼

    2011-01-01

    在研究二硝酰胺铵(ADN)的热行为特性及其与硝化纤维素(NC)相互作用的基础上,利用差示扫描量热法(DSC)研究了稳定剂N-甲基对硝基苯胺(MNA)、二号中定剂(C2)、2-硝基二苯胺(2-NDPA)、六次甲基四胺(HMT)及其复配体系(MNA/C2、MNA/2-NDPA、MNA/HMT)对ADN与NC之间初期相互作用的影响.结果表明,稳定剂MNA和C2可使ADN与NC之间的相互作用得到一定程度的减弱,MNA与C2、2-NDPA和HMT的复配协同作用对ADN与NC之间的初期相互作用产生了较为明显的抑制作用,与NC/ADN二元混合体系相比,NC/(ADN/稳定剂)体系的DSC峰温提前量可由19.2℃缩减至11.9℃.%On the basis of the study of thermal behavior of ammonium dinitramide (ADN) and the interaction between ADN and NC, the influences of stabilizers, such as N-methyl-p-nitroaniline(MNA), 1,3-dimethyl-1,3-diphenylurea(C2 ) ,2-nitrodianiline(2-NDPA) ,hexamethylenetetramine(HMT) and its complex MNA/C2, MNA/2-NDPA and MNA/HMT, on the nascent interactions between ADN and NC were investigated by using the method of DSC.The results show that the interaction between ADN and NC can be decreased to a certain extent by mixing MNA and C2, and the nascent interaction between ADN and NC can be inhibited obviously by mixing the complex of MNA/C2, MNA/2-NDPA and MNA/HMT. Comparing the binary system of ADN/NC, the value of △Tp,which is the DSC exothermic peak temperature different between ADN/stabilizer and NC, can be decreased from 19. 2℃ to 11.9 ℃ by using the mixtures of stabilizers.

  20. The role of stabilization centers in protein thermal stability

    Energy Technology Data Exchange (ETDEWEB)

    Magyar, Csaba [Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok krt 2, H-1117 Budapest (Hungary); Gromiha, M. Michael [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036 (India); Sávoly, Zoltán [Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok krt 2, H-1117 Budapest (Hungary); Simon, István, E-mail: simon.istvan@ttk.mta.hu [Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok krt 2, H-1117 Budapest (Hungary)

    2016-02-26

    The definition of stabilization centers was introduced almost two decades ago. They are centers of noncovalent long range interaction clusters, believed to have a role in maintaining the three-dimensional structure of proteins by preventing their decay due to their cooperative long range interactions. Here, this hypothesis is investigated from the viewpoint of thermal stability for the first time, using a large protein thermodynamics database. The positions of amino acids belonging to stabilization centers are correlated with available experimental thermodynamic data on protein thermal stability. Our analysis suggests that stabilization centers, especially solvent exposed ones, do contribute to the thermal stabilization of proteins. - Highlights: • Stabilization centers contribute to thermal stabilization of protein structures. • Stabilization center content correlates with melting temperature of proteins. • Exposed stabilization center content correlates with stability even in hyperthermophiles. • Stability changing mutations are frequently found at stabilization centers.

  1. Valproate, a mood stabilizer, induces WFS1 expression and modulates its interaction with ER stress protein GRP94.

    Directory of Open Access Journals (Sweden)

    Chihiro Kakiuchi

    Full Text Available BACKGROUND: Valproate is a standard treatment for bipolar disorder and a first-line mood stabilizer. The molecular mechanisms underlying its actions in bipolar disorder are unclear. It has been suggested that the action of valproate is linked to changes in gene expression and induction of endoplasmic reticulum (ER stress-response proteins. PRINCIPAL FINDINGS: Here we show that valproate modulates the ER stress response through the regulation of WFS1, an important component for mitigating ER stress. Therapeutic concentrations of valproate induce expression of WFS1 mRNA and activate the WFS1 promoter. In addition, WFS1 forms a complex with GRP94, an ER stress-response protein, in which valproate dose-dependently enhances its dissociation from GRP94. CONCLUSIONS: These results suggest that the therapeutic effects of valproate in bipolar disorder may be mediated by WFS1 expression and its dissociation from GRP94.

  2. Effects of Soil-Vegetation-Atmosphere Interaction on the Stability of a Clay Slope: A Case Study

    Directory of Open Access Journals (Sweden)

    Pedone Giuseppe

    2016-01-01

    Full Text Available Deep and slow landslide processes are frequently observed in clay slopes located along the Southern Apennines (Italy. A case study representative of these processes, named Pisciolo case study, is discussed in the paper. The geo-hydro-mechanical characteristics of the materials involved in the instability phenomena are initially discussed. Pluviometric, piezometric, inclinometric and GPS monitoring data are subsequently presented, suggesting that rainfall infiltration constitutes the main factor inducing slope movements. The connection between formation of landslide bodies and slope-atmosphere interaction has been demonstrated through a hydro-mechanical finite element analysis, whose results are finally reported in the work. This analysis has been conducted employing a constitutive model that is capable of simulating both saturated and unsaturated soil behaviour, as well as a boundary condition able to simulate the effects of the soil-vegetation-atmosphere interaction.

  3. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

    Science.gov (United States)

    Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

    2017-09-01

    Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

  4. Superspin glass state in a diluted nanoparticle system stabilized by interparticle interactions mediated by an antiferromagnetic matrix

    Science.gov (United States)

    Margaris, G.; Vasilakaki, M.; Peddis, D.; Trohidou, K. N.; Laureti, S.; Binns, C.; Agostinelli, E.; Rinaldi, D.; Mathieu, R.; Fiorani, D.

    2017-01-01

    In nanoparticle systems consisting of two magnetic materials (bi-magnetic nanoparticles or nanoparticles embedded in a magnetic matrix), there is a constantly growing interest in the investigation of the interplay between interparticle interactions and the nanoparticle-matrix interface exchange coupling, because of its enormous impact on a number of technological applications. The understanding of the mechanisms of such interplay is a great challenge, as it would allow controlling equilibrium and non-equilibrium magnetization dynamics of exchange coupled nanoparticles systems and finely tuning their anisotropy. Here, we provide evidence that this interplay leads to a collective superspin glass (SSG) behavior in a system of diluted ferromagnetic (FM) nanoparticles embedded in an antiferromagnetic (AFM) matrix (5% volume fraction of Co particles in Mn film matrix). We have developed a novel mesoscopic model to study the influence of interparticle interaction on the exchange bias (EB) and the dynamical behavior of assemblies of FM nanoparticles embedded in a granular AFM matrix. Our mesoscopic model is based on reducing the amount of simulated spins to the minimum number necessary to describe the magnetic structure of the system and introducing the adequate exchange parameters between the different spins. The model replicates remarkably well the observed static and dynamical SSG properties as well as the EB behavior. In addition, the proposed model well explains the role of the significant Co/Mn alloying and of the granularity of the matrix in mediating interparticle interactions through exchange and dipole-dipole coupling between the uncompensated moments of its grains and the exchange interaction at the Co/Mn interface.

  5. The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability.

    Science.gov (United States)

    Li, Min; Xu, Xiaohua; Liu, Yilun

    2011-05-01

    The conserved RECQ5 DNA helicase is a tumor suppressor in mammalian cells. Defects in RECQ5 lead to the accumulation of spontaneous DNA double-stranded breaks (DSBs) during replication, despite the fact that these cells are proficient in DSB repair by homologous recombination (HR). The reason for this is unknown. Here, we demonstrate that these DSBs are linked to RNA polymerase II (RNAPII)-dependent transcription. In human RECQ5-depleted cells, active RNAPII accumulates on chromatin, and DNA breaks are associated with an RNAPII-dependent transcribed locus. Hence, transcription inhibition eliminates both active RNAPII and spontaneous DSB formation. In addition, the regulatory effect of RECQ5 on transcription and its interaction with RNAPII are enhanced in S-phase cells, supporting a role for RECQ5 in preventing transcription-associated DSBs during replication. Finally, we show that the SET2-RPB1 interaction (SRI) domain of human RECQ5 is important for suppressing spontaneous DSBs and the p53-dependent transcription stress response caused by the stalling of active RNAPII on DNA. Thus, our studies provide novel insights into a mechanism by which RECQ5 regulates the transcription machinery via its dynamic interaction with RNAPII, thereby preventing genome instability.

  6. Stability and Characteristics of the Halogen Bonding Interaction in an Anion-Anion Complex: A Computational Chemistry Study.

    Science.gov (United States)

    Wang, Guimin; Chen, Zhaoqiang; Xu, Zhijian; Wang, Jinan; Yang, Yang; Cai, Tingting; Shi, Jiye; Zhu, Weiliang

    2016-02-04

    Halogen bonding is the noncovalent interaction between the positively charged σ-hole of organohalogens and nucleophiles. In reality, both the organohalogen and nucleophile could be deprotonated to form anions, which may lead to the vanishing of the σ-hole and possible repulsion between the two anions. However, our database survey in this study revealed that there are halogen bonding-like interactions between two anions. Quantum mechanics calculations with small model complexes composed of halobenzoates and propiolate indicated that the anion-anion halogen bonding is unstable in vacuum but attractive in solvents. Impressively, the QM optimized halogen bonding distance between the two anions is shorter than that in a neutral system, indicating a possibly stronger halogen bonding interaction, which is verified by the calculated binding energies. Furthermore, natural bond orbital and quantum theory of atoms in molecule analyses also suggested stronger anion-anion halogen bonding than that of the neutral one. Energy decomposition by symmetry adapted perturbation theory revealed that the strong binding might be attributed to large induction energy. The calculations on 4 protein-ligand complexes from PDB by the QM/MM method demonstrated that the anion-anion halogen bonding could contribute to the ligands' binding affinity up to ∼3 kcal/mol. Therefore, anion-anion halogen bonding is stable and applicable in reality.

  7. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...

  8. Optical stability of 3d transition metal ions doped-cadmium borate glasses towards γ-rays interaction

    Science.gov (United States)

    Marzouk, M.; ElBatal, H.; Eisa, W.

    2016-07-01

    This work reports the preparation of glasses of binary cadmium borate with the basic composition (mol% 45 CdO 55 B2O3) and samples of the same composition containing 0.2 wt% dopants of 3d transition metal (TM) oxides (TiO2 → CuO). The glasses have been investigated by combined optical and Fourier Transform infrared spectroscopic measurements before and after being subjected to gamma irradiation with a dose of 8 Mrad (8 × 104 Gy). Optical absorption of the undoped glass before irradiation reveals strong charge transfer UV absorption which is related to the presence of unavoidable contaminated trace iron impurities (mainly Fe3+) within the raw materials used for the preparation of the base cadmium borate glass. The optical spectra of the 3d TM ions exhibit characteristic bands which are related the stable oxidation state of the 3d TM ions within the host glass. Gamma irradiation produces some limited variations in the optical spectra due to the stability of the host glass containing high percent 45 mol% of heavy metal oxide (CdO) which causes some shielding effects towards irradiation. From the absorption edge data, the values of the optical band gap Eopt and Urbach energy (∆E) have been calculated. The values of the optical energy gap are found to be dependent on the glass composition. Infrared absorption spectral measurements reveal characteristic absorption bands due to both triangular and tetrahedral borate groups with the BO3 units vibrations more intense than BO4 units due to the known limit value for the change of BO3 to BO4 groups. The introduction of 3d TM ions with the doping level (0.2 wt%) causes no changes in the number or position of the IR bands because of the presence of TM ions in modifying sites in the glass network. It is observed that gamma irradiation causes some limited changes in the FT-IR spectral bands due to the stability of the host heavy cadmium borate glass.

  9. Structural Stability, Transitions, and Interactions within SoxYZCD-Thiosulphate from Sulfurimonas denitrificans: An In Silico Molecular Outlook for Maintaining Environmental Sulphur Cycle

    Science.gov (United States)

    Banerjee, Arundhati

    2016-01-01

    Thiosulphate oxidation (an essential mechanism) serves to maintain the global sulphur cycle. Earlier experimental and computational studies dealt with environmental thiosulphate oxidation but none dealt with thiosulphate oxidation from deep ocean belts. Wet-laboratory experimental research shows that epsilon-proteobacteria Sulfurimonas denitrificans possess sox (sulphur-oxidizing) operon and perform thiosulphate oxidation efficiently underneath the oceans. From this specific sox operon, SoxCD complex recycles the thiosulphate-bound SoxY from SoxYZ complex to balance the environmental sulphur cycle. So, four chief proteins were variedly modeled and relevant simulated interactive structures were obtained. The final simulated tetraprotein complex (SoxYZCD) from docked SoxYZ and SoxCD complexes was disclosed to be a highly interactive one with predominant ionic residues. Free energy of folding, solvent accessibility, and conformational shifts (coil-like conformation to helices and sheets) were observed in SoxYZ complex after interacting with SoxCD. The stability of the complex (SoxYZCD) after simulation was also observed through the electrostatic surface potential values. These evaluations were rationalized via biostatistics. This aids SoxCD for recycling SoxY along with thiosulphate, which remains interconnected by four H-bonds with SoxY. Therefore, this novel exploration is endowed with the detailed molecular viewpoint for maintaining the sulphur cycle (globally) including the ocean belts. PMID:27777586

  10. Hydrophobic interactions between polymeric carrier and palmitic acid-conjugated siRNA improve PEGylated polyplex stability and enhance in vivo pharmacokinetics and tumor gene silencing.

    Science.gov (United States)

    Sarett, Samantha M; Werfel, Thomas A; Chandra, Irene; Jackson, Meredith A; Kavanaugh, Taylor E; Hattaway, Madison E; Giorgio, Todd D; Duvall, Craig L

    2016-08-01

    Formation of stable, long-circulating siRNA polyplexes is a significant challenge in translation of intravenously-delivered, polymeric RNAi cancer therapies. Here, we report that siRNA hydrophobization through conjugation to palmitic acid (siPA) improves stability, in vivo pharmacokinetics, and tumor gene silencing of PEGylated nanopolyplexes (siPA-NPs) with balanced cationic and hydrophobic content in the core relative to the analogous polyplexes formed with unmodified siRNA, si-NPs. Hydrophobized siPA loaded into the NPs at a lower charge ratio (N(+):P(-)) relative to unmodified siRNA, and siPA-NPs had superior resistance to siRNA cargo unpackaging in comparison to si-NPs upon exposure to the competing polyanion heparin and serum. In vitro, siPA-NPs increased uptake in MDA-MB-231 breast cancer cells (100% positive cells vs. 60% positive cells) but exhibited equivalent silencing of the model gene luciferase relative to si-NPs. In vivo in a murine model, the circulation half-life of intravenously-injected siPA-NPs was double that of si-NPs, resulting in a >2-fold increase in siRNA biodistribution to orthotopic MDA-MB-231 mammary tumors. The increased circulation half-life of siPA-NPs was dependent upon the hydrophobic interactions of the siRNA and the NP core component and not just siRNA hydrophobization, as siPA did not contribute to improved circulation time relative to unmodified siRNA when delivered using polyplexes with a fully cationic core. Intravenous delivery of siPA-NPs also achieved significant silencing of the model gene luciferase in vivo (∼40% at 24 h after one treatment and ∼60% at 48 h after two treatments) in the murine MDA-MB-231 tumor model, while si-NPs only produced a significant silencing effect after two treatments. These data suggest that stabilization of PEGylated siRNA polyplexes through a combination of hydrophobic and electrostatic interactions between siRNA cargo and the polymeric carrier improves in vivo pharmacokinetics and

  11. Bi-stability in single impurity Anderson model with strong electron–phonon interaction(polaron regime)

    Energy Technology Data Exchange (ETDEWEB)

    Eskandari-asl, Amir, E-mail: amir.eskandari.asl@gmail.com

    2016-09-15

    We consider a single impurity Anderson model (SIAM) in which the quantum dot(QD) is strongly coupled to a phonon bath in polaron regime. This coupling results in an effective e-e attraction. By computing the self energies using a current conserving approximation which is up to second order in this effective attraction, we show that if the interaction is strong enough, in non particle-hole (PH) symmetric case, the system would be bi-stable and we have hysteresis loop in the I–V characteristic. Moreover, the system shows negative differential conductance in some bias voltage intervals.

  12. Bi-stability in single impurity Anderson model with strong electron-phonon interaction(polaron regime)

    Science.gov (United States)

    Eskandari-asl, Amir

    2016-09-01

    We consider a single impurity Anderson model (SIAM) in which the quantum dot(QD) is strongly coupled to a phonon bath in polaron regime. This coupling results in an effective e-e attraction. By computing the self energies using a current conserving approximation which is up to second order in this effective attraction, we show that if the interaction is strong enough, in non particle-hole (PH) symmetric case, the system would be bi-stable and we have hysteresis loop in the I-V characteristic. Moreover, the system shows negative differential conductance in some bias voltage intervals.

  13. Functional discrepancies between tumor necrosis factor and lymphotoxin alpha explained by trimer stability and distinct receptor interactions

    DEFF Research Database (Denmark)

    Schuchmann, M; Hess, S; Bufler, P;

    1995-01-01

    interaction with the human p55TNFR. This was demonstrated in NIH 3T3 cells transfected with the human p55TNFR, where cytotoxicity is mediated exclusively by the transfected receptor. Although the p55ATNFR had virtually identical affinities for TNF and LT alpha, as defined by Scatchard analysis......Tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) are closely related cytokines which bind with nearly identical affinities to the same pair of cell surface receptors, p55 and p75TNFR. Therefore it is assumed that TNF and LT alpha are redundant cytokines. This study, however...

  14. Stability and genotype by environment interaction of provitamin A carotenoid and dry matter content in cassava in Uganda

    Science.gov (United States)

    Esuma, Williams; Kawuki, Robert Sezi; Herselman, Liezel; Labuschagne, Maryke Tine

    2016-01-01

    Efforts are underway to develop staple crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency (VAD), which has afflicted the health of resource-poor people in the developing world. As a staple crop for more than 500 million people in sub-Saharan Africa, cassava enriched with provitamin A carotenoids could have a widespread nutritional impact. To this effect, 13 provitamin A clones were evaluated in a randomized complete block design in six environments to assess genotype by environment interaction (GEI) effects for total carotenoid (TCC) and dry matter content (DMC) in roots. Additive main effect and multiplicative interaction analysis showed significant variation among genotypes for TCC, DMC, fresh root weight and harvest index. Environmental effects were non-significant for TCC, but GEI effects were significantly large for all traits measured. There were significant temporal increments for all traits measured within 12 months after planting. TCC correlated negatively with DMC, illustrating an important challenge to overcome when developing provitamin A cassava varieties without compromising DMC, which is a major farmer-preference trait. Nonetheless, best performing genotypes were identified for TCC, DMC and FRW, and these could constitute genetic resources for advancement or developing breeding populations through hybridization. PMID:27436954

  15. Effects of Dam Removal on Fish Community Interactions and Stability in the Eightmile River System, Connecticut, USA

    Science.gov (United States)

    Poulos, Helen M.; Chernoff, Barry

    2017-02-01

    New multivariate time-series methods have the potential to provide important insights into the effects of ecosystem restoration activities. To this end, we examined the temporal effects of dam removal on fish community interactions using multivariate autoregressive models to understand changes in fish community structure in the Eightmile River System, Connecticut, USA. We sampled fish for 6 years during the growing season; 1 year prior to, 2 years during, and for 3 years after a small dam removal event. The multivariate autoregressive analysis revealed that the site above the dam was the most reactive and least resilient sample site, followed in order by the below-dam and nearby reference site. Even 3 years after the dam removal event, the stream was still in a recovery stage that had failed to approximate the community structure of the reference site. This suggests that the reorganization of fish communities following dam removals, with the goal of ecological restoration, may take decades to centuries for the restored sites to approximate the community structure of nearby undisturbed sites. Results from this study also highlight the utility of multivariate autoregressive modeling for examining temporal interactions among species in response to adaptive management activities both in aquatic systems and elsewhere.

  16. Conditions for the Existence and Stability of the Continuous Attractor in the Classical XY Model with an Associative-Memory-Type Interaction

    Science.gov (United States)

    Yoshida, Risa; Kimoto, Tomoyuki; Uezu, Tatsuya

    2017-03-01

    We analyze the structure of attractors in the classical XY model with an associative-memory-type interaction by the statistical mechanical method. Previously, it was found that when patterns are uncorrelated, points on a path connecting two memory patterns in the space of the order parameters are solutions of the saddle point equations (SPEs) in the case that p is O(1) irrespective of N and N ≫ 1, where p and N are the numbers of patterns and spins, respectively. This state is called the continuous attractor (CA). In this paper, we clarify the conditions for the existence and stability of the CA with and without the correlation a (0 ≤ a 0, we numerically study the case that patterns are subject to external noise and find that pc increases as the noise amplitude increases.

  17. Copper(I) halide complexes of 2,2,5,5-tetramethyl-imidazolidine-4-thione: Synthesis, structures, luminescence, thermal stability and interaction with DNA.

    Science.gov (United States)

    Anastasiadou, D; Psomas, G; Lalia-Kantouri, M; Hatzidimitriou, A G; Aslanidis, P

    2016-11-01

    Five neutral mononuclear copper(I) halide complexes containing 2,2,5,5-tetramethylimidazolidine-4-thione (tmimdtH) and triphenylphosphane (PPh3) or tri-o-tolylphosphane (totp) have been prepared and structurally characterized by X-ray single-crystal analysis. The complexes containing PPh3 adopt the usual distorted tetrahedral geometry, while the presence of the bulkier totp forces the formation of three-coordinated trigonal planar species. The interaction of the compounds with calf-thymus DNA was monitored directly via UV-vis spectroscopy, DNA-viscosity measurements and indirectly via its competition with ethidium bromide for DNA studied by fluorescence emission spectroscopy. Intercalation was revealed as the most possible mode of binding. Furthermore, luminescent properties and thermal stabilities of the complexes were investigated.

  18. A structural rationale for selective stabilization of anti-tumor interactions of 14-3-3 proteins by cotylenin A.

    Science.gov (United States)

    Ottmann, Christian; Weyand, Michael; Sassa, Takeshi; Inoue, Takatsugu; Kato, Nobuo; Wittinghofer, Alfred; Oecking, Claudia

    2009-03-06

    Cotylenin A, a fungal metabolite originally described as a cytokinin-like bioactive substance against plants shows differentiation-inducing and anti-tumor activity in certain human cancers. Here, we present the crystal structure of cotylenin A acting on a 14-3-3 regulatory protein complex. By comparison with the closely related, but non-anticancer agent fusicoccin A, a rationale for the activity of cotylenin A in human cancers is presented. This class of fusicoccane diterpenoids are possible general modulators of 14-3-3 protein-protein interactions. In this regard, specificities for individual 14-3-3/target protein complexes might be achieved by varying the substituent pattern of the diterpene ring system. As the different activities of fusicoccin A and cotylenin A in human cancers suggest, hydroxylation of C12 might be a sufficient determinant of structural specificity.

  19. Validation of a stability-indicating hydrophilic interaction liquid chromatographic method for the quantitative determination of vitamin k3 (menadione sodium bisulfite) in injectable solution formulation.

    Science.gov (United States)

    Ghanem, Mashhour M; Abu-Lafi, Saleh A; Hallak, Hussein O

    2013-01-01

    A simple, specific, accurate, and stability-indicating method was developed and validated for the quantitative determination of menadione sodium bisulfite in the injectable solution formulation. The method is based on zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array detector. The desired separation was achieved on the ZIC-HILIC column (250 mm × 4.6 mm, 5 μm) at 25°C temperature. The optimized mobile phase consisted of an isocratic solvent mixture of 200mM ammonium acetate (NH4AC) solution and acetonitrile (ACN) (20:80; v/v) pH-adjusted to 5.7 by glacial acetic acid. The mobile phase was fixed at 0.5 ml/min and the analytes were monitored at 261 nm using a photodiode array detector. The effects of the chromatographic conditions on the peak retention, peak USP tailing factor, and column efficiency were systematically optimized. Forced degradation experiments were carried out by exposing menadione sodium bisulfite standard and the injectable solution formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The degradation products were well-resolved from the main peak and the excipients, thus proving that the method is a reliable, stability-indicating tool. The method was validated as per ICH and USP guidelines (USP34/NF29) and found to be adequate for the routine quantitative estimation of menadione sodium bisulfite in commercially available menadione sodium bisulfite injectable solution dosage forms.

  20. A model for triple helix formation on human telomerase reverse transcriptase (hTERT) promoter and stabilization by specific interactions with the water soluble perylene derivative, DAPER.

    Science.gov (United States)

    Rossetti, Luigi; D'Isa, Giuliana; Mauriello, Clementina; Varra, Michela; De Santis, Pasquale; Mayol, Luciano; Savino, Maria

    2007-08-01

    The promoter of human telomerase reverse transcriptase (hTERT) gene, in the region from -1000 to +1, contains two homopurine-homopyrimidine sequences (-835/-814 and -108/-90), that can be considered as potential targets to triple helix forming oligonucleotides (TFOs) for applying antigene strategy. We have chosen the sequence (-108/-90) on the basis of its unfavorable chromatin organization, evaluated by theoretical nucleosome positioning and nuclease hypersensitive sites mapping. On this sequence, anti-parallel triplex with satisfactory thermodynamic stability is formed by two TFOs, having different lengths. Triplex stability is significantly increased by specific interactions with the perylene derivative N,N'-bis[3,3'-(dimethylamino) propylamine]-3,4,9,10-perylenetetracarboxylic diimide (DAPER). Since DAPER is a symmetric molecule, the induced Circular Dichroism (CD) spectra in the range 400-600 nm allows us to obtain information on drug binding to triplex and duplex DNA. The drug-induced ellipticity is significantly higher in the case of triplex with respect to duplex and, surprisingly, it increases at decreasing of DNA. A model is proposed where self-stacked DAPER binds to triplex or to duplex narrow grooves.

  1. Structural and denaturation studies of two mutants of a cold adapted superoxide dismutase point to the importance of electrostatic interactions in protein stability.

    Science.gov (United States)

    Merlino, Antonello; Russo Krauss, Irene; Castellano, Immacolata; Ruocco, Maria Rosaria; Capasso, Alessandra; De Vendittis, Emmanuele; Rossi, Bianca; Sica, Filomena

    2014-03-01

    A peculiar feature of the psychrophilic iron superoxide dismutase from Pseudoalteromonas haloplanktis (PhSOD) is the presence in its amino acid sequence of a reactive cysteine (Cys57). To define the role of this residue, a structural characterization of the effect of two PhSOD mutations, C57S and C57R, was performed. Thermal and denaturant-induced unfolding of wild type and mutant PhSOD followed by circular dichroism and fluorescence studies revealed that C→R substitution alters the thermal stability and the resistance against denaturants of the enzyme, whereas C57S only alters the stability of the protein against urea. The crystallographic data on the C57R mutation suggest an involvement of the Arg side chain in the formation of salt bridges on protein surface. These findings support the hypothesis that the thermal resistance of PhSOD relies on optimization of charge-charge interactions on its surface. Our study contributes to a deeper understanding of the denaturation mechanism of superoxide dismutases, suggesting the presence of a structural dimeric intermediate between the native state and the unfolded state. This hypothesis is supported by the crystalline and solution data on the reduced form of the enzyme. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Solid-state interaction of stearic acid with povidone and its effect on dissolution stability of capsules.

    Science.gov (United States)

    Desai, D; Kothari, S; Huang, M

    2008-04-16

    Capsule formulations of two drugs under development showed slower dissolution upon storage; Drug A, after 2.5 weeks at 40 degrees C/23% RH and 4 weeks at 30 degrees C/60% RH, and Drug B, after 6 weeks at 50 degrees C and 40 degrees C/75% RH. The formulations of both drugs contained povidone as a binder and stearic acid as a lubricant. Replacement of stearic acid by magnesium stearate from the formulation of Drug B, which was selected for further studies, provided rapid dissolution profiles under similar storage conditions with no change occurring on storage. In order to investigate the role of stearic acid further, binary mixtures of stearic acid with the drugs and other excipients used in their respective formulations were prepared and stored at 40 degrees C/75% RH and 50 degrees C. After 1 week of storage, it was observed that povidone and stearic acid mixture formed a transparent, hard, glass-like insoluble substance. It is hypothesized that the substance formed by the interaction can reduce the porosity of the granules and thereby reduces the ingress of the dissolution medium leading to slower dissolution. The infrared (IR) spectra of the glass-like substance showed a slight broadening of the povidone carbonyl band at 1662 cm(-1). The powder X-ray diffraction of the stored mixture showed that the crystallinity of stearic acid was lost. Furthermore, repeated heating and cooling cycles of povidone and stearic acid mixtures in various proportions using differential scanning calorimetry (DSC) showed that recrystallization of stearic acid from its melt was strongly affected by the presence of increasing amounts of povidone. Based on the observed solid-state interaction, a combination of stearic and povidone should be avoided for immediate release formulations.

  3. In vitro metabolic stability and intestinal transport of P57AS3 (P57) from Hoodia gordonii and its interaction with drug metabolizing enzymes.

    Science.gov (United States)

    Madgula, Vamsi L M; Avula, Bharathi; Pawar, Rahul S; Shukla, Yatin J; Khan, Ikhlas A; Walker, Larry A; Khan, Shabana I

    2008-08-01

    Hoodia gordonii, a succulent cactus-like plant growing in South Africa, has been used in traditional medicine for its appetite suppressant properties. Its use as a dietary supplement to promote weight loss has recently gained popularity. An oxypregnane steroidal glycoside P57AS3 (P57) is reported to be the active constituent of the sap extract responsible for anorexigenic activity. No information is available about its metabolic stability, intestinal transport and interaction with drug metabolizing enzymes. In the present investigation, the metabolic stability of P57 in human liver microsomes and its interaction with drug metabolizing enzymes (CYP1A2, 2C9, 3A4 and 2D6) were determined. Intestinal transport of P57 was studied in the Caco-2 cell model of intestinal transport and absorption. P57 was metabolically stable in the presence of human liver microsomes. The compound inhibited CYP3A4 activity with an IC50 value of 45 microM, whereas the activity of CYP 1A2, 2C9 and 2D6 was not inhibited. In the Caco-2 model, P57 exhibited a higher transport in the secretory direction than in the absorptive direction with efflux ratios of 3.1 and 3.8 at 100 and 200 microM, respectively. The efflux was inhibited by selective inhibitors of multidrug resistance associated proteins MRP1/MRP2 (MK-571) and P-gp (verapamil). In conclusion, intestinal transport of P57 was mediated by P-gp and MRP transporters. The compound was metabolically stable and showed weak inhibition of CYP 3A4.

  4. The nucleus of the optic tract. Its function in gaze stabilization and control of visual-vestibular interaction

    Science.gov (United States)

    Cohen, B.; Reisine, H.; Yokota, J. I.; Raphan, T.

    1992-01-01

    1. Electrical stimulation of the nucleus of the optic tract (NOT) induced nystagmus and after-nystagmus with ipsilateral slow phases. The velocity characteristics of the nystagmus were similar to those of the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN), both of which are produced by velocity storage in the vestibular system. When NOT was destroyed, these components disappeared. This indicates that velocity storage is activated from the visual system through NOT. 2. Velocity storage produces compensatory eye-in-head and head-on-body movements through the vestibular system. The association of NOT with velocity storage implies that NOT helps stabilize gaze in space during both passive motion and active locomotion in light with an angular component. It has been suggested that "vestibular-only" neurons in the vestibular nuclei play an important role in generation of velocity storage. Similarities between the rise and fall times of eye velocity during OKN and OKAN to firing rates of vestibular-only neurons suggest that these cells may receive their visual input through NOT. 3. One NOT was injected with muscimol, a GABAA agonist. Ipsilateral OKN and OKAN were lost, suggesting that GABA, which is an inhibitory transmitter in NOT, acts on projection pathways to the brain stem. A striking finding was that visual suppression and habituation of contralateral slow phases of vestibular nystagmus were also abolished after muscimol injection. The latter implies that NOT plays an important role in producing visual suppression of the VOR and habituating its time constant. 4. Habituation is lost after nodulus and uvula lesions and visual suppression after lesions of the flocculus and paraflocculus. We postulate that the disappearance of vestibular habituation and of visual suppression of vestibular responses after muscimol injections was due to dysfacilitation of the prominent NOT-inferior olive pathway, inactivating climbing fibers from

  5. FOOD-PACKAGING INTERACTION ON THE STABILITY OF CANNED SWEETENED CUPUAÇU (Theobroma grandiflorum Schum. PUREE

    Directory of Open Access Journals (Sweden)

    MARIA TERESA DE ALVARENGA FREIRE

    2016-01-01

    Full Text Available Cupuaçu ( Theobroma grandiflorum Schum. is an exotic fruit with a promising economic potential, particularly due to its strong aroma and creamy texture. This study aimed to produce sweetened cupuaçu puree and evaluate the effects of packaging corrosion on its sensory properties and shelf - life in tinplated cans. After 240 days of storage, the commercially sterile product had average sensory analysis scores of 5.89 ± 0.21, 5.39 ± 0.30, 5.45 ± 0.21 and 5.49 ± 0.25, for appearance, aroma, flavor and overall appreciation, respectively. Sensory acceptance scores did not change during storage (p>0.05. Corrosion potential and low tin and iron levels in the product, which are parameters used to evaluate food - packaging interaction, demonstrated the product remained food - safe throughout its shelf - life. Tinplate is a promising packaging material for sweetened cupuaçu puree due to its mechanical and protective properties. Furthermore, tin plating is an economically viable food technology to extend the shelf - life of cupuaçu products and expand its domestic and international markets.

  6. Numerical stabilization of entanglement computation in auxiliary-field quantum Monte Carlo simulations of interacting many-fermion systems

    Science.gov (United States)

    Broecker, Peter; Trebst, Simon

    2016-12-01

    In the absence of a fermion sign problem, auxiliary-field (or determinantal) quantum Monte Carlo (DQMC) approaches have long been the numerical method of choice for unbiased, large-scale simulations of interacting many-fermion systems. More recently, the conceptual scope of this approach has been expanded by introducing ingenious schemes to compute entanglement entropies within its framework. On a practical level, these approaches, however, suffer from a variety of numerical instabilities that have largely impeded their applicability. Here we report on a number of algorithmic advances to overcome many of these numerical instabilities and significantly improve the calculation of entanglement measures in the zero-temperature projective DQMC approach, ultimately allowing us to reach similar system sizes as for the computation of conventional observables. We demonstrate the applicability of this improved DQMC approach by providing an entanglement perspective on the quantum phase transition from a magnetically ordered Mott insulator to a band insulator in the bilayer square lattice Hubbard model at half filling.

  7. Copper(II) interaction with peptide fragments of histidine-proline-rich glycoprotein: Speciation, stability and binding details.

    Science.gov (United States)

    La Mendola, Diego; Magrì, Antonio; Santoro, Anna Maria; Nicoletti, Vincenzo G; Rizzarelli, Enrico

    2012-06-01

    GHHPH is the peptide repeat present in histidine-proline rich glycoprotein (HPRG), a plasma glycoprotein involved in angiogenesis process. The copper(II) ions interaction with mono (Ac-GHHPHG-NH(2)) and its bis-repeat (Ac-GHHPHGHHPHG-NH(2)) was investigated by means of potentiometric and spectroscopic techniques. To single out the copper(II) coordination environments of different species formed with Ac-GHHPHG-NH(2), three single point mutated peptides were also synthesized and their ability to coordinate Cu(2+) investigated. Ac-GHHPHG-NH(2) binds Cu(2+) by the imidazole side chain and the amide nitrogen deprotonation that takes place towards the N-terminus. The bis-repeat is able to bind Cu(2+) more efficiently than Ac-GHHPHG-NH(2). This difference is not only due to the number of His residues in the sequence but also to the different binding sites. In fact, the comparison of the potentiometric and spectroscopic data of the copper(II) complexes with a bis-repeatPeg construct Ac-(GHHPHG)-Peg-(GHHPHG)-NH(2) and those of the metal complexes with Ac-HGHH-NH(2), indicates that the central HGHH amino acid sequence is the main copper(II) binding site.

  8. Structural Consequences of Anionic Host-Cationic Guest Interactions in a Supramolecular Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Pluth, Michael D.; Johnson, Darren W.; Szigethy, Geza; Davis, Anna V.; Teat, Simon J.; Oliver, Allen G.; Bergman, Robert G.; Raymond, Kenneth N.

    2008-07-09

    The molecular structure of the self-assembled supramolecular assembly [M{sub 4}L{sub 6}]{sup 12-} has been explored with different metals (M = Ga{sup III}, Fe{sup III}, Ti{sup IV}) and different encapsulated guests (NEt{sub 4}{sup +}, BnNMe{sub 3}{sup +}, Cp{sub 2}Co{sup +}, Cp*{sub 2}Co{sup +}) by X-ray crystallography. While the identity of the metal ions at the vertices of the M{sub 4}L{sub 6} structure is found to have little effect on the assembly structure, encapsulated guests significantly distort the size and shape of the interior cavity of the assembly. Cations on the exterior of the assembly are found to interact with the assembly through either {pi}-{pi}, cation-{pi}, or CH-{pi} interactions. In some cases, the exterior guests interact with only one assembly, but cations with the ability to form multiple {pi}-{pi} interactions are able to interact with adjacent assemblies in the crystal lattice. The solvent accessible cavity of the assembly is modeled using the rolling probe method and found to range from 253-434 {angstrom}{sup 3}, depending on the encapsulated guest. Based on the volume of the guest and the volume of the cavity, the packing coefficient for each host-guest complex is found to range from 0.47-0.67.

  9. On the role of exchange of power and information signals in control and stability of the human-robot interaction

    Science.gov (United States)

    Kazerooni, H.

    1991-01-01

    A human's ability to perform physical tasks is limited, not only by his intelligence, but by his physical strength. If, in an appropriate environment, a machine's mechanical power is closely integrated with a human arm's mechanical power under the control of the human intellect, the resulting system will be superior to a loosely integrated combination of a human and a fully automated robot. Therefore, we must develop a fundamental solution to the problem of 'extending' human mechanical power. The work presented here defines 'extenders' as a class of robot manipulators worn by humans to increase human mechanical strength, while the wearer's intellect remains the central control system for manipulating the extender. The human, in physical contact with the extender, exchanges power and information signals with the extender. The aim is to determine the fundamental building blocks of an intelligent controller, a controller which allows interaction between humans and a broad class of computer-controlled machines via simultaneous exchange of both power and information signals. The prevalent trend in automation has been to physically separate the human from the machine so the human must always send information signals via an intermediary device (e.g., joystick, pushbutton, light switch). Extenders, however are perfect examples of self-powered machines that are built and controlled for the optimal exchange of power and information signals with humans. The human wearing the extender is in physical contact with the machine, so power transfer is unavoidable and information signals from the human help to control the machine. Commands are transferred to the extender via the contact forces and the EMG signals between the wearer and the extender. The extender augments human motor ability without accepting any explicit commands: it accepts the EMG signals and the contact force between the person's arm and the extender, and the extender 'translates' them into a desired position. In

  10. Stability and fate of ferrihydrite during episodes of water/rock interactions on early Mars: An experimental approach

    Science.gov (United States)

    Dehouck, Erwin; McLennan, Scott M.; Sklute, Elizabeth C.; Dyar, M. Darby

    2017-02-01

    The presence on the surface of Mars of ferrihydrite, a nanocrystalline iron oxide species, has long been suspected from spectroscopic observations and is further suggested by recent results from the Mars Exploration Rovers and Mars Science Laboratory robotic missions. However, because ferrihydrite is a metastable species in terrestrial environments, it is unclear what would have been its fate during episodes of water/rock interactions that are known to have occurred at the landing sites of the above-mentioned robotic missions. Accordingly, the laboratory experiments presented in this paper investigate the recrystallization of ferrihydrite under various conditions applicable to early Mars. These included low-temperature experiments (1 month at 40°C) at pH ranging from circum-neutral to strongly acidic, and high-temperature experiments (8 days at 150°C) at circum-neutral pH. The effect of mixtures with other mineral phases (namely, amorphous silica and olivine) was also tested. Results obtained at low temperature are at odds with some earlier studies and suggest that ferrihydrite behaves differently in rock-dominated conditions compared to water-dominated conditions. The coexistence of amorphous silica favored the formation of jarosite under low-temperature, acidic conditions, whereas a sample of pure ferrihydrite produced only goethite under the same conditions. At high temperature, ferrihydrite converted into hematite in all samples, but the ferrihydrite-silica mixture led to hematite with much broader diffraction peaks than other experiments, indicating an inhibiting effect of dissolved silica on the recrystallization process. The implications of these results for the aqueous history of early Mars are discussed.

  11. BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.

    Science.gov (United States)

    Verma, Sharad; Goyal, Sukriti; Tyagi, Chetna; Jamal, Salma; Singh, Aditi; Grover, Abhinav

    2016-06-01

    The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge.

  12. HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins.

    Directory of Open Access Journals (Sweden)

    Valérie Brügger

    Full Text Available The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC-axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2 in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0 were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease.

  13. Efficient expression and purification of human replication fork-stabilizing factor, Claspin, from mammalian cells: DNA-binding activity and novel protein interactions.

    Science.gov (United States)

    Uno, Syuzi; Masai, Hisao

    2011-08-01

    Purification of recombinant proteins of a large size often poses problems of instability or low expression in bacterial or insect cells. Here, we established a method for a high-level expression of large-sized recombinant proteins in mammalian cells and subsequent purification of the full-length proteins. We applied this method to express human Claspin and Tim-Tipin complex, which play important roles in replication checkpoint responses as fork-stabilizing factors, and successfully purified them in functional forms in amount sufficient for enzymatic characterization. Purified Claspin behaves as a monomer and binds preferentially to fork-like DNA. Over-expression of tagged Claspin in mammalian cells facilitated the detection of its interacting factors. Claspin interacts with many factors involved in checkpoint regulation and replication fork machinery, including ATR, ATM, Chk1, Tim, MCM4, MCM10, Cdc45, DNA polymerases α, δ, ε and Cdc7 kinase. We will discuss the potential implication of these findings in architecture of replication fork. We will also discuss the advantage of this system for purification and characterization of those proteins that are large and have been difficult to deal with.

  14. Stability of defects in monolayer MoS2 and their interaction with O2 molecule: A first-principles study

    Science.gov (United States)

    Zhao, B.; Shang, C.; Qi, N.; Chen, Z. Y.; Chen, Z. Q.

    2017-08-01

    The stability of various defects in monolayer MoS2, as well as their interactions with free O2 molecules were investigated by density functional theory (DFT) calculations coupled with the nudged elastic band (NEB) method. The defects including S vacancy (monosulfur and disulfue vacancies), antisite defect (MoS) and external Mo atom can exist steadily in monolayer MoS2, and introduce defect levels in these defective systems, which breaks the surface chemical inertness and significantly enhances the adsorption capacity for free O2. The adsorption energy calculations and electronic properties analysis suggest that there is a strong interaction between O2 molecule and defective system. The adsorbed O2 on the defective surface can dissociate with a lower activation energy barrier, which produce two active oxygen atoms. Especially, two Mo atoms can occupy one Mo lattice site, and adsorbed O2 on the top of the Mo atom can then dissociate directly with the lowest activation energy barrier. Hence, our work may provide useful information to design MoS2-based gas sensor or catalysts.

  15. Insights into the interaction of discodermolide and docetaxel with tubulin. Mapping the binding sites of microtubule-stabilizing agents by using an integrated NMR and computational approach.

    Science.gov (United States)

    Canales, Angeles; Rodríguez-Salarichs, Javier; Trigili, Chiara; Nieto, Lidia; Coderch, Claire; Andreu, José Manuel; Paterson, Ian; Jiménez-Barbero, Jesús; Díaz, J Fernando

    2011-08-19

    The binding interactions of two antitumor agents that target the paclitaxel site, docetaxel and discodermolide, to unassembled α/β-tubulin heterodimers and microtubules have been studied using biochemical and NMR techniques. The use of discodermolide as a water-soluble paclitaxel biomimetic and extensive NMR experiments allowed the detection of binding of microtubule-stabilizing agents to unassembled tubulin α/β-heterodimers. The bioactive 3D structures of docetaxel and discodermolide bound to α/β-heterodimers were elucidated and compared to those bound to microtubules, where subtle changes in the conformations of docetaxel in its different bound states were evident. Moreover, the combination of experimental TR-NOE and STD NMR data with CORCEMA-ST calculations indicate that docetaxel and discodermolide target an additional binding site at the pore of the microtubules, which is different from the internal binding site at the lumen previously determined by electron crystallography. Binding to this pore site can then be considered as the first ligand-protein recognition event that takes place in advance of the drug internalization process and interaction with the lumen of the microtubules.

  16. Intramolecular CH⋯π and CH⋯O interactions in the conformational stability of benzyl methyl ether studied by matrix-isolation infrared spectroscopy and theoretical calculations

    Science.gov (United States)

    Shin-ya, Kei; Takahashi, Osamu; Katsumoto, Yukiteru; Ohno, Keiichi

    2007-02-01

    Contributions of the intramolecular CH⋯π and CH⋯O interactions to the molecular conformation of benzyl methyl ether (BME) have been investigated by matrix-isolation infrared (IR) spectroscopy combined with quantum chemical calculations. Comparative investigations have been carried out for propylbenzene. Quantum chemical calculations predict that there are two conformers for BME; for the ET conformer the methyl ether and the phenyl groups lie in the plane of the benzene ring, while for the AG conformer they are out of the plane. Comparison between the observed and calculated spectra for BME reveals that the ET and AG conformers coexist in an Ar matrix. By measuring matrix-isolation IR spectra of BME deposited at different gas temperatures, the enthalpy difference (Δ H (AG - ET)) between ET and AG conformers was determined to be -1.03 ± 0.06 kJ mol -1. The experimental and calculation results indicate that the AG conformer of BME is stabilized by the intramolecular CH⋯π and CH⋯O interactions.

  17. Oncogenic mutations weaken the interactions that stabilize the p110α-p85α heterodimer in phosphatidylinositol 3-kinase α.

    Science.gov (United States)

    Echeverria, Ignacia; Liu, Yunlong; Gabelli, Sandra B; Amzel, L Mario

    2015-09-01

    Phosphatidylinositol 3-kinase (PI3K) α is a heterodimeric lipid kinase that catalyzes the conversion of phosphoinositol-4,5-bisphosphate to phosphoinositol-3,4,5-trisphosphate. The PI3Kα signaling pathway plays an important role in cell growth, proliferation, and survival. This pathway is activated in numerous cancers, where the PI3KCA gene, which encodes for the p110α PI3Kα subunit, is mutated. Its mutation often results in gain of enzymatic activity; however, the mechanism of activation by oncogenic mutations remains unknown. Here, using computational methods, we show that oncogenic mutations that are far from the catalytic site and increase the enzymatic affinity destabilize the p110α-p85α dimer. By affecting the dynamics of the protein, these mutations favor the conformations that reduce the autoinhibitory effect of the p85α nSH2 domain. For example, we determined that, in all of the mutants, the nSH2 domain shows increased positional heterogeneity as compared with the wild-type, as demonstrated by changes in the fluctuation profiles computed by normal mode analysis of coarse-grained elastic network models. Analysis of the interdomain interactions of the wild-type and mutants at the p110α-p85α interface obtained with molecular dynamics simulations suggest that all of the tumor-associated mutations effectively weaken the interactions between p110α and p85α by disrupting key stabilizing interactions. These findings have important implications for understanding how oncogenic mutations change the conformational multiplicity of PI3Kα and lead to increased enzymatic activity. This mechanism may apply to other enzymes and/or macromolecular complexes that play a key role in cell signaling.

  18. The interaction between sea ice and salinity-dominated ocean circulation: implications for halocline stability and rapid changes of sea ice cover

    Science.gov (United States)

    Jensen, Mari F.; Nilsson, Johan; Nisancioglu, Kerim H.

    2016-11-01

    Changes in the sea ice cover of the Nordic Seas have been proposed to play a key role for the dramatic temperature excursions associated with the Dansgaard-Oeschger events during the last glacial. In this study, we develop a simple conceptual model to examine how interactions between sea ice and oceanic heat and freshwater transports affect the stability of an upper-ocean halocline in a semi-enclosed basin. The model represents a sea ice covered and salinity stratified Nordic Seas, and consists of a sea ice component and a two-layer ocean. The sea ice thickness depends on the atmospheric energy fluxes as well as the ocean heat flux. We introduce a thickness-dependent sea ice export. Whether sea ice stabilizes or destabilizes against a freshwater perturbation is shown to depend on the representation of the diapycnal flow. In a system where the diapycnal flow increases with density differences, the sea ice acts as a positive feedback on a freshwater perturbation. If the diapycnal flow decreases with density differences, the sea ice acts as a negative feedback. However, both representations lead to a circulation that breaks down when the freshwater input at the surface is small. As a consequence, we get rapid changes in sea ice. In addition to low freshwater forcing, increasing deep-ocean temperatures promote instability and the disappearance of sea ice. Generally, the unstable state is reached before the vertical density difference disappears, and the temperature of the deep ocean do not need to increase as much as previously thought to provoke abrupt changes in sea ice.

  19. Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability.

    Science.gov (United States)

    Doerfler, Lillian; Harris, Lorena; Viebranz, Emilie; Schmidt, Kristina H

    2011-10-31

    Genome instability is associated with human cancers and chromosome breakage syndromes, including Bloom's syndrome, caused by inactivation of BLM helicase. Numerous mutations that lead to genome instability are known, yet how they interact genetically is poorly understood. We show that spontaneous translocations that arise by nonallelic homologous recombination in DNA-damage-checkpoint-defective yeast lacking the BLM-related Sgs1 helicase (sgs1Δ mec3Δ) are inhibited if cells lack Mec1/ATR kinase. Tel1/ATM, in contrast, acts as a suppressor independently of Mec3 and Sgs1. Translocations are also inhibited in cells lacking Dun1 kinase, but not in cells defective in a parallel checkpoint branch defined by Chk1 kinase. While we had previously shown that RAD51 deletion did not inhibit translocation formation, RAD59 deletion led to inhibition comparable to the rad52Δ mutation. A candidate screen of other DNA metabolic factors identified Exo1 as a strong suppressor of chromosomal rearrangements in the sgs1Δ mutant, becoming even more important for chromosomal stability upon MEC3 deletion. We determined that the C-terminal third of Exo1, harboring mismatch repair protein binding sites and phosphorylation sites, is dispensable for Exo1's roles in chromosomal rearrangement suppression, mutation avoidance and resistance to DNA-damaging agents. Our findings suggest that translocations between related genes can form by Rad59-dependent, Rad51-independent homologous recombination, which is independently suppressed by Sgs1, Tel1, Mec3 and Exo1 but promoted by Dun1 and the telomerase-inhibitor Mec1. We propose a model for the functional interaction between mitotic recombination and the DNA-damage checkpoint in the suppression of chromosomal rearrangements in sgs1Δ cells.

  20. Hydrophobic interactions between the S5 segment and the pore helix stabilizes the closed state of Slo2.1 potassium channels.

    Science.gov (United States)

    Suzuki, Tomoyuki; Hansen, Angela; Sanguinetti, Michael C

    2016-04-01

    Under normal physiological conditions, Slo2.1K(+) channels are in a closed state unless activated by an elevation in [Na(+)]i. Fenamates such as niflumic acid also activate Slo2.1. Previous studies suggest that activation of Slo2.1 channels is mediated by a conformational change in the selectivity filter, and not a widening of the aperture formed by the S6 segment bundle crossing as occurs in voltage-gated K(+) channels. It is unclear how binding of Na(+) or fenamates is allosterically linked to opening of the presumed selectivity filter activation gate in Slo2.1. Here we examined the role of the S5 transmembrane segment in the activation of Slo2.1. Channels were heterologously expressed in Xenopus laevis oocytes and whole cell currents measured with the voltage-clamp technique. Ala substitution of five residues located on a single face of the S5 α-helical segment induced constitutive channel activity. Leu-209, predicted to face towards Phe-240 in the pore helix was investigated by further mutagenesis. Mutation of Leu-209 to Glu or Gln induced maximal channel activation as did the combined mutation to Ala of all three hydrophobic S5 residues predicted to be adjacent to Phe-240. Together these results suggest that hydrophobic interactions between residues in S5 and the C-terminal end of the pore helix stabilize Slo2.1 channels in a closed state.

  1. Facile Formation of Redox-Active Totally Organic Nanoparticles in Water by In Situ Reduction of Organic Precursors Stabilized through Aromatic-Aromatic Interactions by Aromatic Polyelectrolytes.

    Science.gov (United States)

    Flores, Mario E; Garcés-Jerez, Pablo; Fernández, Daniel; Aros-Perez, Gustavo; González-Cabrera, Diego; Álvarez, Eduardo; Cañas, Ignacio; Oyarzun-Ampuero, Felipe; Moreno-Villoslada, Ignacio

    2016-11-01

    The formation of redox-active, totally organic nanoparticles in water is achieved following a strategy similar to that used to form metal nanoparticles. It is based on two fundamental concepts: i) complexation through aromatic-aromatic interactions of a water-soluble precursor aromatic molecule with polyelectrolytes bearing complementary charged aromatic rings, and ii) reduction of the precursor molecule to achieve stabilized nanoparticles. Thus, formazan nanoparticles are synthesized by reduction of a tetrazolium salt with ascorbic acid using polyelectrolytes bearing benzene sulfonate residues of high linear aromatic density, but cannot be formed in the presence of nonaromatic polyelectrolytes. The red colored nanoparticles are efficiently encapsulated in calcium alginate beads, showing macroscopic homogeneity. Bleaching kinetics with chlorine show linear rates on the order of tenths of milli-meters per minute. A linear behavior of the dependence of the rate of bleaching on the chlorine concentration is found, showing the potential of the nanoparticles for chlorine sensing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Regulation of a dynamic interaction between two microtubule-binding proteins, EB1 and TIP150, by the mitotic p300/CBP-associated factor (PCAF) orchestrates kinetochore microtubule plasticity and chromosome stability during mitosis.

    Science.gov (United States)

    Ward, Tarsha; Wang, Ming; Liu, Xing; Wang, Zhikai; Xia, Peng; Chu, Youjun; Wang, Xiwei; Liu, Lifang; Jiang, Kai; Yu, Huijuan; Yan, Maomao; Wang, Jianyu; Hill, Donald L; Huang, Yuejia; Zhu, Tongge; Yao, Xuebiao

    2013-05-31

    The microtubule cytoskeleton network orchestrates cellular dynamics and chromosome stability in mitosis. Although tubulin acetylation is essential for cellular plasticity, it has remained elusive how kinetochore microtubule plus-end dynamics are regulated by p300/CBP-associated factor (PCAF) acetylation in mitosis. Here, we demonstrate that the plus-end tracking protein, TIP150, regulates dynamic kinetochore-microtubule attachments by promoting the stability of spindle microtubule plus-ends. Suppression of TIP150 by siRNA results in metaphase alignment delays and perturbations in chromosome biorientation. TIP150 is a tetramer that binds an end-binding protein (EB1) dimer through the C-terminal domains, and overexpression of the C-terminal TIP150 or disruption of the TIP150-EB1 interface by a membrane-permeable peptide perturbs chromosome segregation. Acetylation of EB1-PCAF regulates the TIP150 interaction, and persistent acetylation perturbs EB1-TIP150 interaction and accurate metaphase alignment, resulting in spindle checkpoint activation. Suppression of the mitotic checkpoint serine/threonine protein kinase, BubR1, overrides mitotic arrest induced by impaired EB1-TIP150 interaction, but cells exhibit whole chromosome aneuploidy. Thus, the results identify a mechanism by which the TIP150-EB1 interaction governs kinetochore microtubule plus-end plasticity and establish that the temporal control of the TIP150-EB1 interaction by PCAF acetylation ensures chromosome stability in mitosis.

  3. Regulation of a Dynamic Interaction between Two Microtubule-binding Proteins, EB1 and TIP150, by the Mitotic p300/CBP-associated Factor (PCAF) Orchestrates Kinetochore Microtubule Plasticity and Chromosome Stability during Mitosis*

    Science.gov (United States)

    Ward, Tarsha; Wang, Ming; Liu, Xing; Wang, Zhikai; Xia, Peng; Chu, Youjun; Wang, Xiwei; Liu, Lifang; Jiang, Kai; Yu, Huijuan; Yan, Maomao; Wang, Jianyu; Hill, Donald L.; Huang, Yuejia; Zhu, Tongge; Yao, Xuebiao

    2013-01-01

    The microtubule cytoskeleton network orchestrates cellular dynamics and chromosome stability in mitosis. Although tubulin acetylation is essential for cellular plasticity, it has remained elusive how kinetochore microtubule plus-end dynamics are regulated by p300/CBP-associated factor (PCAF) acetylation in mitosis. Here, we demonstrate that the plus-end tracking protein, TIP150, regulates dynamic kinetochore-microtubule attachments by promoting the stability of spindle microtubule plus-ends. Suppression of TIP150 by siRNA results in metaphase alignment delays and perturbations in chromosome biorientation. TIP150 is a tetramer that binds an end-binding protein (EB1) dimer through the C-terminal domains, and overexpression of the C-terminal TIP150 or disruption of the TIP150-EB1 interface by a membrane-permeable peptide perturbs chromosome segregation. Acetylation of EB1-PCAF regulates the TIP150 interaction, and persistent acetylation perturbs EB1-TIP150 interaction and accurate metaphase alignment, resulting in spindle checkpoint activation. Suppression of the mitotic checkpoint serine/threonine protein kinase, BubR1, overrides mitotic arrest induced by impaired EB1-TIP150 interaction, but cells exhibit whole chromosome aneuploidy. Thus, the results identify a mechanism by which the TIP150-EB1 interaction governs kinetochore microtubule plus-end plasticity and establish that the temporal control of the TIP150-EB1 interaction by PCAF acetylation ensures chromosome stability in mitosis. PMID:23595990

  4. Do nonbonded H--H interactions in phenanthrene stabilize it relative to anthracene? A possible resolution to this question and its implications for ligands such as 2,2'-bipyridyl.

    Science.gov (United States)

    Hancock, Robert D; Nikolayenko, Igor V

    2012-08-23

    The problem of whether interactions between the hydrogen atoms at the 1,10-positions in the "cleft" of the "bent" phenanthrene stabilize the latter molecule thermodynamically relative to "linear" anthracene, or whether the higher stability of phenanthrene is due to a more energetically favorable π-system, is considered. DFT calculations at the X3LYP/cc-pVTZ(-f)++ level of the ground state energies (E) of anthracene, phenanthrene, and the set of five benzoquinolines are reported. In the gas phase, "bent" phenanthrene was computed to be thermodynamically more stable than "linear" anthracene by -28.5 kJ mol(-1). This fact was attributed predominantly to the phenomenon of higher aromatic stabilization of the π-system of phenanthrene relative to anthracene, and not to the stabilizing influence of the nonbonding H--H interactions in its cleft. In fact, these interactions in phenanthrene were shown to be destabilizing. Similar calculations for five benzoquinolines (bzq) indicate that ΔE values vary as: 6,7-bzq (linear) ≤ 2,3-bzq (linear) < 5,6-bzq (bent) ≤ 3,4-bzq (bent) < 7,8-bzq (bent, no H--H nonbonding interactions in cleft), supporting the idea that it is a more stable π-system that favors 7,8-bzq over 2,3-bzq and 6,7-bzq, and that the H--H interactions in the clefts of 3,4-bzq and 5,6-bzq are destabilizing. Intramolecular hydrogen bonding in the cleft of 7,8-bzq plays a secondary role in its stabilization relative 6,7-bzq. The question of whether H--H nonbonded interactions between H atoms at the 3 and 3' positions of 2,2'-bipyridyl (bpy) coordinated to metal ions are stabilizing or destabilizing is then considered. The energy of bpy is scanned as a function of N-C-C-N torsion angle (χ) in the gas-phase, and it is found that the trans form is 32.8 kJ mol(-1) more stable than the cis conformer. A relaxed coordinate scan of energy of bpy in aqueous solution as a function of χ is modeled using the PBF approach, and it is found that the trans conformer is

  5. How Mg(2+) ion and water network affect the stability and structure of non-Watson-Crick base pairs in E. coli loop E of 5S rRNA: a molecular dynamics and reference interaction site model (RISM) study.

    Science.gov (United States)

    Shanker, Sudhanshu; Bandyopadhyay, Pradipta

    2017-08-01

    The non-Watson-Crick (non-WC) base pairs of Escherichia coli loop E of 5S rRNA are stabilized by Mg(2+) ions through water-mediated interaction. It is important to know the synergic role of Mg(2+) and the water network surrounding Mg(2+) in stabilizing the non-WC base pairs of RNA. For this purpose, free energy change of the system is calculated using molecular dynamics (MD) simulation as Mg(2+) is pulled from RNA, which causes disturbance of the water network. It was found that Mg(2+) remains hexahydrated unless it is close to or far from RNA. In the pentahydrated form, Mg(2+) interacts directly with RNA. Water network has been identified by two complimentary methods; MD followed by a density-based clustering algorithm and three-dimensional-reference interaction site model. These two methods gave similar results. Identification of water network around Mg(2+) and non-WC base pairs gives a clue to the strong effect of water network on the stability of this RNA. Based on sequence analysis of all Eubacteria 5s rRNA, we propose that hexahydrated Mg(2+) is an integral part of this RNA and geometry of base pairs surrounding it adjust to accommodate the [Formula: see text]. Overall the findings from this work can help in understanding the basis of the complex structure and stability of RNA with non-WC base pairs.

  6. Theoretical and Experimental Analysis of Nanoparticle-Nanoparticle and Nanoparticle-Surface Interactions and their Role in Defining Nanoparticle Stability and Mobility

    Science.gov (United States)

    Cardoso Zies, Camila

    suggest that nanoparticles interact among themselves and with surfaces in the same fashion that has been previously described by traditional colloidal science and the approach and techniques here applied present an effective method for screening nanoparticle stability and transport.

  7. Anionic Polyelectrolyte-Cationic Surfactant Interactions in Aqueous Solutions and Foam Films Stability Interactions entre polyélectrolytes anioniques et tensioactifs cationiques en solutions aqueuses et stabilité des films de mousses

    Directory of Open Access Journals (Sweden)

    Langevin D.

    2006-12-01

    Full Text Available The objective of this work is to study polymer/surfactant interactions in aqueous solution and at the air/water interface. These interations are involved in many physicochemical phenomena, such as colloidal stabilization and wettability which are of major importance in oil application as for exemple drilling muds. More precisely, we have attempted to characterize interactions between a non surface active anionic copolymer (acrylamide/acrylamide sulfonate and an oppositely charged cationic surfactant (C12 TAB. Our results show a synergestic surface tension lowering (coadsorption at extremely low surfactant concentrations (10 to the power of (-3 to 10 to the power of (-1 CMC. At higher concentrations, namely above the so called Critical Aggregation Concentration (CAC, polymer-surfactant complexes form in the bulk and the macromolecules precipitate out of the solution. Foam films made from these mixed solutions are stable while C12TAB films are unstable. Disjoining pressure measurements on mixed films with surfactant concentration two orders of magnitude below the CAC show the existence of long range repulsive forces and a discrete film thickness transition. At the CAC, we obtain mixed films with gel-like networks that are strongly affected by the film thinning rate. L'objectif de cette étude est d'étudier les interactions polymère/tensioactif en solution aqueuse et à l'interface eau/air. Ces interactions interviennent dans de nombreux phénomènes physico-chimiques tels que la stabilisation de suspensions colloïdales et la mouillabilité qui sont d'une importance majeure dans les applications pétrolières comme, par exemple, les boues de forage. Plus précisément, nous avons essayé de caractériser les interactions entre un copolymère anionique n'ayant pas d'activité de surface (acrylamide/acrylamide sulfoné avec un tensioactif de charge opposée cationique (C12TAB. Nos résultats montrent une diminution synergique de la tension

  8. Role of highly conserved pyrimidine-rich sequences in the 3' untranslated region of the GAP-43 mRNA in mRNA stability and RNA-protein interactions.

    Science.gov (United States)

    Kohn, D T; Tsai, K C; Cansino, V V; Neve, R L; Perrone-Bizzozero, N I

    1996-03-01

    We have shown previously that the mRNA for the growth-associated protein GAP-43 is selectively stabilized during neuronal differentiation. In this study, we explored the role of its highly conserved 3' untranslated region (3'UTR) in mRNA stability and RNA-protein interactions. The 3'UTRs of the rat and chicken GAP-43 mRNAs show 78% sequence identity, which is equivalent to the conservation of their coding regions. In rat PC12 cells stably transfected with the full-length rat or chicken GAP-43 cDNAs, the transgene mRNAs decayed with same half-life of about 3 h. The GAP-43 3'UTR also caused the rabbit beta-globin mRNA to decay with a half-life of 4 h, indicating that the major determinants for GAP-43 mRNA stability are localized in its highly conserved 3'UTR. Three brain cytosolic RNA-binding proteins (molecular mass 40, 65 and 95 kDa) were found to interact with both the rat and chicken GAP-43 mRNAs. These RNA-protein interactions were specific and involved pyrimidine-rich sequences in the 3'UTR. Like the GAP-43 mRNA, the activity of these proteins was enriched in brain and increased during development. We propose that highly conserved pyrimidine-rich sequences in the 3'UTR of this mRNA regulate GAP-43 gene expression via interactions with specific RNA-binding proteins.

  9. Ideal Stabilization

    CERN Document Server

    Nesterenko, Mikhail

    2009-01-01

    We define and explore the concept of ideal stabilization. The program is ideally stabilizing if its every state is legitimate. Ideal stabilization allows the specification designer to prescribe with arbitrary degree of precision not only the fault-free program behavior but also its recovery operation. Specifications may or may not mention all possible states. We identify approaches to designing ideal stabilization to both kinds of specifications. For the first kind, we state the necessary condition for an ideally stabilizing solution. On the basis of this condition we prove that there is no ideally stabilizing solution to the leader election problem. We illustrate the utility of the concept by providing examples of well-known programs and proving them ideally stabilizing. Specifically, we prove ideal stabilization of the conflict manager, the alternator, the propagation of information with feedback and the alternating bit protocol.

  10. Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function.

    Science.gov (United States)

    Chen, D; Zhang, Z; Li, M; Wang, W; Li, Y; Rayburn, E R; Hill, D L; Wang, H; Zhang, R

    2007-08-01

    As a major negative regulator of p53, the MDM2 oncogene plays an important role in carcinogenesis and tumor progression. MDM2 promotes p53 proteasomal degradation and negatively regulates p53 function. The mechanisms by which the MDM2-p53 interaction is regulated are not fully understood, although several MDM2-interacting molecules have recently been identified. To search for novel MDM2-binding partners, we screened a human prostate cDNA library by the yeast two-hybrid assay using full-length MDM2 protein as the bait. Among the candidate proteins, ribosomal protein S7 was identified and confirmed as a novel MDM2-interacting protein. Herein, we demonstrate that S7 binds to MDM2, in vitro and in vivo, and that the interaction between MDM2 and S7 leads to modulation of MDM2-p53 binding by forming a ternary complex among MDM2, p53 and S7. This results in the stabilization of p53 protein through abrogation of MDM2-mediated p53 ubiquitination. Consequently, S7 overexpression increases p53 transactivational activities, induces apoptosis, and inhibits cell proliferation. The identification of S7 as a novel MDM2-interacting partner contributes to elucidation of the complex regulation of the MDM2-p53 interaction and has implications in cancer prevention and therapy.

  11. Modulating weak interactions for molecular recognition: a dynamic combinatorial analysis for assessing the contribution of electrostatics to the stability of CH-π bonds in water.

    Science.gov (United States)

    Jiménez-Moreno, Ester; Gómez, Ana M; Bastida, Agatha; Corzana, Francisco; Jiménez-Oses, Gonzalo; Jiménez-Barbero, Jesús; Asensio, Juan Luis

    2015-03-27

    Electrostatic and charge-transfer contributions to CH-π complexes can be modulated by attaching electron-withdrawing substituents to the carbon atom. While clearly stabilizing in the gas phase, the outcome of this chemical modification in water is more difficult to predict. Herein we provide a definitive and quantitative answer to this question employing a simple strategy based on dynamic combinatorial chemistry.

  12. Formation of Pickering emulsions stabilized via interaction between nanoparticles dispersed in aqueous phase and polymer end groups dissolved in oil phase.

    Science.gov (United States)

    Okada, Masahiro; Maeda, Hayata; Fujii, Syuji; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2012-06-26

    The influence of end groups of a polymer dissolved in an oil phase on the formation of a Pickering-type hydroxyapatite (HAp) nanoparticle-stabilized emulsion and on the morphology of HAp nanoparticle-coated microspheres prepared by evaporating solvent from the emulsion was investigated. Polystyrene (PS) molecules with varying end groups and molecular weights were used as model polymers. Although HAp nanoparticles alone could not function as a particulate emulsifier for stabilizing dichloromethane (oil) droplets, oil droplets could be stabilized with the aid of carboxyl end groups of the polymers dissolved in the oil phase. Lower-molecular-weight PS molecules containing carboxyl end groups formed small droplets and deflated microspheres, due to the higher concentration of carboxyl groups on the droplet/microsphere surface and hence stronger adsorption of the nanoparticles at the water/oil interface. In addition, Pickering-type suspension polymerization of styrene droplets stabilized by PS molecules containing carboxyl end groups successfully led to the formation of spherical HAp-coated microspheres.

  13. Interfacial Matrix Stabilization Spectroscopy (IMSS) studies of CO and O2 interactions with thin films of oxide-supported Au nanoparticles

    Science.gov (United States)

    Jarrah, Nina K.; Moore, David T.

    2013-03-01

    Interfacial Matrix Stabilization Spectroscopy (IMSS) employs energy-dissipating cryogenic matrix isolation techniques combined with FTIR to enable stabilization and detection of pre-reactive complexes of CO and O2 formed on oxide-supported gold nanoparticles (AuNPs). Following deposition of CO and O2 in an argon matrix at 10-20K, annealing to warmer temperatures (28-32K) promotes diffusion of isolated dopant molecules through the matrix to binding sites on a thin film of catalyst. Matrix-solvated pre-reactive complexes form at the surface and are characterized spectroscopically. Comparison of observed complexes in IMSS experiments with results from direct adsorption studies, in absence of a matrix, can provide a measure for the stabilizing effects of matrix solvation. Subsequent surface warming following stabilization of the pre-reactive complexes reveals qualitative information about relative binding energies of formed intermediates of CO, O2, and the supported AuNPs. A series of FTIR spectra mapping the evolution of vibrational bands during the annealing process and tracking the various surface-bound species will be presented and comparisons to direct adsorption experiments will be discussed.

  14. Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

    Directory of Open Access Journals (Sweden)

    Kevin A James

    Full Text Available The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD motif in the catalytic loop and the Asp-Phe-Gly (DFG motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not

  15. Crystallographic analysis of the ternary complex of octanoate and N-acetyl-l-methionine with human serum albumin reveals the mode of their stabilizing interactions.

    Science.gov (United States)

    Kawai, Akito; Chuang, Victor T G; Kouno, Yosuke; Yamasaki, Keishi; Miyamoto, Shuichi; Anraku, Makoto; Otagiri, Masaki

    2017-08-01

    During pasteurization and storage of albumin products, Sodium octanoate (Oct) and N-acethyl-l-tryptophan (N-AcTrp) are used as the thermal stabilizer and the antioxidant for human serum albumin (HSA), respectively. We recently reported that N-acethyl-l-methionine (N-AcMet) is an antioxidant for HSA, which is superior to N-AcTrp when it is especially exposed to light during storage. The objective of the present study is to clarify the molecular mechanism responsible for the HSA protective effect of Oct and N-AcMet based on their ternary complex structure. Crystal structure of the HSA-Oct-N-AcMet complex showed that one N-AcMet molecule is bound to the entrance of drug site 1 of HSA, and its side chain, which is susceptible to the oxidation, is exposed to the solvent. At the same time, two Oct binding sites are observed in drug sites 1 and 2 of HSA, respectively, and each Oct molecule occupies the hydrophobic cavity in them. These results indicate the molecular mechanism responsible for the HSA stabilization by these small molecules as follows. N-AcMet seals the entrance of drug site 1 while it acts as an antioxidant for HSA. Oct is chiefly bound to drug site 2 of HSA and it increases the thermal stability of HSA because of the occupying the largest intra-cavity of sub-domain IIIA in HSA. These findings suggest that N-AcMet acts positively as useful stabilizer for albumin formulated products such as functionalized HSA and HSA fusion proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Interactive effects of molasses by homofermentative and heterofermentative inoculants on fermentation quality, nitrogen fractionation, nutritive value and aerobic stability of wilted alfalfa (Medicago sativa L) silage.

    Science.gov (United States)

    Hashemzadeh-Cigari, F; Khorvash, M; Ghorbani, G R; Ghasemi, E; Taghizadeh, A; Kargar, S; Yang, W Z

    2014-04-01

    The effect of adding molasses (0, UM or 50 g/kg on DM basis, M) and two types of inoculant including homofermentative (HO) and a combination of homofermentative and propionate-producing bacterial (HOPAB) inoculants on silage fermentation quality, nitrogen fractionation and aerobic stability of pre-bloom, wilted alfalfa (AS) was determined in laboratory silos. The HOPAB inoculant was more effective than HO in reducing the alfalfa silage pH but increased propionate content in the absence of M (p alfalfa crop with M and HOPAB improved aerobic stability by increasing the concentration of acetate and propionate of AS respectively. Adding M tended (p < 0.10) to increase short-chain fatty acids (SCFA) and cumulative gas production (CGP). HOPAB alone increased DM disappearance at 24 h post-incubation and effective degradability assuming outflow rate of 8%/h relative to untreated AS (p < 0.05). It was concluded that adding M had no pronounced effects on AS fermentation quality, but increased aerobic stability. HOPAB-inoculated AS with no addition of M improved fermentation quality and increased DM degradability compared with HO. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

  17. Interaction of H and F atoms—Origin of the high conductive stability of hydrogen-incorporated F-doped ZnO thin films

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yanmin [State Key Laboratory of Silicon Materials, Department of Materials Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Zhu, Liping, E-mail: zlp1@zju.edu.cn [State Key Laboratory of Silicon Materials, Department of Materials Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027 (China); Li, Yaguang; Niu, Wenzhe; Zhang, Xiangyu; Ye, Zhizhen [State Key Laboratory of Silicon Materials, Department of Materials Science and Engineering, Zhejiang University, Hangzhou 310027 (China)

    2015-08-31

    We intentionally incorporated H into fluorine-doped ZnO thin films (FZO) by plasma treatment. Upon treatment, both mobility and electron concentration have an observable increase, especially the mobility reaches up to 30.1 cm{sup 2}V{sup −1} s{sup −1} (3 times higher than the untreated films). H distributes in the FZO thin films uniformly via plasma treatment. The treated FZO thin films showed good conductive stability at 500 °C and saved for 6 months, until now. Origin of high conductive stability was explained by first principle calculation. The results predicted that hydrogen atoms in interstitial sites next to F{sub O} are attracted by the incorporated fluorine atoms and this configuration has lower formation energy than the hydrogen in oxygen vacancy configuration. Thus, we owed the highly stable conductivity to the hydrogen as interstitial as well as hydrogen in oxygen vacancy. - Highlights: • We incorporated H into fluorine-doped ZnO thin films by plasma treatment. • Both mobility and electron concentration of the treated thin films have an observable increase. • The treated FZO thin films showed good conductive stability. • We owed the highly stable conductivity to the hydrogen as interstitial as well as hydrogen in oxygen vacancy.

  18. Expression of domains for protein-protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stability.

    Science.gov (United States)

    Jordheim, Lars Petter; Cros-Perrial, Emeline; Matera, Eva-Laure; Bouledrak, Karima; Dumontet, Charles

    2014-10-01

    Nucleotide excision repair (NER) is involved in the repair of DNA damage caused by platinum derivatives and has been shown to decrease the cytotoxic activity of these drugs. Because protein-protein interactions are essential for NER activity, we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the amino acid sequences corresponding to the interacting domains between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum, complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum, complementation group F (XPF), all NER proteins. Using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and annexin V staining, we showed that transfected A549 cells were sensitized 1.2-2.2-fold to carboplatin and that transfected HCT116 cells were sensitized 1.4-5.4-fold to oxaliplatin in vitro. In addition, transfected cells exhibited modified in vivo sensitivity to the same drugs. Finally, in particular cell models of the interaction between ERCC1 and XPF, DNA repair was decreased, as evidenced by increased phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic instability was increased, as determined by comparative genomic hybridization studies. The results indicate that the interacting peptides act as dominant negatives and decrease NER activity through inhibition of protein-protein interactions.

  19. La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.

    Science.gov (United States)

    Yang, Ruiqing; Gaidamakov, Sergei A; Xie, Jingwei; Lee, Joowon; Martino, Luigi; Kozlov, Guennadi; Crawford, Amanda K; Russo, Amy N; Conte, Maria R; Gehring, Kalle; Maraia, Richard J

    2011-02-01

    The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and reciprocal immunoprecipitations (IPs) from HeLa cells revealed that LARP4 interacts with RACK1, a 40S ribosome- and mRNA-associated protein. LARP4 cosediments with 40S ribosome subunits and polyribosomes, and its knockdown decreases translation. Mutagenesis of the RNA binding or PABP interaction motifs decrease LARP4 association with polysomes. Several translation and mRNA metabolism-related proteins use a PAM2 sequence containing a critical invariant phenylalanine to make direct contact with the MLLE domain of PABP, and their competition for the MLLE is thought to regulate mRNA homeostasis. Unlike all ∼150 previously analyzed PAM2 sequences, LARP4 contains a variant PAM2 (PAM2w) with tryptophan in place of the phenylalanine. Binding and nuclear magnetic resonance (NMR) studies have shown that a peptide representing LARP4 PAM2w interacts with the MLLE of PABP within the affinity range measured for other PAM2 motif peptides. A cocrystal of PABC bound to LARP4 PAM2w shows tryptophan in the pocket in PABC-MLLE otherwise occupied by phenylalanine. We present evidence that LARP4 expression stimulates luciferase reporter activity by promoting mRNA stability, as shown by mRNA decay analysis of luciferase and cellular mRNAs. We propose that LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis.

  20. Improvement of Thermal Stability via Outer-Loop Ion Pair Interaction of Mutated T1 Lipase from Geobacillus zalihae Strain T1

    Directory of Open Access Journals (Sweden)

    Mahiran Basri

    2012-01-01

    Full Text Available Mutant D311E and K344R were constructed using site-directed mutagenesis to introduce an additional ion pair at the inter-loop and the intra-loop, respectively, to determine the effect of ion pairs on the stability of T1 lipase isolated from Geobacillus zalihae. A series of purification steps was applied, and the pure lipases of T1, D311E and K344R were obtained. The wild-type and mutant lipases were analyzed using circular dichroism. The Tm for T1 lipase, D311E lipase and K344R lipase were approximately 68.52 °C, 70.59 °C and 68.54 °C, respectively. Mutation at D311 increases the stability of T1 lipase and exhibited higher Tm as compared to the wild-type and K344R. Based on the above, D311E lipase was chosen for further study. D311E lipase was successfully crystallized using the sitting drop vapor diffusion method. The crystal was diffracted at 2.1 Å using an in-house X-ray beam and belonged to the monoclinic space group C2 with the unit cell parameters a = 117.32 Å, b = 81.16 Å and c = 100.14 Å. Structural analysis showed the existence of an additional ion pair around E311 in the structure of D311E. The additional ion pair in D311E may regulate the stability of this mutant lipase at high temperatures as predicted in silico and spectroscopically.

  1. Stability Functions

    CERN Document Server

    Burns, Daniel; Wang, Zuoqin

    2008-01-01

    In this article we discuss the role of stability functions in geometric invariant theory and apply stability function techniques to problems in toric geometry. In particular we show how one can use these techniques to recover results of Burns-Guillemin-Uribe and Shiffman-Tate-Zelditch on asymptotic properties of sections of holomorphic line bundles over toric varieties.

  2. Interaction between Laponite and Collagen in Dilute Solutions and Effect on Dispersion Stability%稀溶液中Laponite与胶原的相互作用及其分散稳定性

    Institute of Scientific and Technical Information of China (English)

    张云凤; 李昌朋; 苏帝翰; 林炜; 穆畅道

    2013-01-01

    The formation conditions of stable Laponite - collagen dispersions were studied firstly. Then UV and Zeta potential tests were performed to explore the interaction of Laponite - collagen and the stability of the dispersion. The results indicate that collagen concentration, Laponite dosage and pH have influence on the stability of Laponite - collagen dispersion. UV spectra show that the non - covalent interaction occurs between Laponite and collagen in dilute solutions. Collagen chains tend to aggregate and the stability decreases with the increase of the collagen concentration. Increasing the content of Laponite in the collagen solution leads to the increase of Zeta potential at first and then decrease in the presence of more Laponite, showing that electrostatic interactions between the negative charged surface of Laponite and the positive charged groups of collagen chains dominate the stability of Laponite - collagen dispersion. Although Laponite is more stable in higher pH solutions, the dispersion shows more stable under lower pH conditions.%首先研究了形成稳定合成锂藻土Laponite-胶原分散液的条件,然后通过紫外和Zeta电位测试研究了Laponite 与胶原的相互作用以及分散液的稳定性.结果表明:胶原和Laponite的浓度以及溶液的pH都会影响分散液的稳定性;UV测试表明Laponite与胶原之间是非共价相互作用.当胶原浓度增大时,肽链有聚集趋势而使分散液稳定性降低.随着Laponite在胶原溶液中含量的增加,Zeta电位先升高再降低,说明稀溶液中胶原分子链与Laponite表面之间的静电作用,决定了分散体系的稳定性.尽管单独的Laponite在高pH溶液环境更为稳定,但Laponite-胶原分散体系在低pH值时的Zeta电位值较高,稳定性较好.

  3. Alfven mode stability and wave-particle interaction in the JET tokamak: prospects for scenario development and control schemes in burning plasma experiments

    Energy Technology Data Exchange (ETDEWEB)

    Testa, D [CRPP, Association EURATOM-Confederation Suisse, EPFL, Lausanne (Switzerland); Fasoli, A [CRPP, Association EURATOM-Confederation Suisse, EPFL, Lausanne (Switzerland); Borba, D [Associacao EURATOM/IST (Portugal); EDFA-CSU, Culham Science Centre (United Kingdom); Baar, M de [FOM-Instituut Voor Plasmafysica, Rijnhuizen (Netherlands); Bigi, M [Euratom/UKAEA Fusion Association, Culham Science Centre, Abingdon (United Kingdom); Brzozowski, J [NADA VR-Euratom Association, Royal Institute of Technology, Stockholm (Sweden); Vries, P de [Euratom/UKAEA Fusion Association, Culham Science Centre, Abingdon (United Kingdom)

    2004-07-01

    We have investigated the effect of different ion cyclotron resonance frequency (ICRF) heating schemes, of error field modes, of the plasma shape and edge magnetic shear, and of the ion {nabla}B drift direction on the stability of Alfven eigenmodes (AEs). The use of multi-frequency or 2nd harmonic minority ICRF heating at high plasma density gives rise to a lower fast ion pressure gradient in the plasma core and to a reduced mode activity in the Alfven frequency range. Externally excited low-amplitude error fields lead to a much larger AE instability threshold, which we attribute to a moderate radial redistribution of the fast ions. The edge plasma shape has a clear stabilizing effect on high-n, radially localized AEs. The damping rate of n = 1 toroidal AEs is a factor 3 higher when the ion {nabla}B drift is directed towards the divertor. These results represent a useful step towards the extrapolation of current scenarios to the inclusion of fusion-born alpha particles in ITER, with possible application for feedback control schemes for the various ITER operating regimes.

  4. Fundamental insights into conformational stability and orbital interactions of antioxidant (+)-catechin species and complexation of (+)-catechin with zinc(II) and oxovanadium(IV)

    Science.gov (United States)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Sirichai, Somsak; Ruangpornvisuti, Vithaya

    2013-09-01

    Conformational stability of (+)-catechin species in water has been examined with density functional theory, associated with the polarizable continuum model (PCM) of solvation. Factors such as electron delocalization, lone-pair electron donation and intramolecular hydrogen bonding substantially contribute to the conformational stabilization. Upon deprotonation, the HOMO and LUMO energies for (+)-catechin are both elevated; the energy gaps for the deprotonated species are narrower than the energy gap for the neutral species. The preferential deprotonation occurs at the C3'-, C5-, C7- and C4'-OH groups successively. The pKa value at 9.3 predicted for the most acidic OH group agrees well with previous experimental data; however the values are overestimated for the less acidic OH groups due to limitations of the PCM for charged solutes and/or complex nature of true deprotonation pathways. Formation of hydrogen radicals should be promoted at high pH values following the bond dissociation enthalpies. Complexation of (+)-catechin with either zinc(II) or oxovanadium(IV) is favored at the 1:1 metal-to-ligand (M:L) mole ratio, with the oxovanadium(IV) complex showing higher reaction preference. At M:L = 1:2, formation of two isomeric complexes are plausible for each type of metal ion. Effects of stoichiometry and isomerism on the computational spectral features of the possibly formed metal complexes have been described.

  5. Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling

    Science.gov (United States)

    Adams, Ralph; Burnley, Rebecca J.; Valenzano, Chiara R.; Qureshi, Omar; Doyle, Carl; Lumb, Simon; del Carmen Lopez, Maria; Griffin, Robert; McMillan, David; Taylor, Richard D.; Meier, Chris; Mori, Prashant; Griffin, Laura M.; Wernery, Ulrich; Kinne, Jörg; Rapecki, Stephen; Baker, Terry S.; Lawson, Alastair D. G.; Wright, Michael; Ettorre, Anna

    2017-01-01

    Protein:protein interactions are fundamental in living organism homeostasis. Here we introduce VHH6, a junctional epitope antibody capable of specifically recognizing a neo-epitope when two proteins interact, albeit transiently, to form a complex. Orthogonal biophysical techniques have been used to prove the “junctional epitope” nature of VHH6, a camelid single domain antibody recognizing the IL-6–gp80 complex but not the individual components alone. X-ray crystallography, HDX-MS and SPR analysis confirmed that the CDR regions of VHH6 interact simultaneously with IL-6 and gp80, locking the two proteins together. At the cellular level, VHH6 was able to alter the response of endothelial cells to exogenous IL-6, promoting a sustained STAT3 phosphorylation signal, an accumulation of IL-6 in vesicles and an overall pro-inflammatory phenotype supported further by transcriptomic analysis. Junctional epitope antibodies, like VHH6, not only offer new opportunities in screening and structure-aided drug discovery, but could also be exploited as therapeutics to modulate complex protein:protein interactions. PMID:28134246

  6. Interaction between Yttria fully stabilized Zirconia or Yttria-Zirconia blended face-coat with Ti6Al4V during investment casting

    CSIR Research Space (South Africa)

    Mutombo, K

    2014-10-01

    Full Text Available The interaction between the Ti6Al4V alloy and the mould materials was investigated. The alpha-case was characterized by Vickers hardness tester, optical and scanning electron microscopy equipped with electron dispersive X-ray spectrometry (EDX). X...

  7. Ensuring Stability

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    "Stable"will be a key word for China’s economy in 2012.That’s the beat set at the annual Central Economic Work Conference held in Beijing on December 12-14,which reviewed this year’s development and mapped out plans for the next year.Policymakers at the conference decided to keep macroeconomic policies stable,seek a stable and relatively fast economic growth,stabilize consumer prices and maintain social stability in 2012.On the basis of stability,the government will transform the development model,deepen reform and improve people’s livelihood.

  8. The interaction between reaction forces and stabilization systems during intrusion of the anterior teeth and its effect on the posterior unit.

    Science.gov (United States)

    Van den Bulcke, M M; Dermaut, L R

    1990-11-01

    The aim of this research is to attain a better understanding of the initial reaction forces induced by an intrusion mechanism (acting on the anterior teeth) on the posterior unit and to examine how these forces can be neutralized. The experiments were performed on the dentition of a dry human skull and initial tooth displacements were registered by means of two laser measuring techniques, namely holographic interferometry and the laser reflection technique. It was established that of all reaction forces induced by the intrusion arch, distal tipping of the first molars is the most pronounced. A transpalatal bar connecting the teeth does not counteract this movement. The stabilization of the posterior unit with a transpalatal bar, buccal sectionals, and high-pull headgear proved to be the most effective technique.

  9. Involvement and interaction of microbial communities in the transformation and stabilization of chromium during the composting of tannery effluent treated biomass of Vallisneria spiralis L.

    Science.gov (United States)

    Shukla, O P; Rai, U N; Dubey, Smita

    2009-04-01

    Tannery effluent treated with aquatic macrophyte Vallisneria spiralis L. for 14 d showed significant improvement in physico-chemical properties and reduction in Cr concentration. Accumulation of Cr was found maximum in roots (358 microg g(-1)dw) as compared to shoot (62 microg g(-1)dw) of the plant. A laboratory scale composter was designed with the objectives to investigate the physico-chemical changes and role of microbes in stabilization and transformation of Cr in the composting material. Results revealed that the composting process was quick within 7-21 d as indicated by peak time for various physico-chemical parameters and drop in C/N ratio up to acceptable limit. The profile of microbial communities indicated that population of anaerobic, aerobic and nitrifying bacteria increased quickly at the initial phase, and reached a peak level of 4.2 x 10(6), 9.78 x 10(8) and 9.32 x 10(9) CFU g(-1), respectively at 21 d; while population of actinomycetes and fungi was found maximum i.e. 3.29 x 10(7) and 9.7 x 10(6) CFU g(-1), respectively, after 35 d of composting. Overall bacterial population dominated over the actinomycetes and fungi during the composting process. Cr((VI)) was transformed to Cr((III)) due to the microbial activity during the process. Sequential extraction of Cr fractionation showed its stabilization via changing into organic matter-bound and residual fractions during the composting.

  10. Effect of Rashba Spin-Orbit Interaction on the Stability of Spin-Vortex-Induced Loop Current in Hole-Doped Cuprate Superconductors: A Scenario for the Appearance of Magnetic Field Enhanced Charge Order and Fermi Surface Reconstruction

    Science.gov (United States)

    Morisaki, Tsubasa; Wakaura, Hikaru; Koizumi, Hiroyasu

    2017-10-01

    Rashba type spin-orbit interaction is included in the model Hamiltonian for the spin-vortex-induced loop current (SVILC) mechanism of superconductivity for hole doped cuprate superconductors and its effects are investigated. We assume that a Rashba interaction appears around the small polarons formed by the doped holes in the bulk; its internal electric field is assumed to be in the direction perpendicular to the CuO2 plane and stabilizes the spin polarization lying in the CuO2 plane. We examine 4 × 4, 4 × 6, and 4 × 8 spin-vortex-quartet (SVQ) and perform Monte Carlo simulations to estimate the superconducting transition temperature Tc, where each SVQ is a n × m two dimensional region (in the units of the lattice constant) containing four holes, four spin-vortices, and four SVILCs. We find that the 4 × 6 SVQ is the most stable one among them with the highest Tc; in this case, the hole concentration per Cu atom is x = 0.167, which is close to the optimal doping value x = 0.170, suggesting that the optimal doping may be related to the stabilization of the superconducting state by the Rashba interaction. We also find that the 4 × 8 SVQ becomes more stable than the 4 × 6 SVQ in a current flowing situation; this indicates that the conversion from the 4 × 6 SVQs to 4 × 8 SVQs may occur upon the emergence of a macroscopic current by the application of a magnetic field. This conversion may explain the enhancement of the charge order around x = 0.125 and the Fermi surface reconstruction upon an application of a magnetic field.

  11. ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction.

    Science.gov (United States)

    Dhar, Jesmita; Chakrabarti, Pinak; Saini, Harpreet; Raghava, Gajendra Pal Singh; Kishore, Raghuvansh

    2015-02-01

    Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼ three times per 100 residues. Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. © 2014 Wiley Periodicals, Inc.

  12. Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function

    OpenAIRE

    2014-01-01

    SUMMARY Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear...

  13. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

    Directory of Open Access Journals (Sweden)

    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  14. Stabilizing Niger

    DEFF Research Database (Denmark)

    Hahonou, Eric Komlavi

    international intervention in Niger. Their main objective is to secure their own strategic, economic and political interests by strengthening the Nigerien authorities through direct intervention and capacity building activities. For western states reinforcing state security institutions and stabilizing elite...

  15. A novel Rho-dependent pathway that drives interaction of fascin-1 with p-Lin-11/Isl-1/Mec-3 kinase (LIMK 1/2 to promote fascin-1/actin binding and filopodia stability

    Directory of Open Access Journals (Sweden)

    Jayo Asier

    2012-08-01

    Full Text Available Abstract Background Fascin-1 is an actin crosslinking protein that is important for the assembly of cell protrusions in neurons, skeletal and smooth muscle, fibroblasts, and dendritic cells. Although absent from most normal adult epithelia, fascin-1 is upregulated in many human carcinomas, and is associated with poor prognosis because of its promotion of carcinoma cell migration, invasion, and metastasis. Rac and Cdc42 small guanine triphosphatases have been identified as upstream regulators of the association of fascin-1 with actin, but the possible role of Rho has remained obscure. Additionally, experiments have been hampered by the inability to measure the fascin-1/actin interaction directly in intact cells. We investigated the hypothesis that fascin-1 is a functional target of Rho in normal and carcinoma cells, using experimental approaches that included a novel fluorescence resonance energy transfer (FRET/fluorescence lifetime imaging (FLIM method to measure the interaction of fascin-1 with actin. Results Rho activity modulates the interaction of fascin-1 with actin, as detected by a novel FRET method, in skeletal myoblasts and human colon carcinoma cells. Mechanistically, Rho regulation depends on Rho kinase activity, is independent of the status of myosin II activity, and is not mediated by promotion of the fascin/PKC complex. The p-Lin-11/Isl-1/Mec-3 kinases (LIMK, LIMK1 and LIMK2, act downstream of Rho kinases as novel binding partners of fascin-1, and this complex regulates the stability of filopodia. Conclusions We have identified a novel activity of Rho in promoting a complex between fascin-1 and LIMK1/2 that modulates the interaction of fascin-1 with actin. These data provide new mechanistic insight into the intracellular coordination of contractile and protrusive actin-based structures. During the course of the study, we developed a novel FRET method for analysis of the fascin-1/actin interaction, with potential general

  16. A weak interaction between the U2A' protein and U2 snRNA helps to stabilize their complex with the U2B" protein.

    OpenAIRE

    Boelens, W; Scherly, D; Beijer, R P; Jansen, E J; Dathan, N A; Mattaj, I W; van Venrooij, W J

    1991-01-01

    The U2 snRNP complex contains two specific proteins, U2B" and U2A'. We have analysed the interaction of U2A' with U2B" and with U2 RNA. U2A' can form an weak but detectable RNA-protein complex with U2 RNA and a stable protein complex with U2B". This protein-protein complex binds efficiently and specifically to U2 RNA. Binding experiments with mutant forms of U2A' shows that the region of U2A' essential for binding to U2B" is extensive, being located between amino acid position 1-164. The beha...

  17. On the dynamics of interaction between a moving mass and an infinite one-dimensional elastic structure at the stability limit

    Science.gov (United States)

    Mazilu, Traian; Dumitriu, Mădălina; Tudorache, Cristina

    2011-07-01

    The paper herein deals with the study of the dynamic behaviour generated by the instability of the vibration of a loaded mass, uniformly moving along an Euler-Bernoulli beam on a viscoelastic foundation, induced by the anomalous Doppler waves excited in the beam. This issue is relevant for the case of modern trains travelling along a track with soft soil when the trains speed exceeds the phase velocity of the waves induced in the track. The model corresponds to a railway vehicle reduced to a loaded wheel running along a (half) track. The beam takes account of the bending stiffness of the rail and the mass of the track, including the mass of the rail, semi-sleepers and half of the ballast layer, where the viscoelastic foundation represents the subgrade. The model includes the wheel/rail Hertzian contact and it allows the simulation of the possibility of contact loss. The nonlinear equations of motion are integrated using a numerical approach based on the Green's function method. When the vibration becomes unstable, the system evolution is a limit cycle characterised by a succession of shocks, due to the action of two opposite factors: the anomalous Doppler waves that pump energy at the interface between the moving mass and the beam, thus forcing the mass to take off, and the static load that push the mass downwards. The frequency of the shocks increases at higher velocity and the magnitude of the impact force decreases; the most dangerous velocity is the critical one, which represents the stability limit of the linear approximation of the motion equations. The transient behaviour that precedes the limit cycle appearance is being analysed. The Hertzian contact influences the time history of the limit cycle and the magnitude of the impact force and, therefore, it is essential to be included in the model. To the authors' knowledge, this problem has never been dealt with.

  18. Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function

    Directory of Open Access Journals (Sweden)

    Jia Shen

    2014-04-01

    Full Text Available Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy.

  19. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  20. A bacteriophage-encoded J-domain protein interacts with the DnaK/Hsp70 chaperone and stabilizes the heat-shock factor σ32 of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elsa Perrody

    Full Text Available The universally conserved J-domain proteins (JDPs are obligate cochaperone partners of the Hsp70 (DnaK chaperone. They stimulate Hsp70's ATPase activity, facilitate substrate delivery, and confer specific cellular localization to Hsp70. In this work, we have identified and characterized the first functional JDP protein encoded by a bacteriophage. Specifically, we show that the ORFan gene 057w of the T4-related enterobacteriophage RB43 encodes a bona fide JDP protein, named Rki, which specifically interacts with the Escherichia coli host multifunctional DnaK chaperone. However, in sharp contrast with the three known host JDP cochaperones of DnaK encoded by E. coli, Rki does not act as a generic cochaperone in vivo or in vitro. Expression of Rki alone is highly toxic for wild-type E. coli, but toxicity is abolished in the absence of endogenous DnaK or when the conserved J-domain of Rki is mutated. Further in vivo analyses revealed that Rki is expressed early after infection by RB43 and that deletion of the rki gene significantly impairs RB43 proliferation. Furthermore, we show that mutations in the host dnaK gene efficiently suppress the growth phenotype of the RB43 rki deletion mutant, thus indicating that Rki specifically interferes with DnaK cellular function. Finally, we show that the interaction of Rki with the host DnaK chaperone rapidly results in the stabilization of the heat-shock factor σ(32, which is normally targeted for degradation by DnaK. The mechanism by which the Rki-dependent stabilization of σ(32 facilitates RB43 bacteriophage proliferation is discussed.

  1. The Variation and Stability Analysis of Wheat Dough Stability Time

    Institute of Scientific and Technical Information of China (English)

    TIAN Ji-chun; HU Rui-bo; DENG Zhi-ying; WANG Yan-xun

    2007-01-01

    Farinograph dough stability time is an important index for classifying wheat, and it often indicates the most appropriate end use for the wheat cultivars. This study aimed at the problem of large fluctuations in dough stability time that occurs during the commercial wheat production. The variations in the dough stability time and its consistency across locations and years were analyzed using 12 principal high-quality wheat cultivars (varieties) obtained from Shandong Province,China, which were grown at nine different locations for three successive years. The results showed that the coefficient of variation for the dough stability time ranged from 24.29 to 49.60% across different varieties, locations, and years. Additive main effects and multiplicative interaction (AMMI) analysis indicated that there were significant interactions for the dough stability time between the varieties, the growth locations, and the years. The genotype effect was the most noticeable, followed by the interaction of the genotype and the environment. The environmental effect was the least significant. The interactions between the varieties and the locations differ considerably, however, each cultivar (variety) apparently has a specific adaptability to the growth location. Therefore, for the successful commercial scale production of the high-quality wheat varieties, both the selection of proper cultivars and its most suitable growth locations to meet the desired requirements for the dough mixing stability time are important.

  2. PARALLEL STABILIZATION

    Institute of Scientific and Technical Information of China (English)

    J.L.LIONS

    1999-01-01

    A new algorithm for the stabilization of (possibly turbulent, chaotic) distributed systems, governed by linear or non linear systems of equations is presented. The SPA (Stabilization Parallel Algorithm) is based on a systematic parallel decomposition of the problem (related to arbitrarily overlapping decomposition of domains) and on a penalty argument. SPA is presented here for the case of linear parabolic equations: with distrjbuted or boundary control. It extends to practically all linear and non linear evolution equations, as it will be presented in several other publications.

  3. Interaction between anions and cationic metal complexes containing tridentate ligands with exo-C-H groups: complex stability and hydrogen bonding.

    Science.gov (United States)

    Martínez-García, Héctor; Morales, Dolores; Pérez, Julio; Puerto, Marcos; del Río, Ignacio

    2014-05-05

    [Re(CO)3 ([9]aneS3 )][BAr'4 ] (1), prepared by reaction of ReBr(CO)5 , 1,4,7-trithiacyclononane ([9]aneS3 ) and NaBAr'4 , forms stable, soluble supramolecular adducts with chloride (2), bromide, methanosulfonate (3) and fluoride (4) anions. These new species were characterized by IR, NMR spectroscopy and, for 2 and 3, also by X-ray diffraction. The results of the solid state structure determinations indicate the formation of CH⋅⋅⋅X hydrogen bonds between the anion (X) and the exo-CH groups of the [9]aneS3 ligand, in accord with the relatively large shifts found by (1) H NMR spectroscopy in dichloromethane solution for those hydrogens. The stability of the chloride adduct contrasts with the lability of the [9]aneS3 ligand in allyldicarbonyl molybdenum complexes recently studied by us. With fluoride, in dichloromethane solution, a second, minor neutral dimeric species 5 is formed in addition to 4. In 4, the deprotonation of a CH group of the [9]aneS3 ligand, accompanied by CS bond cleavage and dimerization, afforded 5, featuring bridging thiolates. Compounds [Mo(η(3) -methallyl)(CO)2 (TpyN)][BAr'4 ] (6) and [Mo(η(3) -methallyl)(CO)2 (TpyCH)][BAr'4 ] (7) were synthesized by the reactions of [MoCl(η(3) -methallyl)(CO)2 (NCMe)2 ], NaBAr'4 and tris(2-pyridyl)amine (TpyN) or tris(2-pyridyl)methane (TpyCH) respectively, and characterized by IR and (1) H and (13) C NMR spectroscopy in solution, and by X-ray diffraction in the solid state. Compound 6 undergoes facile substitution of one of the 2-pyridyl groups by chloride, bromide, and methanosulfonate anions. Stable supramolecular adducts were formed between 7 and chloride, bromide, iodide, nitrate, and perrhenate anions. The solid state structures of these adducts (12-16) were determined by X-ray diffraction. Binding constants in dichloromethane were calculated from (1) H NMR titration data for all the new supramolecular adducts. The signal of the bridgehead CH group is the one that undergoes a

  4. Role of the XRCC1 - APE1 interaction in the maintenance of genetic stability; Etude du role de l' interaction entre XRCC1 et APE1 dans la stabilite genetique

    Energy Technology Data Exchange (ETDEWEB)

    Sossou-Becker, M.

    2005-09-15

    This thesis is divided in four chapters: the first one concerns the genetic instability, the second one is devoted to the DNA repair, the third one is related to the XRCC1 and the chapter four concerns APE1. Then, are defined the objectives and the results. This work fits into the studies of repair mechanisms. The physical and functional characterisation of the interaction between XRCC1 and APE1 allowed to understand its involvement in the prevention of the genetic instability at the origin of cancer. (N.C.)

  5. Use of anion-aromatic interactions to position the general base in the ketosteroid isomerase active site.

    Science.gov (United States)

    Schwans, Jason P; Sunden, Fanny; Lassila, Jonathan K; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

    2013-07-09

    Although the cation-pi pair, formed between a side chain or substrate cation and the negative electrostatic potential of a pi system on the face of an aromatic ring, has been widely discussed and has been shown to be important in protein structure and protein-ligand interactions, there has been little discussion of the potential structural and functional importance in proteins of the related anion-aromatic pair (i.e., interaction of a negatively charged group with the positive electrostatic potential on the ring edge of an aromatic group). We posited, based on prior structural information, that anion-aromatic interactions between the anionic Asp general base and Phe54 and Phe116 might be used instead of a hydrogen-bond network to position the general base in the active site of ketosteroid isomerase from Comamonas testosteroni as there are no neighboring hydrogen-bonding groups. We have tested the role of the Phe residues using site-directed mutagenesis, double-mutant cycles, and high-resolution X-ray crystallography. These results indicate a catalytic role of these Phe residues. Extensive analysis of the Protein Data Bank provides strong support for a catalytic role of these and other Phe residues in providing anion-aromatic interactions that position anionic general bases within enzyme active sites. Our results further reveal a potential selective advantage of Phe in certain situations, relative to more traditional hydrogen-bonding groups, because it can simultaneously aid in the binding of hydrophobic substrates and positioning of a neighboring general base.

  6. MiR-17 Downregulation by High Glucose Stabilizes Thioredoxin-Interacting Protein and Removes Thioredoxin Inhibition on ASK1 Leading to Apoptosis.

    Science.gov (United States)

    Dong, Daoyin; Fu, Noah; Yang, Peixin

    2016-03-01

    Pregestational diabetes significantly increases the risk of neural tube defects (NTDs). Maternal diabetes activates an Apoptosis Signal-regulating Kinase 1 (ASK1)-initiated pathway, which triggers neural stem cell apoptosis of the developing neuroepithelium leading to NTD formation. How high glucose of diabetes activates ASK1 is still unclear. In this study, we investigated the mechanism underlying high glucose-induced ASK1 activation. High glucose suppressed miR-17 expression, which led to an increase in its target gene Txnip (Thioredoxin-interacting protein). High glucose-increased Txnip enhanced its binding to the ASK1 inhibitor, thioredoxin (Trx), and thereby sequestered Trx from the Trx-ASK1 complex. High glucose-induced ASK1 activation and consequent apoptosis were abrogated by either the miR-17 mimic or Txnip siRNA knockdown. In contrast, the miR-17 inhibitor or Txnip ectopic overexpression mimicked the stimulative effect of high glucose on ASK1 and apoptosis. Thus, our study demonstrated that miR-17 repression mediates the pro-apoptotic effect of high glucose, and revealed a new mechanism underlying ASK1 activation, in which decreased miR-17 removes Trx inhibition on ASK1 through Txnip. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. A new serotonin 5-HT6 receptor antagonist with procognitive activity – Importance of a halogen bond interaction to stabilize the binding

    Science.gov (United States)

    González-Vera, Juan A.; Medina, Rocío A.; Martín-Fontecha, Mar; Gonzalez, Angel; de la Fuente, Tania; Vázquez-Villa, Henar; García-Cárceles, Javier; Botta, Joaquín; McCormick, Peter J.; Benhamú, Bellinda; Pardo, Leonardo; López-Rodríguez, María L.

    2017-01-01

    Serotonin 5-HT6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer’s disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit. PMID:28117458

  8. Macroeconomic stability

    DEFF Research Database (Denmark)

    Jespersen, Jesper

    2004-01-01

    It is demonstrated that full employment and sustainable development not necessarily are conflicting goals. On the other hand macroeconomic stability cannot be obtained without a deliberate labour sharing policy and a shift in the composition of private consumption away from traditional material...

  9. Acid-base formalism in dispersion-stabilized S-H···Y (Y═O, S) hydrogen-bonding interactions.

    Science.gov (United States)

    Bhattacherjee, Aditi; Matsuda, Yoshiyuki; Fujii, Asuka; Wategaonkar, Sanjay

    2015-02-19

    The role of sulfhydryl (S-H) group as hydrogen bond donor is not as well studied as that of hydroxyl (O-H). In this work we report on the hydrogen-bonding properties of S-H donor in 1:1 complexes of H2S with diethyl ether (Et2O), dibutyl ether (Bu2O), and 1,4-dioxane (DO). The complexes were prepared in supersonic jet and investigated using infrared predissociation spectroscopy based on VUV photoionization detection. The IR spectra of all the complexes showed the presence of a broad, intensity-enhanced, and red-shifted hydrogen-bonded S-H stretching transition. The S-H stretching frequency was red-shifted by 46, 63, and 49 cm(-1) in H2S-Et2O, H2S-Bu2O, and H2S-DO complexes, respectively, suggesting that all the complexes are S-H···O bound. Computationally, two different S-H···O bound structures, namely, "coplanar" and "perpendicular", were obtained as the minimum energy structures for these complexes at the MP2/6-311++G** level, with the former being the global minimum. However, with Dunning-type basis sets (aug-cc-pVDZ and aug-cc-pVTZ) only the perpendicular structures were found to be stable at the MP2 level. The large widths of the bound S-H stretch observed in the experimental spectra (fwhm of 35 to 80 cm(-1)) were attributed to inhomogeneous broadening due to multiple conformations of the alkyl chains in the coplanar and perpendicular structures populated in the jet. The frequency shifts in the hydrogen-bonded S-H stretching mode as well as the bond dissociation energies of all S-H···Y (Y═O,S) complexes of H2S, which includes the H2S dimer and H2S-methanol (H2S-MeOH) complexes reported in our previous work (ChemPhysChem 2013, 14, 905-914), were found to scale linearly with the proton affinity of the acceptor molecule. In this regard the S-H group, like O-H, is found to conform to the widely accepted acid-base nature of hydrogen-bonding interactions.

  10. Interactive Effects of Climate Change and Decomposer Communities on the Stabilization of Wood-Derived Carbon Pools: Catalyst for a New Study

    Energy Technology Data Exchange (ETDEWEB)

    Resh, Sigrid C. [Michigan Technological University

    2014-11-17

    Globally, forest soils store ~two-thirds as much carbon (C) as the atmosphere. Although wood makes up the majority of forest biomass, the importance of wood contributions to soil C pools is unknown. Even with recent advances in the mechanistic understanding of soil processes, integrative studies tracing C input pathways and biological fluxes within and from soils are lacking. Therefore, our research objectives were to assess the impact of different fungal decay pathways (i.e., white-rot versus brown-rot)—in interaction with wood quality, soil temperature, wood location (i.e., soil surface and buried in mineral soil), and soil texture—on the transformation of woody material into soil CO2 efflux, dissolved organic carbon (DOC), and soil C pools. The use of 13C-depleted woody biomass harvested from the Rhinelander, WI free-air carbon dioxide enrichment (Aspen-FACE) experiment affords the unique opportunity to distinguish the wood-derived C from other soil C fluxes and pools. We established 168 treatment plots across six field sites (three sand and three loam textured soil). Treatment plots consisted of full-factorial design with the following treatments: 1. Wood chips from elevated CO2, elevated CO2 + O3, or ambient atmosphere AspenFACE treatments; 2. Inoculated with white rot (Bjerkandera adusta) or brown rot (Gloeophyllum sepiarium) pure fungal cultures, or the original suite of endemic microbial community on the logs; and 3. Buried (15cm in soil as a proxy for coarse roots) or surface applied wood chips. We also created a warming treatment using open-topped, passive warming chambers on a subset of the above treatments. Control plots with no added wood (“no chip control”) were incorporated into the research design. Soils were sampled for initial δ13C values, CN concentrations, and bulk density. A subset of plots were instrumented with lysimeters for sampling soil water and temperature data loggers for measuring soil temperatures. To determine the early

  11. Interactive Effects of Climate Change and Decomposer Communities on the Stabilization of Wood-Derived Carbon Pools: Catalyst for a New Study

    Energy Technology Data Exchange (ETDEWEB)

    Resh, Sigrid C. [Michigan Technological Univ., Houghton, MI (United States)

    2014-11-17

    Globally, forest soils store ~two-thirds as much carbon (C) as the atmosphere. Although wood makes up the majority of forest biomass, the importance of wood contributions to soil C pools is unknown. Even with recent advances in the mechanistic understanding of soil processes, integrative studies tracing C input pathways and biological fluxes within and from soils are lacking. Therefore, our research objectives were to assess the impact of different fungal decay pathways (i.e., white-rot versus brown-rot)—in interaction with wood quality, soil temperature, wood location (i.e., soil surface and buried in mineral soil), and soil texture—on the transformation of woody material into soil CO2 efflux, dissolved organic carbon (DOC), and soil C pools. The use of 13C-depleted woody biomass harvested from the Rhinelander, WI free-air carbon dioxide enrichment (Aspen-FACE) experiment affords the unique opportunity to distinguish the wood-derived C from other soil C fluxes and pools. We established 168 treatment plots across six field sites (three sand and three loam textured soil). Treatment plots consisted of full-factorial design with the following treatments: 1. Wood chips from elevated CO2, elevated CO2 + O3, or ambient atmosphere AspenFACE treatments; 2. Inoculated with white rot (Bjerkandera adusta) or brown rot (Gloeophyllum sepiarium) pure fungal cultures, or the original suite of endemic microbial community on the logs; and 3. Buried (15cm in soil as a proxy for coarse roots) or surface applied wood chips. We also created a warming treatment using open-topped, passive warming chambers on a subset of the above treatments. Control plots with no added wood (“no chip control”) were incorporated into the research design. Soils were sampled for initial δ13C values, CN concentrations, and bulk density. A subset of plots were instrumented with lysimeters for sampling soil water and temperature data

  12. Stabilizing Niger

    DEFF Research Database (Denmark)

    Hahonou, Eric Komlavi

    international intervention in Niger. Their main objective is to secure their own strategic, economic and political interests by strengthening the Nigerien authorities through direct intervention and capacity building activities. For western states reinforcing state security institutions and stabilizing elite...... rule constitute the only realistic path to defend their own interests. The report suggests that international support of Nigerien security forces could be counter-productive for the re-establishment of state authority and legitimacy in the long-term. Brutal repression and violation of human rights...

  13. Non-bonding interactions and non-covalent delocalization effects play a critical role in the relative stability of group 12 complexes arising from interaction of diethanoldithiocarbamate with the cations of transition metals Zn(II), Cd(II), and Hg(II): a theoretical study.

    Science.gov (United States)

    Bahrami, Homayoon; Farhadi, Saeed; Siadatnasab, Firouzeh

    2016-07-01

    The chelating properties of diethanoldithiocarbamate (DEDC) and π-electron flow from the nitrogen atom to the sulfur atom via a plane-delocalized π-orbital system (quasi ring) was studied using a density functional theory method. The molecular structure of DEDC and its complexes with Zn(II), Cd(II), and Hg(II) were also considered. First, the geometries of this ligand and DEDC-Zn(II), DEDC-Cd(II), and DEDC-Hg(II) were optimized, and the formation energies of these complexes were then calculated based on the electronic energy, or sum of electronic energies, with the zero point energy of each species. Formation energies indicated the DEDC-Zn(II) complex as the most stable complex, and DEDC-Cd(II) as the least stable. Structural data showed that the N1-C2 π-bond was localized in the complexes rather than the ligand, and a delocalized π-bond over S7-C2-S8 was also present. The stability of DEDC-Zn(II), DEDC-Cd(II), and DEDC-Hg(II) complexes increased in the presence of the non-specific effects of the solvent (PCM model), and their relative stability did not change. There was π-electron flow or resonance along N1-C2-S7 and along S7-C2-S8 in the ligand. The π-electron flow or resonance along N1-C2-S7 was abolished when the metal interacted with sulfur atoms. Energy belonging to van der Waals interactions and non-covalent delocalization effects between the metal and sulfur atoms of the ligand was calculated for each complex. The results of nucleus-independent chemical shift (NICS) indicated a decreasing trend as Zn(II) < Cd(II) < Hg(II) for the aromaticity of the quasi-rings. Finally, by ignoring van der Waals interactions and non-covalent delocalization effects between the metal and sulfur atoms of the ligand, the relative stability of the complexes was changed as follows:[Formula: see text] Graphical Abstract Huge electronic cloud localized on Hg(II) in the Hg(II)-DEDC complex.

  14. Solvent-dependent dihydrogen/dihydride stability for [Mo(CO)(Cp*)H(2)(PMe(3))(2)](+)[BF(4)](-) determined by multiple solvent...anion...cation non-covalent interactions.

    Science.gov (United States)

    Dub, Pavel A; Belkova, Natalia V; Filippov, Oleg A; Daran, Jean-Claude; Epstein, Lina M; Lledós, Agustí; Shubina, Elena S; Poli, Rinaldo

    2010-01-04

    Low-temperature (200 K) protonation of [Mo(CO)(Cp*)H(PMe(3))(2)] (1) by Et(2)OHBF(4) gives a different result depending on a subtle solvent change: The dihydrogen complex [Mo(CO)(Cp*)(eta(2)-H(2))(PMe(3))(2)](+) (2) is obtained in THF, whereas the tautomeric classical dihydride [Mo(CO)(Cp*)(H)(2)(PMe(3))(2)](+) (3) is the only observable product in dichloromethane. Both products were fully characterised (nu(CO) IR; (1)H, (31)P, (13)C NMR spectroscopies) at low temperature; they lose H(2) upon warming to 230 K at approximately the same rate (ca. 10(-3) s(-1)), with no detection of the non-classical form in CD(2)Cl(2), to generate [Mo(CO)(Cp*)(FBF(3))(PMe(3))(2)] (4). The latter also slowly decomposes at ambient temperature. One of the decomposition products was crystallised and identified by X-ray crystallography as [Mo(CO)(Cp*)(FHFBF(3))(PMe(3))(2)] (5), which features a neutral HF ligand coordinated to the transition metal through the F atom and to the BF(4) (-) anion through a hydrogen bond. The reason for the switch in relative stability between 2 and 3 was probed by DFT calculations based on the B3LYP and M05-2X functionals, with inclusion of anion and solvent effects by the conductor-like polarisable continuum model and by explicit consideration of the solvent molecules. Calculations at the MP4(SDQ) and CCSD(T) levels were also carried out for calibration. The calculations reveal the key role of non-covalent anion-solvent interactions, which modulate the anion-cation interaction ultimately altering the energetic balance between the two isomeric forms.

  15. 小黑麦基因型与环境互作效应及产量稳定性分析%ANALYSIS ON GENOTYPE × ENVIRONMENT INTERACTIONS AND YIELD STABILITY OF TRITICALE

    Institute of Scientific and Technical Information of China (English)

    柴守玺; 常磊; 杨蕊菊; 杨德龙; 程宏波

    2011-01-01

    Genotype × environment interactions ( G × E) and grain yield stability of 26 spring triticale eultivars (lines)were analyzed using GGE biplot (genotype main effects plus genotype × environment interaction) model under different water supply conditions and locations in the alpine farming-pastoral ecotone of Northwest China. Results showed that average grain yield of triticale under natural drought conditions was 1805.5 kg/hm2, increased by 64.5% compared with common wheat control cultivar , and the average yield under irrigation condition was 7196. 1 kg/hm2, increased by 67.2% compared with control. Extremely significant differences were observed among genotypes, environments and G × E. The effects of environments and the G × E on the yield were larger than that of the genotypes, which were up to 25.9 times and 2. 1 times compared to the effect of genotype, respectively. The yield stability, water sensitivity and ecological adaptability of different genotypes showed considerable great difference. The genotypes with strong drought resistance accounted for 7.7% of total tested genotypes of triticale, the genotypes with high yield, good stability and wide adaptability were 15.4% of total tested genotypes. However, some genotypes had specific adaptability to the limited environments, and seven genotypes adapted to drought condition and the nine genotypes adapted to sufficient irrigation condition were selected or suggested.%选用26个小黑麦品种(系),在西北高寒农牧交错区的不同试点和供水条件下,利用GGE双标图法研究了小黑麦基因型与环境互作效应以及稳产性.结果表明:在自然干旱条件下,小黑麦平均籽粒产量为1805.5 ks/hm2,较普通小麦对照增产54.6%;在灌水条件下,小黑麦平均产量为7196.1 kg/hm2,较对照增产67.2%.基因型间、环境间及G×E存在着极显著的差异,环境和G×E对产量的影响远大于基因型,分别为基因型效应的25.9倍和2.1倍.不同小黑麦

  16. Density functional theory and atoms-in-molecule study on the role of two-electron stabilizing interactions in retro Diels-Alder reaction of cycloadducts derived from substituted cyclopentadiene and p-benzoquinone.

    Science.gov (United States)

    Patil, Mahendra P; Sunoj, Raghavan B

    2006-11-07

    A systematic investigation on the cycloreversion reaction of the cycloadduct formed between substituted cyclopentadiene and p-benzoquinone (1-19) is reported at the B3LYP/6-311+G**//B3LYP/6-31G* level of theory. The computed activation barrier exhibits a fairly high sensitivity to the nature of substituents at the C7-position. Gibbs free energy of activation for 1 and 19 are found to be 20.3 and 30.1 kcal mol(-1), respectively, compared to 7, which is estimated to be 24.7 kcal mol(-1). Quantitative analysis of the electronic effects operating in both the cycloadduct as well as the corresponding transition state for the retro Diels-Alder (rDA) reaction performed using the natural bond orbital (NBO) and atoms in molecule (AIM) methods have identified important two-electron stabilizing interactions. Among four major delocalizations, sigma(C7-X) to sigma*(C1-C5) [and to sigma*(C2-C6)] is identified as the key contributing factor responsible for ground state C1-C5 bond elongation, which in turn is found to be crucial in promoting the rDA reaction. A good correlation between the population of antibonding orbital [sigma*(C1-C5)] of the ground state cycloadduct and Gibbs free energy of activation is observed. The importance of factors that modulate ground state structural features in controlling the energetics of rDA reaction is described.

  17. Stabilizing brokerage.

    Science.gov (United States)

    Stovel, Katherine; Golub, Benjamin; Milgrom, Eva M Meyersson

    2011-12-27

    A variety of social and economic arrangements exist to facilitate the exchange of goods, services, and information over gaps in social structure. Each of these arrangements bears some relationship to the idea of brokerage, but this brokerage is rarely like the pure and formal economic intermediation seen in some modern markets. Indeed, for reasons illuminated by existing sociological and economic models, brokerage is a fragile relationship. In this paper, we review the causes of instability in brokerage and identify three social mechanisms that can stabilize fragile brokerage relationships: social isolation, broker capture, and organizational grafting. Each of these mechanisms rests on the emergence or existence of supporting institutions. We suggest that organizational grafting may be the most stable and effective resolution to the tensions inherent in brokerage, but it is also the most institutionally demanding.

  18. STABILIZATION PONDS

    Directory of Open Access Journals (Sweden)

    Sunarsih Sunarsih

    2013-01-01

    Full Text Available This paper presents a model for natural syst ems used in Wastewater Treatment Plant (WWTP Sewon Bantul. The model is m odeling development, derived from the physical and biochemical phenomena involved in the biological treatment process. The numerical solution of the resulting on 13 simultaneous systems of nonlinear equations by the Quasi_Newton. Data validation is measured by facultative pond at the inlet and outlet of the pond to the concentration of b acteria, algae, zooplankton, organic matter, detritus, organic nitrogen, NH3, organi c phosphor, dissolved phosphorus, Dissolved Oxygen (DO, total coliform, faecal coliform and Biochemical Oxygen Demand (BOD. A simulation model is presented to predict performance regime steady state of domestic wastewater treatment facultative stabilization pond. The high degree of significant of at least 10% indicates that the effluent parameters can be reasonably accurately predicted.

  19. Genotype adaptability and stability

    Directory of Open Access Journals (Sweden)

    Dimitrijević Miodrag

    2000-01-01

    Full Text Available One of the primary concerns in breeding programs is a small genotype reaction to environmental factor variation for better usage of yield genetic potential. Particularly if one takes in consideration that yield could van greatly because of more and more variable meteorological conditions. Studies conducted to observe genotype and environmental relations relay on numerous mathematical models, but genotype behavior in various ecological conditions is not, still, precisely defined Major sources of variation influencing genotype behavior in different environments are genotype/environment interaction, genetic background and environmental conditions. These factors could play an important role in establishing growth regions for maximal realization of genotype genetic potential, as well as in selection of genotypes having better response to complex requirements of particular growth region. Stability, the genotype ability to perform high, uniform yield no meter of different environmental conditions, and adaptability, genotype ability to give uniform yield in a different environmental conditions, are two common terms used to define genotype reaction in a consequence of environmental changes. Most of the models dealing with stability and adaptability are based on variation sources appearing under the influence of treatment, multivariate effects and residue. No meter which statistical model is used for GE interaction estimation, there is an opinion that no solid proof for the existence of stable genotypes obtained in breeding programs, which make some space for further investigations. There are still questions to answer dealing with definitions, sources of variation, usage value of existent models and interpretation of the results. .

  20. The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xiayu Wu

    2016-06-01

    Full Text Available Folate-mediated one-carbon metabolism (FMOCM is linked to DNA synthesis, methylation, and cell proliferation. Vitamin B6 (B6 is a cofactor, and genetic polymorphisms of related key enzymes, such as serine hydroxymethyltransferase (SHMT, methionine synthase reductase (MTRR, and methionine synthase (MS, in FMOCM may govern the bioavailability of metabolites and play important roles in the maintenance of genomic stability and cell viability (GSACV. To evaluate the influences of B6, genetic polymorphisms of these enzymes, and gene–nutrient interactions on GSACV, we utilized the cytokinesis-block micronucleus assay (CBMN and PCR-restriction fragment length polymorphism (PCR-RFLP techniques in the lymphocytes from female breast cancer cases and controls. GSACV showed a significantly positive correlation with B6 concentration, and 48 nmol/L of B6 was the most suitable concentration for maintaining GSACV in vitro. The GSACV indexes showed significantly different sensitivity to B6 deficiency between cases and controls; the B6 effect on the GSACV variance contribution of each index was significantly higher than that of genetic polymorphisms and the sample state (tumor state. SHMT C1420T mutations may reduce breast cancer susceptibility, whereas MTRR A66G and MS A2756G mutations may increase breast cancer susceptibility. The role of SHMT, MS, and MTRR genotype polymorphisms in GSACV is reduced compared with that of B6. The results appear to suggest that the long-term lack of B6 under these conditions may increase genetic damage and cell injury and that individuals with various genotypes have different sensitivities to B6 deficiency. FMOCM metabolic enzyme gene polymorphism may be related to breast cancer susceptibility to a certain extent due to the effect of other factors such as stress, hormones, cancer therapies, psychological conditions, and diet. Adequate B6 intake may be good for maintaining genome health and preventing breast cancer.

  1. Ecological stability in response to warming

    NARCIS (Netherlands)

    Fussmann, Katarina E.; Schwarzmueller, Florian; Brose, Ulrich; Jousset, Alexandre; Rall, Bjoern C.

    2014-01-01

    That species' biological rates including metabolism, growth and feeding scale with temperature is well established from warming experiments(1). The interactive influence of these changes on population dynamics, however, remains uncertain. As a result, uncertainty about ecological stability in respon

  2. Ecological stability in response to warming

    NARCIS (Netherlands)

    Fussmann, Katarina E.; Schwarzmueller, Florian; Brose, Ulrich; Jousset, Alexandre|info:eu-repo/dai/nl/370632656; Rall, Bjoern C.

    That species' biological rates including metabolism, growth and feeding scale with temperature is well established from warming experiments(1). The interactive influence of these changes on population dynamics, however, remains uncertain. As a result, uncertainty about ecological stability in

  3. Mechanical stability of bipolar spindle assembly

    CERN Document Server

    Malgaretti, Paolo

    2016-01-01

    Assembly and stability of mitotic spindle is governed by the interplay of various intra-cellular forces, e.g. the forces generated by motor proteins by sliding overlapping anti-parallel microtubules (MTs) polymerized from the opposite centrosomes, the interaction of kinetochores with MTs, and the interaction of MTs with the chromosomes arms. We study the mechanical behavior and stability of spindle assembly within the framework of a minimal model which includes all these effects. For this model, we derive a closed--form analytical expression for the force acting between the centrosomes as a function of their separation distance and we show that an effective potential can be associated with the interactions at play. We obtain the stability diagram of spindle formation in terms of parameters characterizing the strength of motor sliding, repulsive forces generated by polymerizing MTs, and the forces arising out of interaction of MTs with kinetochores. The stability diagram helps in quantifying the relative effec...

  4. Qualitative stability of nonlinear networked systems

    OpenAIRE

    Angulo, Marco Tulio; Slotine, Jean-Jacques

    2016-01-01

    In many large systems, such as those encountered in biology or economics, the dynamics are nonlinear and are only known very coarsely. It is often the case, however, that the signs (excitation or inhibition) of individual interactions are known. This paper extends to nonlinear systems the classical criteria of linear sign stability introduced in the 70's, yielding simple sufficient conditions to determine stability using only the sign patterns of the interactions.

  5. Enhanced colloidal stability of hydroxyapatite

    Science.gov (United States)

    Borum, La Rhonda Terese

    Hydroxyapatite, Ca10(PO4)6(OH) 2 is the most thermodynamically stable calcium phosphate in physiological environments. Hence, it is the main inorganic mineral found in bone and teeth. Its colloidal stability, however, is poor because hydroxyapatite (HAp) particles exhibit sediment formation upon standing at short time periods, where agglomerates form and lead to non-homogeneous suspensions. Surface modification is a promising method to tailor the colloidal stability of hydroxyapatite for biomaterial applications. Three techniques to modify the HAp surface and enhance the colloidal stability of HAp were investigated. Modified particles were characterized by methods sensitive to surface chemistry changes, such as sedimentation studies, diffuse reflectance Fourier transform infrared spectroscopy (DRIFT), Brunauer-Emmett-Teller (BET) surface area, and electrophoresis. Sedimentation studies demonstrated how effective each technique was in improving the colloidal stability of hydroxyapatite particles. Electrophoresis provided information on electrostatic interactions within each system. The first technique entailed an esterification reaction of the HAp surface with dodecyl alcohol at elevated temperatures. DRIFT results showed that dodecyl groups from the alcohol replaced acidic hydroxyl and phosphate sites on the HAp surface, giving rise to enhanced colloidal stability through steric interactions in ethanol suspensions. TGA curves gave insight to the degree of esterification for the esterified particles. Higher reaction temperatures give rise to a higher degree of esterification resulting in better colloidal stability. The second technique applied a silica coating on the HAp surface by the hydrolysis of tetraethyl orthosilicate in ethanol. Silica was coated onto the HAp surface at 5--75 wt% loading amounts. A combination of acid dissolution and x-ray diffraction (XRD), along with BET showed that the silica coating is complete at 50 wt% silica loading. The silica coating

  6. Role of the Sulfonium Center in Determining the Ligand Specificity of Human S-Adenosylmethionine Decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Bale, Shridhar; Brooks, Wesley; Hanes, Jeremiah W.; Mahesan, Arnold M.; Guida, Wayne C.; Ealick, Steven E.; (Moffitt); (Cornell)

    2009-08-13

    S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway. Inhibition of this pathway and subsequent depletion of polyamine levels is a viable strategy for cancer chemotherapy and for the treatment of parasitic diseases. Substrate analogue inhibitors display an absolute requirement for a positive charge at the position equivalent to the sulfonium of S-adenosylmethionine. We investigated the ligand specificity of AdoMetDC through crystallography, quantum chemical calculations, and stopped-flow experiments. We determined crystal structures of the enzyme cocrystallized with 5{prime}-deoxy-5{prime}-dimethylthioadenosine and 5{prime}-deoxy-5{prime}-(N-dimethyl)amino-8-methyladenosine. The crystal structures revealed a favorable cation-{pi} interaction between the ligand and the aromatic side chains of Phe7 and Phe223. The estimated stabilization from this interaction is 4.5 kcal/mol as determined by quantum chemical calculations. Stopped-flow kinetic experiments showed that the rate of the substrate binding to the enzyme greatly depends on Phe7 and Phe223, thus supporting the importance of the cation-{pi} interaction.

  7. Linearity stabilizes discrete breathers

    Indian Academy of Sciences (India)

    T R Krishna Mohan; Surajit Sen

    2011-11-01

    The study of the dynamics of 1D chains with both harmonic and nonlinear interactions, as in the Fermi–Pasta–Ulam (FPU) and related problems, has played a central role in efforts to identify the broad consequences of nonlinearity in these systems. Here we study the dynamics of highly localized excitations, or discrete breathers, which are known to be initiated by the quasistatic stretching of bonds between adjacent particles. We show via dynamical simulations that acoustic waves introduced by the harmonic term stabilize the discrete breather by suppressing the breather’s tendency to delocalize and disperse. We conclude that the harmonic term, and hence acoustic waves, are essential for the existence of localized breathers in these systems.

  8. Flotation control -- A multivariable stabilizer

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, J.H.; Henning, R.G.D.; Hulbert, D.G.; Craig, I.K. [Mintek, Randburg (South Africa)

    1995-12-31

    This paper presents a stabilizing controller for flotation plants which uses a quasi-multivariable technique. The controller monitors all the levels in the plant, and by anticipating interactions between various parts of the plant, is able to stabilize the plant far more successfully than the normal plant control. Once stabilizing control has been achieved, optimization of the process becomes easier and more sustainable. An estimate of the improvement in metallurgical performance is made and a singular value analysis was conducted to verify that the multivariable algorithm will theoretically control better than a collection of individual PID loops. Metallurgical results are presented to show that the improvements are attainable in practice. Control by the Mintek algorithm was alternated with normal plant control, to show that the improvements are statistically significant.

  9. Nuclear structure far from stability

    CERN Document Server

    Vretenar, D

    2005-01-01

    Modern nuclear structure theory is rapidly evolving towards regions of exotic short-lived nuclei far from stability, nuclear astrophysics applications, and bridging the gap between low-energy QCD and the phenomenology of finite nuclei. The principal objective is to build a consistent microscopic theoretical framework that will provide a unified description of bulk properties, nuclear excitations and reactions. Stringent constraints on the microscopic approach to nuclear dynamics, effective nuclear interactions, and nuclear energy density functionals, are obtained from studies of the structure and stability of exotic nuclei with extreme isospin values, as well as extended asymmetric nucleonic matter. Recent theoretical advances in the description of structure phenomena in exotic nuclei far from stability are reviewed.

  10. Nuclear structure far from stability

    Science.gov (United States)

    Vretenar, D.

    2005-04-01

    Modern nuclear structure theory is rapidly evolving towards regions of exotic shortlived nuclei far from stability, nuclear astrophysics applications, and bridging the gap between low-energy QCD and the phenomenology of finite nuclei. The principal objective is to build a consistent microscopic theoretical framework that will provide a unified description of bulk properties, nuclear excitations and reactions. Stringent constraints on the microscopic approach to nuclear dynamics, effective nuclear interactions, and nuclear energy density functionals, are obtained from studies of the structure and stability of exotic nuclei with extreme isospin values, as well as extended asymmetric nucleonic matter. Recent theoretical advances in the description of structure phenomena in exotic nuclei far from stability are reviewed.

  11. Stability Limits in Resonant Planetary Systems

    CERN Document Server

    Barnes, Rory

    2007-01-01

    The relationship between the boundaries for Hill and Lagrange stability in orbital element space is modified in the case of resonantly interacting planets. Hill stability requires the ordering of the planets to remain constant while Lagrange stability also requires all planets to remain bound to the central star. The Hill stability boundary is defined analytically, but no equations exist to define the Lagrange boundary, so we perform numerical experiments to estimate the location of this boundary. To explore the effect of resonances, we consider orbital element space near the conditions in the HD 82943 and 55 Cnc systems. Previous studies have shown that, for non-resonant systems, the two stability boundaries are nearly coincident. However the Hill stability formula are not applicable to resonant systems, and our investigation shows how the two boundaries diverge in the presence of a mean-motion resonance, while confirming that the Hill and Lagrange boundaries are similar otherwise. In resonance the region of...

  12. Effects of core muscle stability training on the weight distribution and stability of the elderly

    OpenAIRE

    Kang, Kwon-Young

    2015-01-01

    [Purpose] This study investigated the effects of core muscle stability training on the weight distribution and stability of the elderly. [Subjects and Methods] Thirty elderly persons were randomly divided into an experimental group which performed core strengthening exercises, and a control group which performed standard strengthening exercises for 8 weeks. A Tetrax Interactive Balance System was used to evaluate the weight distribution index (WDI) and the stability index (SI). [Results] The ...

  13. Plutonium inventories for stabilization and stabilized materials

    Energy Technology Data Exchange (ETDEWEB)

    Williams, A.K.

    1996-05-01

    The objective of the breakout session was to identify characteristics of materials containing plutonium, the need to stabilize these materials for storage, and plans to accomplish the stabilization activities. All current stabilization activities are driven by the Defense Nuclear Facilities Safety Board Recommendation 94-1 (May 26, 1994) and by the recently completed Plutonium ES&H Vulnerability Assessment (DOE-EH-0415). The Implementation Plan for accomplishing stabilization of plutonium-bearing residues in response to the Recommendation and the Assessment was published by DOE on February 28, 1995. This Implementation Plan (IP) commits to stabilizing problem materials within 3 years, and stabilizing all other materials within 8 years. The IP identifies approximately 20 metric tons of plutonium requiring stabilization and/or repackaging. A further breakdown shows this material to consist of 8.5 metric tons of plutonium metal and alloys, 5.5 metric tons of plutonium as oxide, and 6 metric tons of plutonium as residues. Stabilization of the metal and oxide categories containing greater than 50 weight percent plutonium is covered by DOE Standard {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides{close_quotes} December, 1994 (DOE-STD-3013-94). This standard establishes criteria for safe storage of stabilized plutonium metals and oxides for up to 50 years. Each of the DOE sites and contractors with large plutonium inventories has either started or is preparing to start stabilization activities to meet these criteria.

  14. On hovercraft overwater heave stability

    Science.gov (United States)

    Hinchey, M. J.; Sullivan, P. A.

    1993-05-01

    The dynamic heave stability of an air cushion vehicle or hovercraft hovering over deep water without forward motion is investigated analytically. The principal feature of the analysis is the modeling of the motion of the water surface beneath the cushion caused by fluctuations in the pressure of the cushion or cavity air. This surface motion interacts with the vehicle dynamics by modulating both the volume and exit flow area of the cushion. For analytical simplicity, the geometry chosen for study is a 2D section of a rigid wall plenum chamber; this enables exploitation of classical linear wave formulas developed by Lamb for the surface motion generated by a spatially uniform surface pressure oscillating sinusoidally in time. To assess stability characteristics, the Nyquist criterion is applied to the linearized equations. Results are presented for two cases: one is representative of a small test vehicle, and the other of a large ice-breaking platform. They show that the water surface motion significantly affects stability through both of the proposed mechanisms, with cushion exit flow area modulation usually being more important. A feature of the results is that as the weight of a vehicle decreases many stability transitions occur. This suggests that simple guidelines for avoiding instability may not exist, so that stability augmentation devices may be required for vehicles designed to hover for extended periods over water.

  15. RESEARCH ON THE HYDRODYNAMIC STABILITY OF FIBRE SUSPENSIONS

    Institute of Scientific and Technical Information of China (English)

    You Zhen-jiang

    2003-01-01

    The stability of wall-bounded fibre suspensions was studied. The linear stability analysis was performed applying the flow stability theory and slender-body theory. The results of numerical analysis show that fibres and their hydrodynamic interactions reinforce the flow stability. Investigation of fibre orientation and vorticity in the suspension revealed the mechanisms behind the instability. Drag reduction properties in the transition regime were also presented. The experiments using dye emission and PIV techniques verified theoretical results.

  16. Sequential interactions of silver-silica nanocomposite (Ag-SiO2NC) with cell wall, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple antibiotic-resistant bacterium

    Digital Repository Service at National Institute of Oceanography (India)

    Anas, A.; Jiya, J.; Rameez, M.J.; Anand, P.B.; Anantharaman, M.R.; Nair, S.

    The study was carried out to understand the effect of silver-silica nanocomposite (Ag-SiO sub(2)NC) on the cell wall integrity, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple drug-resistant bacterium Bacterial sensitivity...

  17. Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E2P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed; Christensen, Søren Brøgger

    2011-01-01

    anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with ¿-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma...... that modulates interaction of cardiac glycosides with the sodium pump....

  18. Determination of stability constants of tauro- and glyco-conjugated bile salts with the negatively charged sulfobutylether-β-cyclodextrin: comparison of affinity capillary electrophoresis and isothermal titration calorimetry and thermodynamic analysis of the interaction

    DEFF Research Database (Denmark)

    Holm, René; Østergaard, Jesper; Schönbeck, Jens Christian Sidney;

    2014-01-01

    The aim of the present work was to investigate the interaction between bile salts present in the intestine of man, dog and rat with the negatively charged cyclodextrin (CD), sulfobutylether-β-cyclodextrin (SBEβCD). The interactions between bile salts and CDs are of importance for the release of C...

  19. Stabilizing token schemes for population protocols

    CERN Document Server

    Canepa, Davide

    2008-01-01

    In this paper we address the stabilizing token circulation and leader election problems in population protocols model augmented with oracles. Population protocols is a recent model of computation that captures the interactions of biological systems. In this model emergent global behavior is observed while anonymous finite-state agents(nodes) perform local peer interactions. Uniform self-stabilizing leader election or token circulation are impossible in such systems without additional assumptions. Therefore, the classical model has been augmented with the eventual leader detector, $\\Omega?$, that eventually detects the presence or the absence of a leader. In this work we propose some impossibility results related to self-stabilizing implementation of leader election and token circulation in this model. Then we propose deterministic and probabilistic self-stabilizing solutions for token circulation and leader election for various topologies (chains, trees and arbitrary networks). Additionally, we prove the nece...

  20. Relationship Stability through Lenses of Complexity

    Science.gov (United States)

    Karakurt, Gunnur

    2012-01-01

    Research on relationship stability usually considers the effect of couple outcomes and individual differences on relationship stability in isolation from each other. These separate bodies of research often lead to inconsistent results. In order to better understand relationship stability and explain inconsistencies in the literature, it is important to investigate more complex models that integrate couple outcomes and behaviors with individual differences. Motivated by these considerations, we examined the complex interplay between personal characteristics, couple interactions, and relationship stability. In particular, we investigated the relationships among investment model, big five personality traits, attachment dimensions, relationship factors and relationship stability. Participants of this study included 162 individuals (Female N=117) who are currently in a relationship from a large Midwestern university campus. Analyses were conducted using Structural Equation Modeling. Examination of the structural path parameters indicated that attachment had significant direct effect on personality, relationship factors, and relationship stability. Personality also had a significant direct effect on relationship stability. Finally personality had no direct effect on relationship factors and relationship factors had no direct effect on relationship stability. These results suggest that the effect of personality on relationship stability is direct, rather than being mediated by relationship factors. PMID:23124824

  1. On Stabilization in Herman’s Algorithm

    DEFF Research Database (Denmark)

    Kiefer, Stefan; Murawski, Andrzej S.; Ouaknine, Joël

    2011-01-01

    of 0.64N2 on the expected stabilization time, improving on previous upper bounds and reducing the gap with the best existing lower bound. We also introduce an asynchronous version of the protocol, showing a similar O(N2) convergence bound in this case. Assuming that errors arise from the corruption......Herman’s algorithm is a synchronous randomized protocol for achieving self-stabilization in a token ring consisting of N processes. The interaction of tokens makes the dynamics of the protocol very difficult to analyze. In this paper we study the expected time to stabilization in terms...... of the initial configuration. It is straightforward that the algorithm achieves stabilization almost surely from any initial configuration, and it is known that the worst-case expected time to stabilization (with respect to the initial configuration) is Θ(N2). Our first contribution is to give an upper bound...

  2. Stability of Dolos Slopes

    DEFF Research Database (Denmark)

    Brorsen, Michael; Burcharth, Hans F.; Larsen, Torben

    The stability of dolos armour blocks against wave attack has been investigated in wave model studies.......The stability of dolos armour blocks against wave attack has been investigated in wave model studies....

  3. On Stabilization in Herman’s Algorithm

    DEFF Research Database (Denmark)

    Kiefer, Stefan; Murawski, Andrzej S.; Ouaknine, Joël

    2011-01-01

    Herman’s algorithm is a synchronous randomized protocol for achieving self-stabilization in a token ring consisting of N processes. The interaction of tokens makes the dynamics of the protocol very difficult to analyze. In this paper we study the expected time to stabilization in terms...... of some number k of bits, where k is fixed independently of the size of the ring, we show that the expected time to stabilization is O(N). This reveals a hitherto unknown and highly desirable property of Herman’s algorithm: it recovers quickly from bounded errors. We also show that if the initial...

  4. Modularity and stability in ecological communities

    Science.gov (United States)

    Grilli, Jacopo; Rogers, Tim; Allesina, Stefano

    2016-01-01

    Networks composed of distinct, densely connected subsystems are called modular. In ecology, it has been posited that a modular organization of species interactions would benefit the dynamical stability of communities, even though evidence supporting this hypothesis is mixed. Here we study the effect of modularity on the local stability of ecological dynamical systems, by presenting new results in random matrix theory, which are obtained using a quaternionic parameterization of the cavity method. Results show that modularity can have moderate stabilizing effects for particular parameter choices, while anti-modularity can greatly destabilize ecological networks. PMID:27337386

  5. Interaction of L-alanyl-L-valine and L-valyl-L-alanine with organic vapors: thermal stability of clathrates, sorption capacity and the change in the morphology of dipeptide films.

    Science.gov (United States)

    Ziganshin, Marat A; Gubina, Nadezhda S; Gerasimov, Alexander V; Gorbatchuk, Valery V; Ziganshina, Sufia A; Chuklanov, Anton P; Bukharaev, Anastas A

    2015-08-21

    The strong effect of the amino acid sequence in L-alanyl-L-valine and L-valyl-L-alanine on their sorption properties toward organic compounds and water, and the thermal stability of the inclusion compounds of these dipeptides have been found. Generally, L-valyl-L-alanine has a greater sorption capacity for the studied compounds, but the thermal stability of the L-alanyl-L-valine clathrates is higher. Unusual selectivity of L-valyl-L-alanine for vapors of few chloroalkanes was observed. The correlation between the change in the surface morphology of thin film of dipeptides and stoichiometry of their clathrates with organic compounds was found. This discovery may be used to predict the influence of vapors on the morphology of films of short-chain oligopeptides.

  6. K stability and stability of chiral ring

    CERN Document Server

    Collins, Tristan C; Yau, Shing-Tung

    2016-01-01

    We define a notion of stability for chiral ring of four dimensional N=1 theory by introducing test chiral rings and generalized a maximization. We conjecture that a chiral ring is the chiral ring of a superconformal field theory if and only if it is stable. We then study N=1 field theory derived from D3 branes probing a three-fold singularity X, and show that the K stability which implies the existence of Ricci-flat conic metric on X is equivalent to the stability of chiral ring of the corresponding field theory.

  7. Stability of parallel flows

    CERN Document Server

    Betchov, R

    2012-01-01

    Stability of Parallel Flows provides information pertinent to hydrodynamical stability. This book explores the stability problems that occur in various fields, including electronics, mechanics, oceanography, administration, economics, as well as naval and aeronautical engineering. Organized into two parts encompassing 10 chapters, this book starts with an overview of the general equations of a two-dimensional incompressible flow. This text then explores the stability of a laminar boundary layer and presents the equation of the inviscid approximation. Other chapters present the general equation

  8. An equivalent condition for stability properties of Lotka-Volterra systems

    Energy Technology Data Exchange (ETDEWEB)

    Chu Tianguang [Intelligent Control Laboratory, Center for Systems and Control, School of Engineering, Peking University, Beijing 100871 (China)], E-mail: chutg@pku.edu.cn

    2007-08-20

    We give a solvable Lie algebraic condition for the equivalence of four typical stability notions (asymptotic stability, D-stability, total stability, and Volterra-Lyapunov stability) concerning Lotka-Volterra systems. Our approach makes use of the decomposition of the interaction matrix into symmetric and skew-symmetric parts, which may be related to the cooperative and competitive interaction pattern of a Lotka-Volterra system. The present result covers a known condition and can yield a larger set of interaction matrices for equivalence of the stability properties.

  9. Stability Analysis of Ecomorphodynamic Equations

    CERN Document Server

    Bärenbold, Fabian; Perona, Paolo

    2014-01-01

    Although riparian vegetation is present in or along many water courses of the world, its active role resulting from the interaction with flow and sediment processes has only recently become an active field of research. Especially, the role of vegetation in the process of river pattern formation has been explored and demonstrated mostly experimentally and numerically until now. In the present work, we shed light on this subject by performing a linear stability analysis on a simple model for riverbed vegetation dynamics coupled with the set of classical river morphodynamic equations. The vegetation model only accounts for logistic growth, local positive feedback through seeding and resprouting, and mortality by means of uprooting through flow shear stress. Due to the simplicity of the model, we can transform the set of equations into an eigenvalue problem and assess the stability of the linearized equations when slightly perturbated away from a spatially homogeneous solution. If we couple vegetation dynamics wi...

  10. Extrasolar planet interactions

    Science.gov (United States)

    Barnes, Rory; Greenberg, Richard

    2008-05-01

    The dynamical interactions of planetary systems may be a clue to their formation histories. Therefore, the distribution of these interactions provides important constraints on models of planet formation. We focus on each system's apsidal motion and proximity to dynamical instability. Although only 25 multiple planet systems have been discovered to date, our analyses in these terms have revealed several important features of planetary interactions. 1) Many systems interact such that they are near the boundary between stability and instability. 2) Planets tend to form such that at least one planet's eccentricity periodically drops to near zero. 3) Mean-motion resonant pairs would be unstable if not for the resonance. 4) Scattering of approximately equal mass planets is unlikely to produce the observed distribution of apsidal behavior. 5) Resonant interactions may be identified through calculating a system's proximity to instability, regardless of knowledge of angles such as mean longitude and longitude of periastron (e.g. GJ 317 b and c are probably in a 4:1 resonance). These properties of planetary systems have been identified through calculation of two parameters that describe the interaction. The apsidal interaction can be quantified by determining how close a planet is to an apsidal separatrix (a boundary between qualitatively different types of apsidal oscillations, e.g. libration or circulation of the major axes). This value can be calculated through short numerical integrations. The proximity to instability can be measured by comparing the observed orbital elements to an analytic boundary that describes a type of stability known as Hill stability. We have set up a website dedicated to presenting the most up-to-date information on dynamical interactions: http://www.lpl.arizona.edu/~rory/research/xsp/dynamics.

  11. Extrasolar Planet Interactions

    CERN Document Server

    Barnes, Rory

    2008-01-01

    The dynamical interactions of planetary systems may be a clue to their formation histories. Therefore, the distribution of these interactions provides important constraints on models of planet formation. We focus on each system's apsidal motion and proximity to dynamical instability. Although only ~25 multiple planet systems have been discovered to date, our analyses in these terms have revealed several important features of planetary interactions. 1) Many systems interact such that they are near the boundary between stability and instability. 2) Planets tend to form such that at least one planet's eccentricity periodically drops to near zero. 3) Mean-motion resonant pairs would be unstable if not for the resonance. 4) Scattering of approximately equal mass planets is unlikely to produce the observed distribution of apsidal behavior. 5) Resonant interactions may be identified through calculating a system's proximity to instability, regardless of knowledge of angles such as mean longitude and longitude of peri...

  12. Stability of Hyperthermophilic Proteins

    DEFF Research Database (Denmark)

    Stiefler-Jensen, Daniel

    cheaper products. One aspect that can have a large impact on the efficiency of an enzyme is its stability. By increasing the enzyme stability production cost and time can be reduced, and consumers will have a better product with longer activity. In the past it was only possible to increasing enzymes...... stability by randomly generate mutants and lengthy screening processes to identify the best new mutants. However, with the increase in available genomic sequences of thermophilic or hyperthermophilic organisms a world of enzymes with intrinsic high stability are now available. As these organisms are adapted...... to life at high temperatures so are their enzymes, as a result the high stability is accompanied by low activity at moderate temperatures. Thus, much effort had been put into decoding the mechanisms behind the high stability of the thermophilic enzymes. The hope is to enable scientist to design enzymes...

  13. Internet Addiction: Stability and Change

    Science.gov (United States)

    Huang, Chiungjung

    2010-01-01

    This longitudinal study examined five indices of stability and change in Internet addiction: structural stability, mean-level stability, differential stability, individual-level stability, and ipsative stability. The study sample was 351 undergraduate students from end of freshman year to end of junior year. Convergent findings revealed stability…

  14. Internet Addiction: Stability and Change

    Science.gov (United States)

    Huang, Chiungjung

    2010-01-01

    This longitudinal study examined five indices of stability and change in Internet addiction: structural stability, mean-level stability, differential stability, individual-level stability, and ipsative stability. The study sample was 351 undergraduate students from end of freshman year to end of junior year. Convergent findings revealed stability…

  15. Triphenylphosphine Stabilized Silver Carboxylates

    Institute of Scientific and Technical Information of China (English)

    Jian Lin HAN; Ying Zhong SHEN; Yi PAN

    2005-01-01

    A series of novel triphenylphosphine stabilized silver carboxylates, potential precursors for CVD growth of ultrafast interconnection link in microelectronic devices, have been prepared and characterized.

  16. Thermal Stability of Otto Fuel Prepolymer

    Science.gov (United States)

    Tompa, Albert S.; Sandagger, Karrie H.; Bryant, William F., Jr.; McConnell, William T.; Lacot, Fernando; Carr, Walter A.

    2000-01-01

    Otto Fuel II contains a nitrate ester, plasticizer, and 2-NDPA as a stabilizer. Otto Fuel with stabilizers from three vendors was investigated by dynamic and isothermal DSC using samples sealed in a glass ampoule and by Isothermal Microcalorimetry (IMC) using 10 gram samples aged at 75 C for 35 days. DSC kinetics did not show differences between the stabilizer; the samples had an activation energy of 36.7 +/- 0.6 kcal/mol. However, IMC analysis was sensitive enough to detect small differences between the stabilizer, namely energy of interaction values of 7 to 14 Joules. DSC controlled cooling and heating at 5 C/min from 30 to -60 to 40 C experiments were similar and showed a crystallization peak at -48 +/- 1 C during cooling, and upon heating there was a glass transition temperature step at approx. -54 +/- 0.5 C and a melting peak at -28 +/- 0.4 C.

  17. Convection and morphological stability during directional solidification

    Science.gov (United States)

    Coriell, Sam R.; Chernov, A. A.; Murray, Bruce T.; Mcfadden, G. B.

    1994-01-01

    For growth of a vicinal face at constant velocity, the effect of anisotropic interface kinetics on morphological stability is calculated for a binary alloy. The dependence of the interface kinetic coefficient on crystallographic orientation is based on the motion and density of steps. Anisotropic kinetics give rise to traveling waves along the crystal-melt interface, and can lead to a significant enhancement of morphological stability. The stability enhancement increases as the orientation approaches a singular orientation and as the solidification velocity increases. Shear flows interact with the traveling waves and, depending on the direction of the flow, may either stabilize or destabilize the interface. Specific calculations are carried out for germanium-silicon alloys.

  18. A Novel C53/LZAP-interacting Protein Regulates Stability of C53/LZAP and DDRGK Domain-containing Protein 1 (DDRGK1) and Modulates NF-κB Signaling*

    OpenAIRE

    Wu, Jianchun; Lei, Guohua; Mei, Mei; Tang, Yi; Li, Honglin

    2010-01-01

    C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-κB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of C53/LZAP and ...

  19. Relativity stability of quantum gas in a weak magnetic field

    Institute of Scientific and Technical Information of China (English)

    Men Fu-Dian; Liu Hui; Fan Zhao-Lan; Zhu Hou-Yu

    2009-01-01

    Based on the analytical expression of relativistic free energy for a weakly interacting Fermi gas in a weak magnetic field,by using the method of quantum statistics,the stability conditions of the system at both high and low temperatures axe given,and the effects of magnetic field and interpaxticle interactions on the stability of the system are analysed. It is shown that at high temperatures,the stability conditions of the system are completely the same,no matter whether it is the ultrarelativistic case or nonrelativistic case. At extremely low temperatures,the mechanical stability conditions of the system show a similar rule through a comparison between the ultrarelativistic case and nonrelativistic case. At the same time,thermal stability of a relativistic Bose gas in a weak magnetic field is discussed,and the influence of the effect of relativity on the thermal stability of the system is investigated.

  20. Control of Collagen Triple Helix Stability by Phosphorylation.

    Science.gov (United States)

    Acevedo-Jake, Amanda M; Ngo, Daniel H; Hartgerink, Jeffrey D

    2017-03-10

    The phosphorylation of the collagen triple helix plays an important role in collagen synthesis, assembly, signaling, and immune response, although no reports detailing the effect this modification has on the structure and stability of the triple helix exist. Here we investigate the changes in stability and structure resulting from the phosphorylation of collagen. Additionally, the formation of pairwise interactions between phosphorylated residues and lysine is examined. In all tested cases, phosphorylation increases helix stability. When charged-pair interactions are possible, stabilization via phosphorylation can play a very large role, resulting inasmuch as a 13.0 °C increase in triple helix stability. Two-dimensional NMR and molecular modeling are used to study the local structure of the triple helix. Our results suggest a mechanism of action for phosphorylation in the regulation of collagen and also expand upon our understanding of pairwise amino acid stabilization of the collagen triple helix.

  1. Yield stability and relationships among stability parameters in faba bean(Vicia faba L.) genotypes

    Institute of Scientific and Technical Information of China (English)

    Tamene; Temesgen; Gemechu; Keneni; Tadese; Sefera; Mussa; Jarso

    2015-01-01

    Sixteen faba bean genotypes were evaluated in 13 environments in Ethiopia during the main cropping season for three years(2009–2011). The objectives of the study were to evaluate the yield stability of the genotypes and the relative importance of different stability parameters for improving selection in faba bean. The study was conducted using a randomized complete block design with four replications. G × E interaction and yield stability were estimated using 17 different stability parameters. Pooled analysis of variance for grain yield showed that the main effects of both genotypes and environments, and the interaction effect, were highly significant(P ≤ 0.001) and(P ≤ 0.01), respectively. The environment main effect accounted for 89.27% of the total yield variation, whereas genotype and G × E interaction effects accounted for 2.12% and 3.31%, respectively.Genotypic superiority index(Pi) and FT3 were found to be very informative for selecting both high-yielding and stable faba bean genotypes. Twelve of the 17 stability parameters,including CVi, RS, α, λ, S2 di, bi, S(2)i, Wi, σ2i, EV, P59, and ASV, were influenced simultaneously by both yield and stability. They should accordingly be used as complementary criteria to select genotypes with high yield and stability. Although none of the varieties showed consistently superior performance across all environments, the genotype EK 01024-1-2ranked in the top third of the test entries in 61.5% of the test environments and was identified as the most stable genotype, with type I stability. EK 01024-1-2 also showed a17.0% seed size advantage over the standard varieties and was released as a new variety in2013 for wide production and named "Gora". Different stability parameters explained genotypic performance differently, irrespective of yield performance. It was accordingly concluded that assessment of G × E interaction and yield stability should not be based on a single or a few stability parameters but rather

  2. Yield stability and relationships among stability parameters in faba bean (Vicia faba L. genotypes

    Directory of Open Access Journals (Sweden)

    Tamene Temesgen

    2015-06-01

    Full Text Available Sixteen faba bean genotypes were evaluated in 13 environments in Ethiopia during the main cropping season for three years (2009–2011. The objectives of the study were to evaluate the yield stability of the genotypes and the relative importance of different stability parameters for improving selection in faba bean. The study was conducted using a randomized complete block design with four replications. G × E interaction and yield stability were estimated using 17 different stability parameters. Pooled analysis of variance for grain yield showed that the main effects of both genotypes and environments, and the interaction effect, were highly significant (P ≤ 0.001 and (P ≤ 0.01, respectively. The environment main effect accounted for 89.27% of the total yield variation, whereas genotype and G × E interaction effects accounted for 2.12% and 3.31%, respectively. Genotypic superiority index (Pi and FT3 were found to be very informative for selecting both high-yielding and stable faba bean genotypes. Twelve of the 17 stability parameters, including CVi, RS, α, λ, S2di, bi, Si(2, Wi, σi2, EV, P59, and ASV, were influenced simultaneously by both yield and stability. They should accordingly be used as complementary criteria to select genotypes with high yield and stability. Although none of the varieties showed consistently superior performance across all environments, the genotype EK 01024-1-2 ranked in the top third of the test entries in 61.5% of the test environments and was identified as the most stable genotype, with type I stability. EK 01024-1-2 also showed a 17.0% seed size advantage over the standard varieties and was released as a new variety in 2013 for wide production and named “Gora”. Different stability parameters explained genotypic performance differently, irrespective of yield performance. It was accordingly concluded that assessment of G × E interaction and yield stability should not be based on a single or a few

  3. Yield stability and relationships among stability parameters in faba bean (Vicia faba L.) genotypes

    Institute of Scientific and Technical Information of China (English)

    Tamene Temesgen; Gemechu Keneni; Tadese Sefera; Mussa Jarso

    2015-01-01

    Sixteen faba bean genotypes were evaluated in 13 environments in Ethiopia during the main cropping season for three years (2009–2011). The objectives of the study were to evaluate the yield stability of the genotypes and the relative importance of different stability parameters for improving selection in faba bean. The study was conducted using a randomized complete block design with four replications. G × E interaction and yield stability were estimated using 17 different stability parameters. Pooled analysis of variance for grain yield showed that the main effects of both genotypes and environments, and the interaction effect, were highly significant (P≤0.001) and (P≤0.01), respectively. The environment main effect accounted for 89.27% of the total yield variation, whereas genotype and G × E interaction effects accounted for 2.12% and 3.31%, respectively. Genotypic superiority index (Pi) and FT3 were found to be very informative for selecting both high-yielding and stable faba bean genotypes. Twelve of the 17 stability parameters, including CVi, RS,α,λ, S2di, bi, Si(2), Wi,σi2, EV, P59, and ASV, were influenced simultaneously by both yield and stability. They should accordingly be used as complementary criteria to select genotypes with high yield and stability. Although none of the varieties showed consistently superior performance across all environments, the genotype EK 01024-1-2 ranked in the top third of the test entries in 61.5% of the test environments and was identified as the most stable genotype, with type I stability. EK 01024-1-2 also showed a 17.0%seed size advantage over the standard varieties and was released as a new variety in 2013 for wide production and named “Gora”. Different stability parameters explained genotypic performance differently, irrespective of yield performance. It was accordingly concluded that assessment of G × E interaction and yield stability should not be based on a single or a few stability parameters but

  4. Slope stability hazard management systems

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Weather-related geo-hazards are a major concern for both natural slopes and man-made slopes and embankments.Government agencies and private companies are increasingly required to ensure that there is adequate protection of sloping surfaces in order that interaction with the climate does not produce instability. Superior theoretical formulations and computer tools are now available to address engineering design issues related to the near ground surface soil-atmospheric interactions. An example is given in this paper that illustrates the consequences of not paying adequate attention to the hazards of slope stability prior to the construction of a highway in South America. On the other hand, examples are given from Hong Kong and Mainland China where significant benefits are derived from putting in place a hazard slope stability management system. Some results from a hazard management slope stability study related to the railway system in Canada are also reported. The study took advantage of recent research on unsaturated soil behaviour and applied this information to real-time modelling of climatic conditions. The quantification of the water balance at the ground surface, and subsequent infiltration, is used as the primary tool for hazard level assessment. The suggested hazard model can be applied at either specific high risk locations or in a more general, broad-based manner over large areas. A more thorough understanding of unsaturated soil behaviour as it applies to near ground surface soils,along with the numerical computational power of the computer has made it possible for new approaches to be used in slope hazard management engineering.

  5. Mechanism study of stabilization of double-base propellants by using zeolite stabilizers (nano- and micro-clinoptilolite

    Directory of Open Access Journals (Sweden)

    M.A. Zayed

    2017-05-01

    Full Text Available The mechanism of stabilization of double-base rocket propellants (DBPs using inorganic stabilizer (nano- and micro-clinoptilolite was investigated. The surface structures of the stabilizers, the double-base propellants containing the new stabilizers and the effect of the stabilizers on the surface behavior of propellants and vice versa were checked using XRD and Electron Microscope (AFM and TEM techniques. The results obtained from XRD suggested that the crystalline structure of the new inorganic stabilizers was completely changed when it was introduced into the propellants which may be attributed to the pressing processes of DBPs with stabilizers under very high pressure during their mixture preparation. The results obtained from Atomic Force Electron Microscope (AFM and TEM indicated that nano-clinoptilolite particles become more regularly arranged on the propellant surface than micro-clinoptilolite which gives the stabilizer a higher ability to absorb more nitrogen oxide. The work aimed chiefly to use zeolite stabilizers for DBPs instead of classically used organic compounds; in order to avoid the harmful and carcinogenic organic products coming from the reaction of NOx gases with these organic stabilizers. This is achieved by studying the thermal behavior of these zeolites via investigation of their surface interaction with NOx gases obtained during stabilization process and suggesting possible interaction mechanism.

  6. Dental implant stability analysis by using resonance frequency method

    OpenAIRE

    Harirforoush, Reza

    2012-01-01

    The use of dental implants in the rehabilitation of partially and completely edentulous patients has been significantly increased in recent years. Although high survival rates of implants supporting prosthesis have been reported, failure still happens due to bone loss as results of primary and secondary implant stability. Primary stability of an implant mostly comes from mechanical interaction with cortical bone while secondary stability happens through bone regeneration and remodelling at th...

  7. Basic principles of stability.

    Science.gov (United States)

    Egan, William; Schofield, Timothy

    2009-11-01

    An understanding of the principles of degradation, as well as the statistical tools for measuring product stability, is essential to management of product quality. Key to this is management of vaccine potency. Vaccine shelf life is best managed through determination of a minimum potency release requirement, which helps assure adequate potency throughout expiry. Use of statistical tools such a least squares regression analysis should be employed to model potency decay. The use of such tools provides incentive to properly design vaccine stability studies, while holding stability measurements to specification presents a disincentive for collecting valuable data. The laws of kinetics such as Arrhenius behavior help practitioners design effective accelerated stability programs, which can be utilized to manage stability after a process change. Design of stability studies should be carefully considered, with an eye to minimizing the variability of the stability parameter. In the case of measuring the degradation rate, testing at the beginning and the end of the study improves the precision of this estimate. Additional design considerations such as bracketing and matrixing improve the efficiency of stability evaluation of vaccines.

  8. Visual attention and stability

    NARCIS (Netherlands)

    Mathot, Sebastiaan; Theeuwes, Jan

    2011-01-01

    In the present review, we address the relationship between attention and visual stability. Even though with each eye, head and body movement the retinal image changes dramatically, we perceive the world as stable and are able to perform visually guided actions. However, visual stability is not as co

  9. Ornithopter flight stabilization

    Science.gov (United States)

    Dietl, John M.; Garcia, Ephrahim

    2007-04-01

    The quasi-steady aerodynamics model and the vehicle dynamics model of ornithopter flight are explained, and numerical methods are described to capture limit cycle behavior in ornithopter flight. The Floquet method is used to determine stability in forward flight, and a linear discrete-time state-space model is developed. This is used to calculate stabilizing and disturbance-rejecting controllers.

  10. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  11. Stabilizing Randomly Switched Systems

    CERN Document Server

    Chatterjee, Debasish

    2008-01-01

    This article is concerned with stability analysis and stabilization of randomly switched systems under a class of switching signals. The switching signal is modeled as a jump stochastic (not necessarily Markovian) process independent of the system state; it selects, at each instant of time, the active subsystem from a family of systems. Sufficient conditions for stochastic stability (almost sure, in the mean, and in probability) of the switched system are established when the subsystems do not possess control inputs, and not every subsystem is required to be stable. These conditions are employed to design stabilizing feedback controllers when the subsystems are affine in control. The analysis is carried out with the aid of multiple Lyapunov-like functions, and the analysis results together with universal formulae for feedback stabilization of nonlinear systems constitute our primary tools for control design

  12. The statistical stability phenomenon

    CERN Document Server

    Gorban, Igor I

    2017-01-01

    This monograph investigates violations of statistical stability of physical events, variables, and processes and develops a new physical-mathematical theory taking into consideration such violations – the theory of hyper-random phenomena. There are five parts. The first describes the phenomenon of statistical stability and its features, and develops methods for detecting violations of statistical stability, in particular when data is limited. The second part presents several examples of real processes of different physical nature and demonstrates the violation of statistical stability over broad observation intervals. The third part outlines the mathematical foundations of the theory of hyper-random phenomena, while the fourth develops the foundations of the mathematical analysis of divergent and many-valued functions. The fifth part contains theoretical and experimental studies of statistical laws where there is violation of statistical stability. The monograph should be of particular interest to engineers...

  13. Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sujoy Dutta

    Full Text Available Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive "niches". Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7, representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs. Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment.

  14. Insights into the Hendra virus NTAIL-XD complex: Evidence for a parallel organization of the helical MoRE at the XD surface stabilized by a combination of hydrophobic and polar interactions.

    Science.gov (United States)

    Erales, Jenny; Beltrandi, Matilde; Roche, Jennifer; Maté, Maria; Longhi, Sonia

    2015-08-01

    The Hendra virus is a member of the Henipavirus genus within the Paramyxoviridae family. The nucleoprotein, which consists of a structured core and of a C-terminal intrinsically disordered domain (N(TAIL)), encapsidates the viral genome within a helical nucleocapsid. N(TAIL) partly protrudes from the surface of the nucleocapsid being thus capable of interacting with the C-terminal X domain (XD) of the viral phosphoprotein. Interaction with XD implies a molecular recognition element (MoRE) that is located within N(TAIL) residues 470-490, and that undergoes α-helical folding. The MoRE has been proposed to be embedded in the hydrophobic groove delimited by helices α2 and α3 of XD, although experimental data could not discriminate between a parallel and an antiparallel orientation of the MoRE. Previous studies also showed that if the binding interface is enriched in hydrophobic residues, charged residues located close to the interface might play a role in complex formation. Here, we targeted for site directed mutagenesis two acidic and two basic residues within XD and N(TAIL). ITC studies showed that electrostatics plays a crucial role in complex formation and pointed a parallel orientation of the MoRE as more likely. Further support for a parallel orientation was afforded by SAXS studies that made use of two chimeric constructs in which XD and the MoRE were covalently linked to each other. Altogether, these studies unveiled the multiparametric nature of the interactions established within this complex and contribute to shed light onto the molecular features of protein interfaces involving intrinsically disordered regions. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Interactions between exosomes from breast cancer cells and primary mammary epithelial cells leads to generation of reactive oxygen species which induce DNA damage response, stabilization of p53 and autophagy in epithelial cells.

    Science.gov (United States)

    Dutta, Sujoy; Warshall, Case; Bandyopadhyay, Chirosree; Dutta, Dipanjan; Chandran, Bala

    2014-01-01

    Exosomes are nanovesicles originating from multivesicular bodies and are released by all cell types. They contain proteins, lipids, microRNAs, mRNAs and DNA fragments, which act as mediators of intercellular communications by inducing phenotypic changes in recipient cells. Tumor-derived exosomes have been shown to play critical roles in different stages of tumor development and metastasis of almost all types of cancer. One of the ways by which exosomes affect tumorigenesis is to manipulate the tumor microenvironments to create tumor permissive "niches". Whether breast cancer cell secreted exosomes manipulate epithelial cells of the mammary duct to facilitate tumor development is not known. To address whether and how breast cancer cell secreted exosomes manipulate ductal epithelial cells we studied the interactions between exosomes isolated from conditioned media of 3 different breast cancer cell lines (MDA-MB-231, T47DA18 and MCF7), representing three different types of breast carcinomas, and normal human primary mammary epithelial cells (HMECs). Our studies show that exosomes released by breast cancer cell lines are taken up by HMECs, resulting in the induction of reactive oxygen species (ROS) and autophagy. Inhibition of ROS by N-acetyl-L-cysteine (NAC) led to abrogation of autophagy. HMEC-exosome interactions also induced the phosphorylation of ATM, H2AX and Chk1 indicating the induction of DNA damage repair (DDR) responses. Under these conditions, phosphorylation of p53 at serine 15 was also observed. Both DDR responses and phosphorylation of p53 induced by HMEC-exosome interactions were also inhibited by NAC. Furthermore, exosome induced autophagic HMECs were found to release breast cancer cell growth promoting factors. Taken together, our results suggest novel mechanisms by which breast cancer cell secreted exosomes manipulate HMECs to create a tumor permissive microenvironment.

  16. Vacuum stability of asymptotically safe gauge-Yukawa theories

    DEFF Research Database (Denmark)

    Litim, Daniel F.; Mojaza, Matin; Sannino, Francesco

    2016-01-01

    We study the phase diagram and the stability of the ground state for certain four-dimensional gauge-Yukawa theories whose high-energy behaviour is controlled by an interacting fixed point. We also provide analytical and numerical results for running couplings, their crossover scales, the separatrix......, and the Coleman-Weinberg effective potential. Classical and quantum stability of the vacuum is established....

  17. Systematic analysis of stability patterns in plant primary metabolism.

    Directory of Open Access Journals (Sweden)

    Dorothee Girbig

    Full Text Available Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric regulators revealing that the tendency to stability is significantly increased by including experimentally determined regulatory mechanisms that have not yet been integrated into existing kinetic models.

  18. Vacuum stability of asymptotically safe gauge-Yukawa theories

    CERN Document Server

    Litim, Daniel F; Sannino, Francesco

    2016-01-01

    We study the phase diagram and the stability of the ground state for certain four-dimensional gauge-Yukawa theories whose high-energy behaviour is controlled by an interacting fixed point. We also provide analytical and numerical results for running couplings, their crossover scales, the separatrix, and the Coleman-Weinberg effective potential. Classical and quantum stability of the vacuum is established.

  19. The phosphorylation of protein S6 modulates the interaction of the 40 S ribosomal subunit with the 5'-untranslated region of a dictyostelium pre-spore-specific mRNA and controls its stability.

    Science.gov (United States)

    Chiaberge, S; Cassarino, E; Mangiarotti, G

    1998-10-16

    AC914 mRNA, a pre-spore-specific mRNA that accumulates only in the post-aggregation stage of development, is transcribed constitutively as shown by nuclear run-off experiments and by fusing its promoter to the luciferase reporter gene. The same mRNA disappears quickly from disaggregated cells. If the 5'-untranslated region (5'UTR) of the constitutively expressed Actin 15 mRNA is substituted for the 5'UTR of AC914 mRNA, this can no longer be destabilized and accumulates both in growing and disaggregated cells. If the 5'UTR of AC914 mRNA is substituted for the 5'UTR of Actin 15 mRNA, the latter accumulates only in aggregated cells. Pactamycin, but not other inhibitors of protein synthesis, prevents AC914 mRNA from being destabilized in disaggregated cells, suggesting a role of 40 S subunits in the destabilization. This has been confirmed by using an in vitro system in which the in vivo stability of different mRNAs is reproduced. A protein kinase A-dependent phosphorylation of ribosomal protein S6 determines whether 40 S subunits are capable or not of destabilizing AC914 mRNA in the in vitro system.

  20. Neutrino Self-Interactions

    CERN Document Server

    Hasenkamp, Jasper

    2016-01-01

    We propose a theory that equips the active neutrinos with interactions among themselves that are at least three orders of magnitude stronger than the weak interaction. We introduce an Abelian gauge group $U(1)_x$ with vacuum expectation value $v_x \\lesssim \\mathcal{O}(100 \\textrm{ MeV})$. An asymmetric mass matrix implements the active neutrinos as massless mass eigenstates carrying "effective" charges. To stabilize $v_x$, supersymmetry breaking is mediated via loops to the additional sector with the only exception of xHiggs terms. No Standard Model interaction eigenstate carries $U(1)_x$ charge. Thus the dark photon's kinetic mixing is two-loop suppressed.With only simple and generic values of dimensionless parameters, our theory might explain the high-energy neutrino spectrum observed by IceCube including the PeV neutrinos. We comment on the imposing opportunity to incorporate a self-interacting dark matter candidate.

  1. A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB signaling.

    Science.gov (United States)

    Wu, Jianchun; Lei, Guohua; Mei, Mei; Tang, Yi; Li, Honglin

    2010-05-14

    C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-kappaB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of C53/LZAP and DDRGK1) and DDRGK1 (DDRGK domain-containing protein 1). Our co-immunoprecipitation assays confirmed their interactions, while gel filtration assay indicated that C53/LZAP and RCAD may form a large protein complex. Intriguingly, we found that RCAD knockdown led to dramatic reduction of C53/LZAP and DDRGK1 proteins. We also found that C53/LZAP and DDRGK1 became more susceptible to the proteasome-mediated degradation in RCAD knockdown cells, whereas their ubiquitination was significantly attenuated by RCAD overexpression. In addition, we found that RCAD, like C53/LZAP, also plays an important role in regulation of NF-kappaB signaling and cell invasion. Taken together, our findings strongly suggest that RCAD is a novel regulator of C53/LZAP tumor suppressor and NF-kappaB signaling.

  2. A Novel C53/LZAP-interacting Protein Regulates Stability of C53/LZAP and DDRGK Domain-containing Protein 1 (DDRGK1) and Modulates NF-κB Signaling*

    Science.gov (United States)

    Wu, Jianchun; Lei, Guohua; Mei, Mei; Tang, Yi; Li, Honglin

    2010-01-01

    C53/LZAP (also named as Cdk5rap3) is a putative tumor suppressor that plays important roles in multiple cell signaling pathways, including DNA damage response and NF-κB signaling. Yet how its function is regulated remains largely unclear. Here we report the isolation and characterization of two novel C53/LZAP-interacting proteins, RCAD (Regulator of C53/LZAP and DDRGK1) and DDRGK1 (DDRGK domain-containing protein 1). Our co-immunoprecipitation assays confirmed their interactions, while gel filtration assay indicated that C53/LZAP and RCAD may form a large protein complex. Intriguingly, we found that RCAD knockdown led to dramatic reduction of C53/LZAP and DDRGK1 proteins. We also found that C53/LZAP and DDRGK1 became more susceptible to the proteasome-mediated degradation in RCAD knockdown cells, whereas their ubiquitination was significantly attenuated by RCAD overexpression. In addition, we found that RCAD, like C53/LZAP, also plays an important role in regulation of NF-κB signaling and cell invasion. Taken together, our findings strongly suggest that RCAD is a novel regulator of C53/LZAP tumor suppressor and NF-κB signaling. PMID:20228063

  3. Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.

    Science.gov (United States)

    Ahl, Patrick L; Mensch, Christopher; Hu, Binghua; Pixley, Heidi; Zhang, Lan; Dieter, Lance; Russell, Ryann; Smith, William J; Przysiecki, Craig; Kosinski, Mike; Blue, Jeffrey T

    2016-10-01

    Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Stability analysis of ferrofluids

    Directory of Open Access Journals (Sweden)

    Katharina Duda

    2015-09-01

    Full Text Available Superparamagnetic iron oxides (SPIOs are used as tracer for the new imaging technique Magnetic Particle Imaging. The stability of ferrofluids for medical application has a great importance, in addition to the particle size. The shell material, which protects the iron core prior from agglomeration and sedimentation, can be degraded by various processes. Another important aspect of stability is the constant performance of magnetisation. Therefore, the measurement of the magnetisation of the particles must be controlled in order to ensure the stability of the samples.

  5. Life raft stabilizer

    Science.gov (United States)

    Radnofsky, M. I.; Barnett, J. H., Jr.; Harrison, F. L.; Marak, R. J. (Inventor)

    1973-01-01

    An improved life raft stabilizer for reducing rocking and substantially precluding capsizing is discussed. The stabilizer may be removably attached to the raft and is defined by flexible side walls which extend a considerable depth downwardly to one another in the water. The side walls, in conjunction with the floor of the raft, form a ballast enclosure. A weight is placed in the bottom of the enclosure and water port means are provided in the walls. Placement of the stabilizer in the water allows the weighted bottom to sink, producing submerged deployment thereof and permitting water to enter the enclosure through the port means, thus forming a ballast for the raft.

  6. Experimental and theoretical studies on stability of new stabilizers for N-methyl-P-nitroaniline derivative in CMDB propellants.

    Science.gov (United States)

    Tang, Qiufan; Fan, Xuezhong; Li, Jizhen; Bi, Fuqiang; Fu, Xiaolong; Zhai, Lianjie

    2017-04-05

    Although N-methyl-P-nitroaniline (MNA) was a quite effective stabilizer in composite modified double base (CMDB) propellants, it undergoes crystallization easily from nitroglycerin (NG) during storage. In order to improve its solubility in nitroglycerin (NG) and the stability in propellants, several new stabilizers including N-ethyl-p-nitroaniline (ENA), N-n-propyl-p-nitroaniline (n-PNA), N-i-propyl-p-nitroaniline (i-PNA), N-n-butyl-p-nitroaniline (n-BNA) and N-t-butyl-p-nitroaniline (t-BNA) were designed and synthesized to replace MNA by increasing the carbon chain length. The interaction between NG and different stabilizers was simulation by Materials Studio 5.5 and the stability and the high temperature stability performance of those new stabilizers in propellants were calculated by Gaussian 09. It was found that both the solubility of new stabilizers in NG and the stability and the high temperature stability performance of those in propellants were improved when the carbon chain length of substitution groups on nitrogen atom was increased. Thus, the n-BNA was a most potential stabilizer. Then all properties of the stabilizers were studied experimentally, which was agreement well with the theoretical analysis.

  7. Tar DNA binding protein of 43 kDa (TDP-43), 14-3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Volkening, Kathryn; Leystra-Lantz, Cheryl; Yang, Wenchang; Jaffee, Howard; Strong, Michael J

    2009-12-11

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive motor neuron degeneration in association with neurofilament (NF) aggregate formation. This process is accompanied by an alteration in the stoichiometry of NF subunit protein expression such that the steady state levels of the low molecular weight NF (NFL) mRNA levels are selectively suppressed. We have previously shown that each of TDP-43, 14-3-3 and mutant SOD1 can function as NFL mRNA 3'UTR binding proteins that directly affect the stability of NFL transcripts. In this study, we demonstrate that the interaction of TDP-43 with the NFL mRNA 3' UTR involves ribonucleotide (UG) motifs present on stem loops of the 3'UTR as well as the RRM1 and RRM2 motifs of TDP-43. Ex vivo, TDP-43, 14-3-3 and SOD1 proteins interact to modulate NFL mRNA stability, although in vivo, only TDP-43 and either mutant or wild-type SOD1 co-localize in ALS motor neurons. TDP-43 was observed to co-localize to RNA transport granules (Staufen immunoreactive) in both control and ALS spinal motor neurons. In contrast, both stress granules (TIA-1 immunoreactive) and processing bodies (P-bodies; XRN-1 immunoreactive) were more prevalent in ALS motor neurons than in controls and demonstrated strong co-localization with TDP-43. Using RNA-IP-PCR, we further demonstrate that NFL mRNA is preferentially sequestered to both stress granules and P-bodies in ALS. These data suggest that NFL mRNA processing is fundamentally altered in ALS spinal motor neurons to favour compartmentalization within both stress granules and P-bodies, and that TDP-43 plays a fundamental role in this process.

  8. STABILITY OF A SWITCHED LINEAR SYSTEM

    Directory of Open Access Journals (Sweden)

    At-Tasneem Mohd Amin

    2012-12-01

    Full Text Available Hybrid systems are dynamic systems that arise out of the interaction of continuous state dynamics and discrete state dynamics. Switched systems, which are a type of hybrid system, have been given much attention by control systems research over the past decade. Problems with the controllability, observability, converseability and stabilizability of switched systems have always been discussed. In this paper, the trend in research regarding the stability of switched systems will be investigated. Then the variety of methods that have been discovered by researchers for stabilizing switched linear systems with arbitrary switching will be discussed in detail.

  9. Reviewing The Benefits of Health Workforce Stability

    Directory of Open Access Journals (Sweden)

    Buchan James

    2010-12-01

    Full Text Available Abstract This paper examines the issue of workforce stability and turnover in the context of policy attempts to improve retention of health workers. The paper argues that there are significant benefits to supporting policy makers and managers to develop a broader perspective of workforce stability and methods of monitoring it. The objective of the paper is to contribute to developing a better understanding of workforce stability as a major aspect of the overall policy goal of improved retention of health workers. The paper examines some of the limited research on the complex interaction between staff turnover and organisational performance or quality of care in the health sector, provides details and examples of the measurement of staff turnover and stability, and illustrates an approach to costing staff turnover. The paper concludes by advocating that these types of assessment can be valuable to managers and policy makers as they examine which policies may be effective in improving stability and retention, by reducing turnover. They can also be used as part of advocacy for the use of new retention measures. The very action of setting up a local working group to assess the costs of turnover can in itself give managers and staff a greater insight into the negative impacts of turnover, and can encourage them to work together to identify and implement stability measures.

  10. Metallic alloy stability studies

    Science.gov (United States)

    Firth, G. C.

    1983-01-01

    The dimensional stability of candidate cryogenic wind tunnel model materials was investigated. Flat specimens of candidate materials were fabricated and cryo-cycled to assess relative dimensional stability. Existing 2-dimensional airfoil models as well as models in various stages of manufacture were also cryo-cycled. The tests indicate that 18 Ni maraging steel offers the greatest dimensional stability and that PH 13-8 Mo stainless steel is the most stable of the stainless steels. Dimensional stability is influenced primarily by metallurgical transformations (austenitic to martensitic) and manufacturing-induced stresses. These factors can be minimized by utilization of stable alloys, refinement of existing manufacturing techniques, and incorporation of new manufacturing technologies.

  11. Thermally accurate LES of the stability-emission performance of staged gas-turbine combustion; Simulation aux grandes echelles de la combustion etagee dans les turbines a gaz et son interaction stabilite-polluants-thermique

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, P.

    2005-06-15

    Modern gas turbines use turbulent lean partially premixed combustion in order to minimise nitrous oxide (NO{sub X}) emissions while ensuring flashback safety. The Large-Eddy Simulation (LES) of such a device is the goal of this work. Focus is laid on correctly predicting the NO{sub X} emissions, which are influenced by four factors: heat transfer, mixing quality, combustion modelling and thermo-acoustic stability. As NO{sub X} reaction rates are strongly influenced by temperature, heat transfer by radiation and convection is included. Radiation is predicted by a model, which assumes that the gases are optically thin. Convective heat transfer is included via a newly developed and validated wall-function approach based on the logarithmic law of the wall for temperature. An optimised 2-step reduced chemical reaction scheme for lean methane combustion is presented. This scheme is used for the LES in conjunction with an additional third reaction, fitted to produce the same NO{sub X} reaction rates as in the complete reaction mechanism. Turbulence is accounted for with the thickened flame model in a form, which is optimised for changing equivalence ratios and mesh-resolutions. Mixing is essential not only for predicting flame stabilisation, but also for pollutant emissions as NO{sub X} reaction rates depend exponentially on equivalence ratio. Therefore the full burner geometry, including 16 fuel injections is resolved in LES. Additionally, effusion cooling and film cooling is accounted for in a simplified manner. The non-reacting flow is extensively validated with experimental results. As mixture-fraction fluctuations do not only arise from turbulence, but also from thermo-acoustic instabilities, care was taken to provide acoustic boundary conditions that come close to reality. The resulting LES shows a strong thermo-acoustic instability, comparing well with experimental observations. By making the boundaries completely anechoic it is shown that when the instability

  12. Global stability in ecological models with continuous time delays

    Energy Technology Data Exchange (ETDEWEB)

    Post, W M; Travis, C C

    1979-01-01

    This model examines the stability properties of a general system of first-order integro-differential equations which describe the dynamics of interacting species populations. A sufficient condition for the global stability of an equilibrium state is derived. This condition is an improvement over the condition derived by Woerz-Busekros (1978) for similar equations in that this condition has intuitive biological interpretations and is verifiable in a finite number of arithmetical steps. This condition is shown to be both necessary and sufficient for global asymptotic stability of the equilibrium for communities of mutualistically interacting species. Application of the results to an ecological system is also provided. (PCS)

  13. Thermodynamic Stability of Wormholes

    CERN Document Server

    Sajadi, S N

    2016-01-01

    In the context of GR, we study the thermodynamic stability of evolving Lorentzian wormholes at the apparent horizon. The average pressure of the anisotrropic components is considered as the pressure of the wormhole. According to the requirements of stable equilibrium in conventional thermodynamics, we calculate the heat capacity at constant pressure and Gibbs free energy and analyze the local and global thermodynamic stability of the wormhole.

  14. Tetraphenylborate Solids Stability Tests

    Energy Technology Data Exchange (ETDEWEB)

    Walker, D.D. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1997-06-25

    Tetraphenylborate solids are a potentially large source of benzene in the slurries produced in the In-Tank Precipitation (ITP) process. The stability of the solids is an important consideration in the safety analysis of the process and we desire an understanding of the factors that influence the rate of conversion of the solids to benzene. This report discusses current testing of the stability of tetraphenylborate solids.

  15. Food Fortification Stability Study

    Science.gov (United States)

    Sirmons, T. A.; Cooper, M. R.; Douglas, G. L.

    2017-01-01

    This study aimed to assess the stability of vitamin content, sensory acceptability and color variation in fortified spaceflight foods over a period of two years. Findings will help to identify optimal formulation, processing, and storage conditions to maintain stability and acceptability of commercially available fortification nutrients. Changes in food quality were monitored to indicate whether fortification affects quality over time (compared to the unfortified control), thus indicating their potential for use on long-duration missions.

  16. Shearing stability of lubricants

    Science.gov (United States)

    Shiba, Y.; Gijyutsu, G.

    1984-01-01

    Shearing stabilities of lubricating oils containing a high mol. wt. polymer as a viscosity index improver were studied by use of ultrasound. The oils were degraded by cavitation and the degradation generally followed first order kinetics with the rate of degradation increasing with the intensity of the ultrasonic irradiation and the cumulative energy applied. The shear stability was mainly affected by the mol. wt. of the polymer additive and could be determined in a short time by mechanical shearing with ultrasound.

  17. Shearing stability of lubricants

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Y.; Gijyutsu, G.

    1984-03-01

    Shearing stabilities of lubricating oils containing a high mol. wt. polymer as a viscosity index improver were studied by use of ultrasound. The oils were degraded by cavitation and the degradation generally followed first order kinetics with the rate of degradation increasing with the intensity of the ultrasonic irradiation and the cumulative energy applied. The shear stability was mainly affected by the mol. wt. of the polymer additive and could be determined in a short time by mechanical shearing with ultrasound.

  18. PFP solution stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Aftanas, B.L.

    1996-04-30

    This Functional Design Criteria (FDC) addresses remediation of the plutonium-bearing solutions currently in inventory at the Plutonium Finishing Plant (PFP). The recommendation from the Environmental Impact Statement (EIS) is that the solutions be treated thermally and stabilized as a solid for long term storage. For solutions which are not discardable, the baseline plan is to utilize a denitration process to stabilize the solutions prior to packaging for storage.

  19. Automatic Fiscal Stabilizers

    Directory of Open Access Journals (Sweden)

    Narcis Eduard Mitu

    2013-11-01

    Full Text Available Policies or institutions (built into an economic system that automatically tend to dampen economic cycle fluctuations in income, employment, etc., without direct government intervention. For example, in boom times, progressive income tax automatically reduces money supply as incomes and spendings rise. Similarly, in recessionary times, payment of unemployment benefits injects more money in the system and stimulates demand. Also called automatic stabilizers or built-in stabilizers.

  20. METHOD FOR STABILIZING KLYSTRONS

    Science.gov (United States)

    Magnuson, D.W.; Smith, D.F.

    1959-04-14

    High-frequency oscillators for the generation of microwaves, particularly a system for stabilizing frequency-modulated klystron oscillators of the reflex type, are described. The system takos advantage of the fact that a change in oscillator frequency will alter the normal phase displacement between the cavity and its modulator, creating an error voltage which is utilized to regulate the frequency of the oscillator and stabilize it.

  1. Food Fortification Stability Study

    Science.gov (United States)

    Sirmons, T. A.; Cooper, M. R.; Douglas, G. L.

    2016-01-01

    This study aims to assess the stability of vitamin content, sensory acceptability and color variation in fortified spaceflight foods over a period of 2 years. Findings will identify optimal formulation, processing, and storage conditions to maintain stability and acceptability of commercially available fortification nutrients. Changes in food quality are being monitored to indicate whether fortification affects quality over time (compared to the unfortified control), thus indicating their potential for use on long-duration missions.

  2. Stabilization Methods for a Multiagent System with Complex Behaviours

    Science.gov (United States)

    Leon, Florin

    2015-01-01

    The main focus of the paper is the stability analysis of a class of multiagent systems based on an interaction protocol which can generate different types of overall behaviours, from asymptotically stable to chaotic. We present several interpretations of stability and suggest two methods to assess the stability of the system, based on the internal models of the agents and on the external, observed behaviour. Since it is very difficult to predict a priori whether a system will be stable or unstable, we propose three heuristic methods that can be used to stabilize such a system during its execution, with minimal changes to its state. PMID:26097491

  3. Aging of dynamically stabilized microtubules

    CERN Document Server

    Ebbinghaus, M

    2009-01-01

    The microtubule network, an important part of the cytoskeleton, is constantly remodeled by alternating phases of growth and shrinkage of individual filaments. Plus-end tracking proteins (+TIPs) interact with the microtubule and in many cases alter its dynamics. While it is established that the prototypal CLIP-170 enhances microtubule stability by increasing rescues, the plus-end tracking mechanism is still under debate. We present a model for microtubule dynamics in which a rescue factor is dynamically added to the filament while growing. As a consequence, the filament shows aging behavior which should be experimentally accessible and thus allow one to exclude some hypothesized models of the inclusion of rescue factors at the microtubule plus end. Additionally, we show the strong influence of the cell geometry on the quantitative results.

  4. Effects of core muscle stability training on the weight distribution and stability of the elderly.

    Science.gov (United States)

    Kang, Kwon-Young

    2015-10-01

    [Purpose] This study investigated the effects of core muscle stability training on the weight distribution and stability of the elderly. [Subjects and Methods] Thirty elderly persons were randomly divided into an experimental group which performed core strengthening exercises, and a control group which performed standard strengthening exercises for 8 weeks. A Tetrax Interactive Balance System was used to evaluate the weight distribution index (WDI) and the stability index (SI). [Results] The experimental group showed a significant improvement in terms of WDI and the SI. However, the control group showed no significant improvement in either. [Conclusion] Core muscle stability training should be considered as a therapeutic method for the elderly to improve their WDI, and SI, and as a fall prevention measure.

  5. Evolutionary stability concepts in a stochastic environment

    Science.gov (United States)

    Zheng, Xiu-Deng; Li, Cong; Lessard, Sabin; Tao, Yi

    2017-09-01

    Over the past 30 years, evolutionary game theory and the concept of an evolutionarily stable strategy have been not only extensively developed and successfully applied to explain the evolution of animal behaviors, but also widely used in economics and social sciences. Nonetheless, the stochastic dynamical properties of evolutionary games in randomly fluctuating environments are still unclear. In this study, we investigate conditions for stochastic local stability of fixation states and constant interior equilibria in a two-phenotype model with random payoffs following pairwise interactions. Based on this model, we develop the concepts of stochastic evolutionary stability (SES) and stochastic convergence stability (SCS). We show that the condition for a pure strategy to be SES and SCS is more stringent than in a constant environment, while the condition for a constant mixed strategy to be SES is less stringent than the condition to be SCS, which is less stringent than the condition in a constant environment.

  6. 物价稳定目标下通货膨胀与股价关系的经验研究%Empirical Research on the Interaction between Inflation and Stock Price under Price Stability Target

    Institute of Scientific and Technical Information of China (English)

    李世美

    2011-01-01

    The relationship between inflation and stock price includes two aspects:whether stock price contains inflation information provides a theoretical basis for monetary policy to intervene in stock price;whether inflation can affect stock prices can provide a reference for stock investment.By theoretical and empirical analysis of interaction among information, stock price and monetary policy, a general conclusions can be drawn as follows:the monetary policy is mainly adjusted based on inflation; stock prices rarely can provide inflation information,there is no evidence to support monetary policy has reacted to stock price;the impact of inflation on stock prices is mainly through the interest rate adjustment of monetary policy;the inflation impact on stock prices is different under different inflation level.%通货膨胀与股票价格关系包括了两个方面:股票价格是否包含了通货膨胀信息能为货币政策干预股价提供理论依据;通货膨胀是否影响股票价格能够为股票投资提供参考依据。通过对通货膨胀、股票价格和货币政策三者关系的理论与我国的经验分析可以得出一般性结论:我国货币政策主要是根据通货膨胀水平做出调整的:股票价格所反应出来的通货膨胀信息并不明显.没有证据支持货币政策对股价做出了反应:通货膨胀对股票价格的影响主要是通过货币政策的利率调整而产生影响,并且在不同的通货膨胀水平下对股价的影响存在差异。

  7. Interaction webs in arctic ecosystems

    DEFF Research Database (Denmark)

    Schmidt, Niels M.; Hardwick, Bess; Gilg, Olivier;

    2017-01-01

    How species interact modulate their dynamics, their response to environmental change, and ultimately the functioning and stability of entire communities. Work conducted at Zackenberg, Northeast Greenland, has changed our view on how networks of arctic biotic interactions are structured, how they ...... that the combination of long-term, ecosystem-based monitoring, and targeted research projects offers the most fruitful basis for understanding and predicting the future of arctic ecosystems....

  8. Hydrodynamic and hydromagnetic stability

    CERN Document Server

    Chandrasekhar, S

    1981-01-01

    Dr. Chandrasekhar's book received high praise when it first appeared in 1961 as part of Oxford University Press' International Series of Monographs on Physics. Since then it has been reprinted numerous times in its expensive hardcover format. This first lower-priced, sturdy paperback edition will be welcomed by graduate physics students and scientists familiar with Dr. Chandrasekhar's work, particularly in light of the resurgence of interest in the Rayleigh-Bénard problem. This book presents a most lucid introduction to the Rayleigh-Bénard problem: it has also been applauded for its thorough, clear coverage of the theory of instabilities causing convection. Dr. Chandrasekhar considers most of the typical problems in hydromagnetic stability, with the exception of viscous shear flow; a specialized domain deserving a book unto itself. Contents include: Rotation; Stability of More General Flows; Bénard Problem; Gravitational Equilibrium and Instability; Stability of a Magnetic Field; Thermal Instability of a L...

  9. Marital stability and repartnering

    DEFF Research Database (Denmark)

    Martins, Mariana V; Costa, Patrício; Peterson, Brennan D

    2014-01-01

    starting a new cycle of fertility treatment and observed for a 5-year period of unsuccessful treatments. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Marital stability and infertility-related stress. RESULT(S): The majority of patients (86%) remained with their initial partner, but 14% of participants...... separated and repartnered while pursuing fertility treatments. Marital stability significantly predicted the initial status of infertility stress and infertility stress growth levels. Specifically, patients who repartnered had higher infertility stress levels at all time points compared with those who...... a second union have higher initial levels of stress in their original relationship and higher changes in stress levels over the course of treatments. These findings suggest that high infertility-related stress levels before entering fertility treatment can negatively affect the stability of marital...

  10. D-Moduli Stabilization

    CERN Document Server

    Giedt, J

    2002-01-01

    The matter sector of four-dimensional effective supergravity models obtained from the weakly coupled heterotic string contains many moduli. In particular, flat directions of the D-term part of the scalar potential in the presence of an anomalous U(1) give rise to massless chiral multiplets which have been referred to elsewhere as D-moduli. The stabilization of these moduli is necessary for the determination of the large vacuum expectation values of complex scalar fields induced by the corresponding Fayet-Illiopoulos term. This stabilization is of phenomenological importance since these background values determine the effective theory below the scale of the anomalous U(1) symmetry breaking. In some simple models we illustrate the stabilization of these moduli due to the nonperturbative dynamics associated with gaugino condensation in a hidden sector. We find that background field configurations which are stable above the condensation scale no longer represent global minima once dynamical supersymmetry breaking...

  11. Generalized Lotka stability.

    Science.gov (United States)

    Smith, J D H; Zhang, C

    2015-08-01

    The recently developed macroscopic approach to demography describes the age distribution of mothers and the net maternity function for a given human population entirely in terms of five parameters. Tracking of these parameters provides a number of new tools for analyzing populations and predicting their future states. Within the macroscopic approach, the new concept of generalized Lotka stability is presented in this paper, as an extension of a strong version of classic Lotka stability. The two leading parameters of the macroscopic approach, the Malthusian parameter r and the perturbation s, are computed from population data and plotted in two-dimensional parameter space. Generalized Lotka stability is then defined in terms of the movement of the (r,s)-vector over time. It may be observed in a number of human populations at specific periods of their history.

  12. Wetting films stabilized by block-copolymers

    OpenAIRE

    Eliseeva, O.V.

    2006-01-01

    Thin aqueous films formed on a solid surface play an important role in adhesion, spreading, and colloidal stability. These phenomena are all relevant for paint systems. Measuring surface forces in these films is an experimental challenge, and over the years several techniques have been developed to measure the interaction forces as a function of the thickness of the film, the so-called disjoining pressure isotherms. A thin film balance technique (TFB) in combination with an ellipsometer offer...

  13. A stabilized pairing functional

    CERN Document Server

    Erler, J; Reinhard, P --G

    2008-01-01

    We propose a modified pairing functional for nuclear structure calculations which avoids the abrupt phase transition between pairing and non-pairing states. The intended application is the description of nuclear collective motion where the smoothing of the transition is compulsory to remove singularities. The stabilized pairing functional allows a thoroughly variational formulation, unlike the Lipkin-Nogami (LN) scheme which is often used for the purpose of smoothing. First applications to nuclear ground states and collective excitations prove the reliability and efficiency of the proposed stabilized pairing.

  14. Magnetohydrodynamic stability of tokamaks

    CERN Document Server

    Zohm, Hartmut

    2014-01-01

    This book bridges the gap between general plasma physics lectures and the real world problems in MHD stability. In order to support the understanding of concepts and their implication, it refers to real world problems such as toroidal mode coupling or nonlinear evolution in a conceptual and phenomenological approach. Detailed mathematical treatment will involve classical linear stability analysis and an outline of more recent concepts such as the ballooning formalism. The book is based on lectures that the author has given to Master and PhD students in Fusion Plasma Physics. Due its strong lin

  15. Stability of dynamical systems

    CERN Document Server

    Liao, Xiaoxin; Yu, P 0

    2007-01-01

    The main purpose of developing stability theory is to examine dynamic responses of a system to disturbances as the time approaches infinity. It has been and still is the object of intense investigations due to its intrinsic interest and its relevance to all practical systems in engineering, finance, natural science and social science. This monograph provides some state-of-the-art expositions of major advances in fundamental stability theories and methods for dynamic systems of ODE and DDE types and in limit cycle, normal form and Hopf bifurcation control of nonlinear dynamic systems.ʺ Presents

  16. Stability of boundary measures

    CERN Document Server

    Chazal, Frédéric; Mérigot, Quentin

    2007-01-01

    We introduce the boundary measure at scale r of a compact subset of the n-dimensional Euclidean space. We show how it can be computed for point clouds and suggest these measures can be used for feature detection. The main contribution of this work is the proof a quantitative stability theorem for boundary measures using tools of convex analysis and geometric measure theory. As a corollary we obtain a stability result for Federer's curvature measures of a compact, allowing to compute them from point-cloud approximations of the compact.

  17. Thermodynamic Stability of Nanobubbles

    CERN Document Server

    Attard, Phil

    2015-01-01

    The observed stability of nanobubbles contradicts the well-known result in classical nucleation theory, that the critical radius is both microscopic and thermodynamically unstable. Here nanoscopic stability is shown to be the combined result of two non-classical mechanisms. It is shown that the surface tension decreases with increasing supersaturation, and that this gives a nanoscopic critical radius. Whilst neither a free spherical bubble nor a hemispherical bubble mobile on an hydrophobic surface are stable, it is shown that an immobilized hemispherical bubble with a pinned contact rim is stable and that the total entropy is a maximum at the critical radius.

  18. Progress on plutonium stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, D. [Defense Nuclear Facilities Safety Board, Washington, DC (United States)

    1996-05-01

    The Defense Nuclear Facilities Safety Board has safety oversight responsibility for most of the facilities where unstable forms of plutonium are being processed and packaged for interim storage. The Board has issued recommendations on plutonium stabilization and has has a considerable influence on DOE`s stabilization schedules and priorities. The Board has not made any recommendations on long-term plutonium disposition, although it may get more involved in the future if DOE develops plans to use defense nuclear facilities for disposition activities.

  19. Phosphane-stabilized gold clusters: investigation of the stability of [Au(13)(PMe (2)Ph) (10)Cl (2)] (3+).

    Science.gov (United States)

    Li, Jia; Wang, Shu-Guang

    2010-03-01

    The phosphane-stabilized gold cluster [Au(13)(PMe(2)Ph)(10)Cl(2)](3+) was studied using density functional theory. The extraordinary stability of the cluster has been attributed to the stability of the gold core and the protection conferred by ligands. Here, five stability factors of the gold core were explained and verified by investigating the Au (13) (5+) core in detail. Interactions between the gold core and several PR(3) ligands (R = Me, H, I, Br, Cl, F) were investigated according to the different electron donor abilities of each ligand; bonding energy between the ligand and the gold core was found to increase with the electronegativity of the R substituent. Furthermore, two other aspects of the ligands were clarified: how the ligand stabilizes the Au (13) (5+) core, and which kind of ligand provides the best stabilization for the cluster.

  20. Stability Study of the RERTR Fuel Microstructure

    Energy Technology Data Exchange (ETDEWEB)

    Jian Gan; Dennis Keiser; Brandon Miller; Daniel Wachs

    2014-04-01

    The irradiation stability of the interaction phases at the interface of fuel and Al alloy matrix as well as the stability of the fission gas bubble superlattice is believed to be very important to the U-Mo fuel performance. In this paper the recent result from TEM characterization of Kr ion irradiated U-10Mo-5Zr alloy will be discussed. The focus will be on the phase stability of Mo2-Zr, a dominated second phase developed at the interface of U-10Mo and the Zr barrier in a monolithic fuel plate from fuel fabrication. The Kr ion irradiations were conducted at a temperature of 200 degrees C to an ion fluence of 2.0E+16 ions/cm2. To investigate the thermal stability of the fission gas bubble superlattice, a key microstructural feature in both irradiated dispersion U-7Mo fuel and monolithic U-10Mo fuel, a FIB-TEM sample of the irradiated U-10Mo fuel (3.53E+21 fission/cm3) was used for a TEM in-situ heating experiment. The preliminary result showed extraordinary thermal stability of the fission gas bubble superlattice. The implication of the TEM observation from these two experiments on the fuel microstructural evolution under irradiation will be discussed.

  1. Random Access Broadcast: Stability and Throughput Analysis

    CERN Document Server

    Shrader, Brooke

    2007-01-01

    A wireless network in which packets are broadcast to a group of receivers through use of a random access protocol is considered in this work. The relation to previous work on networks of interacting queues is discussed and subsequently, the stability and throughput regions of the system are analyzed and presented. A simple network of two source nodes and two destination nodes is considered first. The broadcast service process is analyzed assuming a channel that allows for packet capture and multipacket reception. In this small network, the stability and throughput regions are observed to coincide. The same problem for a network with N sources and M destinations is considered next. The channel model is simplified in that multipacket reception is no longer permitted. Bounds on the stability region are developed using the concept of stability rank and the throughput region of the system is compared to the bounds. Our results show that as the number of destination nodes increases, the stability and throughput reg...

  2. Designed metalloprotein stabilizes a semiquinone radical

    Science.gov (United States)

    Ulas, Gözde; Lemmin, Thomas; Wu, Yibing; Gassner, George T.; Degrado, William F.

    2016-04-01

    Enzymes use binding energy to stabilize their substrates in high-energy states that are otherwise inaccessible at ambient temperature. Here we show that a de novo designed Zn(II) metalloprotein stabilizes a chemically reactive organic radical that is otherwise unstable in aqueous media. The protein binds tightly to and stabilizes the radical semiquinone form of 3,5-di-tert-butylcatechol. Solution NMR spectroscopy in conjunction with molecular dynamics simulations show that the substrate binds in the active site pocket where it is stabilized by metal-ligand interactions as well as by burial of its hydrophobic groups. Spectrochemical redox titrations show that the protein stabilized the semiquinone by reducing the electrochemical midpoint potential for its formation via the one-electron oxidation of the catechol by approximately 400 mV (9 kcal mol-1). Therefore, the inherent chemical properties of the radical were changed drastically by harnessing its binding energy to the metalloprotein. This model sets the basis for designed enzymes with radical cofactors to tackle challenging chemistry.

  3. Increasing entropy for colloidal stabilization

    Science.gov (United States)

    Mo, Songping; Shao, Xuefeng; Chen, Ying; Cheng, Zhengdong

    2016-11-01

    Stability is of paramount importance in colloidal applications. Attraction between colloidal particles is believed to lead to particle aggregation and phase separation; hence, stability improvement can be achieved through either increasing repulsion or reducing attraction by modifying the fluid medium or by using additives. Two traditional mechanisms for colloidal stability are electrostatic stabilization and steric stabilization. However, stability improvement by mixing attractive and unstable particles has rarely been considered. Here, we emphasize the function of mixing entropy in colloidal stabilization. Dispersion stability improvement is demonstrated by mixing suspensions of attractive nanosized titania spheres and platelets. A three-dimensional phase diagram is proposed to illustrate the collaborative effects of particle mixing and particle attraction on colloidal stability. This discovery provides a novel method for enhancing colloidal stability and opens a novel opportunity for engineering applications.

  4. Relating weak layer and slab properties to snow slope stability

    Directory of Open Access Journals (Sweden)

    J. Schweizer

    2014-07-01

    Full Text Available Snow slope stability evaluation requires considering weak layer as well as slab properties – and in particular their interaction. We developed a stability index from snow micro-penetrometer measurements and compared it to 129 concurrent point observations with the compression test (CT. The index considers the SMP-derived micro-structural strength and the additional load which depends on the hardness of the surface layers. The new quantitative measure of stability discriminated well between point observations rated as either "poor" or "fair" (CT < 19 and those rated as "good" (CT ≥ 19. However, discrimination power within the intermediate range was low. We then applied the index to gridded snow micro-penetrometer measurements from 11 snow slopes to explore the spatial structure and possibly relate it to slope stability. Stability distributions on the 11 slopes reflected various possible strength and load (stress distributions that naturally can occur. Their relation to slope stability was poor possibly because the index does not consider crack propagation. Hence, the relation between spatial patterns of point stability and slope stability remains elusive. Whereas this is the first attempt of a truly quantitative measure of stability, future developments should consider a better reference of stability and incorporate a measure of crack propagation.

  5. Shockwave-boundary layer interactions

    NARCIS (Netherlands)

    Glepman, R.

    2014-01-01

    Shock wave-boundary layer interactions are a very common feature in both transonic and supersonic flows. They can be encountered on compressor and turbine blades, in supersonic jet inlets, on transonic wings, on the stabilization fins of missiles and in many more situations. Because of their major i

  6. Gestural stability in vowels

    Science.gov (United States)

    Purnell, Thomas

    2004-05-01

    In accordance with proper perception of linguistic sound units, past research has demonstrated some degree of acoustic and physiological stability. In contrast, articulatory stability has been thought to be inconsistent because articulations may vary so long as the vocal tract area function results in appropriate formant structure [Atal et al., J. Acoust. Soc. Am. 63, 1535-1555 (1978)]. However, if the area function for the constriction and its anterior region can maintain acoustic stability, articulatory stability should be observed in the relational behavior of four tongue pellets used in xray microbeam data. Previous work examined normalized pellet data in order to arrive at an average posture for each vowel [Hashi et al., J. Acoust. Soc. Am. 104, 2426-2437 (1998)]. But by assuming static (average) gestures, the research fell short of a correct postural characterization. This study of tongue pellet speed and normalized pellet displacement of front vowels spoken by ten microbeam database subjects reports that the tongue tip pellet speed maxima identify vowel edges (end of vowel onset, beginning of offset) while displacement of the three anterior pellets identify changes in formant structure (e.g., two stable regions in the Northern Cities English front low vowel).

  7. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Trandum, Christa; Larsen, Nanna Brink

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (Tm) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C-...

  8. Orbit Stabilization of Nanosat

    Energy Technology Data Exchange (ETDEWEB)

    JOHNSON,DAVID J.

    1999-12-01

    An algorithm is developed to control a pulsed {Delta}V thruster on a small satellite to allow it to fly in formation with a host satellite undergoing time dependent atmospheric drag deceleration. The algorithm uses four short thrusts per orbit to correct for differences in the average radii of the satellites due to differences in drag and one thrust to symmetrize the orbits. The radial difference between the orbits is the only input to the algorithm. The algorithm automatically stabilizes the orbits after ejection and includes provisions to allow azimuthal positional changes by modifying the drag compensation pulses. The algorithm gives radial and azimuthal deadbands of 50 cm and 3 m for a radial measurement accuracy of {+-} 5 cm and {+-} 60% period variation in the drag coefficient of the host. Approaches to further reduce the deadbands are described. The methodology of establishing a stable orbit after ejection is illustrated in an appendix. The results show the optimum ejection angle to minimize stabilization thrust is upward at 86{sup o} from the orbital velocity. At this angle the stabilization velocity that must be supplied by the thruster is half the ejection velocity. An ejection velocity of 0.02 m/sat 86{sup o} gives an azimuthal separation after ejection and orbit stabilization of 187 m. A description of liquid based gas thrusters suitable for the satellite control is included in an appendix.

  9. Sprinkler Bifurcations and Stability

    Science.gov (United States)

    Sorensen, Jody; Rykken, Elyn

    2010-01-01

    After discussing common bifurcations of a one-parameter family of single variable functions, we introduce sprinkler bifurcations, in which any number of new fixed points emanate from a single point. Based on observations of these and other bifurcations, we then prove a number of general results about the stabilities of fixed points near a…

  10. Electronic Stability Control

    Science.gov (United States)

    2013-12-05

    relationship between the steering wheel angle and lateral acceleration varies among vehicles because of differences in steering gear ratios, suspension...on-road, untripped truck rollovers by automatically decelerating the vehicle by applying the foundation brakes and reducing engine torque output...attributes: (1) Augments vehicle directional stability by applying and adjusting vehicle brake torques individually at each wheel position on at least

  11. Stability through cycles

    NARCIS (Netherlands)

    E.A. de Groot (Bert); Ph.H.B.F. Franses (Philip Hans)

    2006-01-01

    textabstractEconomic variables like GDP growth, employment, interest rates and consumption show signs of cyclical behavior. Many variables display multiple cycles, with lengths ranging in between 5 to even up to 100 years. We argue that multiple cycles can be associated with long-run stability of th

  12. Stability through cycles

    NARCIS (Netherlands)

    Groot, de E.A. (Bert); Franses, P.H.P.H.

    2008-01-01

    Economic variables like GDP growth, employment, interest rates and consumption show signs of cyclical behavior. Many variables display multiple cycles, with periods ranging in between 5 to even up to 100 years. We argue that multiple cycles can be associated with long-run stability of the economic s

  13. Stability through cycles

    NARCIS (Netherlands)

    Groot, de E.A. (Bert); Franses, P.H.P.H.

    2006-01-01

    Economic variables like GDP growth, employment, interest rates and consumption show signs of cyclical behavior. Many variables display multiple cycles, with lengths ranging in between 5 to even up to 100 years. We argue that multiple cycles can be associated with long-run stability of the economic s

  14. Pickering emulsions stabilized by oppositely charged colloids: Stability and pattern formation

    Science.gov (United States)

    Christdoss Pushpam, Sam David; Basavaraj, Madivala G.; Mani, Ethayaraja

    2015-11-01

    A binary mixture of oppositely charged colloids can be used to stabilize water-in-oil or oil-in-water emulsions. A Monte Carlo simulation study to address the effect of charge ratio of colloids on the stability of Pickering emulsions is presented. The colloidal particles at the interface are modeled as aligned dipolar hard spheres, with attractive interaction between unlike-charged and repulsive interaction between like-charged particles. The optimum composition (fraction of positively charged particles) required for the stabilization corresponds to a minimum in the interaction energy per particle. In addition, for each charge ratio, there is a range of compositions where emulsions can be stabilized. The structural arrangement of particles or the pattern formation at the emulsion interface is strongly influenced by the charge ratio. We find well-mixed isotropic, square, and hexagonal arrangements of particles on the emulsion surface for different compositions at a given charge ratio. The distribution of coordination numbers is calculated to characterize structural features. The simulation study is useful for the rational design of Pickering emulsifications wherein oppositely charged colloids are used, and for the control of pattern formation that can be useful for the synthesis of colloidosomes and porous shells derived thereof.

  15. Analysis of the gyroscopic stabilization of a system of rigid bodies

    DEFF Research Database (Denmark)

    Kliem, Wolfhard; Seyranian, Alexander P.

    1997-01-01

    We study the gyroscopic stability of a three-body system. A new method of finding stability regions, based on mechanism and criteria for gyroscopic stabilization, is presented. Of particular interest in this connection is the theory of interaction of eigenvalues. This leads to a complete 3......-dimensional analysis, which shows the regions of stability, divergence, and flutter of a simple model of a rotating spaceship....

  16. Plant biodiversity impacts on soil stability

    Science.gov (United States)

    Gould, Iain; Quinton, John; Bardgett, Richard

    2014-05-01

    In recent times, growing threats to global biodiversity have raised awareness from the scientific community, with particular interest on how plant diversity impacts on ecosystem functioning. In the field of plant-soil interactions, much work has been done to research the implications of species loss, primarily focussing on biological processes such as plant productivity, microbial activity and carbon cycling. Consequently, virtually nothing is known about how plant diversity might impact on soil physical properties, and what mechanisms might be involved. This represents a serious gap in knowledge, given that maintaining soils with good structural integrity can reduce soil erosion and water pollution, and can lead to improved plant yield. Therefore, there is a need for a greater understanding of how plant communities and ecological interactions between plant roots and soils can play a role in regulating soil physical structure. Soil aggregation is an important process in determining soil stability by regulating soil water infiltration and having consequences for erodibility. This is influenced by both soil physical constituents and biological activity; including soil organic carbon content, microbial growth, and increased plant rooting. As previously mentioned, plant diversity influences carbon dynamics, microbial activity and plant growth, therefore could have substantial consequences for soil aggregate stability. Here, we present results from a series of plant manipulation experiments, on a range of scales, to understand more about how plant diversity could impact on soil aggregate stability. Soils from both a plant manipulation mesocosm experiment, and a long term biodiversity field study, were analysed using the Le Bissonnais method of aggregate stability breakdown. Increasing plant species richness was found to have a significant positive impact on soil aggregate stability at both scales. In addition to this, the influence of species identity, functional group

  17. Stability of laser-propelled wafer satellites

    Science.gov (United States)

    Srinivasan, Prashant; Hughes, Gary B.; Lubin, Philip; Zhang, Qicheng; Madajian, Jonathan; Brashears, Travis; Kulkarni, Neeraj; Cohen, Alexander; Griswold, Janelle

    2016-09-01

    For interstellar missions, directed energy is envisioned to drive wafer-scale spacecraft to relativistic speeds. Spacecraft propulsion is provided by a large array of phase-locked lasers, either in Earth orbit or stationed on the ground. The directed-energy beam is focused on the spacecraft, which includes a reflective sail that propels the craft by reflecting the beam. Fluctuations and asymmetry in the beam will create rotational forces on the sail, so the sail geometry must possess an inherent, passive stabilizing effect. A hyperboloid shape is proposed, since changes in the incident beam angle due to yaw will passively counteract rotational forces. This paper explores passive stability properties of a hyperboloid reflector being bombarded by directed-energy beam. A 2D cross-section is analyzed for stability under simulated asymmetric loads. Passive stabilization is confirmed over a range of asymmetries. Realistic values of radiation pressure magnitude are drawn from the physics of light-mirror interaction. Estimates of beam asymmetry are drawn from optical modeling of a laser array far-field intensity using fixed and stochastic phase perturbations. A 3D multi-physics model is presented, using boundary conditions and forcing terms derived from beam simulations and lightmirror interaction models. The question of optimal sail geometry can be pursued, using concepts developed for the baseline hyperboloid. For example, higher curvature of the hyperboloid increases stability, but reduces effective thrust. A hyperboloid sail could be optimized by seeking the minimum curvature that is stable over the expected range of beam asymmetries.

  18. Cultivating objects in interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2014-01-01

    is chapter explores patterns of repeated orientations to physical objects in interactants’ visuo-spatial and haptic surround. A number of examples are presented from advice-giving activities in various institutional settings, where participants-in-interaction initially draw on material objects...... on these associations for describing, disambiguating or clarifying aspects of the relatively complex procedural frameworks discussed in the settings. is suggests that the temporal stability of material objects available to participants makes them an ideal resource to be developed as visual motifs....

  19. Explicit Interaction

    DEFF Research Database (Denmark)

    Löwgren, Jonas; Eriksen, Mette Agger; Linde, Per

    2006-01-01

    as an interpretation of palpability, comprising usability as well as patient empowerment and socially performative issues. We present a prototype environment for video recording during physiotherapeutical consultation which illustrates our current thoughts on explicit interaction and serves as material for further......We report an ongoing study of palpable computing to support surgical rehabilitation, in the general field of interaction design for ubiquitous computing. Through explorative design, fieldwork and participatory design techniques, we explore the design principle of explicit interaction...

  20. Floor interaction

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Krogh, Peter; Ludvigsen, Martin;

    2005-01-01

    Within architecture, there is a long tradition of careful design of floors. The design has been concerned with both decorating floors and designing floors to carry information. Ubiquitous computing technology offers new opportunities for designing interactive floors. This paper presents three...... different interactive floor concepts. Through an urban perspective it draws upon the experiences of floors in architecture, and provides a set of design issues for designing interactive floors....

  1. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...

  2. Stability Criterion for Humanoid Running

    Institute of Scientific and Technical Information of China (English)

    LIZhao-Hui; HUANGQiang; LIKe-Jie

    2005-01-01

    A humanoid robot has high mobility but possibly risks of tipping over. Until now, one main topic on humanoid robots is to study the walking stability; the issue of the running stability has rarely been investigated. The running is different from the walking, and is more difficult to maintain its dynamic stability. The objective of this paper is to study the stability criterion for humanoid running based on the whole dynamics. First, the cycle and the dynamics of running are analyzed. Then, the stability criterion of humanoid running is presented. Finally, the effectiveness of the proposed stability criterion is illustrated by a dynamic simulation example using a dynamic analysis and design system (DADS).

  3. Hillslope hydrology and stability

    Science.gov (United States)

    Lu, Ning; Godt, Jonathan

    2012-01-01

    Landslides are caused by a failure of the mechanical balance within hillslopes. This balance is governed by two coupled physical processes: hydrological or subsurface flow and stress. The stabilizing strength of hillslope materials depends on effective stress, which is diminished by rainfall. This book presents a cutting-edge quantitative approach to understanding hydro-mechanical processes across variably saturated hillslope environments and to the study and prediction of rainfall-induced landslides. Topics covered include historic synthesis of hillslope geomorphology and hydrology, total and effective stress distributions, critical reviews of shear strength of hillslope materials and different bases for stability analysis. Exercises and homework problems are provided for students to engage with the theory in practice. This is an invaluable resource for graduate students and researchers in hydrology, geomorphology, engineering geology, geotechnical engineering and geomechanics and for professionals in the fields of civil and environmental engineering and natural hazard analysis.

  4. Stability of Ignition Transients

    Directory of Open Access Journals (Sweden)

    V.E. Zarko

    1991-07-01

    Full Text Available The problem of ignition stability arises in the case of the action of intense external heat stimuli when, resulting from the cut-off of solid substance heating, momentary ignition is followed by extinction. Physical pattern of solid propellant ignition is considered and ignition criteria available in the literature are discussed. It is shown that the above mentioned problem amounts to transient burning at a given arbitrary temperature distribution in the condensed phase. A brief survey of published data on experimental and theoretical studies on ignition stability is offered. The comparison between theory and experiment is shown to prove qualitatively the efficiency of the phenomenological approach in the theory. However, the methods of mathematical simulation as well as those of experimental studying of ignition phenomenon, especially at high fluxes, need to be improved.

  5. STABILIZED TRANSISTOR AMPLIFIER

    Science.gov (United States)

    Noe, J.B.

    1963-05-01

    A temperature stabilized transistor amplifier having a pair of transistors coupled in cascade relation that are capable of providing amplification through a temperature range of - 100 un. Concent 85% F to 400 un. Concent 85% F described. The stabilization of the amplifier is attained by coupling a feedback signal taken from the emitter of second transistor at a junction between two serially arranged biasing resistances in the circuit of the emitter of the second transistor to the base of the first transistor. Thus, a change in the emitter current of the second transistor is automatically corrected by the feedback adjustment of the base-emitter potential of the first transistor and by a corresponding change in the base-emitter potential of the second transistor. (AEC)

  6. Stability of Organic Nanowires

    DEFF Research Database (Denmark)

    Balzer, F.; Schiek, M.; Wallmann, I.;

    2011-01-01

    The morphological stability of organic nanowires over time and under thermal load is of major importance for their use in any device. In this study the growth and stability of organic nanowires from a naphthyl end-capped thiophene grown by organic molecular beam deposition is investigated via...... atomic force microscopy (AFM). Aging experiments under ambient conditions already show substantial morphological changes. Nanoscopic organic clusters, which initially coexist with the nanowires, vanish within hours. Thermal annealing of nanowire samples leads to even more pronounced morphology changes......, such as a strong decrease in nanowire number density, a strong increase in nanowire height, and the formation of new types of crystallites. This happens even before sublimation of organic material starts. These experiments also shine new light on the formation process of the nanowires....

  7. Strategic Stability: Contending Interpretations

    Science.gov (United States)

    2013-02-01

    John Hillas, Mathijus Jansen , Jos Potters, and Dries Ver- meulen, “On the Relation Among Some Definitions of Strategic Stability,” Mathematics of...of those doors. Not only have basic and applied sci- ences grown closer together in many fields, but theo - retical and experimental sciences have...science” bounds problems and provides insights. From the perspective of even the most theo - retical science, the wormhole camera postulated by Sir

  8. Limits of Nuclear Stability

    CERN Document Server

    Nerlo-Pomorska, B; Kleban, M

    2003-01-01

    The modern version of the liquid-drop model (LSD) is compared with the macroscopic part of the binding energy evaluated within the Hartree-Fock- Bogoliubov procedure with the Gogny force and the relativistic mean field theory. The parameters of a liquid-drop like mass formula which approximate on the average the self-consistent results are compared with other models. The limits of nuclear stability predicted by these models are discussed.

  9. Determining postural stability

    Science.gov (United States)

    Lieberman, Erez (Inventor); Forth, Katharine E. (Inventor); Paloski, William H. (Inventor)

    2011-01-01

    A method for determining postural stability of a person can include acquiring a plurality of pressure data points over a period of time from at least one pressure sensor. The method can also include the step of identifying a postural state for each pressure data point to generate a plurality of postural states. The method can include the step of determining a postural state of the person at a point in time based on at least the plurality of postural states.

  10. Stability of laminated composites

    Energy Technology Data Exchange (ETDEWEB)

    Guz`, A.N.; Chekhov, V.N. [Inst. of Mechanics of the Academy of Sciences of the Ukrainian, Kiev (Ukraine)

    1992-02-01

    The characteristic special feature of deformation behavior of modern laminated composite materials and structural elements fabricated from these materials, at current levels of loading and operating conditions is the occurrence of the purely three-dimensional stress-deformed state. In this process some specific mechanical phenomena and effects may occur, which is impossible to describe within the framework of applied or approximate approaches existing currently in deformable solid body mechanics. The structure of massive laminated materials may be included in this class of phenomena when the critical parameters of the problem depend only on the ratio between mechanical and geometrical characteristics of single layers and are independent of the dimensions and the form of the total laminated body as a whole. Since this phenomenon may be the beginning of the process of fracture of these materials, and the loss of the load-carrying capacity of structure elements fabricated from them, we consider below, in three-dimensional formulation, the problem of the surface and internal instability in laminated composite materials under compressive surface loads. The classification of the existing types of stability problems is presented for laminated materials and approaches for their solution presented in the literature. On the basis of three-dimensional linearized stability theory, within the framework of the piecewise-homogeneous media model, the general formulation of the most characteristic classes of stability problems of laminated materials is given in Langrangian coordinates at small and finite, homogeneous and inhomogeneous precritical deformation. Analytic and variational methods of investigation of formulated problems are given with application to various models of laminated bodies models, in accordance with accepted stability criteria. The accuracy of these models is evaluated, based on th example of the solution of certain model problems.

  11. Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

    Directory of Open Access Journals (Sweden)

    Annika Tuomela

    2016-05-01

    Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

  12. Stability of cooperation under image scoring in group interactions.

    Science.gov (United States)

    Nax, Heinrich H; Perc, Matjaž; Szolnoki, Attila; Helbing, Dirk

    2015-07-15

    Image scoring sustains cooperation in the repeated two-player prisoner's dilemma through indirect reciprocity, even though defection is the uniquely dominant selfish behaviour in the one-shot game. Many real-world dilemma situations, however, firstly, take place in groups and, secondly, lack the necessary transparency to inform subjects reliably of others' individual past actions. Instead, there is revelation of information regarding groups, which allows for 'group scoring' but not for image scoring. Here, we study how sensitive the positive results related to image scoring are to information based on group scoring. We combine analytic results and computer simulations to specify the conditions for the emergence of cooperation. We show that under pure group scoring, that is, under the complete absence of image-scoring information, cooperation is unsustainable. Away from this extreme case, however, the necessary degree of image scoring relative to group scoring depends on the population size and is generally very small. We thus conclude that the positive results based on image scoring apply to a much broader range of informational settings that are relevant in the real world than previously assumed.

  13. Molecular principles of protein stability and protein-protein interactions

    OpenAIRE

    Lendel, Christofer

    2005-01-01

    Proteins with highly specific binding properties constitute the basis for many important applications in biotechnology and medicine. Immunoglobulins have so far been the obvious choice but recent advances in protein engineering have provided several novel constructs that indeed challenge antibodies. One class of such binding proteins is based on the 58 residues three-helix bundle Z domain from staphylococcal protein A (SPA). These so-called affibodies are selected from libraries containing Z ...

  14. Visual Fixation for 3D Video Stabilization

    Directory of Open Access Journals (Sweden)

    Hans-Peter Seidel

    2011-03-01

    Full Text Available Visual fixation is employed by humans and some animals to keep a specific 3D location at the center of the visual gaze. Inspired by this phenomenon in nature, this paper explores the idea to transfer this mechanism to the context of video stabilization for a hand-held video camera. A novel approach is presented that stabilizes a video by fixating on automatically extracted 3D target points. This approach is different from existing automatic solutions that stabilize the video by smoothing. To determine the 3D target points, the recorded scene is analyzed with a state-of-the-art structure-from-motion algorithm, which estimates camera motion and reconstructs a 3D point cloud of the static scene objects. Special algorithms are presented that search either virtual or real 3D target points, which back-project close to the center of the image for as long a period of time as possible. The stabilization algorithm then transforms the original images of the sequence so that these 3D target points are kept exactly in the center of the image, which, in case of real 3D target points, produces a perfectly stable result at the image center. Furthermore, different methods of additional user interaction are investigated. It is shown that the stabilization process can easily be controlled and that it can be combined with state-of-the-art tracking techniques in order to obtain a powerful image stabilization tool. The approach is evaluated on a variety of videos taken with a hand-held camera in natural scenes.

  15. Biological Sludge Stabilization; Fenton and Ozonation Processes

    Directory of Open Access Journals (Sweden)

    Miranzadeh M.B.1 PhD,

    2015-09-01

    Full Text Available Aims In biological wastewater treatment processes, a large amount of sludge is produced. Stabilization of sludge is essential before disposal because of the risks to human health and environment. Therefore, selecting an appropriate process for stabilization this sludge may efficiently decrease risks. The aim of this study was to examine the compound efficiency of the advanced Fenton and ozonation oxidation processes in stabilization of biological sludge. Instrument & Methods This experimental study was conducted on raw sludge taken from Kashan University of Medical Sciences’ Wastewater Treatment Plant in Iran during 2014. Fenton and ozonation oxidation processes were used for sludge stabilization. H2O2 and Fe2+ concentration, along with their mutual interaction, were measured using repeated measures model. Then the effects of pH and time reaction on reduction efficiency of volatile solids (VS were examined. Findings The maximum removal efficiencies in Fenton process at pH=3 and in ozonation process in pH=7 were obtained 85.1% and 92.9%, respectively. By increasing the reaction time from 30 to 90min, VS reduction efficiency in Fenton and ozonation processes increased and then reduced after 60min. The maximum reduction efficiencies of VS were obtained at 3000mg/l H2O2 concentration, So that the optimum ratio of Fe2+/H2O2 for sludge stabilization was 1000/3000mg/l with the efficiency of 91.5%. Conclusion Ozonation process efficiency in stabilizing biological wastewater sludge is higher than that of Fenton process.

  16. Manipulating semiconductor colloidal stability through doping.

    Science.gov (United States)

    Fleharty, Mark E; van Swol, Frank; Petsev, Dimiter N

    2014-10-10

    The interface between a doped semiconductor material and electrolyte solution is of considerable fundamental interest, and is relevant to systems of practical importance. Both adjacent domains contain mobile charges, which respond to potential variations. This is exploited to design electronic and optoelectronic sensors, and other enabling semiconductor colloidal materials. We show that the charge mobility in both phases leads to a new type of interaction between semiconductor colloids suspended in aqueous electrolyte solutions. This interaction is due to the electrostatic response of the semiconductor interior to disturbances in the external field upon the approach of two particles. The electrostatic repulsion between two charged colloids is reduced from the one governed by the charged groups present at the particles surfaces. This type of interaction is unique to semiconductor particles and may have a substantial effect on the suspension dynamics and stability.

  17. Teaching Noncovalent Interactions Using Protein Molecular Evolution

    Science.gov (United States)

    Fornasari, Maria Silvina; Parisi, Gustavo; Echave, Julian

    2008-01-01

    Noncovalent interactions and physicochemical properties of amino acids are important topics in biochemistry courses. Here, we present a computational laboratory where the capacity of each of the 20 amino acids to maintain different noncovalent interactions are used to investigate the stabilizing forces in a set of proteins coming from organisms…

  18. Foams Stabilized with Nanoparticles for Gas Well Deliquification

    OpenAIRE

    Knapik Ewa; Stopa Jerzy; Marzec Anna

    2014-01-01

    This study examined the interaction of solid nanoparticles and anionic and non-ionic surfactant at an air–water interface. Aqueous foams stabilized by silica nanoparticles in water with different levels of salinity were studied in detail. The stability of solid/surfactant dispersion was evaluated visually. Nanoparticles content impact and concentration of surfactant on the foamability, deliquification of foams and structure of wet foams were studied. It was found that the foamability of dispe...

  19. Prediction of Factors Determining Changes in Stability in Protein Mutants

    OpenAIRE

    Parthiban, Vijayarangakannan

    2006-01-01

    Analysing the factors behind protein stability is a key research topic in molecular biology and has direct implications on protein structure prediction and protein-protein docking solutions. Protein stability upon point mutations were analysed using a distance dependant pair potential representing mainly through-space interactions and torsion angle potential representing neighbouring effects as a basic statistical mechanical setup for the analysis. The synergetic effect of accessible surface ...

  20. MULTIPLE OSCILLATION STABILIZING CONTROL.

    Energy Technology Data Exchange (ETDEWEB)

    YUE,M.; SCHLUETER,R.; AZARM,M.; BARI,R.

    2004-07-23

    This paper presents a strategy that may be used to guide stabilizing control design for multiple oscillations, which are difficult to control using conventional control design procedures. A multiple oscillation phenomena is observed in an example power system. A local bifurcation and an interarea bifurcation develop in an example power system due to multiple bifurcation parameter variations. The dynamic behaviors of the bifurcating system are complex due to the overlapping of the two different bifurcation subsystems and are shown to be difficult to control. The double bifurcations are studied in this paper and in order to stabilize them, three kind of {mu}-synthesis robust controls are designed, (a) {mu}-synthesis power system stabilizer (MPSS); (b) {mu}-synthesis SVC control (MSVC); and (c) a mixed MPSS/MSVC control. Based on the bifurcation subsystem analysis, the measurement signals and locations of the controls are selected. The control performances of three kind of controls are evaluated and compared. The conclusions are given according to the analysis and time simulation results.